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Drug discovery is a sophisticated process that incorporates scientific innovations and cutting-edge technologies. Compared to traditional bioactivity-based screening methods, encoding and display technologies for combinatorial libraries have recently advanced from proof-of-principle experiments to promising tools for pharmaceutical hit discovery due to their high screening efficiency, throughput, and resource minimization. This review systematically summarizes the development history, typology, and prospective applications of encoding and displayed technologies, including phage display, ribosomal display, mRNA display, yeast cell display, one-bead one-compound, DNA-encoded, peptide nucleic acid-encoded, and new peptide-encoded technologies, and examples of preclinical and clinical translation. We discuss the progress of novel targeted therapeutic agents, covering a spectrum from small-molecule inhibitors and nonpeptidic macrocycles to linear, monocyclic, and bicyclic peptides, in addition to antibodies. We also address the pending challenges and future prospects of drug discovery, including the size of screening libraries, advantages and disadvantages of the technology, clinical translational potential, and market space. This review is intended to establish a comprehensive high-throughput drug discovery strategy for scientific researchers and clinical drug developers.

We administered a questionnaire to participants who received different vaccination regimens to evaluate the effectiveness of Ad5-vectored COVID-19 vaccines. The results showed that administration of intramuscular Ad5-nCoV provided 21.32% more protection against SARS-CoV-2 infection than that of the inactivated COVID-19 vaccine in people who had received only one type of COVID-19 vaccine. Furthermore, aerosolized Ad5-nCoV exhibited good protection, whether it was administered as a homologous booster to people vaccinated with the intramuscular Ad5-nCoV or as a heterologous booster to people vaccinated with inactivated COVID-19 vaccines. Our research indicates that Ad5-nCoV is an effective booster. This finding supports the future selection of COVID-19 immunization strategies.

Interpreting reservoir properties through log data and logging responses in complex strata is critical for efficient petroleum exploitation, particularly for metamorphic rocks. However, the unsatisfactory accuracy of such interpretations in complex reservoirs has hindered their widespread application, resulting in severe inconvenience. In this study, we proposed a multi-mineral model based on the least-square method and an optimal principle to interpret the logging responses and petrophysical properties of complex hydrocarbon reservoirs. We began by selecting the main minerals based on a comprehensive analysis of log data, X-ray diffraction, petrographic thin sections and scanning electron microscopy (SEM) for three wells in the Bozhong 19-6 structural zone. In combination of the physical properties of these minerals with logging responses, we constructed the multi-mineral model, which can predict the log curves, petrophysical properties and mineral profile. The predicted and measured log data are evaluated using a weighted average error, which shows that the multi-mineral model has satisfactory prediction performance with errors below 11% in most intervals. Finally, we apply the model to a new well “x” in the Bozhong 19-6 structural zone, and the predicted logging responses match well with measured data with the weighted average error below 11.8% for most intervals. Moreover, the lithology is dominated by plagioclase, K-feldspar, and quartz as shown by the mineral profile, which correlates with the lithology of the Archean metamorphic rocks in this region. It is concluded that the multi-mineral model presented in this study provides reasonable methods for interpreting log data in complex metamorphic hydrocarbon reservoirs and could assist in efficient development in the future.

BackgroundThere have been conflicting reports about the proarrhythmic risk of p-synephrine (SYN). To address this, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) combined with the microelectrode array (MEA) system have been utilized to assess arrhythmia risks, particularly in the context of adrenomimetic drugs.AimThis study aims to determine whether MEA recordings from hiPSC-CMs could predict the proarrhythmic risk of adrenomimetic drugs and to investigate the cardiovascular effects and mechanisms of SYN.Materials and methodsWe employed MEA recordings to assess the electrophysiological properties of hiPSC-CMs and conducted concentration-response analyses to evaluate the effects of SYN and Isoprenaline (ISO) on beating rate and contractility. A risk scoring system for proarrhythmic risks was established based on hiPSC-CMs in this study. ISO, a classic beta-adrenergic drug, was also evaluated. Furthermore, the study evaluated the risk of SYN and recorded the concentration-response of beating rate, contractility and the change in the presence or absence of selective β1, β2 and β3 adrenergic blockers.ResultsOur results suggested that ISO carries a high risk of inducing arrhythmias, aligning with existing literature. SYN caused a 30% prolongation of the field potential duration (FPD) at a concentration of 206.326 μM, a change significantly different from baseline measurements and control treatments. The half maximal effective concentration (EC50) of SYN (3.31 μM) to affect hiPSC-CM beating rate is much higher than that of ISO (18.00 nM). The effect of SYN at an EC50 of 3.31 μM is about ten times more potent in hiPSC-CMs compared to neonatal rat cardiomyocytes (34.12 μM). SYN increased the contractility of cardiomyocytes by 29.97 ± 11.65%, compared to ISO's increase of 50.56 ± 24.15%. β1 receptor blockers almost eliminated the beating rate increase induced by both ISO and SYN, while neither β2 nor β3 blockers had a complete inhibitory effect.ConclusionThe MEA and hiPSC-CM system could effectively predict the risk of adrenomimetic drugs. The study concludes that the proarrhythmia risk of SYN at conventional doses is low. SYN is more sensitive in increasing beating rate and contractility in human cardiomyocytes compared to rats, primarily activating β1 receptor.

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

Summary: Background: Primary health care is the foundation of high-performing health systems. Achieving an improved primary care system requires a thorough understanding of the current quality of care among various providers within the system. As the world's largest developing country, China has made significant investments in primary care over the past decade. This study evaluates the quality of primary care across different provider types in China, offering in-sights for enhancing China's primary care system. Methods: We merged data from four standardized patient (SP) research projects to compare the quality of five major primary care providers in China: rural clinics, county hospitals, migrant clinics, urban community health cen-ters (CHCs), and online platforms. We evaluated quality of care across process quality (e.g., checklist completion), diagnosis quality (e.g., diagnostic accuracy), and case management (e.g., correct medication), employing multiple regression analyses to explore quality differences by provider type, and their associations with physician characteristics. Findings: We document a poor quality of primary care in China, with no-table disparities across different providers. CHCs emerge as relatively reliable primary care providers in terms of process quality, diagnostic accuracy, and cor-rect medication prescriptions. Online platforms outpace rural clinics, county hospitals, and migrant clinics in many areas, showcasing their potential to en-hance access to quality healthcare resources in under-resourced rural regions. We observe a positive association between the qualifications of physicians and the quality of primary care, underscoring the necessity for a greater presence of more highly qualified practitioners. Interpretation: Primary care quality in China varies greatly among providers, reflecting inequalities in healthcare access. While online platforms indicate po-tential for improving care in under-resourced areas, their high referral rates suggest they cannot completely substitute traditional care. The findings em-phasize the need for more qualified practitioners and stringent regulation to enhance care quality and reduce unnecessary treatments. Funding: No founders had a role in the study design, data collection, data analysis, data interpretation, or writing of the report. We have acknowledged this in the revised manuscript.

