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Abstract The effect of low‐FODMAPs diet on irritable bowel syndrome (IBS) in Western China has not been reported. We aimed to investigate the effect of low‐FODMAPs diet on IBS patients in the area and whether low‐FODMAPs diet‐induced alterations of microbiota could be improved through probiotics. IBS patients were randomized to the control group, low‐FODMAPs diet group, probiotics group, or combined group. IBS Symptom Severity Score questionnaire (IBS‐SSS) and IBS Quality of Life Score questionnaire (IBS‐QOL) were completed at baseline, 2 and 4 weeks to evaluate the severity of symptoms. Fresh feces were collected for analyses of gut microbiota and short‐chain fatty acids at baseline and 4 weeks after intervention. Seventy‐three patients were included in the per protocol analysis. After intervention, there was significant improvement in IBS‐SSS in the low‐FODMAPs group (37.5%, 44.2%), probiotics group (51.4%, 62.0%), and combined group (34.1%, 40.4%) at both 2 weeks and 4 weeks, compared with the baseline (p

Abstract Background Cancer burden from the elderly has been rising largely due to the aging population. However, research on the long‐term epidemiological trends in cancer of the elderly is lacking. Methods Registry data of this population‐based cross‐sectional study were from the Surveillance, Epidemiology, and End Results (SEER) database. The study population aged 65 years or more, from geographically distinct regions. Joinpoint regression and JP Surv method were used to analyze cancer trends and survival. Results Mortality rate during 1975–2020 decreased from 995.20 to 824.99 per 100,000 elderly persons, with an average annual decrease of 0.421% (95% CI, 0.378–0.464). While overall incidence increased with no significance. Prostate (29%) and breast (26%) cancer were the most common malignancies, respectively, in elderly males and females, and the mortality for both of the two (prostate 15%, breast 14%) ranked just behind lung and bronchus cancer, which had the highest mortality rates in males (29%) and females (23%). Many cancers showed adverse trends in the latest follow‐up periods (the last period calculated by the Joinpoint method). For intrahepatic cholangiocarcinoma, incidence (male Annual Percentage Change [APC] = 7.4*; female APC = 6.7*) and mortality (male APC = 3.0*; female APC = 3.3*) increased relatively fast, and its survival was also terrible (3‐year survival only 10%). Other cancers with recent increasing mortality included cancer of anus, anal canal and anorectum, retroperitoneum, pleura, peritoneum, etc. Most cancers had favorable trends of survival during the nearest follow‐up period. Conclusion Against the background of overall improvement, many cancers showed adverse trends. Further research for the underlying mechanisms and targeted implements towards adverse trends is also urgent.

Abstract Background N6‐methyladenosine (m6A) modification is essential for modulating RNA processing as well as expression, particularly in the context of malignant tumour progression. However, the exploration of m6A modification in nasopharyngeal carcinoma (NPC) remains very limited. Methods RNA m6A levels were analysed in NPC using m6A dot blot assay. The expression level of methyltransferase‐like 14 (METTL14) within NPC tissues was analysed from public databases as well as RT‐qPCR and immunohistochemistry. The influences on METTL14 expression on NPC proliferation and metastasis were explored via in vitro as well as in vivo functional assays. Targeted genes of METTL14 were screened using the m6A and gene expression profiling microarray data. Actinomycin D treatment and polysome analysis were used to detect the half‐life and translational efficiency of ANKRD22. Flow cytometry, immunofluorescence and immunoprecipitation were used to validate the role of ANKRD22 on lipid metabolism in NPC cells. ChIP‐qPCR analysis of H3K27AC signalling near the promoters of METTL14, GINS3, POLE2, PLEK2 and FERMT1 genes. Results We revealed METTL14, in NPC, correlating with poor patient prognosis. In vitro and in vivo assays indicated METTL14 actively promoted NPC cells proliferation and metastasis. METTL14 catalysed m6A modification on ANKRD22 messenger ribonucleic acid (mRNA), recognized by the reader IGF2BP2, leading to increased mRNA stability and higher translational efficiency. Moreover, ANKRD22, a metabolism‐related protein on mitochondria, interacted with SLC25A1 to enhance citrate transport, elevating intracellular acetyl‐CoA content. This dual impact of ANKRD22 promoted lipid metabolism reprogramming and cellular lipid synthesis while upregulating the expression of genes associated with the cell cycle (GINS3 and POLE2) and the cytoskeleton (PLEK2 and FERMT1) through heightened epigenetic histone acetylation levels in the nucleus. Intriguingly, our findings highlighted elevated ANKRD22‐mediated histone H3 lysine 27 acetylation (H3K27AC) signals near the METTL14 promoter, which contributes to a positive feedback loop perpetuating malignant progression in NPC. Conclusions The identified METTL14‐ANKRD22‐SLC25A1 axis emerges as a promising therapeutic target for NPC, and also these molecules may serve as novel diagnostic biomarkers.

Abstract As the population ages, the worldwide prevalence of Alzheimer's disease (AD) as the most common dementia in the elderly is increasing dramatically. However, a long‐term challenge is to achieve rapid and accurate early diagnosis of AD by detecting hallmarks such as amyloid beta (Aβ42). Here, a multi‐channel microfluidic‐based plasmonic fiber‐optic biosensing platform is established for simultaneous detection and differentiation of multiple AD biomarkers. The platform is based on a gold‐coated, highly‐tilted fiber Bragg grating (TFBG) and a custom‐developed microfluidics. TFBG excites a high‐density, narrow‐cladding‐mode spectral comb that overlaps with the broad absorption of surface plasmons for high‐precision interrogation, enabling ultrasensitive monitoring of analytes. In situ detection and in‐parallel discrimination of different forms of Aβ42 in cerebrospinal fluid (CSF) are successfully demonstrated with a detection of limit in the range of ≈30–170 pg mL−1, which is one order of magnitude below the clinical cut‐off level in AD onset, providing high detection sensitivity for early diagnosis of AD. The integration of the TFBG sensor with multi‐channel microfluidics enables simultaneous detection of multiple biomarkers using sub‐µL sample volumes, as well as combining initial binding rate and real‐time response time to differentiate between multiple biomarkers in terms of binding kinetics. With the advantages of multi‐parameter, low consumption, and highly sensitive detection, the sensor represents an urgently needed potentials for large‐scale diagnosis of diseases at early stage.

