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Abstract Nowadays, sparse arrays have been a focus for direction‐of‐arrival (DOA). The existing arrays can achieve high degree of freedom (DOF) bigger than the number of sensors when using the spatial smoothing methods. However, the small inter‐element spacing degrades the DOA estimation accuracy when facing severe mutual coupling. In order to alleviate mutual coupling, a coprime linear array using three uniform linear arrays (CLA‐U3) is proposed. The expression of sensor locations is given, and the analysis of DOF is considered. The minimum subarray inter‐element spacing in CLA‐U3 is bigger than that of the existing arrays, which means that CLA‐U3 can be less sensitive to mutual coupling. Moreover, the difference co‐subarrays can fill each other's holes, so CLA‐U3 and other sparse arrays composed of three subarrays have close DOF. Simulation experiments prove the favourable performance of DOA estimation.

ABSTRACT Background Pulmonary resection is an important part of comprehensive treatment of lung cancer. Despite the progress in recent thoracic surgery, reoperation is occasionally inevitable for managing severe perioperative complications. This study aimed to investigate the incidence and causes of perioperative reoperation in lung cancer patients. Methods We retrospectively collected patients who underwent reoperation following pulmonary resection from January 2010 to February 2021 in China‐Japan Friendship Hospital. Results Among the 5032 lung cancer patients who received primary pulmonary resection in our institute, 37 patients underwent perioperative reoperation with the rate being 0.74%. Lobectomy was the most frequently executed procedure (56.8%). The mean duration of the primary surgery was 143.6 ± 65.1 min. About half of the cases received secondary surgery within 24 h of the primary surgery, whereas only one case underwent secondary surgery 30 days after the primary surgery (due to chylous leakage). The major causes of the reoperation were bleeding (73.0%), chylous leakage (13.5%), lobar torsion (5.4%), air leakage (2.7%), atelectasis (2.9%), and cardiac herniation (2.7%). Conclusion The most prevalent reasons for unplanned reoperation following pulmonary resection in lung cancer patients include bleeding, chylous leakage, and lobar torsion. The strict control of the surgical indications and standardization of surgical procedures are fundamental to reduce unplanned secondary operations after pulmonary resections. Timely identification of the need to secondary surgery is also important to ensure patients' safety.

Abstract Frequent intravesical chemotherapy is still the adopted clinical option after bladder cancer surgery with low adhesion, poor selectivity, low permeability, and drug resistance. Herein, we develop an ingenious bladder cancer dissociation method to enhance intravesical chemotherapy and tumor self‐exclusion with urine. Ethylene diamine tetraacetic acid (EDTA), a common Ca2+ chelator, is loaded with the typical clinical bladder instillation drug doxorubicin (Dox) in chitosan‐modified hollow gold nanorods and subsequently coated with cancer cell membranes. After bladder perfusion, the nanoplatform exhibits high affinity toward bladder tumors under homologous targeting, assisting in long‐term retention. Under NIR‐II laser irradiation, the photothermal effect accelerates the unloading of cargo, and the released EDTA then disrupts intratumoral junctions by depriving and chelating Ca2+ from the intercellular calcium‐dependent connexin. The consequential intertumoral dissociation gives access to the deeper penetration of Dox and allows the exclusion of the shed small tumor masses from the body with the urine. This distinctive tumor dissociation concept holds great promise for modern clinical intravesical chemotherapy and perhaps for other gastrointestinal malignancies.

Abstract Wilms tumor‐1(WT1) is a crucial transcription factor that regulates podocyte development. However, the epigenomic mechanism underlying the function of WT1 during podocyte development has yet to be fully elucidated. Here, single‐cell chromatin accessibility and gene expression maps of foetal kidneys and kidney organoids are generated. Functional implications of WT1‐targeted genes, which are crucial for the development of podocytes and the maintenance of their structure, including BMPER/PAX2/MAGI2 that regulates WNT signaling pathway, MYH9 that maintains actin filament organization and NPHS1 that modulates cell junction assembly are identified. To further illustrate the functional importance of WT1‐mediated transcriptional regulation during podocyte development, cultured and implanted patient‐derived kidney organoids derived from the Induced Pluripotent Stem Cell (iPSCs) of a patient with a heterozygous missense mutation in WT1 are generated. Results from single‐cell RNA sequencing (scRNA‐seq) and functional assays confirm that the WT1 mutation leads to delays in podocyte development and causes damage to cell structures, due to its failure to activate the targeting genes MAGI2, MYH9, and NPHS1. Notably, correcting the mutation in the patient iPSCs using CRISPR‐Cas9 gene editing rescues the podocyte phenotype. Collectively, this work elucidates the WT1‐related epigenomic landscape with respect to human podocyte development and identifies the disease‐causing role of a WT1 mutation.

Abstract Background CircRNA‐encoded proteins (CEPs) are emerging as new players in health and disease, and function as baits for the common partners of their cognate linear‐spliced RNA encoded proteins (LEPs). However, their prevalence across human tissues and biological roles remain largely unexplored. The placenta is an ideal model for identifying CEPs due to its considerable protein diversity that is required to sustain fetal development during pregnancy. The aim of this study was to evaluate circRNA translation in the human placenta, and the potential roles of the CEPs in placental development and dysfunction. Methods Multiomics approaches, including RNA sequencing, ribosome profiling, and LC‐MS/MS analysis, were utilised to identify novel translational events of circRNAs in human placentas. Bioinformatics methods and the protein bait hypothesis were employed to evaluate the roles of these newly discovered CEPs in placentation and associated disorders. The pathogenic role of a recently identified CEP circPRKCB119aa in preeclampsia was investigated through qRT‐PCR, Western blotting, immunofluorescence imaging and phenotypic analyses. Results We found that 528 placental circRNAs bound to ribosomes with active translational elongation, and 139 were translated to proteins. The CEPs showed considerable structural homology with their cognate LEPs, but are more stable, hydrophobic and have a lower molecular‐weight than the latter, all of which are conducive to their function as baits. On this basis, CEPs are deduced to be closely involved in placental function. Furthermore, we focused on a novel CEP circPRKCB119aa, and illuminated its pathogenic role in preeclampsia; it enhanced trophoblast autophagy by acting as a bait to inhibit phosphorylation of the cognate linear isoform PKCβ. Conclusions We discovered a hidden circRNA‐encoded proteome in the human placenta, which offers new insights into the mechanisms underlying placental development, as well as placental disorders such as preeclampsia. Key points A hidden circRNA‐encoded proteome in the human placenta was extensively identified and systematically characterised. The circRNA‐encoded proteins (CEPs) are potentially related to placental development and associated disorders. A novel conserved CEP circPRKCB119aa enhanced trophoblast autophagy by inhibiting phosphorylation of its cognate linear‐spliced isoform protein kinase C (PKC) β in preeclampsia.

