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Abstract The high‐voltage pulse discharge technology, which is based on the electrohydraulic effect, can generate powerful, controllable, and repetitive electrohydraulic shock waves (EHSWs) in underground confined space, so it has been applied in the petroleum industry to improve the permeable of the reservoir. In this paper, a numerical model based on LS‐DYNA is built to study the damage analysis of the cement sheath and rock subjected to EHSWs during perforation completion. The results show that the stress state of the cement sheath and rock surrounding the perforation hole is determined by the shock pressure from both the perforation hole and the wellbore; the damage of the cement sheath and rock is mainly caused by tensile stress; the damage zone of the cement sheath is mainly distributed on the inner surface and near the perforation hole, while the damage zone of rock is distributed near the perforation hole; after multiple discharges, the damage of cement sheath and rock gradually accumulates, and the damage zone eventually forms a vertical plane along perforation holes. Overall, these results provide guidance for the safe application of the high‐voltage pulse discharge technology in the oil field.

Abstract Objective High‐risk types of diffuse gliomas in adults include isocitrate dehydrogenase (IDH) wild‐type glioblastomas and grade 4 astrocytomas. Achieving noninvasive prediction of high‐risk molecular subtypes of gliomas is important for personalized and precise diagnosis and treatment. Methods We retrospectively collected data from 116 patients diagnosed with adult diffuse gliomas. Multiple high‐risk molecular markers were tested, and various habitat models and whole‐tumor models were constructed based on preoperative routine and diffusion kurtosis imaging (DKI) sequences to predict high‐risk molecular subtypes of gliomas. Feature selection and model construction utilized Least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM). Finally, the Wilcoxon rank‐sum test was employed to explore the correlation between habitat quantitative features (intra‐tumor heterogeneity score，ITH score) and heterogeneity, as well as high‐risk molecular subtypes. Results The results showed that the habitat analysis model based on DKI performed remarkably well (with AUC values reaching 0.977 and 0.902 in the training and test sets, respectively). The model's performance was further enhanced when combined with clinical variables. (The AUC values were 0.994 and 0.920, respectively.) Additionally, we found a close correlation between ITH score and heterogeneity, with statistically significant differences observed between high‐risk and non‐high‐risk molecular subtypes. Interpretation The habitat model based on DKI is an ideal means for preoperatively predicting high‐risk molecular subtypes of gliomas, holding significant value for noninvasively alerting malignant gliomas and those with malignant transformation potential.

Abstract Disruption of the alveolar barrier can trigger acute lung injury. This study elucidated the association of methyltransferase‐like 3 (METTL3) with Streptococcus pneumoniae (SP)‐induced apoptosis and inflammatory injury of alveolar epithelial cells (AECs). AECs were cultured and then infected with SP. Furthermore, the expression of METTL3, interleukin (IL)‐10, IL‐6, tumor necrosis factor‐alpha (TNF‐α), monocyte chemoattractant protein‐1 (MCP‐1), long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1), mucin 19 (MUC19), N6‐methyladenosine (m6A), and NEAT1 after m6A modification were detected by qRT‐PCR, Western blot, and enzyme‐linked immunosorbent, m6A quantification, and methylated RNA immunoprecipitation‐qPCR analyses, respectively. Moreover, the subcellular localization of NEAT1 was analyzed by nuclear/cytosol fractionation assay, and the binding between NEAT1 and CCCTC‐binding factor (CTCF) was also analyzed. The results of this investigation revealed that SP‐induced apoptosis and inflammatory injury in AECs and upregulated METTL3 expression. In addition, the downregulation of METTL3 alleviated apoptosis and inflammatory injury in AECs. METTL3‐mediated m6A modification increased NEAT1 and promoted its binding with CTCF to facilitate MUC19 transcription. NEAT1 or MUC19 overexpression disrupted their protective role of silencing METTL3 in AECs, thereby increasing apoptosis and inflammatory injury. In conclusion, this is the first study to suggest that METTL3 aggravates SP‐induced cell damage via the NEAT1/CTCF/MUC19 axis.

Abstract At present, the multi‐object tracking method based on transformer generally uses its powerful self‐attention mechanism and global modelling ability to improve the accuracy of object tracking. However, most existing methods excessively rely on hardware devices, leading to an inconsistency between accuracy and speed in practical applications. Therefore, a lightweight transformer joint position awareness algorithm is proposed to solve the above problems. Firstly, a joint attention module to enhance the ShuffleNet V2 network is proposed. This module comprises the spatio‐temporal pyramid module and the convolutional block attention module. The spatio‐temporal pyramid module fuses multi‐scale features to capture information on different spatial and temporal scales. The convolutional block attention module aggregates channel and spatial dimension information to enhance the representation ability of the model. Then, a position encoding generator module and a dynamic template update strategy are proposed to solve the occlusion. Group convolution is adopted in the input sequence through position encoding generator module, with each convolution group responsible for handling the relative positional relationships of a specific range. In order to improve the reliability of the template, dynamic template update strategy is used to update the template at the appropriate time. The effectiveness of the approach is validated on the MOT16, MOT17, and MOT20 datasets.

ABSTRACT Introduction Staged bilateral surgery is widely used to treat synchronous multiple primary lung cancer (SMPLC); however, the prognostic factors for survival outcomes remain unclear. This study aimed to identify prognostic factors and construct a predictive model for overall survival (OS) and recurrence‐free survival (RFS) in patients with SMPLC who underwent staged bilateral surgery. Methods The study included 256 patients diagnosed with SMPLC and treated with staged bilateral surgery at our hospital between January 2010 and July 2017. Multivariate Cox proportional‐hazard regression was used to identify prognostic factors for OS and RFS. Additionally, a predictive model was constructed using time‐dependent receiver operating characteristic curves. Results Among the 256 patients, 10 (3.95%) succumbed to the disease and 24 (9.41%) experienced recurrence. Smoking (hazard ratio [HR]: 5.128; 95% confidence interval [CI]: 1.442–18.233; p = 0.012) and most advanced pathological TNM (pTNM) stage (II + III) (HR: 12.938; 95% CI: 2.650–63.176; p = 0.002) were identified as significant predictors of poor OS. A prognostic model was developed for predicting OS, with a 5‐year area under the curve (AUC) of 0.854. Furthermore, most advanced pTNM stage (II + III) was associated with poor RFS (HR: 5.964; 95% CI: 2.669–13.327; p

Abstract Both sodium‐ion batteries (SIBs) and potassium‐ion batteries (PIBs) are considered as promising candidates in grid‐level energy storage devices. Unfortunately, the larger ionic radii of K+ and Na+ induce poor diffusion kinetics and cycling stability of carbon anode materials. Pore structure regulation is an ideal strategy to promote the diffusion kinetics and cyclic stability of carbon materials by facilitating electrolyte infiltration, increasing the transport channels, and alleviating the volume change. However, traditional pore‐forming agent‐assisted methods considerably increase the difficulty of synthesis and limit practical applications of porous carbon materials. Herein, porous carbon materials (Ca‐PC/Na‐PC/K‐PC) with different pore structures have been prepared with gluconates as the precursors, and the amorphous structure, abundant micropores, and oxygen‐doping active sites endow the Ca‐PC anode with excellent potassium and sodium storage performance. For PIBs, the capacitive contribution ratio of Ca‐PC is 82% at 5.0 mV s−1 due to the introduction of micropores and high oxygen‐doping content, while a high reversible capacity of 121.4 mAh g−1 can be reached at 5 A g−1 after 2000 cycles. For SIBs, stable sodium storage capacity of 101.4 mAh g−1 can be achieved at 2 A g−1 after 8000 cycles with a very low decay rate of 0.65% for per cycle. This work may provide an avenue for the application of porous carbon materials in the energy storage field.

