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Angiogenesis is imperative for bone regeneration, yet the conventional cytokine therapies have been constrained by prohibitive costs and safety apprehensions. It is urgent to develop a safer and more efficient therapeutic alternative. Herein, utilizing the methodologies of Deep Learning (DL) and Natural Language Processing (NLP), we proposed a paradigm algorithm that amalgamates Word2vec with a TF-IDF variant, TF-IIDF, to deftly discern potential pro-angiogenic peptides from intrinsically disordered regions (IDRs) of 262 related proteins, where are fertile grounds for developing safer and highly promising bioactive peptides. After the evaluation of the candidate oligopeptides, one tripeptide, PSP, emerged as particularly notable for its exceptional ability to stimulate the vascularization of endothelial cells (ECs), enhance vascular-osteo communication, and then boost the osteogenic differentiation of bone marrow stem cells (BMSCs), evidenced in mouse critical-sized cranial model. Moreover, we found that PSP serves as a ‘priming’ agent, activating the body's innate ability to produce Osteolectin (Oln) — prompting ECs to release small extracellular vesicles (sEVs) enriched with Oln to facilitate bone formation. In summary, our study established a precise and efficient composite model of DL and NLP to screen bioactive peptides, opening an avenue for the development of various peptide-based therapeutic strategies applicable to a broader range of diseases.

Abstract Background Previous studies have shown a positive correlation between the non-high-density lipoprotein cholesterol/high-density lipoprotein cholesterol(non-HDLc/HDLc ratio) and metabolism-associated steatohepatitis (MASLD), suggesting it is a superior predictor of MASLD.The aim of this study is to assess the predictive value of the non-HDLc/HDLc ratio for MASLD. Methods In this study, we retrospectively analyzed data from 4,498 adult patients at the Health Management Centre of Guangdong Provincial Hospital of Integrative Medicine, regardless of gender, and the diagnostic criteria for MASLD were derived from guidelines. We used univariate and multivariate logistic regression to verify the relationship between the non-HDLc/HDLc ratio and MASLD and assessed the stability of the results through interaction tests. ROC curve analysis was then employed to compare the diagnostic efficacy of several lipid indices, including the non-HDLc/HDLc ratio, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), and the composite lipid profile in diagnosing MASLD. Results These data suggested that non-HDLc/HDLc, LDL-C, TG, and TC were positively correlated with MASLD, while HDL-C was inversely correlated, even after adjusting for confounders such as gender, age, body mass index, ALT, AST, uric acid, blood glucose, and hypertension. Among them, non-HDLc/HDLc ratio(OR: 2.709, 95% CI: 2.316–3.169, p 0.05). ROC analysis confirmed the validity of the non-HDL cholesterol/HDL cholesterol ratio in predicting MASLD incidence, with an AUC of 0.801. Moreover, the composite lipid indices demonstrated greater predictive power for MASLD compared to individual indices (AUC: 0.857), and validation set results were consistent with those of the training set. Conclusion The present study revealed that the non-HDLc/HDLc ratio was positively correlated with the development of MASLD, and the ratio was also effective in predicting MASLD.

Abstract Background Exercise training is fundamental in pulmonary rehabilitation (PR), but patients with chronic obstructive pulmonary disease (COPD) often struggle with exercise intolerance. Respiratory support during exercise in COPD patients may be a beneficial adjunct therapy. In this study, the effect of different respiratory support therapy during pulmonary rehabilitation exercise training in COPD patients was assessed through a network meta-analysis. Methods Five databases were searched to obtain randomized controlled trials involving different respiratory support therapies during PR exercise training in COPD patients. The Cochrane Handbook tool was employed to assess the risk bias of included studies. Network meta-analysis was performed using the STATA software. The study protocol was registered at PROSPERO (CRD42023491139). Results A total of 35 studies involving 1321 patients and 6 different interventions were included. Network meta-analysis showed that noninvasive positive pressure ventilation (NPPV) is superior in improving exercise capacity (6-Minute Walk Test distance, peak work rate, endurance time), dyspnea, and physiological change (peak VO2, tidal volume, minute ventilation and lactate level) in stable COPD patients who were at GOLD stage III or IV during PR exercise training. The final surface under the cumulative ranking curve value indicated that NPPV therapy achieved the best assistive rehabilitation effect. Conclusions The obtained results indicate that NPPV is most powerful in assisting exercise in severe COPD patients under stable condition. Researchers should focus more on the safety, feasibility, and personalization of interventions. Furthermore, there is a need for additional high-quality trials to assess the consistency of evidence across various respiratory support approaches. Trial registration The study was registered at PROSPERO (CRD42023491139).

