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Hao Yu,1,2 Jie Yi,1 Ya-ling Dou,1 Yu Chen,1 Ling-jun Kong,1 Jie Wu1 1Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Laboratory Medicine, Beijing Hepingli Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jie WuDepartment of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel +86 106 915 9701Email wujie_pumch@163.comObjective: Human papillomavirus (HPV) infection, especially with high-risk HPV (HR-HPV) genotypes, is closely associated with cervical cancer. This study aimed to observe the epidemiological characteristics of HPV infection among healthy women in Beijing, China.Materials and Methods: Cervical specimens were collected from 29,436 healthy women, who underwent health check-ups in Peking Union Medical College Hospital between 2016 and 2019. A commercial kit was used for the detection of 15 HR-HPV and two low-risk HPV (LR-HPV) genotypes.Results: A total of 3586 (12.18%) participants tested positive for HPV, 3467 of which were infected with HR-HPVs. The most prevalent genotypes were HPV52, 58, 16, 51, and 56. Moreover, while infection with a single genotype (9.84%) was more prevalent, HPV16+52 was the most common combination in those infected with multiple HPVs. Furthermore, the highest infection rate among age groups was in women aged < 25 years (20.92%). No significant difference in the prevalence was observed from 2016 to 2019. However, HPV incidence in Beijing was significantly different than that in all other areas in China, except for Zhengzhou (p < 0.05).Conclusion: Our findings could serve as potential reference for better understanding of the epidemiological characteristics of HPV infection in Beijing.Keywords: human papillomavirus, cervical cancer, prevalence, genotype

Purpose: The aim of this study was to explore the potential correlation between the nuclear receptor subfamily 3 group C member 2 (NR3C2) and outcomes of colon cancer, along with the mechanisms underlying this association., Method: mRNA (messenger RNA) data and clinical records pertaining to colon cancer were retrieved from The Cancer Genome Atlas (TCGA) database. The analysis of NR3C2 expression discrepancies between normal colon and tumor tissues was conducted using R software. In addition, we also studied the relationship between NR3C2 expression and prognosis, pathological parameters. The relative role of NR3C2 were further predicted through bioinformatics methods and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of NR3C2 in colon cancer. Single-cell data from colon cancer samples in the GEO (Gene Expression Omnibus) database further investigated the mechanism of the lower survival associated with NR3C2 dysregulation. NR3C2 expression in three fresh colon cancer samples and their respective paracancer samples was determined. Furthermore, colon cancer cell models overexpressing NR3C2 and with knockdown NR3C2 were constructed by lentiviral vector transfection. Cell Counting Kit-8 assay, transplantation of tumors in nude mice and transwell assays were used to examine the proliferation, migration and invasion of colon cancer cells. The effect on the Wnt/β-catenin pathway, activities of cellular autophagy and cell apoptosis were examined by assessing the expression levels of several key proteins, including Bcl-2, Bax, and LC3., Results: We found that NR3C2 was found a significantly lower level in colon cancer tissues than in adjacent tissues, which was associated with distant and lymphatic metastases, clinical stage, and poor clinical outcome, and it was an independent prognostic factor and potential marker of colon cancer. Single-cell transcriptome data identified the subset of circulating T and B cells with high expression of NR3C2, which is involved in TNF signaling pathway. Functional experiments show that downregulation of NR3C2 resultsed in the activation of the Wnt/β-catenin signaling pathway, and promotesd the proliferation and invasion of colon cancer cells while suppressing cell autophagy and apoptosis., Conclusion: NR3C2 may regulate Wnt/β-catenin to affect the proliferation, invasion apoptosis and autophagy of colon cancer, and this axis is a potential target for the treatment of colon cancer., (© 2024. The Author(s).)

Mental well-being relates to multitudinous lifestyle behaviours and morbidities and underpins healthy aging. Thus far, causal evidence on whether and in what pattern mental well-being impacts healthy aging and the underlying mediating pathways is unknown. Applying genetic instruments of the well-being spectrum and its four dimensions including life satisfaction, positive affect, neuroticism and depressive symptoms (n = 80,852 to 2,370,390), we performed two-sample Mendelian randomization analyses to estimate the causal effect of mental well-being on the genetically independent phenotype of aging (aging-GIP), a robust and representative aging phenotype, and its components including resilience, self-rated health, healthspan, parental lifespan and longevity (n = 36,745 to 1,012,240). Analyses were adjusted for income, education and occupation. All the data were from the largest available genome-wide association studies in populations of European descent. Better mental well-being spectrum (each one Z-score higher) was causally associated with a higher aging-GIP (β [95% confidence interval (CI)] in different models ranging from 1.00 [0.82-1.18] to 1.07 [0.91-1.24] standard deviations (s.d.)) independent of socioeconomic indicators. Similar association patterns were seen for resilience (β [95% CI] ranging from 0.97 [0.82-1.12] to 1.04 [0.91-1.17] s.d.), self-rated health (0.61 [0.43-0.79] to 0.76 [0.59-0.93] points), healthspan (odds ratio [95% CI] ranging from 1.23 [1.02-1.48] to 1.35 [1.11-1.65]) and parental lifespan (1.77 [0.010-3.54] to 2.95 [1.13-4.76] years). Two-step Mendelian randomization mediation analyses identified 33 out of 106 candidates as mediators between the well-being spectrum and the aging-GIP: mainly lifestyles (for example, TV watching and smoking), behaviours (for example, medication use) and diseases (for example, heart failure, attention-deficit hyperactivity disorder, stroke, coronary atherosclerosis and ischaemic heart disease), each exhibiting a mediation proportion of >5%. These findings underscore the importance of mental well-being in promoting healthy aging and inform preventive targets for bridging aging disparities attributable to suboptimal mental health., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Rationale: Current treatments for ocular angiogenesis primarily focus on blocking the activity of vascular endothelial growth factor (VEGF), but unfavorable side effects and unsatisfactory efficacy remain issues. The identification of novel targets for anti-angiogenic treatment is still needed. Methods: We investigated the role of tsRNA-1599 in ocular angiogenesis using endothelial cells, a streptozotocin (STZ)-induced diabetic model, a laser-induced choroidal neovascularization model, and an oxygen-induced retinopathy model. CCK-8 assays, EdU assays, transwell assays, and matrigel assays were performed to assess the role of tsRNA-1599 in endothelial cells. Retinal digestion assays, Isolectin B4 (IB4) staining, and choroidal sprouting assays were conducted to evaluate the role of tsRNA-1599 in ocular angiogenesis. Transcriptomic analysis, metabolic analysis, RNA pull-down assays, and mass spectrometry were utilized to elucidate the mechanism underlying angiogenic effects mediated by tsRNA-1599. Results: tsRNA-1599 expression was up-regulated in experimental ocular angiogenesis models and endothelial cells in response to angiogenic stress. Silencing of tsRNA-1599 suppressed angiogenic effects in endothelial cells in vitro and inhibited pathological ocular angiogenesis in vivo . Mechanistically, tsRNA-1599 exhibited little effect on VEGF signaling but could cause reduced glycolysis and NAD + /NADH production in endothelial cells by regulating the expression of HK2 gene through interacting with YBX1, thus affecting endothelial effects. Conclusions: Targeting glycolytic reprogramming of endothelial cells by a tRNA-derived small RNA represents an exploitable therapeutic approach for ocular neovascular diseases., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Compared with electrical neural networks, optical neural networks (ONNs) have the potentials to break the limit of the bandwidth and reduce the consumption of energy, and therefore draw much attention in recent years. By far, several types of ONNs have been implemented. However, the current ONNs cannot realize the acceleration as powerful as that indicated by the models like quantum neural networks. How to construct and realize an ONN with the quantum speedup is a huge challenge. Here, we propose theoretically and demonstrate experimentally a new type of optical convolutional neural network by introducing the optical correlation. It is called the correlated optical convolutional neural network (COCNN). We show that the COCNN can exhibit "quantum speedup" in the training process. The character is verified from the two aspects. One is the direct illustration of the faster convergence by comparing the loss function curves of the COCNN with that of the traditional convolutional neural network (CNN). Such a result is compatible with the training performance of the recently proposed quantum convolutional neural network (QCNN). The other is the demonstration of the COCNN's capability to perform the QCNN phase recognition circuit, validating the connection between the COCNN and the QCNN. Furthermore, we take the COCNN analog to the 3-qubit QCNN phase recognition circuit as an example and perform an experiment to show the soundness and the feasibility of it. The results perfectly match the theoretical calculations. Our proposal opens up a new avenue for realizing the ONNs with the quantum speedup, which will benefit the information processing in the era of big data., (© 2024. The Author(s).)

