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Objective(s): Chronic alcohol abuse causes cognitive deficits. Huangqi Gegen Decoction (HGD), a traditional Chinese herbal formula comprising Huangqi and Gegen, has been documented for its therapeutic efficacy in the treatment of alcoholic liver injury. However, its potential neuroprotective effects against alcohol-induced brain injury remain unexplored. This study aims to evaluate the neuroprotection of HGD on alcohol-induced cognitive dysfunction and the associated mechanism.Materials and Methods: Wistar rats were orally administered 50% ethanol for 10 weeks, followed by treatment with HGD at doses of 16, 32, or 64 mg/kg/day for an additional 6 weeks. The spatial learning and memory abilities of rats were assessed through the Morris Water Maze experiment. The pathological condition in the hippocampus was assessed using H&E and Nissl staining. Tight junction proteins, oxidative stress, and inflammation cytokines were measured by IF, ELISA, PCR, and western blot. The mRNA and protein expression of Keap1, Nrf-2, HO-1, and NQO-1 were tested by PCR and western blot.Results: Results showed that HGD effectively mitigated cognitive dysfunction and pathological changes in alcohol-induced rats while enhancing the expression of ZO-1, Occludin, and Claudin-5. Furthermore, HGD effectively mitigated oxidative stress by reducing levels of ROS and MDA, while elevating levels of SOD, CAT, and GSH-PX in brain tissue. Moreover, HGD significantly suppressed microglial activation and down-regulated expressions of IL-1β, IL-6, and TNF-α. Mechanistically, HGD remarkably up-regulated the expression of Nrf-2, HO-1, and NQO-1 while down-regulating Keap1 expression.Conclusion: These findings suggest that HGD may be a promising therapeutic agent for alleviating alcohol-induced cognitive dysfunction.

Abstract Preserving pulp viability and promoting pulp regeneration in pulpitis have attracted widespread attention. Restricted by the oxidative stress microenvironment of dental pulpitis, excessive reactive oxygen and nitrogen species (RONS) trigger uncontrolled inflammation and exacerbate pulp tissue destruction. However, modulating redox homeostasis in inflamed pulp tissue to promote pulp regeneration remains a great challenge. Herein, this work proposes an effective antioxidative system (C-NZ/GelMA) consisting of carbon dot nanozymes (C-NZ) with gelatin methacryloyl (GelMA) to modulate the pulpitis microenvironment for dental pulp regeneration by utilizing the antioxidant properties of C-NZ and the mechanical support of an injectable GelMA hydrogel. This system effectively scavenges RONS to normalize intracellular redox homeostasis, relieving oxidative stress damage. Impressively, it can dramatically enhance the polarization of regenerative M2 macrophages. This study revealed that the C-NZ/GelMA hydrogel promoted pulp regeneration and dentin repair through its outstanding antioxidant, antiapoptotic, and anti-inflammatory effects, suggesting that the C-NZ/GelMA hydrogel is highly valuable for pulpitis treatment.

Abstract Background Sterol side-chain reductase 2 (SSR2) is a key enzyme in the synthesis of plant cholesterol pathway. Despite the importance of watermelon as a horticultural cash crop, the SSR2 gene in watermelon has not been previously studied or reported. Results In this study, 28 SSR2 genes were identified in the watermelon genome. The physicochemical properties of 28 ClaSSR proteins were predicted by bioinformatics methods, and the gene structure, conserved motif, chromosome localization, phylogenetic analysis, cis-acting elements, expression patterns, promoter activity analysis and subcellular localization of ClaSSRs were studied. The 28 ClaSSRs were unevenly distributed on 11 chromosomes, and phylogenetic analysis showed that they could be grouped into 4 groups with other related Cucurbitaceae homologous genes. Analysis of gene structure and motifs revealed similarities in exons/introns and motifs between members of the same group, further supporting phylogenetic results. The RT–qPCR results showed variations in ClaSSRs expression during watermelon fruit development. The analysis of promoter activity for ClaSSR25 showed strong activity. Subcellular localization studies confirmed that ClaSSR25 is mainly located in the cytoplasm, which aligns with the predicted outcomes. We additionally estimated the network of protein–protein interactions for ClaSSR25 and analyzed proteins that could potentially interact with ClaSSR25 in melon and Arabidopsis thaliana. Conclusions We conducted bioinformatics analysis and expression analysis of members of the watermelon SSR2 gene family in this work, and the outcomes set the stage for further investigations into the watermelon SSR2 gene. Graphical Abstract

Background Bronchial asthma (asthma) is the most common chronic respiratory disease in childhood, with long disease course and repeated attacks, which affecting the development and life quality of children. As the main providers of primary healthcare, general practitioners play important role in the early diagnosis and grading management of childhood asthma. Understanding their level of prevention and treatment services for this disease can provide suggestions for improving the quality of primary care childhood asthma prevention and treatment services. Objective To investigate the service level of primary general practitioners in the prevention and treatment of childhood asthma, and the influencing factors on the service level. Methods From April to July 2022, 22 districts (counties) were randomly selected from the 38 districts (counties) in Chongqing Municipality, and conducted a questionnaire survey on primary general practitioners in the sampling. The questionnaire was designed by the research team based on relevant guidelines and literatures, and formed through two rounds of expert consultation and pre-investigation, including four dimensions of knowledge, attitude, behavior and self-evaluation. We investigated the knowledge, attitude, behavior and self-evaluation of primary general practitioners regarding the prevention and treatment of childhood asthma and analyzed the influencing factors. Results A total of 234 general practitioners participated in the questionnaire survey. The knowledge score of general practitioners on the prevention and treatment of childhood asthma was (6.03±2.04) , with a pass rate of 44.9%; the attitude score was (49.42±4.94) , with a pass rate of 100.0%; the behavior score was (30.55±6.66) , with a pass rate of 87.2%; and the self-evaluation score was (21.57±5.30) , with a pass rate of 85.0%. Regarding the selection of referral indications, 98.7% (231/234) of the general practitioners believed that children with moderate or severe acute asthma attack that was not significantly relieved after emergency treatment needed to be referred, and 94.0% (220/234) of the general practitioners believed that children with asthma that could not be controlled effectively after standardized treatment needed to be referred. For children with poorly controlled symptoms, 33.8% (79/234) of the general practitioners would carefully analyze the cause of poor control, and 17.5% (41/234) of the general practitioners would advise patients to follow the doctor's advice, temporarily observe the condition and make an appointment for next reexamination. 33.8% (79/234) of the general practitioners held an uncertain or opposed attitude towards the diagnosis and treatment of childhood asthma in primary medical institutions. The main influencing factors of this attitude was the lack of disease-related knowledge and learning opportunities for general practitioners, reluctance of parents to visit primary medical institutions, strained pediatric doctor-patient relationship, the small number of children suffering from asthma, and the lack of related facilities and equipment. Multiple linear regression analysis showed that professional title and training experience on childhood asthma were the influencing factors of knowledge score (P

Abstract Phase change materials have issues in the automotive industry and in‐memory computing due to their limited thermal stability and high power consumption. Consequently, numerous studies are conducted to enhance the performance of these materials. Uncertainty persists regarding the effects and mechanisms of various doping on the parent material. In this study, four metallic doping elements are selected, and their effects on Sb2Te3 are meticulously analyzed through experiments and ab initio calculations. The thermal stability of Sb2Te3 has been somewhat enhanced by doping these four elements, with Ta doping having the most impact. According to the ab initio molecular dynamics, this improvement results from the tetrahedral centered In and the increased coordination numbers of Ta, Ti, and Sc. Sc located at the center of the octahedron can accelerate the crystallization process. Ta, in particular, exerts the greatest influence on the migration rates of Sb and Te, resulting in the slowest grain growth rate. Simultaneously, it maximizes the delay in the transition from the cubic phase to the hexagonal phase. These features are beneficial for reducing power consumption. The elucidation of the distinct effects of doping elements sets the stage for phase change memory to adapt to various application scenarios.