Abstract Photonic crystals are a new class of optical microstructure materials characterized by a dielectric constant that varies periodically with space and features a photonic bandgap. Inspired by natural photonic crystals such as butterfly scales, a series of artificial photonic crystals are developed for use in integrated photonic platforms, biosensing, communication, and other fields. Among them, colloidal photonic crystals (CPCs) have gained widespread attention due to their excellent optical properties and advantages, such as ease of preparation and functionalization. This work reviews the classification and self‐assembly principles of CPCs, details some of the latest biomedical applications of large‐area, high‐quality CPCs prepared using advanced self‐assembly methods, summarizes the existing challenges in CPC construction and application, and anticipates future development directions and optimization strategy. With further advancements, CPCs are expected to play a more critical role in biosensors, drug delivery, cell research, and other fields, bringing significant benefits to biomedical research and clinical practice.

Abstract Exosomes are small membrane vesicles that are released by cells into the extracellular environment. Tumor‐associated exosomes (TAEs) are extracellular vesicles that play a significant role in cancer progression by mediating intercellular communication and contributing to various hallmarks of cancer. These vesicles carry a cargo of proteins, lipids, nucleic acids, and other biomolecules that can be transferred to recipient cells, modifying their behavior and promoting tumor growth, angiogenesis, immune modulation, and drug resistance. Several potential therapeutic targets within the TAEs cargo have been identified, including oncogenic proteins, miRNAs, tumor‐associated antigens, immune checkpoint proteins, drug resistance proteins, and tissue factor. In this review, we will systematically summarize the biogenesis, composition, and function of TAEs in cancer progression and highlight potential therapeutic targets. Considering the complexity of exosome‐mediated signaling and the pleiotropic effects of exosome cargoes has challenge in developing effective therapeutic strategies. Further research is needed to fully understand the role of TAEs in cancer and to develop effective therapies that target them. In particular, the development of strategies to block TAEs release, target TAEs cargo, inhibit TAEs uptake, and modulate TAEs content could provide novel approaches to cancer treatment.

Abstract Hot Flow anomalies (HFAs), one of the most well‐analyzed transient phenomena in the Earth's foreshock, are known as kinetic structures driven by tangential discontinuities (TDs). Recently, a 2‐dimensional (2D) magnetohydrodynamics (MHD) model reproduced HFAs with either a high‐ or low‐density core. Further investigation of an HFA with two cores observed by the Magnetospheric Multiscale (MMS) mission is reported. The observation via the Acceleration, Reconnection, Turbulence and Electrodynamics of the Moon's Interaction with the Sun (ARTEMIS) mission suggests this MHD HFA is associated with a foreshock density hole‐like structure. The trailing flux tube in simulation may propagate with a TD in the foreshock. Our work suggests that HFAs with two low‐density cores can also be achieved in MHD process. Results show the total ram pressure can be an excellent diagnostic for the presence of transient structures, such as HFAs, at the bow shock.

Abstract Advanced artificial nerve conduits offer a promising alternative for nerve injury repair. Current research focuses on improving the therapeutic effectiveness of nerve conduits by optimizing scaffold materials and functional components. In this study, a novel poly(3,4‐ethylenedioxythiophene) (PEDOT)‐integrated fish swim bladder (FSB) is presented as a conductive nerve conduit with ordered topology and electrical stimulation to promote nerve regeneration. PEDOT nanomaterials and adhesive peptides (IKVAV) are successfully incorporated onto the decellularized FSB substrate through pre‐coating with polydopamine. The obtained PEDOT/IKVAV‐integrated FSB substrate exhibits outstanding mechanical properties, high electrical conductivity, stability, as well as excellent biocompatibility and bioadhesive properties. In vitro studies confirm that the PEDOT/IKVAV‐integrated FSB can effectively facilitate the growth and directional extension of pheochromocytoma 12 cells and dorsal root ganglion neurites. In addition, in vivo experiments demonstrate that the proposed PEDOT/IKVAV‐integrated FSB conduit can accelerate defective nerve repair and functional restoration. The findings indicate that the FSB‐derived conductive nerve conduits with multiple regenerative inducing signals integration provide a conducive milieu for nerve regeneration, exhibiting great potential for repairing long‐segment neural defects.

Abstract To ensure the real‐time operation safety of electric vehicles (EVs), it is essential to diagnose the fault in a battery pack timely and accurately. In this paper, with considering driving condition, a battery voltage fault diagnosis method is proposed based on the real‐world operation data of EVs with a high sampling frequency. Firstly, based on driving behaviour, the driving condition of EVs is classified into four categories, and accordingly, the operation process is divided into four segments. The influencing mechanism of driving condition on battery voltage is revealed by detailed analysis on extracted operation segments. Secondly, four BP neural network (BPNN)‐based voltage prediction models are developed, respectively, for the four kinds of driving conditions. Based on the statistical analysis of prediction error and the comparison with other voltage prediction models, the superiority and stability of the four well‐trained BPNN models are verified. Thirdly, the voltage abnormity levels and thresholds for fault diagnosis are set considering driving condition differences. The effectiveness of the proposed method is verified using the actual operational data. The verification results show that the proposed method can achieve good voltage prediction and fault diagnosis for EVs under various driving conditions during the entire operation process.

Abstract Osteoporosis is a common skeletal disease, especially for the bone health of menopausal women. It is reported that the changes of intestinal environment could affect the occurrence and development of osteoporosis. This study aims to explore the effects of different gut microbiota by antibiotics and bone health in ovariectomized (OVX) C57BL/6 mice and to research the anti‐osteoporosis effect of Lactobacillus plantarum AR495. The results showed that the gut microbiota could alleviate the bone mass loss after treatment of metronidazole, but the bone loss was aggravated after neomycin disturbing the microbiota. Gut microbiota significantly affected bone resorption in OVX mice by regulating intestinal barrier permeability. Through intestinal microbiological analysis, it was found that the abundance of Bifidobacterium and Eubacterium xylanophilum was positively correlated with bone health. In addition, L. plantarum AR495 could restore gut microbiota to normal level in OVX mice, increase the abundance of E. xylanophilum, reduce the expression of osteoclast promoting factors IL‐1, IL‐6, IL‐17, and TNF‐α in tibia, subsequently inhibit receptor activator of NF‐κB ligand/receptor activator of NF‐κB/osteoprotegerin (RANKL/RANK/OPG) pathway. Overall, this finding showed that L. plantarum AR495 reduces bone resorption and effectively improving osteoporosis through gut microbiota.

Abstract Drilling a series of sinuous wellbore trajectories has emerged as a promising operation, offering significant advantages in enhancing reservoir contact. Based on various development cases (Zili and colleagues), it has been observed that horizontal wells with wavy wellbore trajectories tend to exhibit higher production rates. However, extending the length of these wavy trajectories requires careful consideration in terms of safe drilling practices, as the pressure management associated with these intricate trajectories has been seldom explored. In this study, we establish a modified model for annular pressure to predict and assess the open‐hole extend‐reach limit of horizontal wells with wavy wellbore trajectories. The introduced model incorporates dry friction force and annular geometry influenced by cuttings bed, making it more accurate than traditional models based on experimental observations. The wavy wellbore trajectory comprises three types: the up‐dip wellbore, the down‐dip wellbore, and the complex wellbore. Overall, the horizontal interval limits for the down‐dip wellbore and up‐dip wellbore are smaller than those of the corresponding smooth wellbores under varying factors. Notably, the complex wellbore trajectory offers advantages in navigating formations with narrow pressure windows compared to conventionally horizontal wellbores (smooth wellbores), thanks to its longer extended‐reach limit.