Abstract Habitat is fundamental for facilitating various life activities in animals, for instance, snakes procure essential energy for survival and reproduction by selecting ambush microhabitats. While there has been extensive research on the selection of microhabitat for feeding in terrestrial and aquatic snakes, little is known about arboreal snakes. In the present study, we analyzed the ambush microhabitat preferences of Viridovipera stejnegeri, a widely distributed Asian pitviper in China, conducted association analysis between snake microhabitat and prey microhabitat and abundance to determine the ro5le of microhabitat selection in feeding. Employing random forest analysis and habitat selection functions, we further constructed a predictive framework for assessing the probability of ambush site selection by V. stejnegeri. Our results revealed that V. stejnegeri exhibited a distinct microhabitat preference for ambush prey. Among the 13 environmental factors assessed, V. stejnegeri showed pronounced preferences towards 12 of these factors, including climatic factors, geographical factors, and vegetation factors. Furthermore, although the preferences of V. stejnegeri overlapped substantially with those of its prey across multiple habitat factors, food abundance shows no significant association with various habitat factors of V. stejnegeri, and does not have significant predictive effect on habitat selection of V. stejnegeri. Therefore, we infer that V. stejnegeri does not preferentially select microhabitats with the highest food abundance, which does not support the hypothesis that “snakes select habitats based on the spatial distribution of prey abundance.” By analyzing the characteristics of vegetation, geography, and climate, we conclude that V. stejnegeri tends to choose microhabitats with better ambush conditions to increase attack success rate, thereby achieving the optimal feeding success rate at the microhabitat scale, which is in line with the predictions of optimal foraging theory. This study provides new insights into the predation ecology and habitat selection of snakes.

Abstract Ulotaront (SEP‐363856) is a TAAR1 agonist, with 5‐HT1A agonist activity, currently in clinical development for the treatment of schizophrenia. In vitro studies indicate ulotaront is an OCT2‐specific inhibitor with IC50 of 1.27 μM. The primary objective of this study is to determine if a single dose of ulotaront affects the PK of metformin, an index substrate of OCT2, in subjects with schizophrenia. In a randomized, single‐blind, 2‐period crossover study, 25 adults with schizophrenia received a single dose of metformin‐HCl 850 mg (approximately 663 mg metformin) with and without coadministration of 100 mg ulotaront. The plasma samples were analyzed by fully validated LC–MS/MS methods. The primary PK endpoints for metformin were AUCinf, AUClast, Cmax, and tmax. The highest‐anticipated clinical dose of ulotaront (100 mg) had no statistically significant effect on the PK of a single dose of metformin based on Cmax and AUCinf. Geometric least squares mean ratios were 89.98% and 110.63%, respectively, with the 90% confidential interval (CI) for each parameter contained within 80%–125%. Median tmax was comparable across the treatments. Ulotaront does not act as a perpetrator of OCT2‐mediated DDI against metformin. Co‐administration of ulotaront is not expected to require dose adjustment of metformin or other drugs cleared by OCT2.

Abstract In South and Southeast Asia, the habit of chewing betel nuts is prevalent, which leads to oral submucous fibrosis (OSF). OSF is a well‐established precancerous lesion, and a portion of OSF cases eventually progress to oral squamous cell carcinoma (OSCC). However, the specific molecular mechanisms underlying the malignant transformation of OSCC from OSF are poorly understood. In this study, the leading‐edge techniques of Spatial Transcriptomics (ST) and Spatial Metabolomics (SM) are integrated to obtain spatial location information of cancer cells, fibroblasts, and immune cells, as well as the transcriptomic and metabolomic landscapes in OSF‐derived OSCC tissues. This work reveals for the first time that some OSF‐derived OSCC cells undergo partial epithelial–mesenchymal transition (pEMT) within the in situ carcinoma (ISC) region, eventually acquiring fibroblast‐like phenotypes and participating in collagen deposition. Complex interactions among epithelial cells, fibroblasts, and immune cells in the tumor microenvironment are demonstrated. Most importantly, significant metabolic reprogramming in OSF‐derived OSCC, including abnormal polyamine metabolism, potentially playing a pivotal role in promoting tumorigenesis and immune evasion is discovered. The ST and SM data in this study shed new light on deciphering the mechanisms of OSF‐derived OSCC. The work also offers invaluable clues for the prevention and treatment of OSCC.

Abstract Caudal autotomy is a phenomenon observed in many reptile taxa, and tail loss is a pivotal functional trait for reptiles, with potentially negative implications for organism fitness due to its influence on locomotion. Some lizard species can regenerate a lost tail, which sometimes can lead to the development of more than one tail (i.e., abnormal tail regeneration) in the process. However, little is currently known about the impact of abnormal tail regeneration on locomotor performance. In this study, we document abnormal tail regeneration in Eremias yarkandensis, a reptile species native to northwestern China. Additionally, we investigated the sprint speed and endurance performance of these lizards. This study provides the first report on abnormal tail regeneration and its locomotor performance on a Chinese reptile. We suggest that the abnormal regeneration of tails may contribute to the accumulation of food reserves in the species. In light of our findings, we propose that herpetologists continue to share their sporadic observations and assess the locomotor performance of species experiencing abnormal tail regeneration, further expanding our understanding of this intriguing phenomenon.

Abstract An unprecedented Et2Zn‐mediated gem‐dicarboxylation of C─C/C─H single bond of cyclopropanols with CO2 is disclosed, which provides a straightforward and efficient methodology for the synthesis of a variety of structurally diverse and useful malonic acids in moderate to excellent yields. The protocol features mild reaction conditions, excellent functional group compatibility, broad substrate scope, and facile derivatization of the products. DFT calculations confirm that the transition‐metal‐free transformation proceeds through a novel ring‐opening/α‐functionalization/ring‐closing/ring‐opening/β‐functionalization (ROFCOF) process, and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) plays dual important roles in the transformation.

Abstract In order to further improve the accuracy of distributed photovoltaic (DPV) power prediction, this paper proposes a support vector machine (SVM) model based on hybrid competitive particle swarm optimization (HCPSO) with consideration of spatial correlation (SC), for realizing short‐term PV power prediction tasks. Firstly, the spatial correlation analysis is conducted on the distributed PV stations. The k‐means clustering method based on morphological similarity distance improvement and mutual information function is used to select the best reference station and the best delay, which generates strongly correlated PV sequences. Then, a hybrid algorithm of particle swarm optimization (PSO) and sine cosine algorithm (SCA) in a competitive framework (HCPSO) is proposed, aiming to fuse the fast convergence capability of PSO algorithm with the global search capability of SCA algorithm, while enabling the algorithm to effectively handle high‐dimensional optimization problems based on a competitive mechanism. Finally, the HCPSO algorithm is combined with SVM algorithm, which expands the applicable scenarios of the SVM model and effectively improves the accuracy of PV short‐term prediction.

