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Abstract Purpose To determine the optimal angles for independent femoral tunnel drillings in single-bundle anterior cruciate ligament reconstruction (ACLR) in different races and genders with the aim of preventing damage to lateral femoral anatomic structures (LFAS), posterior cortex and medial femoral condyle. Methods This study included 180 volunteers, including 90 Caucasian and 90 matched Chinese. Magnetic resonance imaging (MRI) was used to scan the knees to create three-dimensional bone models, the ACL femoral footprint centre and the LFAS. In each femur model, femoral tunnels were established using a set of 16 distinct angular combinations: 15°, 30°, 45°, and 60° in the axial plane, as well as 15°, 30°, 45°, and 60° in the coronal plane. The minimum distance from the tunnel exit to the LFAS was evaluated, and the tunnel length, posterior cortex damage and medial femoral condyle injury were assessed. Results Among the 180 patients with simulated ACL femoral tunnels, there was damage to the anatomical structure in parts of the model. According to the Cochran Q test results (P

Objective Cartilage and meniscus are important structures that maintain the health of the knee joint. Early detection of changes in the internal components of cartilage and meniscus before morphological changes occur is essential to prevent and delay the development of osteoarthritis (OA). This study was designed to determine the changes in the matrix composition of morphologically intact cartilage and meniscus during the acute phase of an anterior cruciate ligament (ACL) rupture, as well as the effect of different states of meniscus (intact or tear) on adjacent cartilage during the acute phase. Methods This cross‐sectional study compared and analyzed 50 patients in the acute phase of ACL rupture who underwent surgical treatment and 66 age‐, weight‐ and height‐matched healthy volunteers from May 2022 to May 2023 at our institution. Mean T2 relaxation times and effect sizes in different regions of tibiofemoral articular cartilage and meniscus were compared between the two groups using the Mann–Whitney nonparametric t‐test, and correlations between different meniscal states and adjacent cartilage were analyzed. Results Both in the lateral and medial compartments of the knee, T2 relaxation times were significantly higher in all subregions of cartilage and meniscus in the ACL rupture group (p

Abstract Background 99mTc-DMSA scan plays an important role in assessing functional abnormalities in kidneys. As a promising network for deep learning (DL), Mask R-CNN has the capability of simultaneously segmenting and classifying objects in images. In this study, we tested the feasibility and accuracy of Mask R-CNN in diagnosing acute pyelonephritis (APN) and segmenting kidneys in 99mTc-DMSA scintigraphic images. Two hundred and sixty patients with suspected APN were recruited for DMSA scan, of which 358 kidneys were diagnosed as APN. Of the recruited patients, 210 were randomly selected for training and validating Mask R-CNN, and the other 50 patients’ images were used for model testing. Accuracy of the results was assessed by comparing against references from human experts. Results In the validation phase, the trained model provided segmentation masks with intersection over union (mask IoU, for segmentation accuracy) of 86.6%, and classifications with mean average precision at the bounding box IoU ≥ 50% (mAP50, for classification accuracy) of 86.2%. In testing with the 50 independent patients, mask IoU of the model’s segmentation was 90.3%±2.2%, and in classifying the kidneys for APN, the trained model showed accuracy of 89.0%, sensitivity of 84.8% and specificity of 97.0%. In identifying patients with any APN kidney, 3 out of 50 patients were mis-diagnosed, achieving accuracy of 94.0%. Conclusions Mask R-CNN, designed to perform both segmentation and classification for images, showed much promise in analyzing 99mTc-DMSA images for both accurate diagnosis of APN and kidney segmentation.

The treatment of COVID-19 in the post-transplant individuals is challenging, primarily due to the drug-drug interaction between nirmatrelvir/ritonavir and tacrolimus. Deuremidevir hydrobromide tablets (VV116) is an orally small molecule agents target SARS-CoV-2 RdRp and inhibits viral replication. It may have a low likelihood of drug-drug interactions and has a potential to provide new treatment option. We described three cases of renal transplant patients with concomitant impaired renal function who developed COVID-19 pneumonia and were treated with VV116. Despite varying degrees of drug accumulation, these patients achieved rapid viral clearance and showed prompt improvement in pneumonia symptoms. Notably, tacrolimus blood concentrations remained within the therapeutic range throughout treatment, and no clinically significant adverse events were observed despite the drug accumulation.

AimWe aimed to systematically assess whether the level of body roundness index (BRI) is associated with the risk of developing chronic kidney disease (CKD) in US adults.MethodsThe studied data was extracted from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. A total of 29,062 participants aged ≥20 years with complete information about BRI and CKD were included in this study. Logistic regression analysis, multivariate linear regression analysis, restricted cubic spline (RCS) plots curve, stratified analysis and receiver operating characteristic (ROC) curve were performed to investigate the association between BRI and CKD.ResultsA total of 29,062 patients were included, involving 4,623 individuals with CKD and 24,439 individuals without CKD. A higher BRI level was substantially related to an increased prevalence of CKD in US adults. After adjusting for confounding variables, the BRI in the fourth quartile was correlated to a higher CKD prevalence (OR: 1.36; 95% CI: 1.10–1.70) compared to the lowest quartile. After adjusting for confounding variables, the BRI in the fourth quartile was correlated to a higher CKD prevalence (OR: 1.36; 95% CI: 1.10–1.70) compared to the lowest quartile. However, in the subgroup analysis stratified by race and body mass index (BMI), no significant associations between BRI and CKD were observed among Mexican participants (OR: 1.10; 95% CI: 0.98–1.23) and those with underweight or normal weight (OR: 0.95; 95% CI: 0.81–1.05). Moreover, a non-linear relationship was found between BRI and the prevalence of CKD. In ROC analysis, BRI demonstrated higher discriminating for CKD (area under the curve: 0.6247; 95% CI: 0.6161–0.6333; optimal cutoff value: 5.161) compared with other indices.ConclusionIn summary, BRI was independently associated with a higher prevalence of CKD in overweight and obese US adults, excluding Mexican. This may be an important therapeutic target and predictor of CKD. Physicians should advise patients with high BRI scores, especially overweight and obese patients, to embrace healthy lifestyle changes, such as maintaining a balanced diet and engaging in regular physical activity. These changes can help them control their body weight and reduce abdominal fat, ultimately lowering the risk of CKD.

Abstract The repair of diabetic wound still encounters huge challenges, such as disordered inflammatory regulation and impaired neovascularization. Here, a pH/ROS/glucose responsive and photothermal hydrogel is developed for diabetic wound healing. The hydrogel is formed through cross‐linkage between phenylboronic acid‐modified carboxymethyl chitosan (CMCS‐PBA) and oxide dextran (OXD), utilizing Schiff base and phenylboronate ester bonds. Additionally, insulin‐like growth factor 1 C domain (IGF‐1C) and deferoxamine‐loaded polydopamine nanoparticles (D@P) are incorporated into the hydrogel. The hydrogel demonstrates sustained drug release, excellent photo thermal effect, prominent antioxidant, antibacterial and anti‐inflammatory activities, desirable mechanical and tissue adhesive properties, enhanced tube formation, and cell migration. Furthermore, the hydrogel combined with mild heat treatment can regulate chronic inflammation by promoting the transformation of macrophages from M1 phenotype to M2 phenotype and enhance angiogenesis by up‐regulating the expression levels of angiogenesis‐related factors such as hypoxia‐inducible factor‐1 alpha (HIF‐1α), vascular endothelial growth factor (VEGF), CD31, and α‐SMA, thus greatly accelerates the wound healing in streptozotocin (STZ)‐induced diabetic mice. Therefore, this multi‐responsive and multifunctional hydrogel holds potential as a therapeutic strategy for diabetic wounds.

