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This study aimed to explore the potential of ANXA6 as a biomarker and its possible mechanisms, like its expression patterns and clinical significance, as well as exploring its underlying biological functions and regulatory networks in nasopharyngeal carcinoma (NPC). Differentially expressed proteins were identified by proteomics technology. PCR, western blotting, immunohistochemistry, and ELISA analysis of serum were used to analyze ANXA6's clinical role. GEO databases investigated its prognosis relationship. Seven databases predicted transcription factors, and GO, KEGG analyzed ANXA6's mechanism. Immune infiltration and immunotherapy datasets were also examined. ANXA6 was significantly downregulated in NPC, linked to poor survival advantage. Its expression level was closely correlated with primary lesion size, lymph node metastasis, distant metastasis and clinical stage. Low serum ANXA6 was associated with lymph node and distant metastasis. MYC may regulate ANXA6 in NPC. Functional analysis revealed co-expressed genes related to immune cells. ANXA6 was linked to immune infiltration and response. High ANXA6 expression predicted better immunotherapy and influenced drug sensitivity. ANXA6, negatively correlated with NPC development and metastasis, is a potential prognostic biomarker with tumor-suppressing effects. Multi-omics analysis highlights its clinical and immune regulatory roles, offering insights for future biomarker and molecular mechanism studies in NPC., 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 © 2024 Elsevier B.V. All rights reserved.)

Bacterial contamination is an intractable challenge in food safety, environments and biomedicine fields, and places a heavy burden on society. Polydopamine (PDA), a high molecular biopolymer, is considered as a promising candidate to participate in the design of novel antibacterial agents with unique contributions in biocompatibility, adherence, photothermal and metal coordination ability. In this study, coral-like ZIFL-PDA@AgNPs with excellent antibacterial properties and biocompatibility were prepared by embedding AgNPs into the biopolymer PDA-modulated ZIFL-PDA nanostructures by green reduction method to solve the problem with poor stability of AgNPs. Based on the plasma resonance effect of AgNPs, coral-like ZIFL-PDA@AgNPs had enhanced photothermal properties compared with ZIFL-PDA. Due to the synergistic effect between antibacterial metal ions mainly Ag + and the photothermal effect, coral-like ZIFL-PDA@AgNPs showed enhanced anti-mature biofilm and antibacterial properties, which was dependent on its concentration and sterilization time. In addition, regulated by the ZIFL-PDA nanostructure, coral-like ZIFL-PDA@AgNPs demonstrated a unique Ag + long-time sustained release behavior, giving it an extended antibacterial validity period and good biocompatibility. Antibacterial mechanism experiments indicated that coral-like ZIFL-PDA@AgNPs can significantly damage the integrity of bacterial cell membrane, reduce the content of ATP in bacterial by affecting the activity of succinate dehydrogenase, and induce the accumulation of reactive oxygen species, ultimately leading to bacterial death., 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 © 2024 Elsevier B.V. All rights reserved.)

HIF-1 activation is protective in acute kidney injury (AKI), but its underlying mechanism is not fully understood. Stress-induced tRNA derived small RNAs play an emerging role in cellular processes. This study investigated the role of HIF-1 associated tiRNA-Lys-CTT-003 (tiR-Lys) in an AKI mouse model. Our sequencing results showed that ischemia can promote the production of renal tiR-Lys by activating HIF-1α. FG-4592, a HIF-1 inducer, can also upregulate the expression of tiR-Lys in renal tubular cells. Both overexpression of tiR-Lys and FG-4592 pre-treatment could improve mitochondrial damage and lipid peroxidation with alleviated renal function and morphological damage in cisplatin-induced AKI mice. While the anti-ferroptosis effect of FG-4592 were largely eliminated by tiR-Lys inhibitor. Notably, tiR-Lys directly alleviated cell death and MDA accumulation induced by the ferroptosis inducer Erastin, accompanied with restored expression of GPX4. RNA-Pulldown and RIP-qPCR results revealed that tiR-Lys can interact with the RNA-binding protein GRSF1.tiR-lys overexpression can preserve protein expression of GRSF1 decreased by cisplatin. Inhibiting Grsf1 via shRNA eliminated the upregulation of GPX4 by tiR-Lys. In conclusion, our study demonstrates that HIF-1α-induced tiR-Lys is protective in cisplatin-induced AKI, primarily by upregulating the level of GPX4 through interaction with GRSF1, thereby inhibiting ferroptosis in renal tubular epithelial cells., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Optical flow ratio (OFR) is a novel computational fractional flow reserve derived from optical coherence tomography (OCT). However, the impact of combining post-stenting morphology (OCT) and physiology (OFR) remains largely unknown., Methods: OCT and OFR were analysed at an independent core laboratory. Target lesion failure (TLF) was defined as the composite of cardiac death, target lesion myocardial infarction, and target lesion revascularisation. Suboptimal stent deployment was identified with at least 1 TLF-related OCT or OFR characteristic., Results: A total of 448 patients with acute coronary syndrome (459 vessels) were assessed. Stent expansion < 80%, minimal stent area < 4.5 mm 2 , stent edge lipid-rich plaque and OFR < 0.90 were independent predictors of TLF (all P < 0.001). Patients with OCT-suboptimal (adjusted hazard ratio [aHR] 7.88, 95% CI 2.73-22.72,-P < 0.001) or OFR-suboptimal (aHR 5.78, 95% CI 2.54-13.14; P < 0.001) stent deployment showed significantly higher risk of TLF compared with those with optimal stent deployment, with a significant interaction (P interaction < 0.001). OCT and OFR both-suboptimal stent deployment was confirmed as an independent predictor of TLF (aHR 9.39, 95% CI 4.25-20.76; P < 0.001)., Conclusions: Combined OCT and OFR conferred an optimal reclassification of stent deployment, which may aid in decision making regarding a tailored PCI strategy for optimal stent deployment., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: This study aimed to assess state-trait anxiety level changes in Chinese patients with dentofacial discrepancies before and after orthognathic surgery and to explore the feasibility of developing a reference index for the preoperative screening of postoperative patients with high anxiety., Methods: A total of 96 Chinese patients with dentofacial discrepancies who underwent orthognathic surgery were included in this study. Data were collected before orthognathic surgery and at 2 weeks (T2), 3 months, and 6 months (T4) after surgery using the State-Trait Anxiety Inventory. Receiver operating characteristic and linear regression analyses were performed to screen for preoperative indicators of postoperative high-state anxiety., Results: State-trait anxiety levels in patients with dentofacial discrepancies decreased after surgery (F = 18.95, P <0.01; F = 6.90, P <0.01). Trait Anxiety Inventory can be used to screen patients with high-state anxiety from T2 to T4 (area under cover 95% confidence interval: T2, 0.74 [0.62-0.86]; 3 months, 0.79 [0.69-0.90]; T4, 0.77 [0.66-0.87], P <0.01), corresponding to cutoff values of 48.5, 46.5, and 45.5, respectively., Conclusions: All participants' state-trait anxiety levels improved after surgery compared with their preoperative levels. Preoperative trait anxiety levels can be used as a reference indicator to screen patients who may have high-state anxiety levels after orthognathic surgery. The creation of a screening scale will assist health care professionals to more pertinently help patients with high anxiety., (Copyright © 2024. Published by Elsevier Inc.)

