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Abstract The high incidence and mortality rates associated with acute and chronic wound infections impose a significant burden on global healthcare systems. In terms of the management of wound infection, the reconstruction and regeneration of skin appendages are essential for the recovery of mechanical strength and physiological function in the regenerated skin tissue. Novel therapeutic approaches are a requisite for enhancing the healing of infected wounds and promoting the regeneration of skin appendages. Herein, a novel antimicrobial microneedle patch has been fabricated for the transdermal controlled delivery of adipose tissue-derived apoptotic vesicles (ApoEVs-AT@MNP) for the treatment of infected wounds, which is expected to achieve high-quality scarless healing of the wound skin while inhibiting the bacteria in the infected wound. The microneedle patch (MNP) system possesses adequate mechanical strength to penetrate the skin, allowing the tips to remain inside tissue for continuous active release of biomolecules, and subsequently degrades safely within the host body. In vivo transplantation demonstrates that ApoEVs-AT@MNP not only inhibits bacterial proliferation in infected wounds but also significantly promotes effective and rapid scarless wound healing. Particularly noteworthy is the ability of ApoEVs-AT@MNP to promote the rapid formation of mature, evenly arranged hair follicles in infected wounds, observed as early as 8 days following implantation, which is essential for the restoration of skin function. This rapid development of skin appendages has not been reported this early in previous studies. Therefore, ApoEVs-AT@MNP has emerged as an excellent, painless, non-invasive, and highly promising treatment for infected wounds.

Fixed wing UAV takes off and lands on the ground with high requirements，which limits the application and development of fixed wing aircraft. Therefore，a scheme of four-rocket boosting drone to realize short-range takeoff and landing process is proposed，and the takeoff and landing control algorithm of rocket boosting drone is studied. In the process of research，the control strategy of rocket boosting drone takeoff and landing process is designed；The mathematical models of UAV aerodynamic force，booster rocket force，engine thrust and control law are established；The dynamic equation of the takeoff and landing process of UAV is constructed；A control algorithm based on PID control is designed to control the target UAV to complete the take-off and landing process safely and stably under various interference environments. MATLAB software is used for programming and simulation calculation. The simulation results show that the control algorithm and control law designed meet the control requirements of the target UAV during takeoff and landing.

Stimulus-responsive injectable hydrogel has the key characteristics of in situ drug-loading ability and the controlled drug release, enabling efficient delivery and precise release of chemotherapy drugs at the tumor site, thereby being used as a local drug delivery system for sustained tumor treatment. This article designed a smart responsive injectable hydrogel loaded with anti-tumor drugs and nanoparticles to achieve efficient and specific synergistic treatment of tumors. Hyaluronic acid (HA) hydrogel obtained by cross-linking HA-SH (HS) and HA-Tyr (HT) through horseradish peroxidase (HRP), and doxorubicin hydrochloride (DOX) and folic acid-polyethylene glycol-amine (FA-PEG-NH2) modified PDA (denoted as PPF) were encapsulated to construct the HS/HT@PPF/D hydrogel. The hydrogel had good biocompatibility, injectability, and could respond to multiple stimuli at the tumor site, thereby achieving controlled drug release. At the same time, PPF gave it excellent photothermal efficiency, photothermal stability and tumor targeting. In vitro and in vivo experimental results showed that the HS/HT@PPF/D hydrogel combined with near-infrared laser irradiation could significantly improve its anti-tumor effect and could almost eliminate the entire tumor mass without obvious adverse reactions. The HS/HT@PPF/D hydrogel could achieve multi-stimulus-responsive drug delivery and be used for precise chemo-photothermal synergistic tumor treatment, thus providing a new platform for local synergistic tumor treatment.

In this paper, flow over a cluster of three equally spaced circular cylinders was studied by numerical simulation based on the turbulence model k-kl-ω for two incidence angles β = 0° and 60°, at different Reynolds numbers, and flow interference pattern characteristics between cylinders, characteristics of force parameters, and Strouhal number of each cylinder with different spacing ratios ranging from 1.5 to 4 at Re 8 × 104, 2 × 105 and 2 × 106 were obtained. Analyzing the flow field around three cylinders, the following results have been obtained: (1) at incidence angle β = 0° and 60°, the wake was nearly symmetrical if S/D ≥ 2.0; (2) at β = 60°, S/D = 1.5, and Re = 2 × 105, an asymmetric periodic flow pattern occurred in the wake region which produced a significant effect on the surface mechanical parameters and Strouhal number, and this was observed for the first time. The periodic flow regime of the wake region also occurred at S/D = 1.35 and 1.5, without the same phenomenon at S/D = 1.7 and 2.0; this phenomenon is described for the first time in this paper; (3) the phenomenon of periodic flow regime in the wake region was intrinsic and related to Reynolds number and space ratio. In addition, the characteristics of force parameters of three cylinders were mainly affected by the interference between cylinders, at 1.5 < S/D < 4, which indicated that the drag coefficient of three cylinders reduces with different Reynolds numbers and increases with enlargement of the spacing ratio for upstream cylinders at incidence angle 0°. At incidence angle 60° and S/D = 1.5~4, the Strouhal number decreases with the enlargement of spacing ratio for the upstream cylinders, but the Strouhal number increases for the downstream cylinder, which is another prominent flow interference influence. The results indicated the effect of flow interference between cylinders subjected to a cross flow over a cluster of three equally spaced cylinders, considering the flow pattern, surface mechanical parameters and Strouhal number, which should be considered in the establishment of standard design codes in fields such as offshore wind turbine engineering for flow interference around groups of cylinders.

