Search

Purpose: Fibroblast activation protein (FAP) is highly expressed in the mesenchyme of most malignant epithelial tumors, while its expression is low in normal tissues. FAP inhibitors (FAPIs) bind specifically to FAP and are used for tumor-targeted diagnosis and therapy. The aim of this study was to radiosynthesize a novel molecular probe 131I-FAPI and evaluate its in-vitro targeting and biological characteristics. Methods: The structurally modified FAPI was labelled with 131I through the chloramine-T method. The radiolabeling rate was then detected by thin-layer chromatography (TLC). The stability of 131I-FAPI was determined at PBS (room temperature) and serum (37°C). Its hydrophilicity was calculated by measuring its lipid-water partition coefficient. Pancreatic cancer PANC-1 cell line and glioma U87 cell line were cultured in vitro. Cell uptake assay was used to show the binding ability of 131I-FAPI. The CCK-8 assay was used to calculate the inhibitory effects of 131I-FAPI at different time points (4h, 8h, 12h, 24h, 48h) after comparing with the 131I and FAPI. The before-and-after-24h scratch areas of the two cells were determined in order to verify the effect of 131I-FAPI on the migration ability of the cells. Results: The radiolabeling rate was (84.9 ± 1.02) %. The radiochemical purity of 131I-FAPI remained over 80% in both 25°C PBS and 37°C serum. The value of the lipid-water partition coefficient was -0.869 ± 0.025, indicating the hydrophilic of the probe. The cellular uptake assay showed that U87 cells had a specific binding capacity for 131I-FAPI. In cell inhibition assays, the inhibitory effect of 131I-FAPI on U87 cells increased with time. The results of cell scratch assay showed that 131IFAPI had the strongest inhibitory effect on the migratory ability of U87 cells compared with 131I and FAPI (P<0.001). Conclusion: 131I-FAPI was synthesized with good in-vitro stability and hydrophilic properties. It can be specifically bound by U87 cells. The proliferation and migration of U87 cells can be effectively inhibited. 131I-FAPI is promising to become a therapeutic probe. [ABSTRACT FROM AUTHOR]

Deepfake can be used to combine human voices,faces and body movements into fake content,switch gender and change age,etc.There are some problems of gender-forged face images based on generative adversarial image translation networks such as the irrelevant image domain changes easily and insufficient face details in generated images.To solve these problems,an gene-ration model of gender-forged face image based on improved CycleGAN is proposed.Firstly,the generator is optimized by using the attention mechanism and adaptive residual blocks to extract richer facial features.Then,with the aim to improve the ability of the discriminator,the loss function is modified by the idea of relative loss.Finally,a model training strategy based on age constraints is proposed to reduce the impact of age changes on the generated images.Performing experiments on the CelebA and IMDB-WIKI datasets,the experimental results show that,compared with the original CycleGAN method and the UGATIT method,theproposed method can generate more real gender-forged face images.The average content accuracy of fake male images and fake female images is 82.65% and 78.83%,and the average FID score is 32.14 and 34.50,respectively.

Objectives In this study, we aimed to investigate the characteristics of robot-assisted surgery studies registered on ClinicalTrials.gov and identify factors associated with early trial discontinuation and timely results reporting.Design We searched ClinicalTrials.gov to identify interventional studies on robot-assisted surgery on 24 May 2021. All structured information of the potential studies was downloaded and reviewed. A descriptive analysis was performed. Logistic and Cox regression analyses were respectively performed to determine the significance of the association of study characteristics with results reporting and early discontinuation.Results A total of 529 interventional studies on robot-assisted surgery were included, with 45 studies reporting results and 54 studies being stopped early. Of the 289 due studies, only 45 (16%) had submitted their results, and only 6 (2%) had submitted their results within the 1-year deadline. Funding source was associated with results reporting: academic funded were 63% less likely than industry to report results (OR=0.37, 95% CI: 0.16 to 0.83, p=0.02). Studies related to device feasibility were associated with greater risk of early discontinuation compared to treatment-related studies (HR=2.30, 95% CI: 1.08 to 4.89, p=0.03). Surprisingly, National Institutes of Health-funded studies were at greater hazard of discontinuation compared to industry-funded studies (HR=3.30, 95% CI: 1.09 to 10.00, p=0.04).Conclusions There was poor compliance with results reporting requirements for robot-assisted surgical studies. It is important that investigators remain informed about the regulatory requirements, and should be helped to develop a sense of responsibility for reporting results. Also, they need to ensure the careful design of the study protocol and adequate resources to reduce the risk of early discontinuation.