The extraction methods for traditional Chinese medicine (TCM) may have varying therapeutic effects on diseases. Currently, Pueraria lobata (PL) is mostly extracted with ethanol, but decoction, as a TCM extraction method, is not widely adopted. In this study, we present a strategy that integrates targeted metabolomics, 16 s rDNA sequencing technology and metagenomics for exploring the potential mechanism of the water extract of PL (PLE) in treating myocardial infarction (MI). Using advanced analytical techniques like ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we comprehensively characterized PLE's chemical composition. Further, we tested its efficacy in a rat model of MI induced by ligation of the left anterior descending branch of the coronary artery (LAD). We assessed cardiac enzyme levels and conducted echocardiograms. UPLC-MS/MS was used to compare amino acid differences in serum. Furthermore, we investigated fecal samples using 16S rDNA sequencing and metagenomic sequencing to study intestinal flora diversity and function. This study demonstrated PLE's effectiveness in reducing cardiac injury in LAD-ligated rats. Amino acid metabolomics revealed significant improvements in serum levels of arginine, citrulline, proline, ornithine, creatine, creatinine, and sarcosine in MI rats, which are key compounds in the arginine metabolism pathway. Enzyme-linked immunosorbent assay (ELISA) results showed that PLE significantly improved arginase (Arg), nitric oxide synthase (NOS), and creatine kinase (CK) contents in the liver tissue of MI rats. 16 s rDNA and metagenome sequencing revealed that PLE significantly improved intestinal flora imbalance in MI rats, particularly in taxa such as Tuzzerella, Desulfovibrio, Fournierella, Oscillibater, Harryflintia, and Holdemania. PLE also improved the arginine metabolic pathway in the intestinal microorganisms of MI rats. The findings indicate that PLE effectively modulates MI-induced arginine levels and restores intestinal flora balance. This study, the first to explore the mechanism of action of PLE in MI treatment considering amino acid metabolism and intestinal flora, expands our understanding of the potential of PL in MI treatment. It offers fresh insights into the mechanisms of PL, guiding further research and development of PL-based medicines., 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 © 2024. Published by Elsevier B.V.)

Product inhibition caused by organic acids is a serious issue in establishing economical biochemical production systems. Herein, for enhanced production of glutaric acid by overcoming product inhibition triggered by glutaric acid, a whole-cell bioconversion system equipped with biocatalyst recycling process and in situ product recovery by adsorption was developed successfully. From the whole-cell bioconversion reaction, we found that both dissociated and undissociated forms of glutaric acid acted as an inhibitor in the whole-cell bioconversion reaction, wherein bioconversion was hindered beyond 200 mM glutaric acid regardless of reaction pH. Therefore, as the promising solution for the inhibition issue by glutaric acid, the biocatalyst-recycled bioconversion process integrated with in situ product recovery by adsorption was introduced in the whole-cell bioconversion. As a result, 592 mM glutaric acid was produced from 1000 mM 5-aminovaleric acid with 59.2% conversion. We believe that our system will be a promising candidate for economically producing organic acids with high titer., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: This study aimed to compare postsurgical stability between conventional (CSA) and surgery-first (SFA) approaches and investigate its prognostic factors in patients with a skeletal Class Ⅲ extraction., Methods: Twenty and 19 patients treated with LeFort I osteotomy and bilateral sagittal split ramus osteotomy (BSSRO) with premolar extraction were enrolled in SFA and CSA groups, respectively. Serial cone-beam computed tomography images obtained before surgery, immediately after surgery (T1), 3 months after surgery, and 12 months after surgery were used for 3-dimensional quantitative analysis. The condyle was segmented for analyzing volumetric changes. Repeated measures analysis of variance, independent t test, and chi-square test were used to compare time-course and intergroup differences. Pearson and Kendall correlation and multivariate linear regression analyses were used to explore prognostic factors affecting skeletal stability., Results: In both CSA and SFA, postsurgical relapse mainly occurred in the mandible sagittal and vertical dimensions and during the first 3 months after surgery. Stability in SFA was significantly less than that in CSA. Intraoperatively, inferolateral condylar displacement with proximal segment inwards, clockwise rotation, and return movements after surgery were observed regardless of the treatment approach. The condylar volume remained stable over time. Multivariate regression analysis showed that posterior vertical dimension (VD) at T1 (-1.63 mm), surgical amount of mandibular setback (-10.33 mm), surgical condylar downwards displacement (-1.28 mm), and anterior overjet at T1 (6.43 mm) were the most important predictors of early mandibular relapse (r 2  = 0.593)., Conclusions: The risk of early relapse could be reduced by controlling the anterior, middle, and posterior constraints provided by the prediction model., (Copyright © 2023 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Zika virus (ZIKV) is a mosquito-borne virus that has re-emerged as a significant threat to global health in the recent decade. Whilst infections are primarily asymptomatic, the virus has been associated with the manifestation of severe neurological complications. At present, there is still a lack of approved antivirals for ZIKV infections. In this study, chelerythrine chloride, a benzophenanthridine alkaloid, was identified from a mid-throughput screen conducted on a 502-compound natural products library to be a novel and potent inhibitor of ZIKV infection in both in-vitro and in-vivo assays. Subsequent downstream studies demonstrated that the compound inhibits a post-entry step of the viral replication cycle and is capable of disrupting viral RNA synthesis and protein expression. The successful generation and sequencing of a ZIKV resistant mutant revealed that a single S61T mutation on the viral NS4B allowed ZIKV to overcome chelerythrine chloride inhibition. Further investigation revealed that chelerythrine chloride could directly inhibit ZIKV protein synthesis, and that the NS4B-S61T mutation confers resistance to this inhibition. This study has established chelerythrine chloride as a potential candidate for further development as a therapeutic agent against ZIKV infection., 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 © 2023 Elsevier B.V. All rights reserved.)