Abstract Reliable estimates of saturated hydraulic conductivity (Ks) are usually difficult to obtain, as Ks is regulated by a variety of soil processes acting at different spatial scales that may obscure each other's impacts. We hypothesized that these scale‐specific relationships could be well characterized with the aid of the noise‐assisted multivariate empirical mode decomposition (NA‐MEMD), thereby serving as a solid foundation for an accurate Ks prediction. The objective was to evaluate whether the incorporation of NA‐MEMD could improve the estimation of Ks based on the multiscale associations it unraveled. On a typical slope transect of 860 m in the black soil region of northeast China, Ks, mollic epipedon thickness, bulk density, soil organic carbon content, total (ϕ) and effective porosities (ϕe), and particle size distribution were investigated at every 20 m. Prior to NA‐MEMD, Ks was most strongly correlated with ϕe, and the linear regression models based on ϕe solely were satisfactory for Ks estimation at the scale of investigation. Adding other predictors significantly improved Ks prediction in calibration, but impaired it in validation. Upon decomposition by NA‐MEMD, Ks was found to be significantly associated with each attribute at two scales of oscillation at least. Summing up the estimates of each Ks component derived from the properties at the equivalent oscillation scales, the results outperformed the traditional multiple linear regressions made at the investigation scale, when the same sets of predictors were used. The application of NA‐MEMD, moreover, could save the tedious measurements of ϕe and ϕ. Excluding these two porosity‐related properties, Ks estimates obtained by incorporating NA‐MEMD were statistically similar or even better than those involving them before NA‐MEMD. These findings demonstrate the great potential of NA‐MEMD in untangling scale‐dependent relationships of Ks with various processes and hold important implications for future estimations of Ks and other hydraulic properties in the black soil region of northeast China and similar regions.

Abstract Is childhood adversity associated with biological aging, and if so, does sex modify the association, and do lifestyle and mental health mediate the association? A lifespan analysis is conducted using data on 142 872 participants from the UK Biobank to address these questions. Childhood adversity is assessed through the online mental health questionnaire (2016), including physical neglect, physical abuse, emotional neglect, emotional abuse, sexual abuse, and a cumulative score. Biological aging is indicated by telomere length (TL) measured from leukocyte DNA using qPCR, and the shorter TL indicates accelerated biological aging; a lifestyle score is constructed using body mass index, physical activity, drinking, smoking, and diet; mental disorder is assessed using depression, anxiety, and insomnia at the baseline survey. The results reveal a sex‐specific association such that childhood adversity is associated with shorter TL in women after adjusting for covariates including polygenic risk score for TL, but not in men. Unhealthy lifestyle and mental disorder partially mediate the association in women. The proportions of indirect effects are largest for sexual and physical abuse. These findings highlight the importance of behavioral and psychological interventions in promoting healthy aging among women who experienced childhood adversity, particularly sexual and physical abuse.

Abstract Background Undetermined lung nodules are common in locally advanced rectal cancer (LARC) and lack precise risk stratification. This study aimed to develop a radiomic‐based score (Rad‐score) to distinguish metastasis and predict overall survival (OS) in patients with LARC and lung nodules. Methods Retrospective data from two institutions (July 10, 2006—September 24, 2015) was used to develop and validate the Rad‐score for distinguishing lung nodule malignancy. The prognostic value of the Rad‐score was investigated in LARC cohorts, leading to the construction and validation of a clinical and radiomic score (Cli‐Rad‐score) that incorporates both clinical and radiomic information for the purpose of improving personalized clinical prognosis prediction. Descriptive statistics, survival analysis, and model comparison were performed to assess the results. Results The Rad‐score demonstrated great performance in distinguishing malignancy, with C‐index values of 0.793 [95% CI: 0.729–0.856] in the training set and 0.730 [95% CI: 0.666–0.874] in the validation set. In independent LARC cohorts, Rad‐score validation achieved C‐index values of 0.794 [95% CI: 0.737–0.851] and 0.747 [95% CI: 0.615–0.879]. Regarding prognostic prediction, Rad‐score effectively stratified patients. Cli‐Rad‐score outperformed the clinicopathological information alone in risk stratification, as evidenced by significantly higher C‐index values (0.735 vs. 0.695 in the internal set and 0.618 vs. 0.595 in the external set). Conclusions CT‐based radiomics could serve as a reliable and powerful tool for lung nodule malignancy distinction and prognostic prediction in LARC patients. Rad‐score predicts prognosis independently. Incorporation of Cli‐Rad‐score significantly enhances the persionalized clinical prognostic capacity in LARC patients with lung nodules.

Abstract Chloroplasts play a vital role in plant growth and development, which are the main sites of photosynthesis and the production of hormones and metabolites. Despite their significance, the regulatory mechanisms governing chloroplast development remain unclear. In our investigation, we identified a rice mutant with defective chloroplasts in rice (Oryza sativa L.), named albino lethal 13 (osal13), which displayed a distinct albino phenotype in leaves, ultimately resulting in seedling lethality. Molecular cloning revealed that OsAL13 encodes a novel rice protein with no homologous gene or known conserved domain. This gene was located in the chloroplast and exhibited constitutive expression in various tissues, particularly in green tissues and regions of active cell growth. Our study's findings reveal that RNAi‐mediated knockdown of OsAL13 led to a pronounced albino phenotype, reduced chlorophyll and carotenoid contents, a vesicle chloroplast structure, and a decrease in the expression of chloroplast‐associated genes. Consequently, the pollen fertility and seed setting rate were lower compared with the wild type. In contrast, the overexpression of OsAL13 resulted in an increased photosynthetic rate, a higher total grain number per panicle, and enhanced levels of indole‐3‐acetic acid (IAA) in the roots and gibberellin A3 (GA3) in the shoot. These outcomes provide new insights on the role of OsAL13 in regulating chloroplast development in rice.

Abstract Although radiotherapy plays an important role in the treatment of cancer, it may have negative effects in some individuals. Rectal injury is a common adverse effect of abdominal and pelvic radiotherapy. This injury is caused by administering radiation to the abdomen. Appropriate treatment techniques can be determined if doctors have a better understanding of the incidence, risk factors, and clinical symptoms of radiation‐induced rectal injuries. Studies on the underlying pathophysiology of radiation‐induced rectal injury may aid in the development of effective treatment and prevention strategies. The implementation of efficient preventive measures can improve the quality of life of patients with cancer and make it easier for them to complete their treatment. Therefore, comprehensive and accurate assessments are crucial for developing holistic and individualized treatment plans for patients who have already developed symptoms, with early intervention being a priority.

Abstract The recently established Hainan Tropical Rainforest National Park has designated the Hainan gibbon (Nomascus hainanus) as its flagship species, providing new hope for recovery of the last surviving population of the world's rarest primate. However, current monitoring methods are labour‐intensive and only conducted for discrete periods, meaning that detailed information is still lacking on key Hainan gibbon population parameters (such as movement patterns, sleeping site selection and home range size). Alternative monitoring techniques are therefore necessary to supplement traditional methods and provide more accurate estimates of population parameters. Here, we tested whether flying two drones (DJI MAVIC2 Enterprise Advanced), one in the understory and the other above the canopy, could provide new information on Hainan gibbon biology and ecology. During a total of 60 flights, we successfully collected clear RGB and thermal infrared footage of Hainan gibbons. These data provide new baseline information on gibbon movement within the understory and the canopy, their surface body temperatures (23.0–34.7°C), and their movement area during the survey period. The low cost of this equipment could reduce the running costs for Hainan gibbon monitoring. Although drone‐based monitoring has some limitations (e.g. monitoring efficiency could be affected by variation in forest structure and gibbon group size), this new method could complement existing monitoring approaches. Drone‐based monitoring, using multiple drones and a real‐time transmission network, could therefore contribute further towards Hainan Tropical Rainforest National Park's conservation planning for this Critically Endangered primate.