Abstract Human enterovirus A71 (EV‐A71) is a significant etiological agent responsible for epidemics of hand, foot, and mouth disease (HFMD) in Asia‐Pacific regions. There are presently no licensed antivirals against EV‐A71, and the druggable target for EV‐A71 remains very limited. The phenotypic hit 10,10′‐bis(trifluoromethyl) marinopyrrole A derivative, herein termed MPA‐CF3, is a novel potent small‐molecule inhibitor against EV‐A71, but its pharmacological target(s) and antiviral mechanisms are not defined. Here, quantitative chemoproteomics deciphered the antiviral target of MAP‐CF3 as host factor coatomer subunit zeta‐1 (COPZ1). Mechanistically, MPA‐CF3 disrupts the interaction of COPZ1 with the EV‐A71 nonstructural protein 2C by destabilizing COPZ1 upon binding. The destruction of this interaction blocks the coatomer‐mediated transport of 2C to endoplasmic reticulum, and ultimately inhibits EV‐A71 replication. Taken together, our study disclosed that MPA‐CF3 can be a structurally novel host‐targeting anti‐EV‐A71 agent, providing a structural basis for developing the COPZ1‐targeting broad‐spectrum antivirals against enteroviruses. The mechanistic elucidation of MPA‐CF3 against EV‐A71 may offer an alternative COPZ1‐involved therapeutic pathway for enterovirus infection.

Abstract Plants can autonomously adjust their growth direction based on the gravitropic response to maximize energy acquisition, despite lacking nerves and muscles. Endowing soft robots with gravitropism may facilitate the development of self‐regulating systems free of electronics, but remains elusive. Herein, acceleration‐regulated soft actuators are described that can respond to the gravitational field by leveraging the unique fluidity of liquid metal in its self‐limiting oxide skin. The soft actuator is obtained by magnetic printing of the fluidic liquid metal heater circuit on a thermoresponsive liquid crystal elastomer. The Joule heat of the liquid metal circuit with gravity‐regulated resistance can be programmed by changing the actuator's pose to induce the flow of liquid metal. The actuator can autonomously adjust its bending degree by the dynamic interaction between its thermomechanical response and gravity. A gravity‐interactive soft gripper is also created with controllable grasping and releasing by rotating the actuator. Moreover, it is demonstrated that self‐regulated oscillation motion can be achieved by interfacing the actuator with a monostable tape spring, allowing the electronics‐free control of a bionic walker. This work paves the avenue for the development of liquid metal‐based reconfigurable electronics and electronics‐free soft robots that can perceive gravity or acceleration.

Abstract Background The Z0011 and AMAROS trials found that axillary lymph node dissection (ALND) was no longer mandatory for early‐stage breast cancer patients who had one or two metastatic axillary lymph nodes (mALNs). The aim of our study was to establish a nomogram which could be used to quantitatively predict the individual likelihood of high burden mALN (≥3 mALN). Methods We retrospectively analyzed 564 women with early breast cancer who had all undergone both ultrasound (US) and magnetic resonance imaging (MRI) to examine axillary lymph nodes before radical surgery. All the patients were divided into training (n = 452) and validation (n = 112) cohorts by computer‐generated random numbers. Their clinicopathological features and preoperative imaging associated with high burden mALNs were evaluated by logistic regression analysis to develop a nomogram for predicting the probability of high burden mALNs. Results Multivariate analysis showed that high burden mALNs were significantly associated with replaced hilum and the shortest diameter >10 mm on MRI, with cortex thickness >3 mm on US (p

Background Resolvin D2 (RvD2) has been reported to protect against the development of atherosclerosis in animal models. The objective of this study was to examine the prospective association between plasma RvD2 and the risk of atherosclerotic cardiovascular disease (ASCVD) at the population level. Methods and Results A cohort of 2633 community‐dwelling individuals aged 35–60 years was followed for 8 years in this study. Adjusted hazard ratios and 95% CIs for ASCVD outcomes according to baseline RvD2 levels were calculated using Cox proportional hazards models. Mediation analysis was used to test the indirect effect of serum cholesterol indicators on the association between RvD2 and ASCVD probability. In total, 284 new cases of ASCVD were identified during follow‐up. An inverted U‐shaped association between natural log (ln)‐transformed RvD2 and incident ASCVD was determined, and the threshold value for lnRvD2 was 3.87. Below the threshold, each unit increase in lnRvD2 was associated with a 2.05‐fold increased risk of ASCVD (95% CI, 1.13–3.74; P=0.019). Above the threshold, each unit increase in lnRvD2 was associated with a 36% reduced risk of ASCVD (95% CI, 0.51–0.80; P

Abstract This work introduces a novel method to construct Schottky junctions to boost the output performance of triboelectric nanogenerators (TENGs). Perovskite barium zirconium titanate (BZT) core/metal silver shell nanoparticles are synthesized to be embedded into electrospun polyvinylidene fluoride‐co‐hexafluoropropylene (PVDF‐HFP) nanofibers before they are used as tribo‐negative layers. The output power of TENGs with composite fiber mat exhibited >600% increase compared to that with neat polymer fiber mat. The best TENG achieved 1339 V in open‐circuit voltage, 40 µA in short‐circuit current and 47.9 W m−2 in power density. The Schottky junctions increased charge carrier density in tribo‐layers, ensuring a high charge transfer rate while keeping the content of conductive fillers low, thus avoiding charge loss and improving performance. These TENGs are utilized to power radio frequency identification (RFID) tags for backscatter communication (BackCom) systems, enabling ultra‐massive connectivity in the 6G wireless networks and reducing information communications technology systems’ carbon footprint. Specifically, TENGs are used to provide an additional energy source to the passive tags. Results show that TENGs can boost power for BackCom and increase the communication range by 386%. This timely contribution offers a novel route for sustainable 6G applications by exploiting the expanded communication range of BackCom tags.