Fine particulate matter (PM 2.5 )-related health issues have received increasing attention as a worldwide public health problem, and PM 2.5 -related chronic kidney disease (CKD) has been emerging over the years. Limited research has focused on the mechanism of PM 2.5 -induced kidney disease. To investigate the impact of PM 2.5 on the kidney and its potential mechanism, we generated a PM 2.5 -exposed C57BL/6 mouse model by using Shanghai Meteorological and Environment Animal Exposure System (Shanghai-METAS) for 12 weeks, urine, blood and kidney tissues were collected. The pathological changes and the function of the kidney were measured after PM 2.5 exposure for 12 weeks. Along with glomerular damage, tubular damage was also severe in PM 2.5 -induced mice. The results of mRNA-seq indicate that pyroptosis is involved. Pyroptosis is defined as caspase-1-dependent programmed cell death in response to insults. The expression of the nucleotide-binding and oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3), Caspase-1, gasdermin D (GSDMD) and IL-1β was detected. NLRP3 inflammasome activation and subsequent pyroptosis were observed in PM 2.5 -exposed kidney tissues and PM 2.5 -exposed Bumpt cells too. At the meantime, the inhibitors of NLRP3 and caspase-1 were applied to the PM 2.5 exposed Bumpt cells. It turned out to have a significant rescue effect of the inhibitors. This study revealed new insights into PM 2.5 -induced kidney injury and specific kidney pathological damage, as well as morphological changes, and defined the important role of pyroptosis in PM 2.5 -induced kidney dysfunction., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Robot-assisted minimally invasive surgery has been broadly employed in complicated operations. However, the multiple surgical instruments may occupy a large amount of visual space in complex operations performed in narrow spaces, which affects the surgeon's judgment on the shape and position of the lesion as well as the course of its adjacent vessels/lacunae. In this paper, a surgical scene reconstruction method is proposed, which involves the tracking and removal of surgical instruments and the dynamic prediction of the obscured region. For tracking and segmentation of instruments, the image sequences are preprocessed by a modified U-Net architecture composed of a pre-trained ResNet101 encoder and a redesigned decoder. Also, the segmentation boundaries of the instrument shafts are extended using image filtering and a real-time index mask algorithm to achieve precise localization of the obscured elements. For predicting the deformation of soft tissues, a soft tissue deformation prediction algorithm is proposed based on dense optical flow gravitational field and entropy increase, which can achieve local dynamic visualization of the surgical scene by integrating image morphological operations. Finally, the preliminary experiments and the pre-clinical evaluation were presented to demonstrate the performance of the proposed method. The results show that the proposed method can provide the surgeon with a clean and comprehensive surgical scene, reconstruct the course of important vessels/lacunae, and avoid inadvertent injuries., 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 © 2023 Elsevier Ltd. All rights reserved.)

Refractory chronic cough is defined as a clinical condition in which the cause of the cough remains unclear after comprehensive examination and treatment, or the cause is clear but symptomatic treatment is ineffective. Patients with refractory chronic cough experience a variety of physiological and psychological issues that significantly lower their quality of life and place a significant socio-economic burden on society. As a result, research both domestically and internationally has turned heavily toward these patients. Recently, several studies have identified P2X3 receptor antagonists for the treatment of refractory chronic cough, and this paper reviews the background, mechanism of action, evidence-based proof and application prospects of this class of drugs. KEY MESSAGE: There were plenty of studies about P2X3 receptor antagonists in the past, and in recent years this series of drugs are effective in refractory chronic cough. Although review articles summarizing have been published previously, most have focused on their chemical properties rather than their clinical aspects, with some omitting drugs that have been in clinical studies for nearly two years such as Eliapixant and Sivopixant. Focusing on four P2X3 receptor antagonists with proven efficacy in clinical studies, we analyzed the characteristics and disadvantages of each drug by comparing their clinical results of them and theoretically explained the common side effects of these drugs, as well as their potential for treating refractory chronic cough. This article can be used as a reference for the follow-up studies of P2X3 receptor antagonists in chronic cough. Additionally, it also has implications for the clinical focus of the drug and the approaches to relieve some side effects., Competing Interests: Declaration of competing interest The authors of the manuscript entitled “Potential applications of P2X3 receptor antagonists in the treatment of refractory cough”declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Ltd.)

Metal-organic frameworks (MOFs) have a potential application in blood purification, but their microcrystalline nature has hampered their industrial application. Here, novel MOFs-polymer beads based on UiO, sodium alginate, polyacrylic acid, and poly (ethylene imine) were prepared and applied as a whole blood hemoadsorbent for the first time. The amidation among polymers immobilized UiO66-NH 2 into the network of the optimal product (SAP-3), and the NH 2 of UiO66-NH 2 significantly increased the removal rate (70 % within 5 min) of SAP-3 on bilirubin. The adsorption of SAP-3 on bilirubin mainly obeyed the pseudo-second-order kinetic, Langmuir isotherm and Thomas models with a maximum adsorption capacity (q m ) of 63.97 mg·g -1 . Experimental and density functional theory simulation results show that bilirubin was mainly adsorbed by UiO66-NH 2 via electrostatic force, hydrogen bonding, and π-π interactions. Notably, the adsorption in vivo show that the total bilirubin removal rate in the whole blood of the rabbit model was up to 42 % after 1 h of adsorption. Given its excellent stability, cytotoxicity, and hemocompatibility, SAP-3 has a great potential in hemoperfusion therapy. This study proposes an effective strategy for settling the powder property of MOFs and could provide experimental and theoretical references for application of MOFs in blood purification., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: Myocardial infarction with nonobstructive coronary artery (MINOCA) is a heterogeneous syndrome caused by different pathophysiologic mechanisms. There is limited evidence regarding prognosis of patients with MINOCA caused by different mechanisms., Objectives: The present study aimed to assess the underlying mechanisms of MINOCA by optical coherence tomography (OCT) and to correlate with clinical outcomes., Methods: Patients with MINOCA were divided into 2 groups based on OCT findings: atherosclerotic MINOCA (Ath-MINOCA) and nonatherosclerotic MINOCA (non-Ath-MINOCA). Major adverse cardiac events (MACE) were defined as cardiac death, nonfatal MI, target lesion revascularization, stroke, and rehospitalization for unstable or progressive angina., Results: Among 7,423 patients with a clinical diagnosis of MI who underwent angiography, 190 of 294 MINOCA were studied using OCT. The causes of Ath-MINOCA (n = 99, 52.1%) were plaque erosion (n = 64, 33.7%), plaque rupture (n = 33, 17.4%), and calcified nodule (n = 2, 1.1%) whereas the causes of non-Ath-MINOCA (n = 91, 47.9%) were spontaneous coronary artery dissection (n = 8, 4.2%), coronary spasm (n = 9, 4.7%), and unclassified cause (n = 74, 38.9%). The 1-year MACE was 15.3% for Ath-MINOCA vs 4.5% for non-Ath-MINOCA (P = 0.015). An atherosclerotic cause was an independent predictor of MACE (HR: 5.36 [95% CI: 1.08-26.55]; P = 0.040), mainly driven by target lesion revascularization and rehospitalization, despite the composite endpoint including cardiac death and MI showing no difference., Conclusions: OCT identified a cause in 61.1% of MINOCA, in which Ath-MINOCA represents an important and distinct MINOCA subset. Ath-MINOCA were more common and associated with worse outcomes. (Incidence Rate of Heart Failure After Acute Myocardial Infarction With Optimal Treatment; NCT03297164; Paradigm Shift in the Treatment of Patients With ACS; NCT02041650)., Competing Interests: Funding Support and Author Disclosures This work was supported by National Natural Science Foundation of China (grants 81722025, 82061130223, and 81827806 to Dr Jia) and National Key Research and Development Program of China (2016YFC1301101 and 2016YFC1301103 to Dr Yu). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The direction and quantity of surface water - groundwater interaction (SGI) in alpine-arid zones can be tracked using multiple tracers. However, few studies have examined whether the optical indices of dissolved organic matter (DOM) can also track SGI. This study used excitation-emission matrix spectroscopy combined with parallel factor analysis (EEM-PARAFAC) to reveal the optical variations in dissolved organic matter (DOM) in groundwater and surface water with various SGIs in the Datonghe watershed. The results showed that the absorbance spectral indices of DOM did not vary with SGI, whereas DOM fluorescence varied with SGI. PARAFAC indicated that groundwater predominantly recharged by precipitation had significantly lower humic-like (C2 and C3) fluorescence than groundwater predominantly recharged by riverine water. Since humic-like substances were more likely to be retained in the aqueous phase than protein-like substances, significantly fewer protein-like substances (C4) were introduced when surface water was recharged to groundwater. This suggests that C4 can be used as an effective indicator to identify the SGI process from surface water to groundwater. Based on the principal component analysis of DOM and hydrochemical indicators, it was concluded that traditional chemical tracers were significantly and positively correlated with humic-like substances C2 and C3. Given that C3 is more stable and persistent in the environment, it could be used to track SGI processes midstream of the watershed. The findings of this study will assist in accurately identifying the processes and mechanisms of SGI on a regional scale and provide a basis for future water resource management and the protection of water ecosystems., 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 B.V. All rights reserved.)