Abstract Introduction Asthma is a common chronic condition in children. Several studies have explored the potential association between IL10 rs1800896 polymorphism and the risk of asthma in children, but the findings have been inconsistent. To address these discrepancies, we conducted a systematic review and meta‐analysis to assess the relationship between IL10 rs1800896 polymorphisms and the susceptibility to pediatric asthma. Methods A literature search was conducted in PubMed, Scopus, Web of Science, and CNKI databases to identify eligible studies through April 2022. Meta‐analysis was then performed using five genetic models: dominant, recessive, homozygous, heterozygous, and allele. Results A total of 12 studies comprising 1645 cases along with 1447 controls were included in this meta‐analysis. It was found that rs1800896 was not associated significantly with susceptibility to childhood asthma in all genetic models investigated. Subgroup analysis based on the ethnic background of the subjects revealed that rs1800896 was significantly linked to a lower risk of pediatric asthma among Asians in the homozygous model (OR = 0.311, 95% CI = 0.152–0.637, P = 0.001) and in the recessive model (OR = 0.585, 95% CI = 0.405–0.846, P = 0.004), whereas no significant relationship was observed in Egyptians (P > 0.05). Conclusion In conclusion, IL10 rs1800896 polymorphism may be useful as a predictive marker for childhood asthma in Asians, although further studies are needed to validate the study results.

Abstract The massive perception data based on efficient analysis and intelligent decision have put forward higher requirements for high‐precision time synchronisation with the construction and development of smart power grid. However, multi‐reference source time‐frequency synchronisation of power system only selects the best method after comparison, which cannot make the most efficient use of the existing resources. It also cannot meet the need for high‐precision time synchronisation of future power system. The existing multi‐reference source synthesis algorithms cannot take into account both long‐term stability and high‐precision synchronous output. This article presents a multi‐reference source weighted improved noise model and the high‐precision output method. The multi‐reference source error after classification is eliminated by leading into classification vector and classification coefficient. The synthesised frequency offset or the time precision of output can be optimised as the objective function by weighted classification algorithm and genetic algorithm. A simulation example based on the synthesis of two satellite system clock sources and three local caesium reference sources shows that the peak value of long‐term output accuracy is controlled within 10 ns after classification weighted synthesis and optimisation, which is better than that of any single reference source.

Abstract Background Interleukin (IL)‐10 plays a notable role in the inflammatory‐associated mild cognitive impairment (MCI). We aimed to investigate whether IL‐10 and its upstream factors exert an impact on MCI in type 2 diabetes mellitus (T2DM) patients. Methods A total of 117 T2DM patients were recruited and divided into Control group and MCI group based on the presence or absence of MCI. Clinical parameters were collected. The Montreal Cognitive Assessment (MoCA) was conducted for global cognitive function. Digit Span Test (DST), Verbal Fluency Test (VFT), and Trail Making Test‐B (TMTB) were used to evaluate the executive functions of the diabetic patients. Trail Making Test‐A (TMTA) was performed to examine the information processing speed function. Patients' scene memory was examined by Logical Memory Test (LMT). After the baseline data were compared, correlation and regression analyses were performed to explore the relationship among IL‐10, miR‐let‐7c‐5p and cognitive function. Results Compared to 80 patients in the control group, 37 patients in the MCI group exhibited lower IL‐10 in plasma and higher miR‐let‐7c‐5p levels in exosomes from plasma. The IL‐10 level was negatively associated with MoCA. Likewise, miR‐let‐7c‐5p levels were negatively correlated with IL‐10 levels and MoCA. Elevated miR‐let‐7c‐5p levels and decreased IL‐10 levels are risk factors for MCI in T2DM patients. Increased miR‐let‐7c‐5p and downregulated IL‐10 may influence VFT and TMTB, respectively, associated with executive function. Conclusions We demonstrated that IL‐10 is correlated to the executive function of T2DM patients. Decreased IL‐10 may result from the regulation of miR‐let‐7c‐5p in exosomes.

Abstract Using the high‐time‐resolution data from the Magnetospheric Multiscale mission, precursor waves upstream of foreshock transient (FT) shocks are statistically investigated using the four‐spacecraft timing method. The wave frequencies and wave vectors determined in the plasma rest frame (PRF) are shown to follow the cold plasma dispersion relation for whistler waves. Combining with the feature of the right‐hand polarization in the PRF, the precursors are identified as whistler‐mode waves around the lower hybrid frequency. The occurrence of whistler precursors is independent of the Alfvén Mach number and the FT shock normal angle. More importantly, all the whistler precursors have group velocities pointing upstream in the shock frame, suggesting the dispersive radiation to be a possible generation mechanism. The study improves the understanding of not only the whistler precursors but also the overall FT shock dynamics.

Abstract Colloidal crystals are materials self‐assembled from the colloidal nanoparticles. Due to the ordered microstructure, they exhibit significant optical properties and have shown huge potential in the field of biosensing. Besides, the unique macroscopic shapes can also play a critical role in the sensing process. Here, we present a comprehensive discussion on the colloidal crystal‐based biosensors with different topological shapes, including the development strategies of currently reported colloidal crystal particles, films, and fibers, and their recent progress in biosensing. In addition, the faced challenges and the possible solutions are also concluded and discussed. We expect this review can enrich the knowledge and encourage the communication of interdisciplinary researchers, thus promoting the further development and practical applications of colloidal crystal‐based biosensors.

Abstract Drug therapies are the cornerstone of systemic treatment for pancreatic cancer patients. However, the relative outcome of drug evaluation is often hampered by the complex microenvironment of pancreatic cancer due to the lack of reasonable tumor models. Here, we proposed a novel platform that integrated pancreatic adenocarcinoma cells encapsulated into hydrogel microcapsules for three‐dimensional (3D) tumor cultivation and antitumor agent evaluation. These hydrogel microcapsules contain alginate/poly (N‐isopropyl acrylamide) (alginate/PNIPAM) shells and carboxymethyl cellulose cores, which are generated through the microfluidic electrospray technique. The microcapsules have the feature of rapid response to temperature, by which they can regulate the internal pressure environment. Besides, benefiting from good monodispersity, precise size control, and biocompatibility of these microcapsules, these wrapped tumor cells have the capacity for proliferating spontaneously and forming 3D tumor spheroids with good cell viability. We have demonstrated that pancreatic adenocarcinoma cells encapsulated in the composite microcapsules with different PNIPAM concentrations showed different drug sensitivity, which could be ascribed to the influence of external pressures environment. These results indicate that the tumor spheroids coated in these responsive microcapsules have great potential in the analysis of antitumor drug sensitivity.

Abstract Malfunction of neutrophil apoptosis and elevated serum lactate levels are the key cellular mechanism of immune suppressive status in septic patients. However, whether increased lactate affects apoptosis of neutrophils and aggravates sepsis development, and the molecular mechanism remain unknown. In this study, first, we analyzed the transcriptional profiles of blood cells in sepsis patients (n = 39) and healthy volunteers (n = 40) to reveal that there is close correlation between the lactate‐related gene expression changes associated with lactate production and immune function in leukocytes, especially in neutrophils. Further, we explored the close relationship between lactate and delayed neutrophil apoptosis in human neutrophils. Programmed cell death 1 legand (PD‐L1) was highly expressed in septic patients compared with healthy volunteers. Then, we indicated that elevated levels of lactate in human neutrophils decreased neutrophil apoptosis (P < .001) by upregulating PD‐L1 expression. Inhibition of monocarboxylate transporter 1 (MCT1) significantly attenuated neutrophil apoptosis caused by lactate (P < .001). We further performed in vivo experiments in sepsis mice model and determined that increased lactate decreased neutrophil apoptosis (P < .05) and reduces mice survival rate (P < .001), which could also be rescued by MCT1 inhibitor (P < .05). This study revealed that elevated level of lactate in sepsis upregulates PD‐L1 expression to decrease apoptosis through MCT1 in neutrophils, which provides new insight into sepsis treatment strategy by reducing lactate accumulation.

