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Abstract Background Phenotypically unstable Schwann cell-like cells (SCLCs), derived from mesenchymal stem cells (MSCs) require intercellular contact-mediated cues for Schwann cell (SCs)-fate commitment. Although rat dorsal root ganglion (DRG) neurons provide contact-mediated signals for the conversion of SCLCs into fate-committed SCs, the use of animal cells is clinically unacceptable. To overcome this problem, we previously acquired human induced pluripotent stem cell-derived sensory neurons (hiPSC-dSNs) as surrogates of rat DRG neurons that committed rat bone marrow SCLCs to the SC fate. In this study, we explored whether hiPSC-dSNs could mimic rat DRG neuron effects to obtain fate-committed SCs from hBMSC-derived SCLCs. Methods hiPSCs were induced into hiPSC-dSNs using a specific chemical small molecule combination. hBMSCs were induced into hBMSC-derived SCLCs in a specific culture medium and then co-cultured with hiPSC-dSNs to generate SCs. The identity of hBMSC-derived SCs (hBMSC-dSCs) was examined by immunofluorescence, western bolt, electronic microscopy, and RNA-seq. Immunofluorescence was also used to detect the myelination capacity. Enzyme-linked immunosorbent assay and neurite outgrowth analysis were used to test the secretion of neurotrophic factors. Results The hBMSC-dSCs exhibited bi-/tri-polar morphology of SCs and maintained the expression of the SC markers S100, p75NTR, p0, GFAP, and Sox10, even after withdrawing the glia-inducing factors or hiPSC-dSNs. Electronic microscopy and RNA-seq analysis provided evidence that hBMSC-dSCs were similar to the original human SCs in terms of their function and a variety of characteristics. Furthermore, these cells formed MBP-positive segments and secreted neurotrophic factors to facilitate the neurite outgrowth of Neuro2A. Conclusions These results demonstrated that phenotypically stable and functionally mature hBMSC-dSCs were generated efficiently via the co-culture of hiPSC-dSNs and hBMSC-derived SCLCs. Our findings may provide a promising protocol through which stable and fully developed hBMSC-dSCs can be used for transplantation to regenerate myelin sheath. Graphical abstract

Abstract In recent years, evidence for the anti-cancer activity of lichen secondary metabolites has been rapidly increasing. In this study, we synthesised analogues of diffractaic acid, a lichen secondary metabolite, and evaluated their ability to suppress colorectal cancer stem potential. Among the 10 compounds after H/CH₃/benzylation of the diffractaic acid structure or modifications in an aromatic hydrophobic domain, TU3 has a more inhibition effect on the stem potential of colorectal cancer compared to other compounds. The compound TU3 targets ALDH1 and suppresses key signalling pathways such as WNT, STAT3, NF-κB, Hedgehog, and AP-1. Inhibition of these signalling pathways by TU3 contribute to attenuate the survival mechanisms of colorectal cancer stem cell and thus inhibit cancer progression.

Abstract Background ARDS is a heterogeneous syndrome involving different subphenotypes with different clinical features and different responses to treatment strategies. The prone position (PP) is an effective treatment for ARDS; however, whether the effects of prone positioning vary among ARDS patients with different subphenotypes remains unknown. Objectives To evaluated the impact of PP on ventilation-perfusion matching(VQ matching) by contrast-enhanced Electrical impedance tomography (EIT) in ARDS patients with different subphenotypes. Methods This was a prospective, observational study at the medical ICU of Zhongda Hospital, Southeast University. ARDS patients undergoing mechanical ventilation were screened and allocated to different subphenotypes based on lung morphology (focal/non-focal) and D-dimer level (low/high D-dimer). EIT was used in the supine position and 3 h, 6 h, and 12 h after the PP during the first PP session. Results From July 1, 2021, to July 1, 2022, 25 patients were included in this study. 10 patients (40%) were focal ARDS, and 15 were non-focal ARDS based on baseline morphology. 12 patients (48%) were high D-dimer ARDS, and 13 were low D-dimer ARDS based on baseline D-dimer levels. PaO2/FiO2 increased significantly 3 h after prone positioning in focal ARDS patients (130.30[109.94–147.30] vs. 213.50[176.00-256.50] mmHg, p

