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Abstract Lobopodians represent a key step in the early history of ecdysozoans since they were the first animals to evolve legs within this clade. Their Cambrian representatives share a similar body plan with a typically cylindrical annulated trunk and a series of non-jointed legs. However, they do not form a monophyletic group and likely include ancestors of the three extant panarthropod lineages (Tardigrada, Onychophora, Euarthropoda). Some species display astonishing protective devices such as cuticular plates and spines. We describe here the armor and molting process of Microdictyon from the early Cambrian of China. Microdictyon secreted ovoid paired cuticular sclerites that were duplicated in a non-synchronous way along the animal’s body. The reticulated pattern and cuticular architecture of these sclerites have similarities to extant armored tardigrades that recently served in hypothesizing that tardigrades are possibly miniaturized lobopodians. Ecdysis and hard cuticular protection are now well documented in the whole spectrum of early Cambrian ecdysozoans such as soft-bodied scalidophorans, lobopodians and fully articulated euarthropods. We hypothesize that the secretion of sclerotized cuticular elements periodically renewed via ecdysis was a key innovation that opened large-scale evolutionary opportunities to invertebrate animal life, specifically ecdysozoans, both in terms of anatomical functionalities and ecological success.

The pH is a crucial external factor affecting the structure and emulsification characteristics of proteins. The current study aimed to reveal the correlation between the secondary structure changes and tilapia protein isolate (TPI) emulsion stability under different pH (3.0–10.0) prepared by high-pressure homogenization. The results showed that TPI with significantly increased solubility and emulsifying properties when the pH keep away from the isoelectric point (pH 5.0). Meanwhile, TPI emulsions presented significantly enhanced stability (with decreased particle size, increased zeta potential, creaming index close to 0, and uniform dispersion of droplets) at pH 3.0 and 10.0. Interface-adsorbed protein mainly consists of a myosin-heavy chain and actin, and the secondary structure was significantly influenced by pH and high-pressure homogenization. The α-helix will be transformed into β-sheet and β-turn when pH is closer to pH 5.0. However, the high-pressure homogenization induced α-helix conversion to β-sheet. The correlation analysis revealed that emulsion stability is positively correlated with α-helix and negatively correlated with β-sheet. This work provides a deep insight into the correlation between secondary structure changes and the stability of TPI emulsion as affected by pH to offer an alternative way to enhance TPI emulsion stability.

IntroductionThe incidence of hemangioblastoma is low, constituting only 1-5% of all spinal cord tumors. Specifically, intradural extramedullary hemangioblastoma without Von Hippel-Lindau syndrome represents an exceedingly rare condition.MethodsWe report the first documented case of cervical intradural extramedullary hemangioblastoma in China. A 53-year-old male patient presented with a 3-year history of mild right hemiplegia, segmental muscle strength and sensation impairment, and a positive pyramidal tract sign. MRI showed an abnormal oval signal focus in the intradural and extramedullary region at the C6-C7 vertebral level. Before surgery, angiography was performed to identify the supplying arteries and draining veins. Subsequent interventional therapy achieved over 90% occlusion of blood vessels, creating optimal conditions for complete resection of the spinal tumor.ResultsThe patient demonstrated satisfactory postoperative recovery with significant restoration of sensory and motor functions. Pathological examination showed a significant upregulation of CD31 in tumor cells and a substantial presence of the neuro-specific marker S100 in the tumor stroma, consistent with the diagnostic criteria for spinal hemangioblastoma.ConclusionThe rarity of cervical intradural extramedullary hemangioblastoma without Von Hippel-Lindau syndrome was reaffirmed by a comprehensive review of the existing literature. Complete tumor resection remains the optimal approach for managing this uncommon condition, generally resulting in a favorable prognosis. Traditional open fenestration surgery is linked to elevated risks of bleeding and trauma. Meanwhile, endovascular injection of embolic agents may lead to residual lesions and an increased risk of recurrence. Therefore, we recommend a one-time combined treatment conducted in a hybrid operating room to achieve complete resection and effectively reduce intraoperative bleeding risk. Despite presenting challenges and requiring high proficiency, we still recommend this type of combined surgery as a suitable therapeutic option for such diseases.