ObjectiveTo compare the efficacy and safety of programmed cell death 1 inhibitors plus chemotherapy (PD-1 + Chemo) and programmed cell death ligand 1 inhibitors plus chemotherapy (PD-L1 + Chemo) for the treatment of extensive-stage small-cell lung cancer (ES-SCLC).MethodsWe performed a meta-analysis of relevant data using R software, considering overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events (TRAES).ResultsPD-1 + Chemo (OS: hazard ratio [HR] 0.71; PFS: HR 0.59) and PD-L1 + Chemo (OS: HR 0.72; PFS: HR 0.73) significantly prolonged survival and did not increase the incidence of grade ≥3 TRAEs compared with chemotherapy. Indirect comparisons showed no significant difference in clinical efficacy (OS: HR 0.99, 95% CI: 0.86–1.1; PFS: HR 0.80, 95% CI: 0.61–1.0) or safety (HR 1.0, 95% CI: 0.93–1.1) between PD-1 + Chemo and PD-L1 + Chemo. Non-cumulative probability ranking plot ranking results showed that PD-1 + Chemo ranked first in OS and PFS. Patients with PD-L1 expression levels < 1%, PD-1 + Chemo showed a trend of disadvantage (OS: HR 1.3; PFS: HR 1.2), whereas for patients with PD-L1 expression levels ≥ 1%, PD-1 + Chemo showed a trend of advantage (OS: HR 0.85; PFS: HR 0.85).ConclusionsPD-1 + Chemo and PD-L1 + Chemo significantly prolonged OS and PFS in patients with ES-SCLC and did not significantly increase the incidence of grade ≥ 3 TRAES. The efficacy and safety profiles of PD-1 + Chemo and PD-L1 + Chemo appear to be similar.

BackgroundObesity often coincides with non-alcoholic fatty liver disease (NAFLD), yet a significant portion of NAFLD patients exhibit normal body mass index (BMI) but have abdominal obesity. Recognizing this discrepancy, we aimed to delve deeper into this phenomenon through observational studies coupled with two-sample Mendelian randomization (MR) analysis, with waist-to-hip ratio (WHR) serving as the indicator for abdominal obesity. Our objective was to ascertain whether WHR correlates with an increased risk of NAFLD development.MethodsThis study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 to examine the association between WHR and NAFLD through weighted multivariate logistic regression models. On this basis, subgroup analyses were performed to further explore the correlation between WHR and NAFLD. Subsequently, a two-sample MR analysis was conducted using genome-wide association studies (GWAS) data to investigate the potential causal relationship between WHR and NAFLD. Sensitivity analyses were also employed to ensure the robustness of our findings.ResultsA total of 3,732 eligible participants were included in the analysis. Weighted multivariable-adjusted logistic regression models revealed a positive association between WHR and the risk of NAFLD (Q2vsQ1: OR = 1.94 [95% CI: 1.55–2.44]; Q3vsQ1: OR = 2.08 [95% CI: 1.51–2.85]; Q4vsQ1: OR = 3.70 [95% CI: 2.13–6.43], p 0.5), further reinforcing the reliability of the observed associations.ConclusionWHR elevation heightens the susceptibility to NAFLD.