Abstract The development and application of artificial intelligence have led to the exploitation of low‐power and compact intelligent information‐processing systems integrated with sensing, memory, and neuromorphic computing functions. The 2D van der Waals (vdW) materials with abundant reservoirs for arbitrary stacking based on functions and enabling continued device downscaling offer an attractive alternative for continuously promoting artificial intelligence. In this study, full 2D SnS2/h‐BN/CuInP2S6 (CIPS)‐based ferroelectric field‐effect transistors (Fe‐FETs) and utilized light‐induced ferroelectric polarization reversal to achieve excellent memory properties and multi‐functional sensing‐memory‐computing vision simulations are designed. The device exhibits a high on/off current ratio of over 105, long retention time (>104 s), stable cyclic endurance (>350 cycles), and 128 multilevel current states (7‐bit). In addition, fundamental synaptic plasticity characteristics are emulated including paired‐pulse facilitation (PPF), short‐term plasticity (STP), long‐term plasticity (LTP), long‐term potentiation, and long‐term depression. A ferroelectric optoelectronic reservoir computing system for the Modified National Institute of Standards and Technology (MNIST) handwritten digital recognition achieved a high accuracy of 93.62%. Furthermore, retina‐like light adaptation and Pavlovian conditioning are successfully mimicked. These results provide a strategy for developing a multilevel memory and novel neuromorphic vision systems with integrated sensing‐memory‐processing.

Abstract Flavivirus remodels the host endoplasmic reticulum (ER) to generate replication compartments (RCs) as the fundamental structures to accommodate viral replication. Here, a centralized replication mode of flavivirus is reported, i.e., flavivirus concentrates host ER in perinuclear main replication compartments (MRCs) for efficient replication. Superresolution live‐cell imaging demonstrated that flavivirus MRCs formed via a series of events, including multisite ER clustering, growth and merging of ER clusters, directional movement, and convergence in the perinuclear region. The dynamic activities of viral RCs are driven by nonstructural (NS) proteins and are independent of microtubules and actin. Moreover, disrupting MRCs formation by small molecule compounds inhibited flavivirus replication. Overall, the findings reveal unprecedented insight into dynamic ER reorganization by flavivirus and identify a new inhibition strategy.

Abstract Epicardial adipose tissue (EAT) is located between the myocardium and visceral pericardium. The unique anatomy and physiology of the EAT determines its great potential in locally influencing adjacent tissues such as the myocardium and coronary arteries. Classified by research methodologies, this study reviews the latest research progress on the role of EAT in cardiovascular diseases (CVDs), particularly in patients with metabolic disorders. Studies based on imaging techniques demonstrated that increased EAT amount in patients with metabolic disorders is associated with higher risk of CVDs and increased mortality. Then, in‐depth profiling studies indicate that remodeled EAT may serve as a local mediator of the deleterious effects of cardiometabolic conditions and plays a crucial role in CVDs. Further, in vitro coculture studies provided preliminary evidence that the paracrine effect of remodeled EAT on adjacent cardiomyocytes can promote the occurrence and progression of CVDs. Considering the important role of EAT in CVDs, targeting EAT might be a potential strategy to reduce cardiovascular risks. Several interventions have been proved effective in reducing EAT amount. Our review provides valuable insights of the relationship between EAT, metabolic disorders, and CVDs, as well as an overview of the methodological constructs of EAT‐related studies.

Abstract Regular exercise is recommended as an important component of therapy for cardiovascular diseases in clinical practice. However, there are still major challenges in prescribing an optimized exercise regimen to individual patients with established cardiac disease. Here, we tested the effects of different exercise doses on cardiac function in mice with established myocardial infarction (MI). Exercise was introduced to mice with MI after 4 weeks of surgery. Low‐dose exercise (15 min/day for 8 weeks) improved mortality and cardiac function by increasing 44.39% of ejection fractions while inhibiting fibrosis by decreasing 37.74% of distant region. Unlike higher doses of exercise, low‐dose exercise consecutively upregulated cardiac expression of C1q complement/tumor necrosis factor‐associated protein 9 (CTRP9) during exercise (>1.5‐fold). Cardiac‐specific knockdown of CTRP9 abolished the protective effects of low‐dose exercise against established MI, while cardiac‐specific overexpression of CTRP9 protected the heart against established MI. Mechanistically, low‐dose exercise upregulated the transcription factor nuclear receptor subfamily 2 group F member 2 by increasing circulating insulin‐like growth factor 1 (IGF‐1), therefore, upregulating cardiac CTRP9 expression. These results suggest that low‐dose exercise protects the heart against established MI via IGF‐1‐upregulated CTRP9 and may contribute to the development of optimized exercise prescriptions for patients with MI.

Abstract Background Prediction models with high accuracy rates for nonmetastatic cervical cancer (CC) patients are limited. This study aimed to construct and compare predictive models on the basis of machine learning (ML) algorithms for predicting the 5‐year survival status of CC patients through using the Surveillance, Epidemiology, and End Results public database of the National Cancer Institute. Methods The data registered from 2004 to 2016 were extracted and randomly divided into training and validation cohorts (8:2). The least absolute shrinkage and selection operator (LASSO) regression was employed to identify significant factors. Then, four predictive models were constructed, including logistic regression (LR), random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGBoost). The predictive models were evaluated and compared using Receiver‐operating characteristics with areas under the curves (AUCs) and decision curve analysis (DCA), respectively. Results A total of 13,802 patients were involved and classified into training (N = 11,041) and validation (N = 2761) cohorts. By using the LASSO regression method, seven factors were identified. In the training cohort, the XGBoost model showed the best performance (AUC = 0.8400) compared to the other three models (all p

Abstract Much is known about the significance of lycorine, a natural alkaloid, in combating various types of cancer, including breast cancer (BC), but whether it participates in regulating tamoxifen (TAM) resistance and its underlying mechanism remain to be elucidated. Tamoxifen‐resistant (TAMR) BC cells were first established by continuously exposed to increasing concentrations of TAM. Levels of targeted gene including HOXD antisense growth‐associated lncRNA (HAGLR) and Vestigial like family member 4 (VGLL4) were analyzed by qRT‐PCR and western blot, respectively. Cell proliferation ability was assessed by MTT and EdU assays. Flow cytometry was carried out to evaluate the apoptosis. VGLL4 promoter methylation was examined using methylation specific PCR (MSP). The role of HAGLR acting on the expression of VGLL4 via DNA hypermethylation was confirmed by RNA immunoprecipitation (RIP). Here, we reported that lycorine administration reduced the survival ratio of TAMR BC cells, decreased the IC50 of TAM, and strengthened TAM‐induced apoptosis. HAGLR, observed to be highly expressed in TAMR BC cells, was identified to be a downstream effector of lycorine, of which overexpression abolished lycorine‐mediated TAMR inhibition. VGLL4 served as a target of HAGLR in regulating lycorine‐mediated suppression on tamoxifen resistance of TAMR BC cells. Mechanistically, HAGLR epigenetically suppressed VGLL4 expression via DNA methyltransferase 1 (DNMT1)‐mediated DNA hypermethylation. Taken together, our data highlights the pivotal role of lycorine in TAM resistance of BC, which may provide a potential agent for improving the effectiveness and efficacy of BC resistance.