ObjectiveTo characterize the gas production phenomenon in the animal model of left ventricular assist device (LVAD), and study its mechanism.MethodsAn in vitro bubble precipitation experiment was conducted, and the blood samples of Parma spp. animals were divided into ordinary group and oxygen-enriched group according to whether they were oxygenated or not at the time of blood collection, and a static control group was set up respectively. Blood gases were drawn and analyzed before and after the experiment. Activate the pump, and the number of air bubbles in the loop was measured by ultrasound at different rotational speeds; CFD was applied to simulate the flow field in the blood pump, and pressure, fluid velocity vector and shear force diagrams were plotted, and a thrombus model was constructed and the flow field was simulated and plotted as a cloud diagram.ResultsThere was a statistical difference in the number of bubbles in the inflow and outflow tubes of the blood pump (P values of 0.04 and 0.023, respectively), and the number of bubbles in the outflow tubes of both groups was significantly higher than the number of bubbles in the inflow tubes. The number of bubbles in the tubes of both the oxygen-enriched and normal groups was significantly higher than that in the inflow group. In both the normal and oxygen-enriched groups, more gas was produced at higher speeds than at lower speeds. Blood gas analysis showed that the reduced gas composition in the blood was mainly oxygen. Flow field simulation results: the high rotation speed group had lower central pressure and greater scalar shear. The thrombus simulation group was more prone to turbulence, sudden pressure changes, and greater shear than the normal group.ConclusionBlood gas production is associated with higher partial pressures of blood oxygen, higher rotation speed, and intrapump thrombosis, and the mechanism of pump gas production is degassing of dissolved gases rather than cavitation of water, and the gas released is most likely to have oxygen. The degassing phenomenon is an warning factor for pump thrombosis.

Abstract AURKA is an established target for cancer therapy; however, the efficacy of its inhibitors in clinical trials is hindered by differential response rates across different tumor subtypes. In this study, we demonstrate AURKA regulates amino acid synthesis, rendering it a vulnerable target in KEAP1-deficient non-small cell lung cancer (NSCLC). Through CRISPR metabolic screens, we identified that KEAP1-knockdown cells showed the highest sensitivity to the AURKA inhibitor MLN8237. Subsequent investigations confirmed that KEAP1 deficiency heightens the susceptibility of NSCLC cells to AURKA inhibition both in vitro and in vivo, with the response depending on NRF2 activation. Mechanistically, AURKA interacts with the eIF2α kinase GCN2 and maintains its phosphorylation to regulate eIF2α-ATF4-mediated amino acid biosynthesis. AURKA inhibition restrains the expression of asparagine synthetase (ASNS), making KEAP1-deficient NSCLC cells vulnerable to AURKA inhibitors, in which ASNS is highly expressed. Our study unveils the pivotal role of AURKA in amino acid metabolism and identifies a specific metabolic indication for AURKA inhibitors. These findings also provide a novel clinical therapeutic target for KEAP1-mutant/deficient NSCLC, which is characterized by resistance to radiotherapy, chemotherapy, and targeted therapy.

Background: Many colorectal cancer (CRC) patients are initially diagnosed at an advanced stage. Some evidence indicating that TNM staging may not be entirely reliable in forecasting survival outcomes. The research aims to develop accurate prediction models that can determine the survival outcomes of patients with clinically locally advanced colorectal cancer (LACRC). The study aims to provide valuable insights for clinical professionals to make right clinical decisions. Methods: We retrospectively analyzed 636 LACRC patients admitted to the General Hospital of Western Theater Command between Jan 1, 2017, and Dec 31, 2019. Significant factors determining the prognosis of LACRC patients screened by lasso regression and multifactorial cox regression analysis. These factors were utilized to develop a nomogram model, which serves as a valuable predictive tool for estimating the overall survival (OS) of LACRC patients. Next, we validated the nomogram in the validation group. Results: The nomogram emphasized that the TNM stage holds the most prognostic value, followed by CA19–9 levels, smoking history, and MLR. Multiple assessments confirmed the superior discriminatory ability of the nomograms. Conclusions: We have developed and verified nomograms that can predict OS cohort 635 LACRC patients. The survival nomogram may assist clinicians in better strategizing the therapeutic options for patients with LACRC.

Green and low-carbon development is an important part of global sustainable development. Green power trading provides strong support and assurance for promoting green and low-carbon development. Due to the long cycle of green power data chains and their susceptibility to malicious tampering, the integrity and traceability of data are difficult to guarantee. Therefore, this paper first proposes a security provenance model with enhanced relations based on the core structure of PROV and blockchain technology, which can securely capture provenance records, use the transfer time and number of transactions between various links in the traceability network as reasoning clues, realize the correlation tracing of the green electricity transfer process. Under the model, a traceability mechanism of green electricity is designed based on smart contracts. Trustworthy green electricity data collection is achieved through data filling and data verification techniques. Traceability query technique is adopted to achieve trustworthy traceability of green electricity. And the effectiveness of the proposed solution is demonstrated through simulation experiments.