Abstract Hyperhomocysteinemia with hypertension can synergistically increase the risk of stroke. The China stroke primary prevention trial showed that combining 0.8 mg folic acid (FA) with angiotensin‐converting enzyme inhibitor (ACEI) can effectively lower plasma total homocysteine (tHcy) and blood pressure (BP); and reduce first stroke risk by additional 21% compared to ACEI alone. However, intolerance to ACEI is common in Asians and amlodipine can be alternative. This is a multicenter, randomized, double‐blind, parallel‐controlled clinical trial (RCT) which evaluated whether amlodipine combined with FA is more efficacious than amlodipine alone in lowering tHcy and BP among Chinese hypertensive with hyperhomocysteinemia and intolerance to ACEI. 351 Eligible patients were randomly assigned by 1:1:1 ratio to receive amlodipine‐FA tablet daily (amlodipine 5 mg/FA 0.4 mg, A group); amlodipine 5 mg/FA 0.8 mg tablet daily (B group); amlodipine 5 mg daily (C group, control group). Follow‐up was conducted at 2, 4, 6, and 8 weeks. The primary outcome was efficacy of lowering both tHcy and BP at the end of 8‐week treatment. Compared with C group, A group had a significantly higher rate of lowering both tHcy and BP (23.3% vs. 6.0%; Odds Ratio [OR], 8.68; 95% CI, 3.04‐24.78, P

Abstract To date, the restricted capability to fabricate ceramics with independently tailored nano‐ and macroscopic features has hindered their implementation in a wide range of crucial technological areas, including aeronautics, defense, and microelectronics. In this study, a novel approach that combines self‐ and digital assembly to create polymer‐derived ceramics with highly controlled structures spanning from the nano‐ to macroscale is introduced. Polymerization‐induced microphase separation of a resin during digital light processing generates materials with nanoscale morphologies, with the distinct phases consisting of either a preceramic precursor or a sacrificial polymer. By precisely controlling the molecular weight of the sacrificial polymer, the domain size of the resulting material phases can be finely tuned. Pyrolysis of the printed objects yields ceramics with complex macroscale geometries and nanoscale porosity, which display excellent thermal and oxidation resistance, and morphology‐dependent thermal conduction properties. This method offers a valuable technological platform for the simplified fabrication of nanostructured ceramics with complex shapes.

Magnetic soft robots featuring untethered actuation and high mechanical compliance have promising applications ranging from bionics to biomedicine. However, their fixed magnetization profiles pose a challenge for adaptive shape transformation in unpredictable environments and dynamic tasks. Herein, a reprogrammable magnetic soft composite is reported by encapsulating magnetic neodymium–iron–boron microparticles with low melting alloy (LMA) and embedding them into the elastomer. Utilizing the phase transition of the LMA, the magnetic microparticles can be reoriented under an external magnetic field and they can be immobilized through LMA solidification, allowing the robot to obtain a new magnetization profile corresponding to its temporary shape. By changing the LMA composition, the robot with multiple programming temperatures can be fabricated and its local magnetization profiles can be selectively programmed in different temperature ranges. A bioinspired crawler with multimode locomotion, a reconfigurable robotic gripper capable of adaptable grasping, and reconfigurable electronic circuits are also demonstrated. This work may pave the way for the next‐generation magnetic soft robots and reconfigurable devices.

Abstract In recent years, cannabidiol (CBD), a non‐psychotropic cannabinoid, has garnered substantial interest in drug development due to its broad pharmacological activity and multi‐target effects. Diabetes is a chronic metabolic disease that can damage multiple organs in the body, leading to the development of complications such as abnormal kidney function, vision loss, neuropathy, and cardiovascular disease. CBD has demonstrated significant therapeutic potential in treating diabetes mellitus and its complications owing to its various pharmacological effects. This work summarizes the role of CBD in diabetes and its impact on complications such as cardiovascular dysfunction, nephropathy, retinopathy, and neuropathy. Strategies for discovering molecular targets for CBD in the treatment of diabetes and its complications are also proposed. Moreover, ways to optimize the structure of CBD based on known targets to generate new CBD analogues are explored.

Abstract Crops must efficiently allocate their limited energy resources to survival, growth and reproduction, including balancing growth and defense. Thus, investigating the underlying molecular mechanism of crop under stress is crucial for breeding. Chloroplasts immunity is an important facet involving in plant resistance and growth, however, whether and how crop immunity modulated by chloroplast is influenced by epigenetic regulation remains unclear. Here, the cotton lysine 2‐hydroxyisobutyrylation (Khib) and succinylation (Ksuc) modifications are firstly identified and characterized, and discover that the chloroplast proteins are hit most. Both modifications are strongly associated with plant resistance to Verticillium dahliae, reflected by Khib specifically modulating PR and salicylic acid (SA) signal pathway and the identified GhHDA15 and GhSRT1 negatively regulating Verticillium wilt (VW) resistance via removing Khib and Ksuc. Further investigation uncovers that photosystem repair protein GhPSB27 situates in the core hub of both Khib‐ and Ksuc‐modified proteins network. The acylated GhPSB27 regulated by GhHDA15 and GhSRT1 can raise the D1 protein content, further enhancing plant biomass‐ and seed‐yield and disease resistance via increasing photosynthesis and by‐products of chloroplast‐derived reactive oxygen species (cROS). Therefore, this study reveals a mechanism balancing high disease resistance and high yield through epigenetic regulation of chloroplast protein, providing a novel strategy to crop improvements.

Abstract In this letter, a localization algorithm for mixed‐field sources based on fourth‐order cumulant matrix rank reduction is proposed. First, a cumulant matrix is constructed, and a spectral peak search function associated with the direction‐of‐arrival (DOA) of the sources only is constructed using the rank reduction principle to achieve DOA estimation. Then the range estimation is also obtained by a spectral peak search. Compared to existing algorithms, the algorithm is able to utilize all the elements of the cumulant matrix and has a higher accuracy and degrees‐of‐freedom. The simulation results verify the excellence of the algorithm.

Abstract For many clonally propagated species, the accumulation of somatic mutations is the principal driver of declines in yield and quality. However, somatic mutations may also promote genetic diversification. Thus, elucidating somatic mutation rates and patterns is important to understand the genetic basis undergirding the emergence of commercially valuable traits and developmental processes. In this study, we studied the effect of short‐time clonal domestication of Populus alba var. pyramidalis, a species that has been propagated by cutting for the last 67 years. We found that: (1) the somatic mutation rate for P. alba var. pyramidalis is 9.24 × 10−9, which is higher than rates observed in related species; (2) there were more mutations near heterozygous regions, and a larger proportion of CpG and CHG sites were associated with somatic mutations, which may be related to the blocking of DNA repair by methylation; and (3) deleterious mutations were not shared by multiple individuals, and all occurred in heterozygous states, demonstrating the strong selective pressures that act against deleterious mutations. Taken together, the results of our study provide a global view of somatic mutation that will aid efforts to understand the genetic basis of commercially valuable traits and to improve clonally breeding species.

Abstract Deep learning approaches to interactive image segmentation are typically formulated as a binary labeling problem. A model trained to make predictions within a fixed set of labels (i.e., foreground and background labels) cannot be used to directly predict the binary masks of multiple objects of interest, which greatly limits its flexibility and adaptivity. The use of different classes of clicks as input is opted for and the first end‐to‐end learning model for multi‐object segmentation, based on a new designed neural network, is developed. The network consists of a visual feature extractor, a recurrent attention module and a dynamic segmentation head, extracts user click‐adapted appearance embedding features and spatial attention features, and then learns to transform this information into a segmentation of multiple objects. It is also proposed to train the network using a joint loss function, taking the embedding learning into account for segmentation. Comprehensive experiments are conducted on three benchmark datasets to demonstrate the effectiveness of the proposed method. It performs favorably against state‐of‐the‐art approaches on the multiple object segmentation task, for example, with 0.15 s per image, 0.06 s per object and mean IoU & F1 score of 84.90% on Pascal VOC 2012 validation set. It is further shown that the method can be used in numerous vision applications such as image recoloring and colorization.

