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Abstract Objectives The CHROME-G is the first generic preference-based measure developed in China. This study aimed to validate and compare the psychometric properties of the CHROME-G with the EQ-5D-5L and SF-6Dv2 among the Chinese general population. Methods A representative sample of the Chinese general population in terms of age, gender, education, and urban/rural residence was recruited for an online survey. During the survey, respondents completed three instruments (first the CHROME-G, then the EQ-5D-5L and SF-6Dv2 in random order), demographic and health-related questions. The retest survey was carried out after two weeks. Ceiling/floor effects were first assessed. Convergent and divergent validity was examined using Spearman’s rank correlation. Known-group validity was examined using the non-parametric Kruskal–Wallis H test and effect size. Test–retest reliability was assessed using the intraclass correlation coefficient and weighted Kappa statistics. Results One thousand respondents (51.1% male, mean age 44.7 years) completed the first survey, with 378 also completing the retest survey. The mean ± SD completion time was 2.03 ± 0.58 min for the CHROME-G, and 1.37 ± 0.54 and 1.13 ± 0.38 min for the EQ-5D-5L and SF-6Dv2. Only the EQ-5D-5L had a ceiling effect of 35.1%. The range of Spearman rank’s correlations was 0.45–0.62 for convergent validity and 0.14–0.46 for divergent validity. Among different health subgroups, the effect size for the CHROME-G, EQ-5D-5L and SF-6Dv2 was 1.348–3.416, 1.362–3.325 and 1.097–2.228, respectively. The ICC for test–retest was 0.791 for the CHROME-G, compared with 0.994 and 0.971 for the EQ-5D-5L and SF-6Dv2. Conclusions The CHROME-G showed good and comparable psychometric properties with the EQ-5D-5L and SF-6Dv2.

Abstract Within the clinical realm, the complexities of wound healing have consistently presented formidable challenges. Recent advancements, notably in hydrogel technologies, have broadened the therapeutic spectrum. This study focuses on investigating a novel dual responsive composite hydrogel for wound healing. This hydrogel is ingeniously designed to maintain an optimal moist environment, expedite healing, and combat bacterial infection during wound recovery. This study combining carboxymethyl chitosan (CMC), oxidized hyaluronic acid (OHA), and sodium alginate (SA), in addition, tobramycin (TOB) was incorporated to create a CMC/OHA/SA/TOB hydrogel. Hydrogel cross-linking was verified by infrared spectroscopy, and the microstructure was examined with scanning electron microscopy. We explored its swelling and degradation behaviors in different pH environments. The drug release profile and biocompatibility was evaluated via cytotoxicity and hemolysis assays. The antibacterial efficacy of hydrogel was tested in both solid and liquid media. Additionally, the wound models in Sprague–Dawley (SD) rat was employed to investigate the hydrogel’s wound healing capabilities in vivo. Results showed that CMCOHA/SA/TOB hydrogel was effectively cross-linked with a network structure. The hydrogel exhibited pronounced responsiveness in its swelling and degradation characteristics, which was significantly influenced by different levels of pH. In vitro results demonstrated that the CMC/OHA/SA/TOB hydrogel exhibits limited cytotoxicity and hemolysis, coupled with a drug release profile of dual responsive characteristics. Antibacterial activity of the hydrogel against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was confirmed. Furthermore, in vivo experiments underscored the hydrogel’s proficiency in promoting wound healing, highlighting its potential for clinical applications. The CMC/OHA/SA/TOB hydrogel not only fosters a moist environment essential for wound healing and enhances structural stability, but it also exhibits functional dual responsive capabilities in swelling and degradation. These distinctive abilities enable the precise release of TOB, thereby optimizing wound healing.

Abstract Objective To evaluate and compare the measurement properties and consistency between the Chinese versions of EQ-5D-3L and EQ-5D-Y-3L among Chinese adolescent populations aged 15–17 years. Methods Chinese adolescents aged 15–17 studying in high school were recruited through online survey. Social-demographic characteristics and self-reported EQ-5D-3L and EQ-5D-Y-3L responses were collected in the survey. The consistency of responses between the two measures was assessed using redistribution property, and the consistency of utility values was assessed by intraclass correlation coefficients (ICC). Convergent validity and known-group validity were examined using Spearman’s rank correlation, F-test and effect sizes, respectively. Sensitivity was compared using relative efficiency (RE). Results 762 respondents (48.8% male; age 15–17 years;) were recruited. The EQ-5D-3L showed a more severe ceiling effect than EQ-5D-Y-3L (78.2% vs. 66.0%). Respondents reported higher proportions of having problems in four dimensions using the EQ-5D-Y-3L than using the EQ-5D-3L. The consistency of corresponding dimensions between the two measures was relatively good, while non-negligible proportions of inconsistency were observed in “pain/discomfort” (11.4%) and “anxiety/depression” (15.7%) dimensions. The ICC of the utility values between the EQ-5D-3L and EQ-5D-Y-3L was 0.852 (p

Abstract Introduction This systematic review and meta-analysis aimed to provide an updated evidence base for clinical decision-making by comparing the efficacy and safety of aflibercept 2 mg and ranibizumab in treating retinal vein occlusion (RVO). Methods A systematic search was conducted using eight databases up to December 2021. Randomized controlled trials (RCTs) and real-world studies (RWSs) comparing aflibercept and ranibizumab in patients with RVO were evaluated. The primary outcomes assessed were efficacy, number of injections administered, and adverse events. Results Three RCTs (424 patients) and 11 RWSs (1415 patients) were included. For central RVO (CRVO), RCTs demonstrated a comparable efficacy, whereas RWSs showed that mean changes from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were significantly greater with aflibercept compared to ranibizumab; the number of injections of aflibercept was fewer than that of ranibizumab in RCTs, but similar in RWSs. For branch RVO (BRVO), no statistically significant difference in efficacy between the two drugs in RCTs/RWSs was observed, with fewer injections of aflibercept at 12 months in RWSs. The safety profiles of both drugs were similar for both CRVO and BRVO. Conclusions For CRVO, aflibercept had similar efficacy and safety profile but with fewer injections versus ranibizumab in RCTs; RWSs showed greater BCVA improvement and CRT reduction with aflibercept than ranibizumab. For BRVO, RCTs showed similar in efficacy, safety, and injection numbers for both drugs, while RWSs demonstrated that aflibercept required fewer injections at 12 months of follow-up. Overall, this study provides updated evidence for clinical decision-making in the treatment of RVO.

When a strong earthquake occurs, roads are the lifelines of rescue. The rapid development of high-resolution satellite imaging platforms has made the application of remote sensing technology for road damage identification possible. Over the years, road damage identification has required a significant amount of manual involvement, making it difficult to meet the needs of rapid post-disaster response. The automatic recognition of road damage using satellite images has always been difficult. Damaged areas appear in the satellite images with blurry boundaries, versatile sizes, and uneven spatial distributions. With the aim of automatic pixel-level road damage identification, we introduce the first road damage dataset, CAU-RoadDamage, which includes high-resolution satellite images and pixel-level human annotations. Moreover, we propose the application of a pre-trained vision foundation model for the first time to automatically identify road damage. Low-rank adaptation technology is used to fine-tune the foundation model on the satellite images, and two-way attention is used to integrate the foundation model with domain specialist model components. The proposed segmentation model is compared to multiple state-of-the-art methods on the CAU-RoadDamage dataset. Our approach achieves the highest F1 of 76.09%, which is notably higher than that of the other models. The experimental results demonstrate the feasibility of pixel-level road damage recognition and the applicability of vision foundation models for downstream remote sensing tasks. The CAU-RoadDamage dataset will be made publicly available at https://github.com/CAU-HE/RoadDamageExtraction.