Abstract A space‐time coding metasurface (STCM) operating in the sub‐terahertz band to construct new‐architecture wireless communication systems is proposed. Specifically, a programmable STCM is designed with varactor‐diode‐tuned metasurface elements, enabling precise regulation of harmonic amplitudes and phases by adjusting the time delay and duty cycle of square‐wave modulation signal loaded on the varactor diodes. Independent electromagnetic (EM) regulations in the space and time domains are achieved by STCM to realize flexible beam manipulations and information modulations. Based on these features, a sub‐terahertz wireless communication link is constructed by employing STCM as a transmitter. Experimental results demonstrate that the STCM supports multiple modulation schemes including frequency‐shift keying, phase‐shift keying, and quadrature amplitude modulations in a wide frequency band. It is also shown that the STCM is capable of realizing wide‐angle beam scanning in the range of ±45o, which offers an opportunity for user tracking during the communication. Thus, the STCM transmitter with high device density and low power consumption can provide low‐complexity, low‐cost, low‐power, and low‐heat solutions for building the next‐generation wireless communication systems in the sub‐terahertz frequency and even terahertz band.

Abstract Pathological cardiac hypertrophy exhibits complex and abnormal gene expression patterns and progresses to heart failure. Forkhead box protein O6 (FoxO6) is a key transcription factor involved in many biological processes. This study aimed to explore the role of FoxO6 in cardiac hypertrophy. Three groups of mice were established: wild‐type, FoxO6 knockout, and FoxO6‐overexpressing. The mice received daily administration of angiotensin‐II (Ang‐II) or saline for 4 weeks, after which they were examined for cardiac hypertrophy, fibrosis, and function. Elevated cardiac expression of FoxO6 was observed in Ang‐II‐treated mice. FoxO6 deficiency attenuated contractile dysfunction and cardiac remodeling, including cardiomyocyte hypertrophy and fibroblast proliferation and differentiation. Conversely, FoxO6 overexpression aggravated the cardiomyopathy and heart dysfunction. Further studies identified kinesin family member 15 (Kif15) as downstream molecule of FoxO6. Kif15 inhibition attenuated the aggravating effect of FoxO6 overexpression. In vitro, FoxO6 overexpression increased Kif15 expression in cardiomyocytes and elevated the concentration of transforming growth factor‐β1 (TGF‐β1) in the medium where fibroblasts were grown, exhibiting increased proliferation and differentiation, while FoxO6 knockdown attenuated this effect. Cardiac‐derived FoxO6 promoted pathological cardiac remodeling induced by aggravated afterload largely by activating the Kif15/TGF‐β1 axis. This result further complements the mechanisms of communication among different cells in the heart, providing novel therapeutic targets for heart failure.

Abstract Background The use of proteasome inhibitors (PIs), new immune modulators (IMiDs), and other new drugs, as well as high‐dose chemotherapy combined with autologous stem cell transplantation has considerably improved the survival of young patients with multiple myeloma (MM). However, the improvement in survival among elderly patients remains insufficient. Optimal treatment recommendation models for elderly patients with MM have not been developed especially there are quite few study in the real world. Methods We retrospectively analyzed the treatment patterns and outcomes of 328 Chinese patients (≥65 years) with MM in a real‐world setting. Patients were divided into three groups according to induction regimens. Results The median age of the cohort was 70 (65–86) years. The patients were divided into group 1 (PIs based regimens, n = 218), group 2 (IMiDs based regimens, n = 48) and group 3 (PIs + IMiDs, n = 62). Induction regimens in group 3 produced higher overall response rate than group 1 and 2 (85.42% vs. 71.08% vs. 66.67%, p = 0.016). The median follow‐up of the cohort was 30 (interquartile range [IQR] 18–36) months. For the entire cohort median progression‐free survival (PFS) was 26 (IQR 12.00–42.89) months and overall survival (OS) was 60 (IQR 40.00–67.20) months. The PFS were not significantly different among the three groups (28 months vs. 18 months vs. 26 months, p = 0.182). So were the OS (60 months vs. 59 months vs. not reached, p = 0.067). Multivariate analysis revealed that age >70 year, frailty status (Geriatric vulnerability score), induction efficacy

Abstract Seasonal dietary shifts in animals are important strategies for ecological adaptation. An increasing number of studies have shown that seasonal dietary shifts can influence or even determine the composition of gut microbiota. The Turpan wonder gecko, Teratoscincus roborowskii, lives in extreme desert environments and has a flexible dietary shift to fruit‐eating in warm seasons. However, the effect of such shifts on the gut microbiota is poorly understood. In this study, 16S rRNA sequencing and LC–MS metabolomics were used to examine changes in the gut microbiota composition and metabolic patterns of T. roborowskii. The results demonstrated that the gut microbes of T. roborowskii underwent significant seasonal changes, and the abundance of phylum level in autumn was significantly higher than spring, but meanwhile, the diversity was lower. At the family level, the abundance and diversity of the gut microbiota were both higher in autumn. Firmicutes, Bacteroidetes, and Proteobacteria were the dominant gut microbes of T. roborowskii. Verrucomicrobia and Proteobacteria exhibited dynamic ebb and flow patterns between spring and autumn. Metabolomic profiling also revealed differences mainly related to the formation of secondary bile acids. The pantothenate and CoA biosynthesis, and lysine degradation pathways identified by KEGG enrichment symbolize the exuberant metabolic capacity of T. roborowskii. Furthermore, strong correlations were detected between metabolite types and bacteria, and this correlation may be an important adaptation of T. roborowskii to cope with dietary shifts and improve energy acquisition. Our study provides a theoretical basis for exploring the adaptive evolution of the special frugivorous behavior of T. roborowskii, which is an important progress in the study of gut microbes in desert lizards.

Abstract Leveraging the power of computational methods, AI can perform effective strategies in intelligent design. Researchers are pushing the boundaries of AI, developing computational systems to solve complex questions. The authors investigate the association of user preference for UI and deep image features, aiming to predict user preference level using deep convolutional neural networks (DCNNs) trained on a UI design image dataset. A total of 12,186 UI design images were collected from UI.cn and DOOOOR.com. Users' views and likes can help understand the implicit user preference level, which is set as the ground‐truth annotation for the dataset. Six DCNNs, including VGG‐19, InceptionNet‐V3, MobileNet, EfficientNet, ResNet‐50 and NASNetLarge were trained to learn the user preference of UI images. The experiment achieves an optimal result with a mean‐squared error of 0.000214 and a mean absolute error of 0.0103 based on EfficientNet, which indicates that the proposed method provides the possibility in learning the pattern of user aesthetics preference for UI design. On the basis of the prediction model, a mobile application named ‘HotUI’ was developed for UI design recommendations.