Background: Accurately identifying and localizing the five subtypes of intracranial hemorrhage (ICH) are crucial steps for subsequent clinical treatment; however, the lack of a large computed tomography (CT) dataset with annotations of the categorization and localization of ICH considerably limits the development of deep learning-based identification and localization methods. We aimed to construct this large dataset and develop a deep learning-based model to identify and localize the five ICH subtypes, including intraventricular hemorrhage (IVH), intraparenchymal hemorrhage (IPH), subdural hemorrhage (SDH), subarachnoid hemorrhage (SAH), and epidural hemorrhage (EDH), in non-contrast head CT scans. Methods: Based on the public Radiological Society of North America (RSNA) 2019 dataset, we constructed a large CT dataset named RSNA 2019+ that was annotated for bleeding localization of the five ICH subtypes by three radiologists. An improved YOLOv8 architecture with the bidirectional feature pyramid network was proposed and trained using the RSNA 2019+ training dataset and evaluated on the RSNA 2019+ test dataset. The public CQ500, and two private datasets collected from the Xinqiao and Sunshine Union Hospitals, respectively, were also annotated to perform multicenter validation. Furthermore, the performance of the deep learning model was compared with that of four radiologists. Multiple performance metrics, including the average precision (AP), precision, recall and F1-score, were used for performance evaluation. The McNemar and chi-squared tests were performed, and the 95% Wilson confidence intervals were given for the precision and recall. Results: There were 175,125; 4,707; 8,259; and 3,104 bounding boxes after annotation on the RSNA 2019+; CQ500+; and the PD 1 and PD 2 datasets, respectively. With an intersection-over-union threshold of 0.5, the APs of IVH, IPH, SAH, SDH and EDH are 0.852, 0.820, 0.574, 0.639, and 0.558, respectively, yielding a mean average precision (mAP) of 0.688 for our proposed deep learning model on the RSNA 2019+ test dataset. For the multicenter validation involving the three external datasets, the mAPs for CQ500, PD1, and PD2 were 0.594, 0.734, and 0.66, respectively, which is comparable to those of radiologist with eight years of experience in head CT interpretation. Conclusion: The deep learning model developed from the constructed RSNA 2019+ dataset exhibited good potential in identifying and localizing the five ICH subtypes in CT slices and has the potential to assist in the clinical diagnosis.

Abstract Background Inherited metabolic disorders (IMDs) are a significant cause of morbidity and death among children. To determine the cost-effectiveness of newborn screening for IMDs using tandem mass spectrometry (MS/MS) compared to the non-screened group in China. Methods We constructed a decision tree screening model based on the Chinese clinical path of tandem MS/MS screening for inherited metabolic disorders (IMDs) from the medical health system. This model simulated the mechanism of screening in the prevention and treatment of IMDs. The IMDs screening data was collected from Children’s Hospital of Shanghai between 2010 and 2021. The Quality-adjusted life years (QALYs) and life expectancy were obtained from literature, while cost data was mainly sourced from hospital records and literature. Results In the base-case analysis, the total lifetime cost per patient was higher for the MS/MS screened group at 1,000,452 Chinese Yuan (CNY) (USD 143,515), compared to 157,303 CNY (USD 22,565) for the non-screened group. The QALYs gained were 16.47 and 3.97 for the screened and non-screened groups, respectively. The incremental cost-effectiveness ratio (ICER) of the MS/MS screened group compared to the non-screened group was 67,417 CNY (USD 9,671) per QALY gained, which is under the threshold of 3 times per capita GDP of China in 2022 (242,928 CNY, USD 34,848). The benefit-cost ratio (BCR) was 4.23, which means that for every 1 CNY (USD 0.1434506) invested, a return of 4.23 CNY (USD 0.57) can be obtained. The probability of cost-effectiveness was 100% in the MS/MS screened group compared to the non-screened group, indicating that the results of the base case analysis were robust. Conclusion Compared to the non-screened group, the MS/MS screened group incurs higher costs but also yields significantly greater QALY gains. Considering both the costs and benefits, the MS/MS screened group is an attractive cost-effective option at the current willingness-to-pay threshold for IMDs screening in China.

Abstract Background Severe cases of COVID-19 are characterized by an excessive presence of neutrophils. Neutrophil extracellular traps (NETs), released by activated neutrophils due to SARS-CoV-2 infection, contribute to lung epithelial cell death and are key drivers in COVID-19-associated immunothrombosis. However, the mechanism underlying NET formation in COVID-19 remain unclear. Methods Extracellular vesicles (EVs) were isolated from the serum of COVID-19 patients and healthy volunteers, while neutrophils were isolated from blood samples of healthy volunteers. Neutrophils were treated with EVs, and the formation of NETs was observed. To identify the components responsible for the COVID-19-EVs-induced NET formation, we analyzed the expression profiles of microRNA (miRNAs) in COVID-19-EVs. We identified eight highly expressed miRNAs in COVID-19-EVs and explored their potential roles in COVID-19-EVs-mediated NET formation. Additionally, we explored the role of miR-20b-5p in COVID-19-EVs-induced NET formation. Results In this study, we demonstrate that patients with COVID-19 have a higher concentration of serum EVs (COVID-19-EVs) than healthy controls (Normal-EVs). We also found that COVID-19-EVs are internalized by neutrophils to induced NET formation. Through comprehensive miRNA profiling of COVID-19-EVs versus Normal-EVs, we identified 78 differentially expressed miRNAs, with 27 of these being upregulated and 51 being downregulated. Subsequently, we discovered that COVID-19-EVs that were highly abundant with certain miRNAs promote NET formation. Specifically, miR-20b-5p was found to be the strongest inducer of NET formation of the identified miRNAs. Inhibition of miR-20b-5p resulted in a significant decrease in COVID-19-EVs-mediated induction of NET formation. Conclusion Herein, we reveal a previously unknown role of COVID-19-EVs in NET formation, which contributes to COVID-19 progression. This study suggests that miR-20b-5p may serve as a potential therapeutic target for COVID-19 treatment.