In this study, twenty-one novel 2,4-diaminopyrimidine cinnamyl derivatives as inhibitors targeting FAK were designed and synthesized based on the structure of TAE-226, and the inhibitory effects of these compounds on both the FAK enzyme and three cancer cell lines (MGC-803, HCT-116, and KYSE30) were investigated. Among them, compound 12s displayed potent inhibitory potency on FAK (IC 50  = 47 nM), and demonstrated more significant antiproliferative activities in MGC-803, HCT-116 and KYSE30 cells (IC 50 values were 0.24, 0.45 and 0.44 μM, respectively) compared to TAE-226. Furthermore, compound 12s significantly inhibited FAK activation leading to the negative regulation of FAK-related signaling pathways such as AKT/mTOR and MAPK signaling pathways. Molecular docking study suggested that compound 12s could well occupy the ATP-binding pocket site of FAK similar to TAE-226. In addition, compound 12s also efficiently inhibited the proliferation, induced apoptosis and cellular senescence in MGC-803 cells. In conclusion, compound 12s emerges a potent FAK inhibitor that could exert potent inhibitory activity against gastric cancer cells., 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 Inc. All rights reserved.)

This study was to explore the regulatory effect of long non-coding RNA LINC01559 on Docetaxel resistance in breast carcinoma (BCa) and its underlying mechanism. In the present study, we found that LINC01559 expression was elevated and LINC01559 overexpression facilitated docetaxel resistance in BCa cells. Moreover, it was revealed that the upregulation of LINC01559 in BCa cells was induced by FTO-mediated demethylation in an m6A-YTHDF2-dependent manner. Additionally, Dual-luciferase reporter assay confirmed the binding ability between LINC01559 and miR-1343-3p, and Pearson correlation analysis showed a negative correlation between them. Particularly, miR-1343-3p inhibition partly abolished the suppression on docetaxel resistance in BCa cells caused by LINC01559 knockdown. To sum up, FTO-mediated epigenetic upregulation of LINC01559 promoted cell resistance to Docetaxel in BCa by negatively regulating miR-1343-3p., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Human longevity correlates with socio-economic status, and there is evidence that educational attainment increases human lifespan. However, to inform meaningful health policies, we need fine-grained causal evidence on which dimensions of socio-economic status affect longevity and the mediating roles of modifiable factors such as lifestyle and disease. Here we performed two-sample Mendelian randomization analyses applying genetic instruments of education, income and occupation (n = 248,847 to 1,131,881) to estimate their causal effects and consequences on parental lifespan and self-longevity (n = 28,967 to 1,012,240) from the largest available genome-wide association studies in populations of European ancestry. Each 4.20 years of additional educational attainment were causally associated with a 3.23-year-longer parental lifespan independently of income and occupation and were causally associated with 30-59% higher odds of self-longevity, suggesting that education was the primary determinant. By contrast, each one-standard-deviation-higher income and one-point-higher occupation was causally associated with 3.06-year-longer and 1.29-year-longer parental lifespans, respectively, but not independently of the other socio-economic indicators. We found no evidence for causal effects of income or occupation on self-longevity. Mediation analyses conducted in predominantly European-descent individuals through two-step Mendelian randomization suggested that among 59 candidates, cigarettes per day, body mass index, waist-to-hip ratio, hypertension, coronary heart disease, myocardial infarction, stroke, Alzheimer's disease, type 2 diabetes, heart failure and lung cancer individually played substantial mediating roles (proportion mediated, >10%) in the effect of education on specific longevity outcomes. These findings inform interventions for remediating longevity disparities attributable to socio-economic inequality., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

A zinc-infiltration process was adopted to prepare silver-doped copper nanosheet arrays. The larger atomic radius of Ag introduces tensile stress, which lowers the electron density at the s-orbitals of Cu atoms and improves the adsorption capability for hydrogen atoms. As a catalyst for hydrogen evolution, these silver doped copper nanosheet arrays achieved a low overpotential of 103 mV at 10 mA cm -2 in 1 M KOH, which is 604 mV lower than that of pure copper foil.

Holography provides an approach to reconstructing both intensity and phase information, and has many applications for microscopic imaging, optical security, and data storage. Recently, the azimuthal Laguerre-Gaussian (LG) mode index, orbital angular momentum (OAM), has been implemented in holography technologies as an independent degree of freedom for high-security encryption. The radial index (RI) of LG mode, however, has not been implemented as an information carrier in holography. Here we propose and demonstrate the RI holography by using strong RI selectivity in the spatial-frequency domain. Furthermore, the LG holography is realized theoretically and experimentally with the (RI, OAM) spanning from (1, -15) to (7, 15), which leads to a 26bit LG-multiplexing hologram for high-security optical encryption. Based on LG holography, a high-capacity holographic information system can be constructed. In our experiments, a LG-multiplexing holography with a span of 217 independent LG channels has been realized, which is inaccessible at present for the OAM holography.

Single-crystal planes are ideal platforms for catalytic research. In this work, rolled copper foils with predominantly (220) planes were used as the starting material. By using temperature gradient annealing, which caused grain recrystallization in the foils, they were transformed to those with (200) planes. In acidic solution, the overpotential of such a foil (10 mA cm -2 ) was found to be 136 mV lower than that of a similar rolled copper foil. The calculation results show that hollow sites formed on the (200) plane have the highest hydrogen adsorption energy and are active centers for hydrogen evolution. Thus, this work clarifies the catalytic activity of specific sites on the copper surface and demonstrates the critical role of surface engineering in designing catalytic properties.

As an important imaging technique, holography has been realized with different physical dimensions of light, including polarization, wavelength, and time. Recently, quantum holography has been demonstrated by utilizing polarization entangled state with the advantages of high robustness and enhanced spatial resolution, comparing with classical holography. However, the polarization is only a two-dimensional degree of freedom, which greatly limits the capacity of quantum holography. Here, we propose a method to realize high-dimensional quantum holography by using high-dimensional orbital angular momentum (OAM) entanglement. A high-capacity OAM-encoded quantum holographic system can be obtained by multiplexing a wide range of OAM-dependent holographic images. Proof-of-principle experiments with four- and six-dimensional OAM entangled states have been implemented and verify the feasibility of our idea. Our experimental results also demonstrate that the high-dimensional quantum holography shows a high robustness to classical noise. What is more, the level of security of the holographic imaging encryption system can be greatly improved in our high-dimensional quantum holography.

