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Both oxidative stress and the immune response are associated with heart failure (HF). In this study, our aim was to identify the hub genes associated with oxidative stress andimmune infiltration of HF by bioinformatics analysis and experimental verification. The expression profile of GSE36074 was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were screened by GEO2R. The genes related to oxidative stress were extracted from GeneCards websites. Then, the functional enrichment analysis of oxidative stress-related DEGs (OSRDEGs) was performed using DAVID. In addition, we constructed a protein-protein interaction (PPI) network using the STRING database and screened for hub genes with Cytoscape software. We also used CIBERSORTx to analyze immune infiltration in mice heart tissues between the TAC and Sham groups and explored the correlation between immune cells and hub genes. Finally, the hub genes were carried out using reverse transcription quantitative PCR (RT-qPCR), immunohistochemistry (IHC) and western blot. A total of 136 OSRDEGs were found in GSE36074. Enrichment analysis revealed that these OSRDEGs were enriched in the mitochondrion, HIF-1, FoxO, MAPK and TNF signaling pathway. The five hub genes (Mapk14, Hif1a, Myc, Hsp90ab1, and Hsp90aa1) were screened by the cytoHubba plugin. The correlation analysis between immune cells and hub genes showed that Mapk14 was positively correlated with Th2 Cells, while Hif1a and Hsp90ab1exhibited a negative correlation with Th2 Cells; Myc exhibited a negative correlation with Monocytes; whereas, Hsp90aa1 was negatively correlated with NK Resting. Finally, five hub genes were validated by RT-qPCR, IHC and western blot. Mapk14, Hif1a, Myc, Hsp90ab1, and Hsp90aa1 are hub genes of HF and may play a critical role in the oxidative stress of HF. This study may provide new targets for the treatment of HF, and the potential immunotherapies are worthy of further study., Competing Interests: The authors declare there are no competing interests., (©2023 Gu et al.)

The current regulatory site investigation employs the J&E model to predict vapor intrusion risk. However, the J&E model assumes that the source concentration is constant for a given exposure period, which is not consistent with the actual site source under depletion. In this study, we compared the differences between the J&E model (constant source), SD source depletion model, and RBCA source depletion model for predicting indoor concentration variation as well as the risk levels during the exposure period with a case study in Beijing. The results showed that the source and indoor air concentrations predicted by the SD and RBCA models showed exponential decreases, whereas those predicted by the J&E model maintained high concentrations throughout the exposure period, which greatly overestimated the risk. The RBCA predicted source depletion at the fastest rate, but the predicted indoor air concentrations were still lower than those of the SD model, which was related to the fact that the RBCA did not consider the effect of buildings on source depletion and did not follow mass conservation. Further, the sensitivity analysis showed that the pressure difference (dP) had the greatest influence on the source concentration in the SD model. For the calculated carcinogenic risk and hazard quotients, the J&E constant source model, the SD source depletion model, and the RBCA source depletion model were ranked in descending order. The results indicated that in general the J&E model was too conservative, the RBCA model may have underestimated risk, and the SD model was more suitable for quantifying vapor intrusion risk in reality.

Infants and children are vulnerable to mercury (Hg)-induced toxicity, which has detrimental effects on their neurological development. This study measured blood Hg levels (BMLs) and identified potential factors influencing BMLs, including demographic and socioeconomic factors, lifestyle, and daily dietary habits, among 0 to 7-year-old children in Shanghai. Our study recruited 1474 participants, comprising 784 boys and 690 girls. Basic demographic and lifestyle information were obtained and blood Hg were analyzed using the Direct Mercury Analyzer 80. The blood Hg concentrations of children in Shanghai ranged from 0.01 to 17.20 μg/L, with a median concentration of 1.34 μg/L. Older age, higher familial socioeconomic status, higher residential floors, and a higher frequency of consuming aquatic products, rice, vegetables, and formula milk were identified as risk factors. Other potential influencing factors including the mother's reproductive history (gravidity and parity), smoking (passive smoking), supplementation of fish oil and calcium need to be further investigated. These findings can be useful in establishing appropriate interventions to prevent children's high blood Hg concentrations in Shanghai and other similar metropolitan cities., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fluorescent probes with on-site visual detection function have received extensive attention in the detection of chlortetracycline (CTC), which was widely used in aquaculture and animal husbandry. Copper nanoclusters (Cu NCs) with excellent optical properties were prepared using bovine serum albumin (BSA) as a template, and a multicolor fluorescence strategy based on BSA-stabilized Cu NCs (BSA-Cu NCs) for detecting CTC was proposed. BSA-Cu NCs had a red emission at 640 nm. After the addition of CTC, the red emission of BSA-Cu NCs gradually decreased for internal filtering effect, while the green emission of CTC was significantly enhanced under the sensitization of BSA. This simple sensing process can be achieved in real time by directly mixing the target sample with BSA-Cu NCs, and the detection limit (LOD) of the system for CTC was 12.01 nM. Based on this sensing strategy, a fluorescence film sensing detection platform was constructed to achieve ultra-fast detection of CTC within 30 s. This work provided a fluorescent film sensor with the advantages of portability, ultra-fast and low cost, which provided a feasible alternative for on-site ultra-fast screening of CTC., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 Elsevier B.V. All rights reserved.)

High level of tumor-infiltrating lymphocytes (TILs) can predict the rate of total pathological complete remission (tpCR) of breast cancer patients who receive neoadjuvant chemotherapy (NACT). This study focused on evaluating the data of patients whose primary tumor and/or lymph node metastasis show nonresponse (NR) to NACT, trying to provide a basis for the clinical decision which patients will develop NACT resistance. The study included breast cancers from 991 patients who received NACT. ROC curve analysis confirmed that TILs showed significant predictive value for NR of hormone receptor (HR)+HER2- and triple-negative breast cancer (TNBC). Among HR+HER2- breast cancer, TILs ≥ 10% was an independent predictor for low NR rate. Furthermore, positive correlation of TILs with Ki67 index and Miller-Payne grade, and negative correlation with ER and PR H-scores were only identified in this subgroup. In TNBC, TILs ≥ 17.5% was an independent predictor for low NR rate. The predictive value of low TILs on NR may facilitate to screen patients with HR+HER2- or TNBC who may not benefit from NACT. HR+HER2- breast cancer with low levels of TILs should be carefully treated with neoadjuvant chemotherapy, and other alternatives such as neoadjuvant endocrine therapy can be considered., (© 2023. The Author(s).)

The Dandy-Walker malformation (DWM) is characterized by neuron dysregulation in embryonic development; however, the regulatory mechanisms associated with it are unclear. This study aimed to investigate the role of NADH dehydrogenase 1 alpha subcomplex 4 (NDUFA4) in regulating downstream signaling cascades and neuronal proliferation and apoptosis. Ndufa4 overexpression promoted the proliferation of neurons and inhibited their apoptosis in vitro, which underwent reverse regulation by the Ndufa4 short hairpin RNAs. Ndufa4-knockout (KO) mice showed abnormal histological alterations in the brain tissue, in addition to impaired spatial learning capacity and exploratory activity. Ndufa4 depletion altered the microRNA expressional profiles of the cerebellum: Ndufa4 inhibited miR-145a-5p expression both in the cerebellum and neurons. miR-145a-5p inhibited the proliferation of neurons and promoted their apoptosis. Ndufa4 promoted and miR-145a-5p inhibited the expression of human homer protein homolog 1 and cyclin D2 in neurons. Thus, Ndufa4 promotes the proliferation of neurons and inhibits their apoptosis by inhibiting miR-145a-5p, which directly targets and inhibits the untranslated regions of Homer1 and Ccnd2 expression., (© 2023. The Author(s).)