Abstract Background Early treatment and prevention are the keys to reducing the mortality of VTE in patients with thoracic trauma. This study aimed to develop and validate an automatic prediction model based on machine learning for VTE risk screening in patients with thoracic trauma. Methods In this national multicenter retrospective study, the clinical data of chest trauma patients hospitalized in 33 hospitals in China from October 2020 to September 2021 were collected for model training and testing. The data of patients with thoracic trauma at Shanghai Sixth People’s Hospital from October 2021 to September 2022 were included for further verification. The performance of the model was measured mainly by the area under the receiver operating characteristic curve (AUROC) and the mean accuracy (mAP), and the sensitivity, specificity, positive predictive value, and negative predictive value were also measured. Results A total of 3116 patients were included in the training and validation of the model. External validation was performed in 408 patients. The random forest (RF) model was selected as the final model, with an AUROC of 0·879 (95% CI 0·856–0·902) in the test dataset. In the external validation, the AUROC was 0.83 (95% CI 0.794–0.866), the specificity was 0.756 (95% CI 0.713–0.799), the sensitivity was 0.821 (95% CI 0.692–0.923), the negative predictive value was 0.976 (95% CI 0.958–0.993), and the positive likelihood ratio was 3.364. Conclusions This model can be used to quickly screen for the risk of VTE in patients with thoracic trauma. More than 90% of unnecessary VTE tests can be avoided, which can help clinicians target interventions to high-risk groups and ensure resource optimization. Although further validation and improvement are needed, this study has considerable clinical value.

Abstract To compare the early to mid-term clinical efficacy of the direct anterior approach (DAA) versus the posterolateral approach (PLA) in total hip arthroplasty (THA) for middle-aged and elderly patients with femoral neck fractures. The patients in our hospital from January 2021 to January 2023 were retrospectively selected. Patients were divided into the DAA group (n = 64 cases) and PLA group (n = 69 cases) based on a non-randomized concurrent controlled trial method. Baseline clinical characteristics and preoperative and postoperative data of patients were collected. These patients were followed up one year. There were no significant differences in baseline characteristics between the two groups (P > 0.05). Compared to the PLA group, the DAA group had shorter surgery times (66.33 ± 6.27 vs. 83.32 ± 7.17), shorter incision lengths (9.94 ± 1.10 vs. 13.00 ± 1.48), less intraoperative bleeding (177.81 ± 62.55 vs. 306.34 ± 50.49), and shorter times to postoperative ambulation (1.72 ± 0.83 vs. 3.48 ± 0.63), with all differences being statistically significant (P 0.05). However, the DAA group was significantly higher than the PLA group at 1 month, 3 months, and 6 months postoperatively (P 0.05), but the VAS scores were significantly reduced at 1 day, 3 days, 1 week, and 1 month postoperatively in the DAA group (P 0.05). The DAA demonstrates a clear advantage over the PLA in the early to mid-term postoperative period of THA, with less trauma and faster recovery. Given these benefits, the DAA technique is recommended for widespread adoption in clinical practice.

Abstract Chaotic systems have been widely employed in constructing hash functions because of their nonlinear characteristics. Nonetheless, some chaotic hash functions are intricately designed, significantly increasing their computational overhead, and some can only generate a single hash value of fixed length, thus lacking flexibility. To overcome the above problems, a novel hash function based on a 2D linear cross-coupled hyperchaotic map (HF-2DLCHM) is introduced and has a parallel feedback structure. Compared to the typical 1D chaotic maps, 2DLCHM has superior dynamic complexity, allowing HF-2DLCHM to resist phase space reconstruction attacks. A parallelizable structure is introduced, enhancing computational efficiency through concurrent processing of operational units. Simultaneously, the feedback mechanism is incorporated to augment the diffusion effect, ensuring better mixing and distribution of information. Moreover, by controlling the size of the input parameter T, the scheme can generate a hash value of $$32 \times T$$ bits. The experimental results illustrate that this scheme exhibits distribution, confusion, diffusion and collision resistance characteristics approaching their nearly ideal benchmarks while maintaining an acceptable speed. Therefore, this scheme holds substantial practical potential in the domain of data security and privacy protection.

