Highly flexible electromagnetic interference (EMI) shielding material with excellent shielding performance is of great significance to practical applications in next-generation flexible devices. ...However, most EMI materials suffer from insufficient flexibility and complicated preparation methods. In this study, we propose a new scheme to fabricate a magnetic Ni particle/Ag matrix composite ultrathin film on a paper surface. For a ~ 2-µm-thick film on paper, the EMI shielding effectiveness (SE) was found to be 46.2 dB at 8.1 GHz after bending 200,000 times over a radius of ~ 2 mm. The sheet resistance (R□) remained lower than 2.30 Ω after bending 200,000 times. Contrary to the change in R□, the EMI SE of the film generally increased as the weight ratio of Ag–Ni increased, in accordance with the principle that EMI SE is positively related to an increase in electrical conductivity. Desirable EMI shielding ability, ultrahigh flexibility, and simple processing provide this material with excellent application prospects.
•Common defects and anomalies in powder bed fusion metal additive manufacturing.•Formation mechanism and practical mitigation strategies are discussed.•Defects/anomalies are classified as ...powder-related, processing-related, and post-processing related issues.•Properties such as mechanical behavior and corrosion resistance of defective parts are discussed.•Current challenges, gaps, and future trends are discussed.
Metal additive manufacturing is a disruptive technology that is revolutionizing the manufacturing industry. Despite its unrivaled capability for directly fabricating metal parts with complex geometries, the wide realization of the technology is currently limited by microstructural defects and anomalies, which could significantly degrade the structural integrity and service performance of the product. Accurate detection, characterization, and prediction of these defects and anomalies have an important and immediate impact in manufacturing fully-dense and defect-free builds. This review seeks to elucidate common defects/anomalies and their formation mechanisms in powder bed fusion additive manufacturing processes. They could arise from raw materials, processing conditions, and post-processing. While defects/anomalies in laser welding have been studied extensively, their formation and evolution remain unclear. Additionally, the existence of powder in powder bed fusion techniques may generate new types of defects, e.g., porosity transferring from powder to builds. Practical strategies to mitigate defects are also addressed through fundamental understanding of their formation. Such explorations enable the validation and calibration of models and ease the process qualification without costly trial-and-error experimentation.
Piperidine-substituted amino-triazine derivatives were designed, introducing amino to the triazine ring and polar hydrophilic groups to the right wing, with excellent activity against wild-type ...HIV-1.
A novel series of piperidine-linked amino-triazine derivatives were designed, synthesized and evaluated for in vitro anti-HIV activity as non-nucleoside reverse transcriptase inhibitors on the basis of our previous work. Screening results indicated that most compounds showed excellent activity against wild-type HIV-1 with EC50 values in low nanomolar concentration range (especially compound 6b3, EC50=4.61nM, SI=5945) and high activity against K103N/Y181C resistant mutant strain of HIV-1 with EC50 values in low micromolar concentration range. In addition, preliminary structure–activity relationship and molecular modeling of these new analogs were detailed in this manuscript.
Bio-recycling of plastic waste is a promising solution to plastic pollution. As one of the most abundant plastic wastes, polyethylene terephthalate (PET) can be degraded by carboxylic ester ...hydrolases (EC 3.1.1). Nevertheless, the biological PET hydrolysis efficiency is always limited by the low activity and poor thermostability of the enzymes. Herein, to address the above barriers, we rationally mutated the relevant sites of
Thermobifida cellulosilytica
cutinase 1 (ThcCut1) involved in substrate binding. The wider substrate-binding pockets after mutation could facilitate the accessibility of the enzyme to the substrate. Divalent metal-binding sites were further predicted and substituted with disulfide bonds, with the aim of effectively improving the thermostability of the mutant ThcCut1. Coupled with sequence alignment and structural dynamics analysis, the ThcCut1-D205C/E254C/Q93G variant with a melting temperature exceeding the glass transition temperature of recycled PET was constructed. After comprehensively screening the active and thermally stable mutation sites, the resulting ThcCut1-G63A/F210I/D205C/E254C/Q93G (ThcCut1-AICCG) variant exhibited high enzymatic activity at a high temperature (70 °C). As result, 96.2% of the post-consumer PET bottle particles (without energy-intensive melt-quenching pretreatment) can be successfully degraded after 96 h of hydrolysis using ThcCut1-AICCG, which was 87.5 times higher than that using the wild-type ThcCut1. This novel strategy for amino acid site analysis will facilitate the modification of homologous cutinases to improve the catalytic performance, and provide a reliable technical method for constructing a PET hydrolase modification platform.
Background
Although a plethora of studies have employed multiple gallbladder cancer (GBC) cell lines, it is surprisingly noted that there is still lack of a normal gallbladder epithelial cell line as ...a normal counterpart, thus impeding substantially the progress of mechanistic studies on the transformation of normal epithelial cells to cancer. Here, we created a normal gallbladder epithelial cell line named L-2F7 from human gallbladder tissue.
Methods
Gallbladder tissues from a diagnosed cholecystitis female patient were collected, and epithelial cells were enriched by magnetic cell sorting. Then, the cells were immortalized by co-introduction of human telomerase reverse transcriptase (hTERT) and Simian virus 40 large T antigen (LT-SV40)
via
a lentivirus infection system. After clonal selection and isolation, L-2F7 cells were tested for epithelial markers CK7, CK19, CK20, and CD326, genomic feature, cell proliferation, and migration using Western blot, immunofluorescence, whole genome sequencing, karyotyping, and RNA sequencing. L-2F7 cells were also transplanted to Nude (nu/nu) mice to determine tumorigenicity.
Results
We successfully identified one single-cell clone named L-2F7 which highly expressed epithelial markers CD326, CK7, CK19, and CK20. This cell line proliferated with a doubling time of 23 h and the epithelial morphology sustained over 30 passages following immortalization. Transient gene transduction of L-2F7 cells led to expression of exogenous GFP and FLAG protein. L-2F7 cells exhibited both distinct non-synonymous mutations from those of gallbladder cancer tissues and differential non-cancerous gene expression patterns similar to normal tissue. Although they displayed unexpected mobility, L-2F7 cells still lacked the ability to develop tumors.
Conclusion
We developed a non-cancerous gallbladder epithelial cell line, offering a valuable system for the study of gallbladder cancer and other gallbladder-related disorders.
With the booming development of the electricity market, market factors such as electricity trading varieties are growing rapidly. The frequency of transactions has become increasingly real-time, and ...transaction clearing and settlement tasks have become more complex. The increasing demands for concurrent access and carrying capacity in trading systems have made it increasingly difficult for existing systems to support business. This article proposes a transaction support system for large-scale electricity trading market entities, which solves the problems of high concurrency access and massive access data calculation while ensuring system security through business isolation measures. The system uses microservices to treat various functional modules as independent service modules, thus making service segmentation and composition more flexible. By using read–write separation, caching mechanisms, and several data reliability assurance measures, data can be stored and accessed quickly and securely. The use of a three-layer load balancing module consisting of an OpenResty access entry layer, a gateway routing gateway layer, and a WebClient service inter-resource invocation layer can effectively improve the system’s ability to handle concurrent access.
Despite of the high lethality of gallbladder cancer (GBC), little is known regarding molecular regulation of the tumor immunosuppressive microenvironment. Here, we determined tumor expression levels ...of YKL-40 and the molecular mechanisms by which YKL-40 regulates escape of anti-tumor immune surveillance. We found that elevated expression levels of YKL-40 in plasma and tissue were correlated with tumor size, stage IV and lymph node metastasis. Single cell transcriptome analysis revealed that YKL-40 was predominantly derived from M2-like subtype of infiltrating macrophages. Blockade of M2–like macrophage differentiation of THP-1 cells with YKL-40 shRNA resulted in reprogramming to M1-like macrophages and restricting tumor development. YKL-40 induced tumor cell expression and secretion of growth differentiation factor 15 (GDF15), thus coordinating to promote PD-L1 expression mediated by PI3K, AKT and/or Erk activation. Interestingly, extracellular GDF15 inhibited intracellular expression of GDF15 that suppressed PD-L1 expression. Thus, YKL-40 disrupted the balance of pro- and anti-PD-L1 regulation to enhance expression of PD-L1 and inhibition of T cell cytotoxicity, leading to tumor immune evasion. The data suggest that YKL-40 and GDF15 could serve as diagnostic biomarkers and immunotherapeutic targets for GBC.
•Increased YKL-40 in plasma were correlated with tissue expression of YKL-40 and GBC progression.•Blockade of YKL-40 in M2-like macrophages resulted in M1-like macrophage reprogramming.•YKL-40 promoted GDF15 secretion, which in turn inhibited intracellular GDF15 function that suppressed PD-L1 expression.•YKL-40 and GDF15 induced PD-L1 expression and abrogated cytotoxicity of infiltrating CD8+ T lymphocytes.
The aim of this study was to evaluate efficacy and safety of 1470 nm diode laser enucleation of the prostate (DiLEP) and plasmakinetic resection of the prostate (PKRP) in elderly benign prostatic ...hyperplasia (BPH) patients with lower urinary tract symptoms.
A total of 123 elderly patients with BPH were randomized to undergo either 1470 nm DiLEP or PKRP by means of a random number table from September 2020 to April 2022. The perioperative and postoperative data were studied during a 3- and 6-month follow-up.
The patients treated with 1470 nm DiLEP had significantly decreased operation time (74.6 ± 17.0
98.8 ± 18.9 minutes,
< 0.001), hemoglobin loss (1.06 ± 0.49
1.59 ± 0.60 g/dL,
< 0.001), bladder irrigation time (22.1 ± 8.1
33.9 ± 10.0 hours,
< 0.001), catheter duration (3.2 ± 1.3
5.8 ± 1.0 days,
< 0.001), and hospital stay (7.6 ± 1.4
9.6 ± 1.3 days,
< 0.001) compared with the PKRP group. Besides, International Index of Erectile Function-5 score of 1470 nm DiLEP group at postoperative 3- and 6-month follow-up was significantly higher than PKRP group. No differences achieving statistical significance were identified in total prostate-specific antigen, maximum urinary flow rate, International Prostate Symptom Score, quality-of-life score, and the postvoid residual urine volume, transient incontinence, urethral stricture, bladder neck contracture, and retrograde ejaculation at 3- and 6-month follow-up.
1470 nm DiLEP is safer than PKRP, with a smaller effect on sexual function, and it is comparable with the efficacy of PKRP, thus making it more suitable for elderly BPH patients. Clinical Trial Registration number: S2021-463-01.
Most studies on the membrane vibration are limited to discussing small deflection linear problems, but rarely on the study of nonlinear large deflection problems. In practice, however, membrane ...deflection is not necessarily far less than the thickness, so it is necessary to research the large deflection vibration problems of moving membrane. In this paper, the large deflection vibration characteristics and stability of the moving printing membrane are analyzed. Large deflection vibration equation of an axially moving membrane is derived by using Von Karman nonlinear plate theory. The large deflection vibration of rectangle moving membrane with four edges fixed boundary is studied by using the Bubnov–Galerkin method which is a semi-analytical-weighted residual method, and the large deflection vibration complex frequency curves along with the change of speed and aspect ratio in the different initial conditions are obtained. The results show that the large deflection nonlinear vibration can be effectively avoided by increasing membrane aspect ratio and decreasing the membrane dimensionless velocity. The study provides theoretical basis for improving the operation stability of the printing equipment.
Bortezomib is one of the important drugs that have made breakthrough progress in multiple myeloma (MM) in the past 10 years. However, the heterogeneity of its efficacy makes it difficult to predict ...the risk of disease progression. The purpose of this study is to determine the prognostic significance of the (neutrophils + monocytes)/lymphocytes ratio (NMLR) in newly diagnosed MM patients who received BCD regimen therapy in terms of progression-free survival (PFS).
A total of 150 patients who fulfilled the International Myeloma Working Group (IMWG) criteria were enrolled in the study retrospectively. The prognostic value of NMLR was evaluated by 150 patients with MM who were treated with BCD (bortezomib + cyclophosphamide + dexamethasone) regimen therapy. NMLR was calculated by the ratio of (neutrophils + monocyte) to lymphocytes. According to receiver operating characteristic curves, the cutoff value was 1.90. The patients were divided into high NMLR group (H-NMLR, NMLR ≥1.90) and low NMLR group (L-NMLR, NMLR <1.90). The clinical characteristics, treatment responses and PFS of the two groups were analyzed.
The median age of the patients was 61 years. Fifty-five (36.67%) patients showed lower NMLR at initial diagnosis. Although NMLR was unable to discriminate prognosis in ISS stage I/II patients, interestingly, the addition of NMLR to the ISS further defined prognosis particularly in stage III. Low-NMLR group who achieved early immune reconstruction significantly higher than that of the high-NMLR group (
< 0.001). NMLR value was 1.98 ± 1.02 for the patients who achieved early immune reconstruction, which was 3.26 ± 2.52 for the patients without immune reconstruction (
< 0.05). Compared with the H-NMLR group, the levels of β2-microglobulin, serum creatinine and calcium were lower, and the very good partial response or better (≥VGPR) ratio was higher in L-NMLR group. The L-NMLR group experienced a superior median PFS compared with the H-NMLR group (24.0 versus 15.5 months;
< 0.001). In addition, several other prognostic factors of PFS were estimated, including the high-risk cytogenetics, β2-microglobulin and the depth of treatment response 3 months after treatment with BCD regimen. Moreover, NMLR was an independent predictor of PFS including non-high risk cytogenetics (0.587;
= 0.031).
In patients with newly diagnosed MM undergoing BCD regimen, the NMLR <1.90 was an independent prognostic factor for PFS as well as early immune reconstruction and lower disease burden.
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