Abstract The valence states and coordination structures of doped heterometal atoms in two‐dimensional (2D) nanomaterials lack predictable regulation strategies. Hence, a robust method is proposed to form unsaturated heteroatom clusters via the metal‐vacancy restraint mechanism, which can precisely regulate the bonding and valence state of heterometal atoms doped in 2D molybdenum disulfide. The unsaturated valence state of heterometal Pt and Ru cluster atoms form a spatial coordination structure with Pt–S and Ru–O–S as catalytically active sites. Among them, the strong binding energy of negatively charged suspended S and O sites for H+, as well as the weak adsorption of positively charged unsaturated heterometal atoms for H*, reduces the energy barrier of the hydrogen evolution reaction proved by theoretical calculation. Whereupon, the electrocatalytic hydrogen evolution performance is markedly improved by the ensemble effect of unsaturated heterometal atoms and highlighted with an overpotential of 84 mV and Tafel slope of 68.5 mV dec−1. In brief, this metal vacancy‐induced valence state regulation of heterometal can manipulate the coordination structure and catalytic activity of heterometal atoms doped in the 2D atomic lattice but not limited to 2D nanomaterials.

Abstract Over the past decade, the use of deep learning has been widely increasing in the medical image diagnosis field. Deep learning-based methods’ (DLMs) performance strongly relies on training data. Therefore, researchers often focus on collecting as much data as possible from different medical facilities or developing approaches to avoid the impact of inter-category imbalance (ICI), which means a difference in data quantity among categories. However, due to the ICI within each medical facility, medical data are often isolated and acquired in different settings among medical facilities, known as the issue of intra-source imbalance (ISI) characteristic. This imbalance also impacts the performance of DLMs but receives negligible attention. In this study, we study the impact of the ISI on DLMs by comparison of the version of a deep learning model that was trained separately by an intra-source imbalanced chest X-ray (CXR) dataset and an intra-source balanced CXR dataset for COVID-19 diagnosis. The finding is that using the intra-source imbalanced dataset causes a serious training bias, although the dataset has a good inter-category balance. In contrast, the deep learning model performed a reliable diagnosis when trained on the intra-source balanced dataset. Therefore, our study reports clear evidence that the intra-source balance is vital for training data to minimize the risk of poor performance of DLMs.

Abstract High‐performance organic neuromorphic devices with miniaturized device size and computing capability are essential elements for developing brain‐inspired humanoid intelligence technique. However, due to the structural inhomogeneity of most organic materials, downscaling of such devices to nanoscale and their high‐density integration into compact matrices with reliable device performance remain challenging at the moment. Herein, based on the design of a semicrystalline polymer PBFCL10 with ordered structure to regulate dense and uniform formation of conductive nanofilaments, we realize an organic synapse with the smallest device dimension of 50 nm and highest integration size of 1 Kb reported thus far. The as‐fabricated PBFCL10 synapses can switch between 32 conductance states linearly with a high cycle‐to‐cycle uniformity of 98.89% and device‐to‐device uniformity of 99.71%, which are the best results of organic devices. A mixed-signal neuromorphic hardware system based on the organic neuromatrix and FPGA controller is implemented to execute spiking‐plasticity‐related algorithm for decision-making tasks.

Abstract The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell‐surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non‐small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second‐generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first‐generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET‐targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next‐generation sequencing (NGS), reverse transcription‐polymerase chain reaction (RT‐PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.

Friction plays a critical role in dexterous robotic manipulation. However, realizing friction sensing remains a challenge due to the difficulty in designing sensing structures to decouple multi-axial forces. Inspired by the topological mechanics of knots, we construct optical fiber knot (OFN) sensors for slip detection and friction measurement. By introducing localized self-contacts along the fiber, the knot structure enables anisotropic responses to normal and frictional forces. By employing OFNs and a change point detection algorithm, we demonstrate adaptive robotic grasping of slipping cups. We further develop a robotic finger that can measure tri-axial forces via a centrosymmetric architecture composed of five OFNs. Such a tactile finger allows a robotic hand to manipulate human tools dexterously. This work could provide a straightforward and cost-effective strategy for promoting adaptive grasping, dexterous manipulation, and human-robot interaction with tactile sensing.

Biological databases serve as a global fundamental infrastructure for the worldwide scientific community, which dramatically aid the transformation of big data into knowledge discovery and drive significant innovations in a wide range of research fields. Given the rapid data production, biological databases continue to increase in size and importance. To build a catalog of worldwide biological databases, we curate a total of 5825 biological databases from 8931 publications, which are geographically distributed in 72 countries/regions and developed by 1975 institutions (as of September 20, 2022). We further devise a z-index, a novel index to characterize the scientific impact of a database, and rank all these biological databases as well as their hosting institutions and countries in terms of citation and z-index. Consequently, we present a series of statistics and trends of worldwide biological databases, yielding a global perspective to better understand their status and impact for life and health sciences. An up-to-date catalog of worldwide biological databases, as well as their curated meta-information and derived statistics, is publicly available at Database Commons (https://ngdc.cncb.ac.cn/databasecommons/).

Twenty years after the completion and forty years after the proposal of the Human Genome Project (HGP), genomics, together with its twin field — bioinformatics, has entered a new paradigm, where its bioscience-related, discipline-centric applications have been creating many new research frontiers. Beijing Institute of Genomics (BIG), now also known as China National Center for Bioinformation (CNCB), will play key roles in supporting and participating in these frontier research activities. On the 20th anniversary of the establishment of BIG, we provide a brief retrospective of its historic events and ascertain strategic research directions with a broader vision for future genomics, where digital genome, digital medicine, and digital health are so structured to meet the needs of human life and healthcare, as well as their related metaverses.

Abstract Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, and its incidence has been increasing in recent years. Due to the insidious onset and strong local invasiveness of MPM, most patients are diagnosed in the late stage and early screening and treatment for high‐risk populations are crucial. The treatment of MPM mainly includes surgery, chemotherapy, and radiotherapy. Immunotherapy and electric field therapy have also been applied, leading to further improvements in patient survival. The Mesothelioma Group of the Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) developed a national consensus on the clinical diagnosis and treatment of MPM based on existing clinical research evidence and the opinions of national experts. This consensus aims to promote the homogenization and standardization of MPM diagnosis and treatment in China, covering epidemiology, diagnosis, treatment, and follow‐up.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined refractory adult-onset autoinflammatory syndrome caused by somatic mutations in the ubiquitin-like modifier-activating enzyme 1 (UBA1) gene in hematopoietic stem and progenitor cells, resulting in a shift in UBA1 isoform expression. Thus, patients develop a spectrum of systemic inflammatory manifestations and hematologic symptoms. To date, patients respond poorly to immune suppressive drugs, except high-dose glucocorticoids, and no treatment guidelines have been established. Given the high mortality rate, VEXAS syndrome needs to be taken seriously by physicians in all specialties. This article aims to describe the key features, pathogenesis, and clinical manifestations of VEXAS syndrome to better understand the targeted treatment and improve the prognosis of VEXAS syndrome.

