Publication Trends and Hot Spots of ChatGPT's Application in the Medicine.

This study aimed to analyze the current landscape of ChatGPT application in the medical field, assessing the current collaboration patterns and research topic hotspots to understand the impact and trends. By conducting a search in the Web of Science, we collected literature related to the applications of ChatGPT in medicine, covering the period from January 1, 2000 up to January 16, 2024. Bibliometric analyses were performed using CiteSpace (V6.2., Drexel University, PA, USA) and Microsoft Excel (Microsoft Corp.,WA, USA) to map the collaboration among countries/regions, the distribution of institutions and authors, and clustering of keywords. A total of 574 eligible articles were included, with 97.74% published in 2023. These articles span various disciplines, particularly in Health Care Sciences Services, with extensive international collaboration involving 73 countries. In terms of countries/regions studied, USA, India, and China led in the number of publications. USA ot only published nearly half of the total number of papers but also exhibits a highest collaborative capability. Regarding the co-occurrence of institutions and scholars, the National University of Singapore and Harvard University held significant influence in the cooperation network, with the top three authors in terms of publications being Wiwanitkit V (10 articles), Seth I (9 articles), Klang E (7 articles), and Kleebayoon A (7 articles). Through keyword clustering, the study identified 9 research theme clusters, among which "digital health"was not only the largest in scale but also had the most citations. The study highlights ChatGPT's cross-disciplinary nature and collaborative research in medicine, showcasing its growth potential, particularly in digital health and clinical decision support. Future exploration should examine the socio-economic and cultural impacts of this trend, along with ChatGPT's specific technical uses in medical practice.

Case report: Decreased hemoglobin and multiple organ failure caused by ceftizoxime-induced immune hemolytic anemia in a Chinese patient with malignant rectal cancer.

Background: Drug-induced immune hemolytic anemia (DIIHA) is a rare but serious condition, with an estimated incidence of one in 100,000 cases, associated with various antibiotics. This study reports on a case of ceftizoxime-induced hemolysis observed in a patient in China. Case description: A Chinese patient diagnosed with malignant rectal cancer underwent antimicrobial therapy after laparoscopic partial recto-sigmoid resection (L-Dixon). After receiving four doses of ceftizoxime, the patient developed symptoms including rash, itchy skin, and chest distress, followed by a rapid decline in hemoglobin levels, the presence of hemoglobin in the urine (hemoglobinuria), renal failure, and disseminated intravascular coagulation. Laboratory analysis revealed high-titer antibodies against ceftizoxime and red blood cells (RBCs) in the patient's serum, including immunoglobulin M (IgM) (1:128) antibodies and immunoglobulin G (IgG) (1:8) antibodies, with noted crossreactivity to ceftriaxone. Significant improvement in the patient's hemolytic symptoms was observed following immediate discontinuation of the drug, two plasma exchanges, and extensive RBC transfusion. Conclusion: This case, together with previous reports, underscores the importance of considering DIIHA in patients who exhibit unexplained decreases in hemoglobin levels following antibiotic therapy. A thorough examination of the patient's medical history can provide crucial insights for diagnosing DIIHA. The effective management of DIIHA includes immediate cessation of the implicated drug, plasma exchange, and transfusion support based on the identification of specific drug-dependent antibodies through serological testing.

Scalable Customization of Crystallographic Plane Controllable Lithium Metal Anodes for Ultralong-Lasting Lithium Metal Batteries.