IntroductionPrevalence of functional limitations (FLs) and disabled activities of daily living (ADL) cause heavy burdens to the health of the older people. Stratified by gender, this study aimed to explore the effects of FL and ADL on the mortality of the older people in China, and the mechanism was then discussed.MethodsWe used survey data of a prospective 10-year cohort (2008–2018), from the China Longitudinal Healthy Longevity Survey (CLHLS). The primary outcome was all-cause mortality, and Independent variables included FL, basic ADL (BADL), and instrumental ADL (IADL). Covariates involved socio-demographic characteristics, health-related behaviors, and health status of the participants in the CLHLS project.ResultsThere were 967 (19.20%) male and 2,235 (32.36%) female older people performed functional limitations, and their survival time was 60.98 (SE = 0.66) and 55.19 (SE = 0.55) months, respectively. Old adults with FL had significantly poorer survival than the ones without (Log-rank test, P < 0.001). Weibull regression suggested that FL (P < 0.001), abnormal BADL (P < 0.001) and IADL (P < 0.001) were negatively associated with the survival of the older people. Further analysis showed that BADL and IADL performed significantly mediating roles in the relation of FL and survival time in old adults; additionally, for female older people, BADL also exhibited a significant moderating role in the effect of FL on survival.ConclusionsPrevalence of FL was serious among the older people in China, especially for the women. Disabilities of BADL and IADL and FL were negatively associated with the survival time of the older people in China. Regarding the effect of FL on survival, BADL and IADL performed significantly mediating roles, and the moderating role of BADL existed only for the female. These suggested evidence to implement strategies to maintain health in the older people.

Abstract The complex relationships among social support, experienced stigma, psychological distress, and quality of life (QOL) among tuberculosis (TB) patients are insufficiently understood. The purpose of this study was to explore the interrelationships among social support, experienced stigma, psychological distress, and QOL and to examine whether experienced stigma and psychological distress play a mediating role. A cross-sectional survey was conducted between November 2020 and March 2021 in Dalian, Liaoning Province, Northeast China. Data were obtained from 473 TB patients using a structured questionnaire. Structural equation modelling was used to examine the hypothetical model. The research model provided a good fit to the measured data. All research hypotheses were supported: (1) social support, experienced stigma and psychological distress were associated with QOL; (2) experienced stigma fully mediated the effect of social support on psychological distress; (3) psychological distress fully mediated the effect of experienced stigma on QOL; and (4) experienced stigma and psychological distress were sequential mediators between social support and QOL. This study elucidated the pathways linking social support, experienced stigma, and psychological distress to QOL and provides an empirical basis for improving the QOL of TB patients.

Abstract High doses of radiation can cause serious side effects and efficient radiosensitizers are urgently needed. To overcome this problem, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for enhanced low-dose radiotherapy (RT). CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH-OXD) and peroxidase (POD) activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2 Gy) can provide a substantial suppression of tumor proliferation. This is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes. Graphical Abstract

Abstract Background Surgery remains the major treatment for early breast cancer (BC), but surgery itself is also a trauma which might induce alterations in lipid metabolism. The aim of this study was to investigate the changes in lipid profiles and to explore factors associated with lipid changes pre- and postoperation. Methods We retrospectively analyzed the pre- and postoperative serum lipid profiles of 1934 BC patients. Results The levels of triglycerides (TG) (p 24 (34.92%) had a higher incidence of dyslipidemia than patients with BMI ≤ 24 (24.84%; p = 0.001). Moreover, the magnitudes of the TG increase (p

Rib fracture is the most common injury in chest trauma. Most of patients with rib fractures were treated conservatively, but up to 50% of patients, especially those with combined injury such as flail chest, presented chronic pain or chest wall deformities, and more than 30% had long-term disabilities, unable to retain a full-time job. In the past two decades, surgery for rib fractures has achieving good outcomes. However, in clinic, there are still some problems including inconsistency in surgical indications and quality control in medical services. Before the year of 2018, there were 3 guidelines on the management of regional traumatic rib fractures were published at home and abroad, focusing on the guidance of the overall treatment decisions and plans; another clinical guideline about the surgical treatment of rib fractures lacks recent related progress in surgical treatment of rib fractures. The Chinese Society of Traumatology, Chinese Medical Association, and the Chinese College of Trauma Surgeons, Chinese Medical Doctor Association organized experts from cardiothoracic surgery, trauma surgery, acute care surgery, orthopedics and other disciplines to participate together, following the principle of evidence-based medicine and in line with the scientific nature and practicality, formulated the Chinese consensus for surgical treatment of traumatic rib fractures (STTRF 2021). This expert consensus put forward some clear, applicable, and graded recommendations from seven aspects: preoperative imaging evaluation, surgical indications, timing of surgery, surgical methods, rib fracture sites for surgical fixation, internal fixation method and material selection, treatment of combined injuries in rib fractures, in order to provide guidance and reference for surgical treatment of traumatic rib fractures.