Abstract Aims Atrial fibrillation (AF) and heart failure (HF) often co‐exist and are closely intertwined. The impact of AF on the outcome of patients with heart failure with mildly‐reduced ejection fraction (HFmrEF) is not fully clear. This study aimed to investigate the impact of AF on the outcomes of hospitalized HFmrEF patients. Methods and results The study included 1691 consecutive patients with HFmrEF (mean 68.2 years, 64.8% male) including 296 AF patients. Patients completed 1 year and mean of 33 month clinical follow‐up after discharge by telephone interview, clinical visit, or community visit. The primary endpoint was cerebro‐cardiovascular events (CCE, composite of HF rehospitalization, stroke, or cardiovascular death). After propensity score matching, 296 patients were included into the AF group (mean 71.5 years) and 592 patients into the non‐AF group (mean 70.6 years). After propensity score matching, CCE at 1 year (59.1% vs. 48.5%, P = 0.003) and at a mean of 33 month (77.0% vs. 70.6%, P = 0.043). AF was independently associated with increased CCE within 1 year (HR = 1.31, 95% CI 1.07 to 1.61, P = 0.010) and at 33 months (HR = 1.20, 95% CI 1.00 to 1.43, P = 0.050) post‐discharge after adjusted for other clinical confounders including discharge heart rate, NT‐proBNP, haemoglobin, and uric acid. Conclusions AF is independently associated with an increased risk of CCE in HFmrEF patients within 1 year and at a mean of 33 months after discharge.

Abstract To investigate the coupling effect of in situ stress and fluid pore pressure and the propagation law of damaged area during hydraulic fracturing and gas fracturing in heterogeneous fractured reservoirs, according to the effective stress principle and the smooth Rankine stress criterion, this paper establishes a coupled fluid–solid‐damage mathematical model of heterogeneous rock layers and carries out numerical simulations on the characteristic field changes of rock layers under water and nitrogen fracturing. The results show that the continuous injection of nitrogen or water can cause an increase in pore pressure in natural fractures and rock matrices, leading to rock damage and an increase in porosity. Under the same parameters, the damage area and length of the rock mass during nitrogen fracturing are larger than those of hydraulic fracturing, and the changes in pore pressure, permeability, and porosity are consistent with the damage area. The pore pressure near the connected natural fractures is relatively high, resulting in tensile strain; the pore pressure at isolated fractures is relatively low, and some even produce compressive strain. During nitrogen fracturing, the damage evolution is less affected by the in situ stress and the matrix permeability, while hydraulic fracturing is more affected by them. The damage area is the smallest when the horizontal in situ stress is equal. When the initial permeability of the matrix is low, the damaged area mainly follows the natural fractures and is distributed in a strip shape. As the permeability of the matrix increases, the fracturing fluid can enter the matrix, and the damaged area is in the shape of a block.

Abstract To improve the development efficiency of ultradeep fault‐controlled carbonate reservoirs, the deformation and connectivity mechanism of fractures was revealed through large‐scale rock mechanical experiments. The in situ stress field and fracture activity distribution law of fault‐control carbonate reservoirs were clarified through geomechanical modeling. It is revealed that the fracture activity in different directions and the connectivity of the fracture and cavity in different parts are significantly different, the development effect of different well trajectories is analyzed, and the integrated working method of geological engineering is proposed to scientifically guide the well trajectory design and water injection scheme optimization. The results show that: (1) Large‐scale fractures and high‐angle fracture systems in the deformation of strike–slip faults are the key factors affecting reservoir quality. High‐pressure water injection can activate preexisting fractures, and it can extend on the basis of preexisting fractures, and even generate new fractures, which promote the interconnection of fault‐controlled fracture‐cave bodies in the vertical and horizontal directions. (2) During the process of high‐pressure water injection, the coupling change between mechanics and flow occurs inside the fracture body, the seepage environment is improved, and the oil and gas recovery factor is improved through cyclic lifting. (3) According to the shape and occurrence of the fault body and the dynamic shear deformation connectivity of the fault surface, the best well point and well trajectory of the directional well can be optimized, and the water injection scheme can be optimized. (4) The single‐well production increased by 1.45 × 104 t through high‐pressure water injection, the cumulative oil increase of the same fracture‐cavity body increased by 4.63 × 104 t. This method is highly efficient for ultradeep fault‐controlled oil reservoirs. The development provides a good theoretical basis and technical support, and plays a leading and exemplary role.

Abstract Gymnema sylvestre (GS) has been traditionally used to treat diabetes mellitus (DM) and consumed as both food and medicine. The present work aimed to reveal the arresting hypoglycemic properties of GS leaves on type 2 DM (T2DM) rats meditated by gut microbiota pathway. After administration for 30 days, GS treatment observably improved the abnormal fasting blood glucose (FBG) levels, lipid profiles, and the glucose tolerance of the T2DM rats in a dose‐dependent manner. Furthermore, GS treatment reversibly restored the gut microbiota diversities in the T2DM rats based on the decreased Firmicute abundance and boosted Bacteroidetes abundance and Firmicutes/Bacteroidetes ratio. Particularly, the KEGG pathway suggested that GS treatment strongly interfered with the glucose metabolism processes, such as the glycolysis from glucose 6‐phosphate and glucose, along with the changes in the relative abundances of the beneficial bacteria of Clostridium, Lactobacillus, and Bacteroides. In addition, the GS treatment dramatically promoted the contents of the acetic acid, the total short‐chain fatty acids in the T2DM rat feces. This study showcased the remarkable amelioration of GS on the metabolic disorders of blood glucose and lipids via the regulation of gut microbiota in T2DM rats, which could offer a new mechanism of GS as a potential natural antidiabetic food supplement for T2DM.

Abstract Cancer stem cells (CSCs), a rare subset of tumor cells, have been recognized as promotive role on tumor initiation and propagation. Among, aerobic glycolysis, widely clarified in multiple tumor cells, is the key for maintaining cancer stemness. Regrettably, it is largely unknown about the connection of cellular metabolic reprogramming and stemness in gastric carcinoma (GC). Two GC parental cells lines PAMC‐82 and SNU‐16 and their spheroids were obtained to determine the expression status of POU1F1 using quantitative real‐time PCR (qRT‐PCR) and western blotting analysis, respectively. Gain or loss‐of‐function assay was employed to assess its biological effects. Sphere formation and transwell assays were performed to evaluate the stem cell‐like traits, including self‐renewal capacity, migration and invasion. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were conducted for determining the binding relationship of POU1F1 on ENO1 promoter region. Herein, aberrantly upregulated POU1F1 was observed in spheroids, compared with the parental PAMC‐82 and SNU‐16 cells, which promoted stem cell‐like traits, as representing increasing sphere formation, enhanced cell migration and invasion. Additionally, POU1F1 expression was positively with glycolytic signaling, as displaying increasing glucose consumption, lactic acid production, and extracellular acid ratio (ECAR). Furthermore, POU1F1 was identified to be a transcriptional activator of ENO1, of which overexpression remarkably abolished POU1F1 knockdown‐mediated blocking effects. Taken together, we draw a conclusion that POU1F1 facilitated the stem cell‐like properties of GC cells through transcriptionally augmenting ENO1 to enhance glycolysis.

Abstract Background This study aimed to develop a combined model to quantify the net absorption of volatile fatty acids (VFA) in the large intestine (LI) of pigs. Methods Fifteen female growing pigs (Duroc × Large White × Landrace) were ranked by body weight (30 ± 2.1 kg) on day 0 and assigned to one of three treatments, namely the basal diet containing different crude fiber (CF) levels (LCF: 3.0% CF, MCF: 4.5% CF, and HCF: 6.0% CF). The pigs were implanted with the terminal ileum fistula and the cannulation of the ileal mesenteric vein (IMV), portal vein (PV), and left femoral artery (LFA) from days 6 to 7. [13C]‐Labeled VFA and P‐aminohippuric acid were constantly perfused into the terminal ileum fistula and the cannulation of the IMV (day 15), respectively. Blood samples were collected from the PV and the LFA during perfusion (5 h), and LI samples were collected. Results The net flux of [12C]‐acetic acid in the PV was greater for LCF versus MCF (p = 0.045), but no difference was observed in the net flux of [12C]‐propionic acid (p = 0.505) and [12C]‐butyric acid (p = 0.35) in the PV among treatments. The deposition of [12C]‐acetic acid in the LI was greater for LCF versus MCF (p = 0.014), whereas the deposition of [12C]‐propionic acid (p = 0.007) and [12C]‐butyric acid (p = 0.037) in the LI was greater for LCF versus HCF. Conclusions In conclusion, this pig model was found conducive to study the net absorption of VFAs in the LI, and LCF had more net absorption of VFAs in the LI than MCF and HCF.