Spinal arachnoid web is a rare condition characterized by extramedullary bands of arachnoid tissue at the level of the dorsal thoracic spinal cord that may lead to progressive, permanent neurological deficits. To date, this condition has been radiographically characterized by a scalpel sign, which has been pathognomonic in all reported cases of spinal arachnoid webs. In this case, we report the first known patient with confirmed spinal arachnoid web without radiographic evidence of the scalpel sign. In reporting our finding, we encourage a higher clinical suspicion for spinal arachnoid web in patients presenting with progressive thoracic myelopathy following trauma, and radiographic evidence of ventrally displaced spinal cord and turbulent cerebrospinal fluid flow, even in the absence of a scalpel sign.

Abstract A new CTOD calculation method is investigated in this study, considering the FPZ and the effective Young’s modulus. The calculated CTOD values from four theoretical models are compared with the measured CTOD values from the three-point beam experiments, and the differences between them are analyzed. The measured CTOD consists of two parts: (1) the displacement generated by the elastic–plastic deformation in the crack tip region, and (2) the displacement generated by micro-damage in the FPZ. CTOD value caused by micro-damage in the FPZ accounts for 81–92% of the overall CTOD. Thus, the FPZ and the effective Young’s modulus are introduced to modify the models for calculating CTOD. The result indicates that the modified plastic zone model is better than the strip-yield model, the plastic zone model and the modified strip-yield model in calculating CTOD, and CTOD error is reduced from 81 to 90% between the plastic zone model and the experiment to 4–34% between the modified plastic zone model and the experiment, with nearly half of the specimens having an error of less than 10%.

Photodynamic therapy (PDT) is attracting great attention for cancer treatments, while its therapeutic efficacy is limited by unsatisfactory photosensitizers and hypoxic tumor microenvironment (TME). To address these problems, we have developed catalase-loaded manganese-porphyrin frameworks (CAT@MnPFs) for catalytically-assisted PDT of cancer cells. CAT@MnPFs were constructed by the assembly of Mn2+ ions and PpIX into MnPFs and the subsequent loading of catalase. Under 650 nm light irradiation, the porphyrin (Protoporphyrin IX) within the structure of CAT@MnPFs can convert oxygen (O2) into singlet oxygen (1O2), showing the photodynamic effect. Importantly, the loaded catalase can decompose hydrogen peroxide (H2O2) into O2 with a huge elevation of O2 level (13.22 mg L−1) in 600 s, thus promoting 1O2 generation via PDT. As a result, CAT@MnPFs combined with 650 nm light can effectively ablate cancer cells due to the catalase-assisted oxygen-evolving PDT, showing a high therapeutic efficacy. Meanwhile, after the incubation with CAT@MnPFs, unobvious damage can be found in normal and red blood cells. Thus, the obtained CAT@MnPFs integrate the advantage of photosensitizers and catalase for oxygen-evolving PDT, which can provide some insight for treating hypoxic cells.

DLAT has been recognized as a cuproptosis-related gene that is crucial for cuproptosis in earlier research. The study is to look at how DLAT affects individuals with low-grade glioma's prognosis and immune infiltration. The Genotype-Tissue Expression (GTEx) database and the TCGA database were used in this work to download RNAseq data in TPM format. DLAT was found to be overexpressed in LGG by comparing DLAT expression levels between LGG and normal brain tissue, and the expression of DLAT was verified by immunohistochemistry and semi-quantitative analysis. Then, the functional enrichment analysis revealed that the biological functional pathways and possible signal transduction pathways involved were primarily focused on extracellular matrix organization, transmembrane transporter complex, ion channel complex, channel activity, neuroactive ligand-receptor interaction, complement and coagulation cascades, and channel activity. The level of immune cell infiltration by plasmacytoid dendritic cells and CD8 T cells was subsequently evaluated using single-sample gene set enrichment analysis, which showed that high DLAT expression was inversely connected with that level of infiltration. The link between the methylation and mRNA transcription of DLAT was then further investigated via the MethSurv database, and the results showed that DLAT's hypomethylation status was linked to a poor outcome. Finally, by evaluating the prognostic value of DLAT using the Cox regression analysis and Kaplan-Meier technique, a column line graph was created to forecast the overall survival (OS) rate at 1, 3, and 5 years after LGG identification. The aforementioned results demonstrated that high DLAT expression significantly decreased OS and DSS, and that overexpression of DLAT in LGG was significantly linked with WHO grade, IDH status, primary therapy outcome, overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) events. DLAT was discovered as a separate predictive sign of OS in the end. DLAT might thus represent a brand-new predictive biomarker.

Magnesium alloy shows promise of becoming a new generation of degradable biomaterials because of its good biocompatibility and mechanical properties. This paper details the preparation of magnesium alloy by adding calcium and zinc elements to pure magnesium at a specific ratio and strengthened by solid solution treatment and extrusion. The magnesium alloy is subjected to micro-motion wear testing, in vitro degradation product analysis, and in vitro biocompatibility testing and demonstrates excellent performance. The study demonstrates that the prepared Mg-2.0Zn-1.6Ca alloy friction ring has an elliptical shape with a low friction coefficient, which notably enhances the wear resistance of the material. Furthermore, the corrosion of magnesium alloy products in simulated body fluids does not adversely affect the human body. This is because the surface of the magnesium alloy favors cell growth and has excellent antimicrobial properties. The purpose of this paper is to enhance the preparation, surface friction properties, and biocompatibility of magnesium alloys and to provide theoretical and practical guidance for the preparation, processing, and application of high-performance medical magnesium alloys.

Abstract With depth increase of many mines, the damage of surrounding rock by high ground stress cannot be ignored under the blasting excavation method. In view of the strong disturbance of surrounding rock caused by dynamic excavation and unloading under high initial rock stress conditions, based on the elastic unloading theory, the analytical solution of dynamic excavation and unloading stress is given using the residue theorem and Laplace inverse transform. The stress field distribution under the coupling effect of blasting load and initial rock stress is described. By making a rock model and implementing biaxial loading using a drop hammer to simulate the impact load, radial cracks generated by the impact stress wave and circumferential cracks generated by unloading during excavation were captured, and the stress change curve during excavation was monitored. The monitoring curve and theoretical curve have consistency in trend. Under the coupling effect of blasting load and initial stress, surrounding rock will generate tensile stress and broken, and the unloading effect of initial stress occurs after the blasting load, which causes tensile damage to the surrounding rock. The stress field curve plotted by the theory explains well the crack propagation caused by the coupling effect of blasting load and initial stress.

Abstract This study utilizes digital image correlation (DIC) technology to measure the far-field displacements and strains of rock specimens during the entire loading and unloading. Through analyzing the distributions of strain, displacement and their variations per unit length at different stages, the variations of both length and migration velocity of the fracture process zone (FPZ) were studied, and the crack propagation was also investigated. In addition, the entire path of crack propagation was observed by scanning electron microscope (SEM). The results reveal that (1) the fractured ligament can be divided into three zones based on the displacement variation per unit length: intact zone, crack propagation zone, and FPZ. (2) The FPZ length reaches its maximum at the peak load and then decreases, and the minimum length even is only 1/3–1/2 of the maximum length. The FPZ migration velocity is − 48 to 1460 m/s. FPZ’s microscale features are intergranular microcracks, transgranular microcracks, cleavage, and debris on fracture surface and around main crack propagation path. (3) The crack propagation length during peak load to peak-post 90% accounts for more than 1/3–1/4 of the entire post-peak length. Crack propagation is alternating fast and slow, i.e., the velocity of crack propagation varies regularly in the range of 24–700 m/s. The region of crack initial propagation is more severely damaged compared to other propagation regions.