Abstract Aim Attitudes toward older persons could affect services that are provided to them and change the value of the care they receive. The attitude of nursing students toward older persons is very important as it will affect their care of older patients in future. However, in China, the attitude of higher vocational nursing students toward older persons has not been widely studied. The purpose of this study is to explore the attitudes and factors toward older people among nursing students in higher vocational colleges in Heilongjiang Province. Design A cross‐sectional study. Methods A cross‐sectional study was conducted using cluster sampling. A total of 1106 nursing students from two higher vocational colleges in Heilongjiang Province participated. Multiple linear regression analysis was conducted to identify the factors influencing nursing students’ attitudes toward older people. Conclusion This study showed that the vocational college nursing students have a positive attitude towardolder persons. However, the proportion of respondents taking care of older persons as their first choice in their future career needs to be increased. Advanced vocational colleges should pay attention to the attitudes of nursing students toward older persons, and strengthen the education of career development planning, which has practical significance in meeting the diversified health needs of older persons and ensuring healthy aging.

Abstract Aim This study aimed to explore the factors associated with attitudes towards the older adults among nursing students, to clarify the impact of empathy and end‐of‐life care on the attitude of the older adults, and to provide a basis for the follow‐up of education courses related to older adults care and the training of older adults care talents. Design A cross‐sectional study. Methods A cross‐sectional survey on nursing students' knowledge and attitudes towards older adults was conducted from 24 December 2020–24 February 2021. The Chinese versions of the end‐of‐life Attitudes Scale, Jefferson Empathy Scale‐Nursing Version and Kogan Attitudes Scale for the Elderly were used for this cross‐sectional study. We used the purposive sampling method to conduct a questionnaire survey on nursing students at Heilongjiang Nursing College (n = 371, effective response rate: 64.52%). Results The average score of FATCOD‐B was 99.04 (7.71), and the score of C‐JSE‐HPS was 100.67 (12.90). The total average score of nursing students' attitudes towards older adults was 139.91 (15.79). The hierarchical regression analysis showed that education (β = −.125, p = .025) and personal experience (β = −.132, p = .008) correlated negatively with attitudes towards the older adults, while the end‐of‐life care (β = .140, p = .013) and empathy (β = .285, p

Abstract Little is known about the epidemiology and impact of atrial fibrillation (AF) on cardiovascular diseases (CVD) mortality among hypertensive elderly population in northeast China. The community‐based study included 4497 hypertensive elderly residents aged ≥65 years who lived in northeast China from September 2017 to March 2019. Information on CVD deaths was obtained from baseline until July 31, 2021. Cox proportional hazard regression models were performed in the evaluation of CVD mortality. We identified 101 persons with AF. The prevalence of AF was 2.2% among elderly hypertensive population, which increased significantly with age. The prevalence of AF was higher in men than in women. The awareness rate was 51.5%, higher in urban areas than in rural areas (68.8% vs 43.5%, P = .018). Only 4.0% patients received oral anticoagulant (OAC) therapy among AF patients. Moreover, diabetes (26.7%) and dyslipidemia (37.6%) were highly prevalent in AF patients. Furthermore, 212 persons died due to CVD (14.7/1000 person‐years) during a median follow‐up of 3.2 years. AF patients had a 3.42 (95% CI: 2.07‐5.63) times higher risk of CVD mortality than the patients without AF in the fully adjusted model. Therefore, the burden of AF among hypertensive elderly population in northeast China was considerable. Long‐term screening and management strategies for AF and related risk factors are required among hypertensive elderly in northeast China.

Abstract CD73, a cell surface‐bound nucleotidase, facilitates extracellular adenosine formation by hydrolyzing 5′‐AMP to adenosine. Several studies have shown that CD73 plays an essential role in immune escape, cell proliferation and tumor angiogenesis, making it an attractive target for cancer therapies. However, there are limited clinical benefits associated with the mainstream enzymatic inhibitors of CD73, suggesting that the mechanism underlying the role of CD73 in tumor progression is more complex than anticipated, and further investigation is necessary. In this study, CD73 is found to overexpress in the cytoplasm of pancreatic ductal adenocarcinoma (PDAC) cells and promotes metastasis in a nucleotidase‐independent manner, which cannot be restrained by the CD73 monoclonal antibodies or small‐molecule enzymatic inhibitors. Furthermore, CD73 promotes the metastasis of PDAC by binding to the E3 ligase TRIM21, competing with the Snail for its binding site. Additionally, a CD73 transcriptional inhibitor, diclofenac, a non‐steroidal anti‐inflammatory drug, is more effective than the CD73 blocking antibody for the treatment of PDAC metastasis. Diclofenac also enhances the therapeutic efficacy of gemcitabine in the spontaneous KPC (LSL‐KrasG12D/+, LSL‐Trp53R172H/+, and Pdx‐1‐Cre) pancreatic cancer model. Therefore, diclofenac may be an effective anti‐CD73 therapy, when used alone or in combination with gemcitabine‐based chemotherapy regimen, for metastatic PDAC.

Abstract Artificial synapses and neurons are crucial milestones for neuromorphic computing hardware, and memristors with resistive and threshold switching characteristics are regarded as the most promising candidates for the construction of hardware neural networks. However, most of the memristors can only operate in one mode, that is, resistive switching or threshold switching, and distinct memristors are required to construct fully memristive neuromorphic computing hardware, making it more complex for the fabrication and integration of the hardware. Herein, we propose a flexible dual‐mode memristor array based on core–shell CsPbBr3@graphdiyne nanocrystals, which features a 100% transition yield, small cycle‐to‐cycle and device‐to‐device variability, excellent flexibility, and environmental stability. Based on this dual‐mode memristor, homo‐material‐based fully memristive neuromorphic computing hardware—a power‐free artificial nociceptive signal processing system and a spiking neural network—are constructed for the first time. Our dual‐mode memristors greatly simplify the fabrication and integration of fully memristive neuromorphic systems.

Abstract The active and stable palladium (Pd) based catalysts for CH4 conversion are of great environmental and industrial significance. Herein, we employed N2 as an optimal activation agent to develop a Pd nanocluster exsolved Ce‐incorporated perovskite ferrite catalyst toward lean methane oxidation. Replacing the traditional initiator of H2, the N2 was found as an effective driving force to selectively touch off the surface exsolution of Pd nanocluster from perovskite framework without deteriorating the overall material robustness. The catalyst showed an outstanding T50 (temperature of 50% conversion) plummeting down to 350°C, outperforming the pristine and H2‐activated counterparts. Further, the combined theoretical and experimental results also deciphered the crucial role that the atomically dispersed Ce ions played in both construction of active sites and CH4 conversion. The isolated Ce located at the A‐site of perovskite framework facilitated the thermodynamic and kinetics of the Pd exsolution process, lowering its formation temperature and promoting its quantity. Moreover, the incorporation of Ce lowered the energy barrier for cleavage of C─H bond, and was dedicated to the preservation of highly reactive PdOx moieties during stability measurement. This work successfully ventures uncharted territory of in situ exsolution to provide a new design thinking for a highly performed catalytic interface.