Abstract Developing a convenient method to determine the complete structure of single‐walled carbon nanotubes (SWNTs) is important to achieve the fully controlled growth of this nanomaterial. However, approaches that can identify handedness at the atomic level with simple equipment, operation, and data analysis are still lacking. Here, the SWNTs/graphene (Gr) vertical heterostructures are artificially constructed with aligned interfaces to realize the lattice interpretation of SWNT upper and lower walls separately by only one transmission electron microscopy image, thus transforming the 3D handedness information to projected 2D space. Gr displays prominent out‐of‐plane deformation at the interface, promoting the energetic advantage for the aligned interface construction. The interfacial alignment between the SWNT and Gr shows no obvious dependence on either the helical angle or diameter of SWNTs. The half‐wrapping of SWNTs by deformed Gr also triggers diversified alterations in electronic structures based on theoretical calculations. 27 specimens with SWNTs prepared by two disparate methods are examined, implying equal handedness distribution in the randomly aligned SWNTs grown on quartz and potential handedness enrichment in horizontal SWNT arrays grown on a‐sapphire. This work provides a simple strategy for chiral discrimination and lays a characterization foundation for handedness‐selective growth of nanomaterials.

Abstract The exploration of single‐cell 3D genome maps reveals that chromatin domains are indeed physical structures presenting in single cells, and domain boundaries vary from cell to cell. However, systematic analysis of the association between regulatory factor binding and elements and the formation of chromatin domains in single cells has not yet emerged. To this end, a hierarchical chromatin domain structure identification algorithm (named as HiCS) is first developed from individual single‐cell Hi‐C maps, with superior performance in both accuracy and efficiency. The results suggest that in addition to the known CTCF‐cohesin complex, Polycomb, TrxG, pluripotent protein families, and other multiple factors also contribute to shaping chromatin domain boundaries in single embryonic stem cells. Different cooperation patterns of these regulatory factors drive genomic position categories with differential preferences forming boundaries, and the most extensive six types of retrotransposons are differentially distributed in these genomic position categories with preferential localization. The above results suggest that these different retrotransposons within genomic regions interplay with regulatory factors navigating the preference of genomic positions forming boundaries, driving the formation of higher‐order chromatin structures, and thus regulating cell functions in single mouse embryonic stem cells.

Abstract Cancer is a complex disease associated with a combination of abnormal physiological process and exhibiting dysfunctions in multiple systems. To provide effective treatment and diagnosis for cancer, current treatment strategies simultaneously focus on various tumor targets. Based on the rapid development of nanotechnology, nanocarriers have been shown to exhibit excellent potential for cancer therapy. Compared with nanoparticles with single functions, multifunctional nanoparticles are believed to be more aggressive and potent in the context of tumor targeting. However, the development of multifunctional nanoparticles is not simply an upgraded version of the original function, but involves a sophisticated system with a proper backbone, optimized modification sites, simple preparation method, and efficient function integration. Despite this, many well‐designed multifunctional nanoparticles with promising therapeutic potential have emerged recently. Here, to give a detailed understanding and analyzation of the currently developed multifunctional nanoparticles, their platform structures with organic or inorganic backbones were systemically generalized. We emphasized on the functionalization and modification strategies, which provide additional functions to the nanoparticle. We also discussed the application combination strategies that were involved in the development of nanoformulations with functional crosstalk. This review thus provides an overview of the construction strategies and application advances of multifunctional nanoparticles.

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.

To achieve low wavefront error and high throughput with vignetting-free target simulators, a concave-convex-concaveoff-axis spherical system is designed in this paper, which effectively eliminates astigmatism and coma of the system by fields of view (FOVs) and aperture offset and provides theoretical basis for the realization of 100% matching between the exit pupil of the field lens and entrance pupil of the three-mirror anastigmat (TMA) system. Only spherical mirror element is used in this target simulator, which not only reduces the difficulty of manufacturing and cost but also greatly reduces the difficulty of assembling and adjusting. It provides an effective scheme for the design of target simulator and has strong engineering application value.

Abstract Deep neural networks are vulnerable to adversarial examples. However, existing attacks exhibit relatively low efficacy in generating transferable adversarial examples. Improved transferability to address this issue is proposed via a rotation‐invariant attack method that maximizes the loss function w.r.t the random rotated image instead of the original input at each iteration, thus mitigating the high correlation between the adversarial examples and the source models and making the adversarial examples more transferable. Extensive experiments show that the proposed method can significantly improve the transferability of the adversarial examples with almost no extra computational cost and can be integrated into various methods. In addition, when this method is easily applied through a plug‐in, the average attack success rate against six robustly trained models increases by 5.4% over the state‐of‐the‐art baseline method, demonstrating its effectiveness and efficiency. The codes used are publicly available at https://github.com/YeXinD/Rotation‐Invariant‐Attack.

ABSTRACT Medulloblastoma is the most common primary pediatric malignancy of the central nervous system. Recurrent and refractory patients account for approximately 30% of them. Immune cells are an important component of the brain tumor microenvironment, including tumor‐associated macrophages, T lymphocytes, natural killer cells, dendritic cells, neutrophils and B lymphocytes. Understanding how they behave and interact is important in the investigation of the onset and progression of medulloblastoma. Here, we overview the features and recent advances of each component of immune cells in medulloblastoma. Meanwhile, immunotherapy is a promising but also challenging treatment strategy for medulloblastoma. At present, there are a growing number of immunotherapeutic approaches under investigation including immune checkpoint inhibitors, oncolytic viruses, cancer vaccines, chimeric antigen receptor T cell therapies, and natural killer cells in recurrent and refractory medulloblastoma patients.

Abstract High concentrations of active carriers on the surface of a semiconductor through energy/electron transfer are the core process in the photocatalytic hydrogen production from water. However, it remains a challenge to significantly improve photocatalytic performance by modifying simple molecular modulation. Herein, a new strategy is proposed to enhance the photocatalytic hydrogen evolution performance using boron and nitrogen elements to construct B←N coordination bonds. Experimental results show that polynaphthopyridine borane (PNBN) possessing B←N coordination bonds shows a hydrogen evolution rate of 217.4 µmol h−1, which is significantly higher than that of the comparison materials 0 µmol h−1 for polyphenylnaphthalene (PNCC) and 0.66 µmol h−1 for polypyridylnaphthalene (PNNC), mainly attributed to the formation of a strong built‐in electric field that promotes the separation of photo‐generated electrons/holes. This work opens up new prospects for the design of highly efficient polymeric photocatalysts at the molecular level.