Highlights The light management strategy is introduced into two-dimensional Dion-Jacobson (2D DJ) perovskite and subsequently elucidated both experimentally and theoretically. The synthesis of surface-patterned BDAPbBr4 microplates with high crystalline quality demonstrates the first reported instance of growing such 2D DJ-type perovskite microplates. The optimized device exhibits excellent photodetection performance under UV region. Moreover, this work represents the successful demonstration of BDAPbBr4 perovskite for UV weak-light communication, imaging, and polarized light detection.

Cloud interference significantly affects infrared (IR) satellite observations, posing substantial challenges in data assimilation. The geostationary interferometric infrared sounder (GIIRS) onboard Fengyun-4A (FY-4A), the first IR hyperspectral instrument carried on a geostationary satellite, has been extensively evaluated through direct clear-sky assimilation. However, its utility in cloud-affected areas has yet to be thoroughly evaluated. This study investigates the impact of all-sky assimilating long-wave temperature channels from GIIRS on forecasts of binary typhoons Maysak and Haishen (2020) using the Weather Research Forecast model. Quality control procedures, observation error settings, and variational bias corrections are incorporated into the three-dimensional variational data assimilation system for both clear-sky and all-sky scenarios. These approaches mitigate negative observation-minus-background statistics, producing a more symmetric distribution, along with a better brightness temperature simulation under all-sky conditions. Furthermore, assimilating all-sky GIIRS observations enhances the depiction of detailed typhoon structures, such as the upper level warmer distribution in Maysak, accompanied by larger analysis variations. This process also improves subsequent typhoon track and landfall precipitation forecasts. This research highlights the significance of employing high-temporal IR data in cloudy regions for the all-sky assimilation of FY-4A GIIRS data.

Objective: To investigate the potential efficacy and safety of Lutai Danshen Baishao granules (LDBG) for treating female melasma associated with kidney deficiency and blood stasis patterns. Methods: A randomized, double-blind, placebo-controlled trial was conducted at the Third Central Hospital of Tianjin, China from March to December 2023. A total of 110 female patients with melasma linked to kidney deficiency and blood stasis were enrolled and treated with either LDBG or a placebo twice daily for 60 days. Efficacy was assessed through measures such as the total melasma area, reduced melasma area, reduction rate of melasma area, melasma color score, Melasma Area and Severity Index (MASI) score, and traditional Chinese medicine (TCM) symptom score scale. Safety assessments included routine blood and biochemical tests. Results: Participants in both groups were aged 52–63 years, with no significant differences. After the 2-month intervention, the total melasma area decreased in both groups; however, a greater reduction was observed in the test group [462.50 mm2 (12.81%) vs. 100.00 mm2 (3.11%), P

Abstract Introduction The core objective of this study was to precisely locate metastatic lymph nodes, identify potential areas in nasopharyngeal carcinoma patients that may not require radiotherapy, and propose a hypothesis for reduced target volume radiotherapy on the basis of these findings. Ultimately, we reassessed the differences in dosimetry of organs at risk (OARs) between reduced target volume (reduced CTV2) radiotherapy and standard radiotherapy. Methods and materials A total of 209 patients participated in the study. We used image registration techniques to map patients’ neck metastatic lymph nodes onto a template CT of healthy individuals. Using MIM software, we integrated all patients’ lymph node images onto the template CT images and conducted an in-depth analysis of their distribution characteristics and metastatic patterns. Subsequently, we randomly selected the localization images of 30 patients and used paired t test methods to compare the differences in the dosimetry of target volumes and OARs between reduced target volume radiotherapy and standard radiotherapy. Results A total of 2314 metastatic lymph nodes were identified and mapped. There were no metastatic lymph nodes observed at level VIIb or within the lateral border of the common carotid artery. The percentages of metastatic lymph nodes at levels Ia, Ib, IIa, IIb, III, IVa, IVb, Va, Vb, Vc, VIa, VIb, VIIa, VIIb and VIII accounted for 0%, 1.5%, 22.8%, 41.1%, 15.9%, 3.0%, 0%, 4.4%, 1.0%, 0.3%, 0%, 0%, 9.7%, 0% and 0.3%, respectively, of the 2314 metastatic lymph nodes. Further analysis of the dosimetric outcomes revealed a significantly lower mean dose to the oral cavity, laryngeal cavity, esophagus, trachea, pharyngeal constrictor muscles, parotid gland, submandibular gland and thyroid gland with the implementation of reduced-target radiotherapy than with standard radiotherapy. Conclusion IMRT sparing level I, IVb, VI, and VIIb lymph nodes and the area within the lateral border of the common carotid artery for stage II-IVa NPC patients is feasible. This method can significantly reduce the dose to peripheral organs at risk.