Chemically protected sodium butyrate (CSB) is a new kind of sodium butyrate. Our previous study found that 1,000 mg/kg of CSB had the potential capacity of improving growth performance and promoting early development of small intestine in broilers. This study aimed to investigate the effect of long-term antibiotics or CSB supplementation for intestinal microflora dynamical regulation in broilers. One hundred ninety-two 1-day-old Arbor Acres male broilers were randomly allocated into 3 dietary treatment (8 replicates per treatment) and fed with a basal diet (CON), a diet supplemented with the antibiotics (enramycin, 8 mg/kg and aureomycin, 100 mg/kg) (ANT), or a diet supplemented with 1,000 mg/kg of CSB, respectively. Results showed that dietary supplementation of CSB or ANT treatment elevated the weight gain and feed conversion ratio (FCR; P < 0.05), as compared with control (CON) group. Additionally, CON, CSB, or ANT administration dynamically altered the gut microbiota composition as time goes on. The increased presence of potential pathogens, such as Romboutsia and Shuttleworthia, and decreased beneficial bacteria such as Alistipes, Akkermansia, and Bacteroides were verified in new gut homeostasis reshaped by long-term antibiotics treatment, which has adverse effects on intestinal development and health of broilers. Conversely, CSB supplementation could dynamically enhance the relative abundance of Bacteroides, and decrease Romboutsia and Shuttleworthia in new microflora, which has positive effects on intestinal bacteria of broilers compared with CON group. Meanwhile, CSB supplementation was significantly increased the concentration of propionic acid and total short chain fatty acids (total SCFA; P < 0.05) in comparison with CON and ANT groups. Moreover, CSB treatment significantly increased anti-inflammatory and antioxidative capacities (P < 0.05) of broilers compared with ANT group. Taken together, we revealed characteristic structural changes of gut microbiota throughout long-term CSB or ANT supplementation in broilers, which provided a basic data for evaluating the mechanism of action affecting intestinal health by CSB or ANT administration and CSB as an alternative to antibiotics in the broilers industry., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Photodynamic therapy could be one approach to treat colorectal cancer though resistance leads to failure of therapy. Akt activation is a cellular survival response to photodynamic therapy and is also a reason for resistance. Thus, inhibition of Akt is a strategy to decrease resistance. Akt interacts with connexin 43, another protein involved in photodynamic therapy resistance. Connexin 43 is widely expressed in different human tissues and has a complex role in tumor development. However, the mechanism of inhibition of Akt by connexin 43 that sensitizes colorectal cancer cells to photodynamic therapy needs further investigation., Methods: In this study, two colorectal cancer cells with low phosphorylated connexin 43 level were used to explore this mechanism. LY294002 was used as an Akt inhibitor, and connexin 43-pCMV3 was transfected into cells to increase connexin 43 expression., Results: Akt and connexin 43 inhibit each other in both colorectal cancer cell lines. In vitro and in vivo experiments showed that LY294002 and connexin 43 transfection sensitized cells to hematoporphyrin-Photodynamic therapy. LY294002 increased the sensitivity of cells to photodynamic therapy with a pronounced effect in cells with high expression levels of connexin 43., Conclusions: Connexin 43 should be considered an important factor in increasing the phototoxicity of photodynamic therapy in colorectal cancer through Akt inhibition., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

