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Abstract Aims The H2FPEF score is a convenient risk stratification tool for diagnosing heart failure with preserved ejection fraction (HFpEF). This study examined the value of the H2FPEF score for predicting all‐cause mortality and rehospitalization in HFpEF patients. Methods and results This was a retrospective cohort study of patients diagnosed with HFpEF by echocardiography at a single tertiary centre between 1 January 2015 and 30 April 2018. According to the H2FPEF score, the subjects were divided into low (0–1 points), intermediate (2–5 points), and high (6–9 points) score groups. The primary outcomes were all‐cause mortality and rehospitalization. A total of 476 patients (mean age: 70.5 ± 8.4 years, 60.7% female) were included. Of these, 47 (9.9%), 262 (55.0%), and 167 (35.1%) were classified into the low, intermediate, and high score groups, respectively. Over a mean follow‐up of 27.5 months, 63 patients (13.2%) died, and 311 patients (65.3%) were rehospitalized. The mortality rates were 3 (6.4%), 29 (11.1%), and 31 (18.6%), and the number of patients with rehospitalization was 28 (59.6%), 159 (60.7%), and 124 (74.3%) for the low, intermediate, and high score groups, respectively. Multivariate Cox regression identified H2FPEF score as an independent predictor of all‐cause mortality (hazard ratio [HR]: 1.46, 95% CI: 1.23–1.73, P

Abstract This study aimed to observe the safety and clinical efficacy of early application of ruxolitinib to prevent acute graft-versus-host disease (aGVHD) after alternative donor transplantation in acute leukemia. There were 57 patients undergoing allo-HSCT at the Affiliated Cancer Hospital of Zhengzhou University from July 2017 to October 2019. They were divided into control(16 patients) and ruxolitinib (41 patients) groups. For aGVHD prophylaxis, the control group received post-transplantation cyclophosphamide, antithymocyte globulin-Fresenius, cyclosporine A, and mycophenolate mofetil, while in the ruxolitinib group, ruxolitinib 5 mg/d in adults or 0.07–0.1 mg/(kg d) in children was administered from the day of neutrophil engraftment to 100 days post-transplantation based on control group. We found 55 patients had successful reconstitution of hematopoiesis; No significant difference was found in cGVHD, hemorrhagic cystitis, pulmonary infection, intestinal infection, Epstein-Barr virus infection, cytomegalovirus infection, relapse, death, and nonrelapse mortality. The incidences of aGVHD (50 vs. 22%, P = 0.046) and grade II–IV aGVHD (42.9 vs. 12.2%, P = 0.013) were significantly higher in the control group than in the ruxolitinib group. No significant differences were observed in overall survival (P = 0.514), disease-free survival (P = 0.691), and cumulative platelet transfusion within 100 days post-transplantation between two groups. This suggests early application of ruxolitinib can reduce the incidence and severity of aGVHD and patients are well tolerated.

Abstract The widespread use of nanomaterials (NMs) has raised concerns that exposure to them may introduce potential risks to the human body and environment. The liver is the main target organ for NMs. Hepatotoxic effects caused by NMs have been observed in recent studies but have not been linked to liver disease, and the intrinsic mechanisms are poorly elucidated. Additionally, NMs exhibit varied toxicokinetics and induce enhanced toxic effects in susceptible livers; however, thus far, this issue has not been thoroughly reviewed. This review provides an overview of the toxicokinetics of NMs. We highlight the possibility that NMs induce hepatic diseases, including nonalcoholic steatohepatitis (NASH), fibrosis, liver cancer, and metabolic disorders, and explore the underlying intrinsic mechanisms. Additionally, NM toxicokinetics and the potential induced risks in the livers of susceptible individuals, including subjects with liver disease, obese individuals, aging individuals and individuals of both sexes, are summarized. To understand how NM type affect their toxicity, the influences of the physicochemical and morphological (PCM) properties of NMs on their toxicokinetics and toxicity are also explored. This review provides guidance for further toxicological studies on NMs and will be important for the further development of NMs for applications in various fields.

CD4+ T cells differentiate towards different subpopulations through the regulation of lineage-specific cytokines and transcription factors, which flexibly respond to various immune challenges. However, considerable work has demonstrated that the CD4+ T-cell differentiation mechanism is complex and not limited to transcription factors and cytokines. Long noncoding RNAs (lncRNAs) are RNA molecules with lengths exceeding 200 base pairs that regulate various biological processes and genes. LncRNAs have been found to conciliate the plasticity of CD4+ T-cell differentiation. Then, we focused on lncRNAs involved in CD4+ T-cell differentiation and enlisted some molecular thought into the plasticity and functional heterogeneity of CD4+ T cells. Furthermore, elucidating how lncRNAs modulate CD4+ T-cell differentiation in disparate immune diseases may provide a basis for the pathological mechanism of immune-mediated diseases.

The cytochrome c oxidase 20 (COX20) gene encodes a protein with a crucial role in the assembly of mitochondrial complex IV (CIV). Mutations in this gene can result in ataxia and muscle hypotonia. However, ophthalmoplegia and visual failure associated with COX20 mutation have not been examined previously. Moreover, the mechanism causing the phenotype of patients with COX20 variants to differ from that of patients with mutations in other genes impairing CIV assembly is unclear. In this investigation, the aim was to assess the relation between COX20 variants and CIV assembly. We performed detailed clinical, physical, and biochemical investigations of affected individuals. Western blotting, reverse transcription-polymerase chain reaction, and blue native-polyacrylamide gel electrophoresis were used to analyze the expression level of COX20 and oxidative phosphorylation. A Seahorse XF Cell Mito Stress Test and enzymatic activity analysis were performed to evaluate mitochondrial function. Whole-exome sequencing revealed the same compound heterozygous mutations (c.41A > G and c.222G > T, NM_198076) in COX20 in two siblings. This is the first description of ophthalmoplegia and visual failure associated with COX20 variants. In vitro analysis confirmed that the COX20 protein level was significantly decreased, impairing the assembly and activity of CIV in patients' fibroblast. Overexpression of COX20 using a transduced adenovirus partially restored the function of the patients' fibroblasts. Early-onset complex movement disorders may be closely related to COX20 variants. Our results broaden the clinical phenotypes of patients with COX20 variants showing ophthalmoplegia and visual failure. Additionally, dysfunction of COX20 protein can impair the assembly and activity of CIV.

Terrestrial vegetation is the largest contributor of isoprenoids (a group of biogenic volatile organic compounds (BVOCs)) to the atmosphere. BVOC emission data comes mostly from temperate regions, and less is known about BVOC emissions from tropical vegetation, even though it is estimated to be responsible for >70% of BVOC emissions. This review summarizes the available data and our current understanding of isoprenoid emissions from tropical plant species and the spatial and temporal variation in emissions, which are strongly species-specific and regionally variable. Emission models lacking foliar level data for tropical species need to revise their parameters to account for seasonal and diurnal variation due to differences in dependencies on temperature and light of emissions from plants in other ecosystems. More experimental information and determining how emission capacity varies during foliar development are warranted to account for seasonal variations more explicitly.