With the swift advancement of cloud computing and the Internet of Things (IoT), to address the issue of massive data storage, IoT devices opt to offload their data to cloud servers so as to alleviate the pressure of resident storage and computation. However, storing local data in an outsourced database is bound to face the danger of tampering. To handle the above problem, a verifiable database (VDB), which was initially suggested in 2011, has garnered sustained interest from researchers. The concept of VDB enables resource-limited clients to securely outsource extremely large databases to untrusted servers, where users can retrieve database records and modify them by allocating new values, and any attempts at tampering will be detected. This paper provides a systematic summary of VDB. First, a definition of VDB is given, along with correctness and security proofs. And the VDB based on commitment constructions is introduced separately, mainly divided into vector commitments and polynomial commitments. Then VDB schemes based on delegated polynomial functions are introduced, mainly in combination with Merkle trees and forward-secure symmetric searchable encryption. We then classify the current VDB schemes relying on four different assumptions. Besides, we classify the established VDB schemes built upon two different groups. Finally, we introduce the applications and future development of VDB. To our knowledge, this is the first VDB review paper to date.

Abstract Cancer cell receives extracellular signal inputs to obtain a stem-like status, yet how tumor microenvironmental (TME) neural signals steer cancer stemness to establish the hierarchical tumor architectures remains elusive. Here, a pan-cancer transcriptomic screening for 10852 samples of 33 TCGA cancer types reveals that cAMP-responsive element (CRE) transcription factors are convergent activators for cancer stemness. Deconvolution of transcriptomic profiles, specification of neural markers and illustration of norepinephrine dynamics uncover a bond between TME neural signals and cancer-cell CRE activity. Specifically, neural signal norepinephrine potentiates the stemness of proximal cancer cells by activating cAMP-CRE axis, where ATF1 serves as a conserved hub. Upon activation by norepinephrine, ATF1 potentiates cancer stemness by coordinated trans-activation of both nuclear pluripotency factors MYC/NANOG and mitochondrial biogenesis regulators NRF1/TFAM, thereby orchestrating nuclear reprograming and mitochondrial rejuvenating. Accordingly, single-cell transcriptomes confirm the coordinated activation of nuclear pluripotency with mitochondrial biogenesis in cancer stem-like cells. These findings elucidate that cancer cell acquires stemness via a norepinephrine-ATF1 driven nucleus-mitochondria collaborated program, suggesting a spatialized stemness acquisition by hijacking microenvironmental neural signals.

Summary: The late Ediacaran Jiangchuan biota, from the Dengying Formation in eastern Yunnan, is well-known for its diverse macroalgal fossils, opening a window onto eukaryotic-dominated ecosystems from the late Neoproterozoic of South China. Although multiple lines of evidence suggest that metazoans had already evolved by the late Ediacaran, animal fossils have not yet been formally described from this locality. Here, we report a putative disc-shaped macrofossil from the Jiangchuan biota, Lobodiscus tribrachialis gen. et sp. nov. This specimen shows the triradial symmetry characteristic of trilobozoans, a group of Ediacaran macrofossils previously documented in Australia and Russia. Lobodiscus could record the youngest known occurrence of trilobozoans, strengthening taxonomic and ecological continuities between the Ediacaran “White Sea” and “Nama” assemblages. Our findings may expand the known paleogeographical distribution of trilobozoans and provide data for Ediacaran biostratigraphic correlations across the Yangtze block and globally, helping to track the diversification of early metazoan-grade organisms.

Abstract Purpose To investigate the correlation between tumor volume reduction rate (TVRR) and prognosis in patients with diverse clinical types of nasopharyngeal carcinoma (NPC) undergoing chemoradiotherapy, thereby aptly categorizing risks and directing the personalized treatment of NPC. Materials and Methods A total of 605 NPC patients with varying clinical types were enrolled in this study and subsequently segregated into six subgroups based on their clinical types and TVRR. To accentuate the efficacy of grouping, Groups 1–6 underwent clustered analysis of hazard atio (HR) values pertaining to progression‐free survival (PFS), forming three risk clusters denoted as low, intermediate, and high. The log‐rank test was employed to discern differences, and R 4.1.1 was utilized for cluster analysis. Results According to survival rates, we classified the first (G2 and G4), second (G1 and G6), and third (G3 and G5) risk clusters as low‐, intermediate‐, and high‐risk, respectively. When comparing risk stratification with the 8th edition of the TNM staging system, our classification exhibited superior predictive prognostic performance. Subgroup analysis of treatments for each risk cluster revealed that the PFS in the neoadjuvant chemotherapy (NACT) + concurrent chemoradiotherapy (CCRT) group surpassed that of the CCRT group significantly (p

