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Overactive fatty acid metabolism is usually found in hematological malignancies including multiple myeloma (MM), but the underlying mechanisms remain unclear. Here, we reveal that acyl-CoA synthetase long-chain family member 4 (ACSL4) is abnormally overexpressed in MM cell lines and MM patients compared to healthy donors. Knockdown of ACSL4 inhibited MM cell proliferation and reduced fatty acid levels possibly by regulating lipid metabolism genes including c-Myc and sterol regulatory element binding proteins (SREBPs). As a propellent in ferroptosis, ACSL4 also determines the sensitivity of MM cells to ferroptosis inducer RSL3. Knockdown of ACSL4 rendered MM cells resistance to ferroptosis. Our findings suggest that ACSL4 is a double-edged sword target in MM. Based on the high expression of ACSL4, ferroptosis induction represents a promising therapeutic strategy for MM.

Coronavirus Disease 2019 (COVID-19) has been an unprecedented disaster for people around the world. A point particularly worth noting is that herbal medicines have made great contributions to the prevention and treatment of COVID-19 in China. Angiotensin converting enzyme 2 (ACE2) has been identified as the critical functional receptor for SARS-CoV-2. It can bind to the receptor-binding domain (RBD) of the spike protein (S protein), which is responsible for the entry of the coronavirus into host cells. Therefore, ACE2 can be regarded as an important intervention target for COVID-19. Recently, many herbal medicines have exhibited a high affinity for ACE2 in treating COVID-19. The current work summarized these herbal medicines including formulas (such as Lianhua Qingwen capsules, Xuebijing injection, Qingfei Paidu Decoction, Huashi Baidu formula, Shufeng Jiedu capsules, and Maxing Shigan decoction), single herbs including Ephedra sinica Stapf (Mahuang), Scutellariae radix (Huangqin), Lonicera japonica (Jinyinhua), and Houttuynia cordata (Yuxingcao), and active ingredients (such as ursodeoxycholic acid, glycyrrhizic acid, glycyrrhizin, salvianolic acid, quercetin, and andrographidine C), which have exhibited a high affinity for ACE2 in treating COVID-19. We hope this work may provide meaningful and useful information on further research to investigate the mechanisms of herbal medicines against SARS-CoV-2 and follow-up drug discovery.

First-line systemic therapeutic options for advanced esophageal squamous cell carcinoma (ESCC) are limited. In this multicenter, double-blind phase 3 trial, a total of 551 patients with previously untreated, locally advanced or metastatic ESCC and PD-L1 combined positive score of ≥1 were randomized (2:1) to receive serplulimab (an anti-PD-1 antibody; 3 mg/kg) or placebo (on day 1), plus cisplatin (50 mg/m2) (on day 1) and continuous infusion of 5-fluorouracil (1,200 mg/m2) (on days 1 and 2), once every 2 weeks. The study met the primary endpoints. At the prespecified final analysis of progression-free survival (PFS) assessed by the blinded independent radiological review committee, serplulimab plus chemotherapy significantly improved PFS compared with placebo plus chemotherapy (median PFS of 5.8 months and 5.3 months, respectively; hazard ratio, 0.60; 95% confidence interval, 0.48–0.75; P P = 0.0020). Grade 3 or higher treatment-related adverse events occurred in 201 (53%) and 81 (48%) patients in the serplulimab plus chemotherapy group and the placebo plus chemotherapy group, respectively. Serplulimab plus chemotherapy administered every 2 weeks significantly improved PFS and OS in patients with previously untreated, PD-L1-positive advanced ESCC, with a manageable safety profile. This study is registered with ClinicalTrials.gov (NCT03958890).