Summary: Fusobacterium nucleatum (Fn) is primarily colonized in the oral cavity. Recently, Fn has been closely associated with the tumorigenesis of colorectal cancer (CRC). Here, we showed that the relative level of Fn DNA was increased in the saliva of the CRC group compared with the normal colonoscopy, hyperplastic polyp, and adenoma groups. Receiver operating characteristic curve analysis illustrated that Fn DNA was superior to carcinoembryonic antigen and carbohydrate antigen 19-9 in CRC diagnosis. Moreover, levels of Fn DNA were associated with the overall survival and disease-free survival of CRC patients, which was an independent factor for prognostic prediction. Transcriptome sequencing identified 1,287 differentially expressed mRNAs in tumor tissues between CRC patients with high-Fn and low-Fn infection. Kyoto encyclopedia of genes and genomes analysis showed that ECM-receptor interaction and focal adhesion were the top two significant pathways. Overall, salivary Fn DNA may be a noninvasive diagnostic and prognostic biomarker for CRC patients.

Abstract The occurrence and development of insulin resistance (IR) are usually related to the change of gut microbiota. Our previous study showed that arabinogalactan (AG) could selectively increase the relative abundance of Bifidobacterium longum and Faecalibacterium prausnitzii in in vitro fermentation. However, their effect on IR remains unclear. In the current study, we investigated the effects of AG, B. longum, F. prausnitzii and their combinations on insulin‐resistant mice. Intake of AG and those two strains reduced the body weight, fat accumulation, and homeostasis model assessment of IR of the mice with IR, and decreased the level of serum glucose, insulin, and lipids. Meanwhile, they could alleviate the injury of the liver. Moreover, AG, B. longum, and F. prausnitzii regulated the production of short‐chain fatty acids and elevated the abundance of gut probiotics such as Lactobacillus, Lactococcus, and Bifidobacterium. However, the effect of giving only AG or a single strain was weaker than the combination of AG, B. longum, and F. prausnitzii. Our study attempted to find a new way to prevent the development of type 2 diabetes in the early stage and provided evidence for new therapy against IR with a combination of prebiotics and two bacterial strains of gut origin.

Abstract Background Dental pulp stem cells (DPSCs) are a promising cell source in endodontic regeneration and tissue engineering with limited self-renewal and pluripotency capacity. N 6-methyladenosine (m6A) is the most prevalent, reversible internal modification in RNAs associated with stem cell fate determination. In this study, we aim to explore the biological effect of m6A methylation in DPSCs. Methods m6A immunoprecipitation with deep sequencing (m6A RIP-seq) demonstrated the features of m6A modifications in DPSC transcriptome. Lentiviral vectors were constructed to knockdown or overexpress methyltransferase like 3 (METTL3). Cell morphology, viability, senescence, and apoptosis were analyzed by β-galactosidase, TUNEL staining, and flow cytometry. Bioinformatic analysis combing m6A RIP and shMETTL3 RNA-seq functionally enriched overlapped genes and screened target of METTL3. Cell cycle distributions were assayed by flow cytometry, and m6A RIP-qPCR was used to confirm METTL3-mediated m6A methylation. Results Here, m6A peak distribution, binding area, and motif in DPSCs were first revealed by m6A RIP-seq. We also found a relatively high expression level of METTL3 in immature DPSCs with superior regenerative potential and METTL3 knockdown induced cell apoptosis and senescence. A conjoint analysis of m6A RIP and RNA sequencing showed METTL3 depletion associated with cell cycle, mitosis, and alteration of METTL3 resulted in cell cycle arrest. Furthermore, the protein interaction network of differentially expressed genes identified Polo-like kinase 1 (PLK1), a critical cycle modulator, as the target of METTL3-mediated m6A methylation in DPSCs. Conclusions These results revealed m6A methylated hallmarks in DPSCs and a regulatory role of METTL3 in cell cycle control. Our study shed light on therapeutic approaches in vital pulp therapy and served new insight into stem cell-based tissue engineering.

Abstract Attention-deficit/hyperactivity disorder (ADHD) affects 5% of children world-wide. Of these, two-thirds continue to have impairing symptoms of ADHD into adulthood. Although a large literature implicates structural brain differences of the disorder, it is not clear if adults with ADHD have similar neuroanatomical differences as those seen in children with recent reports from the large ENIGMA-ADHD consortium finding structural differences for children but not for adults. This paper uses deep learning neural network classification models to determine if there are neuroanatomical changes in the brains of children with ADHD that are also observed for adult ADHD, and vice versa. We found that structural MRI data can significantly separate ADHD from control participants for both children and adults. Consistent with the prior reports from ENIGMA-ADHD, prediction performance and effect sizes were better for the child than the adult samples. The model trained on adult samples significantly predicted ADHD in the child sample, suggesting that our model learned anatomical features that are common to ADHD in childhood and adulthood. These results support the continuity of ADHD’s brain differences from childhood to adulthood. In addition, our work demonstrates a novel use of neural network classification models to test hypotheses about developmental continuity.

Abstract Background Acute myeloid leukemia (AML) is biologically heterogeneous diseases with adverse prognosis. This study was conducted to find prognostic biomarkers that could effectively classify AML patients and provide guidance for treatment decision making. Methods Weighted gene co-expression network analysis was applied to detect co-expression modules and analyze their relationship with clinicopathologic characteristics using RNA sequencing data from The Cancer Genome Atlas database. The associations of gene expression with patients’ mortality were investigated by a variety of statistical methods and validated in an independent dataset of 405 AML patients. A risk score formula was created based on a linear combination of five gene expression levels. Results The weighted gene co-expression network analysis detected 63 co-expression modules. The pink and darkred modules were negatively significantly correlated with overall survival of AML patients. High expression of FNDC3B, VSTM1 and CALR was associated with favourable overall survival, while high expression of PLA2G4A was associated with adverse overall survival. Hierarchical clustering analysis of FNDC3B, VSTM1, PLA2G4A, GOLGA3 and CALR uncovered four subgroups of AML patients. The cluster1 AML patients showed younger age, lower cytogenetics risk, higher frequency of NPM1 mutations and more favourable overall survival than cluster3 patients. The risk score was demonstrated to be an indicator of adverse prognosis in AML patients Conclusions The FNDC3B, VSTM1, PLA2G4A, GOLGA3, CALR and risk score may serve as key prognostic biomarkers for the stratification and ultimately guide rational treatment of AML patients.

Abstract As a critical subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), CSN6 is upregulated in some human cancers and plays critical roles in tumorigenesis and progression, but its biological functions and molecular mechanisms in melanoma remain unknown. Our study showed that CSN6 expression was upregulated in melanoma patients and cells, and correlated with poor survival in melanoma patients. In melanoma cells, CSN6 knockdown remarkably inhibited cell proliferation, tumorigenicity, migration, and invasion, whereas CSN6 recovery rescued the proliferative and metastatic abilities. Notably, we identified that CSN6 stabilized CDK9 expression by reducing CDK9 ubiquitination levels, thereby activating CDK9-mediated signaling pathways. In addition, our study described a novel CSN6-interacting E3 ligase UBR5, which was negatively regulated by CSN6 and could regulate the ubiquitination and degradation of CDK9 in melanoma cells. Furthermore, in CSN6-knockdown melanoma cells, UBR5 knockdown abrogated the effects caused by CSN6 silencing, suggesting that CSN6 activates the UBR5/CDK9 pathway to promote melanoma cell proliferation and metastasis. Thus, this study illustrates the mechanism by which the CSN6-UBR5-CDK9 axis promotes melanoma development, and demonstrate that CSN6 may be a potential biomarker and anticancer target in melanoma.

