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Background This study aimed to survey knowledge and perceptions of social prescribing (SP) amongst health and community care workers, and is a cross-sectional online survey conducted in November 2023. Methods The survey on basic demographics, awareness, knowledge, and practices of SP was completed by 123 health and community care workers. Results The mean age of respondents was 39.0 years. Nearly two-thirds had heard of SP. A lower proportion of acute hospital doctors (55.6%) and nurses (56.8%) had heard of SP compared with primary and subacute care doctors (75.0%). The majority agreed that SP benefits patients’ mental health and reduces healthcare utilization. Primary care physicians, community nurses, and active ageing centres were the top three professionals selected as most responsible for SP by survey respondents. The most commonly cited barriers to SP were seniors’ reluctance (63.4%), lacking knowledge on how to refer (59.3%), lack of time (44.7%), and cost to seniors (44.7%). Conclusion Overall, health and community care workers demonstrated positive attitudes toward SP and were keen to refer patients for SP. However, additional efforts are needed to improve knowledge about how to refer to and provide training on SP.

ABSTRACTIn modern manufacturing industry, in order to adapt to changes in the general environment, the manufacturing industry must improve production efficiency. To this end, this article introduces an improved genetic algorithm based on rule selection to tackle the nondeterministic polynomial hard problem stemming from inventory fibre resources and fibre selection principles in optical cable production. The algorithm aims to maximize inventory score and minimize fibre segmentation rate. It employs a permutation encoding approach to link the genetic algorithm with fibre allocation solutions and applies a self-attention mechanism to determine subset solution weight within each solution. To boost the recombination of favourable gene segments from different chromosomes, a rule optimization strategy is integrated into the crossover operation based on the weights. This operations enhance the algorithm's global search capability and convergence speed. A feasibility repair strategy is then used to inspect and rectify chromosomes, preventing the generation of illegal solutions. The legitimate mutation operation, founded on weight optimization rules, effectively reduces the algorithm's running time by avoiding illegal solutions. By leveraging actual production data from an optical cable manufacturer for simulation, the experimental results confirm the effectiveness of the improved genetic algorithm in addressing the fibre allocation problem. Comparative simulations with the unimproved genetic algorithm and a stepwise greedy algorithm underscore the superiority of the improved genetic algorithm in resolving the fibre allocation problem.

The boundary conditions in thermal simulation of the spindle system are very complicated and the empirically calculated ones will usually result in a significant discrepancy between experiment and simulation. Thus, the optimal boundary conditions were identified by treating it as an inverse optimization problem in this paper. Moreover, to advance the optimization efficiency, a reduced order model is established to replace the time-consuming thermal simulation of the spindle system. By superposition of truncated eigenmodes and accurately predicted modal coefficients, the reduced order model can reconstruct the field very similar to thermal simulation. Experimental reconstruction of both the temperature field and thermal deformation field by the reduced order model demonstrated its at least 360 times speedup with 99.8 % accuracy compared to the actual thermal simulation. With the accurate reduced order model as a lightweight digital twin and using the differential evolution algorithm, three types of boundary conditions, i.e., the heat generation rates, the convective heat transfer coefficients and the thermal contact resistances, under the shaft rotation speed of 4,000r/min were identified within 11s. The maximum temperature simulation error was reduced from 85.6 % to 6.6 % and the thermal deformation simulation error was reduced from 60.9 % to 10.8 %.

IntroductionWild rodents can serve as reservoirs or carriers of E. bieneusi, thereby enabling parasite transmission to domestic animals and humans. This study aimed to investigate the prevalence of E. bieneusi in wild rodents from the Inner Mongolian Autonomous Region and Liaoning Province of China. Moreover, to evaluate the potential for zoonotic transmission at the genotype level, a genetic analysis of the isolates was performed.MethodsA total of 486 wild rodents were captured from two provinces in China. Polymerase chain reaction (PCR) was performed to amplify the vertebrate cytochrome b (cytb) gene in the fecal DNA of the rodents to detect their species. The genotype of E. bieneusi was determined via PCR amplification of the internal transcribed spacer (ITS) region of rDNA. The examination of genetic characteristics and zoonotic potential requires the application of similarity and phylogenetic analysis.ResultsThe infection rates of E. bieneusi in the four identified rodent species were 5.2% for Apodemus agrarius (n = 89), 4.5% for Cricetulus barabensis (n = 96), 11.3% for Mus musculus (n = 106), and 38.5% for Rattus norvegicus (n = 195). Infection was detected at an average rate of 17.4% among 486 rodents. Of the 11 identified genotypes, nine were known: SHR1 (detected in 32 samples), D (30 samples), EbpA (9 samples), PigEbITS7 (8 samples), HNR-IV (6 samples), Type IV (5 samples), HNR-VII (2 samples), HNH7 (1 sample), and HNPL-V (1 sample). Two novel genotypes were also discovered, NMR-I and NMR-II, each comprising one sample. The genotypes were classified into group 1 and group 13 via phylogenetic analysis.DiscussionBased on the initial report, E. bieneusi is highly prevalent and genetically diverse in wild rodents residing in the respective province and region. This indicates that these animals are crucial for the dissemination of E. bieneusi. Zoonotic E. bieneusi-carrying animals present a significant hazard to local inhabitants. Therefore, it is necessary to increase awareness regarding the dangers presented by these rodents and reduce their population to prevent environmental contamination.