Abstract Background Osteoarthritis (OA), characterized by progressive degeneration of cartilage and reactive proliferation of subchondral bone, stands as a prevalent condition in orthopedic clinics. However, the precise mechanisms underlying OA pathogenesis remain inadequately explored. Methods In this study, Random Forest (RF), Least Absolute Shrinkage and Selection Operator (LASSO), and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) machine learning techniques were employed to identify hub genes. Based on these hub genes, an Artificial Neural Network (ANN) diagnostic model was constructed. The Drug Signatures Database (DSigDB) was utilized to screen small-molecule drugs targeting these hub genes, and molecular docking analyses and molecular dynamics simulations were employed to explore and validate the binding interactions between proteins and small-molecule drugs. Expression changes of the hub genes under inflammatory conditions were validated through in vitro experiments, including RT-qPCR and Western blotting, and the therapeutic effects of the identified small-molecule drug on chondrocytes under inflammatory conditions were further verified in vitro. Lastly, Mendelian randomization analysis was conducted to examine the causal association between progesterone levels and various OA phenotypes. Results In this study, we identified three hub genes: interleukin 1 receptor-associated kinase 3 (IRAK3), integrin subunit beta-like 1 (ITGBL1), and Ras homolog family member U (RHOU). An Artificial Neural Network (ANN) diagnostic model constructed based on these hub genes demonstrated excellent performance in both training and validation phases. Screening with the Drug Signatures Database (DSigDB) identified progesterone as a small-molecule drug targeting these key proteins. Molecular docking analysis using AutoDock Vina revealed that progesterone exhibited binding energies of ≤ -7 kcal/mol with each of the key proteins, indicating strong binding affinity. Furthermore, molecular dynamics simulations validated the stability and strength of these interactions. RT-qPCR and Western blotting confirmed the downregulation of the hub genes in IL-1β-treated chondrocytes. Western blotting also demonstrated the potential therapeutic effects of progesterone on IL-1β-treated chondrocytes. Finally, Mendelian randomization analysis established a significant association between progesterone levels and multiple OA phenotypes. Conclusion In our study, IRAK3, ITGBL1, and RHOU were identified as potential novel diagnostic and therapeutic targets for OA. Progesterone was preliminarily validated as a small-molecule drug with potential effects on OA. Further research is crucial to elucidate the pathogenesis of OA and the specific therapeutic mechanisms involved.

Abstract Background Ewing’s sarcoma (EwS), a common pediatric bone cancer, is associated with poor survival due to a lack of therapeutic targets for immunotherapy or targeted therapy. Therefore, more effective treatment options are urgently needed. Methods Since novel immunotherapies may address this need, we performed an integrative analysis involving single-cell RNA sequencing, cell function experiments, and humanized models to dissect the immunoregulatory interactions in EwS and identify strategies for optimizing immunotherapeutic efficacy. Results EwS is infiltrated by immunosuppressive myeloid populations, T and B lymphocytes, and natural killer cells. We found that SLC40A1 and C1QA macrophages were associated with a poor prognosis, whereas CD8+ T-cell infiltration was associated with a good prognosis. A comparative analysis of paired samples revealed that in tumors with a good chemotherapeutic response, macrophages presented increased antigen presentation and reduced release of protumor cytokines, whereas CD8+ T cells presented increased cytotoxicity and reduced exhaustion. An interaction analysis revealed a vast immunoregulatory network and identified MIF-CD74 as a crucial immunoregulatory target that can simultaneously promote M2 polarization of macrophages and inhibit CD8+ T-cell infiltration. Importantly, MIF blockade effectively reshaped the tumor immune microenvironment, turning cold tumors hot and inhibiting tumor growth. Conclusions Our integrative analysis revealed that the MIF/CD74 axis is a promising target for the treatment of Ewing sarcoma and provides a rationale for this novel immunotherapy.

Abstrct Rotator cuff injury (RCI), characterized by shoulder pain and restricted mobility, represents a subset of tendon-bone insertion injuries (TBI). In the majority of cases, surgical reconstruction of the affected tendons or ligaments is required to address the damage. However, numerous clinical failures have underscored the suboptimal outcomes associated with such procedures. Further investigations have revealed that these failures are largely attributable to delayed healing at the tendon-bone interface, excessive formation of vascularized scar tissue, and inadequate integration of tendon grafts within bone tunnels. As a result, the healing process of rotator cuff injuries faces significant challenges.Bone marrow-derived mesenchymal stem cell exosomes (BMSC-exos) have emerged as a prominent focus of research within the field of bioengineering, owing to their remarkable potential to regulate cellular proliferation and differentiation, modulate immune responses, and facilitate tissue repair and regeneration following cellular damage. In this review, we explore the anti-inflammatory, angiogenic, anti-scarring, and bone metabolism-modulating effects of BMSC-exos in the context of rotator cuff injury. Additionally, we address the limitations and ongoing challenges within current research, offering insights that could guide the clinical application of BMSC-exos in the treatment of rotator cuff injuries in the future.