Abstract Signals from gyros and accelerometers in an inertial navigation system (INS) can be processed to obtain navigation information while its errors accumulate with time. A path with long‐term characteristics is more likely to encounter unpredictable dynamic conditions. To deal with such problems, this work improves the global static path‐planning algorithm based on the A* algorithm, and the local dynamic path‐planning algorithm based on dynamic window approach (DWA). In the global planning algorithm, the gravity index and the heading index are incorporated into the cost function of the A* algorithm to consider the mismatches and the deflection of the path. Furthermore, the search method of the A* algorithm is also improved. In the local planning algorithm, the motion model of the DWA algorithm is improved to a high‐precision model and expressed in a geographic coordinate system. Finally, the improved global static planning and local dynamic planning are combined as the global dynamic path‐planning algorithm of an underwater vehicle. The simulation results show that the global dynamic path‐planning algorithm proposed can realise obstacle‐free navigation of the underwater vehicle.

Abstract Background Nasal nitric oxide (nNO) levels in allergic rhinitis (AR), healthy people or nonallergic rhinitis (NAR) have shown contradicting results in previous studies. By meta‐analysis, we reviewed studies that measured nNO in AR patients to assess nNO's ability to discriminate AR from healthy people or NAR. Methods We systematically searched PubMed, Cochrane, Embase, Ovid, Web of Science, Wanfang Data, CNKI until December 15, 2020. Differences were expressed as standardized mean differences (SMD) with 95% confidence interval (CI), by random‐effects method. Results A total of 10 original studies with 561 AR patients, 327 healthy controls, 123 NAR patients were included in the narrative synthesis and 9 studies in the meta‐analysis. nNO in AR was significantly increased compared with healthy controls (SMD: 0.989; 95% CI: 0.402, 1.576; p = .001) or NAR (SMD: 0.680; 95% CI: 0.101, 1.259; p = 0.021). However, subgroup analysis based on measuring process and patient characteristics showed that no significant differences were detected in nNO between AR patients with nasal polyps or sinusitis or marked ostial obstruction and healthy controls. Conclusions nNO is a potential indicator for recognizing AR. Nasal polyps, sinusitis and marked ostial obstruction should be considered before nNO is applied to detect AR.

Abstract Objectives To explore the correlations among social isolation and symptoms of anxiety and depression among patients with breast cancer in China and to further verify the mediating role of social support in social isolation and symptoms of depression or anxiety. Design A cross‐sectional survey. Settings The cluster sampling method was conducted for 456 female inpatients diagnosed with breast cancer at the Tumor Hospital Affiliated of Harbin Medical University from April 2019–September 2019. Methods Pearson correlation analysis was used for identifying correlations among all the variables. Mediation effect analysis was used to examine the role of social support in social isolation and symptoms of depression or anxiety. Results The results showed a prevalence of 73.26% and 70.44% for anxiety and depression symptoms in patients with breast cancer, respectively. Anxiety was significantly negatively correlated with social support (r = −.334, p

Abstract Background For almost two centuries, ecologists have examined geographical patterns in the evolution of body size and the associated determinants. During that time, one of the most common patterns to have emerged is the increase in body size with increasing latitude (referred to as Bergmann's rule). Typically, this pattern is explained in terms of an evolutionary response that serves to minimize heat loss in colder climates, mostly in endotherms. In contrast, however, this rule rarely explains geographical patterns in the evolution of body size among ectotherms (e.g., reptiles). Location China. Aim In this study, we assembled a dataset comprising the maximum sizes of 211 lizard species in China and examined the geographical patterns in body size evolution and its determinants. Specifically, we assessed the relationship between body size and climate among all lizard species and within four major groups at both assemblage and interspecific levels. Results Although we found that the body size of Chinese lizards was larger in warmer regions, we established that at the assemblage level, size was correlated with multiple climatic factors, and that body size–climate correlations differed within the four major groups. Phylogenetic analysis at the species level revealed that no single climatic factor was associated with body size, with the exception of agamids, for which size was found to be positively correlated with temperature. Main conclusions Geographical patterns in Chinese lizard body size are driven by multiple factors, and overall patterns are probably influenced by those of the major groups. We suggest that our analyses at two different levels may have contributed to the inconsistent results obtained in this study. Further studies investigating the effects of altitude and ecological factors are needed to gain a more comprehensive understanding of the evolution of ectotherm body size.

Abstract Aims To develop and internally validate a nomogram to predict the risk of death within 6 months of onset of stroke in Chinese. Identifying risk factors with potentially direct effects on the nomogram will improve the quality of risk assessment and help nurses implement preventive measures based on patient‐specific risk factors. Design A retrospective study. Methods We performed a least absolute shrinkage and selection operator (LASSO) regression modelling and multivariate logistic regression analysis to establish a prediction model of death risk in stroke patients within 6 months of onset. LASSO and time‐dependent Cox regression models were further used to analyse the 6‐month survival of stroke patients. Data were collected from 21 October 2013–6 May 2019. Results The independent predictors of the nomogram were Barthel index (odds ratio (OR) = 0.980, 95% confidence interval (CI) = 0.961–0.998, p = .03), platelet/lymphocyte ratio (OR = 1.005, 95% CI = 1.000–1.010, p = .04) and serum albumin (OR = 0.854, 95% CI = 0.774–0.931, p

Abstract This study aimed to explore the epidemiological characteristics of breast cancer and establish an Exponential Smoothing (ETS) and Autoregressive Integrated Moving Average (ARIMA) models to predict the development of incidence in Shantou. This study has a large sample size, strong representativeness, and wide‐ranging and comprehensive medical insurance information, which can fill the gaps in basic epidemiological research on breast cancer in Shantou. Successful completion of this study is a helpful tool to understand the epidemiology of Guangdong Province and Southern China. This study also provides data and scientific references for the government and future research on breast cancer prevention and control. This retrospective study was conducted to describe the epidemic intensity, epidemic distribution, and epidemic trend of breast cancer in Shantou, Guangdong Province, from 2006 to 2017, gathered from the Shantou's Medical Security Bureau covers the whole districts of Shantou. ETS and ARIMA models were used to describe the regional distribution, time distribution, and population distribution of breast cancer in Shantou. Moreover, based on the ARIMA model and ETS model, the incidence trend of breast cancer was predicted during 2018–2022. This study included 5,681 breast cancer patients, majority of whom were aged 50–59 years. The male‐to‐female ratio of the breast cancer patients was about 1:107 (the same ratio of the insured population was 1:1). Female patients accounted for 98.61% of the total insured population. The incidence and mortality rates of female breast cancer were 16.42/100,000 and 0.66/100,000, respectively. Based on the ARIMA model or ARIMA and ETS model, a gradually decreasing trend in the incidence of breast cancer is expected in the future. Comparing the performances of the ARIMA model and ETS model, ARIMA (4, 0, 1) (0, 1, 0) model had a lower the root mean squared error and the mean absolute percentage error than ETS (M, N) model. This population‐based retrospective study showed that the high‐risk age for the age‐specific incidence of female breast cancer was 50–55 years. It is recommended that healthcare administration should strengthen program awareness and education regarding breast cancer prevention and control. It is also possible that feasibility of extrapolating the current methodology to other future studies or broader populations in which the cancer registry data are not available.