Abstract Background Existing treatments for cholangiocarcinoma have poor efficacy. However, chimeric antigen receptor‐T (CAR‐T) cells are emerging as a potential therapeutic strategy. Solid tumors possess multiple adverse factors in an immunosuppressive microenvironment that impair CAR‐T cell infiltration and function. This study aimed to improve the function of CAR‐T cells through knock down immune checkpoints and immunosuppressive molecular receptors. Methods We evaluated the expression of epidermal growth factor receptor (EGFR) and B7 homolog 3 protein (B7H3) antigens in cholangiocarcinoma tissues using immunohistochemistry and screened specific immune checkpoints in the cholangiocarcinoma microenvironment via flow cytometry. Subsequently, we engineered CAR‐T cells targeting EGFR and B7H3 antigens. We simultaneously knocked down immune checkpoints and immunosuppressive molecular receptors in CAR‐T cells by constructing two clusters of small hairpin RNAs and evaluated the engineered CAR‐T cells for antitumor activity both in vitro, using tumor cell lines and cholangiocarcinoma organoid models, and in vivo, using humanized mouse models. Results We observed high expression of EGFR and B7H3 antigens in cholangiocarcinoma tissues. EGFR‐CAR‐T and B7H3‐CAR‐T cells demonstrated specific anti‐tumor activity. We found an abundance of programmed cell death protein 1 (PD‐1), T cell immunoglobulin and mucin domain‐containing protein 3 (Tim‐3), and T cell immunoglobulin and ITIM domain (Tigit) on infiltrated CD8+ T cells in the cholangiocarcinoma microenvironment. We then decreased the expression of these 3 proteins on the surface of CAR‐T cells, named PTG‐scFV‐CAR‐T cells. Furthermore, we knocked‐down the expression of transforming growth factor beta receptor (TGFβR), interleukin‐10 receptor (IL‐10R), and interleukin‐6 receptor (IL‐6R) of PTG‐scFV‐CAR‐T cells. Those cells, named PTG‐T16R‐scFV‐CAR‐T cells, potently killed tumor cells in vitro and promoted apoptosis of tumor cells in a cholangiocarcinoma organoid model. Finally, the PTG‐T16R‐scFv‐CAR‐T cells showed greater inhibitory effect on tumor growth in vivo, and were superior in prolonging the survival of mice. Conclusions Our results revealed that PTG‐T16R‐scFV‐CAR‐T cells with knockdown of sextuplet inhibitory molecules exhibited strong immunity against cholangiocarcinoma and long‐term efficacy both in vitro and in vivo. This strategy provides an effective and personalized immune cell therapy against cholangiocarcinoma.

Abstract The development of urban underground space is a critical way to alleviate the lack of urban resources, and improve environmental conditions as well as residents' quality of life, which has important practical significance. As the most densely populated and economically developed areas, coastal cities face many challenges in underground space development owing to their unique environmental geological conditions. This study examined the current situation of underground space development, academic research, technology application, evaluation methods, planning, and legislation in coastal cities in China. On this basis, it analyzed the future development trends, and presented reasonable suggestions for the critical scientific and technical problems faced by the development of underground space in coastal cities. The key suggestions are as follows: it is necessary to define and clarify the critical geological issues, distributions, and hazards that affect underground space development and major engineering construction in coastal cities; the land‐sea integrated detection technology for sea crossing bridges and submarine tunnels needs to be studied; in evaluating the suitability of underground space in coastal cities, the land and sea area evaluation factors should be integrated; and the evaluation system of land‐sea integration needs to be established.

Abstract Aims The study aims to explore the real‐world titration patterns of sacubitril/valsartan in a chronic heart failure (HF) follow‐up management system and the effect on the recovery of ventricular remodelling and cardiac function in China. Methods and results This is a single‐centre, observational study of 153 adult outpatients with HF and reduced ejection fraction who were managed in the chronic HF follow‐up management system and prescribed with sacubitril/valsartan from August 2017 to August 2021 in China. All patients tried to titrated sacubitril/valsartan to the tolerant dose during follow‐up. The primary outcome was the proportion of patients who reached and maintained the target dose of sacubitril/valsartan. The main secondary outcomes were the changes in left atrium diameter, left ventricular end‐diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF) from baseline to 12 months. Among the patients, 69.3% were male, with a median age of 49 years. The baseline systolic blood pressure (SBP) was 117.6 ± 18.3 mmHg before starting the treatment of sacubitril/valsartan. Benefiting from the management system, 117 (76.5%) patients achieved the target dose of sacubitril/valsartan, and the median time to reach the target dose was 3 (IQR 1–5) months. Advanced age and lower SBP may be predictors of failure to reach the target dose. Compared with baseline, standard treatment resulted in a pronounced improvement in left ventricular geometry and cardiac function. The patients showed a significant increase in LVEF [28 (IQR 21–34) % vs. 42 (IQR 37.0–54.3) %, P 40%, and 81.1% experienced an increase in LVEF of ≥10%. After 12 month follow‐up, the proportion of patients with New York Heart Association classification I or II increased from 41.8% to 96.4%. Additionally, there was a significant improvement in N‐terminal pro‐B‐type natriuretic peptide (P

Abstract Noise‐induced hearing loss (NIHL) is a common outcome of excessive reactive oxygen species in the cochlea, and the targeted delivery of antioxidants to the inner ear is a potential therapeutic strategy. In this paper, a novel natural biomaterials‐derived multifunctional delivery system using silk fibroin‐polydopamine (PDA)‐composited inverse opal microcarriers (PDA@SFMCs) is presented for inner ear drug delivery and NIHL therapy. Due to their large specific surface area and interpenetrating nanochannels, PDA@SFMCs can rapidly load active biomolecules making them a convenient medium for the storage and delivery of such molecules. In addition, surface modification of PDA enables the microcarriers to remain in the round window niche, thus facilitating the precise local and directed delivery of loaded drugs. Based on these features, it is demonstrated here that n‐acetylcysteine‐loaded silk microcarriers have satisfactory antioxidant properties on cells and can successfully prevent NIHL in guinea pigs. These results indicate that the natural multifunctional silk microcarriers are promising agents for local inner ear drug delivery in the clinic.

Abstract Introduction Regulator of G protein signalling 1 (RGS1) closely regulates malignant phenotypes and tumour immunity in several cancers, while its clinical value in nonsmall cell lung cancer (NSCLC) is by far rarely reported. Consequently, this study aimed to explore the linkage of blood RGS1 with clinical features and prognosis in surgical NSCLC patients. Methods Two‐hundred and ten surgical NSCLC patients were consecutively enrolled in this study, whose RGS1 in peripheral blood mononuclear cells was determined before treatment via reverse transcriptional‐quantitative polymerase chain reaction. Additionally, the blood RGS1 was also collected from 30 healthy controls (HCs). Results Blood RGS1 was increased in NSCLC patients compared with HCs (P 0.050). Furthermore, blood RGS1 high expression was associated with shortened OS (P = 0.020) in patients with neoadjuvant therapy and with worse DFS (P = 0.028) and OS (P = 0.026) in patients with adjuvant therapy, while blood RGS1 was not linked with DFS or OS in patients without neoadjuvant or adjuvant therapy (all P > 0.050). Conclusion Elevated blood RGS1 correlates with LYN metastasis, neoadjuvant chemotherapy administration, worse DFS and OS, which might serve as a useful prognostic biomarker for surgical NSCLC patients.

