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Objective: Distraction osteogenesis (DO) has been widely used to treat bone defects as its effectiveness in bone regeneration. Currently, distraction devices for establishing DO models are mainly developed for rats or large animals. However, a mouse DO model is in great need for in-depth mechanistic investigations using various transgenic mice. The current study reports the development of a reproducible murine DO model. Methods: A mini-titanium lengthener was designed and fabricated. The mini-lengthener was applied on the murine femur with four threaded pins using a designed clamp as the drilling and insertion guide. After transverse osteotomy using a Gigli saw, and after 5 days of latency, DO procedures started at 0.3 mm/day for 10 days, and the consolidation period was left for 28 days. The bone formation was monitored by radiography and histology. Potential effects on animal locomotion during DO were also measured by behavior tests. Results: Separated bone segments maintained good alignment during the entire DO phases. New bone formation was found as early as the end of the distraction phase. Active bone remodeling was found between the separated bone segments at late distraction and early consolidation phases. At the mature consolidation phase, bone remodeling was mainly observed in the contact cortical bone. Mice underwent DO procedure did not have significant impairment in their locomotion. Conclusion: We have successfully developed a murine femoral DO model, which may be used to study the biological processes of DO. We also developed the mini-lengthener and the guide clamp to ensure the standardization and reproducibility of the mouse DO model.The translational potential of this article: Current study reports the development of a murine femoral DO model. A well-established murine DO model will facilitate further investigations of the biological mechanisms of DO in various transgenic and normal mice.

Abstract Background To compare clinical outcomes of trifocal intraocular lens in patients with and without prior history of laser in situ keratomileusis (LASIK). Methods A retrospective study included patients who underwent bilateral cataract surgery and PanOptix trifocal intraocular lens (IOLs) implantation. Patients were grouped: Group A for patients with history of LASIK and Group B for patients without history of LASIK. Postoperative outcome measures comprised distance, intermediate, and near visual acuity, manifest refraction, defocus curve, contrast sensitivity, visual quality, patient satisfaction, and the rate of spectacle independence. Results A total of 288 eyes (144 patients) were included: 132 eyes in Group A and 156 eyes in Group B. At 6 months post-surgery, patients of both groups achieved a continuous satisfying visual acuity from 33 cm to distance. 73% of eyes in Group A and 75% of eyes in Group B were within ± 0.50 D of emmetropia (P > 0.05). The percentages of eyes within ± 1.00 D of emmetropia were 98% for Group A and 96% for Group B (P > 0.05). The total scores of satisfaction were 52.58 ± 3.46 for Group A and 53.23 ± 3.46 for Group B (P > 0.05). Most of patients (98% for Group A, 99% for Group B) were able to be spectacle independence for daily living. 53% of patients in Group A and 51% in Group B experiencd mild to moderate negative visual symptoms, which made it a little or moderate difficult to drive at night. Conclusions Cataract patients with and without history of LASIK could safely undergo implantation of the PanOptix IOLs, which results in precise refractive outcomes and satisfactory visual acuity. Although contrast sensitivity decreased and some negative visual symptoms were observed, patients’ satisfaction was generally high due to the high rate of spectacles independence. There were no statistically significant differences between the study groups.

Abstract Background Parasitic diseases remain a serious public health problem in China. Health education aimed at disseminating health-related knowledge and promoting healthy behaviours, plays a crucial role in the prevention and control of parasitic diseases. This study aims to develop a tool to measure the parasitic disease health literacy of residents in China. Methods Scale development was based on qualitative and quantitative methods. Qualitative method included focus group discussions and Delphi consultations. A methodological design with multistage sampling and a pilot study was used to evaluate the questionnaire. The scale’s reliability was tested using Cronbach’s α and split-half reliability, while its construct validity was assessed using confirmatory factor analysis. The scale’s passing score was determined using the receiver operating characteristic curve. A cross-sectional survey was conducted in six districts of the prefecture of Jiangsu and residents aged 14–69 years in the participating townships were randomly selected based on their location. Results The health literacy indicator system for parasitic diseases included 3 first-level, 9 s-level and 23 third-level indicators. The 23-item questionnaire demonstrated good internal consistency (Cronbach’s alpha = 0.774) and split-half reliability (Spearman-Brown coefficient = 0.778). The questionnaire’s passing score was 60. A total of 990 valid questionnaires were collected from participants in three cities. The percentage of participants with health literacy regarding parasitic diseases was 15.8%. Their scores were influenced by age, income, employment, and educational level. Conclusions Health literacy of parasitic diseases is an integrated indicator rather than just knowledge or behavior information. The correlation between knowledge and behavior is weak. The capacity for healthy behavior of parasitic disease is associated with the location and culture of the city. For neglected diseases, it is important for people to talk positively about their behaviors with a doctor.

Abstract Background The clinical application of peptide vaccines in tumor immunotherapy holds significant promise. Peptide-based tumor vaccines are currently subject to certain limitations in clinical trials, including the challenge of inducing a sustained response from CD4+ T helper cells and cytotoxic T lymphocytes (CTL), as well as human leukocyte antigen (HLA) restrictions. Methods Through the utilization of biological information methodology, a screening process was conducted to identify three potential long peptides that are specifically targeted by the MAGE-A4 antigen. The candidate long peptides were subjected to in vitro testing using human peripheral blood lymphocytes as samples to evaluate their immunogenicity and immune function. The antitumor properties and preliminary mechanism of the long peptide vaccine were investigated through the use of a mouse model designed for the prevention of triple negative breast cancer (TNBC). Results Three predicted multi-epitope long peptides targeting MAGE-A4 have shown to have a strong immunogenicity, with a total positive rate of 72% across different HLA subtypes in Chinese populations. they can also increase the levels of the costimulatory factor CD137 and tumor necrosis factor-alpha (TNF-α), activate T cells, and boost the cytotoxic activity. Results from an animal study have revealed that the long-peptide vaccine, both on its own and in combination with R848, has displayed impressive anti-tumor and target-specific capabilities. Moreover, it has the ability to increase the expression of effector memory T cells and central memory T cells. Conclusions This study was the first to screen three multi-epitope long peptides targeting MAGE-A4 and assess their immunogenicity, immune function, and potential as adjuvant peptides. The results showed that the MAGE-A4 long peptide vaccine can be used as a novel immunoprophylaxis method to prevent TNBC. Moreover, the proposed development model is capable of screening multiple target antigens, which lead to its clinical application.

Background: Neonatal respiratory failure (NRF) is a critical condition with high morbidity and mortality rates. This study aimed to develop a nomogram prediction model to early predict the risk of death in Chinese neonates with NRF. Methods: A retrospective analysis was conducted on NRF neonates from 21 tertiary neonatal intensive care units (NICUs) across 13 prefecture-level cities in Jiangsu Province, China, from March 2019 to March 2022. NRF neonates from one random NICU were selected as the external validation set, while those from the remaining 20 NICUs were divided into the training set and the internal validation set at a 7:3 ratio. Death was the primary outcome. LASSO regression and multivariate logistic regression were used to identify the predictive factors from the training set and then the nomogram was constructed. Results: A total of 5387 neonates with NRF were included in the analysis. Among them, 3444 were in the training set, 1470 were in the internal validation set, and 473 were in the external validation set. The nomogram was constructed based on the eight predictors of the 1-min Apgar score, birth weight, gestational age, the relationship between birth weight and gestational age, mode of first respiratory support, inhaled nitric oxide, antenatal corticosteroids, and vasoactive drugs. The area under the curve of the nomogram in the training set, internal validation set, and external validation set was 0.763, 0.733, and 0.891, respectively. The P-values of the Hosmer-Lemeshow goodness of fit test were 0.638, 0.273, and 0.253, respectively. Brier scores were 0.066, 0.072, and 0.037, respectively. The decision curve analysis demonstrated a significant net benefit in all cases. These data indicate the good performance of the nomogram. Conclusions: This nomogram can serve as a reference for clinicians to identify high-risk neonates early and reduce the incidence of neonatal mortality.