Abstract Background With the conflict between the promise of ageing in health and longevity and the limited availability of health resources and social support, older adults in China inevitably experience anxieties surrounding health risks. This study aims to investigate how older adults perceive the health risks that come with getting older, explore the degree to which health risks affect older adults, and advocate for active engagement in practices for managing health risks. Methods Using purposive sampling, three districts of Beijing (Xicheng District, Fengtai District, and Daxing District, respectively) were selected for the research. Qualitative semi-structured and in-depth interviews were conducted with 70 community-dwelling older adults who participated in the study. Data were extracted and analyzed based on a thematic framework approach. Results Three main themes were identified: (i) the anxieties of older adults concerning health risks in ageing; (ii) the priorities of older adults for health risk management in ageing; (iii) the expectations of older adults for health risk management in ageing. The primary health concerns among older adults included disease incidence and function decline. It was found that basic health management emerged as a critical need for older adults to mitigate health risks. Moreover, it was observed that healthcare support for older adults from familial, institutional, and governmental levels exhibited varying degrees of inadequacy. Conclusions The primary source of anxieties among older adults regarding health risks predominantly stems from a perceived sense of health deprivation. It is often compounded by persistent barriers to primary care of priorities in managing health risks among older adults. In addition, the expectations of older adults for health risk management emphasize the necessity for integrated care approaches. Therefore, further research should give priority to the prevention and management of health risks, aim to reduce anxieties, provide integrated care to meet the primary needs and expectations of older adults, and ultimately strive toward the overarching goal of promoting health and longevity.

Abstract Purpose To determine whether posterior cruciate ligament (PCL) buckling (angular change) is associated with anterior cruciate ligament (ACL) status (intact or ruptured), meniscal bone angle (MBA), anterior tibial translation (ATT), body weight, femoral-tibial rotation (FTR), posterior tibial slope (PTS), PCL length and femoral-tibial distance (FTD) and to identify the factors that have the greatest influence. Methods All enrolled participants were scanned with a 3.0 T, 8-channel coil MRI system (Magnetom Verio; Siemens). Bone and soft tissue parameters were measured by MIMICS software for each subject and each measured parameter was correlated with PCL buckling phenomena. The correlated and statistically significant parameters were then analyzed by multiple linear regression to determine the magnitude of the effect of the different parameters on the PCL buckling phenomenon. Results A total of 116 subjects (50 ACL ruptured and 66 age, weight and height matched volunteers with uninjured knees) were enrolled. Among all measured parameters, there were 8 parameters that correlated with PCL angle (PCLA), of which ACL status had the strongest correlation with PCLA (r = − 0.67, p =

Abstract Total amount of creatine (Cr) and phosphocreatine, or total creatine (tCr), may have a significant impact on the performance of skeletal muscles. In sports such as bodybuilding, it is popular to take Cr supplements to maintain tCr level. However, no study has explored the quantitative relationship between exercise intensity and the induced change in muscle's tCr. In this well‐controlled study, straight‐leg plantar flexion with specific load and duration was performed by 10 healthy subjects inside an MRI scanner, immediately followed by 1H MR spectroscopy (MRS) for measuring tCr concentration in gastrocnemius. For repeatability assessment, the experiment was repeated for each subject on two different days. Across all the subjects, baseline tCr was 46.6 ± 2.4 mM, ranging from 40.6 to 50.1 mM; with exercise, tCr significantly decreased by 10.9% ± 1.0% with 6‐lb load and 21.0% ± 1.3% with 12‐lb load (p

Abstract Effective therapeutic targets and early diagnosis are major challenges in the treatment of gastrointestinal tract (GIT) cancers. SALL4 is a well-known transcription factor that is involved in organogenesis during embryonic development. Previous studies have revealed that SALL4 regulates cell proliferation, survival, and migration and maintains stem cell function in mature cells. Additionally, SALL4 overexpression is associated with tumorigenesis. Despite its characterization as a biomarker in various cancers, the role of SALL4 in GIT cancers and the underlying mechanisms are unclear. We describe the functions of SALL4 in GIT cancers and discuss its upstream/downstream genes and pathways associated with each cancer. We also consider the possibility of targeting these genes or pathways as potential therapeutic options for GIT cancers.

There has been significant attention from both academics and industries towards the demand for high-strength and crack-free cementitious composites. Nanofibers are a group of promising reinforcement materials due to their high strength, large specific surface area, and high toughness. This paper provides a review of the fracture properties of nanofiber reinforced cement-based composite (NFRC), including the investigation of various types of nanofibers available in the market, test methods, and theoretical analysis models. The effects of different volumes and types of nanofibers are also summarised. Based on the analysis of previous studies, the enhancements in fracture properties are closely associated with the length and aspect ratio of nanofibers. Moreover, several challenges persist in the practical application of NFRC in industries are discussed. Further research efforts are required to address these concerns and advance the industrial application of NFRC.

Esophageal squamous cell carcinoma (ESCC), the most common pathological type of esophageal cancer, is one of the leading causes of cancer death worldwide, but an effective therapeutic avenue is still absent. This study was to evaluate the therapeutic effect of Agaricus blazei Murrill polysaccharides (ABP) and Enteromorpha prolifera polysaccharides (EP) on ESCC. The results showed that both ABP and EP have therapeutic effects on multiple malignant processes of ESCC, such as proliferation, migration, invasion, and apoptosis, in vitro. Moreover, both ABP and EP retard tumor growth in vivo and the growth of ESCC-derived organoids. A series of genes and proteins changed upon treatments with ABP and EP after RNA sequencing and proteomics analysis. Autophagy, mitophagy and ferroptosis were enriched after treatments with these two polysaccharides, suggesting that the consumption of ABP and EP may represent a promising dietary supplement for ESCC therapy.

Abstract Background Kawasaki disease (KD) is an autoimmune disease with cardiovascular disease as its main complication, mainly affecting children under 5 years old. KD treatment has made tremendous progress in recent years, but intravenous immunoglobulin (IVIG) resistance remains a major dilemma. Bibliometric analysis had not been used previously to summarize and analyze publications related to IVIG resistance in KD. This study aimed to provide an overview of the knowledge framework and research hotspots in this field through bibliometrics, and provide references for future basic and clinical research. Methods Through bibliometric analysis of relevant literature published on the Web of Science Core Collection (WoSCC) database between 1997 and 2023, we investigated the cooccurrence and collaboration relationships among countries, institutions, journals, and authors and summarized key research topics and hotspots. Results Following screening, a total of 364 publications were downloaded, comprising 328 articles and 36 reviews. The number of articles on IVIG resistance increased year on year and the top three most productive countries were China, Japan, and the United States. Frontiers in Pediatrics had the most published articles, and the Journal of Pediatrics had the most citations. IVIG resistance had been studied by 1889 authors, of whom Kuo Ho Chang had published the most papers. Conclusion Research in the field was focused on risk factors, therapy (atorvastatin, tumor necrosis factor‐alpha inhibitors), pathogenesis (gene expression), and similar diseases (multisystem inflammatory syndrome in children, MIS‐C). “Treatment,” “risk factor,” and “prediction” were important keywords, providing a valuable reference for scholars studying this field. We suggest that, in the future, more active international collaborations are carried out to study the pathogenesis of IVIG insensitivity, using high‐throughput sequencing technology. We also recommend that machine learning techniques are applied to explore the predictive variables of IVIG resistance.

