Molting in early Cambrian armored lobopodians.

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.

Secure traceability mechanism of green electricity based on smart contracts and provenance model.

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.

IoT data security in outsourced databases: A survey of verifiable database.

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.

Microsurgical Clipping of Multiple Intracranial Aneurysms via the Keyhole Approach.

BACKGROUND: Keyhole surgery has been widely used to clip various intracranial aneurysms. Here, the feasibility of microsurgical clipping of multiple intracranial aneurysms via the keyhole approach was further investigated. METHODS: The clinical data of 80 patients with multiple intracranial aneurysms treated with keyhole surgery were retrospectively analyzed. The patients included 25 males and 55 females, with an average age of 57.5 years. There were 13 patients with unruptured aneurysms, 67 patients with ruptured aneurysms (small aneurysms accounted for 52.2% of ruptured aneurysms), and a total of 198 aneurysms. A 4 cm incision and a bone hole of approximately 2.5 cm were used per craniotomy standards. Forty-eight cases were treated via the supraorbital keyhole approach, 45 cases via the pterional keyhole approach, and 3 cases via the interhemispheric keyhole approach. RESULTS: A bilateral and unilateral keyhole approach was applied in 18 and 62 cases, respectively. A total of 170 ipsilateral and 7 contralateral aneurysms were clipped. The complete clipping rate was 98.9%. During the follow-up period of 6-12 months after surgery, the Glasgow outcome scale score was 5 points in 74 cases, 4 points in 5 cases, and 3 points in 1 case. The prognosis was associated with the preoperative Hunt-Hess classification but not with the number of operative sides, the operation opportunity, or the number of clipped aneurysms. CONCLUSION: Early keyhole surgical clipping of multiple intracranial aneurysms is an effective treatment. Among ruptured aneurysms, small aneurysms are common and need attention and timely treatment.

AURKA emerges as a vulnerable target for KEAP1-deficient non-small cell lung cancer by activation of asparagine synthesis.

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.

Risk stratification of LA-NPC during chemoradiotherapy based on clinical classification and TVRR.

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 < 0.05). CONCLUSION: The reliance on clinical types and TVRR facilitates risk stratification of NPC during chemoradiotherapy, providing a foundation for physicians to tailor therapeutic strategies. Moreover, the risk cluster delineated for NPC patients during the mid-term of chemoradiotherapy stands as an independent prognostic factor for progression-free survival (PFS), overall survival (OS), distantmetastasis-free survival (DMFS), and local recurrence-free (LRRFS) posttreatment. Additionally, individuals in the high-risk cluster are recommended to undergo adjuvant chemotherapy after CCRT.

A putative triradial macrofossil from the Ediacaran Jiangchuan Biota.

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.

Intra-arterial microguidewire electrocoagulation to treat intracranial vascular diseases.

OBJECTIVE: To investigate the therapeutic effect of intra-arterial microguidewire electrocoagulation on intracranial vascular diseases. METHODS: Data from 10 patients with cerebral aneurysms between May 2018 and September 2022 were analysed. Patients were treated with endovascular coil embolisation and microguidewire electrocoagulation. XperCT scans were conducted to identify new intracranial haemorrhage, infarction and hydrocephalus. Follow-up examinations were conducted 1, 3, 6 and 12 months after discharge. RESULTS: After the patients received electrocoagulation for different durations, Raymond Grade 1 embolisation was achieved in all 10 patients. No complications, such as haemorrhage, infarction or hydrocephalus, were found during or after surgery. Ten patients were followed up for 6-12 months, and none had any symptoms or new neurological dysfunction 1 month after their operation. Among them, nine were followed up for 12 months, and digital subtraction angiography showed no recurrence of aneurysms or occlusion of parent arteries. CONCLUSION: Intra-arterial microguidewire electrocoagulation can be used as a supplementary treatment for cerebral aneurysms. In cases of incomplete lesion embolisation and cases where tamponade treatment cannot continue, immediate thrombosis may occur. Thus, intra-arterial microguidewire electrocoagulation can help achieve patients' treatment goals.