Objective To retrospectively assess the mid‐term clinical and radiological results of hip arthroscopic treatment of labral tears in patients with borderline developmental dysplasia of the hip (BDDH). Methods From January 2010 and December 2019, data were retrospectively reviewed for all patients who underwent arthroscopic surgery of the hip for the treatment of intra‐articular abnormalities. Only the Patients who had borderline developmental dysplasia (BDDH) were included. All operations were performed by two senior surgeons, the arthroscopic treatment including labral repair, labral debridement, minimal acetabuloplasty, femoroplasty and capsular closure. The evaluation consisted of pain evaluation (visual analog scale [VAS]), the modified Harris hip score (MHHS), range of motion, the radiological evaluation of plain film and MRI analysis of the hip joint. The plain film evaluation included anteroposterior views of the pelvis to assess lateral center‐edge angle (LCEA) and acetabular inclination (AI), frog‐leg lateral views of the hip to assess α angle. Results There were 34 patients (36 hips) ultimately enrolled in this study. The follow‐up duration of the patients were minimal 2 years (average, 69.2 months) postoperatively. The patient group included seven men and 27 women, the mean age at the time of surgery was 30.9 years. The mean BMI was 22.3 kg/m2. From the pre‐operative status to the final follow‐up visit, mean mHHS score increased from 64.5 to 92.7, mean VAS score decreased from 6.8 to 1.3. All scores exhibited statistically significant differences (P 0.05). However, the mean α angle was significantly decreased from 48.3° to 40.1° (P

Abstract Background Congenital heart disease (CHD) is the most common birth defect and has high heritability. Although some susceptibility genes have been identified, the genetic basis underlying the majority of CHD cases is still undefined. Methods A total of 1320 unrelated CHD patients were enrolled in our study. Exome‐wide association analysis between 37 tetralogy of Fallot (TOF) patients and 208 Han Chinese controls from the 1000 Genomes Project was performed to identify the novel candidate gene WD repeat‐containing protein 62 (WDR62). WDR62 variants were searched in another expanded set of 200 TOF patients by Sanger sequencing. Rescue experiments in zebrafish were conducted to observe the effects of WDR62 variants. The roles of WDR62 in heart development were examined in mouse models with Wdr62 deficiency. WDR62 variants were investigated in an additional 1083 CHD patients with similar heart phenotypes to knockout mice by multiplex PCR‐targeting sequencing. The cellular phenotypes of WDR62 deficiency and variants were tested in cardiomyocytes, and the molecular mechanisms were preliminarily explored by RNA‐seq and co‐immunoprecipitation. Results Seven WDR62 coding variants were identified in the 237 TOF patients and all were indicated to be loss of function variants. A total of 25 coding and 22 non‐coding WDR62 variants were identified in 80 (6%) of the 1320 CHD cases sequenced, with a higher proportion of WDR62 variation (8%) found in the ventricular septal defect (VSD) cohort. WDR62 deficiency resulted in a series of heart defects affecting the outflow tract and right ventricle in mouse models, including VSD as the major abnormality. Cell cycle arrest and an increased number of cells with multipolar spindles that inhibited proliferation were observed in cardiomyocytes with variants or knockdown of WDR62. WDR62 deficiency weakened the association between WDR62 and the cell cycle‐regulated kinase AURKA on spindle poles, reduced the phosphorylation of AURKA, and decreased expression of target genes related to cell cycle and spindle assembly shared by WDR62 and AURKA. Conclusions WDR62 was identified as a novel susceptibility gene for CHD with high variant frequency. WDR62 was shown to participate in the cardiac development by affecting spindle assembly and cell cycle pathway in cardiomyocytes.

Abstract Systolic blood pressure (SBP) and resting pulse rate (RPR) have been linked to mortality and cardiovascular events in younger population. Till now, no studies simultaneously investigate the non‐linear association of SBP and RPR with all‐cause and cardiovascular mortality among population aged 80 and older. Data of 2828 eligible participants were selected from electronic health records linked attended automated office blood pressure measurement system. The dose‐response relationship between the SBP, RPR, and the risk of all‐cause and cardiovascular mortality was analyzed by Cox model with restricted cubic splines. During the 3.6‐year follow‐up, 442 deaths occurred. Comparing with the optimal SBP (117‐145 mmHg), the lower (HR: 1.39, 95% CI: 1.07‐1.81) and higher SBP (HR: 1.34, 95% CI: 1.08‐1.65) were significantly associated with an increasing risk of all‐cause mortality. The higher SBP (>144 mmHg) was associated with cardiovascular mortality, with the HR (95% CI) as 1.51 (1.07‐2.12). The faster RPR showed the higher risk of all‐cause (HR: 1.36, 95% CI: 1.05‐1.76) and cardiovascular (HR: 1.51, 95% CI: 1.07‐2.13) mortality. We found both higher SBP and faster RPR were independently associated with all‐cause and cardiovascular mortality, and lower SBP was only associated with the increased risk of all‐cause mortality in oldest old community‐dwelling Chinese population. Our results demonstrate the prognostic importance of both SBP and RPR in the elderly.

Abstract Due to the growing demand for transportation fuels and concerns about the greenhouse gas emissions derived from the use of fossil fuels, the development of alternative fuels from renewable resources, such as lignocellulosic biomass, is of paramount importance. This is compounded by the fact that there are increasing pressures and limitation on available arable land for renewable biomass production, and therefore, how to obtain more biomass resources and how to make full use of these biomass resources are key issues. Poplar (Populus spp.) is one of the fastest‐growing temperate trees in the world and is a very promising raw material for the production of biofuels and other bio‐based commodities. As the first tree species to have its genome sequenced, and significant continuing efforts towards resequencing of different species/varieties, poplar resources will undoubtedly pave the way for the targeted cultivation of new poplar varieties suitable for biofuel production. In this article, we summarized that the main problems faced by using poplar as a biomass resource for biofuel production are the inherent recalcitrance of lignocellulosic biomass, and highlighted the response status on improving the biomass yield and efforts towards developing efficient poplar varieties for biofuel production.