Background Hepatocellular carcinoma (HCC) is one of the leading causes of death from cancer worldwide. The histopathological features, risk factors, and prognosis of HCC caused by nonalcoholic fatty liver disease (NAFLD) appear to be significantly different from those of HCC caused by other etiologies of liver disease.

In the domain of space rendezvous and docking, visual navigation plays a crucial role. However, practical applications frequently encounter issues with poor image quality. Factors such as lighting uncertainties, spacecraft motion, uneven illumination, and excessively dark environments collectively pose significant challenges, rendering recognition and measurement tasks during visual navigation nearly infeasible. The existing image enhancement methods, while visually appealing, compromise the authenticity of the original images. In the specific context of visual navigation, space image enhancement’s primary aim is the faithful restoration of the spacecraft’s mechanical structure with high-quality outcomes. To address these issues, our study introduces, for the first time, a dedicated unsupervised framework named SpaceLight for enhancing on-orbit navigation images. The framework integrates a spacecraft semantic parsing network, utilizing it to generate attention maps that pinpoint structural elements of spacecraft in poorly illuminated regions for subsequent enhancement. To more effectively recover fine structural details within these dark areas, we propose the definition of a global structure loss and the incorporation of a pre-enhancement module. The proposed SpaceLight framework adeptly restores structural details in extremely dark areas while distinguishing spacecraft structures from the deep-space background, demonstrating practical viability when applied to visual navigation. This paper is grounded in space on-orbit servicing engineering projects, aiming to address visual navigation practical issues. It pioneers the utilization of authentic on-orbit navigation images in the research, resulting in highly promising and unprecedented outcomes. Comprehensive experiments demonstrate SpaceLight’s superiority over state-of-the-art low-light enhancement algorithms, facilitating enhanced on-orbit navigation image quality. This advancement offers robust support for subsequent visual navigation.

This paper proposes a novel nonlinear speed control method for permanent magnet synchronous motors that enhances their robustness and tracking performance. This technique integrates a sliding-mode disturbance observer and variable-gain fractional-order super-twisting sliding-mode control within a vector-control framework. The proposed control scheme employs a sliding-mode control method to mitigate chattering and improve dynamics by implementing fractional-order theory with a variable-gain super-twisting sliding manifold design while regulating the speed of the considered motor system. The aforementioned observer is suggested to enhance the control accuracy by estimating and compensating for the lumped disturbances. The proposed methodology demonstrates its superiority over other control schemes such as traditional sliding-mode control, super-twisting sliding-mode control, and the proposed technique. MATLAB/Simulink simulations and real-time implementation validate its performance, showing its potential as a reliable and efficient control approach for the system under study in practical applications.

ABSTRACT Melioidosis is a severe and often fatal infectious disease caused by Burkholderia pseudomallei, which poses significant challenges due to its high mortality rate and frequent misdiagnosis. To effectively treat infected patients, especially in epidemic regions like Hainan with a high resistance rate to ceftazidime (CAZ), early diagnosis and resistance testing are critical. Here, we designed a strategy that combines RNase-HII-dependent PCR with lateral flow strip assay (LFSA) for simultaneous detection of B. pseudomallei and its CAZ resistance mutation. In this strategy, we utilized rhPCR technology to design specific primers with a C3-spacer modification. These primers target a 115-base pair region within the ORF2 of the B. pseudomallei type III secretion system gene cluster, as well as the P174L mutation in the penA gene, which is a major mutation associated with CAZ resistance in Hainan. The primers contain complementary RNA bases that can be hydrolyzed only in the presence of thermostable RNase-HII enzymes, facilitating subsequent PCR reactions. Additionally, we introduced two pairs of universal probes carrying fluorescein isothiocyanate (FITC) and biotin, as well as digoxin and biotin. The sequences of these universal probes align with specific regions of the primers, resulting in target products labeled with different tags. The resulting amplification products are then subjected to LFSA, where the presence of specific markers is visually interpreted based on color development. These markers flow to test line 1 (T1) and are captured by a fixed anti-FITC antibody, generating a red line that indicates the presence of B. pseudomallei. Similarly, the occurrence of a red line on test line 2 (T2), which is fixed with anti-digoxin antibodies, indicates the presence of the P174L mutation in B. pseudomallei. This protocol serves as an excellent tool for the rapid diagnosis of melioidosis and provides a basis for selecting appropriate antibiotic medication. It has the potential to revolutionize the diagnosis of melioidosis, particularly in resource-limited settings. Furthermore, this technique holds promise as a versatile tool for disease diagnosis in general. IMPORTANCE This study focused on the development of a reaction system using rhPCR to amplify a specific gene, ORF2, of B. pseudomallei and to identify the P174L mutation associated with increased drug resistance to ceftazidime (CAZ). The system incorporated universal primer probes and a simple temperature cycle reaction. The amplified products were then analyzed using lateral flow strip assay (LFSA) for strain identification and mutation interpretation. The developed system provides a reliable basis for diagnosing melioidosis and selecting appropriate drugs. Its potential impact is particularly significant in resource-limited settings where access to advanced diagnostic techniques is limited. This platform stands out for its simplicity, convenience, sensitivity, specificity, and portability. It shows promise as a point-of-care testing method for detecting single nucleotide polymorphism in genes associated with other diseases. By leveraging the advantages of this platform, researchers and healthcare professionals can potentially expand its use beyond melioidosis and apply it to the rapid detection of genetic variations in other disease-related genes.

Abstract Background It has been reported that there are sex differences in plaque composition and hemodynamically significant stenosis. This study aimed to explore the impact of sex on cardiovascular risk factors for specific plaque compositions and hemodynamically significant stenosis. Methods Data regarding demographics and cardiovascular risk factors were collected. Hemodynamically significant stenosis was identified by a computed tomography-derived fractional flow reserve of ≤ 0.8. Associations among cardiovascular risk factors, plaque composition, and hemodynamically significant stenosis were assessed using a multivariate binary logistic regression analysis across sexes. The discriminating capacity of diverse plaque components for hemodynamically significant stenosis was assessed by area under the receiver-operating characteristics curve with 95% confidence intervals. Results A total of 1164 patients (489 men and 675 women) were included. For men, hyperlipidemia and cigarette smoking were risk factors for each plaque component (all P

Abstract Background Cardiomyocyte growth and differentiation rely on precise gene expression regulation, with epigenetic modifications emerging as key players in this intricate process. Among these modifications, N6-methyladenosine (m6A) stands out as one of the most prevalent modifications on mRNA, exerting influence over mRNA metabolism and gene expression. However, the specific function of m6A in cardiomyocyte differentiation remains poorly understood. Results We investigated the relationship between m6A modification and cardiomyocyte differentiation by conducting a comprehensive profiling of m6A dynamics during the transition from pluripotent stem cells to cardiomyocytes. Our findings reveal that while the overall m6A modification level remains relatively stable, the m6A levels of individual genes undergo significant changes throughout cardiomyocyte differentiation. We discovered the correlation between alterations in chromatin accessibility and the binding capabilities of m6A writers, erasers, and readers. The changes in chromatin accessibility influence the recruitment and activity of m6A regulatory proteins, thereby impacting the levels of m6A modification on specific mRNA transcripts. Conclusion Our data demonstrate that the coordinated dynamics of m6A modification and chromatin accessibility are prominent during the cardiomyocyte differentiation.