Recently, artificial intelligence generated content (AIGC) has been receiving increased attention and is growing exponentially. AIGC is generated based on the intentional information extracted from human-provided instructions by generative artificial intelligence (AI) models. AIGC quickly and automatically generates large amounts of high-quality content. Currently, there is a shortage of medical resources and complex medical procedures in medicine. Due to its characteristics, AIGC can help alleviate these problems. As a result, the application of AIGC in medicine has gained increased attention in recent years. Therefore, this paper provides a comprehensive review on the recent state of studies involving AIGC in medicine. First, we present an overview of AIGC. Furthermore, based on recent studies, the application of AIGC in medicine is reviewed from two aspects: medical image processing and medical text generation. The basic generative AI models, tasks, target organs, datasets and contribution of studies are considered and summarized. Finally, we also discuss the limitations and challenges faced by AIGC and propose possible solutions with relevant studies. We hope this review can help readers understand the potential of AIGC in medicine and obtain some innovative ideas in this field.

Abstract Background The weight-adjusted waist index (WWI) is a new measure of obesity, and this study aimed to determine the association between the WWI and stroke. Methods Using the National Health and Nutrition Examination Survey (NHANES) 2011–2020 dataset, cross-sectional data from 23,389 participants were analysed. The correlation between the WWI and stroke was investigated through multivariate logistic regression and smoothing curve fitting. Subgroup analysis and interaction tests were also carried out. Results The research involved 23,389 participants, of whom 893 (3.82%) had a stroke. The fully adjusted model revealed a positive correlation between the WWI and stroke [1.25 (1.05, 1.48)]. Individuals who were in the highest quartile of WWI exhibited a 62% higher likelihood of experiencing a stroke than those in the lowest quartile [1.62 (1.06, 2.48)]. Subgroup analysis and interaction tests revealed that this positive correlation was similar in different population settings (all P for interaction > 0.05). Conclusion A higher WWI was associated with a higher prevalence of stroke. The results of this study underscore the value of the WWI in stroke prevention and management.

Existing statistical data indicates that an increasing number of people now require rehabilitation to restore compromised physical mobility. During the rehabilitation process, physical therapists evaluate and guide the movements of patients, aiding them in a more effective recovery of rehabilitation and preventing secondary injuries. However, the immutability of mobility and the expensive price of rehabilitation training hinder some patients from timely access to rehabilitation. Utilizing virtual reality for rehabilitation training might offer a potential alleviation to these issues. However, prevalent pose reconstruction algorithms in rehabilitation primarily rely on images, limiting their applicability to virtual reality. Furthermore, existing pose evaluation and correction methods in the field of rehabilitation focus on providing clinical metrics for doctors, and failed to offer patients efficient movement guidance. In this paper, a virtual reality-based rehabilitation training method is proposed. The sparse motion signals from virtual reality devices, specifically head-mounted displays hand controllers, is used to reconstruct full body poses. Subsequently, the reconstructed poses and the standard poses are fed into a natural language processing model, which contrasts the difference between the two poses and provides effective pose correction guidance in the form of natural language. Quantitative and qualitative results indicate that the proposed method can accurately reconstruct full body poses from sparse motion signals in real-time. By referencing standard poses, the model generates professional motion correction guidance text. This approach facilitates virtual reality-based rehabilitation training, reducing the cost of rehabilitation training and enhancing the efficiency of self-rehabilitation training.

The major advantage of laser lighting over white light-emitting-diode is the possibility to achieve ultra-high luminance. However, phosphors usually suffer laser-induced luminescence saturation, which limits the peak luminance of laser lighting devices. The aim of the present study is to develop LuAG:Ce/Al2O3 composite ceramics (LACCs) with a high saturation threshold for high-luminance laser lighting. Owning to the rigid crystal structure, proper synthetic process, and optimized thermal design, the LACCs possess small thermal quenching (16% loss in luminescence at 225 ℃), high quantum yield (> 95%), and excellent luminescence properties. When the LACCs are irradiated by blue laser diodes in a reflection mode, a high luminous flux of 4634 lm and luminous efficacy of 283 lm·W−1 are realized. Furthermore, they show no sign of luminescence saturation even when the power density reaches 20.5 W·mm−2. With these favorable properties, the designed LACCs show great potential in high-luminance laser lighting.