Doxorubicin-induced cardiotoxicity (DIC) adversely impacts patients' long-term health and quality of life. Its underlying mechanism is complex, involving regulatory cell death mechanisms, such as ferroptosis and autophagy. Moreover, it is a challenge faced by patients undergoing cardiac rehabilitation. Endurance exercise (E-Exe) preconditioning effectively counters DIC injury, potentially through the adenosine monophosphate-activated protein kinase (AMPK) pathway. However, detailed studies on this process's mechanisms are scarce. Here, E-Exe preconditioning and DIC models were established using mice and primary cultured adult mouse cardiomyocytes (PAMCs). Akin to ferrostatin-1 (ferroptosis inhibitor), rapamycin (autophagic inducer), and MitoTEMPO (mitochondrial free-radical scavenger), E-Exe preconditioning effectively alleviated Fe2+ accumulation and oxidative stress and improved energy metabolism and mitochondrial dysfunction in DIC injury, as demonstrated by multifunctional, enzymatic, and morphological indices. However, erastin (ferroptosis inducer), 3-methyladenine (autophagic inhibitor), adenovirus-mediated AMPKα2 downregulation, and AMPKα2 inhibition by compound C significantly diminished these effects, both in vivo and in vitro. The results suggest a non-traditional mechanism where E-Exe preconditioning, under mild mitochondrial reactive oxygen species generation, upregulates and phosphorylates AMPKα2, thereby enhancing mitochondrial complex I activity, activating adaptive autophagy, and improving myocardial tolerance to DIC injury. Overall, this study highlighted the pivotal role of mitochondria in myocardial DIC-induced ferroptosis and shows how E-Exe preconditioning activated AMPKα2 against myocardial DIC injury. This suggests that E-Exe preconditioning could be a viable strategy for patients undergoing cardiac rehabilitation.

Polyether ether ketone (PEEK) has excellent chemical stability, x-ray transmittance, and elastic modulus close to human cortical bone, which can effectively reduce the stress shielding effect. Therefore, PEEK can be used as a commonly used medical bone implant material to repair damaged bones. However, due to its low surface free energy, PEEK has a certain degree of biological inertness. Surface modification methods are urgently needed to improve this problem. Laser surface texturing is expected to improve the biological inertia of PEEK materials. In this study, an ultraviolet laser with a wavelength of 355 nm was used to construct textures on the surface of PEEK materials. By biomimetic design on the surface of PEEK materials, textures similar in depth and width to the surface topography of natural bones were processed. We explore the specific improvement of corrugated texture, single line texture, and orthogonal texture on PEEK material performance, aiming at improving the service performance of PEEK material and creating conditions for better service of PEEK material in vivo. Through the evaluation of PEEK surface contact angle, friction and wear properties, and biocompatibility, the research results show that laser surface texture treatment can improve many service properties of PEEK materials.

Magnesium alloy, valued for its superior mechanical properties and biocompatibility in biomaterials, faces limitations such as rapid corrosion, poor wear resistance, and unfavorable cell adhesion. To address these challenges and enhance medical magnesium alloy development, this study investigates a magnetic needle grinding process on magnesium alloy. Mg-1.6Ca-2.0Zn alloy, prepared through powder metallurgy and T6 aging treatment, undergoes milling, and magnetic grinding using various needle sizes. The impact is assessed through Vickers hardness, residual stresses, surface roughness, friction and wear tests, electrochemical assessments, and contact angle tests. Results indicate a 22.59% microhardness increase, 30.43 MPa residual compressive stress, increased surface roughness, improved wear and corrosion resistance, and improved hydrophilia after magnetic needle grinding. This research provides a theoretical foundation for advancing medical magnesium alloy industrially.

Pure waterjet surface treatment without abrasive particles has a promising application in the biomedical field, because it induces compressive residual stresses on a metal surface and never leaves the tiny hard particles. In this work, the influence of operation pressure, standoff distance and the number of paths of the waterjet on the surface topography as well as the hardness was studied using the Taguchi method. The results showed that the most essential parameter is the operation pressure. By tuning the operation pressure from 100 to 300 MPa, the surface of Ti6Al4V specimens can be smoothed, roughened or damaged; when the surface layer is eroded, the new-born surface exhibits a clear stochastic nature accompanied by microvoids. The standoff distance benefits finer controlling the height parameters, whilst the number of paths affects the waviness. The hardening effect generated by the waterjet impingement extends to a few hundred-micron depth of the specimens, and the peak value of microhardness was found at a depth of 70 μm, which is an increase by greater than 20 %. The roughness parameters of Arithmetical mean height (Sa), Skewness (Ssk), Auto-correlation length (Sal), and Developed interfacial area ratio (Sdr) as a set are recommended to characterize the biomaterial's surface. The present research results promote the application of waterjet treatment in the field of fine-tuning biomaterial surface morphology.

Objective: To observe the cytological pathological features of secondary thyroid neoplasm (STN) by ultrasound-guided fine-needle aspiration（FNA）. Methods: A total of 5023 cases of thyroid malignancy diagnosed by FNA cytology in The First Affiliated Hospital of Air Force Medical University from January 2011 to May 2021 were collected. Hematoxylin-eosin (HE) staining, Pap staining and cellular immunohistochemistry (IHC) staining were performed on traditional smears, liquid-based preparation and cell wax blocks made from FNA samples of all these STNs respectively. Using medullary thyroid carcinoma smear as a control, two senior cytopathologists analyzed the cytopathological and cellular immunohistochemical features of STN. Based on clinical practice, the key points of cytopathological differentiation between STN and medullary thyroid carcinoma were summarized. Result: Among 5023 cases of thyroid malignancy, there were 8 cases of STN (0.16%), 33 cases of medullary thyroid carcinoma (0.66%), 4955 cases of papillary thyroid carcinoma (98%), 16 cases of lymphoma (0.32%), 7 cases of squamous cell carcinoma (0.14%), and 2 cases each of anaplastic carcinoma and poorly differentiated carcinoma (0.04%). The 33 cases of medullary carcinoma tumor cells were diverse in morphology, including plasmacytoid cells, epithelioid cells, and fusiform cells, with a small number of bizarre giant cells and amyloid in the background. None of the 8 STNs showed typical nuclear features of thyroid papillary carcinoma， three-dimensional papillary and adenoid structures were seen in 1 case of metastatic lung adenocarcinoma， clusters or scattered heterotypic squamous cells were seen in 4/4 cases of metastatic squamous cell carcinoma, combined with their respective characteristic immunophenotypes, the diagnosis can be confirmed. The cytological morphological characteristics of 2 metastatic breast cancers and 1 metastatic small cell lung carcinoma overlapped with medullary thyroid carcinoma. The cells were all small and hyperchromatic nuclei, which required the detection of immunohistochemical markers including estrogen receptor (ER), Progesterone receptor（PR）, Cytokeratin7 (CK7), GATA3, Synaptophysin (Syn), Neural cell adhesion molecule (CD56), Chromogranin A (CgA), Calcitonin (CT), Thyroglobulin(TG), Thyroid transcription factor-1(TTF-1), Paired box gene 8 (PAX-8), and identification were made in the combination with medical history. Conclusions: STN accounts for 0.16% of thyroid malignancies and is relatively rare. In cases with myeloid cancer cell morphology, attention should be paid to the possibility of STN, and differential diagnosis should be made in combination with immunohistochemistry and medical history.

As the power supply of IC chips tends to be low-voltage and high-current, the design of the Power Delivery Network(PDN) of the micro-system module is becoming more and more important, based on 2.5D Through-Silicon-Via(TSV), inverted solder, High Temperature Co-fired Ceramics(HTCC),3D stacking, etc. Chip currents generate output noise through PDN interconnects, which must provide a better signal return path with low-impedance to keep the supply voltage between chip pads constant within a small tolerance range, usually 5% or less. Based on Chip Package System(CPS), the paper proposes a design and optimization method for the micro-system module PDN based on the three-level synergy of TSV silicon substrate, HTCC cases and PCB. This paper expounds the DC design and AC impedance design respectively, and using the Chip Power Model(CPM) combined with the time domain analysis, realizes the low impedance design of the power ripple on PDN.