Objective: To compare the efficacy and feasibility of endoscopic retrograde appendicitis therapy (ERAT) with appendectomy for treating acute uncomplicated appendicitis., Methods: This was a prospective multicenter randomized trial in which consecutive patients were randomized at a ratio of 1:1 to receive either ERAT or appendectomy. The outcomes included technical success rate, procedure time, postoperative pain relief, postoperative analgesic use, time to soft diet intake, length of postoperative hospital stay, postoperative complications, and recurrence rate., Results: From August 2013 to December 2015, 110 patients with acute uncomplicated appendicitis were randomized to ERAT or appendectomy. The technical success rate was 94.55% for ERAT compared with 100% for appendectomy. Recurrence of appendicitis within 3-year follow-up occurred in 8 patients following ERAT. Postoperative abdominal pain was less frequent with ERAT than with appendectomy (21.15% [11/52] vs 87.27% [48/55], P < 0.001). Soft diet intake begun earlier after ERAT than appendectomy (6 h vs 48 h, P < 0.001), and post-procedure hospital stay was shorter (3 days vs 5 days, P < 0.001), as was the use of analgesics postoperatively (9.09% vs 49.09%, P < 0.001)., Conclusions: ERAT is a feasible, safe, and effective alternative approach for the management of acute uncomplicated appendicitis. Compared with appendectomy, advantages of ERAT include no skin wound, organ preservation, reduced postoperative pain, early food intake, quick recovery, fewer postoperative complications, and shorter post-procedure hospitalization. The unsolved problem related to ERAT is the recurrence of appendicitis., (© 2022 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Abnormal co-occurrence medical visit behavior is a form of medical insurance fraud. Specifically, an organized gang of fraudsters hold multiple medical insurance cards and purchase similar drugs frequently at the same time and the same location in order to siphon off medical insurance funds. Conventional identification methods to identify such behaviors rely mainly on manual auditing, making it difficult to satisfy the needs of identifying the small number of fraudulent behaviors in the large-scale medical data. On the other hand, the existing single-view bi-clustering algorithms only consider the features of the time-location dimension while neglecting the similarities in prescriptions and neglecting the fact that fraudsters may belong to multiple gangs. Therefore, in this paper, we present a multi-view bi-clustering method for identifying abnormal co-occurrence medical visit behavioral patterns, which performs cluster analysis simultaneously on the large-scale, complex and diverse visiting record dimension and prescription dimension to identify bi-clusters with similar time-location features. The proposed method constructs a matrix view of patients and visit records as well as a matrix view of patients and prescriptions, while decomposing multiple data matrices into sparse row and column vectors to obtain a consistent patient population across views. Subsequently the proposed method identifies the corresponding abnormal co-occurrence medical visit behavior and may greatly facilitate the safe operations and the sustainability of medical insurance funds. The experimental results show that our proposed method leads to more efficient and more accurate identifications of abnormal co-occurrence medical visit behavior, demonstrating its high efficiency and effectiveness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of traditional Chinese manual therapy (TCMT) in alleviating pain and dysfunction in patients with lumbar disc herniation (LDH)., Methods: Sixty-six patients with LDH were recruited as the study cohort and randomly assigned to an observation group and a control group. The patients in the observation group underwent TCMT, whereas those in the control group underwent conventional lumbar traction (LT). The observed indexes comprised primary index, which referred to clinical efficacy, and secondary indexes, which include Simplified McGill Pain Questionnaire, Oswestry Disability Index (ODI), range of motion (ROM) of the lumbar spine, difference in muscle tone (MT) and pressure pain threshold (PPT) of the bilateral erector spinae, and serum inflammatory factor levels., Results: The total effective rate was significantly higher in the observation group than in the control group (96.67% vs. 66.67%, P < 0.001). Compared with the control group after treatment, patients in the observation group had significantly lower ODI, pain rating index, visual analog scale and present pain intensity scores (all P < 0.05), and had significantly smaller differences in MT and PPT of the bilateral erector spinae (both P < 0.001), but had remarkably greater ROM of the lumbar spine ( P < 0.001). In addition, interleukin (IL)-6, IL-8, and interferon-γ concentrations in the observation group were significantly lower than those in the control group after treatment (all P < 0.05)., Conclusion: TCMT has positive effects on alleviating pain and improving dysfunction of patients with LDH and helps in reducing serum inflammatory factor levels., Competing Interests: None., (AJTR Copyright © 2022.)

Objective: To investigate whether probenecid (PROB) could improve the proliferation and migration ability of rats' pulmonary artery smooth muscle cells induced by platelet-derived growth factor-BB (PDGF-BB)., Methods: Primary pulmonary artery smooth muscle cells (PASMCs) of SD rats were cultured in vitro , and were randomly divided into control group (CON group), PDGF-BB group (10 ng/ml PDGF-BB treatment for 24 h) and PDGF-BB+PROB group (10 ng/ml PDGF-BB and 200 μmol/L PROB treatment for 24 h, PROB is a specific blocker of pannexin-1). CCK-8 method was used to select the suitable intervention concentrations of PROB and PDGF-BB, and to detect the proliferation of PASMCs in each group. The migration ability of PASMCs was detected by Transwell TM assay and cell scratch test. Immunofluorescence cytochemistry and Western blot were used to detect the protein expressions and distribution of osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) in PASMCs., Results: Compared with CON group, the migration and proliferation ability of PASMCs in PDGF-BB group were enhanced ( P ＜0.05). After treated with PROB, the migration and proliferation ability of PASMCs in PDGF-BB+PROB group were decreased significantly ( P ＜0.05). Compared with CON group, the expression and protein levels of OPN and PCNA in PDGF-BB group were increased significantly ( P ＜0.05), while the expression and protein levels of OPN and PCNA in PDGF-BB+PROB were decreased significantly ( P ＜0.05)., Conclusion: Probenecid inhibits the migration and proliferation of PDGF-BB-induced PASMCs by blocking Pannexin-1.

The investigation of effective therapeutic drugs for pulmonary hypertension (PH) is critical. KIR2.1 plays crucial roles in regulating cell proliferation and migration, and vascular remodeling. However, researchers have not yet clearly determined whether KIR2.1 participates in the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) and its role in pulmonary vascular remodeling (PVR) also remains elusive. The present study aimed to examine whether KIR2.1 alters PASMC proliferation and migration, and participates in PVR, as well as to explore its mechanisms of action. For the in vivo experiment, a PH model was established by intraperitoneally injecting Sprague‑Dawley rats monocrotaline (MCT). Hematoxylin and eosin staining revealed evidence of PVR in the rats with PH. Immunofluorescence staining and western blot analysis revealed increased levels of the KIR2.1, osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) proteins in pulmonary blood vessels and lung tissues following exposure to MCT, and the TGF‑β1/SMAD2/3 signaling pathway was activated. For the in vitro experiments, the KIR2.1 inhibitor, ML133, or the TGF‑β1/SMAD2/3 signaling pathway blocker, SB431542, were used to pre‑treat human PASMCs (HPASMCs) for 24 h, and the cells were then treated with platelet‑derived growth factor (PDGF)‑BB for 24 h. Scratch and Transwell assays revealed that PDGF‑BB promoted cell proliferation and migration. Immunofluorescence staining and western blot analysis demonstrated that PDGF‑BB upregulated OPN and PCNA expression, and activated the TGF‑β1/SMAD2/3 signaling pathway. ML133 reversed the proliferation and migration induced by PDGF‑BB, inhibited the expression of OPN and PCNA, inhibited the TGF‑β1/SMAD2/3 signaling pathway, and reduced the proliferation and migration of HPASMCs. SB431542 pre‑treatment also reduced cell proliferation and migration; however, it did not affect KIR2.1 expression. On the whole, the results of the present study demonstrate that KIR2.1 regulates the TGF‑β1/SMAD2/3 signaling pathway and the expression of OPN and PCNA proteins, thereby regulating the proliferation and migration of PASMCs and participating in PVR.