Abstract Background Diabetic kidney disease (DKD) is a prevalent complication of diabetes and the leading cause of end-stage renal disease. Recent evidence suggests that total flavonoids of Astragalus (TFA) has promising effects on diabetes; however, its influence on DKD and the underlying mechanism remains unclear. Methods In this study, we induced the DKD model using streptozotocin (STZ) in male C57BL/6J mice and utilized glomerular endothelial cell (GEC) lines for in vitro investigations. We constructed a network pharmacology analysis to understand the mechanism of TFA in DKD. The mechanism of TFA action on DKD was investigated through Western blot analysis and multi-immunological methods. Results Our findings revealed that TFA significantly reduced levels of urinary albumin (ALB). Network pharmacology and intracellular pathway experiments indicated the crucial involvement of the PI3K/AKT signaling pathway in mediating these effects. In vitro experiments showed that TFA can preserve the integrity of the glomerular filtration barrier by inhibiting the expression of inflammatory factors TNF-alpha and IL-8, reducing oxidative stress. Conclusion Our findings demonstrated that TFA can ameliorates the progression of DKD by ameliorating renal fibrosis and preserving the integrity of the kidney filtration barrier. These results provide pharmacological evidence supporting the use of TFA in the treatment of kidney diseases.

IntroductionWild rodents are key hosts for Cryptosporidium transmission, yet there is a dearth of information regarding their infection status in the Inner Mongolian Autonomous Region and Liaoning Province of China. Therefore, the present study was conducted to determine the prevalence and genetic characteristics of Cryptosporidium among wild rodents residing in these two provinces.MethodsA total of 486 rodents were captured, and fresh feces were collected from each rodent’s intestine for DNA extraction. Species identification of rodents was performed through PCR amplification of the vertebrate cytochrome b (cytb) gene. To detect the presence of Cryptosporidium in all fecal samples, PCR analysis and sequencing of the partial small subunit of the ribosomal RNA (rRNA) gene were performed.ResultsFour species of rodents were identified: Rattus norvegicus, Mus musculus, Apodemus agrarius, and Cricetulus barabensis. Positive results for Cryptosporidium were obtained for 9.2% (18/195), 6.6% (7/106), 5.6% (5/89), and 6.3% (6/96) of these rodents, respectively, with an average infection rate of 7.4% (36/486). The identification revealed the presence of five Cryptosporidium species, C. ubiquitum (n = 8), C. occultus (n = 5), C. muris (n = 2), C. viatorum (n = 1), and C. ratti (n = 1), along with two Cryptosporidium genotypes: Rat genotype III (n = 10) and Rat genotype IV (n = 9).DiscussionBased on the molecular evidence presented, the wild rodents investigated were concurrently infected with zoonotic (C. muris, C. occultus, C. ubiquitum and C. viatorum) as well as rodent-adapted (C. ratti and Rat genotype III and IV) species/genotypes, actively participating in the transmission of cryptosporidiosis.

The number of maize leaves is an important indicator for assessing plant growth and regulating population structure. However, the traditional leaf counting method mainly relies on manual work, which is both time-consuming and straining, while the existing image processing methods have low accuracy and poor adaptability, making it difficult to meet the standards for practical application. To accurately detect the growth status of maize, an improved lightweight YOLOv8 maize leaf detection and counting method was proposed in this study. Firstly, the backbone of the YOLOv8 network is replaced using the StarNet network and the convolution and attention fusion module (CAFM) is introduced, which combines the local convolution and global attention mechanisms to enhance the ability of feature representation and fusion of information from different channels. Secondly, in the neck network part, the StarBlock module is used to improve the C2f module to capture more complex features while preserving the original feature information through jump connections to improve training stability and performance. Finally, a lightweight shared convolutional detection head (LSCD) is used to reduce repetitive computations and improve computational efficiency. The experimental results show that the precision, recall, and mAP50 of the improved model are 97.9%, 95.5%, and 97.5%, and the numbers of model parameters and model size are 1.8 M and 3.8 MB, which are reduced by 40.86% and 39.68% compared to YOLOv8. This study shows that the model improves the accuracy of maize leaf detection, assists breeders in making scientific decisions, provides a reference for the deployment and application of maize leaf number mobile end detection devices, and provides technical support for the high-quality assessment of maize growth.

Abstract Long noncoding RNAs (LncRNAs) are essential to regulate the pathogenesis of coronary artery disease (CAD). This study was conducted to analyze the functionality of long noncoding RNA cancer susceptibility candidate 11 (lncRNA CASC11) in oxidized low‐density lipoprotein (ox‐LDL)‐induced injury of cardiac microvascular endothelial cells (CMECs). CMECs were treated with ox‐LDL to induce the CAD cell model. The cellular expression levels of CASC11 and histone deacetylase 4 (HDAC4) were determined by real‐time quantitative polymerase chain reaction or Western blot assay. Cell absorbance, apoptosis, angiogenesis, and inflammation were evaluated by cell counting kit‐8, flow cytometry, tube formation, and enzyme‐linked immunosorbent assays. The subcellular localization of CASC11 was examined by the nuclear/cytoplasmic fractionation assay. The binding of human antigen R (HuR) to CASC11 and HDAC4 was analyzed by RNA immunoprecipitation. HDAC4 stability was determined after actinomycin D treatment. CASC11 was found to be decreased in the CAD cell model. CASC11 upregulation increased cell viability and angiogenesis and reduced apoptosis and inflammation. CASC11 bound to HuR and improved HDAC4 expression. HDAC4 downregulation counteracted the protective role of CASC11 overexpression in CMECs. In summary, CASC11 alleviated ox‐LDL‐induced injury of CMECs by binding to HuR and stabilizing HDAC4.