A formidable challenge to achieve the practical applications of rechargeable lithium (Li) metal batteries (RLMBs) is to suppress the uncontrollable growth of Li dendrites. One of the most effective solutions is to fabricate Li metal anodes with specific crystal plane, but still lack of a simple and high-efficient approach. Herein, a facile and controllable way for the scalable customization of polished Li metal anodes with highly preferred (110) and (200) crystallographic orientation (donating as polished Li(110) and polished Li(200), respectively) by regulating the times of accumulative roll bonding, is reported. According to the inherent characteristics of polished Li(110)/Li(200), the influence of Li atomic structure on the electrochemical performance of RLMBs is deeply elucidated by combining theoretical calculations with relative experimental proofs. In particular, a polished Li(110) crystal plane is demonstrated to induce Li+ uniform deposition, promoting the formation of flat and dense Li deposits. Impressively, the polished Li(110)||LiFePO4 full cells exhibit unprecedented cycling stability with 10 000 cycles at 10 C almost without capacity degradation, indicating the great potential application prospect of such textured Li metal. More valuably, this work provides an important reference for low-cost, continued, and large-scale production of Li metal anodes with highly preferred crystal orientation through roll-to-roll manufacturability.

N2 cleavage by silylene and formation of H2Si(µ-N)2SiH2.

Fixation and functionalisation of N2 by main-group elements has remained scarce. Herein, we report a fixation and cleavage of the N ≡ N triple bond achieved in a dinitrogen (N2) matrix by the reaction of hydrogen and laser-ablated silicon atoms. The four-membered heterocycle H2Si(µ-N)2SiH2, the H2SiNN(H2) and HNSiNH complexes are characterized by infrared spectroscopy in conjunction with quantum-chemical calculations. The synergistic interaction of the two SiH2 moieties with N2 results in the formation of final product H2Si(µ-N)2SiH2, and theoretical calculations reveal the donation of electron density of Si to π* antibonding orbitals and the removal of electron density from the π bonding orbitals of N2, leading to cleave the non-polar and strong NN triple bond.

Isolation and identification of milk-clotting proteases from Prinsepia utilis Royle and its application in cheese processing.

The aim of this study was to isolate and identify the main milk-clotting proteases from Prinsepia utilis Royle. Protein isolates obtained using precipitation with 20 %-50 % ammonium sulfate (AS) showed higher milk-clotting activity (MCA) at 154.34 + 0.35 SU. Two milk-clotting proteases, namely P191 and P1831, with molecular weight of 49.665 kDa and 68.737 kDa, respectively, were isolated and identified using liquid chromatography-mass spectrometry (LC-MS/MS). Bioinformatic analysis showed that the two identified milk-clotting proteases were primarily involved in hydrolase activity and catabolic processes. Moreover, secondary structure analysis showed that P191 structurally consisted of 40.85 % of alpha-helices, 15.96 % of beta-strands, and 43.19 % of coiled coil motifs, whereas P1831 consisted of 70 % of alpha-helices, 7.5 % of beta-strands, and 22.5 % of coiled coil motifs. P191 and P1831 were shown to belong to the aspartic protease and metalloproteinase types, and exhibited stability within the pH range of 4-6 and good thermal stability at 30-80 °C. The addition of CaCl2 (<200 mg/L) increased the MCA of P191 and P1831, while the addition of NaCl (>3 mg/mL) inhibited their MCA. Moreover, P191 and P1831 preferably hydrolyzed kappa-casein, followed by alpha-casein, and to a lesser extent beta-casein. Additionally, cheese processed with the simultaneous use of the two proteases isolated in the present study exhibited good sensory properties, higher protein content, and denser microstructure compared with cheese processed using papaya rennet or calf rennet. These findings unveil the characteristics of two proteases isolated from P. utilis, their milk-clotting properties, and potential application in the cheese-making industry.

Nanobody activator improves sensitivity of the von Willebrand factor activity assay to multimer size.