Abstract Background Shared decision-making is useful to facilitate cancer treatment decisions. However, it is difficult to make treatment decisions when physician and patient preferences are different. This review aimed to summarize and compare the preferences for cancer treatments between physicians and patients. Methods A systematic literature search was conducted on PubMed, Embase, PsycINFO, CINAHL and Scopus. Studies elicited and compared preferences for cancer treatments between physicians and patients were included. Information about the study design and preference measuring attributes or questions were extracted. The available relative rank of every attribute in discrete choice experiment (DCE) studies and answers to preference measuring questions in non-DCE studies were summarized followed by a narrative synthesis to reflect the preference differences. Results Of 12,959 studies identified, 8290 were included in the title and abstract screening and 48 were included in the full text screening. Included 37 studies measured the preferences from six treatment-related aspects: health benefit, adverse effects, treatment process, cost, impact on quality of life, and provider qualification. The trade-off between health benefit and adverse effects was the main focus of the included studies. DCE studies showed patients gave a higher rank on health benefit and treatment process, while physicians gave a higher rank on adverse effects. Non-DCE studies suggested that patients were willing to take a higher risk of adverse effects or lower health benefit than physicians when accepting a treatment. Conclusions Physicians and patients had important preference differences for cancer treatment. More sufficient communication is needed in cancer treatment decision-making.

Abstract Background Different network meta-analyses (NMAs) on the same topic result in differences in findings. In this review, we investigated NMAs comparing aflibercept with ranibizumab for diabetic macular oedema (DME) in the hope of illuminating why the differences in findings occurred. Methods Studies were searched for in English and Chinese electronic databases (PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP; see detailed search strategy in the main body). Two independent reviewers systematically screened to identify target NMAs that included a comparison of aflibercept and ranibizumab in patients with DME. The key outcome of interest in this review is the change in best-corrected visual acuity (BCVA), including various ways of reporting (such as the proportion of participants who gain ≥ 10 ETDRS letters at 12 months; average change in BCVA at 12 months). Results For the binary outcome of BCVA, different NMAs all agreed that there is no clear difference between the two treatments, while continuous outcomes all favour aflibercept over ranibizumab. We discussed four points of particular concern that are illustrated by five similar NMAs, including network differences, PICO (participants, interventions, comparators, outcomes) differences, different data from the same measures of effect, and differences in what is truly significant. Conclusions A closer inspection of each of these trials shows how the methods, including the searches and analyses, all differ, but the findings, although presented differently and sometimes interpreted differently, were similar.

ObjectiveTo examine the disease burden of cervical cancer in 127 countries along the Belt and Road. MethodsThe 127 countries involved in the analysis were determined based on the information from the website of China's Belt and Road Initiative and the countries were assigned into one of the 6 World Health Organization (WHO) regions. The country-specific data of 2018 on world population based age standardized incidence and mortality rate and disability-adjusted life years (DALYs) of cervical cancer were extracted from WHO cancer registry database for analyzing and comparing between country disparities in disease burden of cervical cancer using descriptive statistics. Cluster analysis was used to assess prevalence intensity of cervical cancer among the countries in different WHO regions. ResultsThe disease burden of cervical cancer in 2018 was significantly different among the 127 countries in various WHO regions along the Belt and Road. The mean age-standardized incidence rate (32.4/100 000) and mortality rate (21.9/100 000) of cervical cancer were the highest for the countries in the WHO African region; while, those for the countries in the WHO Mediterranean region were the lowest (age-standardized incidence and mortality rate: 4.4/100 000 and 2.9/100 000). The mean DALYs of cervical cancer was the highest (458.2/100 000) for the countries in the WHO region of America but the lowest (69 /100 000) for countries in the WHO Eastern Mediterranean region. The results of cluster analysis showed that the prevalence of cervical cancer was at medium-high level for countries in WHO African region and at low level for countries in the WHO European, Western Pacific and Eastern Mediterranean regions. Conclusion Geographical region is the main, but not the only factor affecting the disease burden of cervical cancer for countries along the Belt and Road and the influences of country-specific social and economic development, natural and social environment should be considered in cervical cancer control.

Abstract Maintaining stable and transient quiescence in differentiated and stem cells, respectively, requires repression of the cell cycle. The plant RETINOBLASTOMA-RELATED (RBR) has been implicated in stem cell maintenance, presumably by forming repressor complexes with E2F transcription factors. Surprisingly we find that mutations in all three canonical E2Fs do not hinder the cell cycle, but similarly to RBR silencing, result in hyperplasia. Contrary to the growth arrest that occurs when exit from proliferation to differentiation is inhibited upon RBR silencing, the e2fabc mutant develops enlarged organs with supernumerary stem and differentiated cells as quiescence is compromised. While E2F, RBR and the M-phase regulatory MYB3Rs are part of the DREAM repressor complexes, and recruited to overlapping groups of targets, they regulate distinct sets of genes. Only the loss of E2Fs but not the MYB3Rs interferes with quiescence, which might be due to the ability of E2Fs to control both G1-S and some key G2-M targets. We conclude that collectively the three canonical E2Fs in complex with RBR have central roles in establishing cellular quiescence during organ development, leading to enhanced plant growth.

Abstract Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs increased the relative level of creatine during myoblasts fusion, which was released via activated Pannexin 1 channel. Moreover, we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel, which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.

Here the authors show genome-wide chromatin changes and transcriptional reprogramming occur in response to heat stress in tomato, leading to the transient formation of promoter-enhancer contacts to drive the expression of heat-stress responsive genes. Furthermore, they show chromatin spatial reorganization requires HSFA1a, a transcription factor (TF) essential for heat stress tolerance in tomato.

Abstract Objectives To explore the relationship between cervical cancer burden and HDI and other socioeconomic influence factors in 127 countries. Methods Dividing 127 countries into low-, medium-, high-, ultrahigh-HDI groups, and using statistical method to compare the prevalence trend of cervical cancer in different HDI country groups. Then selecting mortality-to-incidence ratio (MIR) to measure the cancer burden as the dependent variable, HDI and other socioeconomic factors selected from 2020 Human Development Report as independent variables, and using multi-regression model to analyze the correlation between variables. Results Countries with higher HDI were found to have lower prevalence and mortality of cervical cancer, and vice versa. Besides that, air and water pollution, government-coordinated spending, and the intimate partner of 15–49-year-old women and girls have positive correlation impact on cervical cancer burden. Discussion The cancer prevention and control policies in countries with high HDI have achieved relatively ideal implementation effects. Countries with relatively backward social and economic development level, cancer prevention and control policies had little effect, such as lower HPV vaccination coverage, poor regional health resource allocation, and week public education awareness. Therefore, cervical cancer control plan must be integrated into national strategies and implemented in people-oriented comprehensive health services.