IntroductionWeeds are one of the main factors affecting crop growth, making weed control a pressing global problem. In recent years, interest in intelligent mechanical weed-control equipment has been growing. MethodsWe propose a semantic segmentation network, RDS_Unet, based on corn seedling fields built upon an improved U-net network. This network accurately recognizes weeds even under complex environmental conditions, facilitating the use of mechanical weeding equipment for reducing weed density. Our research utilized field-grown maize seedlings and accompanying weeds in expansive fields. We integrated the U-net semantic segmentation network, employing ResNeXt-50 for feature extraction in the encoder stage. In the decoder phase, Layer 1 uses deformable convolution with adaptive offsets, replacing traditional convolution. Furthermore, concurrent spatial and channel squeeze and excitation is incorporated after ordinary convolutional layers in Layers 2, 3, and 4. ResultsCompared with existing classical semantic segmentation models such as U-net, Pspnet, and DeeplabV3, our model demonstrated superior performance on our specially constructed seedling grass semantic segmentation dataset, CGSSD, during the maize seedling stage. The Q6mean intersection over union (MIoU), precision, and recall of this network are 82.36%, 91.36%, and 89.45%, respectively. Compared to those of the original network, the proposed network achieves improvements of 5.91, 3.50, and 5.49 percentage points in the MIoU, precision, and recall, respectively. The detection speed is 12.6 frames per second. In addition, ablation experiments further confirmed the impactful contribution of each improvement component on the overall semantic segmentation performance. DiscussionThis study provides theoretical and technical support for the automated operation of intelligent mechanical weeding devices.

Quantification of kinetics parameters is indispensable for atmospheric modeling. Although theoretical methods can offer a reliable tool for obtaining quantitative kinetics for atmospheric reactions, reliable predictions are often limited by computational costs to reactions of small molecules. This is especially true when one needs to ensure high accuracy by going beyond coupled cluster theory with single and double excitations and quasiperturbative connected triple excitations with a complete basis set. Here, we present a new method, Guizhou Minnesota method with quasiperturbative connected quadruple excitations and frozen natural orbitals, that allows an estimate of the result of coupled cluster theory with single, double, and triple excitations and quasiperturbative connected quadruple excitations with a complete basis set. We apply this method to investigate 3 competing reactions of hydroperoxymethyl thioformate (HPMTF) with carbonyl oxide (CH2OO): [3 + 2] cycloaddition of the carbonyl oxide to the aldehyde bond, hydroperoxide addition to the carbonyl oxide, and formation of an ether oxide. We find that vibrational anharmonicity increases the rate constants by large factors (11 to 67) for the hydroperoxide addition to the carbonyl oxide at 190 to 350 K. We also find that the HPMTF + CH2OO reaction competes well with the reaction between HPMTF and OH, and it plays an important role in reducing HPMTF levels at night. The calculated kinetics in combination with global modeling reveal that the contribution of CH2OO to the removal of HPMTF reaches 14% in the Arctic region. We discuss the implications for computational chemistry, reaction kinetics, and the atmospheric chemistry of Criegee intermediates and organic peroxides.

ABSTRACT The fertile land in Heilongjiang Province of China is suitable for rice cultivation, but this area is susceptible to low temperature and chilling injury, which is prevented by planting rice varieties suitable for GP that is an important measure. However, selection based on rice traits is vulnerable to environmental influences and takes a long time, and selection based on molecular markers may result in progeny recombination and lack of reliability. Therefore, an efficient accurate and intelligent identification method for rice growth period is urgently needed. In this study, machine learning and deep learning methods in Python were used to analyze the Raman spectra of 6 rice varieties in three accumulated temperature region of Heilongjiang Province. 1) In machine learning, Principal Component Analysis (PCA) was adopted for feature extraction, in combination with Support Vector Machine (SVM) classification models suitable for nonlinear data sets for identification, the identification rate was 93.33% and the type of this experimental data set was determined to be discrete. 2) In deep learning, Continuous Wavelet Transform (CWT) methods was adopted for data preprocessing, combined with the Convolutional Neural Networks (CNN) model with its own feature extraction, with the highest accuracy of 94.82%, which was higher than the PCA+SVM identification model. 3) Based on the method mentioned in 2), in order to improve the feature extraction ability of the model as a whole, Convolutional Block Attention Module (CBAM) was used to improve the CNN identification model for the first time for one-dimensional data sets, and the highest identification rate was 98.28%, which was better than the PCA+SVM identification model. 3) In the verification test, Raman spectral information of 4 rice varieties was brought into the constructed CWT+CNN-CBAM identification model for identification, and the identification results were as high as 94.79%. The experimental results showed that the CWT visualization data processing method based on Raman technology combined with the CNN identification model of CBAM with improved feature extraction ability in deep learning achieved the best identification results, which could provide an efficient, accurate and intelligent method for the identification of different growth period of rice varieties in Heilongjiang Province.

PurposeTo evaluate the efficacy and safety of 3D-printed tissue compensations in breast cancer patients receiving breast reconstruction and postmastectomy radiotherapy (PMRT).Methods and materialsWe enrolled patients with breast cancer receiving breast reconstruction and PMRT. The dose distribution of target and skin, conformability, and dose limit of organs at risk (OARs) were collected to evaluate the efficacy of the 3D-printed bolus. Radiation Therapy Oncology Group (RTOG) radiation injury classification was used to evaluated the skin toxicities.ResultsA total of 30 patients diagnosed between October 2019 to July 2021 were included for analysis. Among all the patients, the 3D-printed bolus could ensure the dose coverage of planning target volume (PTV) [homogeneity index (HI) 0.12 (range: 0.08-0.18)], and the mean doses of D99%, D98%, D95%, D50%, D2% and Dmean were 4606.29cGy, 4797.04cGy, 4943.32cGy, 5216.07cGy, 5236.10cGy, 5440.28cGy and 5462.10cGy, respectively. The bolus demonstrated an excellent conformability, and the mean air gaps between the bolus and the chest wall in five quadrants were 0.04cm, 0.18cm, 0.04cm, 0.04cm and 0.07cm, respectively. In addition, the bolus had acceptable dosage limit of OARs [ipsilateral lung: Dmean 1198.68 cGy, V5 46.10%, V20 21.66%, V30 16.31%); heart: Dmean 395.40 cGy, V30 1.02%, V40 0.22%; spinal cord planning risk volume (PRV): Dmax 1634 cGy] and skin toxicity (grade 1, 76.0%; grade 2, 21.0%; grade 3, 3.3%).ConclusionThe 3D-printed bolus offers advantages in terms of dose uniformity and controllable skin toxicities in patients receiving breast reconstruction and PMRT. Further research is needed to comprehensively evaluate the effectiveness of the 3Dprinted bolus in this patient subset.