Abstract Combining the extracted tongue features with other medical indicators can effectively judge the diseases of patients. The previous work usually only analyzes a certain feature of the tongue body and is unable to extract multiple features simultaneously. In this study, a multi‐label classification network named TIM‐Net is proposed, which integrates global and local features to achieve multi‐label intelligent diagnosis of Chinese medicine tongue images. First, a feature extraction network based on ResNet is proposed to capture the features of tongue images more sufficiently. Then, a multi‐label classification algorithm fusing global and local features is proposed, and targeted screening operations are carried out on the class‐related feature maps based on global confidence. In addition, a logical masking algorithm is proposed to ensure that the local features can only correct the feature labels they represent, and do not interfere with other feature labels. The classification accuracy is further improved by using local feature confidence and correcting the global classification results. Finally, the experimental results indicate that the classification accuracy of the tongue images is gradually improved through optimizing the feature extraction network and fusing local features, and it exceeds other state‐of‐the‐art multi‐label classification networks.

Photo-stimuli responsive materials show great potential in the fields of information encryption and storage due to their distinctive spatial or temporal color changes. However, the conventional single or multi-color static outputs by light stimulus difficulty meet practical requirements for high-security optical storage technologies. Here, a novel dynamic irradiation-responsive phosphor of Na2Ba2Si2O7:Eu is demonstrated, exhibiting high storage stability and convenient readout behaviors. The inherent Eu2+ luminescence can be dynamically tuned, instantly read out, and conveniently erased by controlling irradiation duration of a portable diode laser (365 nm). The modulation mechanism is unraveled by optically induced oxidation reactions of Eu2+→Eu3+ and defects as killer centers. The excellent luminescence modulation degree (ΔRt = 89.5%) and the accompanying larger color contrast enable the creation of invisible optical codes with multi-level encryption in bright or dark field. These results indicate potential applications of Na2Ba2Si2O7-based materials in information encryption and invisible optical storage, and are expected to expand more investigations on optically induced PL modulation behaviors based on mixed valences and defects.

Abstract Three methods can be used to evaluate the colour used on architectural heritage: manual evaluation, instrumental measurement, and process restoration. Optical instruments that can obtain relatively accurate chromaticity data are ideal. As architectural heritage sites age, their colour fluctuates. Researchers must screen colour data and analyse the features based on experience with colour perception. This study combines quantitative colour analysis and a scaled perception survey to analyse the Wen Yuan Ge in the Forbidden City and provide a new reference for researching and designing colour in architectural heritage.

Abstract Background Noninvasive biomarkers for the assessment of response to chemotherapy in advanced breast cancer (BCa) are essential for optimized therapeutic decision-making. We evaluated the potential of soluble Periostin (POSTN) in circulation as a novel biomarker for chemotherapy efficacy monitoring. Methods Two hundred and thirty-one patients with different stages of BCa were included. Of those patients, 58 patients with inoperable metastatic disease receiving HER2-targeted or non-targeted chemotherapy were enrolled to assess the performances of markers in recapitulating the chemotherapy efficacy assessed by imaging. POSTN, together with CA153 or CEA at different time points (C0, C2, and C4) were determined. Results POSTN levels were significantly associated with tumor volume (P

Multiple research studies have demonstrated the efficacy of lactic acid bacteria in boosting both innate and adaptive immune responses. We have created a Lactococcus lactis variant that produces a modified combination protein with Fms-like tyrosine kinase 3 ligand and co-stimulator O × 40 ligand, known as HuFOLactis. The genetically modified variant was purposely created to activate T cells, NK cells, and DC cells in a laboratory setting. Furthermore, we explored the possibility of using the tumor-penetrating peptide iRGD to deliver HuFOLactis-activated immune cells to hard-to-reach tumor areas. Following brief stimulation with HuFOLactis, immune cell phenotypes and functions were assessed using flow cytometry. Confocal microscopy was employed to demonstrate the infiltrative and cytotoxic capabilities of iRGD-modified HuFOLactis-activated immune cells within tumor spheroids. The efficacy of iRGD modified HuFOLactis-activated immune cells against tumors was assessed in xenograft mouse models. HuFOLactis treatment resulted in notable immune cell activation, demonstrated by elevated levels of CD25, CD69, and CD137. Additionally, these activated immune cells showed heightened cytokine production and enhanced cytotoxicity against MKN45 cell lines. Incorporation of the iRGD modification facilitated the infiltration of HuFOLactis-activated immune cells into multicellular spheroids (MCSs). Additionally, immune cells activated by HuFOLactis and modified with iRGD, in combination with anti-PD-1 treatment, effectively halted tumor growth and prolonged survival in a mouse model of gastric cancer.

ABSTRACTThe personalized neoantigen nanovaccine (PNVAC) platform for patients with gastric cancer we established previously exhibited promising anti-tumor immunoreaction. However, limited by the ability of traditional neoantigen prediction tools, a portion of epitopes failed to induce specific immune response. In order to filter out more neoantigens to optimize our PNVAC platform, we develop a novel neoantigen prediction model, NUCC. This prediction tool trained through a deep learning approach exhibits better neoantigen prediction performance than other prediction tools, not only in two independent epitope datasets, but also in a totally new epitope dataset we construct from scratch, including 25 patients with advance gastric cancer and 150 candidate mutant peptides, 13 of which prove to be neoantigen by immunogenicity test in vitro. Our work lay the foundation for the improvement of our PNVAC platform for gastric cancer in the future.

Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the pathologic features and clinical outcomes of T-cell PTLD, an extremely rare subtype of PTLD, after allo-HSCT. In this study, six allo-HSCT recipients with T-cell PTLD from five transplant centers in China were enrolled. All the T-cell PTLD were donor-derived, and three patients were with monomorphic and three with polymorphic types, respectively. All patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. Five patients achieved complete response (CR), and one experienced progressive disease (PD). The median time from HSCT to onset was 4 (range: 0.6-72) months, analyzed in combination with the other 16 patients with T-cell PTLD identified from previous reports. About 56.3% of the T-cell samples (9/16) were positive for in situ hybridization with an Epstein–Barr virus (EBV)-encoded small nuclear early region (EBER ISH). CHOP-based chemotherapy might be the optimal strategy for patients who showed no response to empiric therapy with a CR rate of 87.5%. In conclusion, our study observed that T-cell PTLD has distinct clinical manifestations and morphological features, which characterized by less relation to EBV, later occurrence, and poorer prognosis when compared with B-cell PTLD.