Changes in olfactory function are considered to be early biomarkers of Parkinson’s disease. Olfactory dysfunction is one of the earliest non-motor features of Parkinson’s disease, appearing in about 90% of patients with early-stage Parkinson’s disease, and can often predate the diagnosis by years. Therefore, olfactory dysfunction should be considered a reliable marker of the disease. However, the mechanisms responsible for olfactory dysfunction are currently unknown. In this article, we clearly explain the pathology and medical definition of olfactory function as a biomarker for early-stage Parkinson’s disease. On the basis of the findings of clinical olfactory function tests and animal model experiments as well as neurotransmitter expression levels, we further characterize the relationship between olfactory dysfunction and neurodegenerative diseases as well as the molecular mechanisms underlying olfactory dysfunction in the pathology of early-stage Parkinson’s disease. The findings highlighted in this review suggest that olfactory dysfunction is an important biomarker for preclinical-stage Parkinson’s disease. Therefore, therapeutic drugs targeting non-motor symptoms such as olfactory dysfunction in the early stage of Parkinson’s disease may prevent or delay dopaminergic neurodegeneration and reduce motor symptoms, highlighting the potential of identifying effective targets for treating Parkinson’s disease by inhibiting the deterioration of olfactory dysfunction.

This paper investigates a reconfigurable intelligent surface (RIS)-assisted unmanned aerial vehicle (UAV)-enabled wireless powered communication network (WPCN). In the system, a UAV acts as a hybrid access point (HAP) to charge users in the downlink (DL) and receive messages in the uplink (UL). In particular, the RIS is exploited to significantly enhance the efficiency of both the DL and UL transmission. Our objective is to enhance the minimum throughput among all ground users by jointly optimizing the horizontal location of UAVs, the transmit power of users, transmission time allocation, and passive beamforming vectors at the RIS. To address this problem, we present an alternating optimization-based algorithm with low complexity to decompose the problem into four subproblems and solve them sequentially. In particular, we derive a lower bound of the composite channel gain to tighten the constraints and employ successive convex approximation (SCA) to optimize the horizontal location of the UAV. The transmit power closed-form optimum solutions are then obtained, and the problem of time allocation is reformulated as a linear programming problem. Finally, we optimize the passive beamforming vectors by adopting semi-definite relaxation (SDR). The effectiveness of the algorithm is supported by numerical results, which also demonstrate that the RIS-assisted UAV-enabled WPCN outperforms the traditional WPCN in terms of the minimum throughput.

Abstract The polyionic liquid poly-PEGMA-r-METAC (PPM) with quaternary ammonium has been synthesized and evaluated as additive in aqueous lubricating fluids. The rheological behavior of aqueous lubricating fluids with PPM has been characterized to confirm PPM’s function as a viscosity modifier. The tribological behavior of aqueous lubricating fluids with PPM has been investigated on SRV-V and MTM testing machines. It was found that PPM has excellent viscosity-increasing, lubricating, and anti-wear properties as an additive for aqueous, which can be attributed to the ability of PPM to form the protective film and boundary tribofilm generated from complex tribochemical reaction on rubbing surface. The obtained PPM with dual functions of anti-corrosion additives and viscosity index improver can play an important role in diverse lubrication regimes.

Currently, urban renovation activities in China are booming. And promoting the renovation of public buildings is a key feature of urban renovation due to its large scale, high cost, and significant impact to the natural and social environment. To reduce the ambiguity and uncertainty in evaluating the potential for the renovation of existing public buildings, a renovation potential evaluation model integrating a game theory-based combination weighting method and cloud model theory is proposed. This paper constructs a comprehensive evaluation index system based on relevant standards and the literature. Game theory is used to optimize the weights obtained by AHP and entropy weight methods to obtain a combined weight. MATLAB programming is used to calculate the comprehensive cloud parameters of the evaluation index for the potential renovation of existing public buildings and therefore generate cloud Graphs. Through a case study in Nanjing, China, it was demonstrated that the combination weight cloud model can objectively reflect the relationship between the fuzziness and randomness of evaluation indicators for public building renovation potential. The visual expression of cloud Graphs can intuitively reflect the magnitude of renovation and renovation potential and the degree of uncertainty in evaluation results. The research result provides useful references for the sustainable utilization of building resources in the era of building.

Due to their lightweight characteristics, spatial thin-film structures can generate vibrations far exceeding their film thickness when subjected to external loads, which has become a key factor limiting their performance. This study examines the vibration characteristics of tensioned membrane structures with non-uniform elements subjected to impacts in air, leveraging the Absolute Nodal Coordinate Formulation (ANCF). This model takes into account the wrinkling deformation of thin films under pre-tension and incorporates it into the dynamic equation derived using the absolute node coordinate method. A detailed discussion was conducted on the influence of non-uniform elements, situated at different locations and side lengths, on the vibration characteristics of the thin film. The analytical results obtained from the vibration model were compared with the experimental results, validating the effectiveness of the vibration model. This provides a theoretical foundation for the subsequent vibration control of thin films.

Background: Lower urinary tract (LUT) symptoms are reported in more than 80% of patients with multiple sclerosis (MS), most commonly an overactive bladder (OAB). The relationship between brain white matter (WM) changes in MS and OAB symptoms is poorly understood. Objectives: We aim to evaluate (i) microstructural WM differences across MS patients (pwMS) with OAB symptoms, patients without LUT symptoms, and healthy subjects using diffusion tensor imaging (DTI), and (ii) associations between clinical OAB symptom scores and DTI indices. Methods: Twenty-nine female pwMS [mean age (SD) 43.3 years (9.4)], including seventeen with OAB [mean age (SD) 46.1 years (8.6)] and nine without LUT symptoms [mean age (SD) 37.5 years (8.9)], and fourteen healthy controls (HCs) [mean age (SD) 48.5 years (20)] were scanned in a 3T MRI with a DTI protocol. Additionally, clinical scans were performed for WM lesion segmentation. Group differences in fractional anisotropy (FA) were evaluated using tract-based spatial statistics. The Urinary Symptom Profile questionnaire assessed OAB severity. Results: A statistically significant reduction in FA (p = 0.004) was identified in microstructural WM in pwMS, compared with HCs. An inverse correlation was found between FA in frontal and parietal WM lobes and OAB scores (p = 0.021) in pwMS. Areas of lower FA, although this did not reach statistical significance, were found in both frontal lobes and the rest of the non-dominant hemisphere in pwMS with OAB compared with pwMS without LUT symptoms (p = 0.072). Conclusions: This study identified that lesions affecting different WM tracts in MS can result in OAB symptoms and demonstrated the role of the WM in the neural control of LUT functions. By using DTI, the association between OAB symptom severity and WM changes were identified, adding knowledge to the current LUT working model. As MS is predominantly a WM disease, these findings suggest that regional WM involvement, including of the anterior corona radiata, anterior thalamic radiation, superior longitudinal fasciculus, and superior frontal-occipital fasciculus and a non-dominant prevalence in WM, can result in OAB symptoms. OAB symptoms in MS correlate with anisotropy changes in different white matter tracts as demonstrated by DTI. Structural impairment in WM tracts plays an important role in LUT symptoms in MS.