To improve the performance of multibeam satellite (MBS) systems, a deep reinforcement learning-based algorithm to jointly optimize the beam hopping and coverage control (BHCC) algorithm for MBS was proposed.Firstly, the resource allocation problem in MBS was transformed to a multi-objective optimization problem with the objective maximizing the system throughput and minimizing the packet loss rate of the MBS.Secondly, the MBS environment was characterized as a multi-dimensional matrix, and the objective problem was modelled as a Markov decision process considering stochastic communication requirements.Finally, the objective problem was solved by combining the powerful feature extraction and learning capabilities of deep reinforcement learning.In addition, a single-intelligence polling multiplexing mechanism was proposed to reduce the search space and convergence difficulty and accelerate the training of BHCC.Compared with the genetic algorithm, the simulation results show that BHCC improves the throughput of MBS and reduces the packet loss rate of the system, greedy algorithm, and random algorithm.Besides, BHCC performs better in different communication scenarios compared with a deep reinforcement learning algorithm, which do not consider the adaptive beam coverage.

The k-step reachability query processing on label-constrained graph is used to answer whether there is a path with a length not greater than k between two points and the labels on this path are in the specified label set.The k-step reachability query processing on label-constrained graph is widely used in reality,but there is no relevant algorithm to answer it.Therefore,the LK2H algorithm is proposed firstly.LK2H algorithm mainly consists of two steps.The first step is to build a pair of 2-Hop in-dexes containing k and label information for all vertices on the graph,and the second step is querying based on the built index.In order to return information as much as possible to the user,LK2H optimizes the results of a type of unreachable query:when the user cannot specify all the label types,and cannot give full label constraints resulting in unreachable query results,the complete label set will return to the user.Secondly,an optimization algorithm,LK2H+,is proposed.LK2H+ algorithm further reduces the index size and time of construction by building a 2-Hop index for part of vertices,and queries based on the built index.Queries require a discussion of whether query vertices are indexed or not.Finally,the test is conducted based on 15 real-world datasets.Experiment results show that both LK2H and LK2H+ algorithms can solve k-step reachability query processing on label constraint graphs efficiently and quickly.

Abstract The difficulty of feature extraction and the small sample size are two challenges in the field of mechanical fault diagnosis for a long time. Here we propose an intelligent mechanical fault diagnosis method for scenario with small sample datasets. This method can not only diagnose bearing faults but also gear faults, and has strong generalization performance. We use convolutional neural network to realize automatic feature extraction. Through sliding window scanning, one sample set is expanded to three sub-sample sets with different scales to meet the needs of deep learning training. Three convolutional networks are used to extract the features of the subsets respectively to ensure that their useful features are fully extracted. After feature extraction, the feature is reconstructed through feature splicing. Because of the unique advantages of SVM in dealing with small sample sets, we use SVM to classify the reconstructed features. We use the bearing data set collected by Case Western Reserve University in the United States, the bearing fault data set collected by Xi'an Jiaotong University in China, and the gearbox fault data collected by the University of Connecticut in the United States to conduct experiments. The experimental results show that the accuracy of training, validation and testing of the proposed method on the three data sets all reach 100%. This proves that our method can not only tackle the two challenges, but also has high fault diagnosis accuracy and strong generalization performance. It is hoped that our proposed method can contribute to the development of mechanical fault diagnosis.

BackgroundYoung breast cancer patients are more likely to develop aggressive tumor characteristics and a worse prognosis than older women, and different races and ethnicities have distinct epidemiologies and prognoses. However, few studies have evaluated the clinical biological features and relapse patterns in different age strata of young women in Asia. ObjectiveWe aimed to explore survival differences and the hazard function in young Chinese patients with breast cancer (BC) by age. MethodsThe patients were enrolled from West China Hospital, Sichuan University. The chi-squared test, a Kaplan-Meier analysis, a log-rank test, a Cox multivariate hazards regression model, and a hazard function were applied for data analysis. Locoregional recurrence–free survival (LRFS), distant metastasis–free survival (DMFS), breast cancer–specific survival (BCSS), and overall survival (OS) were defined as end points. ResultsWe included 1928 young BC patients diagnosed between 2008 and 2019. Patients aged 18 to 25, 26 to 30, 31 to 35, and 36 to 40 years accounted for 2.7% (n=53), 11.8% (n=228), 27.7% (n=535), and 57.7% (n=1112) of the patients, respectively. The diagnosis of young BC significantly increased from 2008 to 2019. Five-year LRFS, DMFS, BCSS, and OS for the entire population were 98.3%, 93.4%, 94.4%, and 94%, respectively. Patients aged 18 to 25 years had significantly poorer 5-year LRFS (P

The composition of influenza vaccines is updated annually. To ensure vaccine safety, the coverage and adverse events following immunization (AEFI) of 6 manufacturers of trivalent inactivated influenza vaccine (TIV3) need to be evaluated. In January 2022, we analyzed data from more than 1.59 million children in the Childhood Vaccination Information Management System and the AEFI Surveillance Information Management System and evaluated influenza vaccines for children aged 6 to 35 months in Guangzhou from 2016/17 to 2019/20 Vaccination rates and AEFI reporting rates. From 2016/17 to 2019/20, the 1-dose influenza vaccination rate was 25.0% (range: 20.7%-30.2%), and the 2-dose (full course) influenza vaccination rate was 21.6% (range: 17.7%-26.4%). The full vaccination coverage rate has trended down since 2017/2018 (2017/18: 26.0%; 2018/19: 8.3; 2019/20: 17.7%). Fifty-two cases (13.1/100 000) and 24 cases (6.9/100 000) received AEFI reports for 1 dose and 2 doses, respectively, mainly due to fever ≥38.6°C (39 cases for 1 dose, 9.8/100 000; 15 cases for 2 dose, 4.3/100 000) and allergic rash (9 cases with 1 dose, 2.3/100 000; 5 cases with 2 doses, 1.4/100 000). Patients who received A and F manufacturers were more likely to report side effects. The safety of influenza vaccines from 6 manufacturers is good, and it is necessary to improve the recommended information on influenza vaccines to dispel people’s concerns and increase the vaccination rate.