Abstract: A common surgical disease, intervertebral disc degeneration (IVDD), is increasing at an alarming rate in younger individuals. Repairing damaged intervertebral discs (IVDs) and promoting IVD tissue regeneration at the molecular level are important research goals. Exosomes are extracellular vesicles (EVs) secreted by cells and can be derived from most body fluids. Mesenchymal stem cell-derived exosomes (MSC-exos) have characteristics similar to those of the parental MSCs. These EVs can shuttle various macromolecular substances, such as proteins, messenger RNAs (mRNAs), and microRNAs (miRNAs) and regulate the activity of recipient cells through intercellular communication. Reducing inflammation and apoptosis can significantly promote IVD regeneration to facilitate the repair of the IVD. Compared with MSCs, exosomes are more convenient to store and transport, and the use of exosomes can prevent the risk of rejection with cell transplantation. Furthermore, MSC-exo-mediated treatment may be safer and more effective than MSC transplantation. In this review, we summarize the use of bone marrow mesenchymal stem cells (BMSCs), adipose-derived mesenchymal stem cells (AMSCs), nucleus pulposus mesenchymal stem cells (NPMSCs), and stem cells from other sources for tissue engineering and use in IVDD. Here, we aim to describe the role of exosomes in inhibiting IVDD, their potential therapeutic effects, the results of the most recent research, and their clinical application prospects to provide an overview for researchers seeking to explore new treatment strategies and improve the efficacy of IVDD treatment.

Peking Union Medical College was founded in the late Qing Dynasty and the early Republic of China. Since then, society and politics have been rapidly changing, and its architectural aesthetics reflect the idea of advocating the West and inheriting tradition. Through research and actual investigation, this paper summarizes the current status of its building from two aspects, interior decoration art and interior decoration technology, analyzes the interior decoration characteristics of Peking Union Medical College Phase I Project, and records the archives of Peking Union Medical College’s decoration technology.

Prussian blue nanozymes were fabricated for atherosclerosis nanotherapy, which could reduce cellular reactive oxygen species level and exert cytoprotective effects against macrophages apoptosis, significantly boycotting atherosclerosis development.

The sub-50 nm pH-responsive nanoparticles have cross-linked acidic cores and galactosylated shells, which endow them with high targeting efficacy to hepatoma cells, high drug loading efficiency at pH 7.4, and rapid squeezable drug release at pH 5.0.

Background Red blood cell (RBC) indices such as RBC count and RBC distribution width (RDW) are associated with heart failure and coronary artery disease, but the relationship between RBC indices and coronary artery calcification (CAC) is unclear. This study aimed to investigate RBC indices’ correlation with, and predictive value for, the presence and severity of CAC. Methods In this study, 1257 hospitalized patients who received a coronary computed tomography angiography examination were finally selected. Patients were classified into a control group (without CAC, n = 655) and a calcification group (with CAC, n = 602) according to their CAC score. The calcification group was further divided into a low calcification group, medium calcification group, and high calcification group. Results In the calcification group, the RBC count was lower, and the RDW-standard deviation (SD) and RDW-coefficient of variation (CV) were higher, than those in the control group (P Conclusions RBC indices were significantly associated with the presence and severity of CAC, indicating that these RBC indices have the potential to be predictors of CAC.

Japanese encephalitis virus (JEV), an important neurotropic pathogen, belongs to the genus Flavivirus of the family Flaviviridae and has caused huge threat to public health. It is still obscure regarding the functions of stem-loop (SL) and dumbbell (DB) domains of JEV 3��� UTR in viral replication and virulence. In the current study, using the infectious clone of JEV SA14 strain as a backbone, we constructed a series of deletion mutants of 3��� UTR to investigate their effects on virus replication. The results showed that partial deletions within SL or DB domain had no apparent effects on virus replication in both mammalian (BHK-21) and mosquito (C6/36) cells, suggesting that they were not involved in viral host-specific replication. However, the entire SL domain deletion (��VR) significantly reduced virus replication in both cell lines, indicating the important role of the complete SL domain in virus replication. The revertant of ��VR mutant virus was obtained by serial passage in BHK-21 cells that acquired a duplication of DB domain (DB-dup) in the 3��� UTR, which greatly restored virus replication as well as the capability to produce the subgenomic flavivirus RNAs (sfRNAs). Interestingly, the DB-dup mutant virus was highly attenuated in C57BL/6 mice despite replicating similar to WT JEV. These findings demonstrate the significant roles of the duplicated structures in 3��� UTR in JEV replication and provide a novel strategy for the design of live-attenuated vaccines.