In recent years, the integration of robots in minimally invasive surgery has gained significant traction in clinical practice. However, conventional contact-based human-computer interaction poses the risk of bacterial infection, significantly limiting the role of robots in surgery. To address this limitation, we propose an innovative interaction method rooted in gestures and visual tags, allowing surgeons to control and fine-tune surgical robots without physical contact with the environment. By encoding the six gestures collected using LeapMotion, we can effectively control the surgical robot in a non-contact manner. Moreover, utilizing Aruco technology, we have accurately identified the 3D spatial position of the visual label, and developed 12 fine-tuning operations to refine surgical instruments. To evaluate the applicability of our proposed system in surgery, we designed a relevant experimental setup. In the experiment, we achieved enough precision. These results demonstrate that our system meets the clinical standard, providing doctors with a non-contact and flexible means of interacting with robots during surgery.

Robot-assisted minimally invasive surgery (RAMIS) has gained significant traction in clinical practice in recent years. However, most surgical robots rely on touch-based human-robot interaction (HRI), which increases the risk of bacterial diffusion. This risk is particularly concerning when surgeons must operate various equipment with their bare hands, necessitating repeated sterilization. Thus, achieving touch-free and precise manipulation with a surgical robot is challenging. To address this challenge, we propose a novel HRI interface based on gesture recognition, leveraging hand-keypoint regression and hand-shape reconstruction methods. By encoding the 21 keypoints from the recognized hand gesture, the robot can successfully perform the corresponding action according to predefined rules, which enables the robot to perform fine-tuning of surgical instruments without the need for physical contact with the surgeon. We evaluated the surgical applicability of the proposed system through both phantom and cadaver studies. In the phantom experiment, the average needle tip location error was 0.51 mm, and the mean angle error was 0.34 degrees. In the simulated nasopharyngeal carcinoma biopsy experiment, the needle insertion error was 0.16 mm, and the angle error was 0.10 degrees. These results indicate that the proposed system achieves clinically acceptable accuracy and can assist surgeons in performing contactless surgery with hand gesture interaction.

Laser lighting is emerging as a viable replacement for other light sources in applications requiring high luminance not achievable with LEDs. Phosphor materials for laser lighting are often optimized in terms of luminous efficiency and/or colorimetric properties, while the light homogeneity is often neglected. We present a thorough investigation of the homogeneity of the chromaticity and the luminance profile for the most common types of phosphors used in laser lighting. We find that the achievable luminance and homogeneity of the light spot depends significantly on the phosphor used to convert the blue laser light to white light. The findings of these investigations will present guidelines for optimal phosphor material parameters to achieve high luminance combined with homogeneous chromaticity.

Objective To explore patients’ experiences of enhanced recovery after surgery (ERAS) and to identify issues in the implementation of ERAS from the patient’s perspective.Design The systematic review and qualitative analysis were based on the Joanna Briggs Institute’s methodology for conducting synthesis.Data sources Relevant studies published in four databases, that is, Web of Science, PubMed, Ovid Embase and the Cochrane Library, were systematically searched, and some studies were supplemented by key authors and reference lists.Study selection Thirty-one studies were identified, involving 1069 surgical patients enrolled in the ERAS programme. The inclusion and exclusion criteria were formulated based on the Population, Interest of phenomena, Context, Study design criteria recommended by the Joanna Briggs Institute to determine the scope of article retrieval. The inclusion criteria were as follows: ERAS patients’ experiences; qualitative data; English language and published from January 1990 to August 2021.Data extraction Data were extracted from relevant studies using the standardised data extraction tool from Joanna Briggs Institute Qualitative Assessment and Review Instrument for qualitative research.Data synthesis The themes in the structure dimension are as follows: (1) patients cared about the timeliness of healthcare professionals’ help; (2) patients cared about the professionalism of family care; and (3) patients misunderstood and worried about the safety of ERAS. The themes in the process dimension are as follows: (1) patients needed adequate and accurate information from healthcare professionals; (2) patients needed to communicate adequately with healthcare professionals; (3) patients hoped to develop a personalised treatment plan and (4) patients required ongoing follow-up services. The theme in the outcome dimension is as follows: patients wanted to effectively improve severe postoperative symptoms.Conclusions Evaluating ERAS from the patient’s perspective can reveal the omissions and deficiencies of healthcare professionals in clinical care so that problems in patients’ recovery process can be solved in a timely manner, reducing potential barriers to the implementation of ERAS.PROSPERO registration number CRD42021278631.