Abstract Background Acute lung injury (ALI) is a severe inflammatory disease, underscoring the urgent need for novel treatments. Nauclea officinalis Pierre ex Pitard (Danmu in Chinese, DM) is effective in treating inflammatory respiratory diseases. However, there is still no evidence of its protective effect against ALI. Methods Metabolomics was applied to identify the potential biomarkers and pathways in ALI treated with DM. Further, network pharmacology was introduced to predict the key targets of DM against ALI. Then, the potential pathways and key targets were further verified by immunohistochemistry and western blot assays. Results DM significantly improved lung histopathological characteristics and inflammatory response in LPS-induced ALI. Metabolomics analysis showed that 16 and 19 differential metabolites were identified in plasma and lung tissue, respectively, and most of these metabolites tended to recover after DM treatment. Network pharmacology analysis revealed that the PI3K/Akt pathway may be the main signaling pathway of DM against ALI. The integrated analysis of metabolomics and network pharmacology identified 10 key genes. These genes are closely related to inflammatory response and cell apoptosis of lipopolysaccharide (LPS)-induced ALI in mice. Furthermore, immunohistochemistry and western blot verified that DM could regulate inflammatory response and cell apoptosis by affecting the PI3K/Akt pathway, and expression changes in Bax and Bcl-2 were also triggered. Conclusion This study first integrated metabolomics, network pharmacology and biological verification to investigate the potential mechanism of DM in treating ALI, which is related to the regulation of inflammatory response and cell apoptosis. And the integrated analysis can provide new strategies and ideas for the study of traditional Chinese medicines in the treatment of ALI. Graphical Abstract

Summary: Immune system disorders, especially T cell disorders, are important therapeutic targets of mesenchymal stem cells (MSCs) in many autoimmune diseases (ADs). Although extracellular regulated protein kinases (ERKs) play a role in MSC therapy by promoting T cell apoptosis, the mechanism remains unclear. Our findings indicate that ERK1−/− bone marrow MSCs (BMMSCs), but not ERK2−/− BMMSCs, failed to promote T cell apoptosis due to incapacity to activate the ETS2/AURKA/NF-κB/Fas/MCP-1 cascade. Moreover, ERK1−/− BMMSCs were unable to upregulate regulatory T cells and suppress T helper 17 cells. Licochalcone A (LA), which promotes ERK pathway activation, enhanced the therapeutic efficacy of MSC therapy in ulcerative colitis and collagen-induced arthritis mice. Our findings suggest that ERK1, but not ERK2, plays a crucial role in regulating T cells in MSCs. LA-treated MSCs provide a strategy to improve the efficacy of MSC-based treatments for ADs.

Flood events are often accompanied by rainy weather, which limits the applicability of optical satellite images, whereas synthetic aperture radar (SAR) is less sensitive to weather and sunlight conditions. Although remarkable progress has been made in flood detection using heterogeneous multispectral and SAR images, there is a lack of publicly available large-scale datasets and more efforts are required for exploiting deep neural networks in heterogeneous flood detection. This study constructed a pre-disaster Sentinel-2 and post-disaster Sentinel-1 heterogeneous flood mapping dataset named CAU-Flood containing 18 study plots with careful image preprocessing and human annotation. A new deep convolutional neural network (CNN), named cross-modal change detection network (CMCDNet), was also proposed for flood detection using multispectral and SAR images. The proposed network employs a encoder-decoder structure and performs feature fusion at multiple stages using gating and self-attention modules. Furthermore, the network overcomes the feature misalignment issue during decoding by embedding a feature alignment module in the upsampling operation. The proposed CMCDNet outperformed SOTA methods in terms of flood detection accuracy and achieved an intersection over union (IoU) of 89.84%. The codes and datasets are available at: https://github.com/CAU-HE/CMCDNet.

This study aimed to develop a consensus framework for economic evaluations of vaccines as a national guideline in China. Some unique and important aspects were particularly emphasized. Nineteen Chinese experts in the field of health economics and immunization decision-making were nominated to select and discuss relevant aspects of vaccine economic evaluations in China. A workshop attended by external experts was held to summarize unique and important aspects and formulate consensus recommendations. There were ten unique and/or important aspects identified for economic evaluations of vaccines in China, including study perspectives, comparator strategies, analysis types, model choices, costing approaches, utility measures, discounting, uncertainty, equity, and evaluation purposes. Background information and expert recommendations were provided for each aspect. Economic evaluations of vaccines should play an important role in China’s immunization policy-making. This guideline can help improve the quality of economic evaluations as a good practice consensus.

Improving the positioning accuracy and stability of a single BDS/INS sensor system in agricultural machinery is important for expanding the application scenarios of agricultural machinery. This paper proposes a navigation and positioning model based on an improved bee-colony-algorithm-optimized BP network (the IABC-BP model). The main aspect of this work involves introducing adaptive coefficients and speed adjustment coefficients that obey Gaussian distribution to ensure the balance between the rate of convergence, group flexibility, and searchability in the search process. The implicit adaptive layer formula of the BP network is proposed, and the BDS/INS navigation and positioning model for agricultural machinery is established using the IABC algorithm and the Kalman filter. Simulation tests and analyses of real-world application scenarios were conducted on the model, and the results showed that, compared with the original model, the performance of the model improved by 90.65%, 84.11%, and 25.96%, indicating that the proposed model has high accuracy and effectiveness. In the information fusion and compensation correction mode, the algorithm processes errors such as longitude and latitude within the target range and can achieve reliable navigation and positioning accuracy in a short period. At the same time, the model has good stability and generalization ability, and can be applied to other navigation scenarios in the future to expand its application scope.

The rapid and nondestructive detection of tea leaf moisture content (MC) is of great significance to processing tea with an automatic assembly line. This study proposes an MC detection method based on microwave scattering parameters (SPs). Through the established free-space electromagnetic measurement device, 901 different frequency points are taken between 2.45 and 6 GHz using a vector network analyzer (VNA). The SPs of tea leaves with different moisture contents (5.72–55.26%) at different bulk density and different sample thicknesses were measured. The relationship between frequency, S21 amplitude and moisture content, thickness, and bulk density of tea was analyzed using correlation coefficients, significance analysis, and model construction. Back propagation (BP) neural network, decision tree (DT), and random forest (RF) MC prediction models were established with the frequency, amplitude, and phase of the SPs, thickness, and bulk density of the samples as inputs. The results showed that the RF-based model had the best performance, with determination coefficient (R2) = 0.998, mean absolute error (MAE) = 0.242, and root mean square error (RMSE) = 0.614. Compared to other nondestructive testing processes for tea, this method is simpler and more accurate. This study provides a new method for the detection of tea MC, which may have potential applications in tea processing.

Snowstorms frequently hit large parts of the Northern Hemisphere, and their causative factors have been drawing increasing attention in recent years. As the first in-depth study on the mechanisms of a snowstorm associated with a low-level cold front (LLCF) and low-level westerly jet (LLWJ) in the western mountainous region of the Junggar Basin, Xinjiang, based on both observations and numerical simulation, the major findings of this work are as follows: At the early stage, instabilities were mainly dominated by inertial instability (II) occurring near the core region of the LLWJ, while the lower level was mainly controlled by the baroclinic component of moist potential vorticity (MPV2), which was mainly contributed by the vertical shear of the horizontal wind, which is also located near the LLWJ. At the later stage, II was released significantly, whereas the MPV2 still supported snowfall clouds. Further analysis based on the decomposition of the frontogenetical forcing required for the release of the instabilities indicated that the slantwise term was the major contributor, whereas convergence and deformation also played significant roles at low levels above the windward slope. The slantwise term resulted from the combined effects of baroclinicity due to the LLCF and the inhomogeneity of the momentum due to the LLWJ.

Abstract Background The repair of large-scale full-thickness skin defects represents a challenging obstacle in skin tissue engineering. To address the most important problem in skin defect repair, namely insufficient blood supply, this study aimed to find a method that could promote the formation of vascularized skin tissue. Method The phenotypes of ASCs and EPCs were identified respectively, and ASCs/EPCs were co-cultured in vitro to detect the expression of dermal and angiogenic genes. Furthermore, the co-culture system combined with dermal extracellular matrix hydrogel was used to repair the full-scale skin defects in rats. Result The co-culture of ASCs/EPCs could increase skin- and angiogenesis-related gene expression in vitro. The results of in vivo animal experiments demonstrated that the ASCs/EPCs group could significantly accelerate the repair of skin defects by promoting the regeneration of vascularized skin. Conclusion It is feasible to replace traditional single-seed cells with the ASC/EPC co-culture system for vascularized skin regeneration. This system could ultimately enable clinicians to better repair the full-thickness skin defects and avoid donor site morbidity.