The biocompatibility of metal-organic frameworks (MOFs) is necessary to humans but is far from being sufficiently addressed. This study focused on the effects of microsize on the biocompatibility of MOFs by selecting UiO67 with micron and submicron size as the MOFs models. Under the dose metric of surface area, the binding constant between UiO67 and human serum albumin (HSA) gradually increased with increased UiO67 size. Submicron UiO67 induced stronger conformational transformation and more greatly affected the protein surface hydrophobicity than micron UiO67. Micron UiO67 also inhibited the esterase-like activity of HSA through competitive inhibition mechanism, whereas submicron UiO67 inhibited it through noncompetitive inhibition mechanism. The size of UiO67 had little effect on hemocompatibility. A smaller size of UiO67, corresponded with a higher IC50 value for 293 T and LO2 cells, and the adsorption of HSA can effectively improve cytotoxicity. In vivo toxicity evaluations revealed that all UiO67 did not cause obvious distortion of organs, and they were metabolized primarily in the kidney. These results provided useful information about the toxicity of MOFs and experimental references for the development of MOFs-based engineering materials., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: The efficacy of chemoradiotherapy regimen in the treatment of stage Ⅳ nasopharyngeal carcinoma (Ⅳ NPC) is not clear. This retrospective study aimed to reveal the benefit of chemoradiotherapy in Ⅳ-NPC and to develop a survival prognostic model for the disease prediction., Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER) database at https://seer.cancer.gov was retrieved for stage Ⅳ NPC patients between 2004 and 2016. The patients were divided into two groups of radiotherapy and chemoradiotherapy according to the treatment method. Overall survival (OS) and cancer-specific survival (CSS) between the groups were compared using Kaplan-Meier analysis, log-rank test, and propensity matching score (PSM). Cox proportional hazards model, nomogram, and receiver operating characteristic (ROC) curve were employed to establish the prognostic model., Results: A total of 729 patients with Ⅳ NPC were introduced, of whom 44 received radiotherapy and 685 received chemoradiotherapy. Results of statistical tests demonstrated that chemoradiotherapy was associated with improved OS and CSS, especially in the patients with ⅣA NPC (P < 0.05); further multivariate analysis with PSM confirmed that chemoradiotherapy benefited the patients' OS (HR: 0.24, 95% CI: 0.12-0.50; P < 0.001). Moreover, the efficacy of chemoradiotherapy was found significantly correlated to metastasis. Even though chemoradiotherapy had an obvious survival benefit in patients without metastasis, it only helped to improve the CSS in those with metastases., Conclusion: This study indicated that chemoradiotherapy could improve the survival of NPC patients at stage ⅣA and non-metastasis. The nomogram we established may provide reference for clinical treatment of NPC., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Our aim is to build a physiologically based pharmacokinetic and JAK2 occupancy model (PBPK-JO) to simultaneously predict pharmacokinetic (PK) and pharmacodynamic (PD) changes of baricitinib (BAR) in healthy humans when co-administrated with kidney transporters OAT3 and MATE2-K inhibitors, and in patients with hepatic and renal impairment., Methods: Probenecid and vandetanib were selected as OAT3 and MATE2-K competitive inhibitors, respectively. The PBPK-JO model was built using physicochemical and biochemical properties of BAR, and then verified by observed clinical PK. Finally, the model was applied to determine optimal dosing regimens in various clinical situations., Results: Here, we have successfully simulated PK and JAK2 occupancy profiles in humans by PBPK-JO model. Moreover, this modelling reproduced every observed PK data, and every mean relative deviation (MRD) was below 2. The simulation suggested that PK of BAR had a significant change (2.22-fold increase), however PD only had a slight increase of 1.14-fold. Additionally, the simulation also suggested that vandetanib was almost unlikely to affect the PK and PD of BAR. In simulations of hepatic and renal impairment patients, the predictions suggested that significant changes in the PK and PD of BAR occurred. However, there was a lower fold increase in JAK2 occupancy than in PK in patients relative to healthy individuals., Conclusion: Administration dose adjustment of BAR when co-administrated with OAT3 inhibitors or in patients with hepatic or renal impairment should combine PK and PD changes of BAR, instead of only considering PK alteration., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Suitable scaffold structures and mechanical loading are essential for functional tendon engineering. However, the bipolar fibril structure of native tendon collagen is yet to be recaptured in engineered tendons. This study compared the development of Achilles tendons of postnatal rats with and without (via surgical section) mechanical loading to define the mechanism of mechanical stimulation-mediated tendon development. The results demonstrated that the severed tendons weakened mechanically and exhibited disorganization without a bipolar fibril superstructure. Proteomic analysis revealed differentially expressed key regulatory molecules related to the collagen assembly process, including decreased fibromodulin, keratocan, fibroblast growth factor-1, and increased lumican and collagen5a1 in the severed tendons with immunohistochemical verification. Additionally, a complex regulatory network of mechanical stimulation-mediated collagen assembly in a spatiotemporal manner was also revealed using bioinformatics analysis, wherein PI3K-Akt and HDAC4 may be the predominant signaling pathways. A wavy microgrooved surface (Y = 5.47sin(0.015x)) that biomimics tendon topography was observed to enhance the expression of collagen assembly molecules under mechanical loading, and the aforementioned pathways are particularly involved and verified with their respective inhibitors of LY-294002 and LMK-235. Furthermore, an electrospun crimped nanofiber scaffold (approximately 2 μm fiber diameter and 0.12 crimpness) was fabricated to biomimic the tenogenic niche environment; this was observed to be more effective on enhancing collagen production and assembly under mechanical stimulation. In conclusion, the synergistic effect between topographical niche and mechanical stimulation was observed to be essential for collagen assembly and maturation and should be applied to functional tendon engineering in the future. STATEMENT OF SIGNIFICANCE: In biomaterial-mediated tendon regeneration, mechanical stimulation is essential for tendon collagen assembly. However, the underlying mechanisms remain not fully defined, leading to the failure of the native-like collagen regeneration. In this study, a mechanical stimulation deprivation model of rat tendon was established to reveal the mechanisms in tendon development and define the key regulatory molecules including small leucine-rich proteoglycans, lysyl oxidase and collagen V. After ensuring the importance of biomimetic structure in tendon remodeling, crimped nanofibers were developed to verify these regulatory molecules, and demonstrated that mechanical stimulation significantly enhanced collagen assembly via PIK3 and HDAC4 pathways in biomaterial-regulated tendon regeneration. This study provides more insightful perspectives in the physiologically remodeling progression of tendon collagen and design of tendon scaffolds., 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. Published by Elsevier Ltd.)

As a new form of nicotine introduction for novel tobacco products, the interaction of nicotine salt with biological macromolecules may differ from that of free nicotine and thus affect its transport and distribution in vivo. Hence, the mechanism underlying the interaction between 2,6-dihydroxybenzoic acid nicotine salt (DBN) and human serum albumin (HSA) was investigated by multi-spectroscopy, molecular docking, and dynamic simulation. Experiments on steady-state fluorescence and fluorescence lifetime revealed that the quenching mechanism of DBN and HSA was dynamic quenching, and binding constant was in the order of 10^4 L mol -1 . Thermodynamic parameters exhibited that the binding was a spontaneous process with hydrophobic forces as the main driving force. Fluorescence competition experiments revealed that DBN bound to site I of HSA IIA subdomain. According to the results of synchronous fluorescence, 3D fluorescence, FT-IR spectroscopy, circular dichroism (CD) spectroscopy, and molecular dynamics (MD) simulation, DBN did not affect the basic skeleton structure of HSA but changed the microenvironment around the amino acid residues. Computer simulations positively corroborated the experimental results. Moreover, DBN decreased the surface hydrophobicity and weakened the esterase-like activity of HSA, leading to the impaired function of the latter. This work provides important information for studying the interaction between DBN as a nicotine substitute and biological macromolecules and contributes to the further development and application of DBN., 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 B.V. All rights reserved.)

Background: Factor XI (FXI) inhibition offers the promise of hemostasis-sparing anticoagulation for the prevention and treatment of thromboembolic events. Abelacimab (MAA868) is a novel fully human monoclonal antibody that targets the catalytic domain and has dual activity against the inactive zymogen Factor XI and the activated FXI., Objectives: To investigate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of single dose intravenous and multiple dose subcutaneous administration of abelacimab in healthy volunteers and patients with atrial fibrillation, respectively., Patients/methods: In study ANT-003, healthy volunteers were administered single intravenous doses of abelacimab (30-150 mg) or placebo. The ANT-003 study also included a cohort of obese but otherwise healthy subjects. In study ANT-004, patients with atrial fibrillation were administered monthly subcutaneous doses of abelacimab (120 mg and 180 mg), or placebo, for 3 months. Key PK and PD parameters, including activated partial thromboplastin time (aPTT) and free FXI levels, as well as anti-drug antibodies (ADA) were assessed., Results: Following intravenous administration of abelacimab, the terminal elimination half-life ranged from 25 to 30 days. One hour after the start of the intravenous infusion greater than 99% reductions in free FXI levels were observed. Following once monthly subcutaneous administration, marked reductions from baseline in free FXI levels were sustained. Parenteral administration of abelacimab demonstrated a favorable safety profile with no clinically relevant bleeding events., Conclusions: Intravenous and multiple subcutaneous dose administration of abelacimab were safe and well tolerated. The safety, PK, and PD data from these studies support the clinical development of abelacimab., (© 2021 Anthos Therapeutics. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Background: A Chinese surgical robot, Micro Hand S, was introduced for clinical use as a novel robotic platform. This study aimed to comprehensively compare the early experience of the Micro Hand S robot-assisted total mesorectal excision (TME) with conventional approaches., Methods: Between May 2017 and April 2018, 99 consecutive patients who underwent open, laparoscopic and Micro Hand S robot-assisted TME (O-/L-/RTME) for rectal cancer were included. Clinical and pathological outcomes were retrospectively analyzed. Surgical success as the primary endpoint was defined as the absence of (i) conversion, (ii) incomplete TME, (iii) involved circumferential and distal resection margins (CRM/DRM), (iv) severe complications., Results: The rate of surgical success was similar (89.7 vs. 86.4 vs. 84.6%, p = 0.851) in the three groups and the respective incidences were as follows: conversion (not applicable, 4.5 vs. 2.3%, p = 1.000), incomplete TME (6.9 vs. 6.8 vs. 3.8%, p = 0.980), involved CRM/DRM (0 vs. 2.3 vs. 3.8%, p = 0.592), severe complications (3.4 vs. 4.5 vs. 7.7%, p = 0.844). Compared with open and laparoscopic surgery, the robotic surgery was associated with longer operative time, less blood loss, earlier first flatus time and liquid intake time, and shorter length of hospital stay (p < 0.05)., Conclusions: The Micro Hand S assisted TME is safe and feasible, showing comparable outcomes than conventional approaches, with superiority in blood loss, recovery of bowel function, length of hospital stay, but with increased operative time., Competing Interests: Declaration of competing interest All authors declare that they have non-financial conflicts of interest., (Copyright © 2021. Published by Elsevier Taiwan LLC.)