Abstract Background Successful regenerative medicine strategies need the manipulation and control of macrophages’ phenotypic switching. Our previous study indicated that rat and porcine adipose tissue-derived small extracellular vesicles could successfully promote soft tissue repair. However, whether human adipose tissue-derived small extracellular vesicles (h-sEV-AT) showed the same ability to promote soft tissue regeneration and whether adipose tissue-derived small extracellular vesicles (sEV-AT) contribute to modulating the polarization of macrophages were unknown. Methods In this study, we, for the first time, isolated h-sEV-AT from liposuction adipose tissue and characterized the morphology, size distribution, and marker protein. In vitro, we treated adipose-derived stromal/stem cells (ASCs), endothelial cells (ECs), and M1 macrophages with h-sEV-AT. In vivo, the ability of h-sEV-AT to promote soft tissue regeneration and polarize macrophages was investigated. Results The results indicated that h-sEV-AT possessed the characteristics of small extracellular vesicles (sEVs). In vitro, an obvious increase in adipogenesis and angiogenesis was induced by h-sEV-AT. In vivo, h-sEV-AT successfully induced the regeneration of adipose tissue and effectively accelerated full-thickness skin wound healing. Besides, we found that h-sEV-AT showed the ability to increase the percentage of M2 macrophages both in vivo and in vitro, which had been reported to contribute to tissue repair and regeneration. Conclusions Taken together, these results suggested that h-sEV-AT showed the ability to induce soft tissue repair supported by not only the differentiation of ASCs and ECs but also the polarization of macrophages. Considering the abundant sources, high yield, and guaranteed effectiveness, this study provided a cell-free strategy for soft tissue regeneration that directly isolated small extracellular vesicles from human liposuction adipose tissue.

Abstract Background Growth arrest-specific 6 (GAS6) is a vitamin K-dependent protein related to inflammation, fibrosis, as well as platelet function. Genetic ablation of GAS6 in mice protects against cardiac hypertrophy and dysfunction. Nonetheless, the association between plasma GAS6 levels and acute heart failure (AHF) patients is still unknown. Methods We measured plasma GAS6 concentrations in 1039 patients with AHF who were enrolled in the DRAGON-HF trial (NCT03727828). Mean follow-up of the study was 889 days. The primary endpoint is all-cause death. Results In total, there were 195 primary endpoints of all-cause death and 135 secondary endpoints of cardiovascular death during the mean follow-up duration of 889 days. The higher levels of GAS6 were associated with higher rates of all-cause and cardiovascular death (P

Objective To evaluate the safety and efficacy of irreversible electroporation (IRE) combined with neoadjuvant chemotherapy in patients with locally advanced pancreatic cancer. Methods We searched PubMed, Embase, Cochrane Library, Web of Science, China Biomedical Literature Database, CNKI, Wanfang, and VIP databases for articles dated from the establishment of each database to March 2022. Meta-analysis was performed using RevMan5.4 software. Results A total of 3970 patients with locally advanced pancreatic cancer were enrolled in eight studies, including one randomized controlled trial, four retrospective studies, and three prospective studies. The patients were divided into the combined therapy group with 344 patients and the chemotherapy-only group with 3626 patients. Meta-analysis showed that the overall survival of patients in the combined therapy group was significantly higher than that in the chemotherapy-only group (OR=4.52; 95%CI: 2.63-7.77; P < 0.00001). However, no significant difference existed in the disease control rate between the combined therapy group and the chemotherapy-only group (OR=0.58; 95%CI: 0.02-18.74; P=0.76). Moreover, no significant difference existed in the disease progression between the two groups (OR=0.49; 95%CI: 0.23-1.02; P=0.06). The combination of neoadjuvant chemotherapy and IRE had no significant effect on the incidence of adverse reactions of gastrointestinal reaction (OR=0.37; 95%CI: 0.10-1.34; P=0.13) and bone marrow suppression (OR=0.61; 95%CI: 0.26-1.40; P=0.24). Conclusion IRE combined with neoadjuvant chemotherapy can remarkably improve the prognosis of patients with locally advanced pancreatic cancer, and significantly prolong the overall survival.

Abstract Background High-grade glioma (HGG) is the most malignant brain tumor with poor outcomes. Whether anesthetic methods have an impact on the outcome of these patients is still unknown. Retrospective study has found no difference between intravenous and inhalation anesthesia on the overall survival (OS) of the HGG patients, however, intravenous anesthesia with propofol might be beneficial in a subgroup of patients with a Karnofsky Performance Status (KPS) Scale less than 80. Further prospective studies are needed to evaluate the results. Methods This is a single-centered, randomized controlled, parallel-group trial. Three hundred forty-four patients with primary HGG for tumor resection will be randomly assigned to receive either intravenous anesthesia with propofol or inhalation anesthesia with sevoflurane. The primary outcome is the OS of the patients within 18 months. Secondary outcomes include progression-free survival (PFS), the numerical rating scale (NRS) of pain intensity and sleep quality, the postoperative encephaloedema volume, complications, and the length of hospital stay of the patients. Discussion This is a randomized controlled trial to compare the effect of intravenous and inhalation anesthesia maintenance on the outcome of supratentorial HGG patients. The results will contribute to optimizing the anesthesia methods in these patients. Trial registration ClinicalTrials.gov NCT02756312. Registered on 29 April 2016 and last updated on 9 Sep 2020

Background: Nonalcoholic fatty liver disease (NAFLD) is the highest incidence of chronic liver disease worldwide, seriously endangering human health, and its pathogenesis is still unclear. In the recent years, increasing evidence has shown that intestinal flora plays an important role in the occurrence and development of NAFLD. Synbiotics can alter gut microbiota and may be a treatment option for NAFLD in the future. Objectives: To systematically investigate the therapeutic effect of synbiotic supplementation on NAFLD patients. Design: A systematic review and meta-analysis were conducted. Data sources and methods: We conducted a search on four databases (PubMed, Embase, Cochrane Library, and Web of Science) to identify relevant studies. Eligible studies were then screened, and data from the included studies were extracted, combined, and analyzed. Result: This study analyzed 10 randomized controlled trials involving 634 patients with NAFLD. The results showed that synbiotic supplementation could significantly reduce the level of alanine aminotransferase (mean difference (MD) = −8.80; (95% CI [−13.06, −4.53]), p