Ice, Cloud and Land Elevation Satellite-2/Advanced Topographic Laser Altimeter System 06 (ICESat-2/ATL06) data can be widely used for various applications, such as monitoring changes in glacier thickness. In this article, we use field surveys based on continuously operating reference system (CORS) and unmanned aerial vehicles (UAVs) to verify the elevation accuracy of the ATL06 product. A total of 208 ATL06 footprints were selected for an accuracy assessment by obtaining 348 CORS global positioning system (GPS) measurements and deriving a digital elevation model (DEMs) from 2683 UAV images in four experimental areas with different terrain and landform types in the Qilian Mountains, China. The experiments show that ATL06 data have very high vertical accuracy and horizontal positioning accuracy; the average root-mean-square error (RMSE) yielded by CORS is 0.0846 m, and the corresponding RMSE yielded by the UAV data is 0.1517 m. Furthermore, the positioning accuracy was also affected by the terrain slope.

Abstract Posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis is an effective strategie for patients receiving matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) and haploidentical HSCT (haplo-HSCT). We evaluated the effectiveness and safety of reduced-dose cyclophosphamide, 20 mg/kg for 13 patients in MSD-HSCT cohort and 25 mg/kg for 22 patients in haplo-HSCT cohort, on days + 3, + 4 combined with cotransplantation of peripheral blood stem cells (PBSCs) and human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for severe aplastic anemia (SAA). In MSD-PTCy cohort, the times to neutrophil and platelet engraftment were significantly shorter than those in the MSD-control cohort (P

Ozone (O3) is becoming an increasingly concerning air quality problem in China, and previous O3 control strategies focused primarily on reducing anthropogenic volatile organic compounds (AVOCs), while neglecting the role of biogenic VOCs (BVOCs) in O3 formation. In this study, a field campaign was conducted at a suburban site in the Pearl River Delta region of China with high BVOC emissions from 29 August to 3 September 2020. An empirical kinetic modelling approach (EKMA) showed that VOC-limited was the dominant feature for O3 formation at the site. The relative incremental reactivity (RIR) values calculated by the box model (AtChem2-MCM) revealed that isoprene, formaldehyde, methylglyoxal and acetaldehyde had the highest RIRs. Simulation results from the box model also showed that isoprene played a substantial role in the formation of secondary carbonyls, especially contributing 32–92% to the formaldehyde production rate. Box model simulations further showed that during the O3 pollution period with high BVOC emissions, only near zero AVOC emissions could prevent O3 if the levels of nitrogen oxides (NOx) remained unchanged. The results suggest that the presence of high BVOC emissions can greatly impact efforts to control O3 by reducing AVOCs, particularly in regions with relatively high NOx levels (up to 51 ppbv in this study). In the long term, it may be essential to control NOx and choose low BVOC-emitting tree species in urban planning to address this issue, particularly as BVOC emissions are projected to become a more significant source of reactive VOCs with enhanced control of AVOCs.

Recent evidence suggested that N6-methyladenosine (m6A) methylation can determine m6A-modified mRNA fate and play an important role in skeletal muscle development. It was well known that transforming growth factor beta 1 (TGFβ1) is involved in a variety of cellular processes, such as proliferation, differentiation, and apoptosis. However, little is known about the m6A-mediated TGFβ1 regulation in myogenesis. Here, we observed an increase in endogenous TGFβ1 expression and activity during myotube differentiation. However, the knockdown of TGFβ1 inhibits the proliferation and induces cell apoptosis of myoblast. Moreover, we found that m6A in 5′-untranslated regions (5′UTR) of TGFβ1 promote its decay and inhibit its expression, leading to the blockage of the TGFβ1/SMAD2 signaling pathway. Furthermore, the targeted specific demethylation of TGFβ1 m6A using dCas13b-FTO significantly increased the TGFβ1-mediated activity of the SMAD2 signaling pathway, promoting myoblast proliferation. These findings suggest that TGFβ1 is an essential regulator of myoblast growth that is negatively regulated by m6A. Overall, these results highlight the critical role of m6A-mediated post-transcriptional regulation in myogenesis.

Objective: To evaluate the efficacy and safety of transvaginal natural orifice transluminal endoscopic surgery (vNOTES) in the treatment of female infertility. Materials and methods: This study includes 174 female patients with a history of long-standing female infertility. We retrospectively reviewed 41 patients who underwent hysterolaparoscopy (HL) via transvaginal natural orifice transluminal endoscopic surgery (vNOTES) and 133 patients who underwent laparoendoscopic single-site surgery (LESS). Demographic data, operation records, and pregnancy outcomes were collected and analyzed. The deadline for postoperative follow-up was June 2022. All the included patients were followed up for at least 18 months after surgery. Results: Compared with the LESS group, the vNOTES group had a shorter postoperative bowel movement time and less pain at 4 and 12 h (p = 0.004 vs. 0.008); no differences were found in other perioperative indicators. The clinical pregnancy rates of the vNOTES and LESS groups were 87.80% and 74.43% (p = 0.073), respectively. Conclusions: vNOTES represents a new, less invasive approach for infertility diagnosis and treatment that is particularly suitable for women who have special esthetic requirements. vNOTES is safe and practical and may be an ideal choice for scarless infertility surgery.

Due to its quite high theoretical specific-energy density, FeF2 nanomaterial is a good candidate for the cathode material of high-energy lithium-ion batteries. The preparation of FeF2 nanomaterial is very important for its application. At present, the preparation process mostly involves high temperature and an inert atmosphere, which need special or expensive devices. It is very important to seek a low-temperature and mild method, without the need for high temperature and inert atmosphere, for the preparation and following application of FeF2 nanomaterial. This article reports a novel sugar-assisted solvothermal method in which the FeF3∙3H2O precursor is reduced into FeF2 nanomaterial by carbon derived from the dehydration and condensation of sugar. The obtained FeF2 nanomaterials are irregular granules of about 30 nm, with inner pores inside each granule. Electrochemical tests show the FeF2 nanomaterial’s potential as a lithium-ion battery cathode material.

Abstract Background Soluble beta-amyloid (Aβ) can be cleared from the brain through various mechanisms including enzymatic degradation, glial cell phagocytosis, transport across the blood-brain barrier, and glymphatic clearance. However, the relative contribution of each clearance system and their compensatory effects in delaying the pathological process of Alzheimer’s disease (AD) are currently unknown. Methods Fluorescent trace, immunofluorescence, and Western blot analyses were performed to compare glymphatic clearance ability and Aβ accumulation among 3-month-old APP695/PS1-dE9 transgenic (APP/PS1) mice, wild-type mice, aquaporin 4 knock out (AQP4−/−) mice, and AQP4−/−/APP/PS1 mice. The consequence of selectively eliminating microglial cells, or downregulating apolipoprotein E (apoE) expression, on Aβ burden, was also investigated in the frontal cortex of AQP4−/−/APP/PS1 mice and APP/PS1 mice. Results AQP4 deletion in APP/PS1 mice significantly exaggerated glymphatic clearance dysfunction, and intraneuronal accumulation of Aβ and apoE, although it did not lead to Aβ plaque deposition. Notably, microglia, but not astrocytes, increased activation and phagocytosis of Aβ in the cerebral cortex of AQP4−/−/APP/PS1 mice, compared with APP/PS1 mice. Selectively eliminating microglia in the frontal cortex via local injection of clodronate liposomes resulted in deposition of Aβ plaques in AQP4−/−/APP/PS1 mice, but not APP/PS1 mice. Moreover, knockdown of apoE reduced intraneuronal Aβ levels in both APP/PS1 mice and AQP4−/−/APP/PS1 mice, indicating an inhibitory effect of apoE on Aβ clearance. Conclusion The above results suggest that the glymphatic system mediated Aβ and apoE clearance and microglia mediated Aβ degradation synergistically prevent Aβ plague formation in the early stages of the AD mouse model. Protecting one or both of them might be beneficial to delaying the onset of AD.