Background: Antiangiogenic therapy with anti-vascular endothelial growth factor (VEGF) is commonly used to treat diabetic macular edema (DME), which can reduce edema, improve vision, and prevent further visual loss. There is little head-to-head trial data to guide the selection of an individual VEGF inhibitor. Therefore, we aimed to investigate the efficacy and safety of anti-VEGF for patients with DME and to assess the differences between clinically relevant options by using network meta-analysis (NMA).Methods: MEDLINE, Embase, the Cochrane Library, Web of Science, Chinese Biomedical Literature Database, Wanfang, China National Knowledge Infrastructure, and VIP databases were searched for published randomized controlled trials (RCTs) from their inception to November 2020. We included RCTs of anti-VEGF drugs (intravitreal aflibercept (IVT-AFL), intravitreal ranibizumab (IVR), and intravitreal conbercept (IVC)) treating adult patients who were diagnosed with DME, regardless of stage or duration of the disease. We estimated summary odds ratios (ORs) and mean differences (MDs) with 95% credible intervals (CrIs) using a Bayesian NMA. This study’s registration number is CRD42021259335.Results: We identified 43 RCTs comprising 8,234 patients. Beneficial effects were observed in patients who used IVT-AFL compared with those who used other anti-VEGF therapies at 1-year follow-up on corrected visual acuity (BCVA) improvements (all patients: versus IVR: MD 2.83, 95% CrIs 1.64, 4.01, versus IVC: MD 2.41, 95% CrIs −0.52, 5.32; patients with worse baseline visual acuity (VA): versus IVR: MD 3.39, 95% CrIs 1.89, 4.9, versus IVC: MD 3.49, 95% CrIs 0.49, 6.44) and the proportion of patients with a gain of at least 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (all patients: versus IVR: OR 1.55, 95% CrIs 1.11, 2.17, versus IVC: OR 2.78, 95% CrIs 1.23, 6.04; patients with worse baseline VA: versus IVR: OR 2.05, 95% CrIs 1.18, 3.58, versus IVC: OR 2.85, 95% CrIs 1.24, 6.41). The effect of improvement in BCVA was identified for IVT-AFL compared to intravitreal bevacizumab. Based on the surface under the cumulative ranking curve (SUCRA), IVT-AFL had the highest probability of being the most effective option (99.9% and 99.5% in terms of the two primary outcomes, respectively). At the 2-year follow-up, numerical differences were identified favoring IVT-AFL; however, they did not reach statistical significance when comparing IVT-AFL to IVR. In the analysis of adverse events, IVT-AFL showed a lower risk of incidence of ocular adverse events compared to other anti-VEGF therapies at 1-year follow-up (versus IVR: OR 0.45, 95% CrIs 0.28, 0.7; versus IVC: OR 0.36, 95% CrIs 0.21, 0.63).Conclusion: IVT-AFL resulted in greater beneficial effects on BCVA and a higher proportion of patients with a gain of at least 15 ETDRS letters compared to IVR or IVC one year after treatment (especially in DME patients with worse baseline VA). In addition, fewer ocular adverse events occurred in the IVT-AFL group compared to the IVR or IVC groups. After two years, there was insufficient evidence to identify which anti-VEGF has superior efficacy or safety.Clinical Trial Registration:https://www.crd.york.ac.uk/prospero/, PROSPERO; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021259335, CRD42021259335

Abstract Background The role of bone tissue engineering is to regenerate tissue using biomaterials and stem cell-based approaches. Combination of two or more cell types is one of the strategies to promote bone formation. Endothelial progenitor cells (EPCs) may enhance the osteogenic properties of mesenchymal stem cells (MSCs) and promote bone healing; this study aimed to investigate the possible mechanisms of EPCs on promoting osteogenic differentiation of MSCs. Methods MSCs and EPCs were isolated and co-cultured in Transwell chambers, the effects of EPCs on the regulation of MSC biological properties were investigated. Real-time PCR array, and western blotting were performed to explore possible signaling pathways involved in osteogenesis. The expression of osteogenesis markers and calcium nodule formation was quantified by qRT-PCR, western blotting, and Alizarin Red staining. Results Results showed that MSCs exhibited greater alkaline phosphatase (ALP) activity and increased calcium mineral deposition significantly when co-cultured with EPCs. The mitogen-activated protein kinase (MAPK) signaling pathway was involved in this process. p38 gene expression and p38 protein phosphorylation levels showed significant upregulation in co-cultured MSCs. Silencing expression of p38 in co-cultured MSCs reduced osteogenic gene expression, protein synthesis, ALP activity, and calcium nodule formation. Conclusions These data suggest paracrine signaling from EPCs influences the biological function and promotes MSCs osteogenic differentiation. Activation of the p38MAPK pathway may be the key to enhancing MSCs osteogenic differentiation via indirect interactions with EPCs.

Abstract Background The repair of critical-sized bone defect represents a challenging problem in bone tissue engineering. To address the most important problem in bone defect repair, namely insufficient blood supply, this study aimed to find a method that can promote the formation of vascularized bone tissue. Method The phenotypes of ASCs and EPCs were identified respectively, and ASCs/EPCs were co-cultured in vitro to detect the expression of osteogenic and angiogenic genes. Furthermore, the co-culture system combined with scaffold material was used to repair the critical-sized bone defects of the cranial bone in rats. Results The co-culture of ASCs/EPCs could increase osteogenesis and angiogenesis-related gene expression in vitro. The results of in vivo animal experiments demonstrated that the ASC/EPC group could promote bone regeneration and vascularization in the meantime and then significantly accelerate the repair of critical-sized bone defects. Conclusion It is feasible to replace traditional single seed cells with ASC/EPC co-culture system for vascularized bone regeneration. This system could ultimately enable clinicians to better repair the defect of craniofacial bone and avoid donor site morbidity.

Abstract Background While the benefit of adherence to statins on clinical outcomes has been proved, this benefit may be heterogeneous among patients who initiated statins for primary or secondary prevention purpose. This study aimed to investigate the impact of statin adherence on clinical outcomes among patients who initiated statins for primary and secondary prevention in China. Methods Adult patients in Tianjin Urban Employee Basic Medical Insurance database who initiated ≥2 prescriptions of statins from 2012 through 2013 were included and grouped into primary and secondary prevention subgroups according to their cardiovascular diseases (CVD) history during the prior 12-month baseline period. Proportion of days covered (PDC) was used to measure statin adherence in the initial 12-month follow-up. Clinical outcomes were measured by the incidence of major adverse cardiovascular events (MACE) during the 13th–24th months follow-up, and were compared between the patients with PDC ≥ 0.5 and patients with PDC

Frontal corticostriatal circuits (FCSC) are involved in self-regulation of cognition, emotion, and motor function. While these circuits are implicated in attention-deficit/hyperactivity disorder (ADHD), the literature establishing FCSC associations with ADHD is inconsistent. This may be due to study variability in considerations of how fMRI motion regression was handled between groups, or study specific differences in age, sex, or the striatal subregions under investigation. Given the importance of these domains in ADHD it is crucial to consider the complex interactions of age, sex, striatal subregions and FCSC in ADHD presentation and diagnosis. In this large-scale study of 362 8–12 year-old children with ADHD (n = 165) and typically developing (TD; n = 197) children, we investigate associations between FCSC with ADHD diagnosis and symptoms, sex, and go/no-go (GNG) task performance. Results include: (1) increased striatal connectivity with age across striatal subregions with most of the frontal cortex, (2) increased frontal-limbic striatum connectivity among boys with ADHD only, mostly in default mode network (DMN) regions not associated with age, and (3) increased frontal-motor striatum connectivity to regions of the DMN were associated with greater parent-rated inattention problems, particularly among the ADHD group. Although diagnostic group differences were no longer significant when strictly controlling for head motion, with motion possibly reflecting the phenotypic variance of ADHD itself, the spatial distribution of all symptom, age, sex, and other ADHD group effects were nearly identical to the initial results. These results demonstrate differential associations of FCSC between striatal subregions with the DMN and FPN in relation to age, ADHD, sex, and inhibitory control.