Chronic skin wound healing, especially in diabetes mellitus, is still unsolved. Although many efforts have been made to treat diabetic skin wounds, current strategies have achieved limited effectiveness. Nowadays, a great number of studies have shown that exosomes might be a promising approach for treating diabetic wounds. Many studies and reviews have focused on investigating and discussing the effectiveness and mechanism of exosomes. However, maximizing its value in treating skin wounds in diabetes mellitus requires further consideration. In this review, we reviewed and discussed the aspects that could be further improved in this process, including finding a better source of exosomes, engineering exosomes, adjusting dosage and frequency, and combining more efficient delivery methods. This review provided an overview and idea of what we can do to improve the therapeutic effect of exosomes on skin wounds in diabetes mellitus. Only by combining all the factors that affect the effectiveness of exosomes in diabetic wound healing can we further promote their clinical usefulness.

Abstract Background Browning of white adipose tissue (WAT) is a particularly appealing target for therapeutics in the treatment of obesity and related metabolic diseases. Although small extracellular vesicles (sEVs) released from adipose tissue (sEVs-AT) have emerged as novel player that regulate systemic metabolism by connecting different organs, the role of specific contents in sEVs-AT played in WAT browning has not been clarified. Results We revealed Nucleophosmin3 (NPM3), which was mainly transferred by sEVs derived from brown adipose tissue (sEVs-BAT), was served as a batokine that could induce WAT browning by regulating the stability of PRDM16 mRNA. sEVs-BAT enhanced the expressions of browning related genes in 3T3-L1 preadipocytes and WAT while knocking down of NPM3 in BAT impaired sEVs-BAT mediated WAT browning and weight loss in obesity. Conclusion These data provided new insight into the role of NPM3 in regulating the browning of WAT. Our study indicated that a supplement of sEVs-BAT might represent a promising therapeutic strategy to promote thermogenesis and energy expenditure in the future. Graphical Abstract

Objective To explore the application effect of diversified teaching mode in ultrasound-guided interventional procedures for treatment of pain. Methods Thirty learners who studied in the Department of Pain, Peking University Third Hospital from January 2018 to December 2020 were enrolled as participants, and were divided into control group and observation group. The control group adopted conventional teaching mode, while the observation group adopted diversified teaching mode. The clinical skill assessments, teaching quality and satisfaction scores of the two groups were compared. Results The excellent and good rate of clinical skill assessments in the observation group was 93.3%, which was higher than that in the control group, which was 73.3%(P＜0.05). Scores of mastering basic theoretical knowledge, improving clinical thinking ability, motivating learning interests and improving disease diagnosis and treatment ability in observation group were higher than those in control group (P＜0.01). Conclusions Diversified teaching mode improves ultrasound-guided interventional pain management skills, and supports the capacity building of clinical treatment.The method may function as a innovative clinical training pathway for other medical schools and healthcare institutions.

With the development of the times, the existing social security system can no longer meet people’s needs in terms of providing transparent, distributed sharing, tamper-proof, traceable, consensus trust and trustworthy services. Furthermore, they are centralized and subject to a single point of control and failure. In this context, we propose a consortium blockchain-based solution to establish and improve social security informatization to meet the above challenges. In this article, we present specific business situations for three important social security services. Namely, apply for social insurance, apply for social assistance and social benefits online. Our proposed solution also provides a multi-party trust and data sharing mechanism, and also demonstrates the integration of blockchain and Interplanetary File System (IPFS) storage systems to facilitate the security of approval documents, photos and videos related to the processing of social security services Accessibility and traceability. It also introduces the implementation and testing details of the algorithm in the smart contract, and expounds how to apply it in the automatic approval of social security business to reduce the workload of existing manual review. Finally, by comparing with the existing system, it is discussed that our solution has great advantages in promoting the online processing of social security business, and the safe access and traceability of approval documents, photos and videos.

Rapid infiltration of endogenous cells induced by cell-free biomaterials is the first and crucial step in tissue regeneration and macrophage is largely involved. Our previous study reported adipose tissue-derived small extracellular vesicles (sEV-AT) could successfully promote adipose tissue regeneration. However, the role of macrophages in this process was unknown. In this study, we isolated sEV-AT and subcutaneously implanted it into the back of SD rats. The results showed sEV-AT increased macrophage infiltration significantly, which was followed by improving homing of adipocyte precursors (APs) and endothelial cells (ECs). However, when macrophages were depleted by clodronate liposome within 1 week, the homing of APs and ECs, and adipose tissue regeneration were destroyed. In vitro, sEV-AT showed the ability to promote the migration of macrophages directly. Besides, sEV-AT-pretreated macrophages improved the migration of APs and ECs, accompanied by the increase of chemokines (MCP-1, SDF-1, VEGF, and FGF) and the activation of NF-kB signaling pathway. These findings indicated sEV-AT might regulate the secretion of chemokines via activating NF-kB signaling pathway to improve homing of APs and ECs and facilitate adipose tissue regeneration. These findings deepened our understanding of small extracellular vesicle-induced tissue regeneration and laid a theoretical foundation for the clinical application of sEV-AT.