Li-air batteries have attracted extensive attention because of their ultrahigh theoretical energy density. However, the potential safety hazard of flammable organic liquid electrolytes hinders their practical applications. Replacing liquid electrolytes with solidstate electrolytes (SSEs) is expected to fundamentally overcome the safety issues. In this work, we focus on the development and challenge of solid-stateLi-air batteries (SSLABs). The rise of different types of SSEs, interfacial compatibility and verifiability in SSLABs are presented. The corresponding strategies and prospects of SSLABs are also proposed. In particular, combining machine learning method with experiment and in situ (or operando) techniques is imperative to accelerate the development of SSLABs.

Abstract Background Autism spectrum disorder (ASD) is a heritable condition related to brain development that affects a person’s perception and socialization with others. Here, we examined variability in the brain morphology in ASD children and adolescent individuals at the level of brain cortical structural profiles and the level of each brain regional measure. Methods We selected brain structural MRI data in 600 ASDs and 729 normal controls (NCs) from Autism Brain Imaging Data Exchange (ABIDE). The personalized estimate of similarity between gray matter volume (GMV) profiles of an individual to that of others in the same group was assessed by using the person-based similarity index (PBSI). Regional contributions to PBSI score were utilized for brain age gap estimation (BrainAGE) prediction model establishment, including support vector regression (SVR), relevance vector regression (RVR), and Gaussian process regression (GPR). The association between BrainAGE prediction in ASD and clinical performance was investigated. We further explored the related inter‐regional profiles of gene expression from the Allen Human Brain Atlas with variability differences in the brain morphology between groups. Results The PBSI score of GMV was negatively related to age regardless of the sample group, and the PBSI score was significantly lower in ASDs than in NCs. The regional contributions to the PBSI score of 126 brain regions in ASDs showed significant differences compared to NCs. RVR model achieved the best performance for predicting brain age. Higher inter-individual brain morphology variability was related to increased brain age, specific to communication symptoms. A total of 430 genes belonging to various pathways were identified as associated with brain cortical morphometric variation. The pathways, including short-term memory, regulation of system process, and regulation of nervous system process, were dominated mainly by gene sets for manno midbrain neurotypes. Limitations There is a sample mismatch between the gene expression data and brain imaging data from ABIDE. A larger sample size can contribute to the model training of BrainAGE and the validation of the results. Conclusions ASD has personalized heterogeneity brain morphology. The brain age gap estimation and transcription-neuroimaging associations derived from this trait are replenished in an additional direction to boost the understanding of the ASD brain.

Abstract Lung cancer screening using computed tomography (CT) has increased the detection rate of small pulmonary nodules and early-stage lung adenocarcinoma. It would be clinically meaningful to accurate assessment of the nodule histology by CT scans with advanced deep learning algorithms. However, recent studies mainly focus on predicting benign and malignant nodules, lacking of model for the risk stratification of invasive adenocarcinoma. We propose an ensemble multi-view 3D convolutional neural network (EMV-3D-CNN) model to study the risk stratification of lung adenocarcinoma. We include 1075 lung nodules (≤30 mm and ≥4 mm) with preoperative thin-section CT scans and definite pathology confirmed by surgery. Our model achieves a state-of-art performance of 91.3% and 92.9% AUC for diagnosis of benign/malignant and pre-invasive/invasive nodules, respectively. Importantly, our model outperforms senior doctors in risk stratification of invasive adenocarcinoma with 77.6% accuracy [i.e., Grades 1, 2, 3]). It provides detailed predictive histological information for the surgical management of pulmonary nodules. Finally, for user-friendly access, the proposed model is implemented as a web-based system ( https://seeyourlung.com.cn ).

Direct RNA sequencing using nanopore platform can be used to detect N6-methyladenosine (m6A) modifications on mRNAs. Here the authors systematically compare tools used for m6A detection from nanopore direct sequencing.

A new ternary compound, Mg11-xZnxSr in the Mg-Zn-Sr system was observed and studied using Scanning Electron Microscopy (SEM), Energy-Dispersive Spectroscope (EDS), X-Ray Diffraction (XRD) and Transmission Electron Microscopy (TEM). The XRD patterns were refined by the Rietveld refinement method and the results revealed that the crystallized Mg11-xZnxSr phase belonged to tetragonal I41/amd space group and had the Cd11Ba prototype. The Mg atoms were successfully doped into Zn11Sr crystal lattice by occupying Zn atomic sites. Moreover, the Rietveld refinement and computational results demonstrated a gradual decrease in the a-axis and c-axis lattice parameters with decreasing concentration levels of Mg coordination substitution in the lattice of Mg11-xZnxSr compound. The elastic constants and modulus of the Mg11-xZnxSr compounds calculated by first-principles calculations (FPC) indicated they were increased with the increasing of Zn content. The variation of hardness, d-band widths and the total density of states for Mg11-xZnxSr compounds with Zn content was discussed.

Abstract Viruses rely on hosts for life and reproduction, cause a variety of symptoms from common cold to AIDS to COVID-19 and provoke public health threats claiming millions of lives around the globe. RNA editing, as a crucial co-/post-transcriptional modification inducing nucleotide alterations on both endogenous and exogenous RNA sequences, exerts significant influences on virus replication, protein synthesis, infectivity and toxicity. Hitherto, a number of host-mediated RNA editing sites have been identified in diverse viruses, yet lacking a full picture of RNA editing-associated mechanisms and effects in different classes of viruses. Here we synthesize the current knowledge of host-mediated RNA editing in a variety of viruses by considering two enzyme families, viz., ADARs and APOBECs, thereby presenting a landscape of diverse editing mechanisms and effects between viruses and hosts. In the ongoing pandemic, our study promises to provide potentially valuable insights for better understanding host-mediated RNA editing on ever-reported and newly-emerging viruses.