Morphing wingtips have the potential to improve aircraft performance. By connecting the wingtips and the wings with a compliant structure, a continuous aerodynamic surface can be achieved for a better aerodynamic performance. However, how to maintain the shape-changing capability while keeping a high stiffness to carry aerodynamic loads is a key problem. In this paper, based on asymmetric stiffness, a type of single-row corrugated panel is designed to satisfy the limited space around the wingtip. A finite element model of the single-row corrugated panels is established, and parameter analysis is performed to investigate the impact of the thickness characteristics of the corrugated panel on the folding angle. The corrugated panel is then optimised to find the maximum folding angle. Based on the optimisation results, corrugated panels with asymmetric and symmetric stiffness are fabricated and tested. The results demonstrate that the asymmetric stiffness corrugated panels have the capability to increase the wingtip folding angle.

Abstract Emerging evidence indicates that SOX2 is an oncogene for esophageal squamous cell carcinoma (ESCC). However, direct targeting of SOX2 is not feasible given that this transcription factor plays important roles in the maintenance of tissues such as the brain. Here, we identified CDP (Homeobox protein cut-like 1 or CASP) as a unique SOX2 binding partner enriched in ESCC with Duolink proximity ligation assay, bimolecular fluorescence complementation (BiFc) and immunoprecipitation. We then screened a peptide aptamer library using BiFc and immunoprecipitation and identified several peptide aptamers, including P58, that blocked the CDP/SOX2 interaction, leading to the inhibition of ESCC progress in vitro and in vivo. Upon administration, synthetic peptide P58, containing the YGRKKRRQRRR cell-penetrating peptide and the fluorophore TAMRA, also blocked the growth and metastasis of ESCC in both mice and zebrafish. Therefore, targeting the SOX2 binding partner CDP with peptide P58 offers an alternative avenue to treat ESCC with increased SOX2 levels.

Dyslipidemia has long been implicated in elevating mortality risk; yet, the precise associations between lipid traits and mortality remained undisclosed. Our study aimed to explore the causal effects of lipid traits on both all-cause and cause-specific mortality. One-sample Mendelian randomization (MR) with linear and nonlinear assumptions was conducted in a cohort of 407,951 European participants from the UK Biobank. Six lipid traits, consisting of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a), were included to investigate the causal associations with mortality. Two-sample MR was performed to replicate the association between each lipid trait and all-cause mortality. Univariable MR results showed that genetically predicted higher ApoA1 was significantly associated with a decreased all-cause mortality risk (HR[95% CI]:0.93 [0.89–0.97], P value = 0.001), which was validated by the two-sample MR analysis. Higher lipoprotein(a) was associated with an increased risk of all-cause mortality (1.03 [1.01–1.04], P value = 0.002). Multivariable MR confirmed the direct causal effects of ApoA1 and lipoprotein(a) on all-cause mortality. Meanwhile, nonlinear MR found no evidence for nonlinearity between lipids and all-cause mortality. Our examination into cause-specific mortality revealed a suggestive inverse association between ApoA1 and cancer mortality, a significant positive association between lipoprotein(a) and cardiovascular disease mortality, and a suggestive positive association between lipoprotein(a) and digestive disease mortality. High LDL-C was associated with an increased risk of cardiovascular disease mortality but a decreased risk of neurodegenerative disease mortality. The findings suggest that implementing interventions to raise ApoA1 and decrease lipoprotein(a) levels may improve overall health outcomes and mitigate cancer and digestive disease mortality.

Objective: To analyse the research history, development trends and current status of relevant literature in the field of Kawasaki disease, and to provide the basis for future directions in Kawasaki disease (KD) research. Methods: Literature on Kawasaki disease published between January 1974 and December 2022 was searched for in the Web of Science database, and CiteSpace was used to perform visual analyses. Results: The search yielded a total of 6950 articles. The number of publications related to Kawasaki disease showed an increasing trend. A collaborative network analysis revealed that the United States, Japan and mainland China were the most influential countries in this field. The University of California system contributed the most publications and the journal with the most publications was Circulation. JW Newburger was an authoritative author in this field. “Coronary artery lesion”, “Intravenous immunoglobulin” (IVIG) and “Risk factor” were three prominent keywords. Keyword bursts changed from “TNF” and “IVIG”, which focused on aetiology and treatment, to “Long term management”, which emphasized the recovery period, and to “Kawasaki-like disease” and “Multisystem inflammatory syndrome” during the novel coronavirus pandemic. Trends of highly cited references indicated that landmark articles in different periods focused on Kawasaki disease guidelines, gene polymorphisms and multisystem inflammatory syndrome caused by the novel coronavirus. Conclusion: The aetiology of Kawasaki disease remains unclear, but viral infection is likely to play an important role. The combination of evolving sequencing technologies, large-scale epidemiological investigations and prospective cohort studies is likely to be important in exploring Kawasaki disease and improving its prognosis in future.

BackgroundOlder patients with cancer experience cognitive impairment and a series of neurocognitive symptoms known as chemobrain due to chemotherapy. Moreover, older populations are disproportionately affected by chemobrain and heightened negative mental health outcomes after cytotoxic chemical drug therapy. Chinese acupuncture is an emerging therapeutic option for chemotherapy-induced cognitive impairment in older patients with cancer, despite limited supporting evidence. ObjectiveOur study aims to directly contribute to the existing knowledge of this novel Chinese medicine mode in older patients with cancer enrolled at the Department of Oncology/Chinese Medicine, Nanjing First Hospital, China, thereby establishing the basis for further research. MethodsThis study involves a 2-arm, prospective, randomized, assessor-blinded clinical trial in older patients with cancer experiencing chemobrain-related stress and treated with Chinese acupuncture from September 30, 2023, to December 31, 2025. We will enroll 168 older patients with cancer with clinically confirmed chemobrain. These participants will be recruited through screening by oncologists for Chinese acupuncture therapy and evaluation. Electroacupuncture will be performed by a registered practitioner of Chinese medicine. The electroacupuncture intervention will take about 30 minutes every session (2 sessions per week over 8 weeks). For the experimental group, the acupuncture points are mainly on the head, limbs, and abdomen, with a total of 6 pairs of electrically charged needles on the head, while for the control group, the acupuncture points are mainly on the head and limbs, with only 1 pair of electrically charged needles on the head. ResultsEligible participants will be randomized to the control group or the experimental group in 1:1 ratio. The primary outcome of this intervention will be the scores of the Montreal Cognitive Assessment. The secondary outcomes, that is, attentional function and working memory will be determined by the Digit Span Test scores. The quality of life of the patients and multiple functional assessments will also be evaluated. These outcomes will be measured at 2, 4, 6, and 8 weeks after the randomization. ConclusionsThis efficacy trial will explore whether Chinese electroacupuncture can prevent chemobrain, alleviate the related symptoms, and improve the quality of life of older patients with cancer who are undergoing or are just going to begin chemotherapy. The safety of this electroacupuncture intervention for such patients will also be evaluated. Data from this study will be used to promote electroacupuncture application in patients undergoing chemotherapy and support the design of further real-world studies. Trial RegistrationClinicalTrials.gov NCT05876988; https://clinicaltrials.gov/ct2/show/NCT05876988 International Registered Report Identifier (IRRID)DERR1-10.2196/53853

Summary: In eukaryotic genomes, rDNA generally resides as a highly repetitive and dynamic structure, making it difficult to study. Here, a synthetic rDNA array on chromosome III in budding yeast was constructed to serve as the sole source of rRNA. Utilizing the loxPsym site within each rDNA repeat and the Cre recombinase, we were able to reduce the copy number to as few as eight copies. Additionally, we constructed strains with two or three rDNA arrays and found that the presence of multiple arrays did not affect the formation of a single nucleolus. Although alteration of the position and number of rDNA arrays did impact the three-dimensional genome structure, the additional rDNA arrays had no deleterious influence on cell growth or transcriptomes. Overall, this study sheds light on the high plasticity of rDNA organization and opens up opportunities for future rDNA engineering.