BackgroundAs one of the leading causes of child mortality, deaths due to congenital anomalies (CAs) have been a prominent obstacle to meet Sustainable Development Goal 3.2. ObjectiveWe conducted this study to understand the death burden and trend of under-5 CA mortality (CAMR) in Zhejiang, one of the provinces with the best medical services and public health foundations in Eastern China. MethodsWe used data retrieved from the under-5 mortality surveillance system in Zhejiang from 2012 to 2021. CAMR by sex, residence, and age group for each year was calculated and standardized according to 2020 National Population Census sex- and residence-specific live birth data in China. Poisson regression models were used to estimate the annual average change rate (AACR) of CAMR and to obtain the rate ratio between subgroups after adjusting for sex, residence, and age group when appropriate. ResultsFrom 2012 to 2021, a total of 1753 children died from CAs, and the standardized CAMR declined from 121.2 to 62.6 per 100,000 live births with an AACR of –9% (95% CI –10.7% to –7.2%; P

Indoor microorganisms impact asthma and allergic rhinitis (AR), but the associated microbial taxa often vary extensively due to climate and geographical variations. To provide more consistent environmental assessments, new perspectives on microbial exposure for asthma and AR are needed. Home dust from 97 cases (32 asthma alone, 37 AR alone, 28 comorbidity) and 52 age- and gender-matched controls in Shanghai, China, were analyzed using high-throughput shotgun metagenomic sequencing and liquid chromatography-mass spectrometry. Homes of healthy children were enriched with environmental microbes, including Paracoccus, Pseudomonas, and Psychrobacter, and metabolites like keto acids, indoles, pyridines, and flavonoids (astragalin, hesperidin) (False Discovery Rate

We have studied the parameters of preliminary breakdown (PB) pulses in 395 normal and 319 inverted intracloud (IC) flashes observed in Gifu, Japan, and Ningxia, China, respectively, by using a low-frequency mapping system called fast antenna lightning mapping array (FALMA). These parameters are extracted from the first half of the PB pulses. It is found that compared to normal IC flashes, inverted IC flashes exhibited PB pulses with slower rise times (6.8 vs. 3.1 μs), wider half-peak widths (3.8 vs. 2.5 μs), longer zero-crossing times (26.2 vs. 14 μs), and extended fall times (4 vs. 3.2 μs). We further demonstrated that such discrepancies between normal and inverted IC flashes should not be caused by subjective factors, like noise threshold setting, or objective factors, like signal propagation distance. Based on this analysis, finally, we inferred that the discrepancies should be a reflection of the PB channel properties of normal and inverted IC flashes.

Precipitation nowcasting, which involves the short-term, high-resolution prediction of rainfall, plays a crucial role in various real-world applications. In recent years, researchers have increasingly utilized deep learning-based methods in precipitation nowcasting. The exponential growth of spatiotemporal observation data has heightened interest in recent advancements such as denoising diffusion models, which offer appealing prospects due to their inherent probabilistic nature that aligns well with the complexities of weather forecasting. Successful application of diffusion models in rainfall prediction tasks requires relevant conditions and effective utilization to direct the forecasting process of the diffusion model. In this paper, we propose a probabilistic spatiotemporal model for precipitation nowcasting, named LLMDiff. The architecture of LLMDiff includes two networks: a conditional encoder–decoder network and a denoising network. The conditional network provides conditional information to guide the denoising network for high-quality predictions related to real-world earth systems. Additionally, we utilize a frozen transformer block from pre-trained large language models (LLMs) in the denoising network as a universal visual encoder layer, which enables the accurate estimation of motion trend by considering long-term temporal context information and capturing temporal dependencies within the frame sequence. Our experimental results demonstrate that LLMDiff outperforms state-of-the-art models on the SEVIR dataset.

Improving crop water productivity (WP) in the face of drought conditions and optimizing water allocation for irrigated crops are critical steps toward mitigating the challenges associated with agricultural water use. To investigate the effects of regulated deficit irrigation (RDI) at different growth stages on maize yield and WP, a 4-year field experiment was conducted on spring maize under film drip irrigation from 2016 to 2019 in an arid region of northwest China. RDI significantly reduced plant height, leaf area index (LAI) and dry matter accumulation (DM). Notably, the moderate RDI treatment, denoted as 65/80ET (before and after ''/'' represent the irrigation volume relative to fully irrigation in the late vegetative and reproductive growth stages, respectively), reduced crop water consumption. This reduction was accompanied by the maintenance of relatively high grain yield and a significant increase in the harvest index, thereby resulting in a marked improvement in WP. In summary, the results of this study indicate that the 65/80ET treatment can effectively stabilize yield while improving efficiency. As such, it can be considered a viable RDI strategy for achieving water-saving, yield stability and enhanced efficiency in maize production.

Objective Improving accuracy and safety of pedicle screw placement is of great clinical importance. Electronic conductivity device (ECD) can be a promising technique with features of affordability, portability, and real‐time detection capabilities. This study aimed to validate the safety and effectiveness of a modified ECD. Methods The ECD underwent a modification where six lamps of various colors, and it was utilized in a prospectively multicenter randomized controlled clinical trial involving 96 patients across three hospitals from June 2018 to December 2018. The trial incorporated a self‐control randomization with an equal distribution of left or right side of vertebral pedicle among two groups: the free‐hand group and the ECD group. A total of 496 pedicle screws were inserted, with 248 inserted in each group. The primary outcomes focused on the accuracy of pedicle screw placement and the frequency of intraoperative X‐rays. Meanwhile, the secondary indicator measured the time required for pedicle screw placement. Results were presented as means ± SD. Paired samples t‐test and χ2‐test were used for comparison. Furthermore, an updated review was conducted, which included studies published from 2006 onwards. Results Baseline patient characteristics were recorded. The primary accuracy outcome revealed a 96.77% accuracy rate in the ECD group, compared to a 95.16% accuracy rate in the free‐hand group, with no significant differences noted. In contrast, ECD demonstrated a significant reduction in radiation exposure frequency when compared to the free‐hand group (1.11 ± 0.32 vs. 1.30 ± 0.53; p

Train delay prediction is a vital part of railway system, but due to uncertain factors such as the complexity of the railway system and spatial–temporal features, it is often difficult to predict train delay in practice. In this paper, we propose a Spatial–Temporal and Bi-directional Long Short-Term Memory (ST-BiLSTM) model to deal with the train delay prediction problem. The model contains spatial–temporal blocks to capture spatial and temporal features and a bi-directional Long Short-Term Memory (LSTM) block to introduce bi-directional information through an attention mechanism. Experiments demonstrate that ST-BiLSTM outperforms the existing baselines in two evaluation metrics.

Abstract Background The mechanism of hepatitis B virus (HBV)‐induced carcinogenesis remains an area of interest. The accumulation of hepatitis B surface antigen in the endoplasmic reticulum (ER) of hepatocytes stimulates persistent ER stress. Activity of the unfolded protein response (UPR) pathway of ER stress may play an important role in inflammatory cancer transformation. How the protective UPR pathway is hijacked by cells as a tool for malignant transformation in HBV‐related hepatocellular carcinoma (HCC) is still unclear. Here, we aimed to define the key molecule hyaluronan‐mediated motility receptor (HMMR) in this process and explore its role under ER stress in HCC development. Methods An HBV‐transgenic mouse model was used to characterize the pathological changes during the tumor progression. Proteomics and transcriptomics analyses were performed to identify the potential key molecule, screen the E3 ligase, and define the activation pathway. Quantitative real‐time PCR and Western blotting were conducted to detect the expression of genes in tissues and cell lines. Luciferase reporter assay, chromatin immunoprecipitation, coimmunoprecipitation, immunoprecipitation, and immunofluorescence were employed to investigate the molecular mechanisms of HMMR under ER stress. Immunohistochemistry was used to clarify the expression patterns of HMMR and related molecules in human tissues. Results We found sustained activation of ER stress in the HBV‐transgenic mouse model of hepatitis‐fibrosis‐HCC. HMMR was transcribed by c/EBP homologous protein (CHOP) and degraded by tripartite motif containing 29 (TRIM29) after ubiquitination under ER stress, which caused the inconsistent expression of mRNA and protein. Dynamic expression of TRIM29 in the HCC progression regulated the dynamic expression of HMMR. HMMR could alleviate ER stress by increasing autophagic lysosome activity. The negative correlation between HMMR and ER stress, positive correlation between HMMR and autophagy, and negative correlation between ER stress and autophagy were verified in human tissues. Conclusions This study identified the complicated role of HMMR in autophagy and ER stress, that HMMR controls the intensity of ER stress by regulating autophagy in HCC progression, which could be a novel explanation for HBV‐related carcinogenesis.