Optical knots and links have attracted great attention because of their exotic topological characteristics. Recent investigations have shown that the information encoding based on optical knots could possess robust features against external perturbations. However, as a superior coding scheme, it is also necessary to achieve a high capacity, which is hard to be fulfilled by existing knot-carriers owing to the limit number of associated topological invariants. Thus, how to realize the knot-based information coding with a high capacity is a key problem to be solved. Here, we create a type of nested vortex knot, and show that it can be used to fulfill the robust information coding with a high capacity assisted by a large number of intrinsic topological invariants. In experiments, we design and fabricate metasurface holograms to generate light fields sustaining different kinds of nested vortex links. Furthermore, we verify the feasibility of the high-capacity coding scheme based on those topological optical knots. Our work opens another way to realize the robust and high-capacity optical coding, which may have useful impacts on the field of information transfer and storage., (© 2022. The Author(s).)

Iron (Fe) deficiency in alkaline calcium soil is a problem that needs to be solved urgently as Fe is an essential and commonly limiting nutrient for plants. Endophytic fungus, Phomopsis liquidambaris ( P. liquidambaris ), has been reported to promote Fe absorption in peanuts ( Arachis hypogaea L.), however, the mechanisms remain unclear. Under prolonged Fe deficiency, an increase in hydrogen peroxide (H 2 O 2 ) often triggers a series of signaling events and leads to the inhibition of Fe acquisition. The main purpose of this study was to explore whether and how the endophytic fungus P. liquidambaris promote Fe absorption in peanut through regulating H 2 O 2 and assisting in resisting oxidative stress. In this study, we detected the Fe deficiency-induced transcription factor ( FIT ), Fe 2+ transporter ( IRT 1), and ferric reduction oxidase 2 ( FRO2 ) of peanuts, and confirmed that they were negatively related to Fe concentration. Similarly, FIT, IRT 1, and FRO2 were also inhibited by H 2 O 2 . The addition of P. liquidambaris reduces H 2 O 2 under Fe-deficiency with an increase in Fe content, while the exogenous addition of H 2 O 2 further decreases it, and the addition of catalase (CAT) under Fe-deficiency reverses this phenomenon. Through transcriptome analysis, we proved that the expression of FIT, IRT 1, FRO2 and CAT are consistent with our hypothesis, and P. liquidambaris has a stress-mitigating effect on peanuts mainly via CAT, glutathione peroxidase, and malondialdehyde. Our study proved the Fe-absorption promoting effect and stress mitigation effect of P. liquidambaris under Fe-deficiency in peanuts, and their combined usage may help peanuts grow better., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Du, Kong, Cao, Zhang, Zhu, Ma, Sun and Dai.)

On the basis of retaining the technical identification system of medical negligence, the Medical Association Identification Rules of Medical Damage mainly provides technical services for various types of conciliation work about doctor-patient dispute. Its identification work is still influenced by the thinking of medical negligence technical identification and has certain administrative color. Guidance for Judicial Expertise of Medical Malpractice is mainly reflected that the trial of civil cases and pre-trial mediation of courts need service. Its procedures and evidence review are strictly required by the litigation rules and has the characteristics of public legal services provided as a third-party neutral institution. Technical identification of medical damage, whether organized by the Medical Association or the forensic identification institutions, is carried out under the background of the current Regulations on the Prevention and Treatment of Medical Disputes and the Civil Code of the People's Republic of China; both have a corresponding positive role in regulating the medical damage identification activities, and have also laid a certain foundation for the establishment of a unified identification system in the future in China. To understand the different characteristics of the medical damage identification rules issued by the Chinese Medical Association and the Ministry of Justice, and to improve the understanding of the standardization of the forensic identification of medical damage, a comparative study was conducted on Medical Association Identification Rules of Medical Damage and Guidance for Judicial Expertise of Medical Malpractice from seven aspects: Concept and legal status, entrust of identification, identification acceptance, identification procedures, identification presentation meeting, theory of medical malpractice evaluation, consequences and causality of medical damage. The subject of evaluation, the function of evidence review, the role of consulting experts, the technical standard system of malpractice evaluation and other contents were emphatically analyzed.

Background: This study aimed to investigate the diagnostic and therapeutic value of a digital single-operator cholangioscope (SOC) system for endoscopic management of acute appendicitis., Methods: 14 patients with acute uncomplicated simple or supportive appendicitis were evaluated between November 2018 and September 2020. The diagnosis of acute appendicitis was confirmed by direct colonoscopy imaging and cholangioscope. The success rate of digital SOC-assisted endoscopic retrograde appendicitis therapy (ERAT), the procedure time, postoperative length of hospital stay, complications, and recurrence rate were recorded., Results: Technical success rate was 100 %, with high quality imaging of the appendiceal cavity achieved using SOC in all 14 patients. The mean procedure time was 37.8 (standard deviation [SD] 22) minutes. All patients experienced immediate relief from abdominal pain after the procedure. Mean postoperative hospitalization was 1.9 (SD 0.7) days. No recurrence occurred during 2-24 months of follow-up., Conclusion: Digital SOC-assisted ERAT provided a feasible, safe, and effective alternative approach for diagnosis and management of acute uncomplicated appendicitis without the need for X-ray or ultrasonic guidance., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

As the continuation of our work on the development of tubulin inhibitors with potential anticancer activities, novel bis-substituted aromatic amide dithiocarbamate derivatives were designed by contacting bis-substituted aryl scaffolds (potential anti-tubulin fragments) with N-containing heterocycles (potential anti-tubulin fragments) in one hybrid using the anticancer dithioformate unit as the linker. The antiproliferative activity against three digestive tract tumor cells was evaluated and preliminary structure activity relationships were summarized. Among these compounds, compound 20q exhibited most potent antiproliferative activity against MGC-803, HCT-116, Kyse30 and Kyse450 cells with IC 50 values of 0.084, 0.227, 0.069 and 0.078 μM, respectively. In further studies, compound 20q was identified as a novel tubulin inhibitor targeting the colchicine binding site. Compound 20q could inhibit the microtubule assembly and disrupt cytoskeleton in Kyse30 and Kyse450 cells. The results of molecular docking suggested that compound 20q could tightly bind into the colchicine binding site of tubulin by hydrogen bonds and hydrophobic interactions. Compound 20q dose-dependently inhibited the cell growth and colony formation, effectively arrested cells at the G2/M phase and induce mitochondrial apoptosis in Kyse30 and Kyse450 cells. In addition, Compound 20q could regulate the expression of G2/M phase and mitochondrial apoptosis related proteins. Collectively, compound 20q was here reported as a novel tubulin inhibitor with potential anticancer activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objective: To analyze the clinical characteristics and prognosis of 40 children with myelodysplastic syndrome (MDS), and provide ideas for clinical diagnosis and treatment., Methods: The clinical characteristics, risk stratification, and different treatment regimens of 40 cases with MDS admitted in Department of Hematology of Children's Hospital of Soochow University from January 1, 2011 to December 31, 2017 was retrospectively analyzed. Kaplan-Meier survival curve were used to estimate 3-year overall survival (OS) rate and event-free survival (EFS) rate., Results: In 40 cases, the ratio of male to female was 1.4∶1.0, male was more than female, and median age was 6.0 years old. Among them, refractory cytopenia (MDS-RCC) was the most common type, and 11 cases were chromosomal abnormalities, 21 cases genetic abnormalities. Fifteen cases accepted hematopoietic stem cell transplantation (HSCT) treatment, while 25 cases did not but drug therapy alone. The 3-year OS rate of the cases who accepted HSCT or not was (72.2±12.2)% and (35.3±10.2)% (P=0.039), 3-year EFS rate was (65.0±12.9)% and (19.2±8.4)% (P=0.012), respectively. Cox regression analysis showed that age < 7 years old (P=0.0333), initial diagnosed platelet < 50×10 9 /L (P=0.007), presence of complex karyotypes and/or gene mutations (P=0.0002), and treatment without HSCT (P=0.016) were the high-risk factors of prognosis. All the children were classified according to IPSS, WPSS and IPSS-R, while analysis result showed that the above three risk assessment had limitations for risk assessment of MDS in children, they could not comprehensively assess the prognosis of children with MDS., Conclusion: MDS-RCC in children is more common. Cox multivariate analysis shows that age < 7 years old, initial diagnosed platelet < 50×10 9 /L, presence of complex karyotypes and/or gene mutation, and treatment without HSCT are the high-risk factors of prognosis in children with MDS. HSCT is the most effective treatment to cure children with MDS at present. The current methods such as IPSS-R commonly used in assessment of prognosis in children with MDS show obvious limitation.