The conceptual level is an index of personality development. In the field of teaching, the conceptual level is seen as a dynamic learning style. It has important implications for student learning and individual growth, as well as guidance for teaching. However, the lack of a measurement tool with a clear internal structure for the conceptual level of students has slowed the development of the theory and made it difficult to implement the teaching. To address these issues, this study describes the initial development and validation of the Student Conceptual Level Scale (SCLS) with four samples of students (n = 1,321) drawn from eight secondary schools in China. We constructed a second-order three-factor model of the SCLS consisting of three factors—learning awareness level, autonomous input level, and environmental coping level—each with its own independent set of items. This study validated the use of full-scale and subscale scores and examined their relationship with different validity criteria: autonomous learning, mental effort, and academic scores. This updated measure reflects the value and role of the conceptual level in the learning and individual development of students and also provides a more complete frame of reference for the use of the conceptual level in teaching and learning.

Gestational weight gain (GWG) may be affected by the timing of dietary intake. Previous studies have reported contradictory findings, possibly due to inconsistent characterizations of meal timing. We conducted a birth cohort study in Tianjin to determine the effect of daily energy and macronutrient distribution in mid and late pregnancy on GWG. Dietary intake information in the second and third trimesters used three 24-h dietary recalls, and meal timing was defined in relation to sleep/wake timing. The adequacy of GWG was assessed using recommendations from the Institute of Medicine guidelines. Pregnant women who had a relatively high average energy and macronutrient distribution in the late afternoon–early evening time window exhibited a greater GWG rate and a greater total GWG than that in morning time window during the third trimester (β = 0.707; β = 0.316). Carbohydrate intake in the morning of the second and third trimesters (β = 0.005; β = 0.008) was positively associated with GWG rates. Morning carbohydrate intake in the second trimester was also positively associated with total GWG (β = 0.004). Fat intake in the morning of the third trimester (β = 0.051; β = 0.020) was positively associated with the GWG rates and total GWG. Excessive GWG of Chinese pregnant women was related closely to eating behavior focused on the late afternoon–early evening and carbohydrate and fat intake in the morning during the second and third trimesters.

(1) Background: Pancreatic cancer (PC) is one of the most lethal tumors. Mitochondrial dysfunction has been reported to be involved in cancer development; however, its role in PC has remained unclear. (2) Methods: The differentially expressed NMGs were selected between PC and normal pancreatic tissue. The NMG-related prognostic signature was established by LASSO regression. A nomogram was developed based on the 12-gene signature combined with other significant pathological features. An extensive analysis of the 12 critical NMGs was performed in multiple dimensions. The expression of some key genes was verified in our external cohort. (3) Results: Mitochondria-related transcriptome features was obviously altered in PC compared with normal pancreas tissue. The 12-NMG signature showed good performance in predicting prognosis in various cohorts. The high- and low-risk groups exhibited notable diversity in gene mutation characteristics, biological characteristics, chemotherapy response, and the tumor immune microenvironment. Critical gene expression was demonstrated in our cohort at the mRNA and protein levels and in organelle localization. (4) Conclusions: Our study analyzed the mitochondrial molecular characterization of PC, proving the crucial role of NMGs in PC development. The established NMG signature helps classify patient subtypes in terms of prognosis prediction, treatment response, immunological features, and biological function, providing a potential therapeutic strategy targeting mitochondrial transcriptome characterization.

In the present work, the nature of phase evolution of (1−x)(Na0.5Bi0.5)TiO3-xSrTiO3 (NBT-xST) solid solutions with x of 0–0.6 is revealed by characterizing the dielectric and ferroelectric properties. Two unique dielectric anomalies associated with high-temperature nanoregions (PNRs) in the ergodic relaxor (ER) state and low-temperature PNRs in the nonergodic relaxor (NR) state are identified. Characteristic temperatures, including TB, TRT∗, Tm, Td and TT∗, are determined in fresh and poled states on the basis of the characteristics of the evolution of these two dielectric anomalies. The whole evolution of the transition from the NR state to the ER state is reflected by the temperature-dependent polarization versus electric field (P-E) hysteresis loops, i.e., from the square loops, via the double-like loops, to the slim loops. The characteristic temperatures, including TP-N, TN-R and TR-dis, are determined by the characteristics of the evolution of P-E loops. Accordingly, a phase diagram of NBT-xST was constructed according to these characteristic temperatures. Most importantly, the relationship between polarization responses and heterogeneous polar phase coexistence has been established and a schematic diagram is given. This work will help to understand the phase evolution and its impact on the macroscopic properties of NBT and the associated NBT-based solid solutions.

Abstract Background Patients with intracranial tumors are more sensitive to anesthetics than the general population and are therefore more susceptible to postoperative neurologic and neurocognitive dysfunction. Sevoflurane or propofol combined with remifentanil are widely used general anesthetic regimens for craniotomy, with neither regimen shown to be superior to the other in terms of neuroprotective efficacy and anesthesia quality. There is no evidence regarding the variable effects on postoperative neurologic and neurocognitive functional outcome under these two general anesthetic regimens. This trial will compare inhalational sevoflurane or intravenous propofol combined with remifentanil anesthesia in patients with supratentorial gliomas and test the hypothesis that postoperative neurologic function is equally affected between the two regimens. Methods This is a prospective, single-center, randomized parallel arm equivalent clinical trial, which is approved by China Ethics Committee of Registering Clinical Trials (ChiECRCT-20,160,051). Patients with supratentorial gliomas diagnosed by magnetic resonance imaging will be eligible for the trial. Written informed consent will be obtained before randomly assigning each subject to either the sevoflurane-remifentanil or propofol-remifentanil group for anesthesia maintenance to achieve an equal-desired depth of anesthesia. Intraoperative intervention and monitoring will follow a standard anesthetic management protocol. All of the physiological parameters and other medications administered during the intervention will be recorded. The primary outcome will be neurologic function change assessed by National Institute of Health Stroke Scale (NIHSS) within 4 h after general anesthesia when observer’s assessment of alertness/sedation (OAA/S) reaches 4. Secondary outcomes will include NIHSS and modified NIHSS change 1 and 2 days after general anesthesia, hemodynamic stability, intraoperative brain relaxation, quality of anesthesia emergence, quality of anesthesia recovery, postoperative cognitive function, postoperative pain, postoperative neurologic complications, as well as perioperative medical expense. Discussion This randomized equivalency trial will primarily compare the impacts of sevoflurane-remifentanil and propofol-remifentanil anesthesia on short-term postoperative neurologic function in patients with supratentorial gliomas undergoing craniotomy. The exclusion criteria are strict to ensure that the groups are comparable in all aspects. Repeated and routine neurologic evaluations after operation are always important to evaluate neurosurgical patients’ recovery and any newly presenting complications. The results of this trial would help specifically to interpret anesthetic residual effects on postoperative outcomes, and perhaps would help the anesthesiologist to select the optimal anesthetic regimen to minimize its impact on neurologic function in this specific patient population. Trial registration The study was registered and approved by the Chinese Clinical Trial Registry (Chinese Clinical Trial Registry, ChiCTR-IOR-16009177 ). Principle investigator: Nan Lin (email address: linnan127@gmail.com ) and Ruquan Han (email address: hanrq666@aliyun.com ) Date of Registration: September 8th, 2016. Country of recruitment: China.