Abstract Background Widespread biomedical applications of nanomaterials (NMs) bring about increased human exposure risk due to their unique physicochemical properties. Autophagy, which is of great importance for regulating the physiological or pathological activities of the body, has been reported to play a key role in NM-driven biological effects both in vivo and in vitro. The coexisting hazard and health benefits of NM-mediated autophagy in biomedicine are nonnegligible and require our particular concerns. Main body We collected research on the toxic effects related to NM-mediated autophagy both in vivo and in vitro. Generally, NMs can be delivered into animal models through different administration routes, or internalized by cells through different uptake pathways, exerting varying degrees of damage in tissues, organs, cells, and organelles, eventually being deposited in or excreted from the body. In addition, other biological effects of NMs, such as oxidative stress, inflammation, necroptosis, pyroptosis, and ferroptosis, have been associated with autophagy and cooperate to regulate body activities. We therefore highlight that NM-mediated autophagy serves as a double-edged sword, which could be utilized in the treatment of certain diseases related to autophagy dysfunction, such as cancer, neurodegenerative disease, and cardiovascular disease. Challenges and suggestions for further investigations of NM-mediated autophagy are proposed with the purpose to improve their biosafety evaluation and facilitate their wide application. Databases such as PubMed and Web of Science were utilized to search for relevant literature, which included all published, Epub ahead of print, in-process, and non-indexed citations. Conclusion In this review, we focus on the dual effect of NM-mediated autophagy in the biomedical field. It has become a trend to use the benefits of NM-mediated autophagy to treat clinical diseases such as cancer and neurodegenerative diseases. Understanding the regulatory mechanism of NM-mediated autophagy in biomedicine is also helpful for reducing the toxic effects of NMs as much as possible.

Cardio-oncology, a nascent specialty, has evolved as a concerted strategy to address the cardiovascular complications of cancer therapies. On the other hand, emerging evidence has shown that some anti-tumor drugs, such as CD20-targeted rotuximab, also have markedly cardioprotective effects in addition to treating cancers. Rituximab is a CD20-targeted monoclonal antibody and kill tumor B-cells through antibody-mediated and antibody-independent pathways, indicating that B cells participate and promote the progression of cardiovascular diseases. In this review, we mainly present the evidence that B cells contribute to the development of hypertrophy, inflammation, and maladaptive tissue remodeling, with the aim of proposing novel immunomodulatory therapeutic strategies targeting B cells and their products for the treatment of heart failure.

Metal corrosion is a headache in marine industry. The existing technologies can hardly provide an effective long-term corrosion protection. Biomimetic slippery lubricant infused porous surface (SLIPS) has been developed as a potential alternative technique to resolve this problem. Herein, a stable triple-layered slippery surface which consist of compact-nickel-underlayer/porous-nickel-midlayer/PDMS/paraffin infused toplayer was designed and developed for corrosion protection. This composite surface exhibited a low sliding angle with good stability and thermal assitant self-healing property. Simultaneously, it demonstrated good anti-corrosion property with an extremly low corrosion current density and a large impedance of 2.301 × 107 Ω·cm−2, the as-prepared sample even can provide efficient corrosion protection for a long-term immersion in NaCl solution. Furthermore, the interface erosion mechanism was studied via the assistance of electrochemical and surface analysis techniques. The results revealed that no corrosion products were generated which further proved the good anti-corrosion performance. We believe that this triple-layered slippery surface can broaden the application of metals in the field of marine and other industries.

Both tea polysaccharides (TPS) and tea polyphenols (TPP) are promising in the treatment of inflammatory bowel disease (IBD). However, the effects of their combination against IBD are still unknown. In the present study, the therapeutic effects of TPS, TPP and TPS + TPP on dextran sodium sulfate-induced colitis in mice were investigated. Our results showed that administration of TPS + TPP achieved the best effects, followed by TPP and TPS, which were evidenced by the restoration of various physical signs (body weight, colon length and disease activity index) and the promoted intestinal barrier function (colon damage, mucin secretion and tight junction proteins expression). Furthermore, TPP and TPS decreased the relative abundance of Proteobacteria and Enterobacteriaceae, while TPP + TPS increased that of Lactobacillaceae and Lactobacillus. In conclusion, TPS together with TPP had greater effects on alleviating colitis and promoting intestinal barrier function. This result is interesting when developing functional foods against colitis.

As no reliable diagnostic methods are available, gallbladder cancer (GBC) is often diagnosed until advanced stages, resulting in a poor prognosis. In the present study, we assessed whether volatile organic compounds (VOCs) could be used as a diagnostic tool for GBC. The VOCs in bile samples collected from 32 GBC patients were detected by gas chromatography-ion mobility spectrometry (GC-IMS), and 54 patients with benign gallbladder diseases (BGD) were used as controls. Both principal component analysis and unsupervised hierarchical clustering analysis gave a clear separation of GBC and BGD based on the bile VOC data collected from GC-IMS. A total of 12 differentially expressed VOCs were identified, including four upregulated (cyclohexanone, 2-ethyl-1-hexanol, acetophenone, and methyl benzoate) and eight downregulated [methyl acetate, (E)-hept-2-enal, hexanal, (E)-2-hexenal, (E)-2-pentenal, pentan-1-ol, 1-octen-3-one, and (E)-2-octenal] in GBC compared with BGD. ROC analysis demonstrated a 12-VOC panel con-structed by four machine learning algorithms, which was superior to the traditional tumor marker, CA19-9. Among them, support vector machines and linear discriminant analysis provided the highest AUCs of 0.972, with a sensitivity of 100% and a specificity of 94.4% in the diagnosis of GBC. Collectively, VOCs might be used as a potential tool for the diagnosis of GBC.

Abstract Background The failure of treatment for breast cancer usually results from distant metastasis in which the epithelial-mesenchymal transition (EMT) plays a critical role. Hyperinsulinemia, the hallmark of Type 2 diabetes mellitus (T2DM), has been regarded as a key risk factor for the progression of breast cancer. Nuclear receptor subfamily 2, group F, member 2 (NR2F2) has been implicated in the development of breast cancer, however its contribution to insulin-induced EMT in breast cancer remains unclear. Methods Overexpression and knockdown of NR2F2 were used in two breast cancer cell lines, MCF-7 and MDA-MB-231 to investigate potential mechanisms by which NR2F2 leads to insulin-mediated EMT. To elucidate the effects of insulin and signaling events following NR2F2 overexpression and knockdown, Cells’ invasion and migration capacity and changes of NR2F2, E-cadherin, N-cadherin and vimentin were investigated by real-time RT-PCR and western blot. Results Insulin stimulation of these cells increased NR2F2 expression levels and promoted cell invasion and migration accompanied by alterations in EMT-related molecular markers. Overexpression of NR2F2 and NR2F2 knockdown demonstrated that NR2F2 expression was positively correlated with cell invasion, migration and the expression of N-cadherin and vimentin. In contrast, NR2F2 had an inverse correlation with E-cadherin expression. In MDA-MB-231, both insulin-induced cell invasion and migration and EMT-related marker alteration were abolished by NR2F2 knockdown. Conclusions These results suggest that NR2F2 plays a critical role in insulin-mediated breast cancer cell invasion, migration through its effect on EMT.