ObjectivesThis study aimed to estimate the impact of hyperkalemia on 1-year survival and all-cause healthcare resource utilization among patients with chronic kidney disease in China.MethodsAdult new-onset chronic kidney disease patients were identified between 2012 and 2016, among which the hyperkalemia and non-hyperkalemia cohorts were further selected and matched. Survival and all-cause healthcare resource utilization during a 12 month period were compared using Kaplan-Meier curves with log-rank test, Cox proportional hazard model, and Kaplan-Meier sample average method.ResultsAmong 1,003 pairs of patients (mean age 67.2 ± 14.3 years), the 1-year all-cause mortality was 5.39-times higher in the hyperkalemia cohort than the non-hyperkalemia cohort (hazard ratio = 5.39, P < 0.001). The mean costs and number of healthcare services among the hyperkalemia patients were significantly higher (P < 0.05) in each follow-up month. An annual increase cost of ¥38,479 was observed in the hyperkalemia cohort, largely due to the sharp increase in inpatient costs during the first month after hyperkalemia events (¥22,204 vs. 1,032, P < 0.001). Medication costs were the most important cost component for both cohorts [¥26,786 (45%) vs. ¥12,378(60%)]. However, hyperkalemia patients spent more on non-medication treatment [¥13,410(23%) vs. ¥2,335(11%)] including nursing, monitoring, etc. Hyperkalemia patients had more annual inpatient admissions (1.9 vs. 0.7) and length of stays (28.6 vs. 8.7), while the number of outpatient visits (36.8 vs. 36.4) were similar.ConclusionsIn Chinese chronic kidney disease patients, hyperkalemia is associated with substantially increased clinical and economic burdens that are driven by the short period following the hyperkalemia events, which strengthens calls for sufficient supervision and management of serum potassium.

Abstract Mitochondrial dysfunction in tissue‐specific mesenchymal stem cells (MSCs) plays a critical role in cell fate and the morbidity of chronic inflammation‐associated bone diseases, such as periodontitis and osteoarthritis. However, there is still no effective method to cure chronic inflammation‐associated bone diseases by physiologically restoring the function of mitochondria and MSCs. Herein, it is first found that chronic inflammation leads to excess Ca2+ transfer from the endoplasmic reticulum to mitochondria, which causes mitochondrial calcium overload and further damage to mitochondria. Furthermore, damaged mitochondria continuously accumulate in MSCs due to the inhibition of mitophagy by activating the Wnt/β‐catenin pathway under chronic inflammatory conditions, impairing the differentiation of MSCs. Based on the mechanistic discovery, intracellular microenvironment (esterase and low pH)‐responsive nanoparticles are fabricated to capture Ca2+ around mitochondria in MSCs to regulate MSC mitochondrial calcium flux against mitochondrial dysfunction. Furthermore, the same nanoparticles are able to deliver siRNA to MSCs to inhibit the Wnt/β‐catenin pathway and regulate mitophagy of the originally dysfunctional mitochondria. These precision‐engineered nanoparticles, referred to as “nanorepairers,” physiologically restore the function of mitochondria and MSCs, resulting in effective therapy for periodontitis and osteoarthritis. The concept can potentially be expanded to the treatment of other diseases via mitochondrial quality control intervention.

Considering the problems of low soil fragmentation rates, high working resistance, and high energy consumption in the harvesting process of Cyperus esculentus in China, a method of Cyperus esculentus harvesting based on counter-rotation digging is proposed. The mechanism of interaction between the rotary tillage blade and Cyperus esculentus–soil is systematically investigated, and the vertical and horizontal disturbance performance of the positive and counter-rotating harvesting methods on soil and Cyperus esculentus is compared and analyzed. The results of the experiment showed that the intensity of soil and Cyperus esculentus disturbance by counter-rotation increased by 166.67% and 297.78%, respectively, and the effective disturbance time of soil and Cyperus esculentus increased by 133.33% compared to that of positive rotation. The working depth and rotation speed of the rotary tillage blade were the most significant for soil and Cyperus esculentus disturbance intensity. The working depth increased from 150 mm to 170 mm, and the soil disturbance intensity increased by 17.91% and 21.37% for positive and counter-rotating operation, respectively, and the rotation speed of the rotary tillage blade increased from 270 rpm to 330 rpm, and the soil disturbance intensity increased by 28.85% and 35.29%, respectively. Compared with the positive rotation operation, the Cyperus esculentus counter-rotation soil fragmentation rate increased by 4.09%, the Cyperus esculentus damage rate decreased by 10.69%, and the buried fruit rate decreased by 7.38%. This paper helps to understand the interaction mechanism between the rototiller and Cyperus esculentus–soil and lays a theoretical foundation for the subsequent design and optimization of the Cyperus esculentus digging device.

A rapid, sensitive, selective, and accurate HPLC–MS/MS method was developed and validated for the simultaneous determination of chlorogenic acid, naucleactonin C, khaephuoside A 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside in rat plasma and tissues after oral administration of Nauclea officinalis extracts. Chloramphenicol was used as an internal standard (IS). The plasma and tissue samples were extracted by protein precipitation with methanol-ethyl acetate (1 : 1, v/v) including 0.1% (v/v) formic acid. The chromatographic separation was achieved by using an C18 column with gradient elution using mobile phase, which consisted of 0.1% formic acid water (A) and acetonitrile (B) and the flow rate of 0.8 mL/min. Mass spectrometric detection was performed in multiple reaction monitoring (MRM) mode utilizing electrospray ionization (ESI) in negative mode. The developed method exhibited good linearity (determination coefficients, R2 ≥ 0.9849), and the lower limits of quantification were 2, 5, 5, and 25 ng/mL for chlorogenic acid, naucleactonin C, khaephuoside A, and 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside. The intraday and interday precisions (relative standard deviation, RSD) were less than 12.65%, while the accuracy was ranged from 86.31 to 114.17%. The recovery rate were 51.85–97.06%, 75.99–106.68%, 77.46–105.35%, and 68.36–103.75% for chlorogenic acid, naucleactonin C, khaephuoside A, and 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside the matrix effects were 50.17–116.62%, 86.75–115.99%, 45.79–87.44%, and 51.60–92.34% for chlorogenic acid, naucleactonin C, khaephuoside A, and 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside in different matrix. The developed method was successfully applied to a pharmacokinetic study and tissue distribution of four compounds in rats after oral administration of Nauclea officinalis extracts.

The migration path of formation water plays an indispensable role in hydrocarbon accumulation and preservation. The hydrodynamic field controls the content of various ions in formation water and is an important participant in hydrocarbon evolution. Formation water can basically be used to judge the preservation status of oil/gas reservoirs, especially for carbonate reservoirs; the carbonate reservoirs are a typical example in the Gaoqiao area of the Ordos Basin, China. However, it is not easy to evaluate the sealing and integrity of the gas reservoir because hydrocarbon has experienced a multistage charging process and complicated later reconstruction. The geochemical characteristics of Ordovician formation water (100 brine samples from 67 wells in the Ma5 Member) are studied, and their chemical composition is analyzed in the Ordos Basin. The results show that formation water has high overall salinity and is the original sedimentary water of the carbonate reservoir, which is the sealing reservoir and can promote the accumulation of hydrocarbons. This is also associated with stronger water-rock reactions and diagenetic transformations, such as dolomitization. The main (TDS) range is from 40 to 150 g·L−1, with an average of 66.16 g·L−1; the Cl− content in the formation water samples is the highest, followed by Ca2+, Na+, Mg2+, HCO3−, and SO42−. In addition, the (Cl−-Na+)/Mg2+ ratio, Na+/Cl− ratio, Mg2+/Ca2+ ratio, and SO42−×100/Cl− ratio are closely related to gas preservation. The indication function between chemical parameters of formation water and hydrocarbon dynamics can be better understood in carbonate reservoirs by analogy study, so as to improve the accuracy of discriminating favorable hydrocarbon accumulation areas.