Advancing spatially resolved transcriptomics (ST) technologies help biologists comprehensively understand organ function and tissue microenvironment. Accurate spatial domain identification is the foundation for delineating genome heterogeneity and cellular interaction. Motivated by this perspective, a graph deep learning (GDL) based spatial clustering approach is constructed in this paper. First, the deep graph infomax module embedded with residual gated graph convolutional neural network is leveraged to address the gene expression profiles and spatial positions in ST. Then, the Bayesian Gaussian mixture model is applied to handle the latent embeddings to generate spatial domains. Designed experiments certify that the presented method is superior to other state-of-the-art GDL-enabled techniques on multiple ST datasets. The codes and dataset used in this manuscript are summarized at https://github.com/narutoten520/SCGDL., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Intraplaque neovascularization (IPN) is a known indicator of plaque vulnerability, and is thus considered a predictor of stroke. The morphology and location of the carotid plaque may be correlated with plaque vulnerability. Therefore, our study aimed to examine the associations of carotid plaque morphology and location with IPN., Methods: A total of 141 patients with carotid atherosclerosis (mean age, 64.99 ± 10.96 years) who underwent carotid contrast-enhanced ultrasound (CEUS) between November 2021 and March 2022 were retrospectively analyzed. IPN was graded according to the presence and location of microbubbles within the plaque. The association of IPN grade with carotid plaque morphology and location was evaluated using ordered logistic regression., Results: Of the 171 plaques, 89 (52%) were IPN Grade 0, 21 (12.2%) were Grade 1, and 61 (35.6%) were Grade 2. IPN grade significantly associated with both plaque morphology and location, with higher grades observed among Type III morphology and common carotid artery plaques. Significant negative association was further shown between IPN grade and serum high-density lipoprotein cholesterol (HDL-C) level. Plaque morphology and location, and HDL-C remained significantly associated with IPN grade after adjusting for confounding factors., Conclusion: The location and morphology of carotid plaques were significantly associated with the IPN grade on CEUS, and therefore show potential as biomarkers for plaque vulnerability. Serum HDL-C was also identified as a protective factor against IPN, and may play a role in the management of carotid atherosclerosis. Our study provided a potential strategy for identification of vulnerable carotid plaques and elucidated the important imaging predictors of stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gu, Zhang, Chen, Li, Yao, Jia and Wu.)

Aberrant lysosomal alkalization is associated with various biological processes, such as oxidative stress, cell apoptosis, ferroptosis, etc. Herein, we developed a novel aminofluorene-based fluorescence probe named FAN to monitor the lysosomal alkalization-related biological processes by its migration from lysosome to nucleus. FAN possessed NIR emission, large Stokes shift, high pH stability, and high photostability, making it suitable for real-time and long-term bioimaging. As a lysosomotropic molecule, FAN can accumulate in lysosomes first and then migrate to the nucleus by right of its binding capability to DNA after lysosomal alkalization. In this manner, FAN was successfully used to monitor these physiological processes which triggered lysosomal alkalization in living cells, including oxidative stress, cell apoptosis, and ferroptosis. More importantly, at higher concentrations, FAN could also serve as a stable nucleus dye for the fluorescence imaging of the nucleus in living cells and tissues. This novel multifunctional fluorescence probe shows great promise for application in lysosomal alkalization-related visual research and nucleus imaging.

Objectives: We aimed to evaluate the association between β-blocker therapy and mortality in patients with sepsis., Methods: Patients with sepsis were selected from the Medical Information Mart for Intensive Care (MIMIC)-III. Propensity score matching (PSM) was used to balance the baseline differences. A multivariate Cox regression model was used to assess the relationship between β-blocker therapy and mortality. The primary outcome was the 28-day mortality., Results: A total of 12,360 patients were included in the study, involving 3,895 who received β-blocker therapy and 8,465 who did not. After PSM, 3,891 pairs of patients were matched. The results showed that β-blockers were associated with improved 28- (hazards ratio (HR) 0.78) and 90-day (HR 0.84) mortality. Long-acting β-blockers were associated with improved 28-day survival (757/3627 [20.9%] vs. 583/3627 [16.1%], P < 0.001, HR0.76) and 90-day survival (1065/3627 [29.4%] vs.921/3627 [25.4%], P < 0.001, HR 0.77). Short-acting β-blocker treatment did not reduce the 28-day and 90-day mortality (61/264 [23.1%] vs. 63/264 [23.9%], P = 0.89 and 83/264 [31.4%] vs. 89/264 [31.7%], P = 0.8, respectively)., Conclusions: β-blockers were associated with improved 28- and 90-day mortality in patients with sepsis and septic shock. Long-acting β-blocker therapy may have a protective role in patients with sepsis, reducing the 28-day and 90-day mortality. However, short-acting β-blocker (esmolol) treatment did not reduce the mortality in sepsis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ge, Zhang, Ai, Chen, Ye, Zou and Peng.)

Objective: This study aimed to examine the relationship between low T3 syndrome (LT3S) and the prognosis of newly diagnosed multiple myeloma (NDMM) patients. Methods: A retrospective examination of 211 NDMM patients treated at the Department of Hematology, Jiangsu Provincial People's Hospital from July 2009 to December 2020 was performed, and all patients received thyroid function testing to determine if they had LT3S. We investigated the relationship between LT3S and clinical features, as well as its impact on MM prognosis. Results: Of the 211 patients, 119 were males, and 92 were females, with a median age of 60 (33-86) years. Patients with LT3S had significantly higher levels of β(2)-microglobulin, C-reactive protein, and blood creatinine compared to those with normal T3 levels. They also had lower levels of hemoglobin, platelets, and serum albumin, as well as more advanced ISS stages ( P <0.001) . Patients with LT3S had shorter progression-free survival (PFS) (16 months vs 30 months, P =0.003) and overall survival (OS) (57 months vs 75 months, P =0.004) than patients without LT3S. LT3S was found to be a standalone unfavorable factor in multivariate analysis, LT3S was an independent unfavorable factor in predicting both PFS ( HR =2.114, 95% CI 1.271-3.516, P =0.004) and OS ( HR =2.231, 95% CI 1.088-4.577, P =0.029) . Conclusions: Low T3 syndrome was an independent unfavorable prognostic predictor for NDMM.

Vehicle emissions are an important source of anthropogenic volatile organic compound (VOCs) emissions in urban areas and are commonly quantified using vehicle emission inventories. However, most previous studies on vehicle emission inventories have incomplete emission factors and emission processes or insufficient consideration of meteorological parameters. Based on the localized full-process emission factors attained from tested data and previous studies, a method to develop a monthly vehicular VOC emission inventory of full process for the long-term was established, which covered exhaust and evaporative emissions (including running loss, diurnal breathing loss, hot soak loss, and refueling emission). Then, the method was used to develop a full-process vehicular VOC emission inventory in Tianjin from 2000 to 2020. The results showed that the total vehicular VOC emissions in Tianjin rose slowly and then gradually decreased. In 2020, the total emissions were 21400 tons. The light-duty passenger vehicles were the dominant contributors and covered 75.00% of the total emissions. Unlike the continuous decline in exhaust emissions, evaporative emissions showed an inverted U-shaped trend with an increasing contribution to total emissions yearly, accounting for 31.69% in 2020. Monthly emissions were affected by both vehicle activity and emission factors. VOC emissions were high in autumn and winter and low in spring and summer. During the COVID-19 epidemic in 2020, vehicle activity was limited by closure and control, making VOC emissions significantly lower than those during the same period in previous years. The method and data in this study can provide technical reference and a decision-making basis for air pollution prevention and control.

An "AND" logic gate-based NIR fluorescent probe Si-NH2-Glu was developed based on novel meso -amine Si-Rhodamine, which combined γ-glutamyl transpeptidase and pH dual-responsive sites. The features of Si-NH2-Glu enable it to be applied in orthotopic tumor imaging and fluorescence-guided surgery.

Phototheranostics have emerged and flourished as a promising pattern for cancer theranostics owing to their precise photoinduced diagnosis and therapeutic to meet the demands of precision medicine. The diagnosis information and therapeutic effect are directly determined by the fluorescence imaging ability and photothermal conversion efficiency (PCE) of phototheranostic agents. Hence, how to balance the competitive radiative and nonradiative processes of phototheranostic agents is the key factor to evaluate the phototheranostic effect. Herein, molecules named ICRs with high photostaibility  are rationally designed, exhibiting fluorescence emission in the second near-infrared window (NIR-II, 1000-1700 nm) and high PCE, which are related to the strong donor-acceptor (D-A) interaction and high reorganization energy Noteworthily, ICR-Qu with stronger D-A interaction and a large-sized conjugated unit encapsulated in nanoparticles exhibits high PCE (81.1%). In addition, ICR-QuNPs are used for fluorescence imaging (FLI), photoacoustic imaging (PAI), and photothermal imaging (PTI) to guide deep-tissue photonic hyperthermia, achieving precise removal and inhibition of breast cancer. Furthermore, combined with α-PD-1, ICR-QuNPs show huge potential to be a facile and efficient tool for photo-immunotherapy. More importantly, this study not only reports an "all-in-one" polymethine-based phototheranostic agent, but also sheds light on the exploration of versatile organic molecules for future practical applications., (© 2023 Wiley-VCH GmbH.)