Abstract Pyopneumothorax with bronchopleural fistula is a rare complication of lung infection. We herein report a case of pyopneumothorax with bronchopleural fistula caused by Porphyromonas gingivalis infection, a common pathogenic pathogen of periodontitis, in a 49‐year‐old man with periodontitis. The patient was admitted with respiratory failure. Pleural puncture yielded a lot of gas continually and foul‐smelling light brown pus, which was found to be caused due to infection with P. gingivalis by the metagenomic next generation sequencing (mNGS) and anaerobic culture.

Cancer is a noncommunicable disease burden and the second-leading cause of death worldwide. Novel medications and drug possibilities are sought everyday throughout the world in pursuit of cancer therapy. Colorectal cancer as one of the leading cancers across the globe can be treated effectively using TCM via decreasing the incidence and increasing the survival of patients. Gallic acid (GA) is an effective polyphenol used in TCM to treat several disorders including cancer. Our hypothesis was set to determine that GA possesses cytotoxic effects on CRC cells and that apoptosis and/or autophagy could be the rationale behind the mechanism. Therefore, in the current study, we investigated the cytotoxic effects of GA on human colorectal adenocarcinoma HT-29 cells and the mechanisms of such effects. The IC50 for the cytotoxic effects of GA as evidenced by the MTT assay was 37.08 μg/mL. The outcomes indicated that GA can cause changes in MMP and result in the formation or accumulation of exogenous ROS at the IC50 dose. Consequently, the polyphenol can induce mitochondrial- or ER-stress-induced apoptosis and canonical autophagy other than contributing to the induction of ferroptosis in HT-29 cells as evidenced by quantitative PCR and western blotting. Our results indicate that GA is an effective cytotoxic agent for the management of CRC at the preclinical level and is a valuable candidate for clinical trials.

Chronic stress can induce negative emotion states, including anxiety and depression, leading to sympathetic overactivation and disturbed physiological homeostasis in peripheral tissues. While anxiety-related neural circuitry integrates chronic stress information and modulates sympathetic nervous system (SNS) activity, the critical nodes linking anxiety and sympathetic activity still need to be clarified. In our previous study, we demonstrated that the ventromedial hypothalamus (VMH) is involved in integrating chronic stress inputs and exerting influence on sympathetic activity. However, the underlying synaptic and electrophysiological mechanisms remain elusive. In this study, we combined in vitro electrophysiological recordings, behavioral tests, optogenetic manipulations, and SNS activity analyses to explore the role of VMH in linking anxiety emotion and peripheral SNS activity. Results showed that the VMH played an important role in bidirectionally regulating anxiety-like behavior and peripheral sympathetic excitation. Chronic stress enhanced excitatory inputs into VMH neurons by strengthening the connection with the paraventricular hypothalamus (PVN), hence promoting anxiety and sympathetic tone outflow, an important factor contributing to the development of metabolic imbalance in peripheral tissues and cardiovascular diseases.

Abstract Background Nurturing care is necessary for optimal early childhood development. This study aimed to investigate the prevalence of parental risks in rural East China and assess their impacts on early development in children younger than three years old. Methods This community-based cross-sectional survey was conducted among 3852 caregiver-child pairs in Zhejiang Province from December 2019 to January 2020. Children aged 0 to 3 years were recruited from China’s Early Childhood Development Program (ECD). Local child health care providers conducted face-to-face interviews with the primary caregivers. Demographic information of the participants was collected by questionnaire. Each child was screened for parental risk through the Parental Risk Checklist designed by the ECD program. The Ages and Stages Questionnaire (ASQ) was used to identify children with potential developmental delays. Multinomial logistic regression model and linear trend test were applied to assess the association between parental risks and suspected developmental delays. Results Among the 3852 children included in the analyses, 46.70% had at least one parental risk and 9.01% presented suspected developmental delays in any domain of ASQ. Parental risk was statistically associated with the overall suspected developmental delay in young children (Relative Risk Ratio (RRR): 1.36; 95% confidence interval (CI): 1.08, 1.72; P = 0.010) after adjusting potential confounders. Compared with children with no parental risk, children exposed to 3 or more parental risks had 2.59, 5.76, 3.95, and 2.84 times higher risk of the suspected developmental delay in overall ASQ, communication, problem-solving, and personal-social domain, respectively (P values

Abstract Background Early iron deficiency (ID) is a common risk factor for poorer neurodevelopment, limiting children’s potential and contributing to global burden. However, it is unclear how early ID alters the substrate of brain functions supporting high-order cognitive abilities and whether the timing of early ID matters in terms of long-term brain development. This study aimed to examine the effects of ID during fetal or early postnatal periods on brain activities supporting proactive and reactive cognitive control in pre-adolescent children. Methods Participants were part of a longitudinal cohort enrolled at birth in southeastern China between December 2008 and November 2011. Between July 2019 and October 2021, 115 children aged 8–11 years were invited to participate in this neuroimaging study. Final analyses included 71 children: 20 with fetal ID, 24 with ID at 9 months (postnatal ID), and 27 iron-sufficient at birth and 9 months. Participants performed a computer-based behavioral task in a Magnetic Resonance Imaging scanner to measure proactive and reactive cognitive control. Outcome measures included accuracy, reaction times, and brain activity. Linear mixed modeling and the 3dlme command in Analysis of Functional NeuroImages (AFNI) were separately used to analyze behavioral performance and neuroimaging data. Results Faster responses in proactive vs. reactive conditions indicated that all groups could use proactive or reactive cognitive control according to contextual demands. However, the fetal ID group was lower in general accuracy than the other 2 groups. Per the demands of cues and targets, the iron-sufficient group showed greater activation of wide brain regions in proactive vs. reactive conditions. In contrast, such condition differences were reversed in the postnatal ID group. Condition differences in brain activation, shown in postnatal ID and iron-sufficient groups, were not found in the fetal ID group. This group specifically showed greater activation of brain regions in the reward pathway in proactive vs. reactive conditions. Conclusions Early ID was associated with altered brain functions supporting proactive and reactive cognitive control in childhood. Alterations differed between fetal and postnatal ID groups. The findings imply that iron supplement alone is insufficient to prevent persisting brain alterations associated with early ID. Intervention strategies in addition to the iron supplement should consider ID timing.