Summary: Detecting visual features in the environment is crucial for animals’ survival. The superior colliculus (SC) is implicated in motion detection and processing, whereas how the SC integrates visual inputs from the two eyes remains unclear. Using in vivo electrophysiology, we show that mouse SC contains many binocular neurons that display robust ocular dominance (OD) plasticity in a critical period during early development, which is similar to, but not dependent on, the primary visual cortex. NR2A- and NR2B-containing N-methyl-D-aspartate (NMDA) receptors play an essential role in the regulation of SC plasticity. Blocking NMDA receptors can largely prevent the impairment of predatory hunting caused by monocular deprivation, indicating that maintaining the binocularity of SC neurons is required for efficient hunting behavior. Together, our studies reveal the existence and function of OD plasticity in SC, which broadens our understanding of the development of subcortical visual circuitry relating to motion detection and predatory hunting.

Abstract The diagnosis and classification of soft tissue sarcomas (STS) remain challenging because of the rarity and overlapping morphologic manifestations of diverse STS subtypes. Characteristic gene fusions are commonly detected in STS and represent useful diagnostic markers. This study established and validated a custom-designed RNA sequencing panel that identified 64 gene fusions in STS. The analytical performance validation yielded excellent accuracy, with 100% (95% CI, 94.40%-100%) sensitivity and 93.33% (95% CI, 68.05%-99.83%) specificity. Clinical performances were further confirmed with 145 clinical formalin-fixed and paraffin-embedded (FFPE) samples from STS patients. Fusions were detected in 40% of samples (58/145). The common fusions SS18-SSX family, EWSR1-related fusions, COL1A1-PDGFB, FOXO1-associated fusions, and FUS-associated fusions were identified in corresponding STS subtypes. The RNA panel detected specific fusions in several cases where no conclusive diagnosis can be made based on the morphology and immunohistochemistry results. Data collected in this study demonstrate that the RNA fusions panel can better classify STS subtypes and serve as a good supplement for histopathology, exhibiting a great potential for the STS precise diagnosis.

Drought monitoring is crucial for assessing and mitigating the impacts of water scarcity on various sectors and ecosystems. Although traditional drought monitoring relies on soil moisture data, remote sensing technology has have significantly augmented the capabilities for drought monitoring. This study aims to evaluate the accuracy and applicability of two temperature vegetation drought indices (TVDI), TVDINDVI and TVDIEVI, constructed using the Normalized Difference Vegetation Index (NDVI) and the Enhanced Vegetation Index (EVI) vegetation indices for drought monitoring. Using Guangdong Province as a case, enhanced versions of these indices, developed through Savitzky–Golay filtering and terrain correction were employed. Additionally, Pearson correlation analysis and F-tests were utilized to determine the suitability of the Standardized Precipitation Index (SPI) and the Standardized Precipitation Evapotranspiration Index (SPEI) in correlation with TVDINDVI and TVDIEVI. The results show that TVDINDVI had more meteorological stations passing both significance test levels (P

ObjectiveIn this study, we evaluated the role of a multidisciplinary team (MDT) in clinical practice for cervical cancer by analyzing the development of a single-case multidisciplinary consultation for cervical cancer.MethodsPatients in MDT consultations for cervical cancer were retrospectively analyzed for clinical information, decision content of MDT discussion, implementation, and follow-up results.ResultsOf the 392 patients who met the inclusion criteria, 359 had a first episode, of which 284 were stage IA-IIA2 (79.11%) and 75 were stage IIB-IVB (20.89%). Of these 392, 33 had a recurrence (8.42%). A total of 416 cases were analyzed, and neoadjuvant chemotherapy with surgery was recommended in 43 cases, of which 40 cases were implemented, and 36 of the 40 achieved the expected outcome. Surgical treatment was recommended in 241 cases, of which 226 underwent surgery, and 215 of them achieved the expected outcome. Radiotherapy was recommended in 31 cases, of which 26 cases underwent it, and 22 of them achieved the expected efficacy. Concurrent chemoradiotherapy was recommended in 57 cases, of which 49 underwent it, and 39 of them achieved the expected efficacy. Other treatments were recommended in 44 cases, of which 23 cases were implemented, and 10 of them achieved the expected efficacy, with statistically significant differences compared with cases without implementation (P 0.05). Some decisions were not fully implemented due to economic status and fear of certain treatments of the patient.ConclusionThe MDT plays an important role in clinical practice such as clinical staging, treatment plan, and the complete treatment management of patients with cervical cancer, which can significantly improve the near-term treatment effect, whereas its effect on a long-term prognosis needs further clinical observation and active exploration.