SAMD4 protein family is a class of novel RNA-binding proteins that can mediate post-transcriptional regulation and translation repression in eukaryotes, which are highly conserved from yeast to humans during evolution. In mammalian cells, SAMD4 protein family consists of two members including SAMD4A/Smaug1 and SAMD4B/Smaug2, both of which contain common SAM domain that can specifically bind to different target mRNAs through stem-loop structures, also known as Smaug recognition elements (SREs), and regulate the mRNA stability, degradation and translation. In addition, SAMD4 can form the cytoplasmic mRNA silencing foci and regulate the translation of SRE-containing mRNAs in neurons. SAMD4 also can form the cytosolic membrane-less organelles (MLOs), termed as Smaug1 bodies, and regulate mitochondrial function. Importantly, many studies have identified that SAMD4 family members are involved in various pathological processes including myopathy, bone development, neural development, and cancer occurrence and progression. In this review, we mainly summarize the structural characteristics, biological functions and molecular regulatory mechanisms of SAMD4 protein family members, which will provide a basis for further research and clinical application of SAMD4 protein family., (© 2023. The Author(s).)

Objective: To investigate the differences and their clinical significance in the intestinal microbiota in patients with Parkinson's disease (PD) in comparison to those in healthy controls., Materials and Methods: 20 patients with PD who received treatment in the First Affiliated Hospital of Bengbu Medical College between January 2019 and December 2019 were selected as the research subjects to form the PD group, while 20 age- and gender-matched healthy volunteers were selected as the control group. Fecal samples from the two groups were collected, and the V4 region of 16S-ribosomal ribonucleic acid was selected for high-throughput sequencing analysis to explore any differences, as well as their significance, in the intestinal microbiota abundance at the class, family, and genus levels between the two study groups., Results: The operational taxonomic unit cluster analysis revealed a high degree of overlap between the patients with PD and the controls. Compared with the controls, the relative abundance of Coriobacteriia and Coriobacteriaceae was increased in the PD group (p < 0.01), while the relative abundance of Lachnospiraceae was significantly lower (p < 0.01). The relative abundance of Collinsella , Escherichia , and Fusobacterium in the PD group was significantly higher than in the control group (p < 0.05)., Conclusion: Compared with the healthy subjects, the abundance of specific microflora was significantly different in the PD patients at the class, family, and genus level. Intestinal flora may act as a potential biomarker for PD and provide a theoretical basis for microflora transplantation therapy.

Osteoarthritis (OA) is the most common type of degenerative joint disease which affects 7% of the global population and more than 500 million people worldwide. One research frontier is the development of hydrogels for OA treatment, which operate either as functional scaffolds of tissue engineering or as delivery vehicles of functional additives. Both approaches address the big challenge: establishing stable integration of such delivery systems or implants. Adhesive hydrogels provide possible solutions to this challenge. However, few studies have described the current advances in using adhesive hydrogel for OA treatment. This review summarizes the commonly used hydrogels with their adhesion mechanisms and components. Additionally, recognizing that OA is a complex disease involving different biological mechanisms, the bioactive therapeutic strategies are also presented. By presenting the adhesive hydrogels in an interdisciplinary way, including both the fields of chemistry and biology, this review will attempt to provide a comprehensive insight for designing novel bioadhesive systems for OA therapy., (© 2023. The Author(s).)

The low ionic conductivity at room temperature and poor dimensional stability at high temperature of polyethylene oxide (PEO)-based solid electrolytes greatly limit the development and utilization of solid polymer electrolytes (SPEs). To reconcile the contradiction between electrochemical performance and mechanical strength of PEO-based SPEs, a cross-linking structure with active -CH 2 CH 2 O- soft chains that doped with rigid segments is designed and prepared through a method of green ultraviolet irradiation without solvent. The obtained solid film shows a high ionic conductivity of 0.2 mS·cm -1 and an ionic transference number of 0.51 at room temperature. The activation energy value of 1.92 kJ·mol -1 gives evidence for a favorable migration mechanism of PTP-SPE. A combination of flexibility and strength can be realized by molecular structure design with a tensile elongation of 40%. The reversible overpotential in galvanostatic cycling over 500 h of a Li||Li symmetrical cell indicates that the compact PTP-SPE can inhibit the formation of lithium dendrites. This work provides a new strategy for designing high-performance composite solid electrolytes at room temperature., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: Sepsis-associated encephalopathy (SAE) often leads to cognitive impairments. However, the pathophysiology of SAE is complex and unclear. Here, we investigated the role of hippocampus (HPC)-prefrontal cortex (PFC) in cognitive dysfunction in sepsis induced by cecal ligation puncture (CLP) in mice., Methods: The neural projections from the HPC to PFC were first identified via retrograde tracing and viral expression. Chemogenetic activation of the HPC-PFC pathway was shown via immunofluorescent staining of c-Fos-positive neurons in PFC. Morris Water Maze (MWM) and Barnes maze (BM) were used to evaluate cognitive function. Western blotting analysis was used to determine the expression of glutamate receptors and related molecules in PFC and HPC., Results: Chemogenetic activation of the HPC-PFC pathway enhanced cognitive dysfunction in CLP-induced septic mice. Glutamate receptors mediated the effects of HPC-PFC pathway activation in CLP mice. The activation of the HPC-PFC pathway resulted in significantly increased levels of NMDAR, AMPAR, and downstream signaling molecules including CaMKIIa, pCREB, and BDNF in PFC. However, inhibition of glutamate receptors using 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo (F)quinoxaline (NBQX), which is an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR inhibitor), or D-2-amino-5-phosphonopentanoate (D-AP5), which is an NMDA receptor antagonist abolished this increase., Conclusion: Our study reveals the important role of the HPC-PFC pathway in improving cognitive dysfunction in a mouse model of CLP sepsis and provides a novel pathogenetic mechanism for SAE., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis. To provide clinical practice recommendations on the immune function in sepsis, an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed. Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed, Web of Science, and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire. Then, the Delphi method was used to form consensus opinions, and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions. This consensus achieved satisfactory results through two rounds of questionnaire survey, with 2 statements rated as perfect consistency, 13 as very good consistency, and 9 as good consistency. After summarizing the results, a total of 14 strong recommended opinions, 8 weak recommended opinions and 2 non-recommended opinions were produced. Finally, a face-to-face discussion of the consensus opinions was performed through an online meeting, and all judges unanimously agreed on the content of this consensus. In summary, this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis., (© 2022. The Author(s).)

Currently, there are still many challenges in prenatal diagnosis, such as limited or uncertain fetal phenotyping, variant interpretation, and rapid turnaround times. The aim of this study was to illustrate the value of a comprehensive genomic evaluation in prenatal diagnosis. We retrospectively reviewed 20 fetuses with clinically significant copy number variants (CNVs) detected by chromosomal microarray analysis (CMA) and no further exome sequencing testing in our tertiary center between 2019 and 2020. The residual DNA from the prenatal cases was used for the parallel implementation of CNV sequencing (CNV-seq) and trio-based clinical exome sequencing (trio-CES). CMA revealed 26 clinically significant CNVs (18 deletions and eight duplications) in 20 fetuses, in which five fetuses had two or more CNVs. There were eight fetuses with pathogenic CNVs (e.g., del 1p36), nine fetuses with likely pathogenic CNVs (e.g., dup 22q11.21), and three fetuses with variants of unknown significance (VOUS, e.g., dup 1q21.1q21.2). Trio-CES identified four fetuses with likely pathogenic mutations (SNV/InDels). Of note, a fetus was detected with a maternally inherited hemizygous variant in the SLX4 gene due to a 16p13.3 deletion on the paternal chromosome. The sizes of CNVs detected by CNV-seq were slightly larger than that of the SNP array, and four cases with mosaic CNVs were all identified by CNV-seq. In conclusion, microdeletion/duplication syndromes and monogenic disorders may co-exist in a subject, and CNV deletion may contribute to uncovering additional recessive disease alleles. The application of a comprehensive genomic evaluation (CNVs and SNV/InDels) has great value in the prenatal diagnosis arena. CNV-seq based on NGS technology is a reliable and a cost-effective technique for identifying CNVs.