Abstract Background Cytokine-induced memory-like natural killer (CIML NK) cells have been found to possess potent antitumor responses and induce complete remissions in patients with leukemia. However, the poor infiltration of transferred NK cells is a major obstacle in developing adoptive cell immunotherapy for solid tumors. In our study, we explored the potential of using the tumor-penetrating peptide iRGD to deliver activated CIML NK cells deep into tumor tissues. Methods After being briefly stimulated with interleukin-12 (IL-12), IL-15, and IL-18, CIML NK cells were assessed for their phenotype and function with flow cytometry. The penetrating and killing capability of iRGD-modified CIML NK cells in tumor spheroids was revealed by confocal microscopy. The anti-tumor efficacy of these modified CIML NK cells was tested in hepatocellular carcinoma (HCC) xenograft mouse models. Results Treating NK cells with cytokines led to a substantial activation, which was evidenced by the upregulation of CD25 and CD137. After a resting period of six days, CIML NK cells were still able to display strong activation when targeting HepG2 and SK-Hep-1 HCC cell lines. Additionally, CIML NK cells produced increased amounts of cytokines (interferon-gamma and tumor necrosis factor alpha) and exhibited heightened cytotoxicity towards HCC cell lines. The iRGD modification enabled CIML NK cells to infiltrate multicellular spheroids (MCSs) and, consequently, to induce cytotoxicity against the target cancer cells. Moreover, the CIML NK cells modified with iRGD significantly decreased tumor growth in a HCC xenograft mouse model. Conclusion Our findings demonstrate that CIML NK cells possess augmented potency and durability against HCC cell lines in vitro. Additionally, we have seen that the incorporation of iRGD to CIML NK cells facilitates enhanced infiltration and targeted destruction of MCSs. Moreover, the application of iRGD-modified CIML NK cells reveal remarkable anti-tumor efficacy against HCC in vivo.

It is common for diabetic kidney disease (DKD) to be complicated by abnormal blood glucose, blood lipids, and blood pressure rhythms. Thus, it is essential to examine diagnostic and treatment plans from the perspective of circadian disruption. This brief review discusses the clinical relevance of circadian rhythms in DKD and how the core clock gene encoding brain and muscle arnt-like protein 1 (BMAL1) functions owing to the importance of circadian rhythm disruption processes, including the excretion of urinary protein and irregular blood pressure, which occur in DKD. Exploring Bmal1 and its potential mechanisms and signaling pathways in DKD following contact with Sirt1 and NF-κB is novel and important. Finally, potential pharmacological and behavioral intervention strategies for DKD circadian rhythm disturbance are outlined. This review aids in unveiling novel, potential molecular targets for DKD based on circadian rhythms.

The hydraulic joint is the key driving component of a robot. To reduce the joint size of the hydraulic robot, and improve the control accuracy and dynamic response performance, this paper proposes a novel joint structure and control method of a ball double-screw hydraulic robot. Using ball and circular arc spiral groove transmission, the hydraulic joint has a small transmission friction coefficient, compact overall structure and higher transmission accuracy. Aiming to resolve the problems of low control accuracy and motion instability caused by temperature drift in valve-controlled hydraulic systems, the high-precision joint control method based on adaptive fuzzy control compensation is used to improve the control accuracy and stability. The static and dynamic characteristics of the designed hydraulic joint are analyzed by simulation. A test platform was built, and the physical prototype of the hydraulic joint underwent static testing, dynamic control, amplitude frequency response and trajectory tracking tests. The experimental results were similar to the simulation results. The ball double-screw hydraulic robot joint has the characteristics of low starting pressure, high energy density, fast dynamic response, small amplitude frequency attenuation and high control accuracy. The starting pressure is 0.5 MPa, maximum swing frequency is 3 Hz, positioning accuracy is ± 0.03°, tracking accuracy is ± 3.9° and maximum angular velocity at 10 MPa is about 7.6 rad/s, which is close to the angular velocity of the actual human joint.

Abstract Background To evaluate a new method of implantable collamer lens (ICL) sizing based on ultrasound biomicroscopy (UBM) video clips. Methods This observational study included consecutive patients with myopia and myopic astigmatism scheduled for V4c toric ICL (TICL) implantation (STAAR) at Hangzhou MSK Eye Hospital (October 2020 to November 2020). Sulcus-to-sulcus (STS) distance, lens thickness (LT), and clinical refraction were measured preoperatively. The ZZ ICL formula (provides the predicted vault height and refraction based on TICL size, intraocular meridian, power, and eye parameters, including STS distance and LT) was used to select TICL size and predict vault height and residual refraction, which was also compared with the STAAR software recommended. Vault and residual refraction were measured at 3 months postoperatively. Results The analysis included 168 eyes in 84 patients. Postoperative vault size was comparable to that predicted by the ZZ ICL formula (528 ± 193 vs. 545 ± 156 μm, P = 0.227). Vault prediction error (PE) by the ZZ ICL formula was within 100, 300, and 500 μm in 40.48%, 88.10%, and 100% of eyes, respectively. Spherical equivalent (SE) and absolute cylindrical refractive error were 0.36 ± 0.48 and 0.40 ± 0.31 D at 3 months postoperatively. The SE PE, absolute cylindrical PE, and percentages of eyes with an absolute cylindrical PE within ± 0.50 D and ± 1.00 D were lower for the ZZ ICL formula than for the STAAR software (P

Precipitation nowcasting in real-time is a challenging task that demands accurate and current data from multiple sources. Despite various approaches proposed by researchers to address this challenge, models such as the interaction-based dual attention LSTM (IDA-LSTM) face limitations, particularly in radar echo extrapolation. These limitations include higher computational costs and resource requirements. Moreover, the fixed kernel size across layers in these models restricts their ability to extract global features, focusing more on local representations. To address these issues, this study introduces an enhanced convolutional long short-term 2D (ConvLSTM2D) based architecture for precipitation nowcasting. The proposed approach includes time-distributed layers that enable parallel Conv2D operations on each image input, enabling effective analysis of spatial patterns. Following this, ConvLSTM2D is applied to capture spatiotemporal features, which improves the model’s forecasting skills and computational efficacy. The performance evaluation employs a real-world weather dataset benchmarked against established techniques, with metrics including the Heidke skill score (HSS), critical success index (CSI), mean absolute error (MAE), and structural similarity index (SSIM). ConvLSTM2D demonstrates superior performance, achieving an HSS of 0.5493, a CSI of 0.5035, and an SSIM of 0.3847. Notably, a lower MAE of 11.16 further indicates the model’s precision in predicting precipitation.

Abstract Chimeric antigen receptor (CAR)‐T cell therapy is a transformative treatment against advanced malignancies. Unfortunately, once administrated in vivo, CAR‐T cells become out of artificial control, and fierce response to CAR‐T therapy may cause severe adverse events, represented by cytokine‐release syndrome and on‐target/off‐tumor effects. Here, a nanomodified switch strategy is developed, leading to sustained and precise “on‐tumor only” activation of CAR‐T cells. Here, original gelatinase‐responsive nanoparticles (NPs) are used to selectively deliver the heterodimerizing switch, which is the key component of switchable CAR with separated activation modules. The “NanoSwitch” is tumor‐specific, thus inactivated switchable CAR‐T cells do little harm to normal cells, even if the normal cells express the target of CAR‐T. Owing to the sustained‐release effect of NPs, the CAR‐T cells are activated smoothly, avoiding sudden release of cytokine. These data introduce NanoSwitch as a universal and applicable solution to safety problems of CAR‐T therapy regardless of the target.