Alterations in the regulators of RNA methylation modifications, such as N7-methylguanosine (m7G), have been implicated in a variety of diseases. Therefore, the analysis and identification of disease-related m7G modification regulators will accelerate advances in understanding disease pathogenesis. However, the implications of alterations in the regulators of m7G modifications remain poorly understood in prostate adenocarcinoma. In the present study, we analyze the expression patterns of 29 m7G RNA modification regulators in prostate adenocarcinoma using The Cancer Genome Atlas (TCGA) and perform consistent clustering analysis of differentially expressed genes (DEGs). We find that 18 m7G-related genes are differentially expressed in tumor and normal tissues. In different cluster subgroups, DEGs are mainly enriched in tumorigenesis and tumor development. Furthermore, immune analyses demonstrate that patients in cluster 1 have significantly higher scores for stromal and immune cells, such as B cells, T cells, and macrophages. Then, a TCGA-related risk model is developed and successfully validated using a Gene Expression Omnibus external dataset. Two genes ( EIF4A1 and NCBP2) are determined to be prognostically significant. Most importantly, we construct tissue microarrays from 26 tumor specimens and 20 normal specimens, and further confirm that EIF4A1 and NCBP2 are associated with tumor progression and Gleason score. Therefore, we conclude that the m7G RNA methylation regulators may be involved in the poor prognosis of patients with prostate adenocarcinoma. The results of this study may provide support for exploring the underlying molecular mechanisms of m7G regulators, especially EIF4A1 and NCBP2.

Biodegradable hydrogel-based matrices are becoming more widely utilized for a variety of medical applications, including SpaceOAR which is a hydrogel injected into the recto-prostatic space under ultrasound guidance to protect the rectum during prostate radiation therapy. Although a greater number of these procedures are being performed, there are no case reports on the potential complications which may result. In this report, we present the first case of retrograde embolization of SpaceOAR hydrogel into the right common iliac artery during routine office administration, as well as subsequent interventional angiography, inpatient and outpatient management, and clinical and imaging results at 1.5-month patient follow-up.

Objective To evaluate the clinical efficacy of the concurrent chemoradiotherapy (CCRT) combined adjuvant chemotherapy (AC) for locally advanced nasopharyngeal carcinoma (NPC). Methods From April 2011 to January 2019, 318 patients with locally advanced NPC were collected from radiotherapy center of the Second Affiliated Hospital of Army Medical University. According to the results of CCRT, the patients were divided into the adjuvant group and the no-adjuvant group to comparatively analyze the survival outcome and adverse reaction of those patients received adjuvant chemotherapy. Stratification analysis was used to analyze the survival difference of different therapy plans (CCRT, CCRT+AC, IC+CCRT and IC+CCRT+AC) among 318 patients. The survival difference of 99 pairs of patients in the subgroup of clinical parameters was analyzed after the patients in the adjuvant group were paired with the patients in the no-adjuvant group. Results Compared with CCRT, CCRT combined with adjuvant chemotherapy could increase the overall survival(OS), progression-free survival(PFS), distant metastasis-free survival(DMFS)and recurrence-free survival(RFS); Compared with IC plus CCRT(IC+CCRT), IC+CCRT+AC showed a decreasing trend in OS, PFS, DMFS and RFS. According to the results of stratification analysis, for EBV positive, N3 stage and IVA stage patients, adjuvant chemotherapy had a tendency to increase OS, PFS, DMFS and RFS, and increase the RFS for the T4 stage patients. There was no difference in acute radiation mucositis, acute radiation pharyngitis and esophagitis between the two groups. The adjuvant group had higher incidence rate than the non-adjuvant group in ≥2 grade of myelosuppression(68% vs 55%, P=0.020). Conclusion Adjuvant chemotherapy after concurrent chemoradiotherapy cannot significantly increase the survival benefit for patients with locally advanced NPC; For EBV positive, stage N3 and stage ⅣA patients, there is a positive trend in OS, PFS, DMFS and RFS, and for stage T4 patients, they also obtain benefit in PFS.

Objective: This study aimed to explore the regulatory effect of Lactarius hatsudake polysaccharide on intestinal flora. Methods: LHP was extracted from L. hatsudake by hot water. LHP-1 and LHP-2 were further purified and characterized. The effects of LHPs on body weight and intestinal microbiome composition were studied in antibiotic-induced mice. Results: LHP-1 was mainly composed of mannose, glucose and galactose. The molar mass ratio of LHP-1 was 3.44∶61.10∶1.22. LHP-2 is mainly composed of mannose and glucose, with a molar mass ratio of 3.84∶153.00. It has a "neuronal" structure and a chain structure region. LHP intervention can restore the structure and diversity of intestinal flora by increasing beneficial bacteria such as Bacteroides and Akkermansia and reducing harmful bacteria such Enterococcus and Brevundimonas. In particular, the increase of the beneficial bacteria A. muciniphila indicates the great potential of LHP in the regulation of human intestinal flora. Conclusion: Polysaccharide from Lactarius hatsudake can improve intestinal metabolism as potential prebiotics.

Abstract In recent years, along with the development and application of magnesium alloys, magnesium alloys have been widely used in automotive, aerospace, medicine, sports, and other fields. In the field of medical materials, magnesium not only has the advantage of light weight, high strength, and a density similar to that of human bone, but also has good biocompatibility and promotes the growth of human bone. However, the mechanical properties and corrosion resistance of magnesium alloys need to be further improved to meet the requirements for human biodegradable implants. In this study, three alloys (mass fractions: Mg–10Zn, Mg–20Zn, and Mg–30Zn (wt.%)) were prepared using powder metallurgy by homogeneously mixing powders of the above materials in a certain amount with magnesium as the substrate through the addition of zinc elements, which also have good biocompatibility. The effect of zinc on the microstructure, mechanical properties, wear performance, and corrosion resistance of magnesium–zinc alloys was studied when the zinc content was different. The results show that compared with the traditional magnesium alloy using powder metallurgy, prepared magnesium alloy has good resistance to compression and bending, its maximum compressive stress can reach up to 318.96 MPa, the maximum bending strength reached 189.41 MPa, and can meet the mechanical properties of the alloy as a human bone-plate requirements. On the polarization curve, the maximum positive shift of corrosion potential of the specimens was 73 mv and the maximum decrease of corrosion-current density was 53.2%. From the comparison of the above properties, it was concluded that the three prepared alloys of which Mg–20% Zn had the best overall performance. Its maximum compressive stress, maximum bending strength, and corrosion-current density reached 318.96 MPa, 189.41 MPa and 2.08 × 10−5 A·cm−2 respectively, which are more suitable for use as human implant bone splints in human-body fluid environment. The mechanical properties of the sintered Mg–Zn alloys were analyzed using powder-metallurgy techniques, and their microstructure, micromotion wear properties, electrochemical corrosion properties and composition of the physical phases were analyzed and discussed.

IntroductionThe two-spotted spider mite (TSSM) is a devastating pest of cassava production in China. Lignin is considered as an important defensive barrier against pests and diseases, several genes participate in lignin biosynthesis, however, how these genes modulate lignin accumulation in cassava and shape TSSM-resistance is largely unknown.MethodsTo fill this knowledge gap, while under TSSM infestation, the cassava lignin biosynthesis related genes were subjected to expression pattern analysis followed by family identification, and genes with significant induction were used for further function exploration.ResultsMost genes involved in lignin biosynthesis were up-regulated when the mite-resistant cassava cultivars were infested by TSSM, noticeably, the MePAL gene presented the most vigorous induction among these genes. Therefore, we paid more attention to dissect the function of MePAL gene during cassava-TSSM interaction. Gene family identification showed that there are 6 MePAL members identified in cassava genome, further phylogenetic analysis, gene duplication, cis-elements and conserved motif prediction speculated that these genes may probably contribute to biotic stress responses in cassava. The transcription profile of the 6 MePAL genes in TSSM-resistant cassava cultivar SC9 indicated a universal up-regulation pattern. To further elucidate the potential correlation between MePAL expression and TSSM-resistance, the most strongly induced gene MePAL6 were silenced using virus-induced gene silencing (VIGS) assay, we found that silencing of MePAL6 in SC9 not only simultaneously suppressed the expression of other lignin biosynthesis genes such as 4-coumarate--CoA ligase (4CL), hydroxycinnamoyltransferase (HCT) and cinnamoyl-CoA reductase (CCR), but also resulted in decrease of lignin content. Ultimately, the suppression of MePAL6 in SC9 can lead to significant deterioration of TSSM-resistance.DiscussionThis study accurately identified MePAL6 as critical genes in conferring cassava resistance to TSSM, which could be considered as promising marker gene for evaluating cassava resistance to insect pest.