Introduction: Postoperative delirium can increase cognitive impairment and mortality in patients with Parkinson's disease. The purpose of this study was to develop and internally validate a clinical prediction model of delirium after deep brain stimulation of the subthalamic nucleus in Parkinson's disease under general anesthesia., Methods: We conducted a retrospective observational cohort study on the data of 240 patients with Parkinson's disease who underwent deep brain stimulation of the subthalamic nucleus under general anesthesia. Demographic characteristics, clinical evaluation, imaging data, laboratory data, and surgical anesthesia information were collected. Multivariate logistic regression was used to develop the prediction model for postoperative delirium., Results: A total of 159 patients were included in the cohort, of which 38 (23.90%) had postoperative delirium. Smoking (OR 4.51, 95% CI 1.56-13.02, p < 0.01) was the most important risk factor; other independent predictors were orthostatic hypotension (OR 3.42, 95% CI 0.90-13.06, p =0.07), inhibitors of type-B monoamine oxidase (OR 3.07, 95% CI 1.17-8.04, p =0.02), preoperative MRI with silent brain ischemia or infarction (OR 2.36, 95% CI 0.90-6.14, p =0.08), Hamilton anxiety scale score (OR 2.12, 95% CI 1.28-3.50, p < 0.01), and apolipoprotein E level in plasma (OR 1.48, 95% CI 0.95-2.29, p =0.08). The area under the receiver operating characteristic curve (AUC) was 0.76 (95% CI 0.66-0.86). A nomogram was established and showed good calibration and clinical predictive capacity. After bootstrap for internal verification, the AUC was 0.74 (95% CI 0.66-0.83)., Conclusion: This study provides evidence for the independent inducing factors of delirium after deep brain stimulation of the subthalamic nucleus in Parkinson's disease under general anesthesia. By predicting the development of delirium, our model may identify high-risk groups that can benefit from early or preventive intervention., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Yu-Ting Ling et al.)

A multicolor fluorescent nanoprobe has been prepared by loading bovine serum albumin-stabilized copper nanoclusters (BSA-Cu NCs) onto amino clay (AC) and grafting Eu 3+ with auxiliary ligand citric acid (Cit). Tetracycline (TC) can coordinate with Eu 3+ by β-diketone structure and transfer energy to Eu 3+ through antenna effect. When the concentration of TC is in the range 0 to 13 μM, the blue emission intensity of BSA-CuNCs is basically unchanged, and the red emission of Eu 3+ is remarkably enhanced due to the coordination with TC. The emission color gradually changes from blue to red under UV lamp (λ = 365 nm). However, when the TC concentration is in the range 13 to 350 μΜ, the internal amino acid residues of BSA sensitize TC, and the emission color gradually changed from red to green. The nanoprobe has rich color, is simple to prepare, portable, and provide a wide detection range. The limit of detection (LOD) is 3.04 nM, which could be used for real-time visual analysis of trace TC in actual samples (lake water, milk, honey, and bovine serum albumin). In addition, a visual test paper has been designed and combined with the color scanning APP of a smartphone to complete the qualitative and semi-quantitative test of TC. BSA-Cu NCs were loaded on amino clay and graft Eu 3+ to establish ratiometric fluorescent nanoprobe for TC detection. With the increase of TC concentration, the emission color under 365 nm UV lamp gradually changed from blue to red and then to green, and the color changed obviously and can be observed by the naked eye. The visual test paper and smartphone application detection sensor were developed to realize rapid, convenient, real-time, and visual detection of TC in actual samples., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The relationship between hemiplegic shoulder pain (HSP) and subluxation is unclear. This study aimed to determine the differences of magnetic resonance imaging (MRI) findings in HSP patients with or without subluxation after stroke, and to analyze the etiology of shoulder pain. This retrospective study included 53 patients with HSP after stroke from September 2013 to February 2020. Patients underwent MRI of the shoulder because of shoulder pain. Clinical characteristics, including age, sex, stroke duration, body mass index, stroke type, visual analog scale score, Brunnstrom stage, and MRI arthrography findings of the affected shoulder, were recorded. Patients were classified into the glenohumeral subluxation (GHS) group ( n = 27) or non-glenohumeral subluxation (nGHS) group ( n = 26). We found that patients with HSP may be prone to bursa effusion, rotator cuff injury, ligament injury, and cartilage injury, even though there was no significant difference between the GHS and nGHS groups. MRI revealed 14 cases of long bicipital tendon-glenoid labrum injury (51.8%) in the GHS group and 6 cases (23.1%) in the nGHS group ( p = 0.030). We also found 10 cases (37%) of glenoid labrum injury in the GHS group and 2 cases (7.7%) in the nGHS group ( p = 0.026). Eight cases (29.6%) and 1 case (3.8%) of bone marrow edema were found in the GHS and nGHS groups, respectively ( p = 0.033). Compared with painful hemiplegic shoulder patients without subluxation, patients with subluxation may be more susceptible to some injuries, such as long bicipital tendon-glenoid labrum injury, glenoid labrum injury, and bone marrow edema. During rehabilitation, physicians need to pay attention to these injuries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Zhang, Xu, Wang, Wang, Jia and Zhang.)

Polycystic ovary syndrome (PCOS) is a universal endocrine and metabolic disorder prevalent in reproductive aged women. PCOS is often accompanied with insulin resistance (IR) which is an essential pathological factor. Although there is no known cure for PCOS, cangfudaotan (CFDT) decoction is widely used for the treatment of PCOS; nevertheless, the underlying mechanism is not clear. In this study, 40 Sprague-Dawley (SD) rats (female) were randomized to 4 groups, namely the control group, PCOS group, PCOS+CFDT group, and PCOS+metformin group. The rats in the control group were fed a normal-fat diet, intraperitoneally injected with 0.5% carboxymethyl cellulose (CMC, 1 mL/kg/d) for 21 days and orally given saline (1 mL/kg/d) for the next 4 weeks. The rats in the PCOS group, PCOS+CFDT group, and PCOS+Metformin group were fed a high-fat diet (HFD) and intraperitoneally injected with letrozole (1.0 mg/kg) for 21 days. During this period, we recorded the body weight, estrous cycles, and rate of pregnancy in all rats. We also observed the ovarian ultrastructure. Blood glucose indices, serum hormones, and inflammatory factors were also recorded. Then, we detected apoptotic and mitochondrial function, and observed mitochondria in ovarian granular cells by transmission electron microscopy. We also detected genes of ASK1/JNK pathway at mRNA and protein levels. The results showed that CFDT alleviated pathohistological damnification and apoptosis in PCOS rat model. In addition, CFDT improved ovarian function, reduced inflammatory response, inhibited apoptosis of granular cells, and inhibited the operation of ASK1/JNK pathway. These findings demonstrate the occurrence of ovary mitochondrial dysfunction and granular cell apoptosis in PCOS. CFDT can relieve mitochondria-dependent apoptosis by inhibiting the ASK1/JNK pathway in PCOS rats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiang, Tai, Xiao, Zhang, Cui, Qi, Hu, Zhang, Kuang, Meng and Li.)

In this work, Gd 2 O 3 bulks were sintered at temperatures ranging from 1400 °C to 1600 °C for times from 6 h to 24 h, and their microstructure and properties were studied for a wider application of materials in thermal barrier coatings. The densification of the Gd 2 O 3 bulk reached 96.16% when it was sintered at 1600 °C for 24 h. The elastic modulus, hardness, fracture toughness and thermal conductivity of the bulks all increased with the rise in sintering temperature and extension of sintering time, while the coefficient of thermal expansion decreased. When the Gd 2 O 3 bulk was sintered at 1600 °C for 24 h, it had the greatest elastic modulus, hardness, fracture toughness and thermal conductivity of 201.15 GPa, 9.13 GPa, 15.03 MPa·m 0.5 and 2.75 W/(m·k) (at 1100 °C), respectively, as well as the smallest thermal expansion coefficients of 6.69 × 10 -6 /°C (at 1100 °C).

Solar-driven overall water splitting is an ideal way to generate renewable energy while still challenging. For the first time, this work combined covalent organic frameworks (COFs) and piezoelectric material by covalent linkages to form Z-scheme core@shell heterostructure for overall water splitting. Benefiting from the synergistic effect between the polarized electric field and photo-generated charges, as well as the precise adjustment of shell thickness, the carrier separation and utilization efficiency is greatly improved. The optimal BiFeO 3 @TpPa-1-COF photocatalyst revealed hydrogen (H 2 ) and oxygen (O 2 ) production rates of 1416.4 and 708.2 μmol h -1  g -1 under the excitation of ultrasonication coupled with light irradiation, which is the best performance among various piezo- and COF-based photocatalysts. This provides a new sight for the practical application of highly efficient photocatalytic overall water splitting., (© 2022 Wiley-VCH GmbH.)