Abstract Background Studies into ankylosing spondylitis (AS) and its relationship with immune imbalance are controversial, and the correlation between the efficacy of TNF-α inhibitor and changes in immune imbalance is unclear. Methods A total of 40 immune cells were tested with flow cytometry, and the results of 105 healthy control (HC) subjects, 177 active-stage AS patients, and 23 AS cases before and after 12 weeks of TNF-α inhibitor therapy (Anbainuo) were analyzed. Results Compared with the HC group, the proportion of immune cells, such as naïve and central memory CD4+T cells, in AS increased (P

Abstract Background DNA methylation is an epigenetic regulatory form that plays an important role in regulating the gene expression and the tissues development.. However, DNA methylation regulators involved in sheep muscle development remain unclear. To explore the functional importance of genome-scale DNA methylation during sheep muscle growth, this study systematically investigated the genome-wide DNA methylation profiles at key stages of Hu sheep developmental (fetus and adult) using deep whole-genome bisulfite sequencing (WGBS). Results Our study found that the expression levels of DNA methyltransferase (DNMT)-related genes were lower in fetal muscle than in the muscle of adults. The methylation levels in the CG context were higher than those in the CHG and CHH contexts, and methylation levels were highest in introns, followed by exons and downstream regions. Subsequently, we identified 48,491, 17, and 135 differentially methylated regions (DMRs) in the CG, CHG, and CHH sequence contexts and 11,522 differentially methylated genes (DMGs). The results of bisulfite sequencing PCR (BSP) correlated well with the WGBS-Seq data. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation analysis revealed that some DMGs were involved in regulating skeletal muscle development and fatty acid metabolism. By combining the WGBS-Seq and previous RNA-Seq data, a total of 159 overlap genes were obtained between differentially expressed genes (DEGs) and DMGs (FPKM > 10 and fold change > 4). Finally, we found that 9 DMGs were likely to be involved in muscle growth and metabolism of Hu sheep. Conclusions We systemically studied the global DNA methylation patterns of fetal and adult muscle development in Hu sheep, which provided new insights into a better understanding of the epigenetic regulation of sheep muscle development.

Abstract Background Our recent study has revealed that many hospitalized patients with acquired long QT syndrome (ALQTS) are cancer patients. This study aims to determine the risk factors and outcomes of hospitalized cancer patients with ALQTS. Methods We performed a matched case-control study within a cohort of 10,180 cancer patients hospitalized between September 2013 and April 2016. Among them, 150 patients defined as having severe ALQTS with a markedly prolonged QT interval (QTc ≥ 500 ms) were compared with 293 age-, sex- and cancer-type-matched controls (non-ALQTS). Death as the endpoint was followed for up to 2 years. Cox regression and Kaplan-Meier survival analyses were performed to assess the effects of particular clinical variables on all-cause mortality. Multivariate logistic regression was performed to calculate odds ratios (OR) for various predictors of QT prolongation. Results The mortality was significantly higher in ALQTS group (63.3% vs. 33.4%). Hypertension, hypokalemia, hypocalcemia, QT-prolonging drugs, infection, anemia, anti-microtubule agents were contributing factors to ALQTS. Renal insufficiency, male gender and hypokalemia were found to be independent risk factors for all-cause mortality in ALQTS group. Conclusion Markedly prolonged QT interval was seen in 1.5% of hospitalized cancer patients. The all-cause mortality was high in cancer patients with severe ALQTS.

Chrysanthemum morifolium (Chr) is a traditional Chinese medicine (TCM) that has been used in the treatment of inflammation-linked diseases for hundreds of years. Naringenin (Nar) and apigenin (Api) are the major active components in aqueous extracts of C. morifolium. The aim of our study was to clarify the roles of Chr, Nar and Api in ameliorating depression-like behaviour induced by corticosterone. First, the behavioural and biochemical indicators closely related to depression were examined to evaluate the therapeutic effects of Chr/Nar/Api on a depression model. Then, a metabolomics approach was utilized to screen for biomarkers and related pathways between a control group and Chr/Nar/Api groups. The comprehensive results revealed that Chr/Nar/Api exerted anti-depressant effects through interfering with tryptophan metabolism, arginine and prolinemetabolism, citrate cycle, niacin and niacinamide metabolism, phenylalanine metabolism, and alanine, aspartate and glutamate metabolism. The mechanism of Chr/Api/Nar in the treatment of depression was elucidated based on material and energy metabolism. Moreover, Nar could be used as a substitute for Chr for reversing depression-like behaviour, and Api was similar to a positive drug in terms of function on depression. The integrated metabolomics approach demonstrated here should be an effective method for interpreting the function of herbs from TCM and clarifying the mechanism of their components in future studies.

Relationship extraction among diseases, symptoms and tests has always been a concerning research issue in the biomedical field. Disease-pertinent relationship extraction for user-generated content in the online health community represents a research trend. By training the word embedding vectors for the medical-health field, conducting entity recognition and relationship annotation, and using deep learning technology, we construct a relation extraction model for extracting the relationships among diseases, symptoms and tests. Our relationship extraction model of the bidirectional gate recurrent unit (BiGRU) network based on character-level and sentence-level attention mechanisms achieved the best results on question-answer data in the online health community. Our research results can not only help physician diagnoses but also help patients perform health management, which has important industrial application value.

PurposeThe present paper investigated the expression of TLR2 in serum of patients with pulmonary tuberculosis and lung cancer, and verifiedthe effect of TLR2 on the biological characteristics of lung cancer cells. MethodsThe common differentially expressed genes in tuberculosis and lung cancer samples were analyzed by edgeR. The intersection of genes was taken and the enrichment analysis and string interaction analysis were performed. The expression of TLR2, inflammatory factors IL6, IL17 and IL22 in serum of patients with pulmonary tuberculosis or lung cancer and lung cell were detected by ELISA. The mRNA and protein expression levels of TLR2, caspase-3, Bax and Bcl-2 were detected by qRT-PCR and Western blot. CCK-8, colony formation assay, transwell assay and flow cytometry were performed to detect the proliferation, invasion, migration and cells apoptosis of lung cancer cells. ResultsBioinformatics analysis found that high expression of TLR2 is a core regulator in lung cancer and tuberculosis. TLR2 and inflammatory factors IL6, IL17, IL22 are highly expressed in the serum of patients with tuberculosis and lung cancer by ELISA.TLR2 is also highly expressed in lung cancer cells. Silencing TLR2 inhibited the growth, invasion and migration ability of cells, and the expression of IL6, IL17 and IL22. It also promoted the expression of caspase-3 and Baxwith the decreased expression of Bcl-2. ConclusionTLR2 and inflammatory factors IL6, IL17 and IL22 were highly expressed in the serum of patients with pulmonary tuberculosis and lung cancer. Silencing TLR2 could inhibit the growth, invasion and migration ability of lung cancer cells, and promote apoptosis.