Abstract Aim To learn the functional fitness levels in older adults with diabetes combined with sarcopenia and/or frailty. Design A cross‐sectional investigation study. Methods A total of 205 participants with type 2 diabetes were recruited from September 2019 to August 2020. All patients underwent diagnostic screening for sarcopenia and frailty, and were divided into combined group (the patients who had sarcopenia and/or frailty) and non‐combined group (the patient who had no sarcopenia and/or frailty). The diagnostic criteria for sarcopenia applied was proposed by the Asian Working Group on Sarcopenia in 2019 and frailty status was assessed using FRAIL Scale. Functional fitness was measured using the Senior Fitness Test and compared between combined and non‐combined groups. Biochemical data of blood routine, glycolipid, and hepatorenal function tests were acquired from medical records. Logistic regression analysis was applied to explore the factors associated with the sarcopenia and/or frailty in the older adults with diabetes. Results Compared with non‐combined group, the participants in combined group exhibited shorter 6‐min walk distance, fewer repetitions of arm curls and chair stands, smaller back scratch and chair sit‐and‐reach values, and longer time in the 8‐ft up‐and‐go test. The patients in the combined group had significantly lower level of red blood cell, haemoglobin, haematocrit, and higher level of platelet and blood urea nitrogen. Apart from calf circumference, physical activity, and insulin injection treatment, 6‐min walk distance was the factor associated with diabetes combined with sarcopenia and/or frailty.

Abstract The two‐phase reaction of Na3V2(PO4)3 – Na1V2(PO4)3 in Na3V2(PO4)3 (NVP) is hindered by low electronic and ionic conductivity. To address this problem, a surface‐N‐doped NVP encapsulating by N‐doped carbon nanocage (N‐NVP/N‐CN) is rationally constructed, wherein the nitrogen is doped in both the surface crystal structure of NVP and carbon layer. The surface crystal modification decreases the energy barrier of Na+ diffusion from bulk to electrolyte, enhances intrinsic electronic conductivity, and releases lattice stress. Meanwhile, the porous architecture provides more active sites for redox reactions and shortens the diffusion path of ion. Furthermore, the new interphase of Na2V2(PO4)3 is detected by in situ XRD and clarified by density functional theory (DFT) calculation with a lower energy barrier during the fast reversible electrochemical three‐phase reaction of Na3V2(PO4)3 – Na2V2(PO4)3 – Na1V2(PO4)3. Therefore, as cathode of sodium‐ion battery, the N‐NVP/N‐CN exhibited specific capacities of 119.7 and 75.3 mAh g−1 at 1 C and even 200 C. Amazingly, high capacities of 89.0, 86.2, and 84.6 mAh g−1 are achieved after overlong 10000 cycles at 20, 40, and 50 C, respectively. This approach provides a new idea for surface crystal modification to cast intermediate Na2V2(PO4)3 phase for achieving excellent cycling stability and rate capability.

Abstract Background Cells and tissues, such as macrophages, express inducible nitric oxide synthase (INOS) after stimulation by certain factors. INOS helps mediate the macrophage inflammatory reaction, but few studies have explored how INOS affects macrophage function in nonalcoholic fatty liver disease (NAFLD). Objective This study investigated the role of INOS‐mediated macrophage activity in NAFLD. Methods A high‐fat diet was used to establish an NAFLD mouse model. After 12 weeks, blood was collected for immune cell and lipid analyses, and liver tissues were collected for pathological analyses with hematoxylin and eosin and Oil Red O staining. Peritoneal macrophages were extracted in situ, cultured in Dulbecco's modified Eagle's medium, and stimulated with palmitic acid to mimic in vivo conditions for further assays. Real‐time polymerase chain reaction, western blot analysis, and immunofluorescence were used to verify the expression of target genes or proteins. Results In the NAFLD model, INOS expression in macrophages increased, and INOS knockdown significantly decreased the number of macrophages. Pathological examinations confirmed that INOS knockdown slowed NAFLD progression and macrophage infiltration during inflammation. INOS knockdown also enhanced phagocytosis and lipid transport by macrophages, and increased the expression of autophagy‐related molecules in macrophages, which improved the autophagy level, promoted apoptotic cell degradation, and maintained intracellular environment homeostasis. Conclusions These results indicate a correlation between INOS expression and macrophage function in NAFLD.

Abstract In this letter, we developed novel Structure Enhanced Channel Attention Network (SECANet) for scene text image super‐resolution (STISR). The newly proposed SECANet integrates a group of Structure‐Enhanced Attention Modules to focus more on both local and global structural features in the character regions of text images. Moreover, we elaborately formulate a Dual‐Domain Contrastive Learning framework that integrates one pixel‐level contrastive loss and the other semantic‐level contrastive loss to jointly optimize the SECANet for generating more visually pleasing yet better recognizable high‐quality SR images without introducing any additional prior generators in both the training and testing stages, showing promising computational efficiency. Experimental results on the Textzoom dataset indicate that our method can achieve both decent performance in super‐resolving more impressive scene text images from low‐resolution ones and better recognition accuracy than other competitors.

Abstract Background According to the Global Report on Drowning: Preventing a Leading Killer and Preventing Drowning: An Implementation Guide, two documents released by the World Health Organization in 2014 and 2017, respectively, 372,000 people drown each year globally (approximately 42 per hour), half of whom are below 25 years old. Chinese adolescents aged 18–24 years are the main victim group. Intermediate swimming college students are more susceptible to risk‐taking behavior and drowning while swimming. In particular, college students with high‐sensation‐seeking levels have greater confidence in their swimming ability. Consequently, they tend to overestimate their skills and pursue exciting experiences while underestimating or ignoring the risk factors in the situation. The scores of college students in sensation‐seeking show a significant positive correlation with highly risky swimming behavior. However, the correlation with the reaction time to hazards is unclear. In this study, using previous theories, the sensation‐seeking scale, and the measurement of the reaction time to hazards, we clearly explain why “college students with higher levels of sensation‐seeking have a higher risk of drowning.” We examined the reaction time to hazards and eye movement data of intermediate swimming college students with different sensation‐seeking levels, while controlling the obviousness of hazards in the videos for the experiment. Methods We utilized 16 videos of students swimming as experimental stimuli and employed a mixed experimental design of 2 (sensation‐seeking: high, low) × 2 (hazard type: obvious hazard, hidden hazard). Sensation‐seeking, the between‐subjects variable, was categorized into two levels (high and low). The hazard type, the within‐subjects variable, was also divided into two categories (obvious and hidden). We analyzed the disparities in reaction time to hazards and eye‐movement data between intermediate swimming college students with high (N = 28) or low (N = 28) levels of sensation‐seeking. Results Intermediate swimming college students with high levels of sensation‐seeking exhibited significantly longer reaction times to both obvious (F = 6.251, p = .000

Abstract Objective Compared logistic regression (LR) with machine learning (ML) models, to predict the risk of ischemic stroke in an elderly population in China. Methods We applied 2208 records from the Rugao Longitudinal Ageing Study (RLAS) for ischemic stroke risk prediction assessment. Input variables included 103 phenotypes. For 3‐year ischemic stroke risk prediction, we compared the discrimination and calibration of LR model and ML methods, where ML methods include Random Forest (RF), Gaussian kernel Support Vector Machines (SVM), Multilayer perceptron (MLP), K‐Nearest Neighbors Algorithm (KNN), and Gradient Boosting Decision Tree (GBDT) to develop an ischemic stroke risk prediction model. Results Age, pulse, waist circumference, education level, β2‐microglobulin, homocysteine, cystatin C, folate, free triiodothyronine, platelet distribution width, QT interval, and QTc interval were significant induced predictors of ischemic stroke. For ischemic stroke prediction, the ML approach was able to tap more biochemical and ECG‐related multidimensional phenotypic indicators compared to the LR model, which placed more importance on general demographic indicators. Compared to the LR model, SVM provided the best discrimination and calibration (C‐index: 0.79 vs. 0.71, 11.27% improvement in model utility), with the best performance in both validation and test data. Conclusion In a comparison of LR with five ML models, the accuracy of ischemic stroke prediction was higher by combining ML with multiple phenotypes. Combined with other studies based on elderly populations in China, ML techniques, especially SVM, have shown good long‐term predictive performance, inspiring the potential value of ML use in clinical practice.