Background: This study aimed to analyze the pathogenic characteristics of community-acquired pneumonia (CAP) in a children's hospital before and after the coronavirus disease 2019 (COVID-19) pandemic and to provide testimony for preventing CAP in the future., Methods: A retrospective analysis was performed. The information was collected from the electronic medical record system of the hospital. A total of 2739 children were included from February 1, 2019, to January 31, 2021., Results: Among these 2739 patients were 1507 (55.02%) males and 1232 (44.98%) females; the median age was 3.84 years. There were 2364 cases during the pre-COVID-19 period and 375 cases during the post-COVID-19 period. The number of hospitalized children after the pandemic was 84.14% lower. The median age after the onset was 1.5 years younger than that before the onset (4.08 years old) (Z = - 7.885, P < 0.001). After the pandemic, the proportion of CAP in school-age children and Mycoplasma pneumoniae pneumonia (MPP) and influenza virus pneumonia (IVP) decreased significantly. During the pre-COVID-19 period, the proportions of detected pathogens were as follows: MP (59.56%) > bacteria (50.42%) > viruses (29.57%) > fungi (3.43%). During the post-COVID-19 period, the pathogen proportions were bacteria (56.53%) > viruses (53.60%) > MP (23.47%) > fungi (3.73%)., Conclusions: There was a significant decrease in the number of children with CAP hospitalized after the pandemic, especially among school-age children, and the pathogen proportions of CAP with MP and IV were significantly decreased. We inferred that CAP was effectively prevented in school-age children because of the strong mitigation measures., (© 2022. The Author(s).)

Aims: Family with sequence similarity 96 member A and B (FAM96A and FAM96B) are two highly conserved homologous proteins belonging to MIP18 family. Some studies have shown that FAM96A and FAM96B are significantly down-regulated in human gastrointestinal stromal tumors, colon cancer, and liver cancer. However, the molecular mechanisms of FAM96A/B in breast cancer are unknown. This work aims to explore the roles of FAM96A/B in breast cancer progression., Main Methods: Specific siRNAs were used to down-regulate FAM96A/B expression, and recombinant plasmids were used to up-regulate FAM96A/B expression in breast cancer cells. Cell proliferation was measured using MTT and colony formation. Cell cycle and apoptosis were detected by flow cytometry. Cell migration and invasion were examined by wound healing and transwell assays. The relationships among FAM96A/B, EMT and Wnt/β-catenin pathway were determined by analyzing expression changes of classical markers., Key Findings: We found that FAM96A/B expression was down-regulated in breast cancer. FAM96A/B overexpression suppressed breast cancer cell proliferation, invasion and migration, induced cell apoptosis and caused cell cycle arrest. Conversely, FAM96A/B knockdown exhibited the opposite effects. Moreover, our data demonstrated that FAM96A/B overexpression suppressed EMT and Wnt/β-catenin pathway, while FAM96A/B knockdown showed the promoting effects on EMT and Wnt/β-catenin pathway. Furthermore, a Wnt pathway inhibitor, XAV-939 reversed the promoting effects of FAM96A/B knockdown on breast cancer progression., Significance: Our findings suggest that FAM96A/B may function as new tumor suppressor genes and inhibit breast cancer progression via modulating Wnt/β-catenin pathway, which can provide the potential markers for breast cancer diagnosis and therapy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The objective of this study was to investigate whether brain volume changes occur in patients with chronic ankle instability (CAI) using voxel-based morphometry and assessing correlations with clinical tests. Structural magnetic resonance imaging data were prospectively acquired in 24 patients with CAI and 34 healthy controls. CAI symptoms and pain intensity were assessed using the Foot and Ankle Ability Measure (FAAM), Cumberland Ankle Instability Tool (CAIT), American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and visual analog scale (VAS). The gray matter volume (GMV) of each voxel was compared between the two groups while controlling for age, sex, weight, and education level. Correlation analysis was performed to identify associations between abnormal GMV regions and the FAAM score, AOFAS score, VAS score, disease duration, and body mass index. Patients with CAI exhibited reduced GMV in the right precentral and postcentral areas, right parahippocampal area, left thalamus, left parahippocampal area, and left postcentral area compared to that of healthy controls. Furthermore, the right parahippocampal (r = 0.642, p = 0.001), left parahippocampal (r = 0.486, p = 0.016), and left postcentral areas (r = 0.521, p = 0.009) were positively correlated with disease duration. The left thalamus was positively correlated with the CAIT score and FAAM activities of daily living score (r = 0.463, p = 0.023 and r = 0.561, p = 0.004, respectively). A significant positive correlation was found between the local GMV of the right and left parahippocampal areas (r = 0.487, p = 0.016 and r = 0.763, p < 0.001, respectively) and the AOFAS score. Neural plasticity may occur in the precentral and postcentral areas, parahippocampal area, and thalamus in patients with CAI. The patterns of structural reorganization in patients with CAI may provide useful information on the neuropathological mechanisms of CAI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Xing, Chen, Zhang, Qiu, Jia, Zhang and Yu.)

Objective: To investigate the clinicopathological features of angioimmunoblastic T-cell lymphoma pattern Ⅰ (AITL Pattern Ⅰ). Methods: The clinicopathological data of 11 AITL Pattern Ⅰ cases that were diagnosed at the Beijing Friendship Hospital Affiliated to Capital Medical University (10 cases) and Beijing Lu Daopei Hospital (1 cases) from January 2019 to October 2021 were retrospectively collected. Immunophenotype, Epstein-Barr virus infection status and T cell receptor (TCR) clonality of the tumor cells were tested, and clinicopathological features of cases were analyzed. Results: Among the 11 AITL Pattern Ⅰ cases, the male to female ratio was 1.2∶1.0. The median age was 59 years (range 47-78 years). Seven cases had B symptoms, while eleven cases presented with systemic lymphadenopathy. According to Ann Arbor system staging, two cases were classified as stage Ⅰ-Ⅱ, and 9 cases as stage Ⅲ-Ⅳ. Hepatosplenomegaly was present in two cases (2/11), three cases (3/11) had skin rash and pruritus, and two cases (2/11) had pleural effusion. Previously, 6 cases (6/11) were diagnosed as reactive hyperplasia, 1 case (1/11) as EBV-associated lymphoproliferative disorder, and 4 cases (4/11) as hyperplasia of lymphoid tissue, which was unable to exclude lymphoma. Histologically, all the 11 cases showed hyperplastic follicles in the paracortical regions with well-formed germinal centers. The hyperplastic follicles showed ill-defined borders and attenuated mantle zones in 7 cases. Mantle zones completely disappeared in 4 cases. The follicles were surrounded by a thin layer of atypical lymphocytes with bright or faintly stained cytoplasm. In 2 cases, the clear cells were located between the germinal centers and the thin residual mantle cell layers, showing a circular growth pattern. The cells were medium in size, with irregular karyotype, coarse chromatin and indistinct nucleoli. Immunohistochemically, CD21 staining showed that the meshworks of follicular dendritic cells(FDC)were mainly confined to the follicles. There was a subtle expansion of the meshworks of FDC in 4 cases with ill-defined borders. The atypical cells surrounding the follicles expressed CD3 (11/11), CD4 (11/11), PD-1 (11/11), CXCL13 (6/11), ICOS (10/11) and CD10 (7/11). PD-1 staining showed a strong perifollicular pattern, and a small number of positive cells were scattered around the high endothelial veins in the interfollicular region. CXCL13, ICOS and CD10 showed similar distribution patterns. EBV-encoded small RNA probe (EBER) in situ hybridization showed that EBER positive B lymphocytes were scattered in the interfollicular region (5-20/HPF) in all cases. T cell receptor gene rearrangement was monoclonal in all cases. Conclusions: Diagnosing AITL Pattern Ⅰ may be challenging and requires comprehensive analysis of clinical manifestations, histological morphology, immunophenotype and gene rearrangement results.

Objective: We sought to observe the effectiveness and safety of multimode mechanical thrombectomy in the treatment of acute ischemic stroke., Methods: The data from patients with acute intracranial artery occlusion treated with multimode mechanical thrombectomy between November 2018 and December 2019 were collected, and the clinical features, imaging data, treatment, and clinical follow-up results 90 days after the operation were analyzed. Postoperative recanalization and the 90-day modified Rankin Scale score were used as clinically effective endpoints. The incidence of symptomatic intracranial hemorrhage within 72 hours and postoperative 90-day mortality were used to evaluate safety., Results: A total of 70 patients were enrolled, including 18 cases with bridging treatment, 11 cases with stent implantation, and 10 cases with balloon dilatation. During the 90 days of follow-up after surgery, 35.7% of (25/70) patients had a good prognosis (modified Rankin Scale score of 0-2). The incidence of postoperative symptomatic intracranial hemorrhage was 11.4% (8/70), and postoperative mortality was 34.3% (24/70). The onset-to-puncture time in the good-prognosis group and the poor-prognosis group was 270 (225-345) versus 330 (270-420) minutes, respectively, and the onset-to-recanalization time in the 2 groups was 350 (295-405) versus 410 (340-470) minutes, respectively. Successful recanalization in the good-prognosis group and the poor-prognosis group was 96.0% versus 57.8%, respectively, and the incidence of symptomatic intracranial hemorrhage in the 2 groups was 0% versus 17.8%, respectively. The difference between the 2 groups was statistically significant (P < 0.05)., Conclusions: Multimode mechanical thrombectomy is a safe and effective therapy for the intracranial occlusion of large vessels in patients with acute ischemic stroke., (Copyright © 2022 Elsevier Inc. All rights reserved.)