Lineage-specific genes (LSGs) have long been postulated to play roles in the establishment of genetic barriers to intercrossing and speciation. In the genome of Neurospora crassa, most of the 670 Neurospora LSGs that are aggregated adjacent to the telomeres are clustered with 61% of the HET-domain genes, some of which regulate self-recognition and define vegetative incompatibility groups. In contrast, the LSG-encoding proteins possess few to no domains that would help to identify potential functional roles. Possible functional roles of LSGs were further assessed by performing transcriptomic profiling in genetic mutants and in response to environmental alterations, as well as examining gene knockouts for phenotypes. Among the 342 LSGs that are dynamically expressed during both asexual and sexual phases, 64% were detectable on unusual carbon sources such as furfural, a wildfire-produced chemical that is a strong inducer of sexual development, and the structurally-related furan 5-hydroxymethyl furfural (HMF). Expression of a significant portion of the LSGs was sensitive to light and temperature, factors that also regulate the switch from asexual to sexual reproduction. Furthermore, expression of the LSGs was significantly affected in the knockouts of adv-1 and pp-1 that regulate hyphal communication, and expression of more than one quarter of the LSGs was affected by perturbation of the mating locus. These observations encouraged further investigation of the roles of clustered lineage-specific and HET-domain genes in ecology and reproduction regulation in Neurospora, especially the regulation of the switch from the asexual growth to sexual reproduction, in response to dramatic environmental conditions changes.

Abstract Li6PS5Cl (LPSC) solid electrolytes, based on Argyrodite, have shown potential for developing high energy density and safe all‐solid‐state lithium metal batteries. However, challenges such as interfacial reactions, uneven Li deposition, and air instability remain unresolved. To address these issues, a simple and effective approach is proposed to design and prepare a solid electrolyte with unique structural features: Li6PS4Cl0.75‐OF0.25 (LPSC‐OF0.25) with protective LiF@Li2O nanoshells and F and O‐rich internal units. The LPSC‐OF0.25 electrolyte exhibits high ionic conductivity and the capability of “killing three birds with one stone” by improving the moist air tolerance, as well as the interface compatibility between the anode or cathode and the solid electrolyte. The improved performance is attributed to the peculiar morphology and the self‐generating and self‐healing interface coupling capability. When coupled with bare LiCoO2, the LPSC‐OF0.25 electrolyte enables stable operation under high cutoff voltage (≈4.65 V vs Li/Li+), thick cathodes (25 mg cm−2), and large current density (800 cycles at 2 mA cm−2). This rationally designed solid electrolyte offers promising prospects for solid‐state batteries with high energy and power density for future long‐range electric vehicles and aircrafts.

Gastrointestinal (GI) cancers are a heterogeneous group of primary solid tumors, arising in GI tract from the esophagus to rectum. Matrix stiffness (MS) is a critical physical factor for cancer progression; however, its importance in tumor progression remains to be comprehensively recognized. Herein, we conducted a comprehensive pan-cancer analysis of MS subtypes across seven GI-cancer types. Using unsupervised clustering based on literature-derived MS-specific pathway signatures, the GI-tumor samples were divided into three MS subtypes, termed as the Soft, Mixed and Stiff. Then, distinct prognoses, biological features, tumor microenvironments and mutation landscapes among three MS subtypes were revealed. The Stiff tumor subtype was associated with the poorest prognosis, the most malignant biological behaviors, and the immunosuppressive tumor stromal microenvironment. Furthermore, multiple machine learning algorithms were used to develop an 11-gene MS-signature to identify the MS subtypes of GI-caner and predict chemotherapy sensitivity, which were further validated in two external GI-cancer cohorts. This novel MS-based classification on GI-cancers could enhance our understanding of the important role of MS in tumor progression, and may have implications for the optimization of individualized cancer management.

AbstractAntrodia cinnamomea, an edible and medicinal fungus with significant economic value and application prospects, is rich in terpenoids, benzenoids, lignans, polysaccharides, and benzoquinone, succinic and maleic derivatives. In this study, the transcriptome of A. cinnamomea cultured on the wood substrates of Cinnamomum glanduliferum (YZM), C. camphora (XZM), and C. kanehirae (NZM) was sequenced using the high-throughput sequencing technology Illumina HiSeq 2000, and the data were assembled by de novo strategy to obtain 78,729 Unigenes with an N50 of 4,463 bp. Compared with public databases, about 11,435, 6,947, and 5,994 Unigenes were annotated to the Non-Redundant (NR), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genome (KEGG), respectively. The comprehensive analysis of the mycelium terpene biosynthesis-related genes in A. cinnamomea revealed that the expression of acetyl-CoA acetyltransferase (AACT), acyl-CoA dehydrogenase (MCAD), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), mevalonate pyrophosphate decarboxylase (MVD), and isopentenyl diphosphate isomerase (IDI) was significantly higher on NZM compared to the other two wood substrates. Similarly, the expression of geranylgeranyltransferase (GGT) was significantly higher on YZM compared to NZM and XZM, and the expression of farnesyl transferase (FTase) was significantly higher on XZM. Furthermore, the expressions of 2,3-oxidized squalene cyclase (OCS), squalene synthase (SQS), and squalene epoxidase (SE) were significantly higher on NZM. Overall, this study provides a potential approach to explore the molecular regulation mechanism of terpenoid biosynthesis in A. cinnamomea.

Abstract N 6-deoxyadenosine methylation (6mA) is the most widespread type of DNA modification in prokaryotes and is also abundantly distributed in some unicellular eukaryotes. However, 6mA levels are remarkably low in mammals. The lack of a precise and comprehensive mapping method has hindered more advanced investigations of 6mA. Here, we report a new method MM-seq (modification-induced mismatch sequencing) for genome-wide 6mA mapping based on a novel detection principle. We found that modified DNA bases are prone to form a local open region that allows capture by antibody, for example, via a DNA breathing or base-flipping mechanism. Specified endonuclease or exonuclease can recognize the antibody-stabilized mismatch-like structure and mark the exact modified sites for sequencing readout. Using this method, we examined the genomic positions of 6mA in bacteria (E. coli), green algae (C. reinhardtii), and mammalian cells (HEK239T, Huh7, and HeLa cells). In contrast to bacteria and green algae, human cells possess a very limited number of 6mA sites which are sporadically distributed across the genome of different cell types. After knocking out the RNA m6A methyltransferase METTL3 in mouse ES cells, 6mA becomes mostly diminished. Our results imply that rare 6mA in the mammalian genome is introduced by RNA m6A machinery via a non-targeted mechanism.