A developmental critical period for ocular dominance plasticity of binocular neurons in mouse superior colliculus.

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.

Temperature vegetation dryness index (TVDI) for drought monitoring in the Guangdong Province from 2000 to 2019.

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 < 0.001 and P < 0.05) compared to TVDIEVI, and the average Pearson'R correlation coefficient was slightly higher than that of TVDIEVI, indicating that TVDINDVI responded better to drought in Guangdong Province. Our conclusion reveals that drought-prone regions in Guangdong Province are concentrated in the Leizhou Peninsula in southern Guangdong and the Pearl River Delta in central Guangdong. We also analyzed the phenomenon of winter-spring drought in Guangdong Province over the past 20 years. The area coverage of different drought levels was as follows: mild drought accounted for 42% to 64.6%, moderate drought accounted for 6.96% to 27.92%, and severe drought accounted for 0.002% to 1.84%. In 2003, the winter-spring drought in the entire province was the most severe, with a drought coverage rate of up to 84.2%, while in 2009, the drought area coverage was the lowest, at 49.02%. This study offers valuable insights the applicability of TVDI, and presents a viable methodology for drought monitoring in Guangdong Province, underlining its significance to agriculture, environmental conservation, and socio-economic facets in the region.

Clinical analysis of decision implementation by a multidisciplinary team in cervical cancer cases in Ganzhou, China.

Objective: In 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. Methods: Patients in MDT consultations for cervical cancer were retrospectively analyzed for clinical information, decision content of MDT discussion, implementation, and follow-up results. Results: Of 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). MDT decisions were correlated with age; the younger the patients, the higher the implementation efficiency (P <0.05). The difference between MDT expectation in all implementation and partial implementation and age was statistically significant (P <0.05). No significant difference was found between age and MDT expectation in all not fully implemented decisions (P >0.05). Some decisions were not fully implemented due to economic status and fear of certain treatments of the patient. Conclusion: The 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.

Cancer cell employs a microenvironmental neural signal trans-activating nucleus-mitochondria coordination to acquire stemness.

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.

Comment on "Ultrastructure reveals ancestral vertebrate pharyngeal skeleton in yunnanozoans".

Tian et al. (Research Articles, 8 July 2022, abm2708) hypothesized that yunnanozoans are stem-group vertebrates on the basis of "cellular cartilage", "fibrillin microfibers", and "subchordal rod" associated with the branchial arches of yunnanozoans. However, we reject the presence of cellular cartilage, fibrillin, and the phylogenetic proposal of vertebrate affinities based on ultrastructure and morphology of yunnanozoans from more than 8000 specimens.

Spatiotemporal Investigation of Intercellular Heterogeneity via Multiple Photocaged Probes.

Intercellular heterogeneity occurs widely under both normal physiological environments and abnormal disease-causing conditions. Several attempts to couple spatiotemporal information to cell states in a microenvironment were performed to decipher the cause and effect of heterogeneity. Furthermore, spatiotemporal manipulation can be achieved with the use of photocaged/photoactivatable molecules. Here, we provide a platform to spatiotemporally analyze differential protein expression in neighboring cells by multiple photocaged probes coupled with homemade photomasks. We successfully established intercellular heterogeneity (photoactivable ROS trigger) and mapped the targets (directly ROS-affected cells) and bystanders (surrounding cells), which were further characterized by total proteomic and cysteinomic analysis. Different protein profiles were shown between bystanders and target cells in both total proteome and cysteinome. Our strategy should expand the toolkit of spatiotemporal mapping for elucidating intercellular heterogeneity.

Case report: emergent endovascular treatment for carotid cavernous fistulas presenting as intracranial hemorrhage.