Objective The aim of this study was to investigate whether treatment with minimally invasive transforaminal lumbar interbody fusion (Mis‐TLIF) causes patients suffering from lumbar spinal stenosis (LSS) to experience less anxiety and better clinical efficacy than open transforaminal lumbar interbody fusion (TLIF). Methods In this retrospective cohort study, we analyzed 86 patients, including 46 male patients and 41 female patients, who suffered from single‐segmental lumbar spinal stenosis in our department between January 2016 and January 2018. They were divided into two groups: a control group (n = 46), for patients who underwent open TLIF surgery, and an experimental group (n = 40), for patients who underwent Mis‐TLIF surgery. All patients were evaluated based on operation time, intraoperative blood loss, hospital stay, visual analogue scale (VAS), Oswestry disability index (ODI), hospital anxiety depression scale (HADS), fusion rate, and complications (screw misplacement and loosening, cerebrospinal fluid leakage, infection, and delayed wound healing). Patient characteristics were compared within and between groups. Results The average incision length was 3.64 ± 0.476 cm in the experimental group, which was smaller than that (8.11 ± 2.406 cm) in the control group (P 0.05). The low back pain VAS scores on postoperative day 3 and at 3, 6, and 12 months postoperatively were 5.000 ± 0.987, 4.075 ± 0.997, 2.150 ± 0.834, and 1.450 ± 0.639 in the experimental group, respectively; these scores were lower than those in the control group (6.870 ± 1.572, P 0.05). The ODI scores at postoperative months 3, 6, and 12 were 25.225% ± 5.554%, 20.150% ± 7.698%, and 16.125% ± 9.565% in the experimental group; these scores were lower than those in the control group (49.130% ± 14.805%, P 0.05). However, the mean HADS scores on postoperative day 3 in the experimental group was 8.500 ± 2.000, decreasing obviously compared to the preoperative scores (P 0.05). The HADS scores in the experimental group was lower than that in the control group on postoperative day 3 (P

Abstract With the continuous progress in electronic devices, thermal interface materials (TIMs) are urgently needed for the fabrication of integrated circuits with high reliability and performance. Graphene as a wonderful additive is often added into polymer to build composite TIMs. However, owing to the lack of a specific design of the graphene skeleton, thermal conductivity of graphene‐based composite TIMs is not significantly improved. Here a chloroform‐assisted method for rapid growth of vertical graphene (VG) arrays in electric field‐assisted plasma enhanced chemical vapor deposition (PECVD) system is reported. Under the optimum intensity and direction of electric field and by introducing the highly electronegative chlorine into the reactor, the record growth rate of 11.5 µm h−1 is achieved and VG with a height of 100 µm is successfully synthesized. The theoretical study for the first time reveals that the introduction of chlorine accelerates the decomposition of methanol and thus promotes the VG growth in PECVD. Finally, as an excellent filler framework in polymer matrix, VG arrays are used to construct a free‐standing composite TIM, which yields a high vertical thermal conductivity of 34.2 W m−1 K−1 at the graphene loading of 8.6 wt% and shows excellent cooling effect in interfacial thermal dissipation of light emitting diode.

Abstract Herein, a human identification system for smart spaces called Vein‐ID (referred to as VID) is presented, which leverage the uniqueness of vein patterns embedded in dorsum of an individual's hand. VID extracts vein patterns using the depth information and infrared (IR) images, both obtained from a commodity depth camera. Two deep learning models (CNN and Stacked‐Autoencoders) are presented for precisely identifying a target individual from a set of N enrolled users. VID also incorporates a strategy for identifying an intruder—that is a person whose vein patterns are not included in the set of enrolled individuals. The performance of VID by collecting a comprehensive data set of approximately 17,500 images from 35 subjects is evaluated. The tests reveal that VID can identify an individual with an average accuracy of over 99% from a group of up to 35 individuals. It is demonstrated that VID can detect intruders with an average accuracy of about 96%. The execution time for training and testing the two deep learning models on different hardware platforms is also investigated and the differences are reported.

Abstract Objective Neuroblastoma (NBL) is an extra‐cranial solid tumor in children. This study was attempted to investigate the regulatory mechanism of long noncoding RNA LINC01410 (LINC01410) on NBL. Methods The expression of LINC01410, miR‐506‐3p, and WEE1 in NBL was evaluated by quantitative real time polymerase chain reaction. The proliferation and colony formation ability of NBL cells were analyzed by MTT and colony formation assay. Flow cytometry assay was executed to measure the apoptosis and cell cycle. Dual‐luciferase reporter assay was used to detect the targeted relationships among LINC01410, miR‐506‐3p, and WEE1. Additionally, the role of LINC01410 on NBL in vivo was evaluated according to a tumor xenograft model. Results The expression of LINC01410 and WEE1 was enhanced and miR‐506‐3p was inhibited in NBL. LINC01410 knockdown attenuated the cell proliferation, colony formation ability, and inhibited tumor growth. Moreover, LINC01410 silencing facilitated the apoptosis and arrested the cell cycle. LINC01410 interacted with miR‐506‐3p to elevate the WEE1 expression in NBL. Additionally, miR‐506‐3p inhibition or WEE1 overexpression weakened the reduction effects of sh‐LINC01410 on cell proliferation, colony formation ability, apoptosis, and cell cycle. Conclusions Knockdown of LINC01410 inhibited the development of NBL by miR‐506‐3p/WEE1 axis in vitro, which could serve as a potential therapeutic target for NBL therapy.

Abstract Cancer immunotherapy has achieved promising clinical progress over the recent years for its potential to treat metastatic tumors and inhibit their recurrences effectively. However, low patient response rates and dose‐limiting toxicity remain as major dilemmas for immunotherapy. Stimuli‐responsive nanoparticles (srNPs) combined with immunotherapy offer the possibility to amplify anti‐tumor immune responses, where the weak acidity, high concentration of glutathione, overexpressions of enzymes, and reactive oxygen species, and external stimuli in tumors act as triggers for controlled drug release. This review highlights the design of srNPs based on tumor microenvironment and/or external stimuli to combine with different anti‐tumor drugs, especially the immunoregulatory agents, which eventually realize synergistic immunotherapy of malignant primary or metastatic tumors and acquire a long‐term immune memory to prevent tumor recurrence. The authors hope that this review can provide theoretical guidance for the construction and clinical transformation of smart srNPs for controlled drug delivery in synergistic cancer immunotherapy.