Mesenchymal stem cells (MSCs) are intrinsically heterogeneous and are comprised of distinct subpopulations that differ in their differentiation potential. A deeper understanding of the heterogeneity and intercellular communication within these heterogeneous subpopulations has significant implications for the potential of MSC-based therapy from the bench to the clinic. Here, we focused on the clonal osteogenic heterogeneity of periodontal ligament stem cells (PDLSCs) and explored how interclonal communication affects the osteogenic differentiation among these heterogeneous single-cell colonies (SCCs), and sought to determine the underlying mechanisms. Alkaline phosphatase (ALP) and Alizarin red staining identified the presence of SCCs with high (H-SCCs) and low osteogenic ability (L-SCCs). Conditioned medium derived from H-SCCs (H-CM) promoted mineralized nodule formation to a greater extent than that derived from L-SCCs (L-CM), which served as the target cells (TCs). However, treatment with the exosome biogenesis/release inhibitor GW4869 reduced the H-CM- and L-CM-related osteogenic differentiation-promoting potential. We further found that exosomes secreted by H-SCCs (H-Exo) were superior to those secreted by L-SCCs (L-Exo) in promoting the osteogenic differentiation of TCs. Mechanistically, TCs stimulated with H-CM and H-Exo exhibited higher levels of PINK1/Parkin-mediated mitophagy, while gain- and loss-of-function experiments showed that PINK1/Parkin-mediated mitophagy was positively associated with SCC osteogenic differentiation. Furthermore, PINK1 knock-down in H-Exo- and L-Exo-stimulated TCs inhibited their osteogenic differentiation through inhibiting PINK1/Parkin-mediated mitophagy. Our study uncovers a previously unrecognized mechanism that an exosome-mediated PINK1/Parkin-dependent mitophagy regulates interclonal communication among SCCs with osteogenic heterogeneity.

Currently, the mechanized harvesting method of Cyperus esculentus is mainly based on rotary excavation, but there are problems such as high working resistance, high damage rate, and high buried fruit rate in the working process. This paper focuses on the analysis of the movement trajectory of the positive-rotating and counter-rotating Cyperus esculentus excavation device, establishes a agglomerate model of soil-Cyperus esculentus tuber-Cyperus esculentus root system-mechanism, and conducts discrete element simulation tests on Cyperus esculentus agglomerates under different soil layers. According to Expert test optimization, the optimal structural parameters of the counter-rotating blade are determined: the radius of gyration is 151 mm, the inclination angle of the cutting edge is 42.5°, and the working width is 318 mm. The comparative test of the positive-rotating rotary tillage method under the optimal structural parameters shows that the working resistance is reduced by 11.25%, and the torque of the tool shaft is reduced by 16.11%, which proves that the designed anti-rotation excavation structure has the effect of reducing resistance. To further test the harvesting performance of the Cyperus esculentus excavation device, field harvesting tests were conducted, and the results showed that the buried fruit rate of the counter-rotating excavation device was reduced by 11.6%, and the damage rate was reduced by 6.1% year-on-year. This study shows that the design of the counter-rotating excavation device can further improve the harvesting performance of Cyperus esculentus based on reduced resistance harvesting and meet the requirements of Cyperus esculentus harvesting.

When peanuts are harvested, the high rate of pod crush and pods leakage are the main problems in the current peanut fruit picking process. Optimized peanut picking rollers help to improve peanut harvesting efficiency. This paper investigates the fruit picking system of a three-monopoly, six-row semi-feeding peanut combine harvester, in order to reduce the rate of crush and leakage of peanut pods during the picking process. Firstly, this article specifies the structure and basic parameters of peanut picking pairs of rollers. Secondly, this paper combines JKR (Johnson-Kendall-Roberts) model theory, crash model simulation analysis, a field test, and other methods. Motion and force analysis are presented in detail for the peanut picking mechanism and associated harvesting components. The optimum clamping chain speed, the angle of installation of the picking rollers to the clamping chain, and the picking rollers’ speed are determined. A three-factor, three-level regression orthogonal combination test was designed to obtain regression models for pod crushed and pods leakage rate. The regression model’s response surface analysis concluded that when the clamping chain speed is 0.84–1.2 m/s, the fruit picking roller angle is 10°–11.2° and the fruit picking roller speed is 442 r/min–500 r/min. It is the optimal working parameter for the three-monopoly six-row peanut combine harvester. At this point, the peanut harvesting requirements are met, and the overall performance is significantly improved. This paper lays the foundation for the development of the semi-feeding peanut picking system.

Circular RNAs (circRNAs) have been extensively elucidated with regard to their significant implications in oral squamous cell carcinoma (OSCC). This study performed the functional investigation of circRNA dehydrogenase E1 and transketolase domain containing 1 (circDHTKD1) in OSCC. RNA expression levels of different molecules were measured via quantitative real-time polymerase chain reaction (qRT-PCR). Cellular behaviors were detected by 3-(4, 5-dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide (MTT) for cell viability, colony formation assay for clonal capacity, flow cytometry for cell apoptosis, wound healing assay for migration, and transwell assay for migration/invasion. Western blot was used for analyzing protein expression. RNA pull-down and dual-luciferase reporter assays were applied to assess the binding between targets. A xenograft tumor model was established in nude mice for in vivo experiments. Our expression analysis revealed that circDHTKD1 was upregulated in OSCC tissues and cells. circDHTKD1 knockdown was shown to impede OSCC cell growth and metastasis but motivate apoptosis. Additionally, circDHTKD1 served as a microRNA-326 (miR-326) sponge and the function of circDHTKD1 was achieved by sponging miR-326 in OSCC cells. Also, miR-326 inhibited OSCC development via targeting GRB2-associated-binding protein 1 (GAB1). circDHTKD1 could sponge miR-326 to alter GAB1 expression. Furthermore, circDHTKD1 contributed to OSCC progression in vivo via the miR-326/GAB1 axis. These data disclosed a specific circDHTKD1/miR-326/GAB1 signal axis in governing the malignant progression of OSCC, showing the considerable possibility of circDHTKD1 as a predictive and therapeutic target for clinical diagnosis and treatment of OSCC.

Soil blocking and plant entanglement are the main challenges in Cyperus esculentus harvesting and excavating. The structure of the rotary blade is one of the critical factors affecting plant crushing and soil throwing performance. Inspired by the composite motion of longitudinal soil cutting and lateral soil throwing of the oriental mole cricket, a bionic rotary blade was designed with the contour curve of the excavation edge and excavation surface of its forefoot claw toe. The bionic rotary blade’s mechanical and kinematic analysis revealed its cutting mechanism. A flexible plant soil, bionic, rotary blade discrete element model was developed to simulate the Cyperus esculentus digging process. The optimal excavation edge and excavation surface were selected by a single factor experiment, and the optimal operating parameters of the bionic rotary blade were obtained by quadratic regression orthogonal rotational combination design. The results showed that the bionic rotary blade, based on the excavation edge and excavation surface of mole cricket first claw toe, had the longest throwing distance and the largest number of broken bonds. The best combination of operating parameters of the bionic rotary blade was 11.16 mm for blade spacing, 0.66 m/s for forward speed, and 300 rpm for shaft speed. The field experiment was carried out according to the best parameters. The results showed that the bionic rotary blade’s average soil throwing distance and plant crushing rate were 632.30 mm and 81.55%, respectively; thereby, not only meeting the requirements of Cyperus esculentus harvesting, but proving superior to the operation performance of the Chinese standard rotary blade IT245 and rotary blade with optimized cutting edge (IT245P). The results of this study can provide bionic design ideas and methods for the design of soil-cutting-based tillage machinery’s soil-engaging components, such as the rotary blade and returning blade.