Consensus of fractional order singular multi-agent systems is considered in this paper. The model of uncertain systems with actuator faults and external disturbances is established. Firstly, augmented transformations are made to systems in order to estimate state vectors and actuator faults simultaneously. Then new admissible consensus criteria of observer-based fractional order singular multi-agent systems (FOSMAS) are proposed. Finally, for the sake of demonstrating the validity of proposed results, some relevant numerical examples are provided.

Background: Basilar artery fenestration has been proposed as a contributor to ischemic stroke, as unique flow patterns induced by fenestration may be related to thrombus formation or insufficiency. This study aimed to evaluate the hemodynamics of basilar artery fenestration (BAF) using computational fluid dynamics (CFD).Methods: Patients with BAF and normal vertebrobasilar system were recruited and separately evaluated using CFD. Specific geometric vascular models were reconstructed based on 3D-rotational angiography (3D-RA). Patients were divided into the BAF group and control group (i.e., patients with the normal vertebrobasilar system). Hemodynamic and geometric variables were calculated and compared between groups using Student's t-test or Wilcoxon rank-sum test.Results: Overall, 24 patients were included, with 12 patients each in the BAF group and the control group. The BAF group had a significantly smaller basilar artery diameter than the control group (3.1 ± 0.51 vs. 3.76 ± 0.4, p = 0.002). Compared to the control group, the BAF group had higher values of maxOSI (median, 0.3 vs. 0.09, p = 0.028), TAWSSG (median, 983.42 vs. 565.39, p = 0.038) in the flow confluence, higher SAR-TAWSSG in bifurcation (median, 70.22 vs. 27.65, p = 0.002) and higher SAR-TAWSSG in basilar artery (median, 48.75 vs. 16.17, p < 0.001) of the vertebrobasilar artery.Conclusions: This pilot study suggested that hemodynamic differences between BAF and normal vertebrobasilar artery across multiple shear flow parameters. The disturbed flow in the BAF may increase the risk of thrombus formation, plaque instability, and subsequent ischemic cerebrovascular events. These should be confirmed by future studies.

C-arm cone-beam computed tomography (CBCT) offers a high imaging resolution with a wide range of contrast to visualize vessels, soft tissue, and bone. We report the usefulness of CBCT in observing neovascularization, microcalcification, and plaque rupture. A 56-year-old man presented with vertigo and complain of an unsteady gait for 5 months. Catheter angiography demonstrated right severe carotid stenosis with irregular filling defect, which on high-resolution MRI showed vessel wall enhancement. The CBCT showed high density structures and linear contrast enhancement from the vascular lumen to the plaque, related to microstructure and plaque rupture. Carotid endarterectomy was performed, and histopathology confirmed that the high-density areas represented neovascularization and microcalcification, with linear enhancement representing plaque rupture. This is the first report showing that microcalcifications and plaque rupture can be identified by CBCT. Thus, CBCT can be used as a promising supplement to current imaging modalities to evaluate plaque components more accurately.

Introduction Postoperative delirium (POD) is a common complication. The incidence of POD is about 25% in non-cardiac surgery and ranges from 10% to 30% in neurological procedures. A lot of trials show that dexmedetomidine might help to reduce the incidence of delirium in patients undergoing non-cardiac surgery. However, the impact of dexmedetomidine on POD for patients undergoing craniotomy and tumour resections remains unclear.Methods and analysis The study is a prospective, single-centre, randomised, double-blinded, paralleled-group controlled trial. Patients undergoing elective frontotemporal tumour resections will be randomly assigned to the dexmedetomidine group and the control group. After endotracheal intubation, patients in the dexmedetomidine group will be administered with a loading dose of dexmedetomidine 0.6 µg/kg in 10 min followed by continuous infusion at a rate of 0.4 µg/kg/hour until the start of dural closure. In the control group, patients will receive the identical volume of normal saline in the same setting. The primary outcome will be the cumulative incidence of POD within 5 days. The delirium assessment will be performed by using the confusion assessment method in the first 5 consecutive days after surgery. Secondary outcomes include the pain severity assessed by Numerical Rating Scale pain score, quality of postoperative sleep assessed by the Richards Campbell sleep questionnaire and postoperative quality of recovery from anaesthesia by the Postoperative Quality Recovery Scale.Ethics and dissemination The protocol (V.1.0, 10 November 2020) has been approved by the Ethics Review Committee of the Chinese Clinical Trial Registry (number ChiECRCT-20200436). The findings of the study will be disseminated in a peer-reviewed journal and at a scientific conference.Trial registration number NCT04674241.