Introduction Breast cancer has become a common tumour that threatens women’s physical and mental health. Microbial agents play an important role in maintaining the balance of gut microbiota and modulating intestinal immunity, anti-inflammatory and antioxidant effects. Available evidence points to a strong association between them and breast cancer. However, there has been no systematic review of the effects of microbial agents in patients with breast cancer. This protocol aims to explore the effectiveness and safety of probiotics, prebiotics and synbiotics in patients with breast cancer.Methods and analysis We will search the following electronic databases for relevant randomised controlled trials: PubMed, EMBASE, Cochrane Library and Web of Science. Grey literature and reference lists of original studies will also be searched to avoid omissions. We will use the Cochrane Collaboration’s Risk of Bias tool to assess the quality of the included studies. The primary outcomes include patients’ arm oedema volume, changes in gut microbiota composition and anthropometric parameters. Two independent reviewers will perform literature screening, data extraction and risk of bias assessment. Data synthesis will be performed using descriptive analysis or meta-analysis. The quality of the evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation tool.Ethics and dissemination The data for systematic reviews are derived from published original studies and do not require review and approval by the ethics committee. The results will be disseminated through a peer-reviewed journal and conferences.PROSPERO registration number CRD42022311502.

Abstract Background The gastrointestinal microbiome is an important component of the human body and is closely related to human health and disease. This study describes the hotspots of the human gastrointestinal microbiome research and its evolution in the past decade, evaluates the scientific cooperation network, and finally predicts the field’s future development trend using bibliometric analysis and a visualized study. Methods We searched the original articles from January 2010 to February 2021 in the Scopus database using the term “gastrointestinal microbiome” and its synonyms. CiteSpace was used to construct country and author co-occurrence map; conduct journal, citation cocitation analysis, and reference co-citation knowledge map; and form a keywords co-occurrence map, a clustering knowledge map, timeline view of keywords, and burst term map. Result A total of 4444 documents published from January 2010 to February 2021 were analysed. In approximately the past decade, the number of articles on the human gastrointestinal microbiome has increased rapidly, and the research topics focus on different populations, research methods, and detection methods. All countries and regions in the world, led by the US, are studying the human gastrointestinal microbiome, and many research teams with close cooperation have been formed. The research has been published extensively in microbiology journals and clinical medicine journals, and the highly cited articles mainly describe the relationship between gastrointestinal microorganisms and human health and disease. Regarding the research emphasis, researchers' exploration of the human gastrointestinal microbiome (2011–2013) was at a relatively macro and superficial stage and sought to determine how the gastrointestinal microbiome relates to humans. From 2014 to 2017, increasingly more studies were conducted to determine the interaction between human gastrointestinal flora and various organs and systems. In addition, researchers (2018–2021) focused on the gastrointestinal microbial community and the diversity of certain types of microbes. Conclusion Over time, the scope of the research on the clinical uses of the gastrointestinal microbiome gradually increased, and the contents were gradually deepened and developed towards a more precise level. The study of the human gastrointestinal microbiome is an ongoing research hotspot and contributes to human health.

Abstract In order to recapitulate the best available evidence of milk consumption and multiple health-related outcomes, we performed an umbrella review of meta-analyses and systematic reviews in humans. Totally, 41 meta-analyses with 45 unique health outcomes were included. Milk consumption was more often related to benefits than harm to a sequence of health-related outcomes. Dose–response analyses indicated that an increment of 200 ml (approximately 1 cup) milk intake per day was associated with a lower risk of cardiovascular disease, stroke, hypertension, colorectal cancer, metabolic syndrome, obesity and osteoporosis. Beneficial associations were also found for type 2 diabetes mellitus and Alzheimer's disease. Conversely, milk intake might be associated with higher risk of prostate cancer, Parkinson’s disease, acne and Fe-deficiency anaemia in infancy. Potential allergy or lactose intolerance need for caution. Milk consumption does more good than harm for human health in this umbrella review. Our results support milk consumption as part of a healthy diet. More well-designed randomized controlled trials are warranted.