Severe plant entanglement and high power consumption are the main problems of the up-cut rotary blade during Cyperus esculentus harvesting. Optimization of the rotary blade edge can enhance the soil-cutting and plant-crushing performance. In this study, the double-eccentric circle method was used to design the edge curve of the IT245 rotary blade. The edge curve’s dynamic sliding-cutting angle of equidistant points was analyzed to verify that the optimized rotary blade (IT245P) met the requirements of Cyperus esculentus harvesting. In order to accurately simulate the fragmentation of Cyperus esculentus plants after interaction with the rotary blade, the Hertz–Mindlin with Bonding contact model was selected to establish the flexible model of Cyperus esculentus plants. The plant–soil–rotary blade discrete element model was constructed to conduct simulation tests with power consumption and the plant-crushing ratio as evaluation indexes. The field experiment was carried out with tillage depth stability and power consumption as the experimental indexes. The results of the simulation test and field experiment showed that the power consumption of the IT245P rotary blade was reduced by 13.10%, and the plant-crushing rate was increased by 11.75% compared with the IT245 rotary blade. The optimal operating parameters were 1.08 m/s for forward speed, 107.11 mm for tillage depth, and 258.05 r/min for shaft speed. Under such a combination, the tillage depth stability and the power consumption were 94.63% and 42.35 kW. This study showed that a rotary blade with a double-eccentric circular curve could better realize plant-crushing and consumption reduction and meet the operation requirements of Cyperus esculentus and other Chinese medicinal materials’ harvesting.

Traditional plant disease diagnosis methods are mostly based on expert diagnosis, which easily leads to the backwardness of crop disease control and field management. In this paper, to improve the speed and accuracy of disease classification, a plant disease detection and classification method based on the optimized lightweight YOLOv5 model is proposed. We propose an IASM mechanism to improve the accuracy and efficiency of the model, to achieve model weight reduction through Ghostnet and WBF structure, and to combine BiFPN and fast normalization fusion for weighted feature fusion to speed up the learning efficiency of each feature layer. To verify the effect of the optimized model, we conducted a performance comparison test and ablation test between the optimized model and other mainstream models. The results show that the operation time and accuracy of the optimized model are 11.8% and 3.98% higher than the original model, respectively, while F1 score reaches 92.65%, which highlight statistical metrics better than the current mainstream models. Moreover, the classification accuracy rate on the self-made dataset reaches 92.57%, indicating the effectiveness of the plant disease classification model proposed in this paper, and the transfer learning ability of the model can be used to expand the application scope in the future.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by articular destruction and functional loss. Methotrexate (MTX) is effective in RA treatment. However, MTX induces several adverse events and 20%-30% of patients do not respond to MTX. Thus, it is urgent to enhance the therapeutic effects and reduce the side effects of MTX. Recent studies showed that mesenchymal stem cells (MSCs) were participants in anti-inflammation, immunoregulation, and tissue regeneration. However, whether the combined application of MSCs and MTX promotes the therapeutic effects and reduces the side effects of MTX has not been studied. In this study, we used bovine type II collagen to induce rheumatoid arthritis in mice (collagen-induced arthritis, CIA). Then, CIA mice were subjected to MTX or MSC treatment, or both. The therapeutic effect and adverse events of different treatments on RA were evaluated with micro-CT, HE staining, and immunohistochemistry in vivo. Apoptosis and proliferation of MODE-K cells were measured after treated with MTX or/and cocultured with UCs. To test M2 polarization, Raw264.7 macrophages were stimulated by MTX with different concentrations or cocultured with UCs. We found that the combined application of MSCs and MTX increased the therapeutic effects on RA, as evidenced by decreased arthritis score, inflammatory responses, and mortality. Moreover, in this combination remedy, MTX prefers to suppress inflammation by facilitating macrophage polarization to M2 type while UCs prefer to eliminate gastrointestinal side effects of MTX via mitigating the apoptosis of intestinal epithelial cells. Thus, a combination of MTX and UCs is a promising strategy for RA treatment.

Early orthodontic correction of skeletal malocclusion takes advantage of mechanical force to stimulate unclosed suture remodeling and to promote bone reconstruction; however, the underlying mechanisms remain largely unclear. Gli1+ cells in maxillofacial sutures have been shown to participate in maxillofacial bone development and damage repair. Nevertheless, it remains to be investigated whether these cells participate in mechanical force-induced bone remodeling during orthodontic treatment of skeletal malocclusion. In this study, rapid maxillary expansion (RME) mouse models and mechanical stretch loading cell models were established using two types of transgenic mice which are able to label Gli1+ cells, and we found that Gli1+ cells participated in mechanical force-induced osteogenesis both in vivo and in vitro. Besides, we found mechanical force-induced osteogenesis through inositol 1,4,5-trisphosphate receptor (IP3R), and we observed for the first time that inhibition of Gli1 suppressed an increase in mechanical force-induced IP3R overexpression, suggesting that Gli1+ cells participate in mechanical force-induced osteogenesis through IP3R. Taken together, this study is the first to demonstrate that Gli1+ cells in maxillofacial sutures are involved in mechanical force-induced bone formation through IP3R during orthodontic treatment of skeletal malocclusion. Furthermore, our results provide novel insights regarding the mechanism of orthodontic treatments of skeletal malocclusion.

Background The giant cell tumor (GCT) is a benign tumor which consists of three types cells: mononuclear histiocytic cells (MNHCs), multinuclear giant cells (MNGCs), and GCT stromal cells (GCTSCs). Numerous studies claim that GCTSCs have mesenchymal stem cells (MSCs) characters and play an important role in osteoclastogenesis; however, there are no research studies concerning macrophage polarization among GCT, which can be regarded as an ingredient for tumor aggression. Method We tested the effect of GCTSCs from three GCT samples which were collected from patients on proliferation, apoptosis and polarization of macrophage. Result In this article, we verified that GCTSCs expressed MSCs markers and had higher proliferation and relative lower differentiation abilities compared with BMMSCs. What’s more, we found a higher proportion of M2 macrophages among neoplasm. Co-culturing GCTSCs with macrophages resulted in prominent macrophage M2 polarization and increased the release of IL-6 (Interleukin-6) and IL-10 (Interleukin-10)from GCTSCs. In conclusion, GCTSCs, as originating from MSCs, can secret IL-6 and IL-10, which may play a significant role in macrophage M2 polarization.

Abstract Inflammatory microenvironment causes the change of epigenetic modification in periodontal ligament stem cells derived from periodontitis tissues (P-PDLSCs), which results in defective osteogenic differentiation compared to cells from healthy tissues. It’s urgent to explore therapeutic strategies aimed at epigenetic targets associated with the regenerative ability of PDLSCs. Osthole, a small-molecule compound extracted from Chinese herbs, has been documented to promote osteogenesis and cell sheets formation of healthy PDLSCs. However, whether osthole shows same effect on P-PDLSCs and the mechanism of promotive effect is still unknown. The purpose of this study was to determine whether Osthole could restore defective osteogenic differentiation of P-PDLSCs via epigenetic modification. We demonstrated that 10−7 Mol/L of Osthole was the best concentration for osteogenic differentiation and proliferation of P-PDLSCs. Mechanistically, we also found that Osthole upregulated MOZ and MORF, histone acetylases that specifically catalyze acetylation of Histone3 lisine9 (H3K9) and Histone3 lisine14 (H3K14), which are key regulators in osteogenic differentiation of P-PDLSCs. Furthermore, Osthole treatment improved cell sheet formation and enhanced the bone formation of PDLSC sheets in animal models of periodontitis. Our study suggests that Osthole is a promising drug to cure periodontitis via regulating epigenetic modification in cell sheets engineering.