BACKGROUND: The activity of von Willebrand factor (VWF) in facilitating platelet adhesion and aggregation correlates with its multimer size. Traditional ristocetin-dependent functional assays lack sensitivity to multimer sizes. Recently, nanobodies targeting the autoinhibitory module and activating VWF were identified. OBJECTIVES: To develop an assay that can differentiate the platelet-binding activity of VWF multimers. METHODS: A novel enzyme-linked immunosorbent assay (nanobody-triggered glycoprotein Ib binding assay [VWF:GPIbNab]) utilizing a VWF-activating nanobody was developed. Recombinant VWF, plasma-derived VWF (pdVWF), and selected gel-filtrated fractions of pdVWF were evaluated for VWF antigen and activity levels. A linear regression model was developed to estimate the specific activity of VWF multimers. RESULTS: Of the 3 activating nanobodies tested, 6C11 with the lowest activation effect exhibited the highest sensitivity for high-molecular-weight multimers (HMWMs) of VWF. VWF:GPIbNab utilizing 6C11 (VWF:GPIbNab6C11) produced significantly higher activity/antigen ratios for recombinant VWF (>2.0) and HMWM-enriched pdVWF fractions (>2.0) than for pdVWF (∼1.0) or fractions enriched with shorter multimers (<1.0). The differences were much larger than those produced by VWF:GPIbNab utilizing other nanobodies, VWF:GPIbM, VWF:GPIbR, or VWF:CB assays. Linear regression analysis of 5 pdVWF fractions of various multimer sizes produced an estimated specific activity of 2.7 for HMWMs. The analysis attributed >90% of the VWF activity measured by VWF:GPIbNab6C11 to that of HMWMs, which is significantly higher than all other activity assays tested. CONCLUSION: The VWF:GPIbNab6C11 assay exhibits higher sensitivity to HMWMs than ristocetin-based and collagen-binding assays. Future studies examining the application of this assay in clinical settings and any associated therapeutic benefit of doing so are warranted.

Computer-assisted three-dimensional individualized extreme liver resection for hepatoblastoma in proximity to the major liver vasculature.

BACKGROUND: The management of hepatoblastoma (HB) becomes challenging when the tumor remains in close proximity to the major liver vasculature (PMV) even after a full course of neoadjuvant chemotherapy (NAC). In such cases, extreme liver resection can be considered a potential option. AIM: To explore whether computer-assisted three-dimensional individualized extreme liver resection is safe and feasible for children with HB who still have PMV after a full course of NAC. METHODS: We retrospectively collected data from children with HB who underwent surgical resection at our center from June 2013 to June 2023. We then analyzed the detailed clinical and three-dimensional characteristics of children with HB who still had PMV after a full course of NAC. RESULTS: Sixty-seven children diagnosed with HB underwent surgical resection. The age at diagnosis was 21.4 ± 18.8 months, and 40 boys and 27 girls were included. Fifty-nine (88.1%) patients had a single tumor, 39 (58.2%) of which was located in the right lobe of the liver. A total of 47 patients (70.1%) had PRE-TEXT III or IV. Thirty-nine patients (58.2%) underwent delayed resection. After a full course of NAC, 16 patients still had close PMV (within 1 cm in two patients, touching in 11 patients, compressing in four patients, and showing tumor thrombus in three patients). There were 6 patients of tumors in the middle lobe of the liver, and four of those patients exhibited liver anatomy variations. These 16 children underwent extreme liver resection after comprehensive preoperative evaluation. Intraoperative procedures were performed according to the preoperative plan, and the operations were successfully performed. Currently, the 3-year event-free survival of 67 children with HB is 88%. Among the 16 children who underwent extreme liver resection, three experienced recurrence, and one died due to multiple metastases. CONCLUSION: Extreme liver resection for HB that is still in close PMV after a full course of NAC is both safe and feasible. This approach not only reduces the necessity for liver transplantation but also results in a favorable prognosis. Individualized three-dimensional surgical planning is beneficial for accurate and complete resection of HB, particularly for assessing vascular involvement, remnant liver volume and anatomical variations.

Light-induced giant enhancement of nonreciprocal transport at KTaO3-based interfaces.