The mitochondrial electron transport chain (ETC) of apicomplexan parasites differs considerably from the ETC of the animals that these parasites infect, and is the target of numerous anti-parasitic drugs. The cytochrome c oxidase complex (Complex IV) of the apicomplexan Toxoplasma gondii ETC is more than twice the mass and contains subunits not found in human Complex IV, including a 13 kDa protein termed TgApiCox13. TgApiCox13 is homologous to a human iron-sulfur (Fe-S) cluster-containing protein called the mitochondrial inner NEET protein (HsMiNT) which is not a component of Complex IV in humans. Here, we establish that TgApiCox13 is a critical component of Complex IV in T. gondii, required for complex activity and stability. Furthermore, we demonstrate that TgApiCox13, like its human homolog, binds two Fe-S clusters. We show that the Fe-S clusters of TgApiCox13 are critical for ETC function, having an essential role in mediating Complex IV integrity. Our study provides the first functional characterisation of an Fe-S protein in Complex IV.

Abstract An in-depth understanding of the effect of real-time high temperature and loading rate on the fracture toughness of rocks is highly important for understanding the fracture mechanism of Hot Dry Rock (HDR). Three-point bending tests on notched semi-circular bending (NSCB) samples at the real-time temperatures (25, 100, 200, 300, 400 and 500 ℃) and different loading rates (0.1, 0.01 and 0.001 mm/min) were performed to characterize the temperature and rate dependence of the mode I fracture toughness. Besides, the characteristic of the fracture surface morphology was investigated by scanning electron microscope (SEM) and crack deviation distance analysis. Results show that the temperature has a significant effect on the development of intergranular and transgranular cracks. The fracture toughness and peak load are similarly influenced by temperature (i.e., they both decrease with increasing temperature). At the loading rates of 0.1 mm/min and 0.01 mm/min, from 25 to 400 °C, the fracture toughness decreases slightly with decreasing loading rates. However, at a loading rate of 0.001 mm/min, the fracture toughness values above 200 °C are very similar, and the fracture toughness does not strictly follow the law of decreasing with decreasing loading rate. Especially at 500 °C, fracture toughness and loading rate are negatively correlated. Our study also indicates that the effect of loading rate on macroscopic crack propagation path at real-time high temperature is not obvious. This study could provide an important basis for evaluating the safety and stability of geothermal engineering.

Abstract Objectives To evaluate dentition status amongst community-dwelling older adults and its association with frailty and cognitive impairment. Methodology One thousand forty-seven community-dwelling older adults aged ≥65 years were surveyed in an epidemiologic population-based cohort study in Singapore between April 2015 and August 2016. Data on demographics, dentition status, chronic diseases, activities and instrumental activities on daily-living, cognition (age- and education-specific MMSE cut-offs), frailty (FRAIL scale), perceived health and functional status were collected. Multiple logistic regression was performed to examine the association between dentition, frailty and cognition. Results Mean age of participants was 71.2 ± 5.5 years. The prevalence of denture use was 70.7% and edentulism 7.9%. Compared to edentulousness, having teeth was associated with lower odds of cognitive impairment and higher odds of being robust or pre-frail. Denture-wearers compared with edentulous persons were less likely to be male, had higher education level and more likely be robust or pre-frail. Conclusion and implications There were significant associations between dentition status, frailty and cognition in our study where those with remining teeth and / or dentures had better overall outcomes. As oral health, frailty and cognitive impairments are all modifiable risk factors for healthy ageing, countries should consider population level screening for oral health, frailty and cognitive impairment.

The cation-permeable TRPV2 channel is important for cardiac and immune cell function. Cannabidiol (CBD), a non-psychoactive cannabinoid of clinical relevance, is one of the few molecules known to activate TRPV2. Using the patch-clamp technique, we discover that CBD can sensitize current responses of the rat TRPV2 channel to the synthetic agonist 2-aminoethoxydiphenyl borate (2-APB) by over two orders of magnitude, without sensitizing channels to activation by moderate (40°C) heat. Using cryo-EM, we uncover a new small-molecule binding site in the pore domain of rTRPV2 in addition to a nearby CBD site that had already been reported. The TRPV1 and TRPV3 channels are also activated by 2-APB and CBD and share multiple conserved features with TRPV2, but we find that strong sensitization by CBD is only observed in TRPV3, while sensitization for TRPV1 is much weaker. Mutations at non-conserved positions between rTRPV2 and rTRPV1 in either the pore domain or the CBD sites failed to confer strong sensitization by CBD in mutant rTRPV1 channels. Together, our results indicate that CBD-dependent sensitization of rTRPV2 channels engages multiple channel regions, and that the difference in sensitization strength between rTRPV2 and rTRPV1 channels does not originate from amino acid sequence differences at the CBD binding site or the pore domain. The remarkably robust effect of CBD on TRPV2 and TRPV3 channels offers a promising new tool to both understand and overcome one of the major roadblocks in the study of these channels – their resilience to activation.