Objectives: This study aimed to discuss the clinical characteristics and emergent endovascular treatment of carotid cavernous fistulas presenting as intracranial hemorrhage. Methods: The clinical data of five patients with carotid cavernous fistulas, who presented with intracranial hemorrhage and who were admitted from January 2010 to April 2017, were analyzed retrospectively, and the diagnoses were confirmed by head computed tomography. Digital subtraction angiography was carried out in all the patients for the diagnosis and further emergent endovascular procedures. All patients were followed up to assess the clinical outcomes. Results: In total, five patients harbored five mono-lateral lesions; two of them were obliterated by detachable balloons, two by detachable coils, and one by detachable coils and Onyx glue. Only one patient was cured by another detachable balloon in the second session, and the other four patients were cured in the first session. At the 3- to 10-year follow-up, there was no intracranial re-hemorrhage in any of the patients; there was no recurrence of symptoms; and delayed occlusion of the parent artery was noted in one case. Conclusion: Emergent endovascular therapy is indicated for carotid cavernous fistulas presenting as intracranial hemorrhage. Individualized treatment according to the characteristics of different lesions is safe and effective.

Establishing an RNA fusions panel in soft tissue sarcoma with clinical validation.

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.

A Nomogram for Optimizing Sarcopenia Screening in Community-dwelling Older Adults: AB3C Model.

OBJECTIVES: Sarcopenia is associated with significantly higher mortality risk, and earlier detection of sarcopenia has remarkable public health benefits. However, the model that predicts sarcopenia in the community has yet to be well identified. The study aimed to develop a nomogram for predicting the risk of sarcopenia and compare the performance with 3 sarcopenia screen models in community-dwelling older adults in China. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 966 community-dwelling older adults. METHODS: A total of 966 community-dwelling older adults were enrolled in the study, with 678 participants grouped into the Training Set and 288 participants grouped into the Validation Set according to a 7:3 randomization. Predictors were identified in the Training Set by univariate and multivariate logistic regression and then combined into a nomogram to predict the risk of sarcopenia. The performance of this nomogram was assessed by calibration, discrimination, and clinical utility. RESULTS: Age, body mass index, calf circumference, congestive heart failure, and chronic obstructive pulmonary disease were demonstrated to be predictors for sarcopenia. The nomogram (named as AB3C model) that was constructed based on these predictors showed excellent calibration and discrimination in the Training Set with an area under the receiver operating characteristic curve (AUC) of 0.930. The nomogram also showed perfect calibration and discrimination in the Validation Set with an AUC of 0.897. The clinical utility of the nomogram was supported by decision curve analysis. Comparing the performance with 3 sarcopenia screen models (SARC-F, Ishii, and Calf circumference), the AB3C model outperformed the other models regarding sensitivity and AUC. CONCLUSIONS AND IMPLICATIONS: AB3C model, an easy-to-apply and cost-effective nomogram, was developed to predict the risk of sarcopenia, which may contribute to optimizing sarcopenia screening in community settings.

Remote sensing technology for rapid extraction of burned areas and ecosystem environmental assessment.

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.

Rare adult pilocytic astrocytoma of the septum pellucidum with novel RIN2::BRAF fusion.

Pilocytic astrocytoma is mostly a pediatric tumor with the majority of patients under age 20. Although tumors can occur throughout neuraxis, most tumors are in the cerebellum and optic chiasm. Pilocytic astrocytoma in unusual locations is often associated with different genetic alterations than the classic KIAA1549::BRAF fusion. We report a rare adult pilocytic astrocytoma of the septum pellucidum that presented with progressive headache. A detailed genomic evaluation found a fusion between BRAF and a novel partner RIN2, a gene overexpressed in both low-grade glioma and glioblastoma. The RIN2::BRAF transcript encodes a chimeric protein containing a dimerization domain SH2 and an intact kinase domain, consistent with a prototypic oncogenic kinase rearrangement. In addition, we discuss the potential oncogenic mechanisms of BRAF signaling and its implication in targeted therapy with kinase inhibitors.