Objective: The aim of this study was to explore the clinical value of lymph node dissection (LND) for intrahepatic cholangiocarcinoma (ICC)., Methods: Clinical and pathological data were collected from 147 ICC patients who attended two tertiary centers over the past 5 years. The patients were classified into two groups: the LND group (group A) and the no-performance LND (NLND) group (group B). Clinical and pathological parameters were compared between the two groups to analyze the impact of LND on the long-term survival time of ICC patients., Results: Of the 147 patients, 54.4% (80) received LND and 42.5% (34/80) of these were found to have lymph node metastasis (LNM). LND did not increase postoperative complications (27.5%, P = 0.354), but postoperative hospital stays were longer (12.2 ± 6.3 d, P = 0.005) in group A compared with group B (20.9%, 9.5 ± 3.5 d). The 5-year survival rates of groups A and B are almost similar (21% vs 29%, P = 0.905). The overall survival rate of cN0 (diagnosis obtained by imaging) is better than pN1 (diagnosis obtained by histopathology), but lower than pN0 (all P < 0.05). Compared with NLND, the median survival time of LND patients with T1 has not significantly improved (29.3 vs 35.1 months, P = 0.762), but the patients with T2-4 has been significantly increased (29.0 vs 17.1 months, P = 0.040). Elevated CA19-9 level (HR = 1.764, 95% CI: 1.113-2.795, P = 0.016), vascular invasion (HR = 2.697, 95% CI: 1.103-6.599, P = 0.030), and T category (HR = 1.848, 95% CI: 1.059-3.224, P = 0.031) were independent risk factors for poor long-term survival time of the ICC patients (all P values < 0.05)., Conclusion: ICC patients with cN0 may have LNM, and the long-term survival time of LNM patients is usually poor. We suggest that patients with ICC may require routine LND, especially those with T2-4 category., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021. Published by Elsevier Taiwan LLC.)