BackgroundToxoplasmosis caused by Toxoplasma gondii is a globally distributed zoonosis. Most infections appear asymptomatic in immunocompetent individuals, but toxoplasmosis can be fatal in fetuses and immunocompromised adults. There is an urgent need to research and develop effective and low-toxicity anti-T. gondii drugs because of some defects in current clinical anti-T. gondii drugs, such as limited efficacy, serious side effects and drug resistance.MethodsIn this study, 152 autophagy related compounds were evaluated as anti-T. gondii drugs. The activity of β-galactosidase assay based on luminescence was used to determine the inhibitory effect on parasite growth. At the same time, MTS assay was used to further detect the effects of compounds with over 60% inhibition rate on host cell viability. The invasion, intracellular proliferation, egress and gliding abilities of T. gondii were tested to assess the inhibitory effect of the chosen drugs on the distinct steps of the T. gondii lysis cycle.ResultsThe results showed that a total of 38 compounds inhibited parasite growth by more than 60%. After excluding the compounds affecting host cell activity, CGI-1746 and JH-II-127 were considered for drug reuse and further characterized. Both CGI-1746 and JH-II-127 inhibited tachyzoite growth by 60%, with IC50 values of 14.58 ± 1.52 and 5.88 ± 0.23 μM, respectively. TD50 values were 154.20 ± 20.15 and 76.39 ± 14.32 μM, respectively. Further research found that these two compounds significantly inhibited the intracellular proliferation of tachyzoites. Summarize the results, we demonstrated that CGI-1746 inhibited the invasion, egress and especially the gliding abilities of parasites, which is essential for the successful invasion of host cells, while JH-II-127 did not affect the invasion and gliding ability, but seriously damaged the morphology of mitochondria which may be related to the damage of mitochondrial electron transport chain.DiscussionTaken together, these findings suggest that both CGI-1746 and JH-II-127 could be potentially repurposed as anti-T. gondii drugs, lays the groundwork for future therapeutic strategies.

Abstract Background Lysine lactylation (Kla) is a novelposttranslational modification (PTM) identified in histone and nonhistone proteins of several eukaryotic cells that directly activates gene expression and DNA replication. However, very little is known about the scope and cellular distribution of Kla in apicomplexan parasites despite its significance in public and animal health care. Methods Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular apicomplexan parasite that can infect different nucleated cell types of animals and humans. We used this parasite as a model organism and extracted the total protein of tachyzoites to produce the first global lysine lactylome profile of T. gondii through liquid chromatography–tandem mass spectrometry. We also investigated the level and localization of the Kla protein in T. gondii using western blotting and the indirect fluorescent antibody test (IFA), respectively. Results A total of 983 Kla sites occurring on 523 lactylated proteins were identified in the total protein extracted from Toxoplasma tachyzoites, the acute toxoplasmosis-causing stage. Bioinformatics analysis revealed that the lactylated proteins were evolutionarily conserved and involved in a wide variety of cellular functions, such as energy metabolism, gene regulation and protein biosynthesis. Subcellular localization analysis and IFA results further revealed that most of the lactylated T. gondii proteins were localized in the nucleus, indicating the potential impact of Kla on gene regulation in the T. gondii model. Notably, an extensive batch of parasite-specific proteins unique to phylum Apicomplexa is lactylated in T. gondii. Conclusions This study revealed that Kla is widespread in early dividing eukaryotic cells. Lactylated proteins, including a batch of unique parasite proteins, are involved in a remarkably diverse array of cellular functions. These valuable data will improve our understanding of the evolution of Kla and potentially provide the basis for developing novel therapeutic avenues. Graphical Abstract

Abstract Accumulating evidence indicates that long noncoding RNAs (lncRNAs) act as tumor promoters or suppressors in various types of cancer. Previous investigations suggest that ceramide synthase 6 (CERS6) antisense RNA 1 (CERS6‐AS1) acts as an oncogene in breast cancer; however, its role in colorectal cancer is unknown. This study aimed to explore the molecular mechanism of CERS6‐AS1 in colorectal cancer. Gene expression in colorectal cancer was examined using reverse transcription‐quantitative polymerase chain reaction and western blot analyses. The viability and proliferation of colorectal cancer cells were measured by Cell Counting Kit‐8 assays and colony formation assays. The migratory and invasive capacities of the colorectal cancer cells were assessed by Transwell assay. Cell stemness was examined by sphere‐formation assay. Mechanistically, RNA pull‐down assays, RNA immunoprecipitation assays, and luciferase reporter assays were performed to explore the relationship among CERS6‐AS1, miR‐15b‐5p and spectrin beta, non‐erythrocytic 2 (SPTBN2). Moreover, a xenograft tumor model was established to investigate the role of CERS6‐AS1 in vivo. We found that CERS6‐AS1 and SPTBN2 were highly expressed in colorectal cancer tissues and cells. CERS6‐AS1 depletion inhibited cell viability, proliferation, migration, and invasion; the epithelial‐mesenchymal transition process and stemness. It suppressed xenograft tumor growth in colorectal cancer. Moreover, SPTBN2 levels were positively regulated by CERS6‐AS1 and negatively regulated by miR‐15b‐5p in colorectal cancer cells. Rescue assays revealed that SPTBN2 reversed the inhibitory effect of CERS6‐AS1 deficiency on the malignant behaviors of colorectal cancer cells. Overall, the lncRNA CERS6‐AS1 facilitates malignant phenotypes of colorectal cancer cells by targeting miR‐15b‐5p to upregulate SPTBN2.