Nonlinear transport is a unique functionality of noncentrosymmetric systems, which reflects profound physics, such as spin-orbit interaction, superconductivity and band geometry. However, it remains highly challenging to enhance the nonreciprocal transport for promising rectification devices. Here, we observe a light-induced giant enhancement of nonreciprocal transport at the superconducting and epitaxial CaZrO3/KTaO3 (111) interfaces. The nonreciprocal transport coefficient undergoes a giant increase with three orders of magnitude up to 105 A-1 T-1. Furthermore, a strong Rashba spin-orbit coupling effective field of 14.7 T is achieved with abundant high-mobility photocarriers under ultraviolet illumination, which accounts for the giant enhancement of nonreciprocal transport coefficient. Our first-principles calculations further disclose the stronger Rashba spin-orbit coupling strength and the longer relaxation time in the photocarrier excitation process, bridging the light-property quantitative relationship. Our work provides an alternative pathway to boost nonreciprocal transport in noncentrosymmetric systems and facilitates the promising applications in opto-rectification devices and spin-orbitronic devices.

Observation of giant non-reciprocal charge transport from quantum Hall states in a topological insulator.

Symmetry breaking in quantum materials is of great importance and can lead to non-reciprocal charge transport. Topological insulators provide a unique platform to study non-reciprocal charge transport due to their surface states, especially quantum Hall states under an external magnetic field. Here we report the observation of non-reciprocal charge transport mediated by quantum Hall states in devices composed of the intrinsic topological insulator Sn-Bi1.1Sb0.9Te2S, which is attributed to asymmetric scattering between quantum Hall states and Dirac surface states. A giant non-reciprocal coefficient of up to 2.26 × 105 A-1 is found. Our work not only reveals the properties of non-reciprocal charge transport of quantum Hall states in topological insulators but also paves the way for future electronic devices.

3D human pose data augmentation using Generative Adversarial Networks for robotic-assisted movement quality assessment.

In the realm of human motion recognition systems, the augmentation of 3D human pose data plays a pivotal role in enriching and enhancing the quality of original datasets through the generation of synthetic data. This augmentation is vital for addressing the current research gaps in diversity and complexity, particularly when dealing with rare or complex human movements. Our study introduces a groundbreaking approach employing Generative Adversarial Networks (GANs), coupled with Support Vector Machine (SVM) and DenseNet, further enhanced by robot-assisted technology to improve the precision and efficiency of data collection. The GANs in our model are responsible for generating highly realistic and diverse 3D human motion data, while SVM aids in the effective classification of this data. DenseNet is utilized for the extraction of key features, facilitating a comprehensive and integrated approach that significantly elevates both the data augmentation process and the model's ability to process and analyze complex human movements. The experimental outcomes underscore our model's exceptional performance in motion quality assessment, showcasing a substantial improvement over traditional methods in terms of classification accuracy and data processing efficiency. These results validate the effectiveness of our integrated network model, setting a solid foundation for future advancements in the field. Our research not only introduces innovative methodologies for 3D human pose data enhancement but also provides substantial technical support for practical applications across various domains, including sports science, rehabilitation medicine, and virtual reality. By combining advanced algorithmic strategies with robotic technologies, our work addresses key challenges in data augmentation and motion quality assessment, paving the way for new research and development opportunities in these critical areas.

Mechanism study on the influences of buffer osmotic pressure on microfluidic chip-based cell electrofusion.

Cell electrofusion is a key process in many research fields, such as genetics, immunology, and cross-breeding. The electrofusion efficiency is highly dependent on the buffer osmotic pressure properties. However, the mechanism by which the buffer osmotic pressure affects cell electrofusion has not been theoretically or numerically understood. In order to explore the mechanism, the microfluidic structure with paired arc micro-cavities was first evaluated based on the numerical analysis of the transmembrane potential and the electroporation induced on biological cells when the electrofusion was performed on this structure. Then, the numerical model was used to analyze the effect of three buffer osmotic pressures on the on-chip electrofusion in terms of membrane tension and cell size. Compared to hypertonic and isotonic buffers, hypotonic buffer not only increased the reversible electroporation area in the cell-cell contact zone by 1.7 times by inducing a higher membrane tension, but also significantly reduced the applied voltage required for cell electroporation by increasing the cell size. Finally, the microfluidic chip with arc micro-cavities was fabricated and tested for electrofusion of SP2/0 cells. The results showed that no cell fusion occurred in the hypertonic buffer. The fusion efficiency in the isotonic buffer was about 7%. In the hypotonic buffer, the fusion efficiency was about 60%, which was significantly higher compared to hypertonic and isotonic buffers. The experimental results were in good agreement with the numerical analysis results.