Background: Intracranial cerebral atherosclerosis (ICAS) is a leading etiology of ischemic stroke. The diagnosis and assessment of intracranial stenosis are shifting from anatomic to hemodynamic for better risk stratification. However, the relationships between lesion geometry and translesional pressure gradient have not been clearly elucidated.Methods: Patients with symptomatic unifocal M1 middle cerebral artery (M1-MCA) stenosis were consecutively recruited. The translesional pressure gradient was measured with a pressure wire and was recorded as both mean distal/proximal pressure ratios (Pd/Pa) and translesional pressure difference (Pa–Pd). Lesion geometry measured on angiography was recorded as diameter stenosis, minimal lumen diameter, and lesion length. The correlations between pressure-derived and angiography-derived indices were then analyzed.Results: Forty-three patients were analyzed. A negative correlation was found between Pd/Pa and diameter stenosis (r = −0.371; p = 0.014) and between Pa – Pd and minimal lumen diameter (r = −0.507; p = 0.001). A positive correlation was found between Pd/Pa and minimal lumen diameter (r = 0.411; p = 0.006) and between Pa – Pd and diameter stenosis (r = 0.466; p = 0.002).Conclusions: In a highly selected ICAS subgroup, geometric indices derived from angiography correlate significantly with translesional pressure gradient indices. However, the correlation strength is weak-to-moderate, which implies that anatomic assessment could only partly reflect hemodynamic status. Translesional pressure gradient measured by pressure wire may serve as a more predictive marker of ICAS severity. More factors need to be identified in further studies.

Background: Despite advances in non-invasive imaging, the characterization of atherosclerotic plaque remains superior with frequency-domain optical coherence tomography (FD-OCT) in the clinical coronary and experimental cerebrovascular literature. An assessment of the feasibility and safety of FD-OCT for intracranial atherosclerotic stenosis (ICAS) is desirable.Methods: We analyzed a cohort of all consecutive FD-OCT evaluations for ICAS performed at our institution from April 2017 to August 2018 (16 months) in patients who suffered from transient ischemic attack (TIA) or non-disabling stroke despite optimal medical management within 90 days of admission attributable to angiographically verified 70–99% stenosis of an intracranial artery.Results: Thirty-three patients harboring 36 lesions with an average age of (57.6 ± 7.1) years (male sex 27 cases) comprising nine cases of lesions located within the anterior circulation and 24 cases within the posterior circulation were identified. Of the 33 patients with 36 lesions, the FD-OCT imaging catheter detected 35/36 (97%) lesions except in one case in which the FD-OCT catheter failed to navigate excessively tortuous vessels, and FD-OCT images in 27 patients (81.8%) were finally obtained successful, where the target lesion was fully visible, and image quality under at least one pullback was graded 2 or 3. There were no symptomatic complications. Blood flow was the most common artifact encountered (51.9%).Conclusion: FD-OCT is safe and feasible for the assessment of ICAS in the anterior and posterior circulation. The use of diagnostic interferometry will have to be weighed against its cost, and these preliminary findings should be verified by prospective large-scale studies.

Summary Biological approaches are considered promising and eco‐friendly strategies to remediate Hg contamination in soil. This study investigated the potential of two ‘green’ additives, Hg‐volatilizing bacteria (Pseudomonas sp. DC‐B1 and Bacillus sp. DC‐B2) and sawdust biochar, and their combination to reduce Hg(II) phytoavailability in soil and the effect of the additives on the soil bacterial community. The results showed that the Hg(II) contents in soils and lettuce shoots and roots were all reduced with these additives, achieving more declines of 12.3–27.4%, 24.8–57.8% and 2.0–48.6%, respectively, within 56 days of incubation compared to the control with no additive. The combination of DC‐B2 and 4% biochar performed best in reducing Hg(II) contents in lettuce shoots, achieving a decrease of 57.8% compared with the control. Pyrosequencing analysis showed that the overall bacterial community compositions in the soil samples were similar under different treatments, despite the fact that the relative abundance of dominant genera altered with the additives, suggesting a relatively weak impact of the additives on the soil microbial ecosystem. The low relative abundances of Pseudomonas and Bacillus, close to the background levels, at the end of the experiment indicated a small biological disturbance of the local microbial niche by the exogenous bacteria.

In the 4G era,operators have become data service pipelines,while they will actively seek business transformation in the 5G era.According to research institutes,the indoor positioning and IoT market have broad prospects,and operators are working hard to expand vertical industry applications in related fields.However,the existing indoor communication network has a single function and cannot effectively support indoor positioning and IoT services.A communication,navigation and IoT integration 5G indoor communication network was proposed.By integrating the bluetooth module inside the indoor antenna,it achieved some new functions,such as downlink bluetooth positioning,advertisement information push,path loss detection,uplink IoT collection and uplink bluetooth positioning.The proposed technical solution can be applied to smart medical scenarios,such as smart consultation,equipment management,security management,logistical support and one-click alarm.

Based on the Clyne-Davies model,the hot tearing susceptibility(CSC)of MgZn9YxZr0.5(x=1,2,4,6,mass fraction/%) was predicted.The microstructure and morphology of hot tearing regions of the alloys were observed by X-ray diffraction (XRD) and scanning electron microscopy (SEM) and the curves of solidification shrinkage stress with temperature (or time) of MgZn9YxZr0.5 alloys based on the "T" type hot tearing permanent-mold were collected.The results demonstrate that the predicted values of CSC are consistent with that of measured values of crack volume.The hot tearing susceptibility of the alloys from high to low is:MgZn9Y1Zr0.5 > MgZn9Y6Zr0.5 > MgZn9Y2Zr0.5 > MgZn9Y4Zr0.5;the dendrite coherency temperature and the initial temperature of hot tearing decrease with the Y content increasing when w(Y) is not more than 4%.When w(Y) is 6%, the dendrite coherency temperature and the initial temperature of hot tearing increase.With the increase of Y content, the change of precipitation phase type, content and the dendrite tendency of α-Mg in the solidification process of MgZn9YxZr0.5 alloys is considered as the main micro-mechanism that affects crack initiation,propagation and hot tearing in grain boundary.