Abstract Background The aim of the present study was to identify potential race- or gender-specific differences in anterior cruciate ligament (ACL) tibial footprint location from the tibia anatomical coordinate system (tACS) origin, investigate the distances from the tibial footprint to the anterior root of the lateral meniscus (ARLM) and the medial tibial spine (MTS), determine how reliable the ARLM and MTS can be in locating the ACL tibial footprint, and assess the risk of iatrogenic ARLM injuries caused by using reamers with various diameters (7–10 mm). Patients and methods Magnetic resonance images of 91 Chinese and 91 Caucasian subjects were used for the reconstruction of three-dimensional (3D) tibial and ACL tibial footprint models. The anatomical coordinate system was applied to reflect the anatomical locations of scanned samples. Results The average anteroposterior (A/P) tibial footprint location was 17.1 ± 2.3 mm and 20.0 ± 3.4 mm in Chinese and Caucasians, respectively (P

Context Zuojin Pill (ZJP) has been used to treat gastrointestinal problems in China for hundreds of years.Objective To discover more potential active ingredients and evaluate the gastroprotective mechanisms of ZJP.Materials and methods An approach involving UPLC-Q-Orbitrap HRMS and serum pharmacochemistry was established to screen the multiple chemical constituents of ZJP. Male Sprague-Dawley (SD) rats were divided into six groups: normal control, ulcer control, omeprazole (30 mg/kg), and three ZJP groups (1.0, 2.0 and 4.0 g/kg). After oral treatment with ZJP or omeprazole for 7 days, all groups except the normal control group were orally administered 5 mL/kg ethanol to induce gastric ulceration. Histopathological assessment of gastric tissue was performed by haematoxylin and eosin staining. Antioxidant parameters and inflammatory mediators were determined using ELISA Kit and immunohistochemical analysis.Results Ninety components were identified in ZJP. Among them, 23 prototypes were found in rat serum after oral administration of ZJP. The ulcer inhibition was over 90.0% for all the ZJP groups. Compared with the ulcer control rats, ZJP (4.0 g/kg) enhanced the antioxidant capacity of gastric tissue: superoxide dismutase (1.33-fold), catalase (2.61-fold), glutathione (2.14-fold), and reduced the malondialdehyde level (0.48-fold). Simultaneously, the ZJP meaningfully lowered the content of tumour necrosis factor-α (0.76-fold), interleukin-6 (0.66-fold), myeloperoxidase (0.21-fold), and nuclear factor kappa B (p65) (0.62-fold).Discussion and conclusions This study showed ZJP could mitigate ethanol-induced rat gastric ulcers, which might benefit from the synergistic actions of multiple ingredients. The findings could support the quality control and clinical trials of ZJP.

Elevated SOX2 protein levels correspond to the poor prognosis of patients with esophageal squamous cell carcinoma (ESCC). Poor prognosis is closely correlated with the loss or disruption of cellular polarity; however, the relationships between SOX2 protein and polarity proteins in ESCC remain elusive. Herein, we found that the knockdown of SOX2 significantly decreased miR-142-3p expression and can regulate the translation of LLGL2 protein, a member of the Scribble complex. LLGL2 protein levels in ESCC are negatively correlated with miR-142-3p and SOX2 levels. Moreover, LLGL2 protein expression increased upon SOX2 knockdown in ESCC cell lines, and mutating the binding site for this miRNA in the LLGL2 3’-UTR disrupted its ability to inhibit LLGL2 expression. When LLGL2 was overexpressed, ESCC cell proliferation and invasion were inhibited in vitro and in vivo, which could be elucidated based on changes in gene expression after RNA sequencing, targeted proteomic analysis and bioinformatic assays. However, SOX2 protein did not directly bind to the promoter of miR-142-3p after ChIP sequencing. Together, these findings indicate that a SOX2 regulatory axis governs ESCC proliferation, migration, invasiveness, and apoptosis, thereby providing a potential avenue for future therapeutic intervention. Abbreviations CCK-8, Cell Counting Kit 8; Chip, Chromatin Immunoprecipitation; EC, Esophageal cancer; EMT, epithelial-to-mesenchymal transition; ESCC, Esophageal squamous cell carcinomas; LLGL2, lethal (2) giant larvae protein homolog 2; LLGL2ov, LLGL2 overexpression; MET, mesenchymal-epithelial transition; miRNAs, MicroRNAs; PRM-MS, Parallel reaction monitoring-Mass spectrometry; SD, Standard deviation; SOX, sex determining region Y (SRY)-like box; SOX2-Kd, SOX2-knockdwon; TUNEL, TdT-mediated dUTP Nick-End Labeling.

Vegetation change has a non-negligible role in the impact of ecosystem services (ESs). Quantitative assessment of vegetation ecosystem services is the basis for sustainable regional development. Using the Chinese Loess Plateau (LP) as the study area, this study firstly analysed the spatial and temporal characteristics of vegetation change and used a Geodetector model to reveal the driving mechanism. Next, this study applied the InVEST model to quantitatively assess the four services of carbon storage, habitat quality, soil conservation and water yield, and explored the vegetation ecosystem service balance through vegetation type transfer. The results showed that (1) there was a trend towards an increase in the area of all vegetation types, with sparse vegetation being the most pronounced. Areas of damaged vegetation were concentrated in urban and peripheral areas, as well as wasteland and bare ground. (2) Annual precipitation, soil types and cumulative afforestation area ratio were the main drivers of vegetation change on the LP. (3) Restoration of woodland enhanced carbon storage, habitat quality and soil retention services for vegetation on the LP, while water yield decreased by 31.66%. The restoration of vegetation area did not enhance all ecosystem services. This study may provide a reference and basis for the sustainable management of regional ecosystems.

Aiming at the distributed measurement system multi-equipment coordinated measurement, the data measured by each transmitting station are unified under a common coordinate system, which has the problems of complicated operation and high time and cost. In this paper, a fast calibration method for distributed measurement systems based on standard devices is proposed. The method designs a new type of architectural calibration board with non-coplanar measurement nodes, calculates the coordinates of the measurement nodes using geometric relations, solves the initial values of the system parameters, and substitutes the initial values into the L-M least squares algorithm for iterative optimization so that it only needs to carry out one scanning measurement for each reference position in the calibration process to complete the calibration. We designed an experiment in which a distributed measurement system consisting of four transmitting stations measured three standard rods (1650.073, 1156.704, and 875.950 mm) sequentially after calibration in a measuring space of 5 × 5 × 3 m3. The experimental results show that under the premise of ensuring that the measurement accuracy is better than 0.20 mm, the calibration of the parameters of the distributed measurement system can be completed within 20 min.