Objective. To screen the cell differentiation trajectory-related genes and build a cell differentiation trajectory-related signature for predicting the prognosis of lung adenocarcinoma (LUAD). Methods. LUAD single cell mRNA expression profile, TCGA-LUAD transcriptome data were obtained from GEO and TCGA databases. Single-cell RNA-seq data were used for cell clustering and pseudotime analysis after dimensionality reduction analysis, and the cell differentiation trajectory-related genes were acquired after differential expression analysis conducted between the main branches. Then, the consensus clustering analysis was carried out on TCGA-LUAD samples, and the GSEA analysis was performed, then the differences on the expression levels of immune checkpoint genes and immunotherapy response were compared among clusters. The prognostic model was constructed, and the GSE42127 dataset was used to validate. A nomogram evaluation model was used to predict prognosis. Results. Two subsets with distinct differentiation states were found after cell differentiation trajectory analysis. TCGA-LUAD samples were divided into two cell differentiation trajectory-related gene-based clusters, GSEA found that cluster 1 was significantly related to 20 pathways, cluster 2 was significantly enriched in three pathways, and it was also shown that clusters could better predict immune checkpoint gene expression and immunotherapy response. A six cell differentiation-related genes-based prognostic signature was constructed, and the patients in the high-risk group had poorer prognosis than those in the low-risk group. Moreover, a nomogram was constructed based on the prognostic signature and clinicopathological features, and this nomogram had strong predictive performance and high accuracy. Conclusion. The cell differentiation-related signature and the prognostic nomogram could accurately predict survival.

Considering the incomplete contact between the adjacent layers of crossanisotropic multilayered half-space media, an algorithm was derived based on the spectral element method (SEM) to determine the dynamic response at any point of the medium when an axisymmetric harmonic load is applied. The algorithm used two equivalent contact parameters to simulate the relationship between the discontinuity of the displacement and stress. The SEM was employed for the summation in the integral calculation to avoid the infinite integral in the integral transformation and greatly improve the efficiency of the solution to the dynamic response of the crossanisotropic layered half-space medium. The accuracy of the developed method is verified by the numerical examples as well as the efficiency of the developed method. Finally, an extensive parametric analysis of the contact parameters of the interface between the layers of the layered medium, namely, the point of the application of the external load, the excitation frequency, and the heterogeneous properties of the layered medium was conducted, providing a reliable numerical basis for engineering practice.

The Knothe time function is a classical method in predicting the ground mining subsidence. Nevertheless, it does not take the observation data into account in the prediction process. The Kalman filter method can solve this issue at large extent. Taking a coal mining work face of Xishan Coalfield as an example, this research compares the performance of the traditional Knothe time function and that of the improved Knothe time function by using the Kalman filter method. The comparison results show that through an improvement by using the Kalman filter method, the RMSE is improved from 133.4 mm to 78.3 mm; ME, from 91.9 mm to 3.1 mm; and the relative error, from 8.1% to 5.7%. Meanwhile, the improved model has good astringency. These verify that the improved model has higher accuracy and reliability. Hence, this research presents an effective method in predicting ground subsidence of mining area by improving the Knothe time function using the Kalman filter method.

Background. Curcumin is a polyphenol plant-derived compound with anti-inflammatory, antioxidant stress, and anticancer properties that make it have the potential to treat cancer cachexia. However, the role of it in breast cancer cachexia remains unclear. Methods. The 4T1 cells were subcutaneously injected into BALB/c mice to induce breast cancer cachexia. After tumor formation, the animals were divided into groups and given curcumin or saline interventions. The therapeutic effect of curcumin on breast cancer cachexia was characterized by tumor growth, changes in body mass and gastrocnemius mass, muscle function test, histopathology, and serum nutrition indexes. Mitochondrial function in muscle tissue was observed by transmission electron microscopy and ATP detection, muscle inflammatory factors were detected by ELISA, muscle differential metabolites were detected by 1HNMR metabolomics, and the muscle tissue ubiquitination levels and NF-KB expression were also analyzed by RT-qPCR and Western blot. Results. Dynamic in vivo bioluminescence imaging find that curcumin inhibited the growth of tumor in triple-negative breast cancer- (TNBC-) bearing mice, slowed down the loss of body weight and gastrocnemius weight, corrected the mitochondrial dysfunction and malnutrition status, and also significantly improved skeletal muscle function. ELISA analysis found that the level of inflammatory factors in muscle tissue was reduced. 1HNMR metabolomics analysis suggested that curcumin could regulate energy metabolism pathways. RT-qPCR and Western blot analysis found that the expression of myogenic factor myogenin was increased and the expression of myodegradation factor myostatin was decreased in the gastrocnemius; the level of ubiquitination and activation of the NF-κB pathway were also declined. Conclusions. Curcumin reduces ubiquitination, inflammation in skeletal muscle by regulating the NF-KB/UPS axis and improves muscle malignant metabolic phenotype and mitochondrial dysfunction, to alleviate muscle atrophy and loss of function in mice with breast cancer cachexia.

Running metro trains would inevitably influence the vibration deformation in the lower part of the roadbed structure. In order to study the effects of vibration, Qingdao metro line 3 tunnel was taken as the research background. The track coupling model was established using Abaqus-Simpack to analyze the train velocity, train axle load, and trackbed vibration forms for the vertical deformation of roadbed calendar effect to provide the reference in practical engineering design and deformation control. According to the analysis, influenced by the formation of Qingdao Metro Line 3, the time-history curve of the displacement excitation of the trackbed presents the distribution law of “large in the middle and small at both ends.” According to the sensitivity analysis, the deformation of the trackbed is most obviously affected by the form of trackbed; the second was the influence of the axle load of the train. The speed change of the subway train presented relatively little influence on the displacement of the trackbed. Although the deformation control ability of the integral trackbed was better, its vibration reduction performance was poor. The vibration reduction performance of the rubber cushion floating trackbed was the best, followed by the steel spring floating trackbed.

To improve the probability of missile coordinated detection, this paper investigates the control method of multimissile cooperative formation. Based on the missile’s nonlinear dynamics modeling, the formation control algorithm based on the position of the leader missile (or virtual leader missile) is studied. Meanwhile, considering the influence of the communication time delay, a robust adaptive cooperative controller satisfying the time delay network is designed. The simulation verification result indicates that cooperative formation can be achieved quickly with small velocity and position tracking errors when the missiles are fully connected. Therefore, the multimissile cooperative formation control algorithm designed in this paper can meet the requirements of multimissile coordinated detection, thus improving the missile’s cooperative attack capability.

Marine vertical cable seismic (VCS) collects seismic waves by hydrophone array vertically suspended in seawater to prospect the offshore geological structure and monitor the reservoir. Due to its irregular source-receiver geometry, the primary imaging has narrow illustration coverage. Here, we proposed a cross-correlation transformation based on ghost wave interferometry. This method can transform the ghost reflections from the vertical cable seismic profile into the virtual surface seismic primaries just like those excited by the source and recorded by marine seismic towed-streamer below sea surface. After processing these virtual primaries with conventional method, we can obtain the ghost reflection imaging section with high resolution which effectively extend the illustration footprints in the subsurface. By application of this transform, virtual primaries are generated from the first-order ghost reflections of the actual VCS data. Then, migration of these virtual primaries provides a high-resolution image of hydrate-bearing sediments.