The hirth coupling is widely used in the centrifugal air compressor unit due to its characteristic of high torque capacity，self centering and so on. A feasible method for the measuring of pitch plane is illustrated and the offline detection for the accuracy of hirth coupling is carried out by using gear tester， some reference for the measurement of relevant parts and the offline detection are provided.

Urban fabric similarity analysis and classification represent a useful analysis framework in many urban studies. Classical approaches include qualitative descriptions or manually selected indicators, depending largely on the researcher's knowledge. This paper proposes a new method for extracting concise and integrated quantitative indicators to represent urban fabrics via deep learning. Figure-ground images are taken as training data for a convolutional autoencoder (CAE) model, and the outputs of the neurons in the bottleneck layer of the CAE are extracted as the compressed feature vectors (CFVs) to represent the plots. Then, the plots can be compared, clustered and visualized based on these CFVs. In this study, 345 residential plots of Nanjing, China are taken as samples to demonstrate the modeling process, clustering and visualizations. The results show that the CFV is an effective indicator to represent urban fabrics. The generation of the CFV takes into consideration both statistical and geometrical features, with the latter normally described qualitatively as patterns. CFV consists of several aspects of urban fabric without the need to balance the weights. The CFV can serve as a basis for further urban development interpretations, morpho-typology studies and other social, economic and microclimate studies that have relationships with the urban fabric.

Many machine learning problem domains, such as the detection of fraud, spam, outliers, and anomalies, tend to involve inherently imbalanced class distributions of samples. However, most classification algorithms assume equivalent sample sizes for each class. Therefore, imbalanced classification datasets pose a significant challenge in prediction modeling. Herein, we propose a density-based random forest algorithm (DBRF) to improve the prediction performance, especially for minority classes. DBRF is designed to recognize boundary samples as the most difficult to classify and then use a density-based method to augment them. Subsequently, two different random forest classifiers were constructed to model the augmented boundary samples and the original dataset dependently, and the final output was determined using a bagging technique. A real-world material classification dataset and 33 open public imbalanced datasets were used to evaluate the performance of DBRF. On the 34 datasets, DBRF could achieve improvements of 2–15% over random forest in terms of the F1-measure and G-mean. The experimental results proved the ability of DBRF to solve the problem of classifying objects located on the class boundary, including objects of minority classes, by taking into account the density of objects in space.

Objective To evaluate temporal lung changes in coronavirus disease 2019 (COVID-19) in high-resolution computed tomography (HRCT) and to determine the appropriate computed tomographic (CT) follow-up time. Methods Eighty-six patients with two or more HRCT scans who were diagnosed with COVID-19 were included. The CT score and major CT findings were evaluated. Results Eighty-two (95.3%) patients had lesions on the initial HRCT scans. Most scans showed bilateral, multifocal lung lesions, with multiple lobes involved and diffuse distribution. For fifty-seven patients with type I (progress compared with the initial CT score), the CT score reached a peak at 12 days and the nadir at 36 days. For twenty-nine patients with type II (no progress compared with the initial CT score), the lowest CT score was reached at 23 days. On the final HRCT scans (>21 days), patients with a reticular pattern were older than those without a reticular pattern. Conclusion The appropriate follow-up time of CT scans is during the second week (approximately 12 days) and the fourth to fifth weeks (approximately 23–36 days) from the onset of illness. These times could help reduce the CT radiation dose and show timely changes in the course of the disease by CT.

The development of antibody therapeutics relies on animal models that accurately recapitulate disease biology. Syngeneic mouse models are increasingly used with new molecules to capture the biology of complex cancers and disease states, and to provide insight into the role of the immune system. The establishment of syngeneic mouse models requires the ability to generate surrogate mouse counterparts to antibodies designed for humans. In the field of bispecific antibodies, there remains a dearth of technologies available to generate native IgG-like mouse bispecific antibodies. Thus, we engineered a simple co-expression system for one-step purification of intact mouse IgG1 and IgG2a bispecific antibodies from any antibody pair. We demonstrated proof of concept with CD3/CD20 bispecific antibodies, which highlighted both the quality and efficacy of materials generated by this technology.

Objective To investigate the shorter-term curative efficacy and safety of whole brain radio therapy(WBRT) combined with simultaneous integrated boost versus sequential integrated boost using image-guided intensity-modulated radiotherapy (IG-IMRT) for lung cancer patients with 1-4 brain metastases, and to confirm the optimal treatment scheme of lung cancer patients with brain metastases. Methods We analyzed retrospectively the data of 98 patients diagnosed as brain metastases from lung cancer and admitted in our hospital from May 2014 to May 2017. The patients were divided into two groups: WBRT combined with simultaneous integrated boost (observation group, n=49) or WBRT combined with sequential integrated boost (control group, n=49) using image-guided intensity-modulated radiotherapy to compare the curative efficacy and safety. In the process of treatment, cone-beam CT(CBCT) was used to correct the position. Results The total effective rate, local control rate and 1-year survival rate in the observation group were higher than those in the control group(87.80%(43/49) vs. 61.20%(30/49), 95.92%(47/49) vs. 81.60% (40/49), 65.31% (32/49) vs. 44.90% (22/49) (all P < 0.05). Median survival time in the observation group was higher than that in the control group(15 vs. 12 months). In addition, no 3-4 grades acute or late toxicities occurred. The main adverse effects included alopecia, nausea, vomiting, cognitive impairment and memory injury. Conclusion Wholebrain radiotherapy combined with simultaneous integrated boost using image-guided intensity-modulated radiotherapy is a safe and effective treatment for the lung cancer patients with brain metastases.