Photoelectric catalysis is a green and efficient way to degrade pollutants, which has been paid more and more attention by researchers. Among them, Bi2WO3 has been proved to have excellent photocatalytic oxidation activity on its {001} facets. In this study, {001}-oriented facets with high exposure were successfully integrated into Bi2WO6 nanoplate arrays (Bi2WO6 NAs) to create a photoelectrode. This structure was grown in situ on an indium tin oxide (ITO) substrate. To promote photogenerated carrier separation efficiency and reduce agglomeration of Bi2WO6 photocatalysts, the electrochemical deposition of NiFe–layered double hydroxide (NiFe-LDH) and Ti3C2 (MXene) were introduced in this research to synergistically catalyze pollutant degradation. Morphology, spectral characterization, and electrochemical analysis jointly confirmed that the outstanding performance of hole capture behavior with LDH and electron conduction properties with MXene were the main reasons for the improvement in catalytic activity of the photoelectrode. Taking bisphenol A (BPA) as the model pollutant, the rate constant k of the NiFe-LDH/Ti3C2/Bi2WO6 NAs photoelectrode reaches 0.00196 min−1 under photoelectrocatalytic (PEC) conditions, which is 4.5 times that of the pure Bi2WO6 NAs photoelectrode. This work provides a new way to improve the reaction kinetics of the PEC degradation of pollutants.

Abstract Encephalopathy of prematurity (EoP) affects approximately 30% of infants born

ABSTRACT: Galactooligosaccharides are composed mainly of galactosyl lactose, which is important for infant growth and as a functional food additive. Although galactosyl lactose is abundant in goat milk, its complex structure has hindered the separation and analysis of its isomers. In this study, 5 isomers of goat milk galactosyl lactose were separated by HPLC: β6′-galactosyl lactose (β6′-GL), α6′-galactosyl lactose (α6′-GL), β4′-galactosyl lactose (β4′-GL), α3′-galactosyl lactose (α3′-GL), and β3′-galactosyl lactose (β3′-GL). This composition differs from that of commercial galactooligosaccharide products, which comprise mainly β-configuration oligosaccharides. The isomers were then qualitatively and quantitatively compared at different lactation stages using online HPLC-mass spectrometry. Relative quantitative analysis showed that the total content of the 5 galactosyl lactose isomers was highest in transitional goat milk. Specifically, β3′-GL was the main isomer in colostrum and α3′-GL was the main isomer in transitional and mature milk. β6′-Galactosyl lactose and β4′-GL tended to increase and then decrease during lactation. Moreover, α3′-GL content was 2 times higher than in colostrum and 10 times higher in transitional milk than in mature milk; in contrast, for β3′-GL, the values were 5 and 2 times higher, respectively. Absolute quantitative analysis revealed that β3′-GL was the most abundant isomers in colostrum (32.3 mg/L), and α3′-GL was the most abundant in transitional milk (88.1 mg/L) and mature milk (36.3 mg/L). These findings provide an important quantitative basis for understanding the relationship between structure and function of galactosyl lactose in goat milk, as well as its exploitation as a functional food.

BackgroundPredicting intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) can aid early treatment and prevent coronary artery lesions. A clinically consistent predictive model was developed for IVIG resistance in KD.MethodsIn this retrospective cohort study of children diagnosed with KD from January 1, 2016 to December 31, 2021, a scoring system was constructed. A prospective model validation was performed using the dataset of children with KD diagnosed from January 1 to June 2022. The least absolute shrinkage and selection operator (LASSO) regression analysis optimally selected baseline variables. Multivariate logistic regression incorporated predictors from the LASSO regression analysis to construct the model. Using selected variables, a nomogram was developed. The calibration plot, area under the receiver operating characteristic curve (AUC), and clinical impact curve (CIC) were used to evaluate model performance.ResultsOf 1975, 1,259 children (1,177 IVIG-sensitive and 82 IVIG-resistant KD) were included in the training set. Lymphocyte percentage; C-reactive protein/albumin ratio (CAR); and aspartate aminotransferase, sodium, and total bilirubin levels, were risk factors for IVIG resistance. The training set AUC was 0.825 (sensitivity, 0.723; specificity, 0.744). CIC indicated good clinical application of the nomogram.ConclusionThe nomogram can well predict IVIG resistance in KD. CAR was an important marker in predicting IVIG resistance in Kawasaki disease.

Objective To evaluate the current state of family doctor contract services (FDCS) in Beijing, identify the roles of family doctors who have worked with disabled older adults and investigate the barriers and facilitators faced by family doctors in providing care for them.Design A convergent mixed methods study was carried out from October 2020 to January 2021 to collect and analyse both quantitative and qualitative data. The integration strategies in this study were connecting the results of the quantitative phase to data collection of the qualitative phase.Setting A multi-stage sampling strategy was used to select 15 community health centres (CHCs) in four districts of Beijing. Of the four districts, two were from urban areas and two were from rural areas.Participants The inclusion criteria for participants were (1) family doctors, (2) contracted with disabled older adults, (3) engaged in related work for disabled older adults more than 6 months.Methods A cluster sampling of 283 family doctors was used in the questionnaire. A purposive sample of 30 family doctors from the same CHCs was selected during the same period. Frequency and rank, rank-sum test, Kruskal-Wallis test were conducted in qualitative data analysis, the views of the interviewees were analysed through the thematic framework method.Results Currently, family doctors provided various services to satisfy the health needs of disabled older adults, while the usage of FDCS for disabled older adults is affected by many factors. The differences of the importance of family doctors’ role (p

Abstract Background Pneumonia is a common complication of influenza and closely related to mortality in influenza patients. The present study examines cytokines as predictors of the prognosis of influenza-associated pneumonia. Methods This study included 101 inpatients with influenza (64 pneumonia and 37 non-pneumonia patients). 48 cytokines were detected in the serum samples of the patients and the clinical characteristics were analyzed. The correlation between them was analyzed to identify predictive biomarkers for the prognosis of influenza-associated pneumonia. Results Seventeen patients had poor prognosis and developed pneumonia. Among patients with influenza-associated pneumonia, the levels of 8 cytokines were significantly higher in those who had a poor prognosis: interleukin-6 (IL-6), interferon-γ (IFN-γ), granulocyte colony-stimulating factor (G-CSF), monocyte colony-stimulating factor (M-CSF), monocyte chemoattractant protein-1 (MCP-1), monocyte chemoattractant protein-3, Interleukin-2 receptor subunit alpha and Hepatocyte growth factor. Correlation analysis showed that the IL-6, G-CSF, M-CSF, IFN-γ, and MCP-1 levels had positive correlations with the severity of pneumonia. IL-6 and G-CSF showed a strong and positive correlation with poor prognosis in influenza-associated pneumonia patients. The combined effect of the two cytokines resulted in the largest area (0.926) under the receiver-operating characteristic curve. Conclusion The results indicate that the probability of poor prognosis in influenza patients with pneumonia is significantly increased. IL-6, G-CSF, M-CSF, IFN-γ, and MCP-1 levels had a positive correlation with the severity of pneumonia. Importantly, IL-6 and G-CSF were identified as significant predictors of the severity of influenza-associated pneumonia.

Abstract Full matrix focusing method of ultrasonic phased array has been proved with advantages of good signal-to-noise ratio and imaging resolution in the field of Ultrasonic NDT. However, it is still suffering from the time-consuming data acquisition and processing. In order to solve the problem, two simplified matrix focusing methods are provided in the paper. One provided method is a triangular matrix focusing algorithm based on the principle of reciprocity for the multi-channel ultrasonic system. The other provided method is a trapezoidal matrix focusing algorithm based on the energy weight of the different channel to the focusing area. Time of data acquisition and computational is decreased with the provided simplified matrix focusing methods. In order to prove the validity of two provided algorithms, both side-drilled holes and oblique cracks are used for imaging experiments. The experimental results show that the imaging quality of the triangular matrix focusing algorithm is basically consistent to that of the full matrix focusing method. And imaging quality of the trapezoidal matrix focusing algorithm is slightly reduced with the amount of multi-channel data decreasing. Both data acquisition and computational efficiency using the triangular matrix focusing algorithm and the trapezoidal matrix focusing algorithm have been improved significantly compared with original full matrix focusing method.