QR code based visual encryption schemes are still relatively rare, and the existing schemes are mainly implemented by averaging grayscale maps. They become distorted when recovering complex secret images. In this paper, we propose a visual cryptography scheme based on QR codes. We use two adaptive schemes to improve the distortion problem in secret image recovery. The algorithm for generating the QR code shared matrix is improved, and the secret image can be restored quickly. This scheme could ensure the uniform distribution of secret vectors. Meanwhile individual shared QR codes would never reveal any secret information. The proposed algorithm reduces the space consumed by the secret vector and the probability of falling prey to illegal attacks. Compared with other schemes, the secret image recovered via the proposed method is clearer and the scheme is suitable for scenarios in which the secret images are more complex, as it yields better security and practicality.

Study Objective: Emergence delirium is a common complication in preschool children after general anesthesia and may result in undesirable complications. This study aimed to determine whether breathing training after watching an informative video during the pre-operative visit could reduce the incidence of emergence delirium in preschool children after otorhinolaryngologic surgery under general anesthesia., Design: A single-center, double-blinded, randomized controlled trial., Setting: Perioperative care., Patients: A total of 170 children undergoing otorhinolaryngologic surgery, aged 3-7 years, ASA physical status I or II were involved., Interventions: Patients were randomized to receive breathing training during the pre-operative visit (Training group) or to receive pre-operative visit only (Control group) the day before surgery., Measurements: Emergence delirium was measured by the Pediatric Anesthesia Emergence Delirium score during the anesthesia recovery time. Data regarding extubation time and post-anesthesia care unit stay time were collected., Main Results: Children who received breathing training during the pre-operative visit had a significantly lower incidence of emergence delirium than those who only underwent the pre-operative visit (10.4% vs. 35.1%, P < 0.001). The awakening time score and the maximum score in the post-anesthesia care unit were significantly lower in the training group compared with the control group [4.4 ± 3.4 vs. 6.9 ± 4.2, P < 0.001 and 5.0 (5.0) vs 7.0 (7.0), P = 0.001, respectively]. We found no differences in the extubation time and post-anesthesia care unit stay time between groups., Conclusions: We concluded that breathing training based on video learning during the pre-operative visit in preschool children undergoing otorhinolaryngologic surgery could significantly decrease the incidence of emergence delirium., Trial Registration: Chinese Clinical Trial Registry (Reference number: ChiCTR1900026162); registered on September 24, 2019., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To examine whether an abdominal-based early progressive mobilisation program improves gastric motility and reduces feeding intolerance in critically ill patients with endotracheal intubation., Design and Methods: A randomised controlled trial was designed. Adult patients admitted to the intensive care unit who were intubated and had an order for enteral nutrition were randomly assigned to partake in an three stages of abdominal-based progressive mobilisation program (passive abdominal massage, bed-side bicycle and ambulating) or standard of care. Gastric antral motility was measured by bedside ultrasound., Results: A total of 83 critically ill patients were included in the study. The intervention group displayed a statistically significant improvement in the antral motility index than the control group (p < .001), as well as in complications of feeding intolerance, including the incidence of abdominal distention (9.8% vs 33.3%, p = .009), vomiting (0% vs 16.7%, p = .019) and diarrhoea (22% vs 50%, p = .008). However, no significant difference for the full enteral feeding rate on the third day was observed between the groups.Furthermore, time on mechanical ventilation (4.52 ± 2.77 days vs 6.24 ± 3.90 days, p = .023) was shorter in intervention group, but no significant difference of length of intensive care unit stay was observed between the groups., Conclusions: Implementation of an abdominal-based early progressive mobilisation program can improve gastric motility and feeding intolerance in critically ill patients with an endotracheal tube., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: To identify the role and mechanism of a male specific gene, SRY, in I/R-induced hepatic injury., Background: Males are more vulnerable to I/R injury than females. However, the mechanism of these sex-based differences remains poorly defined., Methods: Clinicopathologic data of patients who underwent hepatic resection were identified from an international multi-institutional database. Liver specific SRY TG mice were generated, and subjected to I/R insult with their littermate WT controls in vivo. In vitro experiments were performed by treating primary hepatocytes from TG and WT mice with hypoxia/reoxygen-ation stimulation., Results: Clinical data showed that postoperative aminotransferase level, incidence of overall morbidity and liver failure were markedly higher among 1267 male versus 508 female patients who underwent hepatic resection. SRY was dramatically upregulated during hepatic I/R injury. Overexpression of SRY in male TG mice and ectopic expression of SRY in female TG mice exacerbated liver I/R injury compared with WTs as manifested by increased inflammatory reaction, oxidative stress and cell death in vivo and in vitro. Mechanistically, SRY interacts with Glycogen synthase kinase-3β (GSK-3β) and β-catenin, and promotes phosphorylation and degradation of β-catenin, leading to suppression of the downstream FOXOs, and activation of NF-κBand TLR4 signaling. Furthermore, activation of β-catenin almost completely reversed the SRYoverexpression-mediated exacerbation of hepatic I/R damage., Conclusions: SRY is a novel hepatic I/R mediator that promotes hepatic inflammatory reaction, oxidative stress and cell necrosis via inhibiting Wnt/β-catenin signaling, which accounts for the sex-based disparity in hepatic I/R injuries., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Neurological complications significantly affect the short-and long-term outcomes of patients with extracorporeal membrane oxygenation (ECMO). With the increasing application of ECMO, more and more attention has been paid to the neuromonitoring in ECMO patients. Although many neuromonitoring approaches have already been used clinically, the sensitivity and specificity utilizing one single neuromonitoring assessment to predict brain injury is still insufficient. Therefore, multidisciplinary experts in critical care medicine and extracorporeal life support organization advocate that multimodal monitoring (MMM) should be applied to improve the sensitivity and specificity of monitoring the occurrence of acute brain injury in patients with ECMO. With timely and appropriate intervention, the prognosis of patients with ECMO may be improved. However, there is still a lack of standardized implementation procedures for MMM, which needs further efforts. With continuous verification and improvement in multi-clinical centers, the standardized MMM procedures could be transformed into correct treatment decisions, thus to improve the outcomes of patients with ECMO.

Objective: This study aims to identify the risk factors associated with short stature in children born small for gestational age (SGA) at full-term., Methods: This was a retrospective study. The subjects were full-term SGA infants who were followed up until the age of 2 years. The risk factors for short stature were identified with univariate and multivariate analyses., Results: Of 456 full-term SGA children enrolled in this study, 28 cases had short stature at 2 years of age. A significant decrease in placental perfusion was found in the short children group with intravoxel incoherent motion (IVIM) technology, which was an advanced bi-exponential diffusion-weighted imaging (DWI) model of magnetic resonance imaging (MRI) ( p = 0.012). Compared to non-short children born SGA at full-term, the short children group underwent an incomplete catch-up growth. Mothers who suffered from systemic lupus erythematosus were more likely to have a short child born SGA ( p = 0.023). The morbidity of giant placental chorioangioma was higher in the short children group. The pulsatility index (PI), resistivity index (RI), and systolic-diastolic (S/D) ratio of umbilical artery were higher in the short children group than in the non-short control group ( p = 0.042, 0.041, and 0.043). Multivariate analysis demonstrated that decrease of perfusion fraction ( f p ) in IVIM of placental MRI, chromosomal abnormalities, short parental height, and absence of catch-up growth were associated with a higher risk of short stature in children born SGA at full-term., Conclusion: Risk factors for short stature in full-term SGA children at 2 years of age included a decrease of perfusion fraction f p in IVIM of placental MRI, chromosomal abnormalities, and short parental height., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ling, Chen, Zhang, Pan, Gong, Zhang, Zhao, Chen, Cui and Lu.)

Critical ultrasonography is widely used in ICU and has become an indispensable tool for clinicians. However, besides operator-dependency of critical ultrasonography, lack of standardized training mainly result in the physicians' heterogenous ultrasonic skill. Therefore, standardized training as well as strict quality control plays the key role in the development of critical ultrasonography. We present this quality control standards to promote better development of critical ultrasonography.