Abstract Background Aneurysm of basilar perforator was rarely reported in the literature. It is difficult to treat due to its small size and deep-seated location. Excessive treatment may cause complications that resulted from ischemic events of parent perforators. Therefore, it is important to make clinical strategy for such patients to improve the prognosis. Case presentation One case, who presented as spontaneous subarachnoid hemorrhage, despite the negative result in computed tomography angiography firstly, was diagnosed angiographically as a ruptured aneurysm of the basilar perforator. A good clinical outcome of the case was achieved during the follow-up after conservative observation for 2 months, as well as the disappearance of previous lesion from angiography. Conclusions Aneurysm located at perforator of basilar trunk was rare and difficult to treat. Conservative observation for certain cases with periodic angiography follow-up was considered in order to prevent the patients from potential iatrogenic effects.

Forest fires are one of the significant disturbances in forest ecosystems. It is essential to extract burned areas rapidly and accurately to formulate forest restoration strategies and plan restoration plans. In this work, we constructed decision trees and used a combination of differential normalized burn ratio (dNBR) index and OTSU threshold method to extract the heavily and mildly burned areas. The applicability of this method was evaluated with three fires in Muli County, Sichuan, China, and we concluded that the extraction accuracy of this method could reach 97.69% and 96.37% for small area forest fires, while the extraction accuracy was lower for large area fires, only 89.32%. In addition, the remote sensing environment index (RSEI) was used to evaluate the ecological environment changes. It analyzed the change of the RSEI level through the transition matrix, and all three fires showed that the changes in RSEI were stronger for heavily burned areas than for mildly burned areas, after the forest fire the ecological environment (RSEI) was reduced from good to moderate. These results realized the quantitative evaluation and dynamic evaluation of the ecological environment condition, providing an essential basis for the restoration, decision making and management of the affected forests.

Neurotrophic tyrosine receptor kinase (NTRK) rearrangements are oncogenic drivers of various types of adult and pediatric tumors, including gliomas. However, NTRK rearrangements are extremely rare in glioneuronal tumors. Here, we report a novel NTRK2 rearrangement in a 24-year-old female with dysembryoplastic neuroepithelial tumor (DNT), a circumscribed WHO grade I benign tumor associated with epilepsy. By utilizing targeted RNA next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), reverse transcriptase PCR (RT-PCR), and Sanger sequencing, we verified an in-frame fusion between NTRK2 and the lipoma HMGIC fusion partner-like 3 (LHFPL3). This oncogenic gene rearrangement involves 5’ LHFPL3 and 3’ NTRK2, retaining the entire tyrosine kinase domain of NTRK2 genes. Moreover, the targeted DNA NGS analysis revealed an IDH1 (p.R132H) mutation, a surprising finding in this type of tumor. The pathogenic mechanism of the LHFPL3::NTRK2 in this case likely involves aberrant dimerization and constitutive activation of RTK signaling pathways.

This study proposes a performance optimization scheme of liquid asphalt mixtures (LAMs) based on epoxy resin-based material modification and investigates its various performances. First, thermogravimetric analysis and headspace gas chromatography–mass spectrometry were used to analyze the differences between liquid asphalt before and after curing to clarify the formation mechanism of its adhesive force. Second, a molecular model was established. The best epoxy resin and curing agent types were evaluated using an improved Flory–Huggins model and the quantum computing method. Finally, two performance optimization schemes were established to reinforce the performance defects of the mixture caused by residual diluents. Results show that liquid asphalt solidification is a physical process of volatilization of diluents. Bisphenol A epoxy resin and a polyether amine curing agent are compatible with liquid asphalt and prone to curing reactions; thus, they are most suitable as epoxy resin-based modifiers. A solution obtained by adding 2% waterborne epoxy resin and 30% mineral powder replaced with cement can significantly improve the initial strength, strength generation rate, and low-temperature crack resistance of the LAM while optimizing high-temperature performance. This LAM modification can ensure that roads repaired using the modified LAM in a low-temperature environment can be quickly opened to use and improve the durability of the road surface.