In this study, a skin gas detection system based on quartz enhanced photoacoustic spectroscopy (QEPAS) with a constant temperature collection chamber and an automatic frequency adjustment function was used to collect and monitor carbon dioxide (CO2) emissions from human skin. The detection element of the system is an on-beam structure assembled by a 30.72 kHz quartz tuning fork (QTF). A laser with a wavelength of 4991.26 cm−1 is emitted (with a wavelength adjustment range of 10 cm−1) to excite the QTF. When the integration time is 365 s, the system can achieve a minimum detection limit (MDL) of 2.6 ppmv. The sensitivity of the system is 636.9 ppmv/V. The gas detection system is used to monitor the concentration of CO2 emissions from different parts of the skin and the same part covered by different cosmetics. The CO2 emission rate is defined as the ratio of the skin gas monitoring time of 25 min to the CO2 concentration variable in the gas chamber (volume of 8 mL). The results were collected from three healthy volunteers. Among the six different parts, the cheeks emitted the fastest rate (the average rate was 365.5 ppmv/min) of CO2, and the thighs emitted the slowest rate (the average rate was 56.4 ppmv/min) of CO2. Comparing the experimental results of the six sites at different times, the order of the CO2 emission rate is identical for all six sites. In the experiments with the three cosmetic products (experimental site: forearm), comparing the CO2 emission rate from clean skin with the CO2 emission rate from cosmetic-covered skin shows that sunscreen is the most breathable, followed by barrier cream, and foundation is the least breathable.

The contribution of lymphocyte subset composition of the graft on the outcomes following haploidentical peripheral blood stem cell transplantation (haploPBSCT) is not fully elucidated. We retrospectively analyzed 314 patients with hematological malignancies who underwent haploPBSCT from 2016 to 2020 in our center. We obtained a cutoff value of CD3+ T cell dose (2.96 × 10 8 /kg) that separated the risk of II–IV acute graft-versus-host disease (aGvHD) and divided patients into the low CD3+ T cell dose group (CD3+ low) and the high CD3+ T cell dose (CD3+ high) group. Significantly higher incidences of I-IV aGvHD, II–IV aGvHD, and III–IV aGvHD were identified in the CD3+ high group (50.8%, 19.8%, and 8.1% in the high group, 23.1%, 6.0%, and 0.9% in the low group, P < 0.0001, P = 0.002, and P = 0.02, respectively). We found that CD4+ T cell and its naïve and memory subpopulations of grafts had a significant impact on aGvHD ( P = 0.005, P = 0.018, and P = 0.044). Besides, we found an inferior reconstitution of natural killer (NK) cells in the CD3+ high group than in the low group within the first-year posttransplant (239 cells/μL vs 338 cells/μL, P = 0.0003). No differences in engraftment, chronic GvHD (cGvHD), relapse rate, transplant-related mortality (TRM), and overall survival (OS) were identified between the two groups. In conclusion, our study found that a high CD3+ T cell dose led to a high risk of aGvHD and inferior reconstitution of NK cells in the haploPBSCT setting. In the future, carefully manipulating the composition of lymphocyte subsets of grafts might reduce the risk of aGvHD and improve the transplant outcome.

ObjectiveTo compare the physiological health of Chinese children around the COVID-19 lockdown.MethodsWe extracted data on children's anthropometric and laboratory parameters from May to November in both 2019 and 2020 from the Health Checkup Center, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China. Overall, 2162 children aged 3~18 years without comorbidities in 2019 and 2646 in 2020 were assessed. Mann Whitney U tests were used to compare differences between the above health indicators before and after COVID-19 outbreak. Quantile regression analyses adjusted for age, sex and body mass index (BMI) were also used in analysis. Chi-square tests and Fisher's exact tests were used for comparing differences of categorical variables.ResultsCompared with children examined in 2019 before the outbreak, children in 2020 had a higher median z score of BMI for age (−0.16 vs. −0.31), total cholesterol (TC, 4.34 vs. 4.16 mmol/L), low density lipoprotein cholesterol (LDL-C, 2.48 vs. 2.15 mmol/L), high density lipoprotein cholesterol (HDL-C, 1.45 vs. 1.43 mmol/L) and serum uric acid (290 vs. 282 μmol/L), and a lower hemoglobin (Hb, 134 vs. 133 g/L), triglycerides (TG, 0.70 vs. 0.78 mmol/L) and 25(OH)D (45.8 vs. 52.2 nmol/L), all P < 0.05. No differences were identified for waist height ratio, blood pressure and fasting glucose (both P > 0.05). However, in regression models after adjusting, BMI, TC, LDL-C, blood glucose and sUA were positively correlated with year; while Hb, TG and 25(OH)D were negatively correlated with year (all P < 0.05). Accordingly, children in 2020 had a higher prevalence of overweight/obesity (20.6 vs. 16.7%, P < 0.001), hypercholesterol (16.2%vs. 10.2%, P < 0.001), high LDL-C (10 vs. 2.9%, P < 0.001), hyperuricemia (18.9 vs.15.1%, P = 0.002), vitamin D deficiency (22.6 vs. 8.1%, P < 0.001) and a lower prevalence of high TG (4.3 vs. 2.8%, P = 0.018) compared with children in 2019.ConclusionIn this real-world study, we found that long-term lockdown due to COVID-19 outbreak might cause adverse impact on children's metabolic health, which might increase their future risk of cardiovascular diseases. Thus, parents, health professionals, educationists, and caregivers should pay more attention to children's dietary pattern and lifestyle, especially in this new normal against COVID-19.

With the formation of an aging society, cataract caused by age has become a public common concern about health problem all over the world. Surgery by intraocular lens replacement is the only effective mean to treat cataract. The most important thing to treat cataract is accurately calculating the intraocular lens diopter. However, some patients did not feel satisfied because the error of calculation of intraocular lens diopter. With big data analysis and self-learning, artificial intelligence can deeply analyze and autonomously decide on complex clinical data. Therefore, this technology is expected to improve the calculation accuracy of intraocular lens diopter, to reduce postoperative refractive error and to improve patients' satisfaction. By referring to relevant literature at domestic and abroad, this paper is aimed to introduce the basic principle of artificial intelligence in intraocular lens diopter calculation, analyze and compare the characteristics, advantages and limitations of artificial intelligence based on different principles.

Abstract Background Iron deficiency (ID) impairs patient physical activity, recognition and life quality, which is difficult to perceive but should not be underestimated. Worldwide efforts have been made to lower ID burden, however, whether it decreased equally in different regions and sexes is unclear. This study is to examine regional and sex inequalities in global ID from 1990 to 2017. Methods We conducted a longitudinal, comparative burden-of-disease study. Disability-adjusted life-years (DALYs) of ID were obtained from Global Burden of Disease Report 2017. Human Development Index (HDI) data were obtained from Human Development Report 2017. Gini coefficient and the concentration index were calculated to assess the equities in global burden of ID. Results A downward trend of global ID burden (from 569.3 (95% Uncertainty Interval [UI]: 387.8–815.6) to 403.0 (95% UI: 272.4–586.6), p

Up to 50% of hepatocellular carcinoma (HCC) is caused by hepatitis B virus (HBV) infection, and the surface protein of HBV is essential for the progression of HBV-related HCC. The expression of large HBV surface antigen (LHB) is presented in HBV-associated HCC tissues and is significantly associated with the development of HCC. Gene set enrichment analysis revealed that LHB overexpression regulates the cell cycle process. Excess LHB in HCC cells induced chronic endoplasmic reticulum (ER) stress and was significantly correlated with tumor growth in vivo. Cell cycle analysis showed that cell cycle progression from G1 to S phase was greatly enhanced in vitro. We identified intensive crosstalk between ER stress and cell cycle progression in HCC. As an important regulator of the G1/S checkpoint, p27 was transcriptionally upregulated by transcription factors ATF4 and XBP1s, downstream of the unfolded protein response pathway. Moreover, LHB-induced ER stress promoted internal ribosome-entry-site-mediated selective translation of p27, and E3 ubiquitin ligase HRD1-mediated p27 ubiquitination and degradation. Ultimately, the decrease in p27 protein levels reduced G1/S arrest and promoted the progress of HCC by regulating the cell cycle.