Abstract The vascular system, which transports oxygen and nutrients, plays an important role in wound healing, cardiovascular disease treatment and bone tissue engineering. Angiogenesis is a complex and delicate regulatory process. Vascular cells, the extracellular matrix (ECM) and angiogenic factors are indispensable in the promotion of lumen formation and vascular maturation to support blood flow. However, the addition of growth factors or proteins involved in proangiogenic effects is not effective for regulating angiogenesis in different microenvironments. The construction of biomaterial scaffolds to achieve optimal growth conditions and earlier vascularization is undoubtedly one of the most important considerations and major challenges among engineering strategies. Nanomaterials have attracted much attention in biomedical applications due to their structure and unique photoelectric and catalytic properties. Nanomaterials not only serve as carriers that effectively deliver factors such as angiogenesis-related proteins and mRNA but also simulate the nano-topological structure of the primary ECM of blood vessels and stimulate the gene expression of angiogenic effects facilitating angiogenesis. Therefore, the introduction of nanomaterials to promote angiogenesis is a great helpful to the success of tissue regeneration and some ischaemic diseases. This review focuses on the angiogenic effects of nanoscaffolds in different types of tissue regeneration and discusses the influencing factors as well as possible related mechanisms of nanomaterials in endothelial neovascularization. It contributes novel insights into the design and development of novel nanomaterials for vascularization and therapeutic applications.

Objective Antibiotics have saved hundreds of millions of patient’s lives, but there are also many side effects. This paper mainly studies the regulation of Chinese yam on antibiotic-induced gut dysbiosis in rats. Methods Male Wistar rats were divided into three groups, normal control group, antibiotic group, and Chinese yam group. In the antibiotic group and the yam group, a rat model of intestinal dysfunction was established by intragastric administration of imipenem/cilastatin sodium (antibiotic) for 21 days. The yam group was also given yam decoction for intervention. The fecal samples of each group of rats were analyzed using an ultra-performance liquid chromatography quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method to find potential biomarkers. The DNA in the feces was extracted, and analyzed using 16S rDNA method to find the differential flora. Spearman correlation analysis was performed on differential flora and differential metabolites to determine the main metabolic pathways of the host after intestinal flora dysregulation.Results The administration of antibiotics can lead to disorders of intestinal flora, decreased microbial diversity, and changes in host metabolic phenotype. Chinese yam can significantly improve the intestinal flora, making the host's metabolic phenotype tend toward normal.Conclusion Long-term use of Imipenem/cilastatin sodium can cause disturbance of intestinal flora in normal rats. Chinese yam may regulate intestinal flora disorder and have potential prebiotic effects.

Background: Resistance to oxaliplatin-based chemotherapy is a major cause of recurrence in colorectal cancer (CRC) patients. There is increasing evidence indicating that circHIPK3 is involved in the development and progression of tumours. However, little is known about the potential role of circHIPK3 in CRC chemotherapy and its molecular mechanisms in chemoresistance also remain unclear. Methods: Quantitative real-time PCR was performed to detect circHIPK3 expression in tissues of 2 cohorts of CRC patients who received oxaliplatin-based chemotherapy. The chemoresistant effects of circHIPK3 were assessed by cell viability, apoptosis, and autophagy assays. The relationship between circHIPK3, miR-637, and STAT3 mRNA was confirmed by biotinylated RNA pull-down, luciferase reporter, and western blot assays. Findings: In the pilot study, increased circHIPK3 expression was observed in chemoresistant CRC patients. Functional assays showed that circHIPK3 promoted oxaliplatin resistance, which was dependent on inhibition of autophagy. Mechanistically, circHIPK3 sponged miR-637 to promote STAT3 expression, thereby activating the downstream Bcl-2/beclin1 signalling pathway. A clinical cohort study showed that circHIPK3 was upregulated in tissues from recurrent CRC patients and correlated with tumour size, regional lymph node metastasis, distant metastasis, and survival. Interpretation: circHIPK3 functions as a chemoresistant gene in CRC cells by targeting the miR-637/STAT3/Bcl-2/beclin1 axis and might be a prognostic predictor for CRC patients who receive oxaliplatin-based chemotherapy. Funding: National Natural Science Foundation of China (81301506), Shandong Medical and Health Technology Development Project(2018WSB20002), Shandong Key Research and Development Program (2016GSF201122), Natural Science Foundation of Shandong Province (ZR2017MH044), and Jinan Science and Technology Development Plan(201805084, 201805003). Keywords: Colorectal cancer, Chemoresistance, circHIPK3, Autophagy, miR-637, STAT3

Background: Anti-IL-17A therapy is generally effectively applied in patients with Ankylosing Spondylitis (AS) to achieve and maintain remission. However, the influence of anti-IL-17A on the composition of the immune system is not apparent. Our prospective study was to explore the changes in immune imbalance regarding T cell, B cell and natural killer (NK) cell subsets after secukinumab treatment in AS patients.Methods: Immune cell distribution of 43 AS patients treated with secukinumab for 12 weeks and 47 healthy controls (HC) were evaluated. Flow cytometry using monoclonal antibodies against 25 surface markers was accomplished to explore the frequencies of lineage subsets. The differences between HC, AS pre-treatment, and post-treatment were compared using the paired Wilcoxon test, Mann-Whitney U test, and ANOVA.Results: AS patients had altered immune cell distribution regarding T cell and B cell subsets. Apart from activated differentiation of CD4+ T cell, CD8+ T cell and B cell, higher levels of cytotoxic T (Tc) two cells and Tc17 cells were noted in AS patients. We confirmed that helper T (Th) one cell became decreased; however, Th17 cells and T follicular helper (Tfh) 17 cells went increased in AS. After 12 weeks of secukinumab therapy, CRP and ASDAS became significantly decreased, and meanwhile, the proportions of Th1 cells, Tfh17 cells and classic switched B cells were changed towards those of HC. A decreased CRP was positively correlated with a decrease in the frequency of naïve CD8+ T cells (p = 0.039) and B cells (p = 0.007) after secukinumab treatment. An elevated level of T cells at baseline was detected in patients who had a good response to secukinumab (p = 0.005).Conclusion: Our study confirmed that AS patients had significant multiple immune cell dysregulation. Anti-IL-17A therapy (Secukinumab) could reverse partial immune cell imbalance.

Aims: HFA-PEFF score has been proposed for diagnosing heart failure with preserved ejection fraction (HFpEF). Currently, there are only a limited number of tools for predicting the prognosis. In this study, we evaluated whether the HFA-PEFF score can predict mortality in patients with HFpEF.Methods: This single-center, retrospective observational study enrolled patients diagnosed with HFpEF at the First Affiliated Hospital of Dalian Medical University between January 1, 2015, and April 30, 2018. The subjects were divided according to their HFA-PEFF score into low (0–2 points), intermediate (3–4 points), and high (5–6 points) score groups. The primary outcome was all-cause mortality.Results: A total of 358 patients (mean age: 70.21 ± 8.64 years, 58.1% female) were included. Of these, 63 (17.6%), 156 (43.6%), and 139 (38.8%) were classified into the low, intermediate, and high score groups, respectively. Over a mean follow-up of 26.9 months, 46 patients (12.8%) died. The percentage of patients who died in the low, intermediate, and high score groups were 1 (1.6%), 18 (11.5%), and 27 (19.4%), respectively. A multivariate Cox regression identified HFA-PEFF score as an independent predictor of all-cause mortality [hazard ratio (HR):1.314, 95% CI: 1.013–1.705, P = 0.039]. A Cox analysis demonstrated a significantly higher rate of mortality in the intermediate (HR: 4.912, 95% CI 1.154–20.907, P = 0.031) and high score groups (HR: 5.291, 95% CI: 1.239–22.593, P = 0.024) than the low score group. A receiver operating characteristic (ROC) analysis indicated that the HFA-PEFF score can effectively predict all-cause mortality after adjusting for age and New York Heart Association (NYHA) class [area under the curve (AUC) 0.726, 95% CI 0.651–0.800, P = 0.000]. With an HFA-PEFF score cut-off value of 3.5, the sensitivity and specificity were 78.3 and 54.8%, respectively. The AUC on ROC analysis for the biomarker component of the score was similar to that of the total score.Conclusions: The HFA-PEFF score can be used both to diagnose HFpEF and predict the prognosis. The higher scores are associated with higher all-cause mortality.