Background Rheumatoid arthritis (RA) is a chronic and nonspecific autoimmune disease, which leads to joint destruction and deformity. To investigate the potential of human mesenchymal stem cells (MSCs) as a new therapeutic strategy for patients with RA, we compared the therapeutic effects of bone marrow derived MSCs (BMSCs), umbilical cord derived MSCs (UCs), and stem cells derived from human exfoliated deciduous teeth (SHED) on collagen-induced arthritis (CIA) in mice. Methods A total of 24 DBA/1 mice were infused with type II collagen to induce RA in the experimental model. MSC-treated mice were infused with UCs, BMSCs, and SHED, respectively. Bone erosion and joint destruction were measured by micro-computed tomographic (micro-CT) analysis and hematoxylin and eosin staining. The levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were measured by immunohistochemistry and Enzyme-Linked Immunosorbent Assay (ELISA). Results Systemic delivery of MSCs significantly improved the severity of the symptoms related to CIA to greater extent compared with the untreated control group. Micro-CT revealed reduced bone erosions in the metatarsophalangeal joints upon treatment with MSCs. Additionally, according to histologic evaluation, reduced synovitis and articular destruction were observed in MSC-treated groups. The levels of TNF-α and IL-1β in the serum and joints decreased with treatment by MSCs. Conclusion Our findings suggest that systemic infusion of UCs, BMSCs, and SHED may significantly alleviate the effects of RA. The therapeutic effect of BMSCs was greater than that of SHED, while the UCs were shown to have the best therapeutic effect on CIA mice. In conclusion, compared with BMSCs and SHED, UCs may be a more suitable source of MSCs for the treatment of patients with RA.

Primary cilia are highly conserved microtubule-based organelles that play essential roles in several cellular processes including osteogenesis. Here the authors show that intraflagellar protein IFT80 regulates osteoblast differentiation by balancing signalling though the canonical and non-canonical Hedgehog pathways.

Mesenchymal stem cell transplantation (MSCT) promotes cutaneous wound healing. Numerous studies have shown that the therapeutic effects of MSCT appear to be mediated by paracrine signaling. However, the cell-cell interaction during MSCT between MSCs and macrophages in the region of cutaneous wound healing is still unknown. In this study, early depletion of macrophages delayed the wound repair with MSC injection, which suggested that MSC-mediated wound healing required macrophages. Moreover, we demonstrated that systemically infused bone marrow MSCs (BMMSCs) and jaw bone marrow MSCs (JMMSCs) could translocate to the wound site, promote macrophages toward M2 polarization, and enhance wound healing. In vitro coculture of MSCs with macrophages enhanced their M2 polarization. Mechanistically, we found that exosomes derived from MSCs induced macrophage polarization and depletion of exosomes of MSCs reduced the M2 phenotype of macrophages. Infusing MSCs without exosomes led to lower number of M2 macrophages at the wound site along with delayed wound repair. We further showed that the miR-223, derived from exosomes of MSCs, regulated macrophage polarization by targeting pknox1. These findings provided the evidence that MSCT elicits M2 polarization of macrophages and may accelerate wound healing by transferring exosome-derived microRNA.

Limited data exists in China on the comparative cost of gadolinium ethoxybenzyl diethylenetriamine magnetic resonance imaging (Gd-EOB-DTPA-MRI) with other imaging techniques. This study compared the total cost of Gd-EOB-DTPA-MRI with multidetector computed tomography (MDCT) and extracellular contrast media-enhanced MRI (ECCM-MRI) as initial imaging procedures in patients with suspected hepatocellular carcinoma (HCC). We developed a decision-tree model on the basis of the Chinese clinical guidelines for HCC, which was validated by clinical experts from China. The model compared the diagnostic accuracy and costs of alternative initial imaging procedures. Compared with MDCT and ECCM-MRI, Gd-EOB-DTPA-MRI imaging was associated with higher rates of diagnostic accuracy, i.e. higher proportions of true positives (TP) and true negatives (TN) with lower false positives (FP). Total diagnosis and treatment cost per patient after the initial Gd-EOB-DTPA-MRI evaluation was similar to MDCT (¥30,360 vs. ¥30,803) and lower than that reported with ECCM-MRI (¥30,360 vs. ¥31,465). Lower treatment cost after initial Gd-EOB-DTPA-MRI was driven by reduced utilization of confirmatory diagnostic procedures and unnecessary treatments. The findings reported that Gd-EOB-DTPA-MRI offered higher diagnostic accuracy compared with MDCT and ECCM-MRI at a comparable cost, which indicates Gd-EOB-DTPA-MRI could be the preferred initial imaging procedure for the diagnosis of HCC in China.

Indium thin oxide (ITO)-free planar perovskite solar cells (PSCs) were fabricated at a low temperature (150 °C) in this work based on the transparent electrode of photolithography processed nickel/gold (Ni/Au) mesh and the high conductivity polymer, PH1000. Ultrathin Au was introduced to increase the conductivity of metal mesh, and the optimal hexagonal Ni (30 nm)/Au (10 nm) mesh (line width of 5 μm) shows a transmittance close to 80% in the visible light region and a sheet resistance lower than 16.9 Ω/sq. The conductive polymer PH1000 not only smooths the raised surface of the metal mesh but also enhances the charge collection ability of metal mesh. The fabricated PSCs have the typical planar structure (glass/Ni-Au mesh/PH1000/PEDOT:PSS/MAyFA1−yPbIxCl3−x/PCBM/BCP/Ag) and the champion PSC (0.09 cm2) obtains a power conversion efficiency (PCE) of 13.88%, negligible current hysteresis, steady current density and PCE outputs, and good process repeatability. Its photovoltaic performance and stability are comparable to the reference PSC based on the ITO electrodes (PCE = 15.70%), which demonstrates that the Ni/Au mesh transparent electrodes are a promising ITO alternative to fabricate efficient PSCs. The relatively lower performance of Ni/Au based PSC results from the relatively slower charge extraction and stronger charge recombination than the ITO based PSC. Further, we tried to fabricate the large area (1 cm2) device and achieve a PCE over 6% with negligible hysteresis and steady current density and PCE outputs. The improvements of perovskite film quality and interface modification should be an effective approach to further enhance the device performance of Ni/Au based PSCs, and the Ni/Au mesh electrode may find wider applications in PSCs and flexible devices.

In this study, we designed a chitosan/alginate/hydroxyapatite scaffold as a carrier for recombinant BMP-2 (CAH/B2), and evaluated the release kinetics of BMP-2. We evaluated the effect of the CAH/B2 scaffold on the viability and differentiation of bone marrow mesenchymal stem cells (MSCs) by scanning electron microscopy, MTS, ALP assay, alizarin-red staining and qRT-PCR. Moreover, MSCs were seeded on scaffolds and used in a 8 mm rat calvarial defect model. New bone formation was assessed by radiology, hematoxylin and eosin staining 12 weeks postoperatively. We found the release kinetics of BMP-2 from the CAH/B2 scaffold were delayed compared with those from collagen gel, which is widely used for BMP-2 delivery. The BMP-2 released from the scaffold increased MSC differentiation and did not show any cytotoxicity. MSCs exhibited greater ALP activity as well as stronger calcium mineral deposition, and the bone-related markers Col1α, osteopontin, and osteocalcin were upregulated. Analysis of in vivo bone formation showed that the CAH/B2 scaffold induced more bone formation than other groups. This study demonstrates that CAH/B2 scaffolds might be useful for delivering osteogenic BMP-2 protein and present a promising bone regeneration strategy.