Backgrounds: Enteral immunonutrition (EIN) has received increasing attention, however, evidence on its immunomodulatory and anti-inflammatory function in gastric cancer patients undergoing gastrectomy is poorly investigated. Objectives of this study were to evaluate the effect of EIN on immune function, inflammation response and nutrition status when compared to standard enteral nutrition (SEN). Methods: Totally 124 gastric cancer patients after gastrectomy were randomized to receive early 5-days postoperative EIN (formula enriched with arginine, glutamine, omega-3 fatty acids and nucleotide), or SEN. The primary end-points were CD4+ T-cells, CD3+ T-cells as well as counts of CD4+/CD8+, IgG, IgM, and IgA levels. Second-points included white blood cell (WBC), C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) levels and nutritional index such as serum albumin, prealbumin, and transferrin concentration. Results: There existed significant difference in primary end-points between EIN group and SEN group. The proportion of CD4+ T-cells, CD3+ T-cells and the counts of CD4+/CD8+, IgG, IgM, and IgA were higher in EIN group eventually. Meanwhile, the level of WBC, CRP and TNF-α were significantly lower in EIN group finally. But there were no other significant differences in nutritional markers between two groups. Conclusion: Early postoperative EIN significantly improves immune function and inflammatory response in gastric cancer patients undergoing gastrectomy.

Objective To explore the attitudes and barriers encountered in the implementation of enhanced recovery after surgery (ERAS) in China from the perspective of multidisciplinary team members.Design Based on Donabedian’s structure–process–outcome (SPO) model, a multicentre qualitative study using semistructured interviews was conducted.Setting From September 2020 to December 2020, the participants of this study were interviewed from six tertiary hospitals in Sichuan province (n=3), Jiangsu province (n=2) and Guangxi province (n=1) in China.Participants A total of 42 members, including surgeons (n=11), anaesthesiologists (n=10), surgical nurses (n=14) and dietitians(n=7) were interviewed.Results Multidisciplinary team (MDT) members still face many barriers during the process of implementing ERAS. Eight main themes are described around the barriers in the implementation of ERAS. Themes in the structure dimension are: (1) shortage of medical resources, (2) lack of policy support and (3) outdated concepts. Themes in the process dimension are: (1) poor doctor–patient collaboration, (2) poor communication and collaboration among MDT members and (3) lack of individualised management. Themes in the outcome dimension are: (1) low compliance and (2) high medical costs. The current implementation of ERAS is still based on ideas more than reality.Conclusions In general, barriers to ERAS implementation are broad. Identifying key elements of problems in the application and promotion of ERAS from the perspective of the MDT would provide a starting point for future quality improvement of ERAS, enhance the clinical effect of ERAS and increase formalised ERAS utilisation in China.

Hypothermia therapy is a promising therapeutic strategy for traumatic brain injury (TBI); however, some trials have shown that hypothermia therapy has a negative effect on patients with TBI. The treatment of hypothermia in children with TBI remains controversial. We conducted a search of six online databases to validate the literature on comparing hypothermia with normal therapy for children with TBI. Eight randomized controlled trials (514 patients) were included. The meta-analysis indicated that hypothermia therapy may increase the Glasgow Outcome Scale (GOS) scores. However, in terms of improving the rate of complications, intracranial pressure (ICP), mortality, cerebral perfusion pressure (CPP), and length of stay both in hospital as well as pediatric ICU, the difference was not statistically significant. Hypothermia therapy may have clinical advantages in improving the GOS scores in children with TBI compared with normothermic therapy, but hypothermia therapy may have no benefit in improving the incidence of complications, ICP, mortality, CPP, and length of stay both in pediatric ICU as well as hospital. The decision to implement hypothermia therapy for children with TBI depends on the advantages and disadvantages from many aspects and these must be considered comprehensively.