Background: Cardiogenic embolism caused by patent foramen ovale (PFO) is a common etiology of cryptogenic stroke (CS), particularly in young and middle-aged patients. Studies about right-to-left shunt (RLS) detection using contrast-enhanced transcranial Doppler (c-TCD) are numerous. According to the time phase and number of microbubbles detected on c-TCD, RLS can be classified and graded. We hypothesized that the characteristics of an infarction lesion on diffusion-weighted imaging differs when combining the type and grade of RLS on c-TCD in patients with PFO-related CS., Aim: To explore the characteristics of infarction lesions on diffusion-weighted imaging when combining the RLS type and grade determined by c-TCD., Methods: We retrospectively evaluated CS patients from August 2015 to December 2019 at a tertiary hospital. In total, 111 PFO-related CS patients were divided according to whether RLS was permanent (microbubbles detected both at resting state and after the Valsalva maneuver) or latent (microbubbles detected only after the Valsalva maneuver) on c-TCD. Each group was subdivided into small, mild and large RLS according to the grade of shunt on c-TCD. A normal control group was composed of 33 patients who suffered from simple dizziness. Intragroup and intergroup differences were analyzed in terms of clinical, laboratory and diffusion-weighted imaging lesion characteristics. The correlation between RLS grade evaluated by c-TCD and size of PFO determined by transesophageal echocardiography were also analyzed., Results: In 111 patients with PFO-related CS, 68 had permanent RLS and 43 had latent RLS. Clinical characteristics and laboratory tests were not significantly different among the permanent RLS, latent RLS and normal control groups. The proportion of patients with multiple territory lesions in the permanent RLS group (50%) was larger than that in the latent RLS group (27.91%; P = 0.021). Posterior circulation was more likely to be affected in the latent RLS group than in the permanent RLS group (30.23% vs 8.82%, P = 0.004). Permanent-large and latent-large RLS were both more likely to be related to multiple ( P trend = 0.017 and 0.009, respectively), small ( P trend = 0.035 and 0.006, respectively) and cortical ( P trend = 0.031 and 0.033, respectively) lesions. The grade of RLS evaluated by c-TCD was correlated to the size of PFO determined by transesophageal echocardiography ( r = 0.758, P < 0.001)., Conclusion: Distribution of the infarct suggested the possible type of RLS. Multiple, small and cortical infarcts suggest large RLS induced by a large PFO., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: Endothelial dysfunction is involved in various aspects of vascular biology and different stages of cardiovascular diseases (CVDs). Nucleotide-binding oligomerization domain-containing protein (NOD) 2, a pivotal innate immune receptor for muramyl dipeptide (MDP), has been reported to be a central regulator in CVDs. Previously, we reported that NOD2 played a leading role in MDP-triggered oxidative stress in endothelial cells (ECs). However, whether NOD2 participates in the regulatory mechanism of vascular cell adhesion molecule‑1 (VCAM-1) and endothelin‑1 (ET-1) expression was not elucidated., Methods: Human umbilical vein endothelial cells (HUVECs) were stimulated with MDP for 12 h. mRNA expression of VCAM‑1 and ET‑1 was detected using real time polymerase chain reaction (PCR). Scrambled control small interfering RNA (siRNA) and NOD2 siRNA were transfected into HUVECs using Lipofectamine 2000 reagent (Invitrogen, Waltham, MA, USA). Furthermore, pyrrolidine dithiocarbamate was adopted to investigate the effect of nuclear factor κB (NF-κB) on NOD2-mediated VCAM‑1 and ET‑1 gene expression in MDP-treated HUVECs., Results: Data showed that MDP significantly increased VCAM‑1 and ET‑1 mRNA expression, which was dependent on NOD2. In addition, NF-κB inhibition suppressed NOD2-mediated gene expression of VCAM‑1 and ET‑1., Conclusion: Collectively, we confirmed NOD2 aggravated VCAM‑1 and ET‑1 gene expression through NF-κB in HUVECs treated with MDP., (© 2020. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The pollution of heavy metals and organic compounds has received increased attention in recent years. In the current study, a novel biochar-based iron oxide composite (FeYBC) was successfully synthesized using pomelo peel and ferric chloride solution through one-step process at moderate temperature. Results clearly demonstrate that FeYBC exhibited more efficient removal of Cr(VI) and/or phenol compared with the pristine biochar, and the maximum adsorption amounts of Cr(VI) and phenol by FeYBC could reach 24.37 and 39.32 mg g -1 , respectively. A series of characterization data suggests that several iron oxides such as Fe 2 O 3 , Fe 0 , FeOOH and Fe 3 O 4 were formed on the FeYBC surface as well as oxygen-containing groups. Thermodynamics study indicates that Cr(VI) and phenol adsorption by FeYBC were endothermic and exothermic processes, respectively. Langmuir adsorption isotherm and pseudo-second order models could better explain the Cr(VI) and phenol adsorption behaviors over FeYBC. The Cr(VI) adsorption might be primarily achieved through the ion exchange and surface complexation and reduction, whereas the π-π interaction and electron donor-acceptor complex mainly contributed to phenol adsorption. The findings indicate that the biochar-based iron oxide composites material was an efficient adsorbent for the remediation of industrial effluents containing Cr(VI) and phenol., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background Our aim was to investigate the effects of the protein expression and the function of sodium, potassium, and chloride co-transporter (NKCC1) in the dorsal root ganglion (DRG) after activation of transient receptor potential vanilloid 1 receptor (TRPV1) in capsaicin-induced acute inflammatory pain and the possible mechanism of action. Methods Male Sprague-Dawley rats were randomly divided into control, capsaicin, and inhibitor groups. The expression and distribution of TRPV1 and NKCC1 in rat DRG were observed by immunofluorescence. Thermal radiation and acetone test were used to detect the pain threshold of heat and cold noxious stimulation in each group. The expressions of NKCC1 mRNA, NKCC1 protein, and p-NKCC1 in the DRG were detected by PCR and western blotting (WB). Patch clamp and chloride fluorescent probe were used to observe the changes of GABA activation current and intracellular chloride concentration. After intrathecal injection of protein kinase C (PKC) inhibitor (GF109203X) or MEK/extracellular signal-regulated kinase (ERK) inhibitor (U0126), the behavioral changes and the expression of NKCC1 and p-ERK protein in L 4 - 6 DRG were observed. Result: TRPV1 and NKCC1 were co-expressed in the DRG. Compared with the control group, the immunofluorescence intensity of NKCC1 and p-NKCC1 in the capsaicin group was significantly higher, and the expression of NKCC1 in the nuclear membrane was significantly higher than that in the control group. The expression of NKCC1 mRNA and protein of NKCC1 and p-NKCC1 in the capsaicin group were higher than those in the control group. After capsaicin injection, GF109203X inhibited the protein expression of NKCC1 and p-ERK, while U0126 inhibited the protein expression of NKCC1. In the capsaicin group, paw withdrawal thermal latency (WTL) was decreased, while cold withdrawal latency (CWL) was prolonged. Bumetanide, GF109203X, or U0126 could reverse the effect. GABA activation current significantly increased in the DRG cells of the capsaicin group, which could be reversed by bumetanide. The concentration of chloride in the DRG cells of the capsaicin group increased, but decreased after bumetanide, GF109203X, and U0126 were administered. Conclusion Activation of TRPV1 by exogenous agonists can increase the expression and function of NKCC1 protein in DRG, which is mediated by activation of PKC/p-ERK signaling pathway. These results suggest that DRG NKCC1 may participate in the inflammatory pain induced by TRPV1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Deng, Tang, Chang, Xu, Chen, Cao, Kong, Wang, Ma, Li and Si.)