Abstract Uncontrolled mitosis is one of the most important features of cancer, and mitotic kinases are thought to be ideal targets for anticancer therapeutics. However, despite numerous clinical attempts spanning decades, clinical trials for mitotic kinase-targeting agents have generally stalled in the late stages due to limited therapeutic effectiveness. Alisertib (MLN8237) is a promising oral mitotic aurora kinase A (AURKA, Aurora-A) selective inhibitor, which is currently under several clinical evaluations but has failed in its first Phase III trial due to inadequate efficacy. In this study, we performed genome-wide CRISPR/Cas9-based screening to identify vulnerable biological processes associated with alisertib in breast cancer MDA-MB-231 cells. The result indicated that alisertib treated cancer cells are more sensitive to the genetic perturbation of oxidative phosphorylation (OXPHOS). Mechanistic investigation indicated that alisertib treatment, as well as other mitotic kinase inhibitors, rapidly reduces the intracellular ATP level to generate a status that is highly addictive to OXPHOS. Furthermore, the combinational inhibition of mitotic kinase and OXPHOS by alisertib, and metformin respectively, generates severe energy exhaustion in mitotic cells that consequently triggers cell death. The combination regimen also enhanced tumor regression significantly in vivo. This suggests that targeting OXPHOS by metformin is a potential strategy for promoting the therapeutic effects of mitotic kinase inhibitors through the joint targeting of mitosis and cellular energy homeostasis.

The Changtang Nature Reserve, located in the hinterland of the Qinghai-Tibet Plateau, plays a crucial role in researching ecological and environmental assessment on the plateau. However, the severe natural conditions in the Changtang Plateau have resulted in the absence of meteorological observation stations within the reserve, thereby leading to a lack of fundamental ecological and environmental research data. Remote sensing technology presents an opportunity for ecological monitoring in the Changtang Nature Reserve. In this study, remote sensing ecological indices (RSEI) were utilized to evaluate the ecological environment of the reserve from 2000 to 2020. The MODIS data reconstructed using the Savitzky-Golay filter on the Google Earth Engine (GEE) platform were employed. Principal component analysis was then conducted to construct the RSEI. The results reveal that the overall ecological environment quality in the Changtang Nature Reserve between 2000 and 2020 was relatively poor. Over the past two decades, the mean RSEI of the reserve exhibited a fluctuating trend of decrease and increase, indicating a deteriorating and subsequently improving ecological environment quality. Specifically, during the period of 2000–2010, the RSEI mean decreased from 0.3197 to 0.2269, suggesting degradation of the ecological environment, and the proportion of areas classified as fair and poor increased by 51.99%, while the proportion of areas classified as good and excellent decreased by 32.69%. However, from 2010 to 2020, it increased from 0.2269 to 0.3180, indicating an improvement in the ecological environment, and the proportion of areas classified as good and excellent increased by 6.11%, while the proportion of areas classified as fair and poor decreased by 2.91%. Spatially, the core zone demonstrated higher ecological environment quality compared to the experimental and buffer zones. The findings of this study provide comprehensive and accurate information about the ecological environment, which supports management, decision-making, and emergency response efforts in the Changtang Nature Reserve. Moreover, it offers a scientific basis for conservation and sustainable development strategies in the reserve. The quantitative assessment of the ecological environment dynamics contributes to the understanding of the reserve’s ecological dynamics and facilitates informed decision-making for effective conservation and management practices.

Abstract Background Overexpression of Aurora‐A (AURKA) is a feature of breast cancer and associates with adverse prognosis. The selective Aurora‐A inhibitor alisertib (MLN8237) has recently demonstrated promising antitumor responses as a single agent in various cancer types but its phase III clinical trial was reported as a failure since MLN8237 did not show an apparent effect in prolonging the survival of patients. Thus, identification of potential targets that could enhance the activity of MLN8237 would provide a rationale for drug combination to achieve better therapeutic outcome. Methods Here, we conducted a systematic synthetic lethality CRISPR/Cas9 screening of 507 kinases using MLN8237 in breast cancer cells and identified a number of targetable kinases that displayed synthetic lethality interactions with MLN8237. Then, we performed competitive growth assays, colony formation assays, cell viability assays, apoptosis assays, and xenograft murine model to evaluate the synergistic therapeutic effects of Haspin (GSG2) depletion or inhibition with MLN8237. For mechanistic studies, immunofluorescence was used to detect the state of microtubules and the localization of Aurora‐B and mitotic centromere‐associated kinesin (MCAK). Results Among the hits, we observed that Haspin depletion or inhibition marginally inhibited breast cancer cell growth but could substantially enhance the killing effects of MLN8237. Mechanistic studies showed that co‐treatment with Aurora‐A and Haspin inhibitors abolished the recruitment of Aurora‐B and mitotic centromere‐associated kinesin (MCAK) to centromeres which were associated with excessive microtubule depolymerization, kinetochore‐microtubule (KT‐MT) attachment failure, and severe mitotic catastrophe. We further showed that the combination of MLN8237 and the Haspin inhibitor CHR‐6494 synergistically reduced breast cancer cell viability and significantly inhibited both in vitro and in vivo tumor growth. Conclusions These findings establish Haspin as a synthetic lethal target and demonstrate CHR‐6494 as a potential combinational drug for promoting the therapeutic effects of MLN8237 on breast cancer.