IntroductionUtilization of resistant germplasm is considered as an effective, economical and eco-friendly strategy for cassava pest management. Tetranychus urticae, known as the two-spotted spider mite (TSSM), is a devastating pest in Asian cassava planting countries as well as in China. However, the resistant levels of abundant cassava germplasms to TSSM remains largely unknown.MethodsTo fill this knowledge gap, we conducted screening of 202 cassava germplasm for resistance to TSSM in China based on the classification of mite damage phenotype, under both greenhouse and field conditions.ResultsThe three rounds of large-scale greenhouse experiments had identified two highly resistant (HR) varieties (C1115 and MIANDIAN), five resistant (R) varieties (SC5, SC9, SC15, COLUMBIA-4D and LIMIN) and five highly susceptible (HS) varieties (KU50, BREAD, SC205, TMS60444 and BRA900), besides, these ‘HR’ and ‘R’ varieties would significantly repress the normal development and reproduction of TSSM. In addition, the 12 cassava varieties selected from the greenhouse screening were further subjected to consecutive five years of field validation at Danzhou, Wuming and Baoshan. The seven resistant varieties not only exhibited stable TSSM-resistance performance across the three field environments, but also possessed the same resistant levels as the greenhouse identification, while the resistant varieties SC5 was an exception, which was identified as moderate resistant in Baoshan, indicating the variety-environment interaction may affect its resistance. Furthermore, regional yield estimation suggested that the higher the resistance level was, the better capacity in reducing the yield losses.DiscussionThis study demonstrated that the TSSM-resistant varieties could be considered as ideal materials in mite control or in future breeding programme of mite-resistant cassava plant.

Objective To explore the effects of anti-drug antibody (ADA) on clinical efficacy and adverse reactions in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Methods A total of 26 patients with stage Ⅲ/Ⅳ NSCLC undergoing pembrolizumab or nivolumab treatment from April 2016 to September 2019 were collected from the Second Affiliated Hospital and Daping Hospital of Army Medical University. Blood samples were collected about 2 months after the first infusion of ICIs. The level of ADA in plasma were measured by enzyme-linked immunosorbent assay. The effects of ADA on the clinical efficacy, disease progression and immune-related adverse events (irAEs) of ICIs were analyzed. Results In 12 patients treated with nivolumab, the results of ADA test were negative, the best overall response rate (bOR) was 25.0%, the median progression-free survival (mPFS) was 4.1(1.9~26.9) months, and the median overall survival (mOS) was 12.4 (4.8~26.9) months. In 14 patients treated with pembrolizumab, bOR was 50.0%, mPFS was 10.9 (2.2~25.3) months, and mOS was 19.0 (5.2~29.6) months; 3 of 14 patients were ADA-positive, 11 were ADA-negative. mPFS (9.9 vs 12.4 months, P=0.280), mOS (19.0 vs 29.6 months, P=0.874) and median time to radiographic progression after blood sampling (7.5 vs 8.6 months, P=0.365) were significantly shorter in the ADA-positive patients than the ADA-negative patients. irAEs occurred in 2 (66.7%) ADA positive patients and 3 (27.3%) ADA negative patients. Conclusion ADA monitoring in NSCLC patients has certain clinical value for the treatment of ICIs, and ADA positive of pembrolizumab has an effect on the shorter survival time of patients. However, the effect of ADA status is not significant on bOR and irAEs.

The experimental investigation of the dynamic mechanical behavior of graphene aerogel is still lacking due to its low impendence. The present work, therefore, reports on the preliminary experimental characterization of the energy absorption characteristics of graphene aerogel by using the split Hopkinson pressure bar emphasis on the influence of the drying method. The graphene aerogels were synthesized by the sol-gel method and dried, either by supercritical CO2 drying (SD) or by freeze-drying methods (FD). It was observed that under dynamic uniaxial compression, the SD samples exhibited a negative Poisson's ratio throughout gradual compression. However, FD samples failed by radial shattering without this auxetic behavior. The energy dissipation ratios of SD samples increased from 41% to 73% as expected with the specimen thickness increasing from 3 mm to 12 mm, being overall higher in comparison with FD samples which rises from 35% to 43%. SD graphene aerogels have a large number of random pores (∼50 nm), which is beneficial for absorbing the kinetic energy through plastic deformation and pore walls’ collapse. By contrast, the FD graphene aerogels’ pore walls buckle readily under the impact, and fail due to their ordered porous structure at the micron scale (∼1μm), which impairs their energy absorption capability.

Doxorubicin (Dox)-induced cardiotoxicity (DIC) seriously threatens the health of related patients. Studies have confirmed that 14–3–3γ and protein kinase C epsilon (PKCε) are the endogenous protective proteins. Puerarin (Pue) is a bioactive ingredient isolated from the root of Pueraria lobata. It possesses many pharmacological properties, which have been widely used in treating and adjuvant therapy of cardiovascular diseases. In the study, we intended to explore the effects and mechanism of Pue pretreatment to protect the myocardium against DIC injury. Adult mice and H9c2 cells were pretreated with Pue, and the injury model was made with Dox. Results showed that Pue pretreatment alleviated DIC injury, as revealed by increased cell viability, decreased LDH activity and apoptosis, inhibited excess oxidative stress, maintained mitochondrial function and energy metabolism, and improved myocardial function. Furthermore, Pue pretreatment upregulated 14–3–3γ expression, interacted with PKCε, phosphorylated and impelled migration to mitochondria, activated adaptive autophagy, and protected the myocardium. However, pAD/14–3–3γ-shRNA or εV1–2 (a PKCε activity inhibitor) or 3-methyladenine (an autophagy inhibitor) could weaken the above effects of Pue pretreatment. Together, Pue pretreatment could activate adaptive autophagy by the 14–3–3γ/PKCε pathway and protect the myocardium against DIC injury.

The two-spotted spider mite (TSSM) is a destructive cassava pest. Intensive demonstration of resistance mechanism greatly facilitates the creation of TSSM-resistant cassava germplasm. Gene to metabolite network plays a crucial role in modulating plant resistance, but little is known about the genes and related metabolites which are responsible for cassava resistance to TSSM. Here, a highly resistant (HR) and a highly susceptible (HS) cassava cultivar were used, integrative and comparative transcriptomic and metabolomic analyses between these two cultivars after TSSM infestation revealed that several genes and metabolites were closely related and significantly different in abundance. In particular, the expression of leucoanthocyanidin reductase (LAR) and anthocyanidin reductase (ANR) genes showed a high positive correlation with most of the metabolites in the tannin biosynthesis pathway. Furthermore, transgenic cassava lines overexpressing either of the genes elevated tannin concentrations and conferred cassava resistance to TSSM. Additionally, different forms of tannins possessed distinct bioactivity on TSSM, of which total condensed tannins (LC50 = 375.68 mg/l) showed maximum lethal effects followed by procyanidin B1 (LC50 = 3537.10 mg/l). This study accurately targets LAR, ANR and specific tannin compounds as critical genes and metabolites in shaping cassava resistance to TSSM, which could be considered as biomarkers for evaluation and creation of pest-resistant cassava germplasm.

High-speed machining of γ-TiAl alloy is a significant challenge due to high cutting temperatures. From the perspective of environmental protection and improving tool life, appropriate cooling strategies should be adopted. Compared with dry and conventional flood cooling conditions, the feasibility of machining γ-TiAl in cryogenic LN2 cooling conditions was discussed. The cutting force, tool wear and its mechanism, and surface roughness, as well as sub-surface morphology characteristics, were studied by combining macro and micro techniques. The results revealed that the wear morphology of the rake and flank face under the three cooling media shows different degrees. The crater wear of the rake face is expanded at high speeds and then progresses into more serve flaking and notching wear. The main wear pattern on the flank face is gradually transformed from adhesive wear to diffusion and oxidation wear at high speeds in dry machining. In the LN2 condition, the diffusion of workpiece elements and cutting-edge oxidation were restrained. The wear pattern is still mainly adhesive wear. In addition, cryogenic machining shows significant advantages in reducing cutting force, suppressing heat-affected zone, improving surface quality, and inhibiting micro-lamellar deformation.