In recent years, ultra-fine-grained Fe–C alloy have received widespread attention because of their high levels of strength, hardness, and wear resistance. However, these alloy have strict requirements on control of the process parameters during production to meet product specifications. This study was aimed at designing a prediction model for their mechanical properties, which could ultimately promote the industrial development of ultra-fine-grained Fe–C alloy. The effect of process parameters on the mechanical properties of ultra-fine-grained Fe–C alloy was analyzed by electron backscatter diffraction (EBSD) and scanning electron microscope (SEM). By fusing experimental combinations of alloy composition, rolling process, annealing process, and resultant mechanical properties into a dataset for training and verification, a machine-learning-based prediction model of mechanical properties of ultra-fine-grained Fe–C alloy was constructed and tested. When choosing the machine learning algorithm, the best network model was obtained for this application by optimizing a conventional backpropagation (BP) network structure: a three-layer network structure, with a learning rate of 0.5, 18 hidden layer neurons, and activation functions of the hidden and output layers, namely Tansig and Purelin (MATLAB functions), respectively. Finally, the sample data was divided into training set and verification set, and the prediction accuracy, efficiency and generalization ability of BP neural network (BPNN), genetic neural network (GA-BP) and support vector machine (SVM) were compared and analyzed. The superiority of BPNN in the prediction of mechanical properties of ultrafine grained Fe–C alloy was determined, and the mean absolute percentage error (MAPE) of the BPNN for tensile strength, yield strength and uniform elongation are 3.02%, 4.47% and 6.47% respectively, and the number of training steps is 412, which are less than the other two models. The result lays a foundation for the production of high stability and high performance steel products.

Abstract This paper proposes an effective fault management scheme for medium‐voltage direct current (MVDC) networks, which includes a virtual‐impedance‐based fault current limiter (VI‐FCL) on the DC side and a positive‐negative‐sequence (PNS) control scheme on the AC side. Depending on the fault current value, different protection strategies are adopted, which include either isolating the fault by opening circuit breakers or riding through the fault with the proposed VI‐FCL. It is known that unbalanced grid voltage can be found in conventional AC distribution feeders due to unbalanced loading conditions among three phases. The unbalanced grid voltage could induce double line‐frequency (2ω) ripples on both DC voltage and current, which could thereby trigger protection malfunction in the DC sub‐sections. Therefore, the PNS control scheme is used to eliminate the 2ω ripples of both DC voltages and currents caused by unbalanced AC voltages. Furthermore, a detailed 2ω mathematical model of the MVDC network under unbalanced AC voltage condition is derived to investigate how the 2ω ripple propagates across the network. A voltage source converter based multi‐terminal MVDC network is built to test DC faults with different fault currents, unbalanced AC voltages, and different control schemes. The test results verify both the proposed fault management scheme and the 2ω ripple propagation analysis.

Musculoskeletal soft tissue injuries are very common and usually occur during both sporting and everyday activities. The intervention of adjuvant therapies to promote tissue regeneration is of great importance to improving people’s quality of life and extending their productive lives. Though many studies have focused on the positive results and effectiveness of the LIPUS on soft tissue, the molecular mechanisms standing behind LIPUS effects are much less explored and reported, especially the intracellular signaling pathways. We incorporated all research on LIPUS in soft tissue diseases since 2005 and summarized studies that uncovered the intracellular molecular mechanism. This review will also provide the latest evidence-based research progress in this field and suggest research directions for future experiments.