PurposeA combined model was established based on the MRI-radiomics of pre- and mid-treatment to assess the risk of disease progression or death in locally advanced nasopharyngeal carcinoma.Materials and MethodsA total of 243 patients were analyzed. We extracted 10,400 radiomics features from the primary nasopharyngeal tumors and largest metastatic lymph nodes on the axial contrast-enhanced T1 weighted and T2 weighted in pre- and mid-treatment MRI, respectively. We used the SMOTE algorithm, center and scale and box-cox, Pearson correlation coefficient, and LASSO regression to construct the pre- and mid-treatment MRI-radiomics prediction model, respectively, and the risk scores named P score and M score were calculated. Finally, univariate and multivariate analyses were used for P score, M score, and clinical data to build the combined model and grouped the patients into two risk levels, namely, high and low.ResultA combined model of pre- and mid-treatment MRI-radiomics successfully categorized patients into high- and low-risk groups. The log-rank test showed that the high- and low-risk groups had good prognostic performance in PFS (P

In recent years, the intersection of 3D printing and “smart” stimuli‐responsive materials has led to the development of 4D printing, an emerging field that is a subset of current additive manufacturing research. By integrating existing printing processes with novel materials, 4D printing enables the direct fabrication of sensors, controllable structures, and other functional devices. Compared to traditional manufacturing processes for smart materials, 4D printing permits a high degree of design freedom and flexibility in terms of printable geometry. An important branch of 4D printing concerns electroactive materials, which form the backbone of printable devices with practical applications throughout biology, engineering, and chemistry. Herein, the recent progress in the 4D printing of electroactive materials using several widely studied printing processes is reviewed. In particular, constituent materials and mechanisms for their preparation and printing are discussed, and functional electroactive devices fabricated using 4D printing are highlighted. Current challenges are also described and some of the many data‐driven opportunities for advancement in this promising field are presented.

Abstract Background Artiopodan euarthropods represent common and abundant faunal components in sites with exceptional preservation during the Cambrian. The Chengjiang biota in South China contains numerous taxa that are exclusively known from this deposit, and thus offer a unique perspective on euarthropod diversity during the early Cambrian. One such endemic taxon is the non-trilobite artiopodan Sinoburius lunaris, which has been known for approximately three decades, but few details of its anatomy are well understood due to its rarity within the Chengjiang, as well as technical limitations for the study of these fossils. Furthermore, the available material does not provide clear information on the ventral organization of this animal, obscuring our understanding of phylogenetically significant details such as the appendages. Results We employed X-ray computed tomography to study the non-biomineralized morphology of Sinoburius lunaris. Due to the replacement of the delicate anatomy with pyrite typical of Chengjiang fossils, computed tomography reveals substantial details of the ventral anatomy of Sinoburius lunaris, and allow us to observe in detail the three-dimensionally preserved appendicular organization of this taxon for the first time. The dorsal exoskeleton consists of a crescent-shaped head shield with well-developed genal spines, a thorax with seven freely articulating tergites, and a fused pygidium with lateral and median spines. The head bears a pair of ventral stalked eyes that are accommodated by dorsal exoskeletal bulges, and an oval elongate ventral hypostome. The appendicular organization of the head is unique among Artiopoda. The deutocerebral antennae are reduced, consisting of only five podomeres, and bear an antennal scale on the second podomere that most likely represents an exite rather than a true ramus. The head includes four post-antennal biramous limb pairs. The first two biramous appendages are differentiated from the rest. The first appendage pair consists of a greatly reduced endopod coupled with a greatly elongated exopod with a potentially sensorial function. The second appendage pair carries a more conventionally sized endopod, but also has an enlarged exopod. The remaining biramous appendages are homonomous in their construction, but decrease in size towards the posterior end of the body. They consist of a basipodite with ridge-like crescentic endites, an endopod with seven podomeres and a terminal claw, and a lamellae-bearing exopod with a slender shaft. Contrary to previous reports, we confirm the presence of segmental mismatch in Sinoburius lunaris, expressed as diplotergites in the thorax. Maximum parsimony and Bayesian phylogenetic analyses support the monophyly of Xandarellida within Artiopoda, and illuminate the internal relationships within this enigmatic clade. Our results allow us to propose a transformation series explaining the origin of archetypical xandarellid characters, such as the evolution of eye slits in Xandarella spectaculum and Phytophilaspis pergamena as derivates from the anterolateral notches in the head shield observed in Cindarella eucalla and Luohuilinella species. In this context, Sinoburius lunaris is found to feature several derived characters within the group, such as the secondary loss of eye slits and a high degree of appendicular tagmosis. Contrary to previous findings, our analyses strongly support close affinities between Sinoburius lunaris, Xandarella spectaculum and Phytophilaspis pergamena, although the precise relationships between these taxa are sensitive to different methodologies. Conclusions The revised morphology of Sinoburius lunaris, made possible through the use of computed tomography to resolve details of its three-dimensionally preserved appendicular anatomy, contributes towards an improved understanding of the morphology of this taxon and the evolution of Xandarellida more broadly. Our results indicate that Sinoburius lunaris possesses an unprecedented degree of appendicular tagmosis otherwise unknown within Artiopoda, with the implication that this iconic group of Palaeozoic euarthropods likely had a more complex ecology and functional morphology than previously considered. The application of computer tomographic techniques to the study of Chengjiang euarthropods holds exceptional promise for understanding the morphological diversity of these organisms, and also better reconstructing their phylogenetic relationships and evolutionary history.