Reduced expression of the uptake transporter, OCTN1 (SLC22A4), has been reported as a strong predictor of poor event‐free and overall survival in multiple cohorts of patients with acute myeloid leukemia (AML) receiving the cytidine nucleoside analog, cytarabine (Ara‐C). To further understand the mechanistic basis of interindividual variability in the functional expression of OCTN1 in AML, we hypothesized a mechanistic connection to DNA methylation‐based epigenetic repression of SLC22A4. We found increased basal SLC22A4 methylation was associated with decreased Ara‐C uptake in AML cell lines. Pre‐treatment with hypomethylating agents, 5‐azacytidine, or decitabine, restored SLC22A4 mRNA expression, increased cellular uptake of Ara‐C, and was associated with increased cellular sensitivity to Ara‐C compared with vehicle‐treated cells. Additionally, lower SLC22A4 methylation status was associated with distinct clinical advantages in both adult and pediatric patients with AML. These findings suggest a regulatory mechanism is involved in the interindividual variability in response to Ara‐C, and provides a basis for the integration of hypomethylating agents into Ara‐C‐based treatment regimens.

Abstract Objective Based on the eighth TNM staging system, T3a renal cell carcinoma (RCC) is identified as an anatomical extrarenal invasion and does not consider the size of the tumor; however, it may not fully predict the prognosis of the patient. The objective of this study was to evaluate the prognostic value of tumor size effects on prognosis in T3a RCC and propose an alternative tumor stage system combined with T1‐2. Methods Data relating to T1‐3aN0M0 RCC (n = 49586) were obtained from the Surveillance, Epidemiology, and End Results database (2004–2015). Survival analyses were conducted by Cox regression and Fine and Gray regression. Harrell's concordance index (c‐index) was used to assess the discriminatory ability of the prognostic factors. Results A 1‐cm increase in T3a RCC resulted in an 8% increase in all‐cause mortality (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.06–1.10, p 7] cm) demonstrated good RCC‐special survival predictive accuracy (c‐index: 0.729), which was higher than that shown by the current eighth edition T‐staging system (c‐index: 0.720). Conclusion Tumor size should be taken into consideration for T3aN0M0 RCC rather than based on anatomical features alone.

Abstract Objective To compare the survival outcomes of local ablation (LA) and partial nephrectomy (PN) for T1N0M0 renal cell carcinoma (RCC). Method We identified 38,155 T1N0M0 RCC patients treated with PN or LA in 2004‐2016 from the retrospective Surveillance, Epidemiology, and End Results databases. Among them, there were 4656 LA and 33,499 PN. A Cox proportional hazards regression model, cause‐specific Cox regression and Fine and Gray sub‐distribution hazard ratio (sHR) with inverse probability of treatment weighting (IPTW) adjusting was utilized to compare the effects of LA vs PN on all‐, RCC‐, and non‐RCC–caused mortality. Results Within the IPTW analysis, patients who underwent PN experienced a better overall survival (OS) (HR, 1.56; 95% CI, 1.40‐1.74; P 85 years (HR, 1.14; 95% CI, 0.73‐1.79, P = .577), chromophobe RCC (HR, 1.68; 95% CI, 0.94‐3.00, P = .078), and tumor size 85 years (sHR, 0.89; 95% CI, 0.52‐1.27, P = .520) and tumor size 85), small RCC (

Background. Vaspin is an important adipokine that is involved in cardiovascular diseases. This study is aimed at investigating whether vaspin participates in sepsis-induced cardiac injury and explored the possible mechanism. Methods. First, cecal ligation and puncture (CLP) and lipopolysaccharide (LPS) were used to establish a mouse model of sepsis, and cardiac vaspin expression was examined. In addition, after pretreatment with vaspin or phosphate-buffered saline (PBS), wild-type (WT) mice underwent CLP to establish a septic model and received sham as a control. Finally, WT mice and kallikrein 7 (KLK7-/-) mice were underwent CLP with or without vaspin pretreatment. Results. Mice that underwent CLP and were administered LPS exhibited increased vaspin expression in both the heart and serum compared with sham- or saline-treated mice. In CLP mice, pretreatment with vaspin reduced mortality and alleviated the expression of cardiac injury markers and cardiac dysfunction. In addition, vaspin reduced the cardiac levels of CD45+ cells and CD68+ cells, alleviated the cardiac inflammatory response, and reduced cardiomyocyte apoptosis. The protective effects of vaspin on CLP mice were masked by the deletion of KLK7, which was demonstrated to be a downstream signal of vaspin. Conclusions. Vaspin alleviates cardiac inflammation and plays a protective role in sepsis-induced cardiac injury by reducing KLK7 expression.

Radiation heat transfer plays a dominant role in high-temperature flow field. Rapid and reliable calculation of spectral radiation properties is beneficial for thermal analysis and detection of radiation target. In this paper, a multiscale-band k-distribution model is proposed for the study of radiation properties in high-temperature gases. The accurate absorption coefficients are firstly calculated using the line-by-line model. The slope of the accurate absorption coefficient line and its slope threshold are then extracted and analyzed, which act as a basis to divide the absorption coefficient line into multiple segments. For different segments, different bandwidths are chosen for the corresponding band k-distribution model. In the model, the 7-point Gauss–Lobatto method is employed to obtain the optimized absorption coefficients. These optimized absorption coefficients formed the absorption coefficient database. The radiation intensities of gases are finally calculated and analyzed based on the optimized database. Experimental results suggest that the multiscale-band k-distribution model can improve the efficiency up to 35% compared with the widely used narrow-band k-distribution model. Simultaneously, the relative calculation error is less than 5% compared with the most accurate line-by-line model.