Loss of FLG causes ichthyosis vulgaris. Reduced FLG expression compromises epidermal barrier function and is associated with atopic dermatitis, allergy, and asthma. The flaky tail mouse harbors two mutations that affect the skin barrier, Flg ft , resulting in hypomorphic FLG expression, and Tmem79 ma , inactivating TMEM79. Mice defective only for TMEM79 featured dermatitis and systemic atopy, but also Flg ft/ft BALB/c congenic mice developed eczema, high IgE, and spontaneous asthma, suggesting that FLG protects from atopy. In contrast, a targeted Flg-knockout mutation backcrossed to BALB/c did not result in dermatitis or atopy. To resolve this discrepancy, we generated FLG-deficient mice on pure BALB/c background by inactivating Flg in BALB/c embryos. These mice feature an ichthyosis phenotype, barrier defect, and facilitated percutaneous sensitization. However, they do not develop dermatitis or atopy. Whole-genome sequencing of the atopic Flg ft BALB/c congenics revealed that they were homozygous for the atopy-causing Tmem79 matted mutation. In summary, we show that FLG deficiency does not cause atopy in mice, in line with lack of atopic disease in a fraction of patients with ichthyosis vulgaris carrying two Flg null alleles. However, the absence of FLG likely promotes and modulates dermatitis caused by other genetic barrier defects., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has survival benefits in patients with intraperitoneal malignant lesions, but there is no study specific to intrahepatic cholangiocarcinoma (ICC)., Purpose: To compare the prognosis of patients with advanced ICC undergoing CRS + HIPEC compared with CRS alone., Methods: This study was a retrospective cohort study of patients with advanced ICC treated at the Shanghai Eastern Hepatobiliary Surgery Hospital between 01/2014 and 12/2018. The patients were divided into either CRS + HIPEC or CRS group based on the treatment they received. Overall survival (OS), complications, hospital stay, biochemical indicators, tumor markers, and number of HIPEC were examined., Results: There were 51 and 61 patients in the CRS + HIPEC and CRS groups, respectively. There were no differences between the groups regarding preoperative CA19-9 levels (421 ± 381 vs. 523 ± 543 U/mL, P = 0.208). The hospital stay was longer in the CRS + HIPEC group (22.2 ± 10.0 vs. 18.6 ± 7.6 days, P = 0.033). The occurrence of overall complications was similar in the two groups (37.2% vs. 34.4%, P = 0.756). The postoperative CA19-9 levels were lower in the CRS + HIPEC group compared with the CRS group (196 ± 320 vs. 337 ± 396 U/mL, P = 0.044). The median OS was longer in the CRS + HIPEC group than in the CRS group (25.53 vs. 11.17 months, P < 0.001). Compared with the CRS group, the CRS + HIPEC group showed a higher occurrence of leukopenia (7.8% vs. 0, P = 0.040) but a lower occurrence of total bilirubin elevation (15.7% vs. 37.7%, P = 0.032)., Conclusion: CRS + HIPEC could be a treatment option for patients with advanced ICC, with improved OS and similar complications and adverse events compared with CRS alone., Competing Interests: Declaration of competing interest All authors declare that they have no competing interests., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. However, data concerning the epidemiological features, viral shedding, and antibody dynamics between asymptomatic SARS-CoV-2 carriers and COVID-19 patients remain controversial., Methods: We enrolled 193 SARS-CoV-2 infected subjects in Ningbo and Zhoushan, Zhejiang, China, from January 21 to March 6, 2020. All subjects were followed up to monitor the dynamics of serum antibody immunoglobulin M (IgM) and IgG against SARS-CoV-2 using colloidal gold-labeled and enzyme-linked immunosorbent assays., Results: Of those, 31 were asymptomatic SARS-CoV-2 carriers, 148 symptomatic COVID-19 patients, and 14 presymptomatic COVID-19 patients. Compared to symptomatic COVID-19 patients, asymptomatic carriers were younger and had higher levels of white blood cell and lymphocyte, lower level of C-reactive protein, and shorter viral shedding duration. Conversion of IgM from positive to negative was shorter in asymptomatic carriers than in COVID-19 patients (7.5 vs. 25.5 days, P = 0.030). The proportion of those persistently seropositive for IgG against SARS-CoV-2 was higher in COVID-19 patients than in asymptomatic carriers (66.1% vs. 33.3%, P = 0.037). Viral load was higher in symptomatic patients than presymptomatic patients (P = 0.003) and asymptomatic carriers (P = 0.004). Viral shedding duration was longer in presymptomatic COVID-19 patients than in asymptomatic carriers (48.0 vs. 24.0 days, P = 0.002). Asymptomatic carriers acquired infection more from intra-familial transmission than did COVID-19 patients (89.0% vs. 61.0%, P = 0.028). In 4 familial clusters of SARS-CoV-2 infection, asymptomatic carriers were mainly children and young adults while severe COVID-19 was mainly found in family members older than 60 years with comorbidities., Conclusion: Asymptomatic carriers might have a higher antiviral immunity to clear SARS-CoV-2 than symptomatic COVID-19 patients and this antiviral immunity should be contributable to innate and adaptive cellular immunity rather than humoral immunity. The severity of COVID-19 is associated with older age and comorbidities in familial clustering cases., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The spatiotemporal trend of renal involvement in coronavirus disease 2019 (COVID-19) patients is still unclear. Therefore, the aim of this study was to reveal the dynamics of renal involvement superimposed COVID-19 according to time and space., Methods: COVID-19 patients reporting renal involvement were included in this study. The following information was collected from relevant articles: first author, patient demographics, patient enrollment period, location, definition of acute kidney injury (AKI), prevalence of AKI, and use of renal replacement therapy (RRT)., Results: A total of 17 134 patients were finally included. The overall prevalence of AKI in COVID-19 patients was 19%, with 7% of them undergoing RRT. The overall risk of AKI in patients enrolled before March 1, 2020 (9%) was significantly lower than that after March 1, 2020 (36%) (P < 0.00001). Moreover, the overall risk of AKI outside Asia (35%) was significantly higher than that in Asia (10%) (P < 0.00001). Additionally, similar to patients requiring RRT, AKI patients were more likely to become seriously ill or even to die (P < 0.00001)., Conclusions: This study found that renal involvement superimposed COVID-19, a comorbidity portending a poor prognosis, has become an increasingly serious problem over time and is more common outside Asia. Thus, more attention should be paid to the management of this specific group of patients., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the diagnostic performance of magnetic resonance hysterosalpingography for fallopian tubal occlusion in the context of female infertility when compared to the diagnostic performance of conditional X-ray hysterosalpingography., Methods: PubMed, EMBASE, Web of Science, EBSCO, Cochrane Library database, Scopus were searched for studies in which magnetic resonance hysterosalpingography and X-ray hysterosalpingography were used as diagnostic tools for tubal occlusion assessment; databases were searched through April 2020. Two researchers conducted study inclusion assessment, data extraction, a systematic review, and pooled meta-analysis independently. Stata 15.1 software was used to analyze the pooled sensitivity, specificity, diagnostic odds ratio, positive and negative likelihood ratios, and the area under the summary receiver-operating characteristic curve of magnetic resonance hysterosalpingography., Results: A total of five studies involving 101 patients and 198 fallopian tubes were finally included. Compared with the conditional X-ray hysterosalpingography (the imaging gold standard), the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve of magnetic resonance hysterosalpingography for tubal occlusion were 0.91 (95% CI: 0.48-0.99), 1.00 (95% CI: 0.87-1.00), 230.47 (95% CI: 6.79-7824.72), 0.09 (95% CI: 0.01-0.80), 2676.10 (95% CI: 61.35-120,000), and 1.00 (95% CI: 0.99-1.00), respectively. Subgroup analyses revealed that viscosity of contrast agent (P = 0.024) and test order (P = 0.036) affected the accuracy of MR-HSG to evaluate tubal occlusion., Conclusions: Our meta-analysis indicated magnetic resonance hysterosalpingography may serve as an alternative for further evaluation of fallopian tubal occlusion of female infertility., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To investigate the epidemiological dynamics, transmission patterns, and the clinical outcomes of Coronavirus disease 2019 (COVID-19) in familial cluster patients in Wuhan, China., Methods: Between January 22, 2020, and February 4, 2020, we enrolled 214 families for this retrospective study. The COVID-19 cases were diagnosed using real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The number of COVID-19 subjects in a family, their relationship with index patients, the key time-to-event, exposure history, and the clinical outcomes were obtained through telephone calls., Results: Overall, 96 families (44.9%) met the criteria of a familial cluster, which is at least one confirmed case in addition to the index patient in the same household. The secondary attack rate was 42.9%, and nearly 95% of index patients transmitted the infection to ≤2 other family members. High transmission pattern was noted between couples (51.0%) and among multi-generations (27.1%). The median serial interval distribution in familial clusters was 5 days (95% CI, 4 to 6). The case fatality rate was 8.7% in index patients and 1.7% in non-familial clusters patients (p = 0.023)., Conclusions: There is a related higher attack rate and worse clinical outcomes in COVID-19 family clusters., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: This study aimed to identify the most useful ultrasound (US) features associated with definite neonatal necrotizing enterocolitis (NEC) and their prognostic values, particularly the calculated markers combined with important features., Methods: A total of 213 suspected NEC cases were collected from the neonatal department of our hospital from January 2015 to August 2017. Each infant received both X-ray and US examinations., Results: No differences were found in sex composition and delivery modes between groups. NEC-positive neonates had poorer prognosis compared to negative ones. The NEC group showed a higher frequency of abnormal signals. US showed higher NEC-related frequencies in different parameters. A variable (named predictor in US [PUS]) with five features was constructed. For NEC diagnosis, this variable provided a much higher area under the curve Q2 (AUC) (0.965) than other parameters. In this model, PUS had a cutoff value of 0.376 with a 0.900 sensitivity and 0.922 specificity. In prognosis, the closest factors were selected to draw a receiver operating characteristic curve, as well as a novel calculated variable US prognostic (USPro) marker. USPro had a much higher AUC (0.86) than other single features and showed a cutoff value of 0.18145, with 0.75 sensitivity and 0.84 specificity. This variable had a weaker power in prognosis when compared with PUS in diagnosis., Conclusions: The application of abdominal color Doppler US can provide high accuracy and sensitivity in NEC diagnosis and also contribute to its prognosis, without induction of radiation. Suspected neonates should be examined using this technique as early as possible.