Abstract Background Autism spectrum disorder (ASD) is characterized by a spectrum of social and communication impairments and rigid and stereotyped behaviors that have a neurodevelopmental origin. Although many imaging studies have reported structural and functional alterations in multiple brain regions, clinically useful diagnostic imaging biomarkers for ASD remain unavailable. Methods In this study, we applied machine learning (ML) models to regional volumetric and cortical thickness data from the largest structural magnetic resonance imaging (sMRI) dataset available from the Enhancing Neuro Imaging Genetics Through Meta‐Analysis (ENIGMA) consortium (1833 subjects with ASD and 1838 without ASD; age range: 1.5–64; average age: 15.6; male/female ratio: 4.2:1). Results The highest classification accuracy on a hold‐out test set was achieved using a stacked Extra Tree Classifier. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.62 (95% confidence interval [CI]: 0.57, 0.68) and the area under the precision‐recall curve was 0.58. Learning curve analysis showed the good fit of the model and suggests that more training examples will not likely benefit model performance. Conclusions Our results suggest that sMRI volumetric and cortical thickness data alone may not provide clinically sufficient useful diagnostic biomarkers for ASD. Developing clinically useful imaging classifiers for ASD will benefit from combining other data modalities or feature types, such as functional MRI data and raw images that can leverage other machine learning (ML) techniques such as convolutional neural networks.

The ISTTWN algorithm overcame the defect of separating the production process of skeleton points and skeleton lines in tree branch point cloud skeleton extraction and improved the accuracy of the extracted initial skeletons, but the skeletons need further optimization. In the existing skeleton optimization, it is difficult to see the stump adjustment, and most of the bifurcation optimization and skeleton smoothness adopt fitting. Based on the characteristics of the initial skeletons extracted by the ISTTWN algorithm, this research optimizes the skeleton from four aspects. An algorithm for the stump adjustment for reconstructing the stump based on the layer and hierarchical relationship and an algorithm for the bifurcation optimization based on the local branch point cloud and cosine correlation are proposed, and an existing pruning method and a skeleton smoothing method are used. The results show that the skeleton optimization method proposed or used in this research has a high computational efficiency in general and can ultimately retain the necessary skeleton lines. In a visual analysis, the optimized skeleton is obviously much more natural and more in line with the actual topology of trees. In the quantitative analysis, the completeness, accuracy and effectiveness reached 97.82%, 95.72% and 89.47%, respectively. In this study, in addition to the existing tree parameters extracted by the skeleton or generalized cylinder model, the generated skeleton is used to extract the branch attributes. The R2 of the deflection angle of the branch tip, distance from branch tip and branch length are about 0.897, 0.986 and 0.988, respectively, which illustrates that their models are very good. This research can further expand the application of the skeleton.

This study explores the effect of phosphorus (P) fractions, under P addition or not, based on a common vetch-rape model cropping system in alkaline soil. A two year field experiment was conducted at Tuzuo Banner modern agricultural Park in Inner Mongolia, China. Two phosphorus levels, including P0 (no fertilizer) and P45 (45 kg·ha−1 P), were performed in common vetch and rape either grown alone or intercropped. We analyzed the changes of the physicochemical properties and phosphorus fractions in the rhizosphere soil. Intercropping enhanced the common vetch and rape yield by 42.05% and 24.91%, on average, compared with corresponding sole cropping on an equivalent area basis. The average land equivalent ratio (LER) was 1.34. Intercropping had a significant AP concentration, of 65.32% and 33.99% at the P0 level, and 62.83% and 36.19% at the P45 level, respectively, compared to that of the sole common vetch and rape. With the application of P, intercropping improved the Resin-Pi and NaHCO3-Pi fraction (61.17%, 87.03% at the P0 level and 96.50%, 41.85% at the P45 level, compared to monocropped common vetch and rape in 2019). The changes in NaOH-Pi and NaOH-Po (except for NaOH-Pi in 2019) showed no significant difference between cropping systems. Intercropping significantly accumulated concentrations of HCl-P, while depleting Residual-P, in 2020. In conclusion, common vetch/rape with the addition of P polyculture stimulated rhizosphere soil P mobilization and had a yield advantage over sole cropping.

Cardiotoxicity is one of the major side effects of anti-cancer therapy affecting the overall prognosis of patients and possibly leading to the discontinuation of chemotherapy. Traditional cardiovascular tests such as electrocardiography and transthoracic echocardiography have limited sensitivity and specificity for the early detection of myocardial injury. Cardiovascular imaging generally detects cancer therapy-related cardiac dysfunction (CTRCD) at advanced stages, whereas biomarkers are inexpensive, easily detected, reproducible, and capable of detecting even minimal cardiomyocyte damage or mild hemodynamic fluctuations. The presence of circulating cardiac biomarkers has been investigated as early indicators of cardiotoxicity and predictors of subsequent CTRCD. Currently, the most frequently used cardiac biomarkers are cardiac troponin (cTn) and natriuretic peptides (NPs). This review presents the evidence gathered so far regarding the usefulness and limitations of cardiac biomarkers in the field of cardio-oncology.

A combined solar phase-change thermal-storage heating system is proposed, wherein erythritol is used as the phase-change material (PCM) used to fill the thermal-storage device, and the storage cavity is heated and stored with a disc concentrator. The Solidification/Melting, Volume-of-Fluid (VOF) model of ANSYS Fluent software was used to simulate the phase-change process of erythritol inside the thermal-storage device. The thermal-storage device was designed based on our numerical calculations, and its performance was tested. We found that larger PCM-volume fractions correlated with lower PCM volume-expansion rates and longer total melting times during the heat storage process. When the φ value equaled 80%, the PCM solid–liquid-phase interface and temperature distribution were most uniform and showed the best heat storage. In addition, the size of the heat-storage device affected the heat-exchange area, and the total melting time of the PCM decreased and then increased as the width-to-height ratio (I) increased. With this design capacity, the late stage of the charging process of the heat-storage device accounted for 70% of the total time, and the heat energy-utilization rate during the boiling process was 66.3%. Overall, this combined heating system can be considered a very efficient solar energy-utilization terminal for basic domestic energy needs.

Mechanotransduction is the process by which cells convert external forces and physical constraints into biochemical signals that control several aspects of cellular behavior. A number of approaches have been proposed to investigate the mechanisms of mechanotransduction; however, it remains a great challenge to develop a platform for dynamic multivariate mechanical stimulation of single cells and small colonies of cells. In this study, we combined polydimethylsiloxane (PDMS) and PDMS/Mxene nanoplatelets (MNPs) to construct a soft bilayer nanocomposite for extracellular mechanical stimulation. Fast backlash actuation of the bilayer as a result of near-infrared irradiation caused mechanical force stimulation of cells in a controllable manner. The excellent controllability of the light intensity and frequency allowed backlash bending acceleration and frequency to be manipulated. As gastric gland carcinoma cell line MKN-45 was the research subject, mechanical force loading conditions could trigger apoptosis of the cells in a stimulation duration time-dependent manner. Cell apoptotic rates were positively related to the duration time. In the case of 6 min mechanical force loading, apoptotic cell percentage rose to 34.46% from 5.5% of the control. This approach helps apply extracellular mechanical forces, even with predesigned loading cycles, and provides a solution to study cell mechanotransduction in complex force conditions. It is also a promising therapeutic technique for combining physical therapy and biomechanics.