Islet transplantation (IT) is considered the most effective endocrine replacement therapy for diabetes mellitus (DM). Studies have demonstrated that IT can repair testicular structural injury caused by inflammatory and oxidative stress in a diabetic rat model. However, highly effective exogenous antioxidant and anti-inflammatory drugs can achieve this effect. Testicular interstitial fibrosis caused by long-term hyperglycemia is however difficult to reverse or recover. Thus far, there are no effective drugs that prevent or relieve testicular interstitial fibrosis. Therefore, it is necessary to explore the potential benefit of IT on testicular interstitial fibrosis induced by DM and its underlying molecular mechanisms. In the present study, Wistar rats were used to establish a DM model by intraperitoneal injection of streptozotocin. The diabetic models then underwent IT or received insulin treatment after 12 weeks. IT was more effective than insulin treatment in ameliorating diabetic-induced testicular interstitial fibrosis, Leydig cells apoptosis, testosterone deficiency and poor sperm motility. IT and insulin treatment both significantly inhibited the upregulation of TGF-β1 and phosphorylated Smad2 in DM, with IT being more effective than insulin. The present study's findings proved that IT effectively protects diabetic-induced testicular interstitial fibrosis probably by inhibiting the TGF-β1/Smad2 signaling pathway, which offers hope in male patients with DM complicating with testicular interstitial fibrosis.

Objective: To observe the analgesic effect of manipulation loading on chronic low back pain (CLBP) model rats and the expression of inflammatory factors in psoas major muscle tissue, and to explore the improvement of manipulation on local inflammatory microenvironment., Methods: Thirty two SPF male SD rats weighing 340-360g were randomly divided into blank group, sham operation group, chronic low back pain model group and treatment group, with 8 rats in each group. In the model group, L 4 -L 6 lumbar vertebrae were implanted with external link fixation system (ELFS). After implantation of ELFS, the treatment group received manualintervention with 5N force and 2Hz frequency on both sides of the spine, 15 min / time, once a day, for 14 consecutive days. Paw with drawl threshold (PWT) and paw withdrawl latency (PWL) was measured before modeling and on the 1st, 3rd, 7th, 10th and 14th day after intervention. At the end of the treatment cycle, the concentrations of calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF) in psoas muscle were detected by enzyme-linked immunosorbent assay (ELISA)., Results: There was no significant difference in PWT and PWL between the blank group and the sham operation group after modeling ( P >0.05);after modeling, PWT and PWL in the CLBP model group and the treatment group were significantly decreased( P <0.01);PWT in the treatment group was not significantly improved than that in the CLBP model group on the 1st and 3rd day after manual loading( P >0.05);on the 7th day after manual loading, the pain threshold value in the treatment group was higher than that in the CLBP model group, but there was no significant difference There was no significant difference between the two groups ( P =0.056>0.05). On the 10th and 14th day of treatment, the mechanical pain threshold of the treatment group began to rise, and it was statistically significant compared with CLBP model rats ( P <0.05, P < 0.01);on the 1st and 3rd day after manual treatment, the PWL of the treatment group was not significantly improved compared with CLBP model group ( P >0.05);on the 7th day, the PWL of the treatment group was significantly higher than that of CLBP model group, there was statistical significance ( P =0.016<0.05). Manual loading improved thermal hyperalgesia in CLBP rats until the end of the experiment. The contents of CGRP and NGF in psoas major muscle of CLBP model group were higher than those of blank group and sham operation group ( P <0.01). After treatment, the contents of CGRP and NGF decreased significantly( P <0.01)., Conclusion: Local massage loading has analgesic effect on CLBP rats, at the same time, it can inhibit the content of CGRP and NGF in psoas muscle tissue of CLBP rats, and improve the local inflammatory microenvironment.

Abscisic acid (ABA) is an important phytohormone regulating plant growth, development and stress responses. A multitude of key factors implicated in ABA signaling have been identified; however, the regulation network of these factors needs for further information. AtS40.4, a plant-specific DUF584 domain-containing protein, was identified previously as a senescence regulator in Arabidopsis . In this study, our finding showed that AtS40.4 was negatively involved in ABA signaling during seed germination and early seedling growth. AtS40.4 was highly expressed in seeds and seedlings, and the expression level was promoted by ABA. AtS40.4 was localized both in the nucleus and the cytoplasm. Moreover, the subcellular localization pattern of AtS40.4 was affected by ABA. The knockdown mutants of AtS40.4 exhibited an increased sensitivity to ABA, whereas the overexpression of AtS40.4 decreased the ABA response during seed germination and seedling growth of Arabidopsis . Furthermore, AtS40.4 was involved in ABRE-dependent ABA signaling and influenced the expression levels of ABA INSENTIVE ( ABI ) 1-5 and SnRK2.6 . Further genetic evidence demonstrated that AtS40.4 functioned upstream of ABI4. These findings support the notion that AtS40.4 is a novel negative regulator of the ABA response network during seed germination and early seedling growth., Competing Interests: D-FL was employed by the company Shandong Lufeng Group Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shi, Ren, Qi, Lin, Wang, Li, Kong and Wang.)

Abstract: From January 15 to March 3, 2020, seven editions of the guidelines for the diagnosis and treatment of COVID-19 have been issued successively by the National Health Commission of the People's Republic of China, and the guidelines' name was changed from Guidelines for Diagnosis and Treatment of Novel Coronavirus Pneumonia to Diagnosis and Treatment for COVID-19. It optimized and perfected the etiology, clinical manifestations and types, diagnostic procedures and specific treatment measures of the disease, so that the clinical management of the cases was more scientific. In the revision process of guidelines for diagnosis and treatment, forensic medicine experts have also made some positive suggestions on clinical diagnosis and treatment. Especially regarding the pathological changes of COVID-19, they have repeatedly called for rapid autopsy at different levels. With the support, understanding and cooperation of all parties, pathological examination of more than ten cases of the remains were carried out, which made an important contribution to the understanding of the clinical characteristics and pathological characteristics of the disease and the improvement of treatment plans., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Objective: To investigate the factors related to recanalization of intramural hematoma-type carotid artery dissection (CAD). Methods: Retrospective analysis was performed on 56 patients (61 CADs) with intramural-hematoma type CAD confirmed by multimodal imaging examination based on cervical vascular ultrasound (CDU) in the Stroke Center of the First Affiliated Hospital of Suzhou University from August 2015 to May 2019. The clinical and imaging data were collected, and the time from onset to visit is bounded by 14 days. CDU follow-up was performed at 3, 6, and 12 months after the onset. According to the results of the 12-month follow-up, patients were divided into complete recanalization group and incomplete recanalization group. The clinical data, ultrasonic manifestations and drug treatment of patients between the two groups were compared. Multivariate logistic regression analysis was used to analyze the related factors affecting vascular recanalization. Results: Vascular recanalization: the rates of complete recanalization at 3, 6 and 12 months were 42.6% (26/61), 55.7% (34/61) and 59.0% (36/61), respectively. While among the 25 vessels in the incomplete recanalization group, 26.2% (16/61) showed residual stenosis and 14.8% (9/61) showed persistent occlusion. Comparison between the complete recanalization group and the incomplete recanalization group: the differences in the proportion of time from onset to visit ≤ 14 days, the echo type of intramural hematoma, and the proportion of vascular occlusion were statistically significant (all P< 0.05). Multivariate logistic regression analysis showed that the time from onset to visit ≤14 days ( OR= 5.625, 95 %CI: 1.302-24.293, P= 0.021), and the hypoechoic intramural hematoma ( OR= 4.888, 95 %CI: 1.304-18.320, P= 0.019) were positively correlated with complete recanalization, while the dissection vascular occlusion ( OR= 0.234, 95 %CI: 0.059-0.932, P= 0.039) was negatively correlated with complete recanalization. Conclusions: CDU showed that hypoechoic intramural hematoma-type CAD treated with standard medications in the acute phase had a higher complete recanalization rate, while the recanalization rate of patients with dissecting vessel occlusion decreased. Early evaluation can provide a basis for clinical individualized treatment.