Global trends of acupuncture clinical research on analgesia from 2010 to 2023: a bibliometric and visualization analysis.

Objective: Acupuncture, acknowledged as a potent non-pharmacological therapy, is frequently employed to alleviate pain. Despite its widespread use, there has been a lack of overarching bibliometric analysis of clinical research on acupuncture analgesia. We aimed to summarize current patterns, hotspots, and development trends in this field through bibliometric analysis. Methods: This study evaluates academic publications retrieved from the Web of Science database (2010.01-2023.09) concerning acupuncture analgesia in clinical settings. All primary and secondary studies on humans were included. To track global developmental trends, we employed several software for analyzing annual publication volumes, countries/regions, institutions, authors, cited authors, journals, cited journals, references, and keywords and to draw collaborative networks and reference co-citation network maps. Results: The final search encompassed 7,190 relevant studies, including 1,263 randomized controlled trials (RCTs) and 1,293 systematic reviews and meta-analyses. The results indicated a gradual increase in the number of annual publications on acupuncture analgesia in clinical practice. Among countries and institutions, China (2,139) and Chengdu University of Traditional Chinese Medicine (258) ranked first. Liang FR (89 articles) was the most prolific author, while MacPherson H (604) was the most cited author. MEDICINE (455) was the most productive journal, and Pain (2,473/0.20) ranked first in both the frequency and centrality of cited journals. Notably, the most frequently cited reference was a systematic review of individual patient data on acupuncture carried out for chronic pain that was published by Vickers Andrew J in 2012 (156). Burst analysis identified frontier research areas for 2010-2020, encompassing network meta-analysis, case reports, dry needling, lumbar disc herniation, cancer, post-herpetic neuralgia, insomnia, and bibliometric analysis. Conclusion: This study outlines current trends and potential future research hotspots in clinical acupuncture analgesia over the past decade. Findings emphasize the necessity for enhanced international collaboration to improve research output and translation.

Relationships among anxiety, depression, and health-related quality of life in adult epilepsy: A network analysis.

OBJECTIVE: Comorbid depression and anxiety in patients with epilepsy (PWE) are common and frequently under-treated, thus, causing poor health-related quality of life (HRQoL). However, little is known regarding the interconnections between anxious/depressive symptoms and the dimensions of HRQoL. Therefore, we conducted a network analysis to explore these relationships in detail among Chinese adult PWE. METHODS: A cohort of adult PWE was consecutively recruited from the First Affiliated Hospital of Chongqing Medical University. HRQoL, depression, and anxiety were measured with Quality of Life in Epilepsy Inventory-31, Neurological Disorders Depression Inventory for Epilepsy, and Generalized Anxiety Disorder 7-Item Scale, respectively. A regularized partial correlation network was constructed to investigate the interconnections between symptoms of anxiety/depression and the dimensions of HRQoL. We calculated expected influence (EI) and bridge expected influence (BEI) values to identify the most influential nodes. RESULTS: A total of 396 PWE were enrolled in this study, 78.1% of whom had focal onset epilepsy. The prevalence of anxiety and depression was 30.3% and 28.8%, respectively. The symptoms "frustrated" and "uncontrollable worry" had the highest EI values, whereas "emotional well-being", "seizure worry", "difficulty finding pleasure", and "nervousness or anxiety" had the highest BEI values. CONCLUSION: This study provides new insights into the relationships among anxiety, depression, and HRQoL. Critical central symptoms and bridge symptoms identified in the network might help to quickly identify PWE comorbid anxiety and depression in busy outpatient settings, thereby enabling early intervention and enhancing quality of life.

Electrochemical Lithium Deposition on LixTi5O12.