Central nervous system (CNS) complications can occur in 9%–15% of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical manifestations of the CNS complications are non-specific, with most of them being disturbances of consciousness, convulsions, headaches, fever, and epilepsy, making it difficult to infer the cause of the complications based on clinical manifestations. We retrospectively analyzed the sensitivity and feasibility of metagenomic next generation sequencing (mNGS) in the diagnosis of CNS infections after allo-HSCT. Lumbar punctures were performed on 20 patients with CNS symptoms after receiving alternative donor HSCT(AD-HSCT) at the Affiliated Cancer Hospital of Zhengzhou University from February 2019 to December 2020, and their cerebrospinal fluid (CSF) was collected. The mNGS technique was used to detect pathogens in the CSF. Routine CSF testing, biochemical analyses, G experiments, GM experiments, ink staining, acid-fast staining, and bacterial cultures were carried out, and quantitative PCR (qPCR) tests were used to detect cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK polyomavirus (BKPyV), and human alphaherpesvirus (HHV). A total of 29 tests were performed with 21 of them being positive. Of the five negative patients, three were diagnosed with a posterior reversible encephalopathy syndrome, one as having transplantation-associated thrombotic microangiopathy, and one with transient seizure caused by hypertension. Fifteen patients tested positive, of which four had single infections and eleven had mixed infections. Five cases of fungal infections, six cases of bacterial infections, and 13 cases of viral infections were detected. Among the 13 cases of viral infections, ten cases were CMV(HHV-5); three were BKPyV; two were Torque teno virus (TTV); Two were HHV-1,two were EBV(HHV4), and one each of HpyV5 and HHV-6B. Thirteen patients tested positive for virus while the qPCR detection method of 6 identical specimens were below the minimum detection limit(

Aims: Evidence-based guidelines for heart failure management depend mainly on current left ventricular ejection fraction (LVEF). However, fewer studies have examined the impact of prior LVEF. Patients may enter the heart failure with midrange ejection fraction (HFmrEF) category when heart failure with preserved ejection fraction (HFpEF) deteriorates or heart failure with reduced ejection fraction (HFrEF) improves. In this study, we examined the association between change in LVEF and adverse outcomes.Methods: HFmrEF patients with at least two or more echocardiograms 3 months apart at the First Affiliated Hospital of Dalian Medical University between September 1, 2015 and November 30, 2019 were identified. According to the prior LVEF, the subjects were divided into improved group (prior LVEF < 40%), stable group (prior LVEF between 40 and 50%), and deteriorated group (prior LVEF ≥ 50%). The primary outcomes were cardiovascular death, all-cause mortality, hospitalization for worsening heart failure, and composite event of all-cause mortality or all-cause hospitalization.Results: A total of 1,168 HFmrEF patients (67.04% male, mean age 63.60 ± 12.18 years) were included. The percentages of improved, stable, and deteriorated group were 310 (26.54%), 334 (28.60%), and 524 (44.86%), respectively. After a period of follow-up, 208 patients (17.81%) died and 500 patients met the composite endpoint. The rates of all-cause mortality were 35 (11.29%), 55 (16.47%), and 118 (22.52%), and the composite outcome was 102 (32.90%), 145 (43.41%), and 253 (48.28%) for the improved, stable, and deteriorated groups, respectively. Cox regression analysis showed that the deterioration group had higher risk of cardiovascular death (HR: 1.707, 95% CI: 1.064–2.739, P = 0.027), all-cause death (HR 1.948, 95% CI 1.335–2.840, P = 0.001), and composite outcome (HR 1.379, 95% CI 1.096–1.736, P = 0.006) compared to the improvement group. The association still remained significant after fully adjusted for both all-cause mortality (HR = 1.899, 95% CI 1.247–2.893, P = 0.003) and composite outcome (HR: 1.324, 95% CI: 1.020–1.718, P = 0.035).Conclusion: HFmrEF patients are heterogeneous with three different subsets identified, each with different outcomes. Strategies for managing HFmrEF should include previously measured LVEF to allow stratification based on direction changes in LVEF to better optimize treatment.

Perihilar cholangiocarcinoma (PHCCA) has a poor prognosis, mainly due to diagnosis at an advanced stage. Cripto-1 functions as an oncogene and is highly expressed in several human cancers, however, its clinical application in PHCCA is poorly understood. Herein, we identified that Cripto-1 was released by PHCCA cells via exosomes in vitro and in vivo. Furthermore, an ELISA method was developed to detect exosomal Cripto-1 in the serum of 115 PHCCA patients, 47 cholangitis patients and 65 healthy controls, and it was found that exosomal Cripto-1 was increased in PHCCA patients and associated with metastasis. Compared with traditional serum tumor markers, CA19-9 and CEA, exosomal Cripto-1 demonstrated a larger area under ROC curve for PHCCA diagnosis. The cutoff value of exosomal Cripto-1 was 0.82, achieving a sensitivity of 79.1% and a specificity of 87.5%. As expected, exosomal Cripto-1 levels in immunohistochemically Cripto-1-high cases were significantly elevated compared to in Cripto-1-low cases. When measured 1-week postoperatively, Cripto-1 levels decreased on average from 1.25(0.96-3.26) to 0.85(0.62-1.82). Immunohistochemistry analysis showed Cripto-1 expression was negatively correlated with E-cadherin and was an independent prognostic biomarker for poor survival in PHCCA patients. In conclusion, exosomal Cripto-1 in sera can reflect its expression in the tissue of PHCAA patients and has the potential be a non-invasive biomarker for diagnosis and prognosis of PHCCA.

ObjectiveEvaluate the MRI evidence of active inflammatory and chronic structural damages in radiographic axial spondyloarthritis (r-axSpA) and non-radiographic axial spondyloarthritis (nr-axSpA).MethodsA retrospective review of 253 patients who underwent sacroiliac joint (SIJ) MRI between June 2014 and December 2019 was performed. MRI images including short tau inversion recovery scan and T1-weighted spin echo scans were assessed using the Spondyloarthritis Research Consortium of Canada (SPARCC) score and SPARCC MRI SIJ structural score by two independent readers.ResultsHigher mean score of inflammatory (SPARCC) was seen in r-axSpA patients when compared with nr-axSpA patients (8.08 vs 4.37, P

Background: We aimed to explore the influencing factors of clinical adverse blood transfusion reactions, to provide theoretical basis and support for clinical safe blood transfusion, and to minimize the occurrence of adverse blood transfusion reactions. Methods: The method was to retrospectively analyze the report of adverse blood transfusion reports from 6 hospitals in Linyi area, Shandong, China to the blood station in Linyi City center from 2013 to 2020. We aimed to classify factors, analyze the occurrence of adverse transfusion reactions, and discuss the correlation between the occurrence of adverse transfusion reactions and the above factors. Results: Overall, 248 patients (77.98%) had a history of blood transfusion. The difference between this group and the group with no history was statistically significant (P