A theoretical analysis based on mirror symmetry is proposed to analyze and predict the symmetry in intensity, phase and polarization distributions of the tightly focused vector optical field (VOF). We extend the analysis to more cases including more complicated polarization states and weak focusing cases. We further show the symmetric tightly focused fields of the eccentric cylindrical VOF and the redesigned VOF with a radially variant polarization state, which are achieved by redesigning the polarization state of the incident VOF based on the symmetry analysis. We also take the laser fabrication as an example to further show how to apply this symmetry analysis in a specific application area. Such a theoretical analysis can improve the calculation efficiency, provide new insights into the tight focusing process and offer a convenient way to engineer the field distributions in the focal plane, which may have potential applications in areas needing flexibly controllable tightly focused fields, such as laser fabrication, optical trapping, and optical storage.

Background and Aim: Natural orifice transluminal endoscopic surgery (NOTES) cholecystectomy is an emerging technology. Interest is ongoing and developments have been rapid but NOTES cholecystectomy has failed to gain traction. Here, we share our experience of snare-assisted pure NOTES retrograde cholecystectomy using porcine models., Materials and Methods: Under general anesthesia, an incision was created on the posterior vagina wall and an endoscope with a snare attached to the transparent cap was introduced into the pelvic cavity and then upward into peritoneal cavity. After locating the liver and gallbladder, the fundic wall of gallbladder was grasped using a biopsy forceps and the snare was released to ligate the fundus. The gallbladder was then carefully dissected from the gallbladder bed using hook/IT knives with the assistance of the snare. The cystic duct and cystic artery were identified, clipped twice and isolated from the gallbladder using the hook knife to cut between the clips. The specimen was then removed through the vagina using the snare., Results: This procedure was successfully performed in 8 consecutive pigs. The average procedure time was 53 min (range 40-60 min). No severe bleeding or other complication was observed either during or after the procedure. Normal diets were given on the same day of the procedure. All animals recovered uneventfully., Conclusion: We successfully performed snare-assisted pure NOTES retrograde cholecystectomy in pigs using standard endoscopic instruments. In our experience, pure NOTES cholecystectomy using the retrograde approach performed with a single channel flexible endoscope proved safe and feasible with a short procedure time and quick recovery. The translation of this technique to human subjects seems straight forward and provides a new fitting path to pure NOTES.

Uranium (U(VI)) is radioactive and the primary raw material in the production of nuclear energy. Hence the research associated with uranium removal gained a lot of importance because to reduce the threat of uranium contamination to ecology and its environment surroundings. Thus, economically as well as environmentally friendly sorbents with a good sorption capacity have to be acquired for the removal of U(VI) pollutants from the aqueous and polluted sea samples. In this study magnetic- Momordica charantia leaf powder impregnated into chitosan (m-MCLPICS) was prepared through the impregnation method. After preparation the adsorbent undergone through various characterizations such as BET, XRD, FTIR, SEM with elemental mapping, and VSM analysis. The specific surface area (93.12 m 2 /g), pore size (0.212 cm 3 /g) and pore volume (15.35 nm) of m-MCLPICS was obtained from the BET analysis. A pH value of 5 and 0.5 g of adsorbent dose were selected as an optimum values for U(VI) removal. Kinetic data follows the pseudo-second-order model, and the equilibrium data fitted well with the Langmuir isotherm model. ΔG° (-1.6999, -2.4994, -3.5476 and -4.5147 kJ/mol), ΔH 0 (25.1 kJ/mol) and ΔS 0 (0.089 kJ/mol K) indicates that the U(VI) sorption process is feasible, spontaneous and endothermic., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this study m-AHLPICS (magnetic Arachis hypogaea leaves powder impregnated into chitosan) was prepared and utilized as an adsorbent to remove U(VI) from aqueous and real polluted wastewater samples. m-AHLPICS was characterized by using the BET, XRD, FTIR, SEM with elemental mapping and magnetization measurements. Different experimental effects such as pH, dose, contact time, and temperature were considered broadly. Chitosan modified magnetic leaf powder (m-AHLPICS) exhibits an excellent adsorption capacity (232.4 ± 5.59 mg/g) towards U(VI) ions at pH 5. Different kinetic models such as pseudo-first-order, and pseudo-second-order models were used to know the kinetic data. Langmuir, Freundlich and D-R isotherms were implemented to know the adsorption behavior. Isothermal information fitted well with Langmuir isotherm. Kinetic data followed by the pseudo-second-order kinetics (with high R 2 values, i.e., 0.9954, 0.9985 and 0.9971) and the thermodynamic data demonstrate that U(VI) removal using m-AHLPICS was feasible, and endothermic in nature., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Recently, clean-up of resistant organic compounds has attracted growing attention. In this study, a novel heterogeneous ultrasound-enhanced sludge biochar catalyst/persulfate (BC/PS/US) process was firstly developed for the degradation of bisphenol A (BPA) in water. The results revealed that BC/PS/US process could successfully achieve a positively synergistic effect between sonochemistry and catalytic chemistry on the degradation of BPA compared to its corresponding comparative process. Nearly 98% of BPA could be degraded within 80 min at optimum reaction conditions. The coexisting substances including Cl - , SO 4 2- and NO 3 - had no obvious inhibition on the BPA degradation, whereas HCO 3 - and humic acid (HA) had significant inhibition effects on that. PS decomposition of BC/PS/US process was superior to that of BC/PS or US/PS process. Both SO 4 - and HO participated in the degradation of BPA, but SO 4 - was predominant radical in the BC/PS/US process. A possible pathway of BPA degradation was proposed, and the BPA molecule was attacked by SO 4 - and degraded into five kinds of intermediate products through hydroxylation and demethylation processes. This study helps to comprehend the application of sludge biochar catalyst as a persulfate activator for the degradation of organic compounds under ultrasound irradiation, and provides a new strategy in wastewater treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Phase memory is an effect in which the interaction between a coherent pump beam and a nonlinear crystal generates photon pairs via the spontaneous parametric down-conversion process, then the down-converted photons (signal and idler) can carry the phase information of the pump beam. There has been much research on the memory of the dynamic phase so far; however, there is no report on the memory of non-dynamic phase, to the best of our knowledge. Here we acquire a Pancharatnam-Berry (PB) geometric phase in a physical system when light travels along a trajectory in polarization-state space. Induced coherence occurs in a cascaded scheme composed of two nonlinear crystals, when the idler photons in both crystals are aligned to be indistinguishable. A NOON ($N\; = \;{2}$N=2) state is established when blocking the two idler photons. We explore the PB geometric phase memory of the NOON state and induced coherence. We find that the first-order interference of the two-photon state or signal photons can be controlled by introducing the PB geometric phase to the pump light. This may facilitate precise control of the phase of the down-converted photons.