Background The comorbidity of cardiovascular disease (CVD) and depression has been well established, as depression usually presents simultaneously with CVD risk factors. However, the potential association between cumulative exposure to CVD risk and depression remains unclear, so we conducted the current investigation. To our knowledge, this is the first study that employs the cumulative risk model to examine the effect of CVD risk factors on depression using nationally representative population and gender, age and CVD status-stratified subpopulations.Aims To systematically study the possible individual and cumulative effect of 18 CVD risk factors on depression.Methods A cross-sectional, secondary analysis investigated associations between 18 CVD risk factors and depression. The interaction effect between CVD risk factors and age, gender and CVD status was also examined. Enrolment included 20 816 participants from the US National Health and Nutrition Examination Survey 2005–2016. Participants with Patient Health Questionnaire-9 scores over 15 or who were using an antidepressant were considered depressive; 18 known cardiovascular risk factors were incorporated in the present study.Results At the individual risk factor level, smoking, drinking, living alone, sleep quality, body mass index, waist circumference and diabetes status had differential associations with depression risk according to the gender, age or CVD status of the participants. Most importantly, gender-stratified cumulative risk analysis indicated that similar depression risk was found in both genders with a small number of CVD risk factors (odds ratio (OR)adjusted=1.32; 95% confidence interval (CI): 0.87 to 1.99), but females had a significantly higher depression risk compared with males under high cumulative risk exposure (ORadjusted=2.86; 95% CI: 1.79 to 4.59).Conclusions Clarifying the association of numerous CVD risk factors with depression according to gender, age and overall CVD status may be beneficial for risk stratification and the prevention of depression in clinical practice. Moreover, the observed novel evidence of high cumulative risk exposure-mediated gender disparities in depression risk may shed light on the underlying mechanism of females’ greater vulnerability to depression.

The metaverse, where the virtual and real world are fused, is currently under rapid development. Immersive and vivid experience in the metaverse requires human–machine interaction devices that, unlike those currently available, are simultaneously imperceptible, convenient to use, inexpensive, and safe. Herein, an optical‐nanofiber‐based gesture‐recognition wristband that can accurately recognize gestures and be used to interact with a robotic hand is proposed and realized. Requiring only three optical‐nanofiber‐based pressure sensors, the wristband is simple in structure, convenient to use, and remarkably imperceptible to the user. With the assistance of a machine‐learning algorithm, a maximum recognition accuracy of 94% is achieved for testers with different physiques. A robotic hand can be remotely controlled by the wristband through gestures. The wristband has broad application prospects and is a promising solution for advanced human–machine‐interaction devices. An interactive preprint version of the article can be found here: https://doi.org/10.22541/au.167022827.77928491/v1.

Introduction: Cancer selectivity, including targeted internalization and accelerated drug release in tumor cells, remains a major challenge for designing novel stimuli-responsive nanocarriers to promote therapeutic efficacy. The hypoxic microenvironment created by photodynamic therapy (PDT) is believed to play a critical role in chemoresistance.Methods: We construct dual-responsive carriers (DANPCT) that encapsulate the photosensitizer chlorin e6 (Ce6) and hypoxia-activated prodrug tirapazamine (TPZ) to enable efficient PDT and PDT-boosted hypoxia-activated chemotherapy.Results and discussion: Due to TAT masking, DANPCT prolonged payload circulation in the bloodstream, and selective tumor cell uptake occurred via acidity-triggered TAT presentation. PDT was performed with a spatially controlled 660-nm laser to enable precise cell killing and exacerbate hypoxia. Hypoxia-responsive conversion of the hydrophobic NI moiety led to the disassembly of DANPCT, facilitating TPZ release. TPZ was reduced to cytotoxic radicals under hypoxic conditions, contributing to the chemotherapeutic cascade. This work offers a sophisticated strategy for programmed chemo-PDT.

Abstract Excessive inflammatory responses contribute to the pathogenesis and lethality of highly pathogenic human coronaviruses, but the underlying mechanism remains unclear. In this study, the N proteins of highly pathogenic human coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), middle east respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were found to bind MASP-2, a key serine protease in the lectin pathway of complement activation, resulting in excessive complement activation by potentiating MBL-dependent MASP-2 activation, and the deposition of MASP-2, C4b, activated C3 and C5b-9. Aggravated inflammatory lung injury was observed in mice infected with adenovirus expressing the N protein. Complement hyperactivation was also observed in SARS-CoV-2-infected patients. Either blocking the N protein:MASP-2 interaction, MASP-2 depletion or suppressing complement activation can significantly alleviate N protein-induced complement hyperactivation and lung injury in vitro and in vivo. Altogether, these data suggested that complement suppression may represent a novel therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses.

Abstract Background Napsin B Aspartic Peptidase, Pseudogene (NAPSB) was associated with CD4 + T cell infiltration in pancreatic ductal adenocarcinoma. However, the biological role of NAPSB in hepatocellular carcinoma (HCC) remains to be determined. Methods The expression of NAPSB in HCC as well as its clinicopathological association were analyzed using data from several public datasets. qRT-PCR was used to verify the relative expression of NAPSB in patients with HCC using the Zhongnan cohort. Kaplan–Meier analyses, and univariate and multivariate Cox regression were conducted to determine the prognosis value of NAPSB on patients with HCC. Then enrichment analyses were performed to identify the possible biological functions of NAPSB. Subsequently, the immunological characteristics of NAPSB in the HCC tumor microenvironment (TME) were demonstrated comprehensively. The role of NAPSB in predicting hot tumors and its impact on immunotherapy and chemotherapy responses was also analyzed by bioinformatics methods. Results NAPSB was downregulated in patients with HCC and high NAPSB expression showed an improved survival outcome. Enrichment analyses showed that NAPSB was related to immune activation. NAPSB was positively correlated with immunomodulators, tumor-infiltrating immune cells, T cell inflamed score and cancer-immunity cycle, and highly expressed in immuno-hot tumors. High expression of NAPSB was sensitive to immunotherapy and chemotherapy, possibly due to its association with pyroptosis, apoptosis and necrosis. Conclusions NAPSB was correlated with an immuno-hot and inflamed TME, and tumor cell death. It can be utilized as a promising predictive marker for prognosis and therapy in HCC.

KaKs_Calculator 3.0 is an updated toolkit that is capable of calculating selective pressure on both coding and non-coding sequences. Similar to the nonsynonymous/synonymous substitution rate ratio for coding sequences, selection on non-coding sequences can be quantified as the ratio of non-coding nucleotide substitution rate to synonymous substitution rate of adjacent coding sequences. As testified on empirical data, KaKs_Calculator 3.0 shows effectiveness to detect the strength and mode of selection operated on molecular sequences, accordingly demonstrating its great potential to achieve genome-wide scan of natural selection on diverse sequences and identification of potentially functional elements at a whole-genome scale. The package of KaKs_Calculator 3.0 is freely available for academic use only at https://ngdc.cncb.ac.cn/biocode/tools/BT000001.