Lithium metal batteries (LMBs) have been regarded as one of the most promising next-generation high-energy-density storage devices. However, uncontrolled lithium dendrite growth leads to low Coulombic efficiencies and severe safety issues, hindering the commercialization of LMBs. Reducing the diffusion barrier of lithium is beneficial for uniform lithium deposition. Herein, a composite is constructed with Li4Ti5O12 as the skeleton of metallic lithium (Li@LixTi5O12) because Li4Ti5O12 is a "zero-strain" material and exhibits a low lithium diffusion barrier. It was found that the symmetric cells of Li@LixTi5O12 can stably cycle for over 400 h at 1 mA cm-2 in the carbonate electrolyte, significantly exceeding the usual lifespan (∼170 h) of the symmetric cell using a lithium metal electrode. In a full cell with Li@LixTi5O12 as the anode, the cathode LiFePO4 delivers a capacity retention of 78.2% after 550 cycles at 3.6C rate and an N/P ratio = 8.0. This study provides new insights for designing a practical lithium anode.

A therapeutic ERCP in an only 5.9 kg infant with obstruction jaundice using JF-260V duodenoscope.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has found extensive use in pediatric patients; however, challenges persist in the application of therapeutic ERCP in infants. CASE PRESENTATION: This case report details the presentation of a 5.9-kilogram infant with obstructive jaundice and suspected hemolytic anemia who underwent ERCP to alleviate biliary obstruction. The infant was admitted due to clay-colored stools, jaundice, and liver injury. Ultrasound and magnetic resonance cholangiopancreatography (MRCP) revealed dilation of the common bile duct (CBD) accompanied by the presence of stones. ERCP was conducted using a JF-260V duodenoscope under general anesthesia. Successful stone extraction and biliary drainage were achieved. CONCLUSIONS: In centers with considerable expertise in ERCP and pediatric anesthesia, the use of a conventional adult duodenoscope for therapeutic ERCP in infants can be considered safe and feasible, provided careful and stringent patient selection criteria are applied. In the future, clear guidelines and standardized protocols for the indications and procedures of pediatric ERCP should be established.

Complete Prevention of Bubbles in a PDMS-Based Digital PCR Chip with a Multifunction Cavity.

In a chamber-based digital PCR (dPCR) chip fabricated with polydimethylsiloxane (PDMS), bubble generation in the chambers at high temperatures is a critical issue. Here, we found that the main reason for bubble formation in PDMS chips is the too-high saturated vapor pressure of water at an elevated temperature. The bubbles should be completely prevented by reducing the initial pressure of the system to under 13.6 kPa to eliminate the effects of increased-pressure water vapor. Then, a cavity was designed and fabricated above the PCR reaction layer, and Parylene C was used as a shell covering the chip. The cavity was used for the negative generator in sample loading, PDMS degassing, PCR solution degassing in the digitization process and water storage in the thermal reaction process. The analysis was confirmed and finally achieved a desirable bubble-free, fast-digitization, valve-free and no-tubing connection dPCR.

Immune modulatory roles of radioimmunotherapy: biological principles and clinical prospects.

Radiation therapy (RT) not only can directly kill tumor cells by causing DNA double-strand break, but also exerts anti-tumor effects through modulating local and systemic immune responses. The immunomodulatory effects of RT are generally considered as a double-edged sword. On the one hand, RT effectively enhances the immunogenicity of tumor cells, triggers type I interferon response, induces immunogenic cell death to activate immune cell function, increases the release of proinflammatory factors, and reshapes the tumor immune microenvironment, thereby positively promoting anti-tumor immune responses. On the other hand, RT stimulates tumor cells to express immunosuppressive cytokines, upregulates the function of inhibitory immune cells, leads to lymphocytopenia and depletion of immune effector cells, and thus negatively suppresses immune responses. Nonetheless, it is notable that RT has promising abscopal effects and may achieve potent synergistic effects, especially when combined with immunotherapy in the daily clinical practice. This systematic review will provide a comprehensive profile of the latest research progress with respect to the immunomodulatory effects of RT, as well as the abscopal effect of radioimmunotherapy combinations, from the perspective of biological basis and clinical practice.