Spatial information network is a kind of satellite network with high speed node movement and fast dynamic topology change. With the increasing number of low-orbit satellites, the research on the subnets topology and dynamic optimization of space information networks has become an important direction to study the destructibility of spatial information network. In this paper, two common objective functions in inter-satellite link assignment, network observation position and network communication factor are studied, and a multi-objective optimization model is constructed. Depth first search, simulated annealing, NSGA-II and adaptive optimization simulated annealing were used to analyze and solve the model. By comparing the solving efficiency of the model through simulation experiments, the difference of the results caused by the four algorithms is verified.

Abstract Background Stone cells in fruits of pear (Pyrus pyrifolia) negatively influence fruit quality because their lignified cell walls impart a coarse and granular texture to the fruit flesh. Results We generate RNA-seq data from the developing fruits of 206 pear cultivars with a wide range of stone cell contents and use a systems genetics approach to integrate co-expression networks and expression quantitative trait loci (eQTLs) to characterize the regulatory mechanisms controlling lignocellulose formation in the stone cells of pear fruits. Our data with a total of 35,897 expressed genes and 974,404 SNPs support the identification of seven stone cell formation modules and the detection of 139,515 eQTLs for 3229 genes in these modules. Focusing on regulatory factors and using a co-expression network comprising 39 structural genes, we identify PbrNSC as a candidate regulator of stone cell formation. We then verify the function of PbrNSC in regulating lignocellulose formation using both pear fruit and Arabidopsis plants and further show that PbrNSC can transcriptionally activate multiple target genes involved in secondary cell wall formation. Conclusions This study generates a large resource for studying stone cell formation and provides insights into gene regulatory networks controlling the formation of stone cell and lignocellulose.

Fucoxanthin is the most abundant marine carotenoid derived from edible brown seaweeds and has been used as a functional ingredient for the treatment of obesity. However, poor brain bioavailability of fucoxanthin has limited its application in combating neurological diseases. In this study, we demonstrated that 40 % fucoxanthin was released from polylactic-co-glycolic acid-polyethylene glycol (PLGA-PEG) nanoparticles at one day after incubation. Fucoxanthin nanoparticles (20–40 mg/kg, i.v.) significantly prevented neurological and behavioral deficits in middle cerebral artery occlusion/reperfusion (MCAO)-treated rats via the reduction of M1 microglial activation, decrease of pro-inflammatory factor production, inactivation of the nuclear factor-κB (NF-κB) pathway, and elevation of the nuclear factor-E2-related factor 2 (Nrf2) pathway in ischemic penumbra. Moreover, fucoxanthin nanoparticles (5–15 μg/mL) inhibited hypoxia-stimulated neurotoxicity in a mouse hippocampal neuron cell line (HT22 cells). These results suggest that fucoxanthin nanoparticles enhanced brain bioavailability and produced neuroprotection against ischemic stroke in vivo with much lower effective concentrations than fucoxanthin itself, providing further support for the development of fucoxanthin as a functional ingredient for the prevention of ischemic stroke with proper nanoparticle formulations.

IntroductionBlueberries have a high antioxidant content and are produced as healthy food worldwide. Long non-coding RNAs (lncRNAs) are a type of regulatory RNAs that play a variety of roles in plants. Nonetheless, information on lncRNAs and their functions during blueberry fruit development is scarce in public databases.MethodsIn the present study, we performed genome-wide identification of lncRNAs in a southern highbush blueberry using strand-specific RNA sequencing (ssRNA-Seq). Differentially expressed lncRNAs (DE-lncRNAs) and their potential target genes were analyzed at four stages of fruit development. Cis-regulatory DE-lncRNAs were predicted using co-localization analysis.ResultsThese findings included a total of 25,036 lncRNAs from 17,801 loci. Blueberry lncRNAs had shorter transcript lengths, smaller open reading frame (ORF) sizes, fewer exons, and fewer isoforms than protein-coding RNAs, as well as lower expression levels and higher stage-specificity during fruit development. A total of 105 DE-lncRNAs were identified among the comparison group of PAD vs. CUP, 443 DE-lncRNAs were detected when comparing CUP with PINK fruits, and 285 DE-lncRNAs were revealed when comparing PINK and BLUE fruits. According to Kyoto Encyclopedia of Genes and Genomes annotation, target genes of DE-lncRNAs were primarily enriched in the “Autophagy-other”, “DNA replication”, “Endocytosis”, ‘photosynthesis’ and ‘chlorophyll metabolism’ pathways, suggesting that lncRNAs may pay potential roles in fruit expansion and ripening. Moreover, several lncRNAs have been proposed as cis-regulators of the key genes involved in flavonoid biosynthesis. MSTRG.107242.6, and its putative target gene, BTB/POZ and TAZ domain-containing protein, might play critical roles in anthocyanin accumulation in blueberries.DiscussionThese findings highlight the regulatory function of lncRNAs and aid in elucidating the molecular mechanism underlying blueberry fruit growth.

IntroductionBlueberry (Vaccinium corymbosum L.) is a popular fruit with an abundance of anthocyanins in its leaves and fruits. Light is one of the pivotal environmental elements that affects plant growth and development, but the regulatory mechanism between light quality and anthocyanin formation is poorly understood.MethodsAn integrated transcriptome and metabolome analysis was performed to investigate the effects of white (control), blue (B), red (R), and red/blue (60R/40B) light on blueberry growth and reveal the potential pathway controlling anthocyanin biosynthesis in blueberry leaves.ResultsThe anthocyanin content was significantly improved by the blue and red/blue light when compared with white light, whereas there was a significant reduction in the photosynthesis under the blue light, showing an inverse trend to that of anthocyanin accumulation. Transcriptomic analysis resulted in the assembly of 134,709 unigenes. Of these, 22 were differentially expressed genes (DEGs) that participate in the anthocyanin biosynthesis pathway, with the majority being significantly up-regulated under the blue light. Most of the photosynthesis-related genes that were down-regulated were expressed during anthocyanin accumulation. Targeted metabolome profiling identified 44 metabolites associated with anthocyanin biosynthesis. The contents of most of these metabolites were higher under blue light than the other light conditions, which was consistent with the transcriptome results. The integrated transcriptome and metabolome analysis suggested that, under blue light, leucoanthocyanidin dioxygenase (LDOX), O-methyltransferase (OMT), and UDP-glucose flavonoid glucosyltransferase (UFGT) were the most significantly expressed, and they promoted the synthesis of cyanidin (Cy), malvidin (Mv), and pelargonidin (Pg) anthocyanidins, respectively. The expression levels of dihydroflavonol 4-reductase (DFR) and OMT, as well as the accumulation of delphinidin (Dp), peonidin (Pn), and petunidin (Pt), were significantly increased by the red/blue light.DiscussionThe blue and red/blue lights promoted anthocyanin biosynthesis via inducing the expression of key structural genes and accumulation of metabolites involved in anthocyanin synthesis pathway. Moreover, there was a possible feedback regulating correlation between anthocyanin biosynthesis and photosynthesis under different light qualities in blueberry leaves. This study would provide a theoretical basis for elucidating the underlying regulatory mechanism of anthocyanin biosynthesis of V. corymbosum.