As part of our research group’s continuous efforts to find alternative treatments for cancer, the aqueous ethanol extract of Sesbania sesban L. Merr. (SS, Egyptian riverhemp) demonstrated an antileukemic activity against K562 cell line. Bioguided fractionation of SS leaves hydroethanolic extract resulted in the isolation of one new compound (33) named as hederatriol 3-O-β-D-glucuronic acid methyl ester as well as 34 known compounds. Seven compounds ((34), (22), (20), (24), (21), (19), and (35)) showed high antiproliferative effects (IC50 = 22.3, 30.8, 31.3, 33.7, 36.6, 37.5, and 41.5 μM, respectively), while four compounds ((32), (5), (29), and (1)) showed milder activities (IC50 = 56.4, 67.6, 83.3, and 112.3 μM, respectively). A mechanistic study was further carried out on a molecular genetics level against several transcription factors signaling pathways that are incorporated in the incidence of cancer. The results showed that compounds (22) and (21) demonstrated a specific inhibition of Wnt pathway (IC50 = 3.8 and 4.6 μM, respectively), while compound (22) showed a specific inhibition of Smad pathway (IC50 = 3.8 μM). Compound (34) strongly altered the signaling of Smad and E2F pathways (IC50 = 5 μM). The bioactive metabolites were further investigated in silico by docking against several targets related to K562 cell line. The results showed that compounds (22) and (34) exhibited a strong binding affinity towards topoisomerase (docking score = −7.81 and −9.30 Kcal/Mole, respectively). Compounds (22) and (34) demonstrated a strong binding affinity towards EGFR-tyrosine kinase (docking score = −7.12 and −7.35 Kcal/Mole, respectively). Moreover, compound (34) showed a strong binding affinity towards Abl kinase (docking score = −7.05 Kcal/Mole).

Although 19p13.13 microdeletion syndrome has been consistently associated with intellectual disability, overgrowth, and macrocephaly, the underlying mechanisms remain unclear. MAST1, a member of the microtubule‐associated serine/threonine kinase family, has been suggested as a potential candidate gene responsible for neurologic abnormalities in 19p13.13 microdeletion syndrome, but its role in nervous system development remains to be elucidated. Here, we investigated how MAST1 contributes to neuronal development. We report that MAST1 is upregulated during neuronal differentiation of the human neuroblastoma cell line, SH‐SY5Y. Inhibition of MAST1 expression by RNA interference attenuated neuronal differentiation of SH‐SY5Y cells. Cell cycle analyses revealed that MAST1‐depleted cells did not undergo cell cycle arrest after RA treatment. Consistent with this observation, the number of EdU‐positive cells significantly increased in MAST1 knockdown cells. Intriguingly, levels of P27, a cyclin‐dependent kinase inhibitor, were also increased during neuronal differentiation, and MAST1 knockdown reduced the expression of P27. Moreover, reduced neuronal differentiation caused by MAST1 depletion was rescued partially by P27 overexpression in SH‐SY5Y cells. Collectively, these results suggest that MAST1 influences nervous system development by affecting neuronal differentiation through P27.

Abstract Tamoxifen‐based hormone therapy is central for the treatment of estrogen receptor positive (ER+) breast cancer. However, the acquired tamoxifen resistance, typically co‐exists with hypoxia, remains a major challenge. We aimed to develop a non‐invasive, targeted ultrasound imaging approach to dynamically monitory of tamoxifen resistance. After we assessed acquired tamoxifen resistance in 235 breast cancer patients and a list of breast cancer cell lines, we developed poly(lactic‐co‐glycolic acid)‐poly(ethylene glycol)‐carbonic anhydrase IX mono antibody nanobubbles (PLGA‐PEG‐mAbCAIX NBs) to detect hypoxic breast cancer cells upon exposure of tamoxifen in nude mice. We demonstrate that carbonic anhydrase IX (CAIX) expression is associated with breast cancer local recurrence and tamoxifen resistance both in clinical and cellular models. We find that CAIX overexpression increases tamoxifen tolerance in MCF‐7 cells and predicts early tamoxifen resistance along with an oscillating pattern in intracellular ATP level in vitro. PLGA‐PEG‐mAbCAIX NBs are able to dynamically detect tamoxifen‐induced hypoxia and tamoxifen resistance in vivo. CAIX‐conjugated NBs with noninvasive ultrasound imaging is powerful for dynamically monitoring hypoxic microenvironment in ER+ breast cancer with tamoxifen resistance.

Abstract Selecting superior clones is the first step for commercial short‐rotation coppice cultures to provide biomass and bioenergy. Till date, such selection for hybrid Populus clones in middle China is absent. Here we describe the growth, aboveground biomass production and cell wall composition of 27 hybrid poplar clones in Henan, China for two 3‐year rotations. Significant variation in these three characteristics over two triennial rotation coppices among the 27 poplar clones was observed. During two 3‐year rotation coppices, clones ‘276’, ‘02‐17’, and ‘599’ showed relatively higher tree heights and larger basal diameters than those of the other clones. However, the most productive clones were ‘36’ and ‘01‐30’. At the end of the second triennial rotation, the aboveground biomass production reached 18 Mg ha−1 year−1. For the cell wall composition analysis, the cellulose contents of clones ‘01‐243’ and ‘2001’ were relatively high, while the xylose contents of clones ‘01‐30’ and ‘65’ were relatively high. Cluster analysis based on height, basal diameter, biomass, heat value, cellulose content, and survival rate revealed five growth potential classes. Accordingly, clones ‘03‐332’, ‘36’, and ‘599’ exhibited high biomass and growth and had the greatest potential to serve as excellent biomass producers in Henan, China. In addition, the expression patterns of 20 key regulatory genes were analyzed, and an integrated coexpression network was constructed. This field trial provides a comprehensive quantification and evaluation of the agronomic performance of 27 poplar clones in Henan, China. The results of this study and the analytical strategies provide an efficient mechanism for selecting clones that will perform well agronomically in local environments. The expression of key genes and the integrated coexpression network provide the molecular mechanisms of poplar biomass performance.

Abstract Aims/Introduction Increased blood lipopolysaccharide (LPS) or free fatty acid (FFA) levels correlate with an increased risk of type 2 diabetes. The purpose of the present study was to evaluate the interactive effect of serum LPS and FFA levels on the prevalence of type 2 diabetes. Materials and Methods This cross‐sectional study included 2,553 community‐dwelling Chinese adults. Fasting serum LPS levels were determined using the Limulus Amebocyte Lysate Chromogenic Endpoint assay, and FFA levels were determined using an enzymatic method. The participants were divided into three groups according to the tertiles of LPS or FFA levels or nine groups according to the tertiles of LPS and FFA levels. The odd ratios (ORs) for type 2 diabetes were estimated using logistic regression analysis. Results We found that higher serum LPS or FFA levels were associated with higher high‐sensitivity C‐reactive protein levels (P