Parathyroid hormone (PTH) plays a role in maintaining calcium and phosphorus homeostasis, and in secondary hyperparathyroidism excess PTH secretion contributes to bone loss. Here the authors report an optogenetic approach to inhibit PTH secretion in human hyperplastic parathyroid cells, and prevented hyperplastic parathyroid tissue-induced bone loss in mice.

Here, the authors show that expression of kindlin-2 is increased in patients with nonalcoholic fatty liver disease (NAFLD). In mouse models, specific deletion of kindlin-2 in liver ameliorates, while its overexpression exacerbates, NAFLD by modulating Foxo1 in hepatocytes.

Abstract Objectives The signet‐ring cell carcinoma (SRCC) of the stomach is highly invasive. Patients with stage III gastric SRCC usually experience tumor recurrence within 2 years after radical surgery. Unfortunately, there is no effective treatment to postpone recurrence following adjuvant chemotherapy. Our study aimed to explore the safety and efficacy of neoantigen‐reactive T lymphocytes (NRTs) in patients with stage III gastric SRCC. Methods The study included 20 patients with stage III gastric SRCC who received radical surgery and adjuvant chemotherapy. Following the adjuvant chemotherapy, they underwent treatment with a range of one to four cycles of personalised neoantigen‐reactive T cells. The primary endpoint was the median progression‐free survival (mDFS). The secondary endpoint was safety and immune responses. The median duration of follow‐up was 41 months (95% CI: 39–42.9 months). Results Our results showed that patients who received adjuvant neoantigen‐reactive T‐cell immunotherapy demonstrated a propensity towards prolonged disease‐free survival (DFS) and overall survival (OS) in comparison to previous studies. The 2‐year DFS and OS rates reached 73.7% and 95%, respectively, whereas the 5‐year DFS and OS rates were 44% and 69%. The median DFS was 41 months (95% CI: 28.9–53.1 months) and the median OS was not reached. In addition, there was a significant increase in serum concentrations of IL‐2, IL‐4, IL‐6, IL‐10, TNF‐α and IFN‐γ after cell immunotherapy. The adverse reactions were mild. Conclusion In conclusion, adjuvant immunotherapy with NRTs showed promising efficacy alongside a manageable safety profile.

As a critical prerequisite for semantic facade reconstruction, accurately separating wall and protrusion points from facade point clouds is required. The performance of traditional separation methods is severely limited by facade conditions, including wall shapes (e.g., nonplanar walls), wall compositions (e.g., walls composed of multiple noncoplanar point clusters), and protrusion structures (e.g., protrusions without regularity, repetitive, or self-symmetric features). This study proposes a more widely applicable wall and protrusion separation method. The major principle underlying the proposed method is to transform the wall and protrusion separation problem as a ground filtering problem and to separate walls and protrusions using ground filtering methods, since the 2 problems can be solved using the same prior knowledge, that is, protrusions (nonground objects) protrude from walls (ground). After transformation problem, cloth simulation filter was used as an example to separate walls and protrusions in 8 facade point clouds with various characteristics. The proposed method was robust to the facade conditions, with a mean intersection over union of 90.7%, and had substantially higher accuracy compared with the traditional separation methods, including region growing-, random sample consensus-, multipass random sample consensus-based, and hybrid methods, with mean intersection over union values of 69.53%, 49.52%, 63.93%, and 47.07%, respectively. Besides, the proposed method was general, since existing ground filtering methods (including the maximum slope, progressive morphology, and progressive triangular irregular network densification filters) can also perform well.

Abstract Personalized neoantigen vaccines have shown strong immunogenicity in clinical trial, but still face various challenges in facilitating an efficient antitumor immune response. Here, a personalized neoantigen nanovaccine (PNVAC) platform for adjuvant cancer immunotherapy is generated. PNVAC triggers superior protective efficacy against tumor recurrence and promotes longer survival than free neoantigens, especially when combined with anti‐PD‐1 treatment in a murine tumor model. A phase I clinical trial (ChiCTR1800017319) is initiated to evaluate the safety, immunogenicity, and prophylactic effect of PNVAC on preventing tumor recurrence in patients with high‐risk gastric/gastroesophageal junction cancer after adjuvant chemotherapy of postsurgical resection. The one‐ and two‐year disease‐free survival rates are significantly higher than historical record. PNVAC induces both CD4+ and CD8+ T cell responses as well as antigen‐experienced memory T cell phenotype. Furthermore, the immune response is persistent and remains evident one year after the vaccination. This work provides a safe and feasible strategy for developing neoantigen vaccines to delay gastric cancer recurrence after surgery.

Abstract Background Williams syndrome (WS) is a multisystem neurodevelopmental disorder caused by microdeletions in 7q11.23. This study aims to characterize the clinical phenotypes of Chinese children with WS to help for the early diagnosis and intervention of this disease. Methods 231 children diagnosed with WS were retrospectively recruited to the study. Clinical data were analyzed to obtain the incidence of different clinical phenotypes. The occurrence of phenotypes and the influence of gender and age on the incidence of different phenotypes were analyzed. Results All WS exhibited facial dysmorphism (100.0%). The majority had neurodevelopmental disorder (91.8%), hoarseness (87.4%) and cardiovascular anomalies (85.7%). The incidence of short stature (46.9%), inguinal hernia (47.2%), hypercalciuria (29.10%), hypercalcemia (9.1%), subclinical hypothyroidism (26.4%) and hypothyroidism (7.4%) were relatively higher. Gender differences were found in supravalvular aortic stenosis (SVAS, p

Accurate and rapid estimation of canopy cover (CC) is crucial for many ecological and environmental models and for forest management. Unmanned aerial vehicle-light detecting and ranging (UAV-LiDAR) systems represent a promising tool for CC estimation due to their high mobility, low cost, and high point density. However, the CC values from UAV-LiDAR point clouds may be underestimated due to the presence of large quantities of within-crown gaps. To alleviate the negative effects of within-crown gaps, we proposed a pit-free CHM-based method for estimating CC, in which a cloth simulation method was used to fill the within-crown gaps. To evaluate the effect of CC values and within-crown gap proportions on the proposed method, the performance of the proposed method was tested on 18 samples with different CC values (40−70%) and 6 samples with different within-crown gap proportions (10−60%). The results showed that the CC accuracy of the proposed method was higher than that of the method without filling within-crown gaps (R2 = 0.99 vs 0.98; RMSE = 1.49% vs 2.2%). The proposed method was insensitive to within-crown gap proportions, although the CC accuracy decreased slightly with the increase in within-crown gap proportions.