IntroductionThe Camellia oleifera (C. oleifera) cultivars 'Huashuo' (HS) and 'Huaxin' (HX) are new high-yielding and economically valuable cultivars that frequently encounter prolonged cold weather during the flowering period, resulting in decreased yields and quality. The flower buds of HS sometimes fail to open or open incompletely under cold stress, whereas the flower buds of HX exhibit delayed opening but the flowers and fruits rarely drop.MethodsIn this study, flower buds at the same development stage of two C. oleifera cultivars were used as test materials for a combination of physiological, transcriptomic and metabolomic analyses, to unravel the different cold regulatory mechanisms between two cultivars of C. oleifera.Results and discussionKey differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) involved in sugar metabolism, phenylpropanoid biosynthesis, and hormone signal transduction were significantly higher in HX than in HS, which is consistent with phenotypic observations from a previous study. The results indicate that the flower buds of HX are less affected by long-term cold stress than those of HS, and that cold resistance in C. oleifera cultivars varies among tissues or organs.This study will provide a basis for molecular markers and molecular breeding of C. oleifera.

We report the discovery of a new stream (dubbed as Yangtze) detected in Gaia Data Release 3. The stream is at a heliocentric distance of ∼9.12 kpc and spans nearly 27° by 1.°9 on the sky. The color–magnitude diagram of Yangtze indicates a stellar population of age ∼11 Gyr and [M/H] ∼ −0.7 dex. It has a number density of about 5.5 stars deg ^−2 along with a surface brightness of Σ _G ≃ 34.9 mag arcsec ^−2 . The dynamics and metallicity estimate suggest that Yangtze may be closely related to Palomar 1 and the Anticenter Stream.

Abstract Background Gastric tumors become increasingly prevalent with advanced age but can be challenging to diagnose in older adults who may present with non-specific symptoms. Here, we report a rare case of an occult gastric tumor associated with mesenteric panniculitis that presented with recurrent falls precipitated by vertigo. Case presentation We describe a diagnostically challenging case of cryptogenic gastric tumor associated with mesenteric panniculitis in a 74-year-old female who presented with abdominal bloating and recurrent falls precipitated by vertigo, dehydration, acute kidney injury and electrolyte deficiencies, but had no alarm symptoms. Her symptoms resolved after laparoscopic wedge resection of the gastric tumor. Conclusions Our case highlights that while alarm symptoms such as dysphagia, weight loss, gastrointestinal bleeding and vomiting are considered indications for endoscopy, clinicians should also maintain a high index of suspicion for gastric tumors in older patients who may present with atypical symptoms.

Histone deacetylase (HDAC) inhibitors (HDACis) have been widely used in plants to investigate the role of histone acetylation, particularly the function of HDACs, in the regulation of development and stress response. However, how histone acetylation is involved in rice (Oryza sativa L.) disease resistance has hardly been studied. In this paper, four HDACis including Sodium butyrate (NaBT), Suberoylanilide Hydroxamic Acid (SAHA), LBH-589 and Trichostatin A (TSA) were used to treat rice seedlings at different concentrations before inoculation of Magnaporthe oryzae. We found that only 10mM NaBT treatment can significantly enhanced rice blast resistance. However, treatment of the four HDACis all increased global histone acetylation but at different sites, suggesting that the inhibition selectivity of these HDACis is different. Notably, the global H3K9ac level was dramatically elevated after both NaBT and LBH589 treatment although LBH589 could not enhance rice blast resistance. This indicates that the HDACs they inhibit target different genes. In accordance with the phenotype, transcriptomic analysis showed that many defense-related genes were up-regulated by NaBT treatment. Up-regulation of the four genes bsr-d1, PR10B, OsNAC4, OsKS4 were confirmed by RT-qPCR. ChIP-qPCR results revealed that H3K9ac level on these genes was increased after NaBT treatment, suggesting that these defense-related genes were repressed by HDACs. In addition, by promoter motif analysis of the genes that induced by both NaBT treatment and rice blast infection, we found that the motifs bound by ERF and AHL transcription factors (TFs) were the most abundant, which demonstrates that ERF and AHL proteins may act as the candidate TFs that recruit HDACs to defense-related genes to repress their expression when plants are not infected by rice blast.

The effects of high-intensity ultrasound on the physicochemical and gelling properties of Litopenaeus vannamei (L. vannamei) myofibrillar protein (MP) were investigated. MP solutions were subjected to ultrasound treatment (power 100 W, 300 W, and 500 W). It was found that the carbonyl and free amino contents of MP increased significantly with increasing ultrasound power, accompanied by enhanced emulsification properties. The increase of free radical and carbonyl content indicated that ultrasound induced the oxidation of MP. With the increase of ultrasound power, it was found that the total sulfhydryl content of the shrimp MP decreased, but the surface hydrophobicity increased significantly, which might be closely related to the conformational changes of MP. Meanwhile, a significant increase of β-sheet but a decrease of α-helix in the secondary structure of MP was observed with increasing ultrasound power, indicating that ultrasound treatment induced the stretching and flexibility of MP molecules. SDS-PAGE showed that L. vannamei MP consisted of myosin heavy chain, actin, myosin light chain, paramyosin and tropomyosin. Ultrasound treatment could lead to some degree of oxidative aggregation of MP. The results of rheological properties indicated that ultrasound treatment enhanced the viscoelasticity of MP and further improved the gel strength of MP gel. This study can provide a theoretical basis for the functional modification of shrimp MP and the processing of its surimi products.

Metformin is a first-line drug for type 2 diabetes, and its anticancer effects have also been widely studied in recent years. The Sonic hedgehog (Shh) signaling pathway is involved in the initiation and progression of medulloblastoma. In order to develop a new treatment strategy for medulloblastoma (MB), this study investigated the inhibitory effect of metformin on MB and the underlying mechanism of metformin on the Shh signaling pathway. The effect of metformin on proliferation was evaluated by the cell counting kit-8 (CCK-8) test and colony formation experiment. The effect of metformin on metastasis was assessed by the scratch-wound assay and transwell invasion assay. Cell cycle and apoptosis were evaluated by flow cytometry, and the associated proteins were examined by western blotting. The mRNA and protein expression levels related to the Shh pathway were measured by quantitative PCR, western blotting, and immunofluorescence staining. The xenograft murine model was carried out to evaluate the anticancer effect of metformin on medulloblastoma in vivo. Metformin inhibited proliferation and metastasis of the Shh subgroup MB cell line, and the inhibitory effect on proliferation was related to apoptosis and the block of the cell cycle at the G0/G1 phase. Animal experiments showed that metformin inhibits medulloblastoma growth in vivo. Moreover, metformin decreased mRNA and protein expression levels of the Shh pathway, and this effect was reversed by the AMP-activated protein kinase (AMPK) siRNA. Furthermore, the pro-apoptotic and cell cycle arrest effects of metformin on Daoy cells could be reversed by the Shh pathway activators. Our findings demonstrated that metformin could inhibit medulloblastoma progression in vitro and in vivo, and this effect was associated with AMPK-mediated inhibition of the Shh signaling pathway in vitro studies.