Objective: To observe the efficacy and prognosis of cladribine (2-CdA) combined with cytarabine (Ara-C) regimen in the treatment of relapsed refractory Langerhans cell histiocytosis (LCH) in children., Methods: Nine patients with relapsed refractory LCH treated with the 2-CdA combined with Ara-C regimen in the Department of Hematology and Oncology of Wuhan Children's Hospital from July 2014 to February 2020 were retrospectively analyzed, and the efficacy and disease status were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009) and the Disease Activity Score (DAS), the drug toxicity were evaluated according to the World Health Organization（WHO） grading criteria for chemotherapy. All patients were followed up for survival status and disease-related sequelae., Results: Before the treatment combining 2-CdA and Ara-C, 7 of 9 patients were evaluated as active disease worse (ADW), and 2 as active disease stable (ADS) with a median disease activity score of 8 (4-15). Of 9 patients, 6 cases achieved non active disease (NAD) and 3 achieved active disease better (ADB) with a median disease activity score of 0 (0 to 5) after 2-6 courses of therapy. All 9 patients experienced WHO grade IV hematologic toxicity and 3 patients had hepatobiliary adverse effects (WHO grade I～II) after treatment. The median follow-up time was 31(1 to 50) months with all 9 patients survived, 3 of the 9 patients experienced sequelae to the disease with 2 combined liver cirrhosis as well as cholestatic hepatitis and 1 with oral desmopressin acetate tablets for diabetes insipidus., Conclusion: 2-CdA combined with Ara-C is an effective regimen for the treatment of recurrent refractory LCH in children, and the main adverse effect is hematologic toxicity, which is mostly tolerated in children. Early treatment with this regimen may be considered for patients with multisystem LCH with risky organ involvement who have failed first-line therapy and for patients with relapse.

Objective: To analyze the incidence and risk factors of otologic disorders in patients with Turner syndrome (TS), so as to provide management strategies for ear health. Methods: This study is a prospective study based on questionnaires and a cross-sectional study. The TS patients who visited our hospital from 2010 January to 2021 March were included (A total of 71 patients with TS were included in this study. the age of TS diagnosed was 3- to 11-year-old, age of visiting ENT department was 4- to 27-year-old) and the incidence of otologic diseases in different age groups was investigated by questionnaires. The cross-sectional study included ear morphology and auditory function assessment, and further analysis of the risk factors that related to ear disease. Prism was used for data analysis. Results: The investigation found that the incidence of acute otitis media in patients aged 3-6 and 7-12 years was higher than that of patients over 12 years old, which was 33.8%(24/71), 42.9%(30/70)and 23.5%(8/34), respectively; 21.1% (15/71) of patients were recurrent acute otitis media in patients aged 3-6 years, and about 46.6% (7/15)of them persisted beyond 6-year. The prevalence of otitis media with effusion in the three groups was 32.4%(23/71), 34.3%(24/70)and 38.2%(13/34), respectively; the recurrence rate of tympanocentesis was 100%(7/7), 42.9%(3/7)and 50.0%(1/2), which was significantly higher than that of grommet insertion. For age groups of 3-6 and 7-12 years, the prevalence of acute otitis media and secretory otitis media was lower in the X chromosome structure abnormal patients; while for patients older than 12 years, otitis media with effusion was the highest prevalence in Y-chromosome-containing karyotypes. In addition, the prevalence of acute otitis media and otitis media with effusion in patients with other system diseases were increased significantly. A cross-sectional study found that 7.0% (5/71)of the lower auricular, 4.2% (3/71)of the external auditory canal narrow, and 38.0% (27/71)of the tympanic membrane abnormality. 35.2%(25/71) had abnormal hearing, including 17 cases of conductive deafness, 6 cases of sensorineural hearing loss, and 2 cases of mixed deafness. The rest of the patients had normal hearing, but 6 of them had abnormalities in otoacoustic emission. Eustachian tube function assessment found that the eustachian tube dysfunction accounted for 38%(27/71). Hearing loss and abnormal Eustachian tube function were not significantly related to karyotype(Chi-square 2.83 and 2.84, P value 0.418 and 0.417), but significantly related to other system diseases(Chi-square 13.43 and 7.53, P value<0.001). Conclusions: The incidence of TS-related otitis media and auditory dysfunction is significantly higher than that of the general population. It not only occurs in preschool girls, but also persists or develops after school age. Accompanied by other system diseases are risk factors for ear diseases. Clinicians should raise their awareness of TS-related ear diseases and incorporate ear health monitoring into routine diagnosis and treatment.

Objective: The purpose of this study was to investigate the effects of different durations of static progressive stretching (SPS) on posttraumatic knee contracture in rats, including range of motion (ROM), gait analysis, myofibroblast proliferation, and collagen regulation., Methods: The posttraumatic knee contracture model was established, and male Wistar rats were randomly divided into the 20-minute SPS treatment, 30-minute SPS treatment (S30), 40-minute SPS treatment, untreated, immobilization, and control groups. At Week 1, 2, and 4 of treatment intervention, joint ROM and gait were measured and compared. Knee joint samples stained with hematoxylin and eosin and Masson trichrome were used to observe alterations in pathological structures. Collagen density and cell numbers in the posterior joint capsule were used to assess joint capsule fibrosis and inflammation. Immunohistochemistry was used to detect type I collagen and α-smooth muscle actin expression., Results: The S30 group improved the most; ROM, stance, mean intensity, print area, and stride length were 115 (SD = 5) degrees, 0.423 (SD = 0.074) seconds, 156.020 (SD = 7.952), 2.116 (SD = 0.078) cm2, and 11.758 (SD = 0.548) cm, respectively. The numbers of myofibroblasts, fibroblasts, and inflammatory cells decreased, and collagen proliferation was significantly suppressed in the S30 group compared with the other groups., Conclusion: S30 significantly improved posttraumatic knee contracture in rats, with reduced type I collagen and α-smooth muscle actin expression, decreased the numbers of myofibroblasts and inflammatory cells, suppressed fibrotic and inflammatory changes in the joint capsule, and increased joint mobility. This study provided basic evidence for an optimal standard-of-care treatment approach for posttraumatic knee joint contracture in rats, which may have significance for humans., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A modulated structure with symmetrical characteristic higher than three-dimensional is a fascinating crystallographic type, and it is randomly encountered by researchers. Herein, we prepared 0.1 mm level single crystals of Na 3 La(VO 4 ) 2 and determined its structure to be a (3 + 1)-dimensional modulated structure using the X-ray diffraction analysis method for single crystals. Its super space group was determined to be Pca 2 1 (0β0)000. On the other hand, we introduced Tb 3+ into the Na 3 La(VO 4 ) 2 host lattice to fabricate phosphors Na 3 La 1- x (VO 4 ) 2 : x Tb 3+ and studied their photoluminescence properties. Interestingly, for the strong absorption of the Na 3 La(VO 4 ) 2 host lattice in the range of 200-400 nm, the traditional 330-385 nm light is unable to efficiently excite Tb 3+ ions in the Na 3 La(VO 4 ) 2 host to generate luminescence of Tb 3+ . Instead, Na 3 La 1- x (VO 4 ) 2 : x Tb 3+ is suitable to be excited by 487 nm to generate emitting light at 543, 584, and 622 nm, due to Tb 3+ characteristic 4f → 4f transitions of 5 D 4 → 7 F J ( J = 5, 4, 3). Hence, the Tb 3+ -doped Na 3 La(VO 4 ) 2 phosphors have potential applications for white-light-emitting diodes.

The present study was aimed to explore the involvement of dopamine D1 receptor of the anterior cingulate cortex (ACC) in the regulation of chronic inflammatory pain-related emotion. On the first day, the rats were acclimated to the environment and the baseline indices were measured. On the second day, the rats were administered with the dopamine D1 receptor antagonist SCH-23390 or agonist SKF38393 in the ACC, and then they were subcutaneously injected with complete Freund's adjuvant (CFA, 0.08 mL) in the left hind paw to establish conditioned place avoidance (CPA) response after pairing with specific environment. On the third day, the CPA response and the firing frequency of ACC neurons were observed synchronously, and the open-field behavior, mechanical pain behavior and paw withdrawal latency (PWL) tests were also observed subsequently. In other experiments, rats were given subcutaneous injection of normal saline (NS) on the left hind paw after SCH-23390 or SKF-38393 was administered in the ACC, and then the same observations were performed. The results showed that: (1) Compared with the control group, the PWL and mechanical pain thresholds of rats injected with CFA on the left hind paw were significantly decreased (P < 0.05); (2) The residence time of rats injected with CFA in the "pain environment" and open field center was significantly shortened (P < 0.05); (3) Pre-injection of antagonist SCH-23390 in ACC (10 μg) alleviated the anxiety-like negative behavior response induced by CFA (P < 0.05) and reversed CFA-induced increases of discharge frequency of ACC neurons (P < 0.05); (4) Pre-injection of agonist SKF-38393 in the ACC (10 μg) induced CPA-like behavioral response in rats injected with NS in the left hind paw, and increased the firing frequency of ACC neurons (P < 0.05); (5) Immunofluorescence detection showed that dopamine D1 receptor and NMDA receptor were co-expressed in the same neuron. These results suggest that inhibition of dopamine D1 receptor in ACC can alleviate the negative emotional response induced by persistent pain.