BackgroundThe purpose was to develop and validate a nomogram for prediction on radiation-induced temporal lobe injury (TLI) in patients with nasopharyngeal carcinoma (NPC).MethodsThe prediction model was developed based on a primary cohort that consisted of 194 patients. The data was gathered from January 2008 to December 2010. Clinical factors associated with TLI and dose–volume histograms for 388 evaluable temporal lobes were analyzed. Multivariable logistic regression analysis was used to develop the predicting model, which was conducted by R software. The performance of the nomogram was assessed with calibration and discrimination. An external validation cohort contained 197 patients from January 2011 to December 2013.ResultsAmong the 391 patients, 77 patients had TLI. Prognostic factors contained in the nomogram were Dmax (the maximum point dose) of temporal lobe, D1cc (the maximum dose delivered to a volume of 1 ml), T stage, and neutrophil-to-lymphocyte ratios (NLRs). The Internal validation showed good discrimination, with a C-index of 0.847 [95%CI 0.800 to 0.893], and good calibration. Application of the nomogram in the external validation cohort still obtained good discrimination (C-index, 0.811 [95% CI, 0.751 to 0.870]) and acceptable calibration.ConclusionsThis study developed and validated a nomogram, which may be conveniently applied for the individualized prediction of TLI.

The mountainous vegetation is important to regional sustainable development. However, the topographic effect is the main obstacle to the monitoring of mountainous vegetation using remote sensing. Aiming to retrieve the reflectance of frequently-used red–green–blue and near-infrared (NIR) wavebands of rugged mountains for vegetation mapping, we developed a new integrated topographic correction (ITC) using the SCS + C correction and the shadow-eliminated vegetation index. The ITC procedure consists of image processing, data training, and shadow correction and uses a random forest machine learning algorithm. Our study using the Landsat 8 Operational Land Imager (OLI) multi-spectral images in Fujian province, China, showed that the ITC achieved high performance in topographic correction of regional mountains and in transferability from the sunny area of a scene to the shadow area of three scenes. The ITC-corrected multi-spectral image with an NIR–red–green composite exhibited flat features with impressions of relief and topographic shadow removed. The linear regression of corrected waveband reflectance vs. the cosine of the solar incidence angle showed an inclination that nearly reached the horizontal, and the coefficient of determination decreased to 0.00~0.01. The absolute relative errors of the cast shadow and the self-shadow all dramatically decreased to the range of 0.30~6.37%. In addition, the achieved detection rate of regional vegetation coverage for the three cities of Fuzhou, Putian, and Xiamen using the ITC-corrected images was 0.92~6.14% higher than that using the surface reflectance images and showed a positive relationship with the regional topographic factors, e.g., the elevation and slope. The ITC-corrected multi-spectral images are beneficial for monitoring regional mountainous vegetation. Future improvements can focus on the use of the ITC in higher-resolution imaging.