With the depletion of fossil energy sources, clean energy has become a growing concern for scholars. Vortex-Induced Vibration Aquatic Clean Energy (VIVACE), a device that uses water flow energy to generate electricity, has attracted much attention for its broad applicability and other advantages. Particle Image Velocimetry (PIV) experiments were conducted to improve the efficiency of the VIVACE device in low-velocity areas. The present study investigated the effects of the Blockage ratio (Br), Reynolds number (Re = ρU0D/μ), and Aspect ratio (Ar = B/D, width-to-height) of rectangular cylinders on flow characteristics. The influence of the Ar, Br, and Re on the flow field structure was systematically analyzed in terms of the time-averaged flow field, Reynolds shear stress, space–time correlation, vorticity field, and water pressure characteristics. The vorticity field was deconstructed by Proper Orthogonal Decomposition (POD). The results show that the first two orders of POD modal energy accounted for 75% of the total energy, indicating that the first two modes can be used to identify the large-scale vortex structure. The main water pressure frequency and vortex shedding frequency (f) had a high degree of consistency. Thus, vortex shedding was the main cause of wall water pressure fluctuations. Given the blockage effect, the shear layer’s development spanwise was restricted. Moreover, the blockage effect increased the local flow velocity and accelerated the vortex shedding. The dimensionless time-averaged flow velocity U/U0 increased to 1.5, and the frequency of vortex shedding increased by approximately 25% when the Br increased from 0.067 to 0.25. The frequency increased by 25% when the Ar decreased from 0.5 to 0.2. The experimental results also provide a new idea for optimizing the VIVACE device.

This study aimed to explore the application of surface-enhanced Raman scattering (SERS) in the rapid diagnosis of gastric cancer. The SERS spectra of 68 serum samples from gastric cancer patients and healthy volunteers were acquired. The characteristic ratio method (CRM) and principal component analysis (PCA) were used to differentiate gastric cancer serum from normal serum. Compared with healthy volunteers, the serum SERS intensity of gastric cancer patients was relatively high at 722cm−1, while it was relatively low at 588, 644, 861, 1008, 1235, 1397, 1445 and 1586cm−1. These results indicated that the relative content of nucleic acids in the serum of gastric cancer patients rises while the relative content of amino acids and carbohydrates decreases. In PCA, the sensitivity and specificity of discriminating gastric cancer were 94.1% and 94.1%, respectively, with the accuracy of 94.1%. Based on the intensity ratios of four characteristic peaks at 722, 861, 1008 and 1397cm−1, CRM presented the diagnostic sensitivity and specificity of 100% and 97.4%, respectively, and the accuracy of 98.5%. Therefore, the three peak intensity ratios of I722/I861, I722/I1008 and I722/I1397 can be considered as biological fingerprint information for gastric cancer diagnosis and can rapidly and directly reflect the physiological and pathological changes associated with gastric cancer development. This study provides an important basis and standards for the early diagnosis of gastric cancer.

Tin oxide (SnO2), as electron transport material to substitute titanium oxide (TiO2) in perovskite solar cells (PSCs), has aroused wide interests. However, the performance of the PSCs based on SnO2 is still hard to compete with the TiO2-based devices. Herein, a novel strategy is designed to enhance the photovoltaic performance and long-term stability of PSCs by integrating rare-earth ions Ln3+ (Sc3+, Y3+, La3+) with SnO2 nanospheres as mesoporous scaffold. The doping of Ln promotes the formation of dense and large-sized perovskite crystals, which facilitate interfacial contact of electron transport layer/perovskite layer and improve charge transport dynamics. Ln dopant optimizes the energy level of perovskite layer, reduces the charge transport resistance, and mitigates the trap state density. As a result, the optimized mesoporous PSC achieves a champion power conversion efficiency (PCE) of 20.63% without hysteresis, while the undoped PSC obtains an efficiency of 19.01%. The investigation demonstrates that the rare-earth doping is low-cost and effective method to improve the photovoltaic performance of SnO2-based PSCs.

The issue of robust admissibility and control for singular fractional-order systems (FOSs) with polytopic uncertainties is investigated in this paper. Firstly, a new method based on linear matrix inequalities (LMIs) is presented to solve the admissibility problems of uncertain linear systems. Then, a solid criterion of robust admissibility and a corresponding state feedback controller are derived, which overcome the conservatism of the existing results. Finally, for the sake of demonstrating the validity of proposed results, some relevant examples are provided.

Nanobodies (Nbs) have great potential in immunoassays due to their exceptional physicochemical properties. With the immortal nature of Nbs and the ability to manipulate their structures using protein engineering, it will become increasingly valuable to understand what structural features of Nbs drive high stability, affinity, and selectivity. Here, we employed an anti-quinalphos Nb as a model to illustrate the structural basis of Nbs' distinctive physicochemical properties and the recognition mechanism. The results indicated that the Nb-11A-ligand complexes exhibit a "tunnel" binding mode formed by CDR1, CDR2, and FR3. The orientation and hydrophobicity of small ligands are the primary determinants of their diverse affinities to Nb-11A. In addition, the primary factors contributing to Nb-11A's limited stability at high temperatures and in organic solvents are the rearrangement of the hydrogen bonding network and the enlargement of the binding cavity. Importantly, Ala 97 and Ala 34 at the active cavity's bottom and Arg 29 and Leu 73 at its entrance play vital roles in hapten recognition, which were further confirmed by mutant Nb-F3. Thus, our findings contribute to a deeper understanding of the recognition and stability mechanisms of anti-hapten Nbs and shed new light on the rational design of novel haptens and directed evolution to produce high-performance antibodies.