Objective To explore the value of smart glasses in monitoring the visual behavior of school-age children. Methods A total of 46 myopic children aged 9 to 11 years who visited our hospital during April to August 2019 were included in this study. Questionnaires were used to record the participants' daily outdoor time, near-work time, and parental supervision to obtain the baseline value of children's visual behavior. Besides, Akeso smart glasses were used to objectively record the daily wearing time, outdoor time, and near-work time of all participants from September 2019 to December 2019. Subsequently, we compared the differences in the children's visual behavior recorded by the questionnaire and Akeso smart glasses. In addition, we also compared the differences in the children's visual behavior on school days and weekends recorded by Akeso smart glasses, and analyzed the impact of parental supervision on the length of time the child wears glasses. Results The number of children corresponding to the different outdoor time recorded by the questionnaire was as follows: ≤30 min (n=5), >30 to 60 min (n=6), >60 to 120 min (n=23), >120 min (n=12), and this children's visual behavior parameter recorded by Akeso smart glasses was ≤30 min (n=16), >30 to 60 min (n=26), >60 to 120 min (n=4), >120 min (n=0). There were statistical differences between the results recorded by the above methods (P < 0.001). The results of Akeso smart glasses also showed significant differences were in the outdoor time spent on school days and weekends [24 (4, 56) vs 15 (3, 43) min/d, P < 0.001], and in the near-work time spent on school days and weekends (363.36±98.55 vs 329.08±105.90 min/d, P < 0.001). The children with parental supervision wore glasses for 711.80±101.63 min every day, while the wearing time for those without was 641.64±84.79 min, and there were statistical differences between these 2 groups (P=0.026). Conclusion Akeso smart glasses is able to objectively record children's visual behavior and can be used to supplement or replace questionnaires in the prevention and control myopia research.

Methods that capture the features of single voxels of resting-state fMRI (RS-fMRI) could precisely localize the abnormal spontaneous activity and hence guide precise brain stimulation. As one of these metrics, the amplitude of low-frequency fluctuation (ALFF) has been used in numerous studies, however, it is frequency-dependent and the division of frequency bands is still controversial. Based on the well-accepted power law of time series, this study proposed an approach, namely, power spectrum slope (PSS), to characterize the RS-fMRI time series of single voxels. Two metrics, i.e., linear coefficient b and power-law slope b’ were used and compared with ALFF. The reliability and validity of the PSS approach were evaluated on public RS-fMRI datasets (n = 145 in total) of eyes closed (EC) and eyes open (EO) conditions after image preprocessing, with 21 subjects scanned two times for test–retest reliability analyses. Specifically, we used the paired t-test between EC and EO conditions to assess the validity and intra-class correlation (ICC) to assess the reliability. The results included the following: (1) PSS detected similar spatial patterns of validity (i.e., EC–EO differences) and less test–retest reliability with those of ALFF; (2) PSS linear coefficient b showed better validity and reliability than power-law slope b’; (3) While the PPS showed less validity in most regions, PSS linear coefficient b showed exclusive EC–EO difference in the medial temporal lobe which did not show in ALFF. The power spectrum plot in the parahippocampus showed a “cross-over” of power magnitudes between EC and EO conditions in the higher frequency bands (>0.1 Hz). These results demonstrated that PSS (linear coefficient b) is complementary to ALFF for detecting the local spontaneous activity.

Phase change memory (PCM), a typical representative of new storage technologies, offers significant advantages in terms of capacity and endurance. However, among the research on phase change materials, thermal stability and switching speed performance have always been the direction where breakthroughs are needed. In this research, as a high-speed and good thermal stability material, Ta was proposed to be doped in Sb3Te1 alloy to improve the phase transition performance and electrical properties. The characterization shows that Ta-doped Sb3Te1 can crystallize at temperatures up to 232 °C and devices can operate at speeds of 6 ns and 8 × 104 operation cycles. The reduction of grain size and the density change rate (3.39%) show excellent performances, which are both smaller than that of Ge2Sb2Te5 (GST) and Sb3Te1. These properties conclusively demonstrate that Ta incorporation of Sb3Te1 alloy is a material with better thermal stability and faster crystallization rates for PCM applications.

The complete mitochondrial genome of Aucklandia lappa was sequenced for the first time. The mitochondrial genome length was 320,439 bp, with 45.05% GC contents. There were 67 genes annotated, including 31 known protein-coding genes, 25 tRNAs, and six rRNAs. The maximum likelihood method was used to establish the phylogenetic tree of 37 species. Results have shown that A. lappa and Arctium lappa were sister groups. It reveals the genetic relationship between different species and provides a theoretical basis for the establishment of a classification system.

Objective To analyze the real-world data about immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) based on the modified RECIST 1.1 for immune based therapeutics (iRECIST). Methods According to real-world research methods, all advanced NSCLC patients treated with immune checkpoint inhibitors (ICIs) in our hospital from August 10, 2016 to July 10, 2019 were enrolled in this study. The efficacy, including best overall response (bOR), progression-free survival (PFS) and duration of response (DoR) was evaluated in first-line monotherapy, first-line combination, second-line monotherapy and second-line combination based on iRECIST. Also, immune-related adverse events (irAEs) were evaluated. Results A total of 61 patients (54 males and 7 females) with stage IV NSCLC were included, at a median age of 58 years, and there were 31 cases of adenocarcinoma and 30 cases of squamous carcinoma. The bOR and mPFS were 27.3% and 11.8 months, respectively, for first-line monotherapy; 47.1% and not reached (NR), respectively, for first-line combination, and 35.9% and 11.8 months, respectively, for first-line totally. And the bOR and mPFS were 30% and 6.0 months, respectively, for the second-line monotherapy; were 41.7% and NR, respectively, for second-line combination; and were 36.4% and 6.3 months, respectively for second-line totally. The most common irAEs was grade 1~2 skin toxicity (5 cases, 8.2%). Conclusion Our results show that bOR and PFS of first-line monotherapy, first-line combination, second-line monotherapy are better than the results of previous RCT, and bOR and PFS of second-line combination are significantly better than second-line monotherapy. irAEs are controllable study.

The Fourier-based gradient field integration method can efficiently reconstruct transparent surfaces from the measured gradient data in the Shape-from-polarization method. However, for the differentiation operator having large truncation errors and lacking constraints on adjacent heights, it will increase the reconstructing error of the Fourier-based integration method. This paper presents an accurate Fourier-based integration approach to improve the reconstruction accuracy, in which a new differentiation operator is derived by limiting the truncation error and increasing heights and slopes in the operator. In order to modify the data obtained by the new operator to meet the requirements of both periodicity and size for the use of the discrete Fourier transform, we propose a method to extend the raw gradient data by first performing antisymmetric extension and then performing periodic extension. A series of simulations and experiments have been developed to verify the performance of the proposed method. By comparing the approach of this paper with other Fourier-based approaches, including Frankot-Chellappa, Southwell-FT and Simpson-FT, both of the simulation and experiment results show that the proposed Fourier-based integration method performs a higher accuracy than other approaches. In the reconstruction experiment, the reconstruction error can be reduced from 0.065 ~ 0.081 mm to 0.020 mm for the spherical surface, and from 0.060 ~ 0.12 mm to 0.016 mm for the free-form surface.

The construction of the relation between the critical energy release rate, GIc, and the mode I fracture toughness, KIc, is of great significance for understanding the fracture mechanism and facilitating its application in engineering. In this study, fracture experiments using NSCB and CCCD specimens were conducted. The effects of specimen sizes, loading rate and lithology on the relation between GIc and KIc were studied. GIc was calculated by integrating the load–displacement curve according to Irwin’s approach. Based on the measured KIc and GIc of the rock specimens, a relation between GIc and KIc was found to be different from the classical formula under linear elasticity. It was found that both specimen size and loading rate do not influence this relation.