Chimeric antigen receptor (CAR)-T cell therapy is an innovative treatment for CD19-expressing lymphomas. CAR-T cells are primarily manufactured via lentivirus transfection or transposon electroporation. While anti-tumor efficacy comparisons between the two methods have been conducted, there is a current dearth of studies investigating the phenotypes and transcriptome alterations induced in T cells by the two distinct manufacturing methods. Here, we established CAR-T signatures using fluorescent imaging, flow cytometry, and RNA-sequencing. A small fraction of CAR-T cells that were produced using the PiggyBac transposon (PB CAR-T cells) exhibited much higher expression of CAR than those produced using a lentivirus (Lenti CAR-T cells). PB and Lenti CAR-T cells contained more cytotoxic T cell subsets than control T cells, and Lenti CAR-T cells presented a more pronounced memory phenotype. RNA-sequencing further revealed vast disparities between the two CAR-T cell groups, with PB CAR-T cells exhibiting greater upregulation of cytokines, chemokines, and their receptors. Intriguingly, PB CAR-T cells singularly expressed IL-9 and fewer cytokine release syndrome-associated cytokines when activated by target cells. In addition, PB CAR-T cells exerted faster in vitro cytotoxicity against CD19-expressing K562 cells but similar in vivo anti-tumor efficacy with Lenti CAR-T. Taken together, these data provide insights into the phenotypic alterations induced by lentiviral transfection or transposon electroporation and will attract more attention to the clinical influence of different manufacturing procedures.

Introduction As direct-to-consumer teleconsultation (hereafter referred to as ‘teleconsultation’) has gained popularity, an increasing number of patients have been leaving online reviews of their teleconsultation experiences. These reviews can help guide patients in identifying doctors for teleconsultation. However, few studies have examined the validity of online reviews in assessing the quality of teleconsultation against a gold standard. Therefore, we aim to use unannounced standardised patients (USPs) to validate online reviews in assessing both the technical and patient-centred quality of teleconsultations. We hypothesise that online review results will be more consistent with the patient-centred quality, rather than the technical quality, as assessed by the USPs.Methods and analysis In this cross-sectional study, USPs representing 11 common primary care conditions will randomly visit 253 physicians via the three largest teleconsultation platforms in China. Each physician will receive a text-based and a voice/video-based USP visit, resulting in a total of 506 USP visits. The USP will complete a quality checklist to assess the proportion of clinical practice guideline-recommended items during teleconsultation. After each visit, the USP will also complete the Patient Perception of Patient-Centeredness Rating. The USP-assessed results will be compared with online review results using the intraclass correlation coefficient (ICC). If ICC >0.4 (p

Background: Pyrotinib, a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor, shows encouraging anticancer activity and acceptable tolerability in multiple phase II and phase III randomized clinical trials, but the real-world data of pyrotinib, especially the outcomes in HER2-positive metastatic breast cancer, have been rarely reported. Here, we evaluated the treatment outcomes of pyrotinib in real-world practice in patients with HER2-positive metastatic breast cancer (MBC).Methods: This was a prospective, real-world, observational cohort study. Through the Breast Cancer Information Management System, HER-2 positive MBC patients treated with pyrotinib between 2017/06 and 2020/09 were included. Provider-reported objective response rate, progression-free survival (PFS), and overall survival (OS) were considered in the assessment of treatment outcomes. Tumor responses to pyrotinib treatment were calculated using RECIST 1.1. Adverse events were evaluated using clinical records.Results: The trial involved 113 individuals who were receiving pyrotinib treatment, with an average age of 51 years. Complete response, partial response and stable disease were observed in 9 (8.0%), 66 (58.4%), and 17 (15.0%) patients, respectively, while progressive disease was recorded in 20 (17.7%) patients. After a median follow-up of 17.2 months, the median PFS was 14.1. The most common adverse events of any grade were diarrhea (87.6%), vomiting (31.9%), and palmar-plantar erythrodysesthesia (26.6%). Among the patients with brain metastases, the median PFS and OS were 15.2 and 19.8 months, respectively. In addition, pyrotinib has similar efficacy in various subtypes of HER2-positive MBC patients, as shown by the lack of a significant difference of PFS and OS among pyrotinib-treated patients with or without brain metastases, or patients using pyrotinib as first-line, second-line, third-line or beyond therapies.Conclusion: Our real-world results demonstrated equivalent clinical efficacy in HER-2 positive MBC patients compared to phase II and phase III clinical trials with pyrotinib, and promising outcomes in patients with brain metastases.

Traditional Chinese medicine injection (TCMI) refers to the use of modern technology to make Chinese patent medicines in injectable forms, which shorten the onset time of the traditional Chinese medicine (TCM). Although there have been clinical cases in which Shenmai injection (SMI) was used to treat cardiovascular diseases (CVDs), there are no pharmacological experiments that investigate the efficacy of the drug in vitro or the underlying mechanisms. Aim of the study: We aimed to systemically evaluate the efficacy and investigate the mechanisms of SMI in modulating electrophysiology and calcium (Ca2+) signaling using a microelectrode array (MEA) and a genetically encoded Ca2+ indicator, GCaMP6s, respectively, in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Materials and methods: A MEA system was employed to record field potentials (FPs) in hiPSC-CMs. The QT interval is corrected by the RR interval, the reciprocal of the beating rate. GCaMP6s was used to measure Ca2+ signaling in hiPSC-CMs. Meanwhile, the transcriptome changes in hiPSC-CMs treated with 2% SMI were examined using RNAseq. In addition, the ingredients of SMI were investigated using liquid chromatography-mass spectrometry (LC-MS). Results: It was found that 0.5%, 1%, and 2% (v/v) SMIs could increase corrected QT (QTc) but did not change other FP parameters. GCaMP6s was successfully applied to measure the chronic function of SMI. The full width at half maximum (FWHM), rise time, and decay time significantly decreased after treatment with SMI for 1 h and 24 h, whereas an increased Ca2+ transient frequency was observed. Conclusions: We first used the Ca2+ indicator to measure the chronic effects of TCM. We found that SMI treatment can modulate electrophysiology and calcium signaling and regulate oxidative phosphorylation, cardiac muscle contraction, and the cell cycle pathway in hiPSC-CMs.

The rare edible and medicinal fungus Antrodia cinnamomea has a substantial potential for development. In this study, Illumina HiSeq 2000 was used to sequence its transcriptome. The results were assembled de novo, and 66,589 unigenes with an N50 of 4413 bp were obtained. Compared with public databases, 6,061, 3,257, and 2,807 unigenes were annotated to the Non-Redundant, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes databases, respectively. The genes related to terpene biosynthesis in the mycelia of A. cinnamomea were analyzed, and acetyl CoA synthase (ACS2 and ACS4), hydroxymethylglutaryl CoA reductase (HMGR), farnesyl transferase (FTase), and squalene synthase (SQS) were found to be upregulated in XZJ (twig of C. camphora) and NZJ (twig of C. kanehirae). Moreover, ACS5 and 2,3-oxidized squalene cyclase (OCS) were highly expressed in NZJ, while heme IX farnesyl transferase (IX-FIT) and ACS3 were significantly expressed in XZJ. The differential expression of ACS1, ACS2, HMGR, IX-FIT, SQS, and OCS was confirmed by real-time quantitative reverse transcription PCR. This study provides a new concept for the additional exploration of the molecular regulatory mechanism of terpenoid biosynthesis and data for the biotechnology of terpenoid production.