Background and Aims. The adequate myotomy length during peroral endoscopic myotomy (POEM) is still controversial. We performed this systematic review and meta-analysis to determine the efficacy and safety of the modified POEM with shorter myotomy (SM) and compare the outcomes between SM and longer myotomy (LM) in achalasia patients. Methods. A comprehensive literature search was conducted in PubMed, EMBASE, Cochrane Library, and Web of Science databases from inception to May 28, 2021. The primary outcome was clinical success rate and incidence of reflux-relative adverse events (AEs). Fixed- or random-effect models were adopted for the analysis according to the heterogeneity. Results. Five studies involving 225 patients in SM group and 222 patients in LM group were included. The overall clinical success of SM was 96.6% (95% confidence interval (CI) 92.7 to 98.4%). SM showed noninferior response as compared to LM (risk ratio (RR) 1.02, 95% CI 0.98 to 1.06, P=0.41, I2=0%). Based on the abnormal acid reflux by pH monitoring, its incidence was significantly lower in the SM group than that in the LM group (RR 0.58, 95% CI 0.36 to 0.94, P=0.03, I2=0%). With respect to procedure-related parameters, the total procedure time of SM was significantly shorter than that of LM (mean difference (MD) -16.30, 95% CI -23.10 to -9.49, P

Compared with traditional energy aircraft, electric/hybrid aircraft show the advantages of environmental protection and low carbon and have been considered one of the most promising directions for the future development of the aviation industry. However, the battery (battery box) structure employed in electric/hybrid aircraft generally faces several problems (e.g., insufficient rigidity/strength and low structural load-bearing efficiency). In this study, the composite cap-type-reinforced wall plate structure commonly applied in electric aircraft is developed to fill the battery structure using the internal cavity of the cap type, which leads to the formation of an integrated structure type of a composite cap-type-reinforced wall plate filled battery. The basic static strength analysis of the integrated structure was conducted to measure its basic load-bearing capacity. To investigate the impact resistance of the integrated structure, a series of bird collision simulations were conducted to analyze the impact position, impact angle, impact speed, and other factors on the integrated structure and the design direction of the composite cap-type-reinforced wall plate-filled battery-integrated structure against bird collision was summarized.

Object. The study compared the efficacy and tolerability of two different low-volume split-dose polyethylene glycol electrolytes solution (PEG-ELS) bowel preparation for morning colonoscopy. Methods. A total of 120 patients were randomized to receive either the control group (n = 64) or the experimental group (n = 65). Patients in the control group adopted the low-volume split-dose regimen one, and patients in the experimental group adopted the low-volume split-dose regimen two. Those randomized to regimen one were instructed to take 0.75 L PEG two hours after dinner the day before the colonoscopy and 1.5 L PEG 4 hours before the colonoscopy. Patients assigned to regimen two were invited to consume 1.5 L PEG two hours after dinner the day before the colonoscopy and 0.75 L PEG 4 hours before the colonoscopy. The quality of bowel preparation, rated according to a Boston Bowel Preparation Scale (BBPS), represented the primary outcome measure. Tolerability, satisfaction, and lesions detection rated were secondary outcomes. Results. There was no significant difference between the transverse colon and right colon scores between the two groups (P>0.05). The low-volume split-dose regimen two showed a higher success rate for cleansing of the right colon and overall colon (P0.05). However, regimen two had significantly less nausea, vomiting, and fatigue than regimen one (24.62% vs. 42.19%, P=0.034; 10.77% vs. 25.00%, P=0.035; 6.15% vs. 21.88%, P=0.010, respectively). Patient-reported satisfaction and willingness to repeat the bowel preparation were significantly higher for low-volume split-dose regimen two than for low-volume split-dose regimen one (P=0.011; P=0.015). Conclusions. In early morning colonoscopies, the bowel-cleansing efficacy and patient tolerability of low-volume split-dose regimen two were superior to low-volume split-dose regimen one.

Abstract LncRNAs have been shown to play essential roles in bladder cancer (BC) progress. Our microarrays of clinical samples firstly screened that lncRNA muscleblind‐like 1 antisense RNA 1 (MBNL1‐AS1) was poorly expressed in BC tissues. However, its biological function in BC remains not well understood. Here we examined the clinical correlations with MBNL1‐AS1 in BC patients. Then, 5673 and T24 cell lines were employed to investigate the role of MBNL1‐AS1 in the proliferation and apoptosis of BC cells in vitro and in vivo. Furthermore, miR‐135a‐5p (miR‐135a)/PHLPP2/FOXO1 axis was focused to explore its regulatory mechanism in BC. The results showed that MBNL1‐AS1 was significantly downregulated in bladder tumor tissues, and associated with BC progression. In vitro, MBNL1‐AS1 knockdown increased the number of viable cells and bromodeoxyuridine‐positive cells, accelerated cell cycle, and dysregulated proliferative regulators (Ki67, p21, p27, and Cyclin D1) in BC cells. The apoptotic cells and the cleavages of caspase‐3/9 were reduced in MBNL1‐AS1‐silenced BC cells. Overexpression of MBNL1‐AS1 had opposite effects on BC cell proliferation and apoptosis. Moreover miR‐135a was demonstrated to interact with MBNL1‐AS1, and inhibiting miR‐135a reversed the effects of shMBNL1‐AS1 on BC cells. The downstream effectors (PHLPP2 and FOXO1) were positively regulated by MBNL1‐AS1, but negatively regulated by miR‐135a. Similar results were also observed in xenograft tumors. In conclusion, this study firstly suggests that MBNL1‐AS1 acts as a tumor suppressor of BC by targeting miR‐135a/PHLPP2/FOXO1 axis, providing a novel insight for BC diagnosis and treatment.

Fms‐like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations, common in pediatric acute myeloid leukemia (AML), associate with early relapse and poor prognosis. Past studies have suggested additional cooperative mutations are required for leukemogenesis in FLT3‐ITD+ AML. Using RNA sequencing and a next‐generation targeted gene panel, we broadly characterize the co‐occurring genomic alterations in pediatric cytogenetically normal (CN) FLT3‐ITD+ AML to gain a deeper understanding of the clonal patterns and heterogeneity at diagnosis and relapse. We show that chimeric transcripts were present in 21 of 34 (62%) of de novo samples, 2 (6%) of these samples included a rare reoccurring fusion partner BCL11B. At diagnosis, the median number of mutations other than FLT3 per patient was 1 (range 0–3), which involved 8 gene pathways; WT1 and NPM1 mutations were frequently observed (35% and 24%, respectively). Fusion transcripts and high variant allele frequency (VAF) mutants, which included WT1, NPM1, SMARCA2, RAD21, and TYK2, were retained from diagnosis to relapse. We did observe reduction in VAF of simple or single mutation clones, but VAFs were preserved or expanded in more complex clones with multiple mutations. Our data provide the first insight into the genomic complexity of pediatric CN FLT3‐ITD+ AML and could help stratify future targeted treatment strategies.

In this study, the thermal conductivity and P-wave velocity of silty clay soil with different water contents are investigated through experiments at different temperatures, and a theoretical correlation between thermal conductivity and wave velocity is established. With temperature decline, the unfrozen water content is reduced and frost heave cracks propagate in soil samples. The variations in thermal conductivity and P-wave velocity are summarized as four phases. The freezing temperature of silty clay soil is between −2°C and −4°C. There is an inversely proportional relationship between thermal conductivity and P-wave velocity for silty clay soil at temperatures below freezing. The experimental results show that the theoretical correlation can well explain the relationship between P-wave velocity and thermal conductivity. These findings provide a possibility for determining the thermal conductivity easily and quickly in geothermal systems and underground engineering projects.