Hemophilia A is a monogenic disease with a blood clotting factor VIII (FVIII) deficiency caused by mutation in the factor VIII (F8) gene. Current and emerging treatments such as FVIII protein injection and gene therapies via AAV-delivered F8 transgene in an episome are costly and nonpermanent. Here, we describe a CRISPR/Cas9-based in vivo genome editing method, combined with non-homologous end joining, enabling permanent chromosomal integration of a modified human B domain deleted-F8 (BDD-F8) at the albumin (Alb) locus in liver cells. To test the approach in mice, C57BL/6 mice received tail vein injections of two vectors, AAV8-SaCas9-gRNA, targeting Alb intron 13, and AAV8-BDD-F8. This resulted in BDD-F8 insertion at the Alb locus and FVIII protein expression in the liver of vector-, but not vehicle-, treated mice. Using this approach in hemophilic mice, BDD-F8 was expressed in liver cells as functional human FVIII, leading to increased plasma levels of FVIII and restoration of blood clotting properties in a dose-dependent manor for at least 7 months, with no detectable liver toxicity or meaningful off-target effects. Based on these findings, our BDD-F8 genome editing approach may offer an efficacious, long-term and safe treatment for patients with hemophilia A.

It is well-known that heavy metals are non-biodegradable and have been showing remarkable impacts on the environment, public health and economics. Because of high toxic tendency, lead (Pb), is one of the foremost considerable hazardous metal with high environmental impacts. Chitosan is a polysaccharide, and can be utilized in wastewater treatment because of its good sorption ability. Amino and hydroxyl groups (C-3 position) on chitosan can serve as electrostatic interaction and complexation sites for metal cations. Chemical crosslinking can effectively enhance the stability of chitosan in acidic media. Hence a novel, cost-effective and eco-friendly ZnO incorporated into aminated chitosan Schiff's base (ACSSB@ZnO) has been synthesized, characterized (BET, XRD, FTIR, SEM, TEM and 1 H NMR), and utilized as an adsorbent for the removal of Pb(II) ions from the aqueous environment. The various operating parameters, such as pH (2-8), agitation speed (30-180), adsorbent dose (0.1-0.8 g), contact time (0-140 min), metal ion concentration and temperature (303-323 K) were investigated. The maximum sorption capacity of Pb(II) onto ACSSB@ZnO was found to be 55.55 mg/g. The equilibrium, and kinetic studies suggested that the adsorption process followed the Langmuir isotherm and Pseudo-Second-Order model. Thermodynamic data showed that the sorption process was feasible, spontaneous, and endothermic., (Copyright © 2019. Published by Elsevier B.V.)

Mammalian cell expression systems are the most commonly used platforms for producing biotherapeutic proteins. However, development of recombinant mammalian cell lines is often hindered by the unstable and variable transgene expression associated with random integration. We have developed an efficient strategy for site-specific integration of genes of interest (GOIs). This method enables rapid and precise insertion of a gene expression cassette at defined loci in mammalian cells, resulting in homogeneous transgene expression. We identified the Hipp11 (H11) gene as a "safe harbor" locus for gene knock-in in CHO-S cells. Using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 mediated homologous recombination, we knocked in a DNA cassette (the landing pad) that includes a pair of PhiC31 bacteriophage attP sites and genes facilitating integrase-based GOI integration. A master cell line, with the landing pad inserted correctly in the H11 locus, was established. This master cell line was used for site-specific, irreversible recombination, catalyzed by PhiC31 integrase. Using this system, an integration efficiency of 97.7% was achieved with green fluorescent protein (GFP) after selection. The system was then further validated in HEK293T cells, using an analogous protocol to insert the GFP gene at the ROSA26 locus, resulting in 90.7% GFP-positive cells after selection. In comparison, random insertion yielded 0.68% and 1.32% GFP-positive cells in the CHO-S and HEK293T cells, respectively. Taken together, these findings demonstrated an accurate and effective protocol for generating recombinant cell lines to provide consistent protein production. Its likely broad applicability was illustrated here in two cell lines, CHO-S and HEK293T, using two different genomic loci as integration sites. Thus, the system is potentially valuable for biomanufacturing therapeutic proteins., Competing Interests: All authors are employees of Applied StemCell, Inc. We filed a patent on the system (Kong, L.-J., Tsai, R., Site specific integration of transgenes. PCT/US2017/027073). These do not alter our adherence to PLOS ONE policies on sharing data and materials.

In mammalians and yeast, the splicing factor U2AF65/Mud2p functions in precursor messenger RNA (pre-mRNA) processing. Arabidopsis AtU2AF65b encodes a putative U2AF65 but its specific functions in plants are unknown. This paper examines the function of AtU2AF65b as a negative regulator of flowering time in Arabidopsis. We investigated the expression and function of AtU2AF65b in abscisic acid (ABA)-regulated flowering as well as the transcript abundance and pre-mRNA splicing of flowering-related genes in the knock-out mutants of AtU2AF65b. The atu2af65b mutants show early-flowering phenotype under both long-day and short-day conditions. The transcript accumulation of the flowering repressor gene FLOWERING LOCUS C (FLC) is reduced in the shoot apex of atu2af65b, due to both increased intron retention and reduced transcription activation. Reduced transcription of FLC results, at least partially, from the abnormal splicing and reduced transcript abundance of ABSCISIC ACID-INSENSITIVE 5 (ABI5), which encodes an activator of FLC in ABA-regulated flowering signaling. Additionally, the expression of AtU2AF65b is promoted by ABA. Transition to flowering and splicing of FLC and ABI5 in the atu2af65b mutants are compromised during ABA-induced flowering. ABA-responsive AtU2AF65b functions in the pre-mRNA splicing of FLC and ABI5 in shoot apex, whereby AtU2AF65b is involved in ABA-mediated flowering transition in Arabidopsis., (© 2019 The Authors. New Phytologist © 2019 New Phytologist Trust.)

High-dimensional Bell-like states are necessary for increasing the channel capacity of the quantum protocol. However, their preparation and measurement are still huge challenges, especially for the latter. Here, we prepare an initial eight-dimensional Bell-like state based on hyperentanglement of spin and orbital angular momentum (OAM) of the first and the third orders. We design simple unitary operations to produce eight Bell-like states, which can be distinguished completely in theory among each other. We propose and illustrate a multiple projective measurement scheme composed of only linear optical elements and experimentally demonstrate that all the eight hyperentangled Bell-like states can be completely distinguished by our scheme. Our idea of manipulating the eight Bell-like states is beneficial to achieve the 3-bit channel capacity of quantum protocol, opening the door for extending applications of OAM states in future quantum information technology.

Pre-mRNA splicing is an important step for gene expression regulation. Yeast Bud13p (bud-site selection protein 13) regulates the budding pattern and pre-mRNA splicing in yeast cells; however, no Bud13p homologs have been identified in plants. Here, we isolated two mutants that carry T-DNA insertions at the At1g31870 locus and shows early embryo lethality and seed abortion. At1g31870 encodes an Arabidopsis homolog of yeast Bud13p, AtBUD13. Although AtBUD13 homologs are widely distributed in eukaryotic organisms, phylogenetic analysis revealed that their protein domain organization is more complex in multicellular species. AtBUD13 is expressed throughout plant development including embryogenesis and AtBUD13 proteins is localized in the nucleus in Arabidopsis. RNA-seq analysis revealed that AtBUD13 mutation predominantly results in the intron retention, especially for shorter introns (≤100 bases). Within this group of genes, we identified 52 genes involved in embryogenesis, out of which 22 are involved in nucleic acid metabolism. Our results demonstrate that AtBUD13 plays critical roles in early embryo development by effecting pre-mRNA splicing., (© 2019 The Authors The Plant Journal © 2019 John Wiley & Sons Ltd.)

We design and realize a generator that can convert an orbital angular momentum (OAM) state into a vector polarization state. The generator is integrated by several commonly used optical elements and easy to make or glued. Compared with traditional interferometric ways for generating the vector optical fields, this integrated generator has compact and robust advantages and especially a high-efficiency of 87%.