This paper focuses on a new test method and theoretical model for measuring and evaluating the reopening pressure during hot dry rock hydraulic fracturing. Firstly, rock blocks of four lithologies were collected from the hot dry rock strata. Hydraulic fracturing tests at high temperatures in real-time were conducted using drilled cubic specimens and drilled cubic specimens with a pre-crack. Breakdown pressure, reopening pressure, and fracture toughness were measured, respectively. In addition, Brazilian splitting tests at high temperatures in real-time were performed using Brazilian disc specimens to measure tensile strength. Secondly, an empirical equation for evaluating the reopening pressure during hot dry rock secondary fracturing was developed based on fracture mechanics and hydraulic fracturing theory. Third, the values calculated by the new equation, considering breakdown pressure, fracture toughness, and tensile strength, were compared to the values determined by the classical equation and to measurement results. It was found that the new equation predicted closer reopening pressure to the measurement results, regardless of the lithology of the hot dry rock. Moreover, with increasing temperature in the specimens, the error between the value calculated by the new equation and the measurement value remained low. In contrast, the difference between the classical equation predictions and the measurement results was widened. In addition, the reopening pressure was positively correlated with tensile strength and fracture toughness. Variations in lithology and temperature affected tensile strength and fracture toughness, which then changed the hot dry rock reopening pressure.

Abstract Extracellular vesicles (EVs) are cellular-derived versatile transporters with a specialized property for trafficking a variety of cargo, including metabolites, growth factors, cytokines, proteins, lipids, and nucleic acids, throughout the microenvironment. EVs can act in a paracrine manner to facilitate communication between cells as well as modulate immune, inflammatory, regenerative, and remodeling processes. Of particular interest is the emerging association between EVs and stem cells, given their ability to integrate complex inputs for facilitating cellular migration to the sites of tissue injury. Additionally, stem cell-derived EVs can also act in an autocrine manner to influence stem cell proliferation, mobilization, differentiation, and self-renewal. Hence, it has been postulated that stem cells and EVs may work synergistically in the process of tissue repair and that dysregulation of EVs may cause a loss of homeostasis in the microenvironment leading to disease. By harnessing the property of EVs for delivery of small molecules, stem cell-derived EVs possess significant potential as a platform for developing bioengineering approaches for next-generation cancer therapies and targeted drug delivery methods. Although one of the main challenges of clinical cancer treatment remains a lack of specificity for the delivery of effective treatment options, EVs can be modified via genetic, biochemical, or synthetic methods for enhanced targeting ability of chemotherapeutic agents in promoting tumor regression. Here, we summarize recent research on the bioengineering potential of EV-based cancer therapies. A comprehensive understanding of EV modification may provide a novel strategy for cancer therapy and for the utilization of EVs in the targeting of oncogenic processes. Furthermore, innovative and emerging new technologies are shifting the paradigm and playing pivotal roles by continually expanding novel methods and materials for synthetic processes involved in the bioengineering of EVs for enhanced precision therapeutics.

Reports indicate that the mechanism of doxorubicin (Dox)-induced cardiotoxicity is very complex, involving multiple regulatory cell death forms. Furthermore, the clinical intervention effect is not ideal. Iron dependence, abnormal lipid metabolism, and excess reactive oxygen species generation, three characteristics of ferroptosis, are potential therapeutic intervention targets. Here, we confirmed in vitro and in vivo that at least autophagy, apoptosis, and ferroptosis are involved in Dox cardiotoxicity-induced damage. When the neonatal rat cardiomyocytes and H9C2 cells or C57BL/6 mice were subjected to Dox-induced cardiotoxicity, epigallocatechin-3-gallate pretreatment could effectively decrease iron accumulation, inhibit oxidative stress and abnormal lipid metabolism, and thereby alleviate Dox cardiotoxicity-induced ferroptosis and protect the myocardium according to multiple functional, enzymatic, and morphological indices. The underlying mechanism was verified to involve the upregulation and activation of AMP-activated protein kinase α2, which promoted adaptive autophagy, increased energy supply, and maintained mitochondrial function. We believe that epigallocatechin-3-gallate is a candidate phytochemical against Dox-induced cardiotoxicity.

Objectives: This study aimed to identify the trends in antibiotics utilization and patients costs, evaluating the effect of the policy and exploring factors associated with the irrational use of antibiotics.Methods: Based on the Cooperation Project Database of Hospital Prescriptions, data were collected from 89 tertiary hospitals in nine cities in China during 2016–2019. The study sample consisted of prescription records with antibiotics for 3,422,710 outpatient and emergency visits and 26, 118, 436 inpatient hospitalizations.Results: For outpatients, the proportion of treated with antibiotics declined from 14.72 to 13.92% significantly (p < 0.01). The proportion of antibiotic costs for outpatients decreased from 5.79 to 4.45% significantly (p < 0.01). For emergency patients, the proportion of treated with antibiotics increased from 39.31 to 43.45% significantly (p < 0.01). The proportion of antibiotic costs for emergency patients decreased from 36.44 to 34.69%, with no significant change (p = 0.87). For inpatients, the proportion of treated with antibiotics increased from 23.82 to 27.25% significantly (p < 0.01). The proportion of antibiotic costs for outpatients decreased from 18.09 to 17.19% with no statistical significance (p = 0.89). Other β-lactam antibacterials (1,663.03 ten thousand DDD) far exceeded other antibiotics categories. Stablely ranked first, followed by Macrolides, lincosamide and streptogramins (965.74 ten thousand DDD), Quinolone antibacterials (710.42 ten thousand DDD), and β-lactam antibacterials, penicillins (497.01 ten thousand DDD).Conclusions: The proportion of treated with antibiotics for outpatients and inpatients meet the WHO standards. The antibiotics use varied by different survey areas, clinical departments, patient gender, patient age and antibiotics categories. More efforts should focus on improving the appropriateness of antibiotics use at the individual level.

Magnesium alloy has great potential as a new medical metal material because of its good biocompatibility and biodegradability. However, because of the active chemical properties of magnesium alloy, it is easy to react with oxygen and cutting fluid to release hydrogen. In this paper, by cutting magnesium alloys prepared under different cooling conditions, the phase composition of the machined surface was studied. Tensile strength and elongation were studied through tensile experiments at different temperatures. The effect of cryogenic milling on the service performance of a magnesium alloy machined surface was studied by the friction and wear test and electrochemical corrosion test. The results show that cryogenic milling contributes to the formation of the second phase of magnesium alloy, which has the effect of corrosion resistance, and has better tensile strength and elongation. Through the friction and wear test, it is found that the average friction coefficient decreases by about 7.4%, and the wear amount decreases by about 10% in the liquid nitrogen cooling environment. Through the electrochemical corrosion test, it was found that the oxide film formed in the liquid nitrogen cooling environment was more compact and uniform, and the crystal refinement of the surface layer was better.

The complete mitogenome sequence of Ochotona coreana was determined using long PCR. The genome was 17,283 bp in length and contained 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, 1 origin of L strand replication, and 1 control region. The overall base composition of the heavy strand is A (31.5%), C (28.7%), T (26.2%), and G (13.6%). The base compositions present clearly the A–T skew, which is most obviously in the control region and protein-coding genes. Mitochondrial genome analyses based on MP, ML, NJ and Bayesian analyses yielded identical phylogenetic trees. This study verifies the evolutionary status of O. coreana in Ochotonidae at the molecular level. The mitochondrial genome would be a significant supplement for the O. coreana genetic background. The seven Ochotona species formed a monophyletic group with the high bootstrap value (100%) in all examinations.

The complete mitogenome sequence of Blarinella griselda was determined using long PCR. The genome was 16,947 bp in length and contained 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, 1 origin of L strand replication and 1 control region. The overall base composition of the heavy strand is A (33.1%), C (22.6%), T (31.6%) and G (12.7%). The base compositions present clearly the A–T skew, which is most obviously in the control region and protein-coding genes. Mitochondrial genome analyses based on MP, ML, NJ and Bayesian analyses yielded identical phylogenetic trees. This study verifies the evolutionary status of Blarinella griselda in Soricidae at the molecular level. The mitochondrial genome would be a significant supplement for the Blarinella griselda genetic background. The three Blarinella species formed a monophyletic group with the high bootstrap value (100%) in all examinations.