Hydrogels prepared from natural polymer have attracted extensive attention in biomedical fields such as drug delivery, wound healing, and regenerative medicine due to their good biocompatibility, degradability, and flexibility. This review outlines the commonly used natural polymer in hydrogel preparation, including cellulose, chitosan, collagen/gelatin, alginate, hyaluronic acid, starch, guar gum, agarose, and dextran. The polymeric structure and process/synthesis of natural polymers are illustrated, and natural polymer-based hydrogels including the hydrogel formation and properties are elaborated. Subsequently, the biomedical applications of hydrogels based on natural polymer in drug delivery, tissue regeneration, wound healing, and other biomedical fields are summarized. Finally, the future perspectives of natural polymers and hydrogels based on them are discussed. For natural polymers, novel technologies such as enzymatic and biological methods have been developed to improve their structural properties, and the development of new natural-based polymers or natural polymer derivatives with high performance is still very important and challenging. For natural polymer-based hydrogels, novel hydrogel materials, like double-network hydrogel, multifunctional composite hydrogels, and hydrogel microrobots have been designed to meet the advanced requirements in biomedical applications, and new strategies such as dual-cross-linking, microfluidic chip, micropatterning, and 3D/4D bioprinting have been explored to fabricate advanced hydrogel materials with designed properties for biomedical applications. Overall, natural polymeric hydrogels have attracted increasing interest in biomedical applications, and the development of novel natural polymer-based materials and new strategies/methods for hydrogel fabrication are highly desirable and still challenging.

The CBEM spiking neuron model establishes a new connection between the statistics of neural coding and the biophysical model. In order to narrow the gap between the CBEM model and the biophysical model, a coupled CBEM spike neuron model is proposed. A coupling filter was used to couple the single CBEM model. The correlation between different spiking sequences is considered in the coupled CBEM spiking neuron model, and the correlation information is used for sequence fitting. Through the spike rate visualization, Single-spike information and the AIC criterion show that the proposed coupled CBEM model can obtain more real spiking sequences simulation results, more spiking sequences information and the low model complexity while retaining the biophysical interpretability.

Abstract Background Retinol binding protein 4 (RBP4) has been proposed to play a role in the pathophysiology of coronary artery disease (CAD), but previous findings on the association of RBP4 levels with CAD are inconsistent. Methods A meta-analysis based on observational studies was conducted to evaluate the association between circulating RBP4 levels and CAD. Databases including PubMed, Web of Science, Embase, Google Scholar and ClinicalTrials.gov database were searched for eligible studies published up to 12 July 2021. Standard mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using the inverse variance heterogeneity (IVhet) and random-effects model for data with moderate and high heterogeneity (I 2 > 30%) and data with low heterogeneity were analysed using a fixed-effects model (I 2 ≤ 30%). Moreover, a bias-adjusted quality-effects model was generated, and the prediction interval was also calculated under the random-effects model. Results Two nested case-control studies, one cohort study and twelve case–control studies with a total of 7111 participants were included. Circulating RBP4 levels in patients with CAD were comparable to those in the controls under the IVhet model (SMD: 0.25, 95% CI: − 0.29-0.79, I 2 : 96.00%). The quality-effects model produced consistent results. However, the association turned to be significant under the random-effect model (SMD: 0.46, 95% CI: 0.17–0.75, I 2 : 96.00%), whereas the 95% predictive interval (PI) included null values (95% PI: − 0.82-1.74). Subgroup analyses illustrated a positive relationship between CAD and RBP4 levels in patients with complications (SMD: 1.34, 95% CI: 0.38–2.29, I 2 : 96.00%). The meta-regression analysis revealed that the mean BMI of patients (P = 0.03) and complication status (P = 0.01) influenced the variation in SMD. Conclusions There was low-quality evidence that patients with CAD exhibited similar circulating RBP4 levels compared with controls, and high inter-study heterogeneity was also observed. Thus, RBP4 might not be a potential risk factor for CAD. Comparisons among different subtypes of RBP4 with larger sample size are needed in the future.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder, which is pathologically characterized by the deposits of β-amyloid (Aβ), and plays an important role in neuronal death. Indirubin-3′-monoxime (I3M) showed neuroprotective effects against Aβ-induced neuronal apoptosis. However, the use of I3M in AD treatment is limited due to its low bioavailability. Herein, PLGA-PEG nanoparticles were synthesized for I3M loading. I3M could release sustainedly sustain release from the I3M-loaded PLGA-PEG nanoparticles (PLGA-PEG-I3M NPs) without obvious burst release. What's more, the PLGA-PEG-I3M NPs could significantly promote the uptake of I3M by PC12 ​cells through nanoparticle-mediated transport, and improve the efficacy of I3M on the inhibition of Aβ fibrillization and oligomerization as well as the neuroprotective activity of I3M on Aβ oligomers-induced neuronal death. Thus, the PLGA-PEG-I3M NPs may be a promising platform for AD therapy.

Few studies have explored the trajectories of Chinese early adolescent depressive symptoms or comprehensively considered the factors of family and peers. The present study aimed to identify the trajectories of depressive symptoms in early adolescence using a school-based sample assessed in three waves. The study also examined whether family and peer factors were significant predictors. A total of 586 Chinese primary and middle school students participated in the survey. A growth mixture model was used to find the trajectories of depressive symptoms, and multinominal logistic regression was used to identify the predictors. Three trajectories were identified, including a stable-low class, an increasing class, and a high-decreasing class. Results indicated that gender, parental psychological aggression and neglect, parental psychological control, traditional bullying/cyberbullying victimization, and friendship quality were significant predictors. However, witnessing intimate partner violence, parental behavior control, and traditional bullying/cyberbullying perpetration could not significantly predict the trajectories. The findings of this study can provide an empirical basis for teachers and clinical interveners to determine different development trajectories of depressive symptoms and carry out prevention and intervention.

As the largest artificial ecosystem on Earth, croplands not only secure the basic living materials for people but also provide ecological service values for human society. For croplands, ecosystem services have proven to be of great value and are closely linked to human activities and climate change. However, spatiotemporal patterns of cropland ecosystem services and their drivers still need to be further assessed quantitatively. In this study, we provided a comprehensive evaluation of ecosystem services across China's cropland ecosystems over the past two decades using gross ecosystem product (GEP) as a single metric of the monetary evaluation of final ecosystem services. The values of material services, regulating services, and cultural services were calculated to summarize the GEP value of cropland ecosystems in China. Our results showed that the multiyear mean value of GEP was 4.35 × 107 million CNY. The value of regulating services reached 3.86 × 107 million CNY, followed by material services of 4.76 × 106 million CNY and cultural services of 1.16 × 105 million CNY. GEP value was different among provinces, leading to a heterogeneous spatial pattern associated with population and cultivated area. Moreover, we analyzed the trends in the GEP value at the provincial and national scales. The results showed that the GEP value of China's cropland ecosystems has increased over the period. The values of the material, regulating, and cultural services have increased at a rate of (0.35 ± 0.01) × 106 million CNY a−1, (1.12 ± 0.10) × 106 million CNY a−1, and (0.002 ± 0.0002) × 106 million CNY a−1, respectively (P < 0.05). The majority of provinces had an increasing trend in GEP, yet some developed provinces, e.g., Beijing and Shanghai, showed a decreasing trend. Furthermore, we evaluated the impacts of social-economic and natural factors on changes in GEP. We found that rising prices for agricultural products and services boosted an increase in GEP. Meanwhile, the spatiotemporal patterns of GEP were also associated with the adjustments of planting area in each province. Overall, our findings highlight the importance of assessing spatiotemporal patterns of cropland ecosystem services for decision-makers.