Bisulfite and hydrazine are harmful to the environment safety and human health. Therefore, it is of great value to develop a smart fluorescent probe with high selectivity for detection of bisulfite and hydrazine. In our report, a dual-response fluorescent probe EDBI with high selectivity, rapid response, and low detection limit for discriminative determination HSO 3 - and N 2 H 4 was exploited. The probe EDBI is capable of distinctive sensing HSO 3 - and N 2 H 4 based on nucleophilic addition reactions by taking advantage of ratiometric fluorescence and fluorescence "on-off" mode, respectively. The dual-responses behaviors of probe EDBI toward HSO 3 - and N 2 H 4 were attribute to different reaction sites, which it has been confirmed by HRMS. More importantly, cytotoxicity experiment authenticated that probe possesses low toxicity and good penetration. The probe EDBI with excellent performance, it was successfully employed to distinguishable sense HSO 3 - and N 2 H 4 in living cells by diverse channel patterns. Therefore, this simple dual-response fluorescence probe is expected to be used for real-time monitoring bisulfite and hydrazine in biological samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Paraneoplastic neurological syndrome (PNS) is a nonmetastatic complication of malignant tumors that may lead to immune-mediated neuronal dysfunction or death. The occurrence of PNS results from the binding of anti-neuronal antibodies to neuronal cell surface antigens or intracellular antigens, which hinders the function of target proteins and promotes cell death. The aim of this study is to research the effect and immune mechanism of the neuronal ELAV-like protein (HuD antibody) on PNS-related syndrome. Neuronal cells were co-cultured with monocyte macrophages with or without HuD antibody. Next, we detected the apoptosis of neuronal cells by flow cytometry. Meantime, macrophage M1/M2 polarization factors and the secretion of inflammatory factors in the co-culture system were also detected by quantitative polymerase chain reaction (qPCR), Western blots and ELISA technologies. The results showed that after adding the HuD antibody in the co-culture system, the apoptosis level of the neuroma cells were significantly increased, and the apoptosis level were not significant changed when co-culture with monocytes without HuD antibody. In addition, the level of factors of M1 macrophages TNF-α, IL-12, TGF-β and IFN-γ increased, while the level of factors of M2 macrophages IL-10, IL-4, and Arg-1 decreased. The outcomes demonstrated that absorption of the HuD antibody by cerebellar neuronal cells could promote the proliferation of M1 macrophages and stimulates macrophages to secrete inflammatory factors, further damage the neuronal cells, eventually resulting in the occurrence of PNS. This finding provided a theoretical basis for the subsequent treatment and prevention of PNS.

In the summer of 2019, field measurements of ozone (O 3 ) and its precursors[volatile organic compounds (VOCs) and nitrogen oxides (NO x )] were carried out at an urban site in Ji'nan. We found that the daily maximum 8-hour averages φ (O 3 ) were (103.0±14.5)×10 -9 . The average φ (NO x ) and φ (VOCs), which are ozone precursors, were (16.7±11.3)×10 -9 and (22.4±9.4)×10 -9 , respectively. The ·OH reactivity of VOCs was determined (9.6±3.8) s -1 . Ji'nan suffered from serious O 3 pollution. An observation-constrained chemical box model was deployed to evaluate in situ photochemical O 3 production, which indicated that chemical reactions made positive contributions to O 3 production rates between 07:00 and 19:00 LT, with the average hourly O 3 production rate of 35.6×10 -9 h -1 . To evaluate the effectiveness of various ozone precursor control strategies in reducing ozone pollution, we combined the observation-based model (OBM) with the relative incremental reactivity (RIR) method. The key indicators that affect the local ozone production rate were identified. Ji'nan was under VOC-limited conditions and the key VOC precursors were alkenes. The O 3 formation mechanism changed from the VOC-limited regime in the morning to the transitional regime in the afternoon. Correspondingly, the simulated local O 3 production rate was increased from 18.3×10 -9 h -1 to 29.6×10 -9 h -1 . To further explore the role of anthropogenic emissions in ozone pollution, we used the positive matrix factorization (PMF) model to identify the major sources contributing to VOCs. The major sources in Ji'nan were vehicular exhaust and gasoline evaporation, accounting for more than 50% of the observed VOCs. Therefore, constraints on vehicular emissions is the most effective strategy to control O 3 pollution in Ji'nan.

TRK-fused gene (TFG) is known to be involved in protein secretion and plays essential roles in an antiviral innate immune response. However, its function in LPS-induced inflammation and pyroptotic cell death is still unknown. Here, we reported that TFG promotes the stabilization of Unc-51 like autophagy activating kinase (ULK1) and participates in LPS plus nigericin (Ng) induced pyroptotic cell death. Our results showed that TFG-deficient THP-1 macrophages exhibit higher mitochondrial ROS production. LPS/Ng stimulation triggers a much higher level of ROS and induces pyroptotic cell death. ULK1 undergoes a rapid turnover in TFG-deficient THP-1 cells. TFG forms complex with an E3 ligase, tumor necrosis factor receptor-associated factor 3 (TRAF3), and stabilizes ULK1 via disturbing ULK1-TRAF3 interaction. Knockdown of TFG facilitates the interaction of ULK1 with TRAF3 and subsequent K48-linked ULK1 ubiquitination and proteasome degradation. Rescue of ULK1 expression blocks LPS/Ng-induced cell death in TFG-deficient THP-1 macrophages. Taken together, TFG plays an essential role in LPS/Ng-induced pyroptotic cell death via regulating K48-linked ULK1 ubiquitination in macrophages., (© 2022. The Author(s).)

Objective: To analyze the prenatal diagnosis results and pregnancy outcomes of conotruncal defects (CTD) fetuses, and to explore the correlation between the CTD and chromosome diseases. Methods: A total of 297 cases of invasive prenatal diagnosis and chromosome analysis were collected at the Prenatal Diagnosis Center of Guangzhou Women and Children's Medical Center due to CTD from January 1st, 2011 to December 31th, 2019. According to ultrasonic diagnosis, CTD fetuses were divided into 6 subtypes: tetralogy of Fallot (109 cases), pulmonary atresia (30 cases), transposition of the great arteries (77 cases), double outlet right ventricle (53 cases), truncus arteriosus (14 cases) and interrupted aortic arch (14 cases). According to whether they were combined with intracardiac or extracardiac abnormalities, they were divided into simple group (134 cases), combined with other intracardiac abnormalities group (86 cases), combined with extracardiac abnormalities group (20 cases), combined with intracardiac and extracardiac abnormalities group (37 cases) and only combined with ultrasound soft marker group (20 cases), the last 4 groups were referred as non-simple types. The chromosome test results and pregnancy outcomes of each type and group were analyzed retrospectively. Results: Among the 297 CTD fetuses, the chromosome abnormality rate was 17.5% (52/297). There were 21 cases of abnormal chromosome number, 28 cases of pathogenetic copy number variantions and 3 cases of mosaics. All the 19 cases of micropathogenic fragments smaller than 5 Mb were detected by chromosomal microarray analysis (CMA). Among all the subtypes of CTD, the chromosomal abnormality rate of truncus arteriosus was the highest, at 7/14; while the rate of transposition of the great arteries was the lowest, at 5.2% (4/77). There were significant differences in the rate of chromosomal abnormalities between simple and non-simple types [10.4% (14/134) vs 23.3% (38/163); χ ² = 8.428, P =0.004]. In each group, the chromosomal abnormality rate was the highest in the combined with intracardiac and extracardiac abnormalities group, at 37.8% (14/37), and the lowest in the simple group, at 10.4% (14/134). There was no significant difference in the rate of chromosomal abnormalities in all subtypes of simple group (all P >0.05). Among 112 cases of live birth, 1 case was 22q11.2 microdeletion syndrome, 5 cases of postnatal clinical diagnosis and prenatal ultrasound diagnosis were not completely consistent, 5 cases died after birth. Conclusions: The incidence of chromosomal abnormalities is high in fetuses with CTD. CTD fetuses with concurrent extrapardiac malformations are more likely to incorporate chromosomal abnormalities. CMA technology could be used as a first-line genetic detection method for CTD. After excluding chromosomal abnormalities, most of the children with CTD have good prognosis.