Objective To design a novel plasma external reference (PLACON) to detect and analyze human plasma mRNA and miRNA. Methods A conserved sequence was selected from the genome of the low-level species Caenorhabditis elegans. It was designed as a novel plasma external reference and BLAST was used to detect the specificity of PLACON sequences. Plasma samples of patients with malignant tumors and cancer cell supernatants were collected. And PLACON, β-actin, GAPDH, and U6 which were added to the plasma or cell supernatant respectively, were used for amplification comparison to detect plasma mRNA, miRNA and cell supernatant mRNA, by quantitative real-time PCR (RT-qPCR). Results BLAST detected that the PLACON sequence had good specificity and no cross-correlation with the human genome. Melting curves showed high specificity in RT-qPCR reaction. The cycle threshold values of mRNA levels were significantly lower in plasma of PLACON group than the GAPDH and β-actin groups (P < 0.01). The cycle threshold (CT) value of miRNA level amplification in plasma in PLACON group was significantly lower than that in U6 group (P < 0.01). PLACON was validated in mRNA amplification experiments in cancer cell supernatants, and similar results were obtained. Conclusion PLACON sequence is specific, and shows better amplification advantage as internal reference in plasma, with high stability and efficient amplification. It can be used for quantitative detection of plasma mRNA and miRNA.

Objective To analyze the clinical characteristics and survival of patients with pulmonary large cell neuroendocrine carcinoma (PLCNEC) and construct a nomogram model for predicting its prognosis. Methods We searched the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of patients diagnosed with PLCNEC between 2004 and 2013. Kaplan-Meier method was used for survival analysis of the patients. A Cox proportional hazard model was used to identify the factors affecting the overall survival (OS), and the significant factors were used to construct a nomogram model for predicting the patients' 1-year survival probability. The discrimination power of this model was assessed based on the C-index, and the calibration was evaluated with a bootstrap procedure. Results A total of 1 656 cases of PLCNEC with complete record of the clinical characteristics were collected. Of these patients, 55.37% were male, 52.05% were above 65 years of age at diagnosis, and 84.12% were white; 51.93% of the patients received chemotherapy, 40.94% had surgeries, and 37.80% had radiotherapy. Kaplan-Meier survival analysis showed that the median OS of patients with PLCNEC was 11 months, and their 1-year survival rate was 46.5%. Multivariate analysis identified a female gender, black race, surgery, radiotherapy and chemotherapy as the protective factors, while an age ≥65 years, an increased tumor size, invasion of adjacent tissues, lymph node involvement and distant metastasis were the risk factors for poor prognosis; the primary tumor sites did not significantly affect the survival outcomes of the patients. We established a nomogram model for predicting the 1-year survival probability of the patients based on the significant factors identified in the multivariate analysis. The C-index of this prediction model was 0.76, and assessment of calibration showed that the 1-year survival rate predicted by this model was highly consistent with the observed 1-year survival rate of the patients. Conclusion According to the data from SEER, patients with PLCNEC have a median OS of 11 months and a 1-year survival rate of 46.5%. Gender, age, race, tumor size, tumor growth and metastasis and interventions are all associated with the OS of the patients. The nomogram model we established based on the clinical characteristics of PLCNEC is capable of predicting the 1-year survival probability of the patients.

Objective To analyze the specificity of metastatic sites and prognostic differences of different metastatic patterns in non-small cell lung cancer (NSCLC) based on a large population-based dataset. Methods The metastatic NSCLC patients diagnosed between 2010 and 2014 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival analysis and log-rank test were used for survival analysis, and Cox proportional hazard model was performed to determine the factors related to improved overall survival (OS). Results A total of 38 755 NSCLC cases with metastases to bone, liver, brain and/or lungs were collected from the SEER database. At the time of diagnosis, 93.89% of the patients were over the age of 50 years, and the caucasian accounted for 77.38%. Among all enrolled cases, the moderately differentiated tumors (grade Ⅱ) accounted for 12.50%, and those with poor differentiation (grade Ⅲ) for 25.55%. The major histological subtype was adenocarcinoma, accounting for 72.52%. The most common single metastatic site was bone (22.43%), and the least common was liver (5.87%) for NSCLC. As for multi-site metastases, bone and lung was the most common 2-site metastasis (7.40%), and bone, liver and lung was the most common 3-site metastasis (3.16%). An isolated liver metastasis had the worst OS among single metastasis (P < 0.001). Furthermore, for patients with multi-site metastases, liver combined metastases had worst OS among various combinations(P < 0.001). Conclusion For NSCLC, bone is the most commonly targeted site, no matter for single- or multi-organ metastases. NSCLC patients with metastasis to liver alone or in combination with other organs have a poorer prognosis, while isolated lung metastasis has the best outcomes.

Objective To analyze the relationship between the clinical parameters and the efficacy of epidermal growth factorreceptor-tyrosine kinase inhibitors (EGFR-TKIs) as the first-line therapy in patients with stage Ⅳ non-small cell lung cancer (NSCLC) and identify the clinical markers for predicting the patients' responses to the treatment. Methods The clinical data were retrospectively reviewed for the patients with stage Ⅳ EGFR mutation-positive NSCLC receiving EGFR-TKIs (erlotinib, gefitinib, and icotinib) as the first-line therapy in our hospital between January, 2010 and December, 2016, and the relationship between the patients' clinical parameters and responses to the treatment were analyzed. Results A total of 123 patients (43 males and 80 females, aged ranging from 28 to 84 years) were included in this study. The objective response rate (ORR) of the overall patients was 47.97%, the disease control rate (DCR) was 100%, the median progression-free survival (mPFS) time was 11.0 months, and the median overall survival (OS) time was 22.7 months. Univariate analysis showed that the patients with low levels of neuronspecific enolase (NSE), carbohydrate antigen 125 (CA125) or Cyfra21-1 before the treatment had significantly prolonged mPFS time (NES: 14.2 vs 9.1 months, P < 0.001; CA125: 12.4 vs 9.5 months, P=0.024; Cyfra21-1: 12.3 vs 9.5 months, P=0.033); the mOS time was significantly prolonged in patients with ECOG performance status of 0~1 (24.0 vs 16.5 months, P=0.001) and low levels of NSE (27.7 vs 17.3 months, P < 0.001), CA125 (25.4 vs 20.2 months, P=0.002), Cyfra21-1 (25.7 vs 18.1 months, P=0.027) or CA15-3 (25.5 vs 18.7 months, P=0.009). Multivariate analysis suggested that CA125 and NSE were independent prognostic factors of PFS, and CA125, NSE, CA15-3, hepatic metastasis and performance status were independent prognostic factors of the OS time. Combined analysis of CA125, Cyfra21-1, CA15-3 and NSE showed that compared with those with elevation of a single factor, the patients with elevation of multiple factors had shorter mPFS time (9.3 vs 11.8 months, P=0.045) and also shorter mOS time (18.7 vs 27.4 months, P=0.001). Conclusion Low levels of CA125 or NSE before first-line EGFR-TKIs treatment are associated with longer PFS time of the patients with stage Ⅳ NSCLC, while performance status of 0~1 and low levels of NSE, CA125 or CA15-3 are associated with a longer OS time of the patients. The combination of CA125, Cyfra21-1, CA15-3 and NSE is expected to serve as a simple indicator for predicting the efficacy of firstreceptor-line EGFR-TKIs therapy in patients with stage Ⅳ NSCLC.

Phase change memory (PCM), due to the advantages in capacity and endurance, has the opportunity to become the next generation of general−purpose memory. However, operation speed and data retention are still bottlenecks for PCM development. The most direct way to solve this problem is to find a material with high speed and good thermal stability. In this paper, platinum doping is proposed to improve performance. The 10-year data retention temperature of the doped material is up to 104 °C; the device achieves an operation speed of 6 ns and more than 3 × 105 operation cycles. An excellent performance was derived from the reduced grain size (10 nm) and the smaller density change rate (4.76%), which are less than those of Ge2Sb2Te5 (GST) and Sb2Te3. Hence, platinum doping is an effective approach to improve the performance of PCM and provide both good thermal stability and high operation speed.