IntroductionAcupuncture and acupressure are widely used for treating cancer pain and depression and recognized as safe and effective by the international medical community. In this study, we systematically evaluated the efficacy, safety, and clinical significance of acupuncture and acupressure in treating cancer-related depression.MethodsWe searched MEDLINE, PubMed, Science Direct, Google Scholar, Web of Science and Embase and Chinese-language databases for randomized clinical trials (RCTs). To assess efficacy, rating scales administered by clinicians or experts were preferred, including the Hamilton Depression Rating Scale (HAMD), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and Quality of Life Questionnaire-Core 30 (QLQ-C30) and the total effective rate after treatment. In all, Sixteen RCTs involving 1019 cancer patients were included in the Meta-analysis.ResultsEleven (69%) of these studies reported the post-treatment total effective rate. Three hundred fifty-three patients received antidepressants; the total effective rate was 72.5%. Three hundred sixty-one patients underwent acupuncture and acupressure; the total effective rate was 90%. Meta-analysis results showed I2 = 0%, no heterogeneity, (Z = 5.84, p < 0.00001); and combined OR = 3.55, (95% CI = 2.32 to 5.43).DiscussionThis study found that acupuncture and acupressure are as effective as medication in the treatment of cancer-related depression, provide a reliable basis for the clinical use of acupuncture to treat cancer-related depression, help promote nonpharmacological treatment for cancer-related complications. These approaches thus help reduce drug resistance and adverse reactions and improve patients’ quality of life.

Continuum robots have good adaptability in unstructured and complex environments. However, affected by their inherent nature of flexibility and slender structure, there are challenges in high-precision motion and load. Thus, stiffness adjustment for continuum robots has consistently attracted the attention of researchers. In this paper, a stiffness adjustment mechanism (SAM) is proposed and built in a growth-controllable continuum robot (GCCR) to improve the motion accuracy in variable scale motion. The self-stiffness adjustment is realized by antagonism through cable force transmission during the length change of the continuum robot. With a simple structure, the mechanism has a scarce impact on the weight and mass distribution of the robot and required no independent actuators for stiffness adjustment. Following this, a static model considering gravity and end load is established. The presented theoretical static model is applicable to predict the shape deformations of robots under different loads. The experimental validations showed that the maximum error ratio is within 5.65%. The stiffness of the robot can be enhanced by nearly 79.6%.

Voice information processing technology is developing rapidly under the impetus of deep learning.The combination of speech synthesis and voice conversion technology can achieve real-time high-fidelity voice output of designated objects and content,and has broad application prospects in man-machine interaction,pan-entertainment and other fields.This paper aims to provide an overview of speech synthesis and voice conversion technology based on deep learning.First,this paper briefly reviews the development of speech synthesis and voice conversion technology.Next,it enumerates the common public datasets in these fields so that it is convenient for researchers to carry out related explorations.Then,it discusses the TTS models,including the classic and cutting-edge models and algorithms in terms of style,rhythm,speed,and compares their effects and development potentials respectively.Then,it reviews voice conversion by summarizing the voice conversion methods and optimization methods.Finally,it summarizes the applications and challenges of speech synthesis and voice conversion,and looks forward to their future development direction in model compression,few-shot learning and forgery detection,based on the problems faced by them in terms of model,application and regulation.

Abstract Background The deubiquitinase (DUB) family constitutes a group of proteases that regulate the stability or reverse the ubiquitination of many proteins in the cell. These enzymes participate in cell-cycle regulation, cell division and differentiation, diverse physiological activities such as DNA damage repair, growth and development, and response to stress. However, limited information is available on this family of genes in woody plants. Results In the present study, 88 DUB family genes were identified in the woody model plant Populus trichocarpa, comprising 44 PtrUBP, 3 PtrUCH, 23 PtrOTU, 4 PtrMJD, and 14 PtrJAMM genes with similar domains. According to phylogenetic analysis, the PtrUBP genes were classified into 16 groups, the PtrUCH genes into two, the PtrOTU genes into eight, the PtrMJD genes into two, and the PtrJAMM genes into seven. Members of same subfamily had similar gene structure and motif distribution characteristics. Synteny analysis of the DUB family genes from P. thrchocarpa and four other plant species provided insight into the evolutionary traits of DUB genes. Expression profiles derived from previously published transcriptome data revealed distinct expression patterns of DUB genes in various tissues. On the basis of the results of analysis of promoter cis-regulatory elements, we selected 16 representative PtrUBP genes to treatment with abscisic acid, methyl jasmonate, or salicylic acid applied as a foliar spray. The majority of PtrUBP genes were upregulated in response to the phytohormone treatments, which implied that the genes play potential roles in abiotic stress response in Populus. Conclusions The results of this study broaden our understanding of the DUB family in plants. Analysis of the gene structure, conserved elements, and expression patterns of the DUB family provides a solid foundation for exploration of their specific functions in Populus and to elucidate the potential role of PtrUBP gene in abiotic stress response.