Introduction: Birth defects are a leading cause of infant death. Pregnant women spend a large amount of time indoors, and little research from population-based studies has investigated the association between indoor air pollution and birth defects. We aimed to examine whether using coal, biomass, or electromagnetic stoves for cooking is associated with risk of birth defects compared to using gas stoves., Methods: A birth cohort study was conducted from 2010 to 2012 in Lanzhou, China. Cases (n = 264) were singleton births with birth defects, which were defined as abnormalities of structure or function, including metabolism, presented at birth based on the International Classification of Diseases (ICD)-10 codes. Controls (n = 9926) were defined as singleton live births without birth defects. Unconditional logistic regression models were employed to estimate the association adjusting for confounding variables., Results: Compared to gas stoves for cooking, biomass (OR = 2.66, 95%CI: 1.38-5.13), and electromagnetic stove (OR = 1.90, 95%CI: 1.26-2.88) for cooking were associated with an increased risk of birth defects. The significant associations remained among non-congenital heart disease (CHD) defects but not CHDs., Conclusions: Using biomass or electromagnetic stoves for cooking during pregnancy was associated with an increased risk of birth defects. Additional studies are warranted to confirm these novel findings. Studies with larger sample size or greater statistical power are also warranted to better estimate the associations for individual birth defects., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Fibers produced from electrospinning are well-known to be extremely fine with diameters ranging from tens of nanometers to a few microns. Such ultrafine fibers not only allow for engineering scaffolds resembling the ultrastructure of the native extracellular matrix, but also offer possibility to explore the remodeling behavior of cells in vitro, due to their mechanically 'adequate' softness endowed by their ultrafine fineness. However, the remodeling effect of cells on the biomimicking fibrous substrates remains to be understood, because the crisscrossing and entangling among nanofibers in those tightly packed fibrous mats ultimately lead to merely a topological phenomenon, similar to that of the nanofiber-like topography embossed on the surface of a solid matter. In this study, the effect of nanofiber density on cellular response behavior was investigated by reducing the density of electrospun fiber networks. Using polycaprolactone (PCL) as a model polymer, randomly oriented fiber networks with various densities, namely, 37.7 ± 16.3 μg/cm 2 (D1), 103.8 ± 16.3 μg/cm 2 (D2), 198.2 ± 40.0 μg/cm 2 (D3), and 471.8 ± 32.7 μg/cm 2 (D4), were prepared by electrospinning for varied collection durations (10 s, 50 s, 100 s, and 10 min, respectively). By examining the responsive behavior of the human induced pluripotent stem cell-derived mesenchymal stem cells (hiPS-MSCs) cultured on these nanofibrous networks, we showed that the fiber network with a moderate density (D2) is beneficial to the cell attachment, spreading, actin polymerization, contractility and migration. There also showed an increased tendency in nuclear localization of the Yes-associated protein (YAP) and subsequent activation of YAP responsive gene transcription, and cell proliferation and collagen synthesis were also enhanced on the D2. However, further increasing the fiber density (D3, D4) gave rise to weakened induction effect of fibers on the cellular responses. These results enrich our understanding on the effect of fiber density on cell behavior, and disclose the dependence of cellular responses on fiber density. This study paves the way to precisely design biomimetic fibrous scaffolds for achieving enhanced cell-scaffold interactions and tissue regeneration., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ambient ammonia exposure has been known to perturb lipid metabolism in farm animals, but the underlying mechanism is unclear. The current study was conducted to investigate how ambient ammonia exposure influences lipid metabolism in the pig model. Twelve pigs were randomly divided into two groups, either exposed to 0 or 35 mg/m 3 atmospheric ammonia for 25 days. Serum ammonia remained unchanged (p > 0.05), but increased serum urea concentration was found (p < 0.05) after ammonia exposure. Ammonia exposure also caused an increased C18:0, C18:2n6c, C18:3n6, C18:3n3, C20:0, C20:2, C20:3n6, C20:3n3, C22:0 concentrations and fat content in the longissimus dorsi muscle (p < 0.05), and also serum total triglyceride (p = 0.0294) and ApoB (p = 0.0061) contents. Analysis of serum free amino acids profile revealed that concentrations of ornithine, tyrosine, asparagine, histidine, phenylalanine, leucine, isoleucine, glutamine and valine were significantly increased in the pigs exposed to 35 mg/m 3 ammonia (p < 0.05). RNA-Seq analysis showed that genes encoding enzymes involved in lipid synthesis (FASN, SCD and FADS1) and uptake (LDLR) were up-regulated, whereas genes related to lipolysis (PNPLA4, ANGPTL4 and CEL), transport (CPT1A, CPT1B and CPT2) and β-oxidation (ACADL, ACADVL, UCP2 and UCP3) were down-regulated. Furthermore, exposure to 35 mg/m 3 atmospheric ammonia increased expression of mTOR (p = 0.0377) and its downstream P70S6K (p = 0.0139) and p-P70S6K (p = 0.0431), but decreased AMPK (p < 0.0001) and p-AMPK (p = 0.0071) in the longissimus dorsi muscle. In conclusion, high concentration of atmospheric ammonia exposure greatly interferes with amino acid metabolism, resulting in increased BCAAs and aromatic amino acids. The increased BCAAs production can up-regulate lipid synthesis and down-regulate β-oxidation by activating mTOR signaling and inhibiting AMPK signaling., 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 © 2020 Elsevier B.V. All rights reserved.)

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a significant impact on social and economic activities. As a high infectious pathogen, the existence of SARS-CoV-2 in public space is very important for its transmission. During the COVID-19 pandemic, hospitals are the main places to deal with the diseases. In this work, we evaluated the exposure risk of SARS-CoV-2 in hospital environment in order to protect healthcare workers (HCWs). Briefly, air and surface samples from 6 different sites of 3 hospitals with different protection levels were collected and tested for the SARS-CoV-2 nucleic acid by reverse transcription real-time fluorescence PCR method during the COVID-19 epidemic. We found that the positive rate of SARS-CoV-2 nucleic acid was 7.7 % in a COVID-19 respiratory investigation wards and 82.6 % in a ICUs with confirmed COVID-19 patients. These results indicated that in some wards of the hospital, such as ICUs occupied by COVID-19 patients, the nucleic acid of SARS-CoV-2 existed in the air and surface, which indicates the potential occupational exposure risk of HCWs. This study has clarified retention of SARS-CoV-2 in different sites of hospital, suggesting that it is necessary to monitor and disinfect the SARS-CoV-2 in hospital environment during COVID-19 pandemic, and will help to prevent the iatrogenic infection and nosocomial transmission of SARS-CoV-2 and to better protect the HCWs., Competing Interests: The authors declare no competing interests., (© 2020 Elsevier Ltd. All rights reserved.)

Introduction: Incorporating fully assembled microvascular networks into bioengineered dental pulp constructs can significantly enhance functional blood flow and tissue survival upon transplantation. Endothelial cells (ECs), cellular building blocks of vascular tissue, play an essential role in the process of prevascularization. However, obtaining sufficient ECs from a suitable source for translational application is challenging. Dental stem cells (DSCs), which exhibit a robust proliferative ability and immunocompatibility because of their autologous origin, could be a promising alternative cell source for the derivation of endothelial lineages. Under specific culture conditions, DSCs differentiate into osteo/odontogenic, adipogenic, chondrogenic, and neurogenic cell lineages., Methods: Recently, a new approach has been developed to directly reprogram cells using chemical cocktails and growth factors. Compared with the traditional reprogramming approach based on the forced expression of exogenous transcription factors, the chemical strategy avoids the risk associated with lentiviral transduction while offering a more viable methodology to drive cell lineage switch. The aim of this review was to unveil the concept of the use of small-molecule compounds and growth factors modulating key signaling pathways to derive ECs from DSCs., Results: In addition, our preliminary study showed that stem cells from the apical papilla could be induced into EC-like cells using small-molecule compounds and growth factors. These EC-like cells expressed endothelial specific genes (CD31 and VEGFR2) and proteins (CD31, VEGF receptor 2, and vascular endothelial cadherin) as well as gave rise to vessel-like tubular structures in vitro., Conclusions: Our preliminary results suggest that chemical reprogramming might offer a novel way to generate EC-like cells from dental stem cells., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)