Reduction-Tolerance Electrolyte Design for High-Energy Lithium Batteries.

Lithium batteries employing Li or silicon (Si) anodes hold promise for the next-generation energy storage systems. However, their cycling behavior encounters rapid capacity degradation due to the vulnerability of solid electrolyte interphases (SEIs). Though anion-derived SEIs mitigate this degradation, the unavoidable reduction of solvents introduces heterogeneity to SEIs, leading to fractures during cycling. Here, we elucidate how the reductive stability of solvents, dominated by the electrophilicity (EPT) and coordination ability (CDA), delineates the SEI formed on Li or Si anodes. Solvents exhibiting lower EPT and CDA demonstrate enhanced tolerance to reduction, resulting in inorganic-rich SEIs with homogeneity. Guided by these criteria, we synthesized three promising solvents tailored for Li or Si anodes. The decomposition of these solvents is dictated by their EPTs under similar solvation structures, imparting distinct characteristics to SEIs and impacting battery performance. The optimized electrolyte, 1 M lithium bis(fluorosulfonyl)imide (LiFSI) in N-Pyrrolidine-trifluoromethanesulfonamide (TFSPY), achieves 600 cycles of Si anodes with a capacity retention of 81 % (1910 mAh g-1). In anode-free Cu||LiNi0.5Co0.2Mn0.3O2 (NCM523) pouch cells, this electrolyte sustains over 100 cycles with an 82 % capacity retention. These findings illustrate that reducing solvent decomposition benefits SEI formation, offering valuable insights for the designing electrolytes in high-energy lithium batteries.

Characterization of a pangolin SARS-CoV-2-related virus isolate that uses the human ACE2 receptor.

Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins, showing a potential threat to humans. Here we report the infectivity and pathogenicity of the SARS-CoV-2-related virus, PCoV-GX/P2V, which was isolated from a Malayan pangolin (Manis javanica). PCoV-GX/P2V could grow in human hepatoma, colorectal adenocarcinoma cells, and human primary nasal epithelial cells. It replicated more efficiently in cells expressing human angiotensin-converting enzyme 2 (hACE2) as SARS-CoV-2 did. After intranasal inoculation to the hACE2-transgenic mice, PCoV-GX/P2V not only replicated in nasal turbinate and lungs, but also caused interstitial pneumonia, characterized by infiltration of mixed inflammatory cells and multifocal alveolar hemorrhage. Existing population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V infection. These findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.

Bile acid profiling as an effective biomarker for staging in pediatric inflammatory bowel disease.

Rapid and accurate clinical staging of pediatric patients with inflammatory bowel disease (IBD) is crucial to determine the appropriate therapeutic approach. This study aimed to identify effective, convenient biomarkers for staging IBD in pediatric patients. We recruited cohorts of pediatric patients with varying severities of IBD to compare the features of the intestinal microbiota and metabolites between the active and remitting disease stages. Metabolites with potential for staging were targeted for further assessment in both patients and colitis model mice. The performance of these markers was determined using machine learning and was validated in a separate patient cohort. Pediatric patients with IBD exhibited distinct gut microbiota structures at different stages of disease activity. The enterotypes of patients with remitting and active disease were Bacteroides-dominant and Escherichia-Shigella-dominant, respectively. The bile secretion pathway showed the most significant differences between the two stages. Fecal and serum bile acid (BA) levels were strongly related to disease activity in both children and mice. The ratio of primary BAs to secondary BAs in serum was developed as a novel comprehensive index, showing excellent diagnostic performance in stratifying IBD activity (0.84 area under the receiver operating characteristic curve in the primary cohort; 77% accuracy in the validation cohort). In conclusion, we report profound insights into the interactions between the gut microbiota and metabolites in pediatric IBD. Serum BAs have potential as biomarkers for classifying disease activity, and may facilitate the personalization of treatment for IBD.