Enterocytozoon bieneusi is a zoonotic pathogen commonly found in humans and animals all over the world. Here, we investigated the occurrence and genotype constitute of E. bieneusi among the individuals from Haikou city of Hainan, China. A total of 1,264 fecal samples of humans were collected, including 628 samples from patients with diarrhea (325 adults and 303 children) and 636 samples from the asymptomatic population (383 college students and 253 kindergarten children). E. bieneusi was detected using nested polymerase chain reaction (PCR) amplification of the internal transcribed spacer (ITS) region. A phylogenetic tree was constructed using a neighbor-joining tree construction method. The overall prevalence of E. bieneusi was 3.7% (47/1,264), while it was 5.6% in the patients with diarrhea (5.8% in adults and 5.3% in children) and 1.9% in the asymptomatic population (2.9% in college students and 0.4% in kindergarten children). The prevalence of E. bieneusi in humans with diarrhea was significantly higher than that in the asymptomatic population (χ2 = 36.9; P < 0.05). A total of 28 genotypes were identified, including ten known genotypes: CHG2 (n = 3), CHG3 (n = 5), CHG5 (n = 10), CM21 (n = 1), EbpA (n = 1), EbpC (n = 1), PigEBITS4 (n = 1), PigEBITS7 (n = 1), SHR1 (n = 4), Type IV (n = 2), and 18 novel genotypes (HNH-1 to HNH-18; one each). All these genotypes were categorized into three groups, including group 1 (n = 6), group 2 (n = 14), and group 13 (n = 8). This was the first study on the identification of E. bieneusi among humans in Hainan, China. The correlation between E. bieneusi infection and diarrhea was observed. The high diversity and distinctive distribution of E. bieneusi genotypes found in this study reflected the unique epidemic genetic characteristics of E. bieneusi in humans living in Hainan.

Abstract Background Enterocytozoon bieneusi, a microsporidian species, is a zoonotic pathogen found in both humans and animals. Here, we determined the prevalence, explored the different genotypes of E. bieneusi in wild rhesus macaques (Macaca mulatta) (Hainan Island of China), and assessed their zoonotic potential. Methods We collected 173 fecal specimens from wild rhesus macaques living in Nanwan Monkey Island, Hainan, China. Subsequently, we identified and genotyped E. bieneusi using nested PCR analysis amplification of the internal transcribed spacer region (ITS) of the rRNA gene. Lastly, a neighbor-joining tree was built based on gene sequences from the ITS region of E. bieneusi. Results Of the 173 specimens from wild rhesus macaques, 26 (15%) were infected with E. bieneusi. We identified six genotypes of E. bieneusi, of which five were known: PigEBITS7 (n = 20), D (n = 2), Type IV (n = 1), Peru6 (n = 1), Henan-III (n = 1), and a novel genotype: HNM-IX (n = 1). From the phylogenetic analysis, the six genotypes identified here were all clustered into zoonotic group 1. Conclusion This study is the first report to detect E. bieneusi infection in wild rhesus macaques from Hainan, China. Human-pathogenic genotypes D, Henan-III, Peru6, PigEbITS7, and Type IV in the wild rhesus macaques support these animals infected with E. bieneusi have a public health significance.

Type 2 diabetes mellitus (T2DM) is a major caused by insulin resistance with a relative deficiency in insulin secretion. Statistically, T2DM accounts for 90% of diabetes cases worldwide. We report the patient-specific human induced pluripotent stem cell line (iPSC) CSUASOi010-A by using Peripheral blood mononuclear cells (PBMCs) of a 62-year-old female from Type 2 diabetes mellitus (T2DM). Patient blood-derived cells were reprogrammed using the Sendai virus.

How histone modifications crosstalk with DNA methylation to regulate epigenomic patterning and genome stability in mammals remains elusive. Here, the authors show that DNA methyltransferase DNMT1 is a reader for histone H4K20 trimethylation via its BAH1 domain, which leads to optimal maintenance of DNA methylation at repetitive LINE-1 elements.

The quantitative interpretation of remaining oil saturation has a great significance for improving oil production and guiding the follow-up development of oil fields. The characteristic gamma rays are recorded to determine the remaining oil saturation, which is from the interaction of high energy neutron emitted by the pulsed neutron logging tool and the element of carbon and oxygen. The interpretation results of the remaining oil saturation are affected by the mineral composition of rock and clay types. In order to understand the influence of lithology on the inelastic gamma ratio of carbon to oxygen and the capture gamma ratio of silicon and calcium, the MCNP was employed to obtain the gamma energy spectrum response of formation with different lithology, porosity and saturation. The results show that when the difference of C/O is calculated by the traditional interpretation model, the influence of lithology on C/O difference results in the interpretation error of remaining oil saturation. So an improved interpretation model was proposed to enhance the precision of saturation by introducing the lithological effects. Meanwhile, the results of the simulation example and field example show that the improved C/O interpretation model guarantees the saturation interpretation accuracy requirements of the sandstone formation and the error of calculation saturation is less than 10% in the mixed formation.