Abstract Methane seepage, generated from natural processes or gas hydrate dissociation, drives the development of cold seep ecosystems and leads to atmosphere methane emission, thereby influencing climate change. Uncovering the intrinsic interactions among methane seepage intensities, biogeochemical processes in the sediment, and benthic community characteristics at the seafloor is essential to clarify and predict the ultimate fate of methane leakage from the deep sea. Here, we conducted a systematic investigation of methane intensity, pore fluid migration characteristics, sediment mineral fraction features, and the evolution of biological communities in areas with different methane intensities. Furthermore, analyses of high‐resolution images, pore fluid geochemical feature, and lithologic characteristics of the sediment in the Haima cold seep were also carried out in this study. The results showed that, in areas with different methane intensities, organic matter sulfate reduction and anaerobic oxidation of methane were heterogeneous. The heterogeneity led to the methane transformation zones at different depths, which changed the mineral composition of the sediment and biological communities in the seabed. In addition, a hypothesis of successional sequence of biomes in cold seep was established. This study revealed that the methane seepage intensity was a key factor in determining the biogeochemical process in the sediment of cold seep. The coupling effects of biogeochemical processes and methane seepage intensities dominated the community succession of cold seep. These findings could provide important implications for understanding the dynamic deep marine methane cycle mechanism and the contribution of deep‐sea methane released to climate change.

Abstract Aims To describe the home care experience, challenges and coping strategies of caregivers with children on automatic peritoneal dialysis (PD) in mainland China during the early stage of the COVID‐19 outbreak. Design A qualitative descriptive approach was adopted. Semi‐structured telephone interviews were conducted among 14 families with children on automatic peritoneal dialysis from February 2nd to 10th, 2020. The care routine, stress and coping strategies of caregivers of children on peritoneal dialysis were collected. The data were analysed using thematic analysis. Methods Four key themes were defined: (1) concerns about PD treatment intertwined with worries about COVID‐19; (2) retaining a sense of normality in the middle of the challenges; (3) staying safe; and (4) staying positive and carrying on. Results Families with children on automatic PD addressed the stress from COVID‐19 and its containment measures by closely adhering to COVID‐19 preventative measures, actively adjusting mentality and maintaining a sense of normality during the outbreak. This implies that healthcare staff need to be more aware of the complex medical needs of families with children on automatic PD, advocate for them and facilitate their navigation through the repurposed healthcare system.

Abstract Background Though the efficacy of anti C‐type lectin‐like molecule‐1 (CLL1) CAR T‐cells in refractory/relapsed acute myeloid leukemia (R/R‐AML) have been occasionally reported, the influence of co‐stimulatory domain CAR T‐cells is not investigated so far. Method Seven R/R‐AML children treated with anti‐CLL1 CAR T‐cells were enrolled onto this preliminary comparison study. Among these seven patients, four received CD28/CD27‐based CAR T‐cells therapy, and three received 4‐1BB‐based CAR T‐cells therapy. Result The overall response rates were 75% and 66.7% in CD28/CD27 and 4‐1BB group respectively. All patients experienced grade 1 to 2 cytokine release syndrome, with only one patient experiencing grade 2 immune effector cell‐associated neurotoxicity syndrome. The maximum CAR T‐cells durations were 156 and 274 days for CD28/CD27 group and 4‐1BB group respectively. The 1‐yr overall survival rate was 57.1%. Conclusions A preliminary similar efficacy/safety index was observed in anti‐CLL1‐based CAR T‐cells with 4‐1BB or CD28/CD27 co‐stimulatory elements in treating pediatric R/R‐AML.

Discoid lateral meniscus (DLM) is the most common congenital variant of the lateral meniscus, which is prone to degeneration and lesions, and often leads to knee osteoarthritis. At present, there is no consensus on the clinical practice of DLM, and this expert consensus and practice guidelines on DLM was developed and approved by Chinese Society of Sports Medicine according to the Delphi method. Among 32 statements drafted, 14 statements were excluded for redundant information, and 18 statements achieved consensus. This expert consensus focused on the definition, epidemiology, etiology, classification, clinical manifestations, diagnosis, treatment, prognosis, and rehabilitation of DLM. Restoring the normal shape, retaining appropriate width and thickness, and ensuring the stability of the remnant meniscus is critical to sustaining the physiological function of the meniscus and preserving the knee. The partial meniscectomy with or without repair should be the first‐line treatment when possible, given that the clinical and radiological long‐term outcomes of total or subtotal meniscectomy are worse.

Abstract Approximately one‐third children with anaplastic large cell lymphoma (ALCL) relapse after completion of chemotherapy, particularly for those high‐risk patients. The introduction of novel therapeutic modalities is much needed for these sub‐group patients. Two groups (n = 3, n = 4) of ALCL patients were treated with crizotinib‐ and alectinib‐included ALCL‐99 therapy, respectively, achieving complete remission rates of 66.7% and 100%. Two patients of crizotinib group relapsed, while none relapsed among the alectinib‐treated patients. Adding alectinib instead of crizotinib sufficiently suppressed and maintained the deep NPM‐ALK molecular response. ALK inhibitors were well tolerated with only grade 1 adverse events in both groups. Though a relatively small case number, this study raised the possibility that alectinib‐included therapeutic regimens may benefit the early response, in‐depth molecular remission, and persistent remission to some extent. Further studies are warranted to validate our preliminary findings.

Abstract The conventional single variable indirect model predictive control (SIMPC) of LCL‐type three‐level grid‐ connected inverter (GCI) is to indirectly control the grid current by controlling the output current of the inverter, which usually produces large errors and reduces the system anti‐disturbance performance. Although the previously proposed multivariable weighted model predictive control (MWMPC) method of LCL‐type GCI can directly control many variables, such as grid current, it requires setting the weight coefficient for each variable and involves a substantial amount of calculation. To due with these problems, this paper proposes a multivariable sequential model predictive control (MSMPC) method for LCL‐type three‐level GCI. The inverter output current, the filter capacitor voltage, and the grid current are gradually predicted and optimized under the variable control sequence of the LCL‐type GCI mathematical model. Under the premise of achieving direct control of the variables above, this method can reduce the number of weighting coefficients and gradually contract the optimization space to reduce the computation required for multivariable prediction and optimization. This paper compares the proposed MSMPC to the conventional SIMPC and MWMPC in steady state, transient state performance, and anti‐disturbance performance. The effectiveness of the proposed MSMPC is demonstrated through simulation and experimentation.

Abstract Aims Peripartum cardiomyopathy (PPCM) are more vulnerable to intracardiac thrombus than other types of cardiomyopathies, although explicit anticoagulant strategy is not sure. Too aggressive anticoagulation therapy can lead to severe bleeding events. Hence, we want to construct a risk stratification model for intracardiac thrombus in PPCM patients. Methods and results A total of 159 suspected PPCM cases were initially screened, whereas 123 confirmed cases were enrolled in the final analysis. The study population was randomly assigned as derivation group (N = 83) and validation group (N = 40). The derivation cohort was utilized to develop the model, and the validation cohort was used to internal validate the discriminatory ability of the model. Formation of intracardiac thrombus was detected in 22 patients. After adjusted by multivariable logistic regression analysis, left ventricle ejection fraction (LVEF, OR 0.772, 95% CI 0.665–0.897, P = 0.001), haemoglobin levels (OR 1.050, 95% CI 1.003–1.099, P = 0.038), and thrombocyte counts (OR 1.018, 95% CI 1.006–1.029, P = 0.003) were identified as risk factors independently associated with intracardiac thrombus and were finally included in the tentative risk stratification model with a C‐indexes of 0.916 (95% CI: 0.850–0.982, P