Abstract Objective Cellular prion protein (PrPC), the primary form of prion diseases pathogen, has received increasing attention for its protective effect against ischaemic stroke. Little is known about its role in peripheral immune responses after cerebral ischaemia/reperfusion (I/R) injury. This study is to detect the variation of splenic CD4+ T lymphocytes differentiation and the concentration of inflammatory cytokines after murine cerebral I/R injury in the context of PRNP expression as well as its influence on the ischaemic neuronal apoptosis. Methods We established the cerebral ischaemic murine model of different PRNP genotypes. We detected the percentage of splenic CD4+PrPC+ T cells of PRNP wild‐type mice and the ratio of splenic Th1/2/17 lymphocytes of mice of different PRNP expression. The relevant inflammatory cytokines were then measured. Oxygen glucose deprivation/reperfusion (OGD/R) HT22 mouse hippocampal neurons were co‐cultured with the T‐cell‐conditioned medium harvested from the spleen of modelled mice and then the neuronal apoptosis was detected. Results CD4+ PrPC+ T lymphocytes in wild‐type mice elevated after MCAO/R. PRNP expression deficiency led to an elevation of Th1/17 phenotypes and the promotion of pro‐inflammatory cytokines, while PRNP overexpression led to the elevation of Th2 phenotype and upregulation of anti‐inflammatory cytokines. In addition, PrPC‐overexpressed CD4+T cells weakened the apoptosis of OGD/R HT‐22 murine hippocampal neurons caused by MCAO/R CD4+ T‐cell‐conditioned medium, while PrPC deficiency enhanced apoptosis. Interpretation PrPC works as a neuron protector in the CNS when I/R injury occurs and affects the peripheral immune responses and defends against stroke‐induced neuronal apoptosis.

Abstract Background Paraneoplastic neurological syndromes (PNSs) are broad-spectrum disorders that can affect any part of the nervous system varying in core symptoms. Onconeural antibodies, including Hu, Yo, Ri, anti-CV2, amphiphysin, Ma2, and Tr are well-characterized and commonly used for the diagnosis of definite PNS. Generally, anti-CV2 antibodies have usually been associated with cerebellar ataxia, chorea, peripheral and autonomic neuropathies, myelopathy, optic neuritis, and retinitis. However, Parkinsonism has not been reported as the core symptom in patients with anti-CV2 antibodies. Case presentation We report a patient with anti-CV2 antibody manifested as Parkinsonism and autonomic dysfunction, which may lead to the diagnosis of multiple system atrophy with predominant Parkinsonism (MSA-P). A lumbar puncture examination was undergone to find a positive anti-CV2 antibody in cerebrospinal fluid. PET-CT showed no tumor. Immunotherapy was adopted and the symptoms were relieved for 5 months. However, with no evidence of tumor, he died after 8 months. Conclusions Our findings indicate that PNS with anti-CV2 antibody can be shown as MSA-P mimic. Considering that MSA is a neurodegenerative disease with a poor prognosis, screening for other treatable or controllable factors like PNS presented in this case is necessary when encountering a rapid progressive MSA-mimic patient.

Abstract Background To study the competency of general practitioners (GPs) in Shanghai, China on prevention and management of type 2 diabetes, also understand factors that may prohibit it. Methods A survey questionnaire with 25 questions was designed based on 2013 Chinese Type 2 Diabetes Prevention Guidelines and Chinese Type 2 Diabetes Prevention Guidelines (Grassroots Edition) and conducted among 789 GPs who work at 54 community healthcare centers (CHCs) within 16 districts at Shanghai, China. Excel 2016 and SPSS 24.0 were used for data analysis, and a difference of P

Breast cancer, the most common malignant tumor in women, has become a worldwide burden for family and society. MicroRNAs (miRNAs or miRs) are recognized as critical mediators of cancer-related processes, since they have the ability to coordinately suppress multiple target genes. In this study, we aim to find out specific miRNAs involved in the progression of breast cancer and explore the underlying molecular mechanism. Bioinformatics analysis suggested miR-301 as a differentially overexpressed miRNA in breast cancer, which was confirmed by expression determination. Functional assays were employed to explore the effect of miR-301 and its downstream effectors cytoplasmic polyadenylation element-binding protein 1 (CPEB1), SIRT1, and SOX2 on malignant phenotypes of breast cancer. The interaction among these factors was explained using luciferase and RNA immunoprecipitation (RIP) assays. In addition, the in vivo impact of miR-301 on breast cancer was assessed by cellular tumorigenicity in nude mice. We found that miR-301 overexpression restricted CPEB1 level and further promoted cell proliferation, metastasis, and cell cycle progression and impeded apoptosis. Moreover, CPEB1 regulated breast cancer development by mediating the SIRT1/SOX2 pathway. Further, miR-301 overexpression accelerated tumor formation in nude mice. Our results indicate that miR-301 overexpression accelerates the progression of breast cancer through the CPEB1/SIRT1/SOX2 axis.

Registration of unmanned aerial vehicle laser scanning (ULS) and ground light detection and ranging (LiDAR) point clouds in forests is critical to create a detailed representation of a forest structure and an accurate retrieval of forest parameters. However, tree occlusion poses challenges for those registration methods used artificial markers, and some automated registration methods have low time-efficiency due to the process of object (e.g., tree, crown) segmentation. In this study, we propose an automated and time-efficient method to register ULS and ground LiDAR (including terrestrial and backpack laser scanning) forest point clouds. Registration involves coarse alignment and fine registration, where the coarse alignment is divided into vertical and horizontal alignment. The vertical alignment is implemented by rotating grounds to the horizontal plane, and the horizontal alignment is achieved by canopy image matching. During image matching, vegetation points are projected onto the horizontal plane to obtain two binary images, and then, canopy shape feature, which is described by a two-point congruent set and canopy overlap, is used to match the binary images. Finally, we implement coarse alignment of ULS and ground LiDAR datasets by combining the results of ground alignment and image matching and finish fine registration in six plantation forest plots with sizes of 0.03 ha to 0.25 ha. Experimental results show that the ULS and ground LiDAR data in different plots are registered, of which the coarse alignment errors are less than 0.20 m in the horizontal direction, the final registration accuracy is less than 0.15 m, and the average runtime is less than 1 s. Our study demonstrates the effectiveness of the proposed strategy and has able to perform accurate and quick registration of ULS and ground LiDAR data from plantation forests with different attributes.

Rainfall loss by canopy interception comprises a substantial portion of the water budget in forested ecosystems, and accurately measuring and simulating this process is critical for the effective management of forest water resources. Pinus sylvestris var. mongolica is a main afforested species in northeastern China; however, little work has been carried out assessing the canopy interception loss of this plant species in semi-humid areas. Accordingly, a rainfall interception experiment was conducted for P. sylvestris plots in a semi-humid area of northeastern China from June to September 2019. The revised Gash analytical model was then applied to the canopy interception values, and its regional applicability was tested. During the experimental process, incident rainfall (P), throughfall (Tf), and stemflow events (Sf) were collected and measured, while meteorological data were simultaneously obtained on-site. The Penman (PM) equation and the Gash regression method were used to estimate evaporation rates (E) from the saturated canopy, and the Leyton constraint method was applied to obtain canopy storage capacity (S). Parameters such as E, S, stemflow partitioning coefficient (pt), and trunk storage capacity (St) were scaled to the canopy cover fraction per unit area (producing Ec, Sc, ptc, and Stc in the revised Gash analytical model, respectively) for use in the simulated rainfall interception. The proportions of measured canopy interception (I), Sf, and Tf accounted for 17.2 %, 6.0 %, and 76.8 % of P, respectively; whereas the Sc, ptc, and Stc were calculated as 1.60 mm, 0.067, and 0.21 mm, respectively, over the experimental period. The revised Gash analytical model with Ec varied from 0.37 to 0.93, and Ec/R varied from 0.62 to 1.55 (acquired via the PM equation), thus indicating its ability to accurately simulate P. sylvestris canopy interception. These findings can provide a theoretical foundation for understanding correlated ecological and hydrological processes, allowing land managers to predict the impacts of afforestation on water inputs for current and future rainfall scenarios in typical coniferous forests of semi-humid regions.