Abstract Background The association between bedside ventilatory parameters—specifically arterial carbon dioxide pressure (PaCO2) and ventilatory ratio (VR)—and mortality in patients with acute respiratory distress syndrome (ARDS) remains a topic of debate. Additionally, the persistence of this association over time is unclear. This study aims to investigate the relationship between 28-day mortality in ARDS patients and their longitudinal exposure to ventilatory inefficiency, as reflected by serial measurements of PaCO2 and VR. Methods We conducted a secondary analysis of four randomized controlled trials (FACTT, ALTA, EDEN, and SAILS) from the ARDS Network. All included patients were intubated and received mechanical ventilation. Patients were excluded if they underwent extracorporeal life support or were on mechanical ventilation for less than one day. The primary outcome was 28-day mortality. Bayesian joint models were employed to estimate the strength of associations over time. Results A total of 2,851 patients were included in our analysis. The overall 28-day mortality rate was 21.3%, with a median duration of invasive mechanical ventilation of 9 days (IQR: 4–28 days). After adjustment, each daily increment in PaCO2 (HR 1.008, 95% CI 0.997–1.018) was not associated with mortality, while a daily increment in VR (HR 1.548, 95% CI 1.309–1.835) was associated with increased mortality. This association persisted during the prolonged stages (Days 0–23) of mechanical ventilation. Furthermore, a significant increase in the risk of death was related to daily exposure to VR > 2 (HR 1.088 per day, 95% CI 1.034–1.147) and its cumulative effect (HR 1.085 per area, 95% CI 1.050–1.122), whereas PaCO2 was found to be insignificant. Conclusion VR, which reflects ventilatory inefficiency, should be closely monitored during invasive mechanical ventilation. Cumulative exposure to high intensities of VR may be associated with increased mortality in patients with ARDS.

With the aggravation of global ecological and environmental problems, coordinating the development of the relationship between natural resources and seeking sustainable social and economic development has become an important topic of concern to the scientific community today. Economic forecasting serves for economic decision-making, which is to improve the scientific level of economic management, reduce the blindness of economic decision-making and improve the correctness of decision-making. This article constructs the prediction model of urban circular economy development based on artificial neural network (ANN), and puts forward the innovation strategy of urban circular economy development path. Simulation results show that the response speed of this method is 21.55% higher than that of the comparison method, and the accuracy rate reaches 97.78%. Moreover, it has obvious advantages over the traditional algorithm in terms of error and recall rate. Compared with the actual economic data, the economic data predicted by the model is quite consistent, and the prediction of future data by the model basically accords with the development goal of the regional master plan. Therefore, it is feasible to use this method to analyze the development path of urban circular economy.

Background: Extracorporeal membrane oxygenation (ECMO) has been proven to be a support method and technology for patients with cardiopulmonary failure. However, the transport of patients under ECMO support is challenging given the high-risk technical maneuvers and patient-care concerns involved. Herein, we examined the safety of ECMO during the transport of critically ill patients and its impact on mortality rates, to provide more secure and effective transport strategies in clinical practice. Method: To assess the safety of ECMO patient transport, this study conducted a retrospective analysis on critically ill adults who required ECMO support and transport at the intensive care unit (ICU) center between 2017 and 2023. The study utilized standard ECMO transport protocols and conducted a comprehensive statistical analysis of the collected clinical data and transport processes. The 28-day survival rate for ECMO patients was determined using Kaplan–Meier analysis, while logistic regression identified prognostic factors. Result: Out of 303 patients supported with ECMO, 111 (36.6%) were transported. 69.4% of the transport group were male, mean age was (42.0±17.0) years, mean body mass index was (24.4±4.6) kg/m2, and veno-arterial-ECMO accounted for 52.5%. The median transportation distance was 190 (interquartile range [IQR]: 70–260) km, and the longest distance was 8100 km. The median transit time was 180 (IQR: 100–260) min, and the maximum duration was 1720 min. No severe adverse events including death or mechanical failure occurred during transportation. The 28-day survival rate was 64.7% (n=196) and ICU survival rate was 56.1% (n=170) for the entire cohort; whereas, the 28-day survival rate was 72.1% (n=80) and ICU survival rate was 66.7% (n=74) in the transport group. A non-significant difference in 28-day survival was observed between the two groups after propensity score matching (P=0.56). Additionally, we found that acute physiology and chronic health evaluation II score (odds ratio [OR]=1.06, P 5 mmol/L, OR=2.80, P=0.01), and renal replacement therapy initiation (OR=3.03, P

Abstract. Neurological diseases are a major health concern, and brain injury is a typical pathological process in various neurological disorders. Different biomarkers in the blood or the cerebrospinal fluid are associated with specific physiological and pathological processes. They are vital in identifying, diagnosing, and treating brain injuries. In this review, we described biomarkers for neuronal cell body injury (neuron-specific enolase, ubiquitin C-terminal hydrolase-L1, αII-spectrin), axonal injury (neurofilament proteins, tau), astrocyte injury (S100β, glial fibrillary acidic protein), demyelination (myelin basic protein), autoantibodies, and other emerging biomarkers (extracellular vesicles, microRNAs). We aimed to summarize the applications of these biomarkers and their related interests and limits in the diagnosis and prognosis for neurological diseases, including traumatic brain injury, status epilepticus, stroke, Alzheimer’s disease, and infection. In addition, a reasonable outlook for brain injury biomarkers as ideal detection tools for neurological diseases is presented.

Abstract Human-machine interaction has emerged as a revolutionary and transformative technology, bridging the gap between human and machine. Gesture recognition, capitalizing on the inherent dexterity of human hands, plays a crucial role in human-machine interaction. However, existing systems often struggle to meet user expectations in terms of comfort, wearability, and seamless daily integration. Here, we propose a handwriting recognition technology utilizing an intelligent hybrid-fabric wristband system. This system integrates spun-film sensors into textiles to form the smart fabric, enabling intelligent functionalities. A thermal encapsulation process is proposed to bond multiple spun-films without additional materials, ensuring the lightweight, breathability, and stretchability of the spun-film sensors. Furthermore, recognition algorithms facilitate precise accurate handwriting recognition of letters, with an accuracy of 96.63%. This system represents a significant step forward in the development of ergonomic and user-friendly wearable devices for enhanced human-machine interaction, particularly in the virtual world.

Abstract Background The study is to evaluate the efficacy and safety of combined anlotinib and EGFR-tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) who had gradual, oligo, or potential progression after previous EGFR-TKIs treatment. Methods We conducted an open-label, single-arm, multicenter, phase II trial in China. Eligible patients were 18–75 years old with histologically or cytologically confirmed NSCLC who were EGFR mutation positive and showed gradual, oligo, or potential progression after EGFR-TKIs. Anlotinib (12 mg/day) was administered orally for 2 weeks and then off 1 week in a 3-week cycle. EGFR-TKIs were continue used. The primary endpoint was progression-free survival (PFS). The secondary endpoints included 6- and 12-month PFS rate, objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results From July 2019 to December 2022, 120 patients were enrolled. The median PFS (mPFS) was 9.1 months (95% CI 6.8–11.7). The PFS rates at 6 and 12 months was 68.5% and 38.8% respectively. For 86 patients with first-line 1st /2nd generation EGFR-TKIs, the mPFS was 9.2 months (95% CI 6.7–12.6). For 32 patients with first-line 3rd generation EGFR-TKIs, the mPFS was 10.3 months (95% CI 6.1–13.3). Overall ORR and DCR were 6.7% (95% CI 2.9–12.7) and 87.5% (95% CI 80.2–92.8), respectively. 52.5% of patients had grade 3 or higher treatment-emergent adverse events (TEAEs). Conclusion Anlotinib in combination with continuation of EGFR-TKIs prolonged the clinical benefit of EGFR-TKIs, demonstrating favorable survival outcomes and manageable toxicity in NSCLC treated with EGFR-TKIs and had specific progression modes, such as gradual progression. Trial registration NCT04007835.

Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery. Therefore, there is an urgent need to develop new methods for the treatment of this condition. Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions. They have low immunogenicity, good stability, high delivery efficiency, and the ability to cross the blood–brain barrier. These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke. The rapid development of nanotechnology has advanced the application of engineered exosomes, which can effectively improve targeting ability, enhance therapeutic efficacy, and minimize the dosages needed. Advances in technology have also driven clinical translational research on exosomes. In this review, we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke, including their anti-inflammation, anti-apoptosis, autophagy-regulation, angiogenesis, neurogenesis, and glial scar formation reduction effects. However, it is worth noting that, despite their significant therapeutic potential, there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes. Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke. Ultimately, our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.

Abstract Among the existing research on the treatment of disorders of consciousness (DOC), deep brain stimulation (DBS) offers a highly promising therapeutic approach. This comprehensive review documents the historical development of DBS and its role in the treatment of DOC, tracing its progression from an experimental therapy to a detailed modulation approach based on the mesocircuit model hypothesis. The mesocircuit model hypothesis suggests that DOC arises from disruptions in a critical network of brain regions, providing a framework for refining DBS targets. We also discuss the multimodal approaches for assessing patients with DOC, encompassing clinical behavioral scales, electrophysiological assessment, and neuroimaging techniques methods. During the evolution of DOC therapy, the segmentation of central nuclei, the recording of single-neurons, and the analysis of local field potentials have emerged as favorable technical factors that enhance the efficacy of DBS treatment. Advances in computational models have also facilitated a deeper exploration of the neural dynamics associated with DOC, linking neuron-level dynamics with macroscopic behavioral changes. Despite showing promising outcomes, challenges remain in patient selection, precise target localization, and the determination of optimal stimulation parameters. Future research should focus on conducting large-scale controlled studies to delve into the pathophysiological mechanisms of DOC. It is imperative to further elucidate the precise modulatory effects of DBS on thalamo-cortical and cortico-cortical functional connectivity networks. Ultimately, by optimizing neuromodulation strategies, we aim to substantially enhance therapeutic outcomes and greatly expedite the process of consciousness recovery in patients.

Abstract The blood–brain barrier (BBB) is the most central component of the neurovascular unit (NVU) and is crucial for the maintenance of the internal environment of the central nervous system and the regulation of homeostasis. A multitude of neuroprotective agents have been developed to exert neuroprotective effects and improve the prognosis of patients with ischemic stroke. These agents have been designed to maintain integrity and promote BBB repair. Statins are widely used as pharmacological agents for the treatment and prevention of ischemic stroke, making them a cornerstone in the pharmacological armamentarium for this condition. The primary mechanism of action is the reduction of serum cholesterol through the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which results in a decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in cholesterol clearance. Nevertheless, basic and clinical research has indicated that statins may exert additional pleiotropic effects beyond LDL-C reduction. Previous studies on ischemic stroke have demonstrated that statins can enhance neurological function, reduce inflammation, and promote angiogenic and synaptic processes following ischemic stroke. The BBB has been increasingly recognized for its role in the development and progression of ischemic stroke. Statins have also been found to play a potential BBB protective role by affecting members of the NVU. This review aimed to provide a comprehensive theoretical basis for the clinical application of statins by systematically detailing how statins influence the BBB, particularly focusing on the regulation of the function of each member of the NVU. Graphical Abstract

The Joint Video Experts Team (JVET) has announced the latest generation of the Versatile Video Coding (VVC, H.266) standard. The in-loop filter in VVC inherits the De-Blocking Filter (DBF) and Sample Adaptive Offset (SAO) of High Efficiency Video Coding (HEVC, H.265), and adds the Adaptive Loop Filter (ALF) to minimize the error between the original sample and the decoded sample. However, for chaotic moving video encoding with low bitrates, serious blocking artifacts still remain after in-loop filtering due to the severe quantization distortion of texture details. To tackle this problem, this paper proposes a Convolutional Neural Network (CNN) based VVC in-loop filter for chaotic moving video encoding with low bitrates. First, a blur-aware attention network is designed to perceive the blurring effect and to restore texture details. Then, a deep in-loop filtering method is proposed based on the blur-aware network to replace the VVC in-loop filter. Finally, experimental results show that the proposed method could averagely save 8.3% of bit consumption at similar subjective quality. Meanwhile, under close bit rate consumption, the proposed method could reconstruct more texture information, thereby significantly reducing the blocking artifacts and improving the visual quality.

Abstract The diagnostic and prognostic value of quantitative electroencephalogram (qEEG) in the the onset of postoperative delirium (POD) remains an area of inquiry. We aim to determine whether qEEG could assist in the diagnosis of early POD in cardiac surgery patients. We prospectively studied a cohort of cardiac surgery patients undergoing qEEG for evaluation of altered mental status. Delirium was assessed with the Confusion Assessment Method for the intensive care unit (CAM-ICU). The qEEG were interpreted by clinician, and reports were reviewed to identify features such as amplitude-integrated EEG (aEEG), relative band energy in ɑ/β/θ/δ frequencies, α variability and spectral entropy. The raw EEG was also preprocessed offline for nonlinear analysis including Multi-scale Entropy analysis (MSE) and Detrended Fluctuation Analysis (DFA). Linear regression was performed to quantify associations among EEG findings, delirium, and clinical outcomes. Receiver operating characteristic (ROC) analysis was used to assess the accuracy of the qEEG as POD prediction index. Meanwhile, a comprehensive comparison of dynamic complexity across time scales and DFA exponent α was conducted between the non-delirium and delirium groups. Among those recruited initially (n = 64), 60 patients were evaluated and 29 patients (48.3%) met delirium criteria. When comparing delirious and non-delirious participants, significant differences were found in terms of age (p = 0.03), APACHE II scores (p = 0.004), lactate (p = 0.03), and hospital days (p = 0.048). Multivariate regression analysis revealed that the first quartile (Q1) and fourth quartile (Q4) of peak or valley value of F3-P3/F4-P4 derivation (for example, Q1 of peak value for F3-P3 derivation: OR 12.4, 95% CI 1.72–89.76, p = 0.012) showed a higher association with the incidence of POD. ROC analysis demonstrated qEEG could predict POD with high sensitivity and specificity, yielding an overall good accuracy. For instance, the peak value of F3-P3 derivation (the area under the curve of 0.81), as a predictor of POD showed a sensitivity of 90% and specificity pf 72% (p

Abstract This study aims to compare the incidences of neurological deterioration (ND) and poor outcome (a modified Ranking scale > 2 points at discharge) among patients with different atherosclerotic stroke patterns. A total of 688 participants were categorized into 4 groups according to atherosclerotic stroke pattern: multiple small infarcts (MSI), single subcortical infarction (SSