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Lupus nephritis (LN) poses a severe risk for individuals with systemic lupus erythematosus (SLE), prompting extensive research into targeted delivery systems capable of modulating immune responses and clearing cell-free DNA (cfDNA). Here, we propose a novel renal homing nanogel that acts as a cfDNA scavenger and a dexamethasone (DXM) delivery carrier for LN treatment. Based on the generation 3 polylysine dendrimers, the created cationic nanogels (G3DSP) exhibit minimal toxicity and outstanding DXM loading efficiency. Our studies confirm that these nanogels can competitively bind with anionic cfDNA in vitro, leading to the suppression of toll-like receptor 9 (TLR9) activation. When administered systemically to MRL/lpr mice, the nanogels preferentially localize to and are retained in the inflamed kidneys, releasing their payload in response to reactive oxygen species (ROS), therefore effectively ameliorating SLE symptoms. Consequently, G3DSP nanogels emerge as a promising effective combined therapy for LN, minimizing cfDNA accumulation in vital organs and delivering immunomodulatory benefits through DXM.

Abstract Engineered liver lobule is highly practical in hepatic disease treatment, while constructing a 3D biomimetic lobule with a heterogeneous architecture on a large scale is challenging. Here, inspired by the natural architectural construction of hepatic lobules, biomimetic hepatic lobules are proposed with coaxially through‐pores for nutrient exchange via microfluidic technology. This multi‐channel microfluidic chip is made by parallelly installing capillaries. Sodium alginate (Alg) is pumped through its central channel, while Ca2+‐loaded gelatin methacrylate (GelMA) solutions encapsulating hepatocytes, mesenchymal stem cells, and endothelia cells are pumped through surrounding channels, respectively. The rapid gelation of Alg and Ca2+ brings about an in situ formation of Alg fiber, with heterogeneous multi‐cell‐laden GelMA microcarriers forming around it. The peeled‐off microcarriers each featured with a coaxially through pore, simulating the cord‐like structure of hepatic lobule and facilitating nutrients exchange. Meanwhile, the spatially anisotropic arrangement of cells highly simulates the hepatic architecture. It is demonstrated that by transplanting these biomimetic microparticles into liver in situ, the failed liver in rat shows increased regeneration and decreased necrosis. These results indicated that the microfluidic multi‐compartmental microcarriers provide a new strategy to engineer 3D artificial livers for clinical translation.

Abstract Reactive oxygen species (ROS) have certain effect in cancer treatment, thus many studies have been focused on developing functional systems to generate ROS in tumor. Here, inspired by the multi‐enzyme biocatalysis in organisms, novel ultrasound‐triggered temporospatial catalytic cascades systems are presented based on barium titanate (BTO) and platinum (Pt) co‐loaded multi‐component microparticles (Pt/BTO@MCMPs) to successively achieve oxygen and ROS production for tumor sonodynamic therapy. By using a customized capillary microfluidic device, the Pt/BTO@MCMPs are fabricated with Pt nanoparticles located in their core part and BTO nanocubes located in their peripheral part, alternating with blank porous hydrogel components for increasing interaction areas between the encapsulated nanomaterials and the ambient substrates. In the microparticles, the Pt can catalyze hydrogen peroxide from the tumor microenvironment to generate O2 and H2O serving as substrates for piezoelectric catalytic reactions, contributing to additional generation of ROS under US activation. Based on the system, it is demonstrated that the Pt/BTO@MCMPs are featured with excellent biocompatibility under normal biological conditions and show desired tumor eradication properties under ultrasound irradiation in mice carrying pancreatic tumors. These results indicate that the proposed ultrasound‐triggered temporospatial catalytic cascades systems are promising for clinic anti‐tumor applications.

Abstract Nano‐delivery systems hold great promise for the treatment of rheumatoid arthritis (RA). Current research efforts are primarily focused on enhancing their targeting capabilities and efficacy. Here, this study proposes a novel viral‐mimicking ternary polyplexes system for the controlled delivery of the anti‐inflammatory drug Cyclosporin A (CsA) to effectively treat RA. The ternary polyplexes consist of a nanogel core loaded with CsA and a hyaluronic acid shell, which facilitates CD44‐mediated targeting. By mimicking the Trojan Horse strategy employed by viruses, these polyplexes undergo a stepwise process of deshielding and disintegration within the inflamed joints. This process leads to the release of CsA within the cells and the scavenging of pathogenic factors. This study demonstrates that these viral‐mimicking ternary polyplexes exhibit rapid targeting, high accumulation, and prolonged persistence in the joints of RA mice. As a result, they effectively reduce inflammation and alleviate symptoms. These results highlight the potential of viral‐mimicking ternary polyplexes as a promising therapeutic approach for the targeted and programmed delivery of drugs to treat not only RA but also other autoimmune diseases.

ObjectsThe aim of this study was to investigate the morphologic changes of a novel fully biodegradable implantable device after closing a perimembranous ventricular septal defect (Pm-VSD) and to evaluate the effect of the occluder on the myocardial function in patients during a 3-year follow-up period.MethodsOne-year, 2-year, and 3-year follow-ups were carried out after implantation with a total of 30 Pm-VSD patients who had successful closure by the fully biodegradable occluder. In total, 30 healthy children were enrolled as controls. At discharge and at every follow-up visit, the lengths of the left and right discs of the novel device were measured in the apical three- and four-chamber as well as short-axis views. At the end of the follow-up, using three-dimensional speckle-tracking conditions, the values of myocardial deformation, including global longitudinal strain, global circumferential strain, and global area strain, were acquired.ResultsThe fully bioabsorbable double-disc occluder gradually decreased over time and was eventually invisible under echocardiographic scanning during the follow-up (p 0.05).ConclusionThe novel fully biodegradable occluder is a safe, effective, and perfect alternative for the treatment of VSD. Echocardiography plays a crucial role in the follow-up of this new type of occluder implantation.

Objective: The advancement of neuroimaging and genetic research has revealed the presence of morphological abnormalities and numerous risk genes, along with their associations. We aimed to estimate magnetic resonance imaging-derived cortical thickness across multiple brain regions. Methods: The cortical thickness of 129 schizophrenia patients, 42 of their unaffected siblings, and 112 healthy controls was measured and the candidate genes were sequenced. Comparisons were made of cortical thickness (including 68 regions of the Desikan-Killiany Atlas) and genetic variants (in 108 risk genes for schizophrenia) among the three groups, and correlation analyses were performed regarding cortical thickness, clinical symptoms, cognitive tests (such as the N-back task and the logical memory test), and genetic variants. Results: Schizophrenia patients had significantly thinner bilateral frontal, temporal, and parietal gyri than healthy controls and unaffected siblings. Association analyses in target genes showed that four single nucleotide variants (SNVs) were significantly associated with schizophrenia, including thioredoxin-related transmembrane protein 2-catenin, cadherin-associated protein, delta 1 (SNV20673) (positive false discovery rate [PFDR] = 0.008) and centromere protein M (rs35542507, rs41277477, rs73165153) (PFDR = 0.030). Additionally, cortical thickness in the right pars triangularis was lower in carriers of the SNV20673 variant than in non-carriers (PFDR = 0.048). Finally, a positive correlation was found between right pars triangularis cortical thickness and logical memory in schizophrenia patients (r = 0.199, p = 0.032). Conclusions: This study identified regional morphological abnormalities in schizophrenia, including the right homologue of Broca’s area, which was associated with a risk variant that affected delta-1 catenin and logical memory. These findings suggest a potential association between candidate gene loci, cortical thickness, and schizophrenia.

Abstract Purpose Our study aims to discuss glaucoma patients’ needs and Internet habits using big data analysis and Natural Language Processing (NLP) based on deep learning (DL). Methods In this retrospective study, we used web crawler technology to crawl glaucoma-related topic posts from the glaucoma bar of Baidu Tieba, China. According to the contents of topic posts, we classified them into posts with seeking medical advice and without seeking medical advice (social support, expressing emotions, sharing knowledge, and others). Word Cloud and frequency statistics were used to analyze the contents and visualize the keywords of topic posts. Two DL models, Bidirectional Long Short-Term Memory (Bi-LSTM) and Bidirectional Encoder Representations from Transformers (BERT), were trained to identify the posts seeking medical advice. The evaluation matrices included: accuracy, F1 value, and the area under the ROC curve (AUC). Results A total of 10,892 topic posts were included, among them, most were seeking medical advice (N = 7071, 64.91%), and seeking advice regarding symptoms or examination (N = 4913, 45.11%) dominated the majority. The following were searching for social support (N = 2362, 21.69%), expressing emotions (N = 497, 4.56%), and sharing knowledge (N = 527, 4.84%) in sequence. The word cloud analysis results showed that ocular pressure, visual field, examination, and operation were the most frequent words. The accuracy, F1 score, and AUC were 0.891, 0.891, and 0.931 for the BERT model, 0.82, 0.821, and 0.890 for the Bi-LSTM model. Conclusion Social media can help enhance the patient-doctor relationship by providing patients’ concerns and cognition about glaucoma in China. NLP can be a powerful tool to reflect patients’ focus on diseases. DL models performed well in classifying Chinese medical-related texts, which could play an important role in public health monitoring.

Abstract Tumor tissue engineering holds great promise for replicating the physiological and behavioral characteristics of tumors in vitro. Advances in this field have led to new opportunities for studying the tumor microenvironment and exploring potential anti‐cancer therapeutics. However, the main obstacle to the widespread adoption of tumor models is the poor understanding and insufficient reconstruction of tumor heterogeneity. In this review, the current progress of engineering heterogeneous tumor models is discussed. First, the major components of tumor heterogeneity are summarized, which encompasses various signaling pathways, cell proliferations, and spatial configurations. Then, contemporary approaches are elucidated in tumor engineering that are guided by fundamental principles of tumor biology, and the potential of a bottom‐up approach in tumor engineering is highlighted. Additionally, the characterization approaches and biomedical applications of tumor models are discussed, emphasizing the significant role of engineered tumor models in scientific research and clinical trials. Lastly, the challenges of heterogeneous tumor models in promoting oncology research and tumor therapy are described and key directions for future research are provided.

Abstract Mesenchymal stem cell (MSC) therapy is a promising candidate for inflammatory bowel disease (IBD) treatment, while overcoming the limitations of naive seeding cells function and realizing efficient intestinal targeting remains a challenge. Here, a bioadhesive microparticle carrying interleukin‐27 (IL‐27) MSC‐derived extracellular vesicles (MSCIL‐27 EVs) is developed to treat IBD. The MSCIL‐27 EVs prepared through lentivirus‐mediated gene transfection technology show ideal anti‐inflammatory and damage repair function. By encapsulating MSCIL‐27 EVs into dopamine methacrylamide‐modified hydrogel, a bioadhesive EVs microcarrier via microfluidic technology is fabricated. The resultant microcarriers exhibit ideal MSCIL‐27 EVs sustained release effect and effective wet adhesion property. Furthermore, the therapeutic potential of MSCIL‐27 EVs‐loaded microcarriers in treating IBD is demonstrated. Through giving IBD rats a rectal administration, it is found that the microcarriers can firmly anchor to the surface of colon, reduce the inflammatory response, and repair the damaged barrier. Therefore, the bioadhesive MSCIL‐27 EVs‐loaded microcarriers provide a promising strategy for the biomedical application of MSC‐derived EVs, and broaden the clinical potential of MSC therapy.

Ultrasound (US)-responsive microparticles show broad potential in controlled drug delivery systems. Compare with the traditional micron-scale material fabrication methods, capillary microfluidic technology features superior advantages in large-scale production, batch-to-batch similarity, high encapsulation efficiency, low cost, and so on. The excellent maneuverability and customizability of the capillary microfluidic devices allow the production of microparticles with various functionalities and fine-tuned chemical compartments. Moreover, the flexible regulation of the particle size and core-shell ratio can be easily realized by modulating the capillary orifices and flow rates of microfluidic channels. In this review, we introduce the fabrication of US-responsive microparticles with specific core-shell structures via capillary microfluidic methods, from single emulsion to triple emulsions. Then, we address some particular examples, where the drug delivery and US-triggered cargo release capacity of these microfluidic microparticles are demonstrated. Finally, we conclude the advanced achievements of the US-responsive microfluidic microparticles, summarize the obstacles to the development of this interdisciplinary field, and prospect their future applications.

Abstract Based on the hourly rainfall gauge data and ERA5 reanalysis for the period 1980–2020, typical synoptic patterns responsible for summer regional hourly extreme precipitation events (RHEPE) over the middle and lower Yangtze River basin have been objectively identified using a circulation clustering method. It is found that the Meiyu front with different locations and intensities imbedded in the East Asian summer monsoon, and landfalling typhoons are the leading contributors. As the dominant synoptic pattern, the Meiyu front pattern is associated with ∼92% of the total RHEPE occurrence and can be categorized into a southerly strong‐Meiyu type and a northerly weak‐Meiyu type. The RHEPE occurrence shows a predominant morning peak associated with the southerly strong‐Meiyu type and a secondary late afternoon peak related to the northerly weak‐Meiyu type, in which the Meiyu front is pushed northward by the strengthened western North Pacific subtropical high accompanied by accelerated low‐level southwesterly flow.

Abstract The tumor‐suppressing efficacy of either chemotherapeutics or gaseous drugs has been confirmed in treating the triple negative breast cancer (TNBC), while the efficacy of single treatment is usually dissatisfactory. Herein, a novel ultrasound responsive natural pollen delivery system is presented to simultaneously load chemotherapeutics and gaseous drugs for synergistic treatment of TNBC. The hollow structure of pollen grains carries oxygen‐enriched perfluorocarbon (PFC), and the porous spinous process structure adsorbs the chemotherapeutic drug doxorubicin (DOX) (PO/D‐PGs). Ultrasound can trigger the oxygen release from PFC and excite DOX, which is not only a chemotherapeutic but also a sonosensitizer, to realize chemo‐sonodynamic therapy. The PO/D‐PGs are demonstrated to effectively enhance oxygen concentration and increase the production of reactive oxygen species in the presence of low‐intensity ultrasound, synergistically enhancing the tumor killing ability. Thus, the synergistic therapy based on ultrasound‐facilitated PO/D‐PGs significantly enhances the antitumor effect in the mouse TNBC model. It is believed that the proposed natural pollen cross‐state microcarrier can be used as an effective strategy to enhance chemo‐sonodynamic therapy for TNBC.

In East Asia, the climate variability in boreal winter is dominated by the East Asian winter monsoon, one of the most energetic monsoon systems that can lead to disasters. The key variable, the East Asian winter surface air temperature (SAT), has significantly changed over the past century and has substantially impacted agriculture, ecosystems, economics, and public health. However, its projections are limited by considerable uncertainties. Here, we identify the first leading mode that explains almost 29.6% of the inter-model spread in future SAT change. Our research delves into the evolution of present-day biases under future scenarios and their consequential impact on the SAT. Models with stronger western currents’ heat transport in the North Pacific exhibit a warmer North Pacific at mid-latitudes during historical periods. Additionally, these models consistently demonstrate stronger western currents in the future, contributing to the amplified warming of the western North Pacific, thereby warming Eurasia via the weakened trough and subtropical jet through barotropic responses to the warm North Pacific. Incorporating observational sea surface temperature constraints reduces uncertainties by 9.40%, revealing a more reliable SAT change pattern by the end of the 21st century.

Abstract Background Cardiac damage is the leading cause of death in uremic patients. This study aimed to evaluate the application of non-invasive myocardial work index (NIMWI) by echocardiography in assessing the left ventricular (LV) systolic function in uremic patients. Methods Twenty-six uremic patients and 27 age- and sex-matched healthy volunteers were enrolled in the study. Except for the conventional echocardiographic parameters, the LV myocardial work (MW) parameters including GWI (myocardial global work index), GCW (global constructive work), GWW (global wasted work), and GWE (global work efficiency) were calculated in study participants. Differences in MW parameters between the uremic and normal groups were compared by independent-sample t-test. Receiver operating characteristic (ROC) curves were constructed for MW parameters to detect abnormal LV systolic function in uremic patients. Results Compared with the normal group, GWW was significantly increased and GWE decreased in the uremic group (P

Abstract Micro‐ and nanorobots (MNRs) propelled by external actuations have broad potential in biomedical applications. Among the numerous external excitations, ultrasound (US) features outstanding practical significance with merits of its noninvasiveness, tunability, penetrability, and biocompatibility. Attributing to various physiochemical effects of US, it can propel the MNRs with sophisticated structures through asymmetric acoustic streaming, bubble oscillation, and so on. In this review, we introduce several advanced and representative US‐propelled MNRs with inhomogeneous density distribution, asymmetric shape, hollow cavity, etc. The potential biomedical applications of these cutting‐edge MNRs are also presented, including intracellular delivery, harmful substances collection, and so on. Furthermore, we conclude the advantages and limitations of US‐propelled MNRs and prospect their future developments in multidisciplinary fields.

Ultrasound (US) is a biofavorable mechanical wave that has shown practical significance in biomedical fields. Due to the cavitation effect, sonoluminescence, sonoporation, pyrolysis, and other biophysical and chemical effects, a wide range of matters have been elucidated to be responsive to the stimulus of US. This review addresses and discusses current developments in US-responsive matters, including US-breakable intermolecular conjugations, US-catalytic sonosensitizers, fluorocarbon compounds, microbubbles, and US-propelled micro- and nanorobots. Meanwhile, the interactions between US and advanced matters create various biochemical products and enhanced mechanical effects, leading to the exploration of potential biomedical applications, from US-facilitated biosensing and diagnostic imaging to US-induced therapeutic applications and clinical translations. Finally, the current challenges are summarized and future perspectives on US-responsive matters in biomedical applications and clinical translations are proposed.

Neurofibromatosis type 1 (NF1) is a benign peripheral nerve sheath tumor, which can primarily cause neurocutaneous manifestations. We herein present a rare case of periportal neurofibromatosis with intrahepatic, retroperitoneal and pelvic involvement. The patient underwent abdominal ultrasound (US), magnetic resonance imaging, and a positron emission tomography-computed tomography. Despite these various imaging features, a diagnosis of lymphomas could not be entirely excluded. The patient therefore underwent US-guided biopsy, and a diagnosis of intrahepatic neurofibromatosis was made. Through retrospective analysis of this case along with literature review, we concluded that distributing along the Glisson’s sheath may be a characteristic in the diagnosis of NF that involves liver.

The regenerative function of liver can be destroyed by viral infection, drug poisoning and tumorigenesis, resulting in irreversible damage. Numerous approaches in promoting liver repair intend to replace liver transplantation, which is faced with a shortage of donors. Owing to the significant advantages in cell programming and bioscaffold engineering, liver tissue engineering is considered to be the most promising alternative for mimicking liver microstructure, maintaining hepatic function or implanting whole liver. Cell sources gradually develop from primary hepatocytes, tumor cells, stem cell-induced cells to multiple cell coculture formats, spheroids and organoids, which have realized the improvement of cell function, overcome the problem of large-scale cell expansion and avoid the risk of immune rejection. Scaffolds, biocompatible materials are applied as cell carriers, and decellularized scaffolds and three-dimensional bioprinting liver pipeline structures are also used to accelerate cell colonization and proliferation. We enumerate sufficient research concerning liver tissue engineering in this review, including single and multiple cell sources, implantable and extracorporeal scaffold materials, and so on, providing critical conclusions and future implications of tissue engineering in liver regenerative applications.

Abstract Revealing the synoptic patterns related to hourly extreme precipitation (EP) is very important to deepen our recognition and understanding of EP formation. The predominant synoptic patterns associated with the summer regional hourly EP events (RHEPE) over the central‐eastern Tibetan Plateau (CETP) and Sichuan Basin (SCB) have been systematically identified. Results show the summer RHEPE over CETP and SCB are dominated by the background large‐scale circulations featured by the configuration of eastward‐extended South Asia high (SAH) and westward‐extended Western North Pacific Subtropical High (WNPSH) and their northward advance, except for that an obvious low‐level vortex imbedded in the background large‐scale circulations is mainly responsible for the summer RHEPE over SCB. The frequency and intensity of the total summer RHEPE over CETP and SCB all show an obvious increasing trend during 2000–2020, which is largely contributed by the synoptic pattern characterized by the configuration of eastward extended SAH and westward extended WNPSH.

Management of infected wounds has raised worldwide concerns. Attempts in this field focus on the development of intelligent patches for improving the wound healing. Here, inspired by the cocktail treatment and combinational therapy stratagem, we present a novel Janus piezoelectric hydrogel patch via 3-dimensional printing for sonodynamic bacteria elimination and wound healing. The top layer of the printed patch was poly(ethylene glycol) diacrylate hydrogel with gold-nanoparticle-decorated tetragonal barium titanate encapsulation, which realizes the ultrasound-triggered release of reactive oxygen species without leaking nanomaterials. The bottom layer is fabricated with methacrylate gelatin and carries growth factors for the cell proliferation and tissue reconstruction. Based on these features, we have demonstrated in vivo that the Janus piezoelectric hydrogel patch can exert substantial infection elimination activity under the excitation of ultrasound, and its sustained release of growth factors can promote tissue regeneration during wound management. These results indicated that the proposed Janus piezoelectric hydrogel patch had practical significance in sonodynamic infection alleviation and programmable wound healing for treating different clinical diseases.

Abstract Increasingly extreme temperature events under global warming can have considerable impacts on sectors such as industrial activities, health, and transportation, suggesting that risk for these kinds of events under climate change and its regional sensitivity should be reassessed. In this study, the observation and multi-model simulations from CMIP6 are comprehensively used to explore the regional differences of the extreme temperature response to climate change from the perspective of return period (RP). The Gumbel model of generalized extremum distribution is applied to estimate the RP for the annual extremum of temperature based on Gaussian distribution of daily temperature. The analysis on the observation in selected three sites indicates that the regional inconsistency of RP variation is not only existed in extreme high temperature (HTx) but also in low temperature (LTn) during the past several decades. The annual amplitude of temperature extremum in the Northeast China is enlarged with summer becoming hotter and winter becoming colder while the opposite situation is detected in Huang-Huai River Basin with cooler summer and relatively stable winter, and South China is characterized by hotter summer and slight warmer winter. From the spatial distribution of the HTx and LTn variations of fix RP, it is found that the Northeast China and Jiang-Huai River Basin is the most sensitive areas, respectively, in the response of extreme low temperature and high temperature to global warming. However, the regional inconsistency of the extreme temperature change is only observed under SSP1-2.6 scenario in the CMIP6 simulation but gradually disappeared from SSP2-4.5 to SSP5-8.5.

Abstract Antibiotics provide promising strategies for treating periodontitis, while their delivery and controllable release with desired oral retention remain challenging. Here, inspired by the unique suction‐cup structures of abalones, a novel adhesive and photo‐responsive microparticle (MP) delivery system is developed to treat periodontitis through microfluidic electrospray technology. Such MPs are generated by quickly ionic cross‐linking of sodium alginate together with photo‐curing of poly(ethylene glycol) diacrylate of the distorted microfluidic droplets during their high‐speed dropping into calcium chloride solution. Attributing to their unique concave structures, the abalone‐inspired MPs exhibit desired underwater adhesion ability and stability under running water. In addition, due to the loading of antibiotics minocycline hydrochloride and near‐infrared (NIR)‐responsive black phosphorus during their fabrication, the resultant MPs can not only eradicate bacteria directly, but also realize a controllable and effective drug release upon NIR irradiation. Based on these features, it is demonstrated from in vivo periodontitis that the abalone‐inspired MPs are firmly adhesive and can controlled‐release drugs on the tooth, and thus have outstanding antibacterial efficacy against Porphyromonas gingivalis. These results indicate the particular values of the abalone‐inspired MPs for oral‐related disease treatment.

BackgroundThe capacity to distinguish hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) based on morphological features obtained by conventional echocardiography is limited. We investigated the global myocardial work of the left ventricle in two types of hypertrophies using the non-invasive myocardial work index (NMWI).MethodsConventional echocardiography was performed on 107 subjects with preserved left ventricular ejection fraction (LVEF ≥ 50%), who comprised patients with HCM (n = 40), H-LVH (n = 35), and healthy people with normal blood pressure and left ventricular structure (n = 32). Except for the conventional echocardiographic parameters, the left ventricular myocardial work parameters based on pressure-strain loops, including global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), were evaluated in three groups. Multivariate discriminant analysis and receiver operating characteristic (ROC) curve were used to evaluate the incremental value of NMWI for distinguishing HCM from H-LVH.ResultsCompared to the control group, GWI and GCW were significantly lower in HCM patients (P < 0.05), whereas GWI was significantly higher in H-LVH patients. GWW was higher and GWE was significantly decreased in both HCM and H-LVH patients than in the control group (P < 0.05). Multivariate discriminant analysis and ROC curve revealed that the inter-ventricular septum thickness (IVST)/left ventricular posterior wall thickness (LVPWT) and GCW were each able to distinguish HCM from H-LVH. The combination of IVST/LVPWT and GCW discriminated HCM and H-LVH with a higher predictive accuracy of 94.7%.ConclusionNMWI may provide additional information in evaluating the myocardial function in patients with HCM and H-LVH. Myocardial work combined with conventional echocardiography could improve the clinical diagnostic accuracy of distinguishing HCM and H-LVH.

Liver plays a critical role in drug metabolism and nowadays multi-cellular culture systems aiming at imitating liver-specific morphology and functionality are advancing robustly. Numerous immortalized or stem cell-induced hepatic cell lines have been investigated to enhance the hepatic phenotype in establishing co-culture systems. Owing to the robust progresses of microtechnology and bioengineering, two-dimensional (2D) co-cultures such as sandwich culture and micropatterned co-culture systems have emerged. Controllably arranging the hepatocytes and fibroblasts allows bio-mimic homotypic and heterotypic interactions, and the miniaturized co-culture platform realizes high-throughput and sensitive drug screening. Yet, to address the rapid dedifferentiation and the decreased maintenance of hepatic functions existing in 2D cellular systems, various three-dimensional (3D) and dynamic hepatocyte co-culturing formats have been established to obtain more physiologically relevant liver microsystems and prolonged hepatic functionalities, such as spheroid barcodes, liver organoids, bioengineered hepatic spheroids, and microfluidic perfused liver-on-a-chip. In this review, we first introduce the typical structural color spheroid barcodes which facilitate multiple screening and testing. Then we sketch various advances in liver-imitating cellular co-culture protocols through representative examples. Meanwhile, we summarize current difficulties and propose the prospects of bioengineered liver-on-barcode systems for reliable and high-throughput drug screening.

BackgroudNoninvasive myocardial work, estimated by left ventricular (LV) pressure-strain loop (PSL), has been introduced for assessing LV myocardial performance. Based on both blood pressure and speckle-tracking derived strain data, noninvasive myocardial work is considered to be less load-dependent than global longitudinal strain (GLS). In some conditions, such as hypertension or aortic coarctation, the increased afterload will affect strain measurements, and myocardial work can serve as a more robust metric.ObjectiveWe prospectively recruited healthy children to explore the relationship between myocardial work indices and body size parameters, and to determine the reference values of noninvasive myocardial work indices in healthy children.Methods183 healthy children (aged 1–18 years, males: 52.5%) were enrolled in the study. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), were assessed by LVPSL and compared according to age and sex.ResultsThe mean for GWI was 1,448.7 ± 265.0 mm Hg%, 1,859.8 ± 290.7 mm Hg% for GCW, and the median (interquartile range) for GWW was 54.0 (33.0–82.0) mm Hg% and 97.0 (95.0–99.0) % for GWE. male had greater GWI and GCW) than female (1,572.5 ± 250.2 mm Hg% vs. 1,312.2 ± 208.7 mm Hg% and 1,944.3 ± 299.2 mm Hg% vs. 1,766.6 ± 251.5 mm Hg%, respectively, all P < 0.001). GWI and GCW were significantly correlated with baseline parameters, including age, height, weight, BSA, body mass index, heart rate, and blood pressure. After indexed to BSA, GWI (BSA), GCW (BSA) remained significantly negatively correlated with age (P < 0.001).Conclusionswe proposed the normal reference values and regression equations for GWI and GCW based on age and BSA in healthy children. This might provide a basis of reference for the evaluation of cardiac function in children with cardiopulmonary disease.

Microorganisms play an important role in natural material and elemental cycles. Many common and general biology research techniques rely on microorganisms. Machine learning has been gradually integrated with multiple fields of study. Machine learning, including deep learning, aims to use mathematical insights to optimize variational functions to aid microbiology using various types of available data to help humans organize and apply collective knowledge of various research objects in a systematic and scaled manner. Classification and prediction have become the main achievements in the development of microbial community research in the direction of computational biology. This review summarizes the application and development of machine learning and deep learning in the field of microbiology and shows and compares the advantages and disadvantages of different algorithm tools in four fields: microbiome and taxonomy, microbial ecology, pathogen and epidemiology, and drug discovery.

As an effective combination chemotherapy, FOLFIRINOX regimen (fluorouracil, leucovorin, irinotecan, and oxaliplatin) has shown definite antitumor efficacy for treating pancreatic cancer (PC) nowadays. However, the traditional systematic administration of these chemotherapeutics limits the drug targeting and causes unwanted effects. Herein, we present a novel Christmas tree-shaped adhesive microneedle (MN) patch coloading fluorouracil, leucovorin, irinotecan, and oxaliplatin simultaneously to realize spatiotemporal FOLFIRINOX therapy in situ. Such MN patch was fabricated by using a layer-by-layer mold replication method, in which oxaliplatin and leucovorin are encapsulated in the top MNs, while irinotecan and fluorouracil are encapsulated in the bottom MNs. The multilayer structure imparts the MNs with enhanced adhesive ability and spatiotemporal drug release property, contributing to the antitumor effect on PC organoid models. Therefore, our Christmas tree-shaped MN patch represents an innovative approach for spatiotemporal multiple-drug delivering and realizes the combination chemotherapy for PC in a single platform.

Ultrasound (US) is a kind of acoustic wave with frequency higher than 20 kHz. Learning from the echo detection ability of bats and dolphins, scientists applied US for clinical imaging by sending out US waves and detecting echoes with shifted intensities and frequencies from human tissue. US has long played a critical role in noninvasive, real-time, low-cost and portable diagnostic imaging. With the in-depth study of US in multidisciplinary fields, US and US-responsive materials have shown practical value in not only disease diagnosis, but also disease treatment. In this review, we introduce the recently proposed and representative US-responsive materials for biomedical applications, including diagnostic and therapeutic applications. We focused on US-mediated physicochemical therapies, such as sonodynamic therapy, high-intensity focused US ablation, sonothermal therapy, thrombolysis, etc, and US-controlled delivery of chemotherapeutics, gases, genes, proteins and bacteria. We conclude with the current challenges facing the clinical translation of smart US-responsive materials and prospects for the future development of US medicine.

Background: Type 2 diabetes mellitus (T2DM) is a common risk factor for cardiovascular diseases. The aims of this study were to evaluate the changes in the left ventricular myocardial work in T2DM patients using the left ventricular pressure-strain loop (PSL) technique, and to explore the risk factors for the left ventricular myocardial work impairment.Methods: Fifty patients with T2DM and 50 normal controls (NCs) were included in the study. In addition to conventional echocardiography and two-dimensional speckle tracking echocardiography, the left ventricular myocardial work parameters were measured using PSL technology.Results: The absolute value for global longitudinal strain (GLS), global work index (GWI) and, global constructive work (GCW) were significantly decreased in the T2DM group (P < 0.05), while the left ventricular ejection fraction (LVEF) was not significantly different between the T2DM and NC groups. Multivariable linear regression analysis showed that hemoglobin A1c (HbA1c) was independently related to GWI (β = −0.452, P < 0.05), while HbA1c and the diabetes duration were independently related to GCW (β = −0.393, P < 0.05 and β = −0.298, P < 0.05, respectively).Conclusions: Changes in the left ventricular myocardial systolic function in T2DM patients were identified using PSL technology. HbA1c was shown to be an independent risk factor affecting GWI, while HbA1c and diabetes duration were demonstrated to be independent risk factors affecting GCW.

Objectives: To analyze the association between global myocardial work indices evaluated by non-invasive left ventricular (LV) pressure-strain loop (PSL) and LV myocardial fibrosis in patients with dilated cardiomyopathy (DCM).Methods: A total of 57 patients with DCM were included in this prospective study. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE) and global longitudinal strain (GLS) were measured using LVPSL. LV volumes and LV ejection fraction (LVEF) were evaluated using cardiac magnetic resonance imaging (CMRI), LV myocardial fibrosis was estimated at CMRI by qualitative assessment of late gadolinium enhancement (LGE). According to the CMRI, the studied population was divided into two groups, namely: patients without LGE (LGE-) and patients with LGE (LGE+).Results: The LGE+ group presented with increased age, LV end systolic volume (LVESV) index and reduced GWI, GCW, GWE, GLS, CMRI-derived LVEF (LVEFCMRI), the differences between the two groups were statistically significant (P < 0.05). After correcting for age and LVESV index, LVEFCMRI, GLS, GWI, GCW, and GWE retained independent associations with LV myocardial fibrosis. According to receiver operating characteristics (ROC) analysis, LVEFCMRI, and GCW showed larger AUC and higher accuracy, sensitivity, and specificity than GLS, the accuracy of predicting LV myocardial fibrosis ranged from high to low as: LVEFCMRI, GCW, GWE, GWI, and GLS.Conclusions: LVEFCMRI, GWI, GCW, GWE, and GLS remained significant predictors of LV myocardial fibrosis. LVEFCMRI, and GCW appeared to better predict LV myocardial fibrosis compared with GLS.

Betel quid (BQ) is one of the most popular addictive substances in the world. However, the neurophysiological mechanism underlying BQ addiction remains unclear. This study aimed to investigate whether and how BQ chewing would affect brain function in the framework of a dynamic brain network model. Resting-state functional magnetic resonance imaging scans were collected from 24 male BQ-dependent individuals and 26 male non-addictive healthy individuals before and promptly after chewing BQ. Switching rate, a measure of temporal stability of functional brain networks, was calculated at both global and local levels for each scan. The results showed that BQ-dependent and healthy groups did not significantly differ on switching rate before BQ chewing (F = 0.784, p = 0.381, analysis of covariance controlling for age, education, and head motion). After chewing BQ, both BQ-dependent (t = 2.674, p = 0.014, paired t-test) and healthy (t = 2.313, p = 0.029, paired t-test) individuals showed a significantly increased global switching rate compared to those before chewing BQ. Significant corresponding local-level effects were observed within the occipital areas for both groups, and within the cingulo-opercular, fronto-parietal, and cerebellum regions for BQ-dependent individuals. Moreover, in BQ-dependent individuals, switching rate was significantly correlated with the severity of BQ addiction assessed by the Betel Quid Dependence Scale scores (Spearman's rho = 0.471, p = 0.020) before BQ chewing. Our study provides preliminary evidence for the acute effects of BQ chewing on brain functional dynamism. These findings may provide insights into the neural mechanisms of substance addictions.

Background: Mitral valve (MV) morphology after MV repair affects postoperative left ventricular (LV) blood flow pattern and long-term cardiac function. Pilot data suggest that LV diastolic vortex flow pattern changes after operation, but specific quantifiers remain unknown. We aimed to explore the role of vector flow mapping (VFM) in LV diastolic vortex flow pattern in patients who underwent MV repair. Methods: A total of 70 patients with degenerative mitral regurgitation were consecutively enrolled and 30 age- and gender-matched controls were recruited. 50 Patients who underwent MV repair were eventually included in our study. LV average energy loss (EL-AVE) during diastole was measured in the MV repair group by VFM one week before and one month after the operation, and compared with that of controls using one-way analysis of variance. The effect of surgical techniques and the extension of leaflet degeneration on postoperative EL-AVE were analyzed using muti-way analysis of variance, and patients were categorized into a resection subgroup (n = 29) and a non-resection subgroup (n = 21). Results: The EL-AVE one month after operation in the MV repair group was decreased (p < 0.001) compared to that one week before the operation, and was increased (p < 0.001) compared to that in controls. Mitral leaflet resection had a statistically significant effect on postoperative EL-AVE. The EL-AVE of the resection subgroup was higher than that of non-resection subgroup (p < 0.001). Conclusions: VFM can be used to evaluate the diastolic blood flow pattern of LV after MV repair, and to observe the changes of LV blood flow pattern caused by different surgical techniques. VFM may be a potential new hemodynamic evaluation method after MV repair.

Glioma is the most common primary brain tumor with poor prognosis and high mortality. The purpose of this study was to use the epigenetic signature to predict prognosis and evaluate the degree of immune infiltration in gliomas. We integrated gene expression profiles and DNA methylation data of lower-grade glioma and glioblastoma to explore epigenetic differences and associated differences in biological function. Cox regression and lasso analysis were used to develop an epigenetic signature based on eight DNA methylation sites to predict prognosis of glioma patients. Kaplan–Meier analysis showed that the overall survival time of high- and low-risk groups was significantly separated, and ROC analysis verified that the model had great predictive ability. In addition, we constructed a nomogram based on age, sex, 1p/19q status, glioma type, and risk score. The epigenetic signature was obviously associated with tumor purity, immune checkpoints, and tumor-immune infiltrating cells (CD8+ T cells, gamma delta T cells, M0 macrophages, M1 macrophages, M2 macrophages, activated NK cells, monocytes, and activated mast cells) and thus, it may find application as a guide for the evaluation of immune infiltration or in treatment decisions in immunotherapy.

Background/Aims: Evidence suggests that IL-6 affects bone mass by modulating osteocyte communication towards osteoclasts. However, the mechanism by which IL-6 enhances osteocyte-mediated osteoclastogenesis is unclear. We aimed to investigate the inflammatory factors in serum after orthodontic surgery and their relationship between osteocytes and osteoclasts. Methods: Serum was obtained from 10 orthognathic surgery patients, and inflammatory factors were detected by ELISA. We treated the osteocyte-like cell line MLO-Y4 with recombinant mouse IL-6 and IL-6 receptor (IL-6R), and used quantitative RT-PCR and Western blotting to explore Receptor activator of nuclear factor-κB ligand (RANKL) expression at both the mRNA and protein level. MLO-Y4 cells were co-cultured with osteoclast precursor cells, and the formation of osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining. To explore the role of JAK2 in the osteocyte-mediated osteoclastogenesis, AG490, a JAK2 inhibitor, was used to inhibit the JAK2-STAT3 pathway in osteocytes. Results: In our study, we found that IL-6 and RANKL were stimulated in serum 3-7 days after orthognathic surgery. Therefore, IL-6 and IL-6 receptor enhanced the expression of RANKL at both the mRNA and protein level in MLO-Y4. Furthermore, when MLO-Y4 cells were co-cultured with osteoclast precursor cells, it significantly stimulated osteoclastogenesis. Our study indicated that osteocytes could promote osteoclastic differentiation and the formation of TRAP-positive multinucleated cells after stimulation with IL-6 and IL-6R. Our results also indicated that treatment with IL-6 and IL-6R increased RANKL mRNA expression and the RANKL/OPG expression ratio. Meanwhile, the phosphorylation of Janus kinase 2 (JAK2) and Signal transducer and activator of transcription (STAT3) also correlated with RANKL levels. Furthermore, we investigated the effects of a specific JAK2 inhibitor, AG490, on the expression of RANKL in osteocyte-like MLO-Y4 cells and osteocyte-mediated osteoclastogenesis. The results showed that AG490 inhibited (p)-JAK2 and RANKL expression. Osteoclastic differentiation was decreased after pretreatment in MLO-Y4 with mouse IL-6/IL-6R and AG490; therefore, we concluded that IL-6 increased osteocyte-mediated osteoclastic differentiation by activating JAK2 and RANKL. Conclusion: The effects of IL-6/il-6R and AG490 on osteocyte-mediated osteoclastogenesis contribute to our understanding of the role of inflammatory factors in the interaction between osteocytes and osteoclast precursors. IL-6 and RANKL are key factors for bone remodelling after the orthodontic surgery, and their roles in bone remodelling may be fundamental mechanisms accelerating tooth movement by orthodontic surgery.

Background: Large language models (LLMs), such as ChatGPT, have considerable implications for various medical applications. However, ChatGPT's training primarily draws from English-centric internet data and is not tailored explicitly to the medical domain. Thus, an ophthalmic LLM in Chinese is clinically essential for both healthcare providers and patients in mainland China. Methods: We developed an LLM of ophthalmology (MOPH) using Chinese corpora and evaluated its performance in three clinical scenarios: ophthalmic board exams in Chinese, answering evidence-based medicine-oriented ophthalmic questions and diagnostic accuracy for clinical vignettes. Additionally, we compared MOPH's performance to that of human doctors. Results: In the ophthalmic exam, MOPH's average score closely aligned with the mean score of trainees (64.7 (range 62-68) vs 66.2 (range 50-92), p=0.817), but achieving a score above 60 in all seven mock exams. In answering ophthalmic questions, MOPH demonstrated an adherence of 83.3% (25/30) of responses following Chinese guidelines (Likert scale 4-5). Only 6.7% (2/30, Likert scale 1-2) and 10% (3/30, Likert scale 3) of responses were rated as 'poor or very poor' or 'potentially misinterpretable inaccuracies' by reviewers. In diagnostic accuracy, although the rate of correct diagnosis by ophthalmologists was superior to that by MOPH (96.1% vs 81.1%, p>0.05), the difference was not statistically significant. Conclusion: This study demonstrated the promising performance of MOPH, a Chinese-specific ophthalmic LLM, in diverse clinical scenarios. MOPH has potential real-world applications in Chinese-language ophthalmology settings. [ABSTRACT FROM AUTHOR]

A two-dimensional mathematical model is used to simulate the influence of water flow on the piers of a bridge for different incidence angles. In particular, a finite volume method is used to discretize the Navier-Stokes control equations and calculate the circumferential pressure coefficient distribution on the bridge piers' surface. The results show that the deflection of the flow is non-monotonic. It first increases and then decreases with an increase in the skew angle. [ABSTRACT FROM AUTHOR]

Extreme summer precipitation often associated with flash floods has devastating impact on the local economies and livelihood of millions of people over East China. Tracking down the drivers of those extreme events will help to understand their formation mechanisms and to improve forecasts. Here the synoptic patterns associated with summer extreme precipitation events over East China during 1961-2018 have been identified systematically and quantitatively using a circulation clustering method. The results show that regional events over East China are dominated by the Eastern Asian summer monsoon associated Meiyu front, landfalling tropical cyclones and low-pressure vortices. Most sub-regions have seen increasing trends of extreme rainfall events during the past 6 decades with comparable contributions from the two main drivers. There was a decreasing trend over the North China Plain driven by the lowlevel southeasterly winds. Plain Language Summary Closely linked to flash floods, extreme precipitation is one of the high impacts but low probability weather phenomena that challenge modern numerical predictions. However, models are generally more skillful in predicting synoptic weather systems than precipitation itself. Taking East China as an example, this paper demonstrates the links between extreme precipitation events and synoptic weather systems using circulation clustering. Two major weather systems, the Eastern Asian Summer Monsoon and landfalling tropical cyclones are responsible for most extreme precipitation events (about 70%) over East China during the summer season. If models can accurately predict the strength and position of these weather systems, there may be enhanced potential of predicting regional precipitation extremes. Such implications are not regionally limited. [ABSTRACT FROM AUTHOR]

After a CO2 increase, whether the early transient and final equilibrium climate change patterns are similar has major implications. Here, we analyze long-term simulations from multiple climate models under increased CO2, together with the extended simulations from CMIP5, to compare the transient and equilibrium climate change patterns under different forcing scenarios. Results show that the normalized warming patterns (per 1 K of global warming) are broadly similar among different forcing scenarios (including abrupt 2 × CO2, 4 × CO2, and 1% CO2 increase per year) and during different time periods, except for the first 50 years or so when warming is weaker over the North Atlantic and Southern Ocean but stronger over most continents. During the first 200 years, this consistency is stronger over land than over ocean, but is lower in midlatitudes than other regions. Normalized precipitation change patterns are also similar, albeit to a lesser degree, among different forcing scenarios and across different time periods, although noticeable differences exist during the first few hundred years with smaller increases over the tropical Pacific. Precipitation over many subtropical oceans and land areas decreases consistently under different forcing scenarios and over all time periods. In particular, the transient and near-equilibrium change patterns for both surface air temperature and precipitation are similar over most of the globe, except for the North Atlantic warming hole, which is mainly a transient feature. The Arctic amplification and land–ocean warming contrast are largest during the first 100–200 years after CO2 quadrupling but they still exist in the equilibrium response. [ABSTRACT FROM AUTHOR]

Huang et al. recently reported that opposite phases of the interdecadal Pacific oscillation (IPO) and the Atlantic multidecadal oscillation (AMO) can affect the shift of the East Asian polar front jet (EAPJ) and the East Asian subtropical jet (EASJ) in the boreal winter. To give a full image of the relationship among the IPO, AMO, and concurrent variation of jets throughout the whole year, this study investigates the changes in summer jets response to the combinations of the IPO and AMO, and mostly focuses on the quantitative analysis in the role of the IPO and AMO. Both of the diagnostic analysis and atmospheric model simulations confirm that combinations of the negative phase of the IPO (“−IPO”) and the positive phase of the AMO (“+AMO”) can significantly enhance the EAPJ and reduce the EASJ in the summer, via the meridional temperature gradient and the Eady growth rate, and vice versa in the “+IPO −AMO” combination. The reanalysis data show that this relationship is particularly evident between the periods of 1999–2014 and 1979–98. Based on the simulations, the multilinear regression has indicated that −IPO plays a more important role than +AMO, particularly for the reduced EASJ. We have further revealed two pathways of the stationary Rossby wave activity anomaly, eastward from the North Atlantic to East Asia along 60°N and westward from the North Pacific to East Asia along 40°N. The two activities are associated with anomalous anticyclone along the active regions between EAPJ and EASJ, and therefore affect the jet variations. [ABSTRACT FROM AUTHOR]

After a CO2 increase, whether the early transient and final equilibrium climate change patterns are similar has major implications. Here, we analyze long-term simulations from multiple climate models under increased CO2, together with the extended simulations from CMIP5, to compare the transient and equilibrium climate change patterns under different forcing scenarios. Results show that the normalized warming patterns (per 1 K of global warming) are broadly similar among different forcing scenarios (including abrupt 2 × CO2, 4 × CO2, and 1% CO2 increase per year) and during different time periods, except for the first 50 years or so when warming is weaker over the North Atlantic and Southern Ocean but stronger over most continents. During the first 200 years, this consistency is stronger over land than over ocean, but is lower in midlatitudes than other regions. Normalized precipitation change patterns are also similar, albeit to a lesser degree, among different forcing scenarios and across different time periods, although noticeable differences exist during the first few hundred years with smaller increases over the tropical Pacific. Precipitation over many subtropical oceans and land areas decreases consistently under different forcing scenarios and over all time periods. In particular, the transient and near-equilibrium change patterns for both surface air temperature and precipitation are similar over most of the globe, except for the North Atlantic warming hole, which is mainly a transient feature. The Arctic amplification and land–ocean warming contrast are largest during the first 100–200 years after CO2 quadrupling but they still exist in the equilibrium response. [ABSTRACT FROM AUTHOR]

Hong Kong needs a comprehensive and formal regime of corporate rescue that is supported by statute. In Hong Kong, the old «Scheme of Arrangement» has received too much criticism, and the Law Reform Commission proposed «Provisional Supervision»in the Companies Bill, but the Bill did not pass the voting by legislature council of Hong Kong because of too much resistance that come from shareholders and creditors. While UK has already successfully gone through reforms of corporate rescue regime and now administration procedure plays a significant role in UK corporate rescue regime. This article will compare the problems of statutory corporate rescue regime in Hong Kong with UK's way to improve their corporate rescue regime. First, a historical study of corporate rescue will be conducted. Second, problems of corporate rescue in Hong Kong will be analyzed. And finally, the author will compare the regime in UK and HK, and then give a new framework for corporate rescue in the near future. [ABSTRACT FROM AUTHOR]