Infantile spasms (IS) is a common epilepsy syndrome in infancy. Genetically based birth defects are among the many causes of infantile spasms. Genetic diagnosis can reveal the etiology of IS and guide treatment strategies and genetic counseling, but significant challenges surround the choice of appropriate genetic diagnostic strategies to improve the diagnostic yield in IS.For a cohort of Chinese patients with IS, appropriate genetic testing methods were selected according to etiological classification. Methods included karyotyping, copy number variation detection, single-gene sequencing, targeted sequencing panel, and whole-exome sequencing.A total of 728 children with IS from fifteen provinces and municipalities in China from June 2015 to October 2020 were recruited in the study. Among them, 436 were males (59.9%). The median age was 9.46 months. The diagnostic yield of our study was 31.5% (185/587). The top five causative genes were TSC2 (n = 91), STXBP1 (n = 21), TSC1 (n = 15), SCN2A (n = 6), and CDKL5 (n = 6). The genetic diagnostic yield was 100% in Down syndrome (n = 1), neurofibromatosis (n = 2), and methylmalonic acidemia (n = 2), 83.5% in tuberous sclerosis complex (n = 127), and 16.7% in unsolved infantile spasms (n = 442). Different genetic testing methods for different etiologies show large differences in diagnostic yields.This study demonstrates that appropriate genetic testing procedures for different phenotypes can ensure a high diagnostic yield.

Perinatal and childhood adverse outcomes associated with assisted reproductive technology (ART) has been reported, but it remains unknown whether the initial leukocyte telomere length (LTL), which is an indicator of age-related phenotypes in later life, is affected. Here, we estimated the LTLs of 1,137 individuals from 365 families, including 202 children conceived by ART and 205 children conceived spontaneously from two centers of the China National Birth Cohort, using whole-genome sequencing (WGS) data. One-year-old children conceived by ART had shorter LTLs than those conceived spontaneously (beta, -0.36; P = 1.29 × 10

This work aims to advance the understanding of the synergistic mechanism of lecithin and polymers (alginate, CMC, and PVP) in stabilizing curcumin, with a major focus on understanding the nanocomplex formation process and the main binding energy between molecules. It is demonstrated that lecithin and polymers have a synergistic effect in increasing the thermal acid, light, and digestion stability of curcumin. The potential mechanism is that the hydrophobic parts of curcumin molecules are first anchored at the region of the hydrophobic cavity of lecithin by van der Waals, while the hydrophilic parts are outward and are further encapsulated by hydrophilic polymers by van der Waals and electrostatic interaction to form a protective shell. This study contributes to our understanding of the synergistic mechanism of lecithin, polymers, and hydrophobic compounds, which can promote the synergistic use of lecithin and polymers to prepare nanocomplexes as an important tool for delivering bioactive compounds.

This paper investigates the free vibration analysis of kevlar/glass/epoxy resin hybrid composite laminates. The ABAQUS software is studied to obtain the natural frequency with different fiber hybridization effects. The 3D shell element models evaluate natural frequency and mode shape in the quasi-isotropic laminated composite. The numerical analysis results are studied and compared between ABAQUS and ANSYS software. It was shown that the natural frequency value between ABAQUS and ANSYS software provided almost the same value. The error value between ABAQUS and ANSYS ranged from 1.03 % to 2.30 %. It was found that the error between the experimental and numerical results was from 1.15 % to 13.51 %. It was concluded that the percentage error value was significantly dependent on the mesh size. Furthermore, the reasonable agreement between experimental and ANSYS results can better analyze the free vibration of composite laminates.