Point set registration is one of the basic problems in computer vision. When the overlap ratio between point sets is small or the relative transformation is large, local methods cannot guarantee the accuracy. However, the time complexity of the branch and bound (BnB) optimization used in most existing global methods is exponential in the dimensionality of parameter space. Therefore, seven-Degrees of Freedom (7-DoF) similarity transformation is a big challenge for BnB. In this paper, a novel rotation and scale invariant feature is introduced to decouple the optimization of translation, rotation, and scale in similarity point set registration, so that BnB optimization can be done in two lower dimensional spaces. With the transformation decomposition, the translation is first estimated and then the rotation is optimized by maximizing a robust objective function defined on consensus set. Finally, the scale is estimated according to the potential correspondences in the obtained consensus set. Experiments on synthetic data and clinical data show that our method is approximately two orders of magnitude faster than the state-of-the-art global method and more accurate than a typical local method. When the outlier ratio with respect to the inliers is up to 1.0, our method still achieves accurate registration.

Classical swine fever (CSF) caused by classical swine fever virus (CSFV) is one of the most detrimental diseases, and leads to significant economic losses in the swine industry. Despite efforts by many government authorities to stamp out the disease from national pig populations, the disease remains widespread. Here, antiviral small hairpin RNAs (shRNAs) were selected and then inserted at the porcine Rosa26 (pRosa26) locus via a CRISPR/Cas9-mediated knock-in strategy. Finally, anti-CSFV transgenic (TG) pigs were produced by somatic nuclear transfer (SCNT). Notably, in vitro and in vivo viral challenge assays further demonstrated that these TG pigs could effectively limit the replication of CSFV and reduce CSFV-associated clinical signs and mortality, and disease resistance could be stably transmitted to the F1-generation. Altogether, our work demonstrated that RNA interference (RNAi) technology combining CRISPR/Cas9 technology offered the possibility to produce TG animal with improved resistance to viral infection. The use of these TG pigs can reduce CSF-related economic losses and this antiviral strategy may be useful for future antiviral research.

BACKGROUND: In 2015, the U.S. Consumer Product Safety Commission (CPSC) received and then, in 2017, granted a petition under the Federal Hazardous Substances Act to declare certain groups of consumer products as banned hazardous substances if they contain nonpolymeric, additive organohalogen flame retardants (OFRs). The petitioners asked the CPSC to regulate OFRs as a single chemical class with similar health effects. The CPSC later sponsored a National Academy of Sciences, Engineering, and Medicine (NASEM) report in 2019, which ultimately identified 161 OFRs and grouped them into 14 subclasses based on chemical structural similarity. In 2021, a follow-up discussion was held among a group of scientists from both inside and outside of the CPSC for current research on OFRs and to promote collaboration that could increase public awareness of CPSC work and support the class-based approach for the CPSC’s required risk assessment of OFRs. OBJECTIVES: Given the extensive data collected to date, there is a need to synthesize what is known about OFR and how class-based regulations have previously managed this information. This commentary discusses both OFR exposure and OFR toxicity and fills some gaps for OFR exposure that were not within the scope of the NASEM report. The objective of this commentary is therefore to provide an overview of the OFR research presented at SOT 2021, explore opportunities and challenges associated with OFR risk assessment, and inform CPSC’s work on an OFR class-based approach. DISCUSSION: A class-based approach for regulating OFRs can be successful. Expanding the use of read-across and the use of New Approach Methodologies (NAMs) in assessing and regulating existing chemicals was considered as a necessary part of the class-based process. Recommendations for OFR class-based risk assessment include the need to balance fire and chemical safety and to protect vulnerable populations, including children and pregnant women. The authors also suggest the CPSC should consider global, federal, and state OFR regulations. The lack of data or lack of concordance in toxicity data could present significant hurdles for some OFR subclasses. The potential for cumulative risks within or between subclasses, OFR mixtures, and metabolites common to more than one OFR all add extra complexity for class-based risk assessment. This commentary discusses scientific and regulatory challenges for a class-based approach suggested by NASEM. This commentary is offered as a resource for anyone performing class-based assessments and to provide potential collaboration opportunities for OFR stakeholders. [ABSTRACT FROM AUTHOR]