Luminescence bioimaging and biosensing in the second near‐infrared (NIR‐II) spectral window (1,000–1,700 nm wavelengths) is a newly emerging technique that is extensively used in fundamental research and clinical practice. Owing to its advantages, including deep tissue penetration and excellent temporal resolution, this technique has shown tremendous promise for target‐specific imaging and noninvasive monitoring. However, developing bioimaging modalities that enable target‐specific imaging with high resolution and sensitivity remains a great challenge today. Compared with NIR‐II fluorescence imaging, NIR‐II luminescence lifetime imaging with advantages such as lower background noises, higher sensitivity, and higher spatial resolution has opened up new avenues for deep tissue imaging and biomedical applications. Herein, various types of long‐lived NIR‐II luminescent probes, including complex dyes, rare‐earth‐doped nanoparticles, organic compound‐loaded nanoparticles, inorganic‐based dots and nanotubes, as well as the main types of time‐resolved luminescence techniques including time‐domain (e.g., time‐correlated single‐photon counting, time‐gated detection, pulse sampling, etc.) and frequency‐domain systems are first summarized. The unique advantages of long‐lived NIR‐II luminescent probes and their critical roles in bioimaging and biosensing are also highlighted. Finally, the present challenges and future directions of long‐lived NIR‐II luminescent probes in biomedical research, translational research, and (pre‐)clinical studies are discussed.

BackgroundDermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous tumor in children. Most published articles are sporadic or small series and lack systematically molecular analyses. The aim of our study is to better understand the clinicopathologic and genetic features of these rare lesions.MethodsAll patients diagnosed with DFSP aged ≤ 18 years were retrospectively reviewed from January 2006 to May 2022.ResultsA total of 66 cases (32 male and 34 female patients) were identified, with ages ranging from 0.3 to 18 years (median, 13 years). Tumor locations predominantly occurred on the trunk (38/66, 57.6%), followed by the extremities (20/66, 30.3%) and head/neck (8/66, 12.1%). Histological findings revealed classic (41/66, 62.1%), myxoid (4/66, 6.1%), pigmented (6/66, 9.1%), plaque-like (3/66, 4.5%), giant cell fibroblastoma (GCF; 6/66, 9.1%), and fibrosarcomatous (6/66, 9.1%) variants of DFSP. Immunochemistry revealed minority tumors (9/66, 13.6%) showing patchy or negative staining for CD34. Fluorescence in situ hybridization (FISH) indicated that 49 of 53 tested cases including all detected biopsy specimens (11/11) contained COL1A1-PDGFB fusion, in which the average copy number gain of COL1A1-PDGFB was 0.68. There were four cases negative for COL1A1-PDGFB rearrangement, one of which was found to harbor a novel COL3A1-PDGFB fusion by next-generation sequencing (NGS). Treatment for 63 patients comprised 40 marginal excisions and 23 wide local excisions (WLEs), including 1 with imatinib therapy. Follow-up information was available on 49 patients with a duration of 12–161 months (median, 60 months). Fourteen patients developed tumor recurrence, all with initial marginal excisions. The others survived with no evidence of disease.ConclusionsThis study of pediatric DFSP indicates certain discrepancies in clinicopathologic characteristics between children and adults. The majority of pediatric DFSPs contain COL1A1-PDGFB fusion, the same as their adult counterparts. The COL3A1-PDGFB chimerism might be associated with the special morphology of GCF, which needs further investigation. FISH is valuable in biopsy tissues and cases with atypical CD34 immunostaining, while supplementary NGS could be helpful to identify the cytogenetically cryptic DFSP. Overall, an urgent accurate diagnosis is needed to formulate an optimal therapeutic strategy in the pediatric population.

BackgroundThe shortage of medical resources in rural China reflects the health inequity in resource-limited settings, whereas telemedicine could provide opportunities to fill this gap. However, evidence of patient acceptance of telemedicine services from low- and middle-income countries is still lacking. ObjectiveWe aimed to understand the profile of patient end-user telemedicine use and identify factors influencing telemedicine service use in rural China. MethodsOur study followed a mixed methods approach, with a quantitative cross-sectional survey followed by in-depth semistructured interviews to describe telemedicine use and its associated factors among rural residents in Guangdong Province, China. In the quantitative analysis, explanatory variables included environmental and context factors, household-level factors, individual sociodemographic factors, access to digital health care, and health needs and demand factors. We conducted univariate and multivariate analyses using Firth logistic regression to examine the correlations of telemedicine uptake. A thematic approach was used, guided by the Social Cognitive Theory for the qualitative analysis. ResultsA total of 2101 households were recruited for the quantitative survey. With a mean age of 61.4 (SD 14.41) years, >70% (1364/2101, 72.94%) of the household respondents were male. Less than 1% (14/2101, 0.67%) of the respondents reported experience of using telemedicine. The quantitative results supported that villagers living with family members who had a fever in the past 2 weeks (adjusted odds ratio 6.96, 95% CI 2.20-21.98; P=.001) or having smartphones or computers (adjusted odds ratio 3.71, 95% CI 0.64-21.32; P=.14) had marginally higher telemedicine uptake, whereas the qualitative results endorse these findings. The results of qualitative interviews (n=27) also supplemented the potential barriers to telemedicine use from the lack of knowledge, trust, demand, low self-efficacy, and sufficient physical and social support. ConclusionsThis study found extremely low use of telemedicine in rural China and identified potential factors affecting telemedicine uptake. The main barriers to telemedicine adoption among rural residents were found, including lack of knowledge, trust, demand as well as low self-efficacy, and insufficient physical and social support. Our study also suggests strategies to facilitate telemedicine engagement in low-resource settings: improving digital literacy and self-efficacy, building trust, and strengthening telemedicine infrastructure support.

Air properties are very important for predicting the flow filed characteristics of aircraft. At present, Sutherland formula is always used to predict the flow filed characteristics of inflatable reentry decelerator. However, high temperature can be observed in high speed reentry flow around inflatable reentry decelerator, thus the Sutherland formula is not suitable for reentry flow simulation of inflatable reentry decelerator. In order to investigate the effect of the air properties on the flow filed characteristics of inflatable reentry decelerator, and provides the theoretical references for the inflatable reentry decelerator design, the Gupta fitting formula and Sutherland formula are used to describe the air properties, respectively, for studying the flow filed characteristics of inflatable reentry decelerator. The results show that the reentry flow temperature with Gupta fitting formula used is lower than that with Sutherland formula used, and the temperature difference is more obvious in the high inflow Mach number and temperature cases. The results in the windward of inflatable reentry decelerator show that the Sutherland formula underestimates the heat flux and pressure, and the heat flux difference is much more obvious. Such as case 5, the peak heat flux obtained by Gupta fitting formula is by 29% higher than that obtained by Sutherland formula.