Molecular property prediction is essential for drug screening and reducing the cost of drug discovery. Current approaches combined with deep learning for drug prediction have proven their viability. Based on the previous deep learning networks, we propose the Molecular Information Fusion Neural Network (MIFNN). The features of MIFNN are as follows: (1) we extracted directed molecular information using 1D-CNN and the Morgan fingerprint using 2D-CNN to obtain more comprehensive feature information; (2) we fused two molecular features from one-dimensional and two-dimensional space, and we used the directed message-passing method to reduce the repeated collection of information and improve efficiency; (3) we used a bidirectional long short-term memory and attention module to adjust the molecular feature information and improve classification accuracy; (4) we used the particle swarm optimization algorithm to improve the traditional support vector machine. We tested the performance of the model on eight publicly available datasets. In addition to comparing the overall classification capability with the baseline model, we conducted a series of ablation experiments to verify the optimization of different modules in the model. Compared with the baseline model, our model achieved a maximum improvement of 14% on the ToxCast dataset. The performance was very stable on most datasets. On the basis of the current experimental results, MIFNN performed better than previous models on the datasets applied in this paper.

A high malignancy rate and poor prognosis are common problems with triple-negative breast cancer (TNBC). There is increasing evidence that glycolysis plays vital roles in tumorigenesis, tumor invasion, immune evasion, chemoresistance, and metastasis. However, a comprehensive analysis of the diagnostic and prognostic significance of glycolysis in TNBC is lacking.Transcriptomic and clinical data of TNBC patients were obtained from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, respectively. Glycolysis-related genes (GRGs) were collected from the Molecular Signatures Database (MSigDB). Differential comparative analysis was performed to obtain the differentially expressed (DE)-GRGs associated with TNBC. Based on the DE-GRGs, a glycolysis-related risk signature was established using Least Absolute Shrinkage and Selector Operation (LASSO) and multivariable Cox regression analyses. The prognostic value, tumor microenvironment, mutation status, and chemotherapy response of different risk groups were analyzed. An independent cohort from the METABRIC database was used for external validation. Furthermore, the expression patterns of five genes derived from the prognostic model were validated by quantitative real-time polymerase chain reaction (RT-qPCR).The glycolysis-related prognostic signature included five genes (IFNG, ACSS2, IRS2, GFUS, and GAL3ST1) and predicted the prognosis of TNBC patients independent of clinical factors (p 0.05). Patients were divided into high- and low-risk groups based on the median risk score. Compared to low-risk TNBC patients, high-risk patients had significantly decreased overall survival (HR = 2.718, p 0.001). Receiver operating characteristic and calibration curves demonstrated that the model had high performance in terms of predicting survival and risk stratification. The results remained consistent after external verification. Additionally, the tumor immune microenvironment significantly differed between the risk groups. Low-risk TNBC patients had a better immunotherapy response than high-risk patients. High-risk TNBC patients with a poor prognosis may benefit from targeted therapy.This study developed a novel glycolysis and prognosis-related (GRP) signature based on GRGs to predict the prognosis of TNBC patients, and may aid clinical decision-making for these patients.

Vitamin B5, also called D-pantothenic acid (D-PA), is a necessary micronutrient that plays an essential role in maintaining the physiological function of an organism. It is widely used in: food, medicine, feed, cosmetics, and other fields. Currently, the production of D-PA in industry heavily relies on chemical processes and enzymatic catalysis. With an increasing demand on the market, replacing chemical-based production of D-PA with microbial fermentation utilizing renewable resources is necessary. In this review, the physiological role and applications of D-PA were firstly introduced, after which the biosynthesis pathways and enzymes will be summarized. Subsequently, a series of cell factory development strategies for excessive D-PA production are analyzed and discussed. Finally, the prospect of microbial production of D-PA production has been prospected.

Systemic lupus erythematosus (SLE) is a complicated autoimmune disease affecting multiple systems and organs. It is highly heterogeneous, and it preferentially affects women at childbearing age, causing worldwide social burden. The pathogenesis of SLE mostly involves genetic predisposition, epigenetic dysregulation, overactivation of the immune system, and environment factors. Human microbiome, which is mostly composed of microbiota colonized in the gut, skin, and oral cavity, provides a natural microbiome barrier against environmental risks. The past decade of research has demonstrated a strong association between microbiota and metabolic diseases or gastrointestinal diseases. However, the role of microbiota in autoimmunity remains largely unknown until recently, when the technological and methodological progress facilitates further microbiota research in SLE. In this review, the latest research about the role and mechanisms of microbiota in SLE and the advances in the development of diagnostic and therapeutic strategies based on microbiota for SLE were summarized.

The current situation of frequent small-scale accidents shows that the existing methods have not completely solved the problem of bearing failures, and new research methods need to be used to complete the study of bearing failures. To prevent the failure of rolling bearings and meet the need for timely detection of faults, this research is based on deep learning. Using the combination of deep transfer learning and metric learning methods, the identification and analysis of bearing multi-state vibration signals under different working conditions are carried out. The combination of SSAE-based similarity measurement criteria and deep transfer learning can reduce the differences between different domains. It is difficult to distinguish the data samples at the boundary and diagnose the problems that the physical meaning is difficult to understand. Through the bearing fault diagnosis analysis, the validity of the deep learning diagnosis model proposed in this paper is verified. The results show that the detection accuracy of the rolling bearing fault detection method based on LCM-SSAE is 0.6 percentage points higher than that of the rolling bearing fault detection method based on SSAE, which proves that the method is suitable for the fault detection of rolling bearing, and it also shows the effectiveness and robustness of the fault detection system of rolling bearing.

Loss of motor function in the trapezius muscle is one complication of radical neck dissection after cutting the accessory nerve (AN) during surgery. Nerve repair is an effective method to restore trapezius muscle function, and includes neurolysis, direct suture, and nerve grafting. The suprascapular nerve (SCN) and AN are next to each other in position. The function of the AN and SCN in shoulder elevation and abduction movement is synergistic. SCN might be considered by surgeons for AN reanimation.To obtain anatomical and clinical data for partial suprascapular nerve-to-AN transfer.Ten sides of cadavers perfused with formalin were obtained from the Department of Human Anatomy, Histology and Embryology, Peking University Health Science Center. The SCN (The whole length of the AN in the trapezius muscle was 16.89 cm. The average numbers of branches distributed in the descending, horizontal and ascending portions were 3.8, 2.6 and 2.2, respectively. The diameter of the AN was 1.94 mm at the anterior border of the trapezius. The length of the suprascapular nerve from the origin of the brachial plexus to the scapular notch was longer than the distance of the suprascapular nerve from the origin point to the point where the accessory nerve entered the upper edge of the trapezius muscle. The amplitude of trapezius muscle electromyography indicated that both the horizontal and ascending portions of the trapezius muscle on the right side had better function than the left side nine months after surgery. The results showed that the right-sided supraspinatus and infraspinatus muscles did not lose more function than the left side.Based on anatomical data and clinical application, partial suprascapular nerve-to-AN transfer could be achieved and may improve innervation of the affected trapezius muscle after radical neck dissection.

In response to prolonged stimulation by tumour antigens, T cells gradually become exhausted. There is growing evidence that exhausted T cells not only lose their potent effector functions but also express multiple inhibitory receptors. Checkpoint blockade (CPB) therapy can improve cancer by reactivating exhausted effector cell function, leading to durable clinical responses, but further improvements are needed given the limited number of patients who benefit from treatment, even with autoimmune complications. Here, we suggest, based on recent advances that tumour antigens are the primary culprits of exhaustion, followed by some immune cells and cytokines that also play an accomplice role in the exhaustion process, and we also propose that chronic stress-induced hypoxia and hormones also play an important role in promoting T-cell exhaustion. Understanding the classification of exhausted CD8

Off-label drug use embodies a thorough clinical diagnosis and evaluation of treatment needs and should not be confused with unreasonable drug use, but it also faces potential risks with drug safety and legal issues.We first established a guideline working group. Following the guideline development process recommended by the World Health Organization Handbook and the Chinese Medical Association, the key questions were determined through literature searches of PubMed, CNKI (Chinese National Knowledge Infrastructure) and other databases. Both the evidence and the clinicians' diagnosis and treatment workload were considered to formulate the initial recommendations. Finally, two rounds of Delphi surveys and one expert seminar were organized to determine the final recommendations of this guideline. Meanwhile, we graded the recommendations based on the body of evidence.We determined nine questions and proposed a total of 23 recommendations regarding the definition of off-label use of drugs, applicable circumstances, classification of evidence, informed consent, legal basis, adverse drug reaction monitoring and evaluation, management procedure, responsibilities and obligations of different stakeholders, medical insurance reimbursement, and the national approval system.This guideline standardized clinical off-label drug use and provided suggestions and references for the management of off-label drug use.

With the rapid development of information technology, the amount of all kinds of data information is increasing rapidly. As an important means to collect, store, and manage massive data, and then analyze and predict the habits and characteristics of certain groups of people and even the development trend of a certain industry, big data technology provides a comprehensive strategic basis for management decision makers that the traditional processing mode cannot match. Contemporary management accounting serves the whole process of enterprise internal control, so it will produce a large number of various data. With the explosive growth of network data and the increasing scale of database, more and more people begin to study data mining, and the classification algorithm, as the key technology in data mining, has also received extensive attention. In order to further improve the information technology level of enterprise management accounting and increase the depth of information application, many enterprises began to pay more attention to data mining, and through deep data mining, the depth and breadth of enterprise data analysis were improved. In the research of data and accounting informatization, data mining technology accounts for about 50% of informatization, which is the way for future development. With the advent of the information age, the dependence of enterprises on information technology in the process of accounting management has been further improved. If enterprises want to achieve better development in the information age, they need to pay more attention to the information technology of management accounting and improve the application ability of enterprise staff in information.

Polymorphisms have been identified to predispose to primary gouty arthritis (GA) and hyperuricemia (HUA). Here, we accessed the five polymorphisms of rs10754558, rs35829419, rs3738448, rs3806268, and rs7525979 in NLRP3 on GA and HUA susceptibility. We collected 1198 samples (314 GA, 377 HUA, and 507 controls) for this case-control study. Our data detected that the rs3806268 (GA vs. AA: OR = 0.65 , p = 0.012 ) was significantly associated with the susceptibility to GA. The rs3738448 (TT vs. GG: OR = 2.05 , p = 0.024 ) and rs7525979 (TT vs. CC: OR = 1.96 , p = 0.037 ) were significantly associated with the susceptibility to HUA. The rs3806268 AG genotype presented decreased risk of GA among the hypertension ( OR = 0.54 , p = 0.0093 ), smoking ( OR = 0.59 , p = 0.018 ), and no obesity ( OR = 0.60 , p = 0.0097 ) subjects compared to the GG genotype group. The rs3738448 TT genotype demonstrated increased risk of HUA among the hypertension ( OR = 4.10 , p = 0.0056 ) and no drinking population ( OR = 3.56 , p = 0.016 ) compared to the GG genotype group. The rs7525979 TT genotype demonstrated increased risk of HUA among the hypertension ( OR = 4.01 , p = 0.0064 ) and no drinking population ( OR = 3.24 , p = 0.034 ) compared to the CC genotype group. Furthermore, a significant haplotype effect of rs10754558/C-rs35829419/C-rs3738448/G-rs3806268/A-rs7525979/C was found ( OR = 1.60 , p = 0.0046 ) compared with GCGAC haplotype. Bioinformatics analyses indicated that rs3738448, rs3806268, and rs7525979 might influence the gene regulation, while the T-allele of rs3738448 increased the stability of NLRP3-mRNA. Collectively, our case-control study confirms NLRP3 polymorphisms might participate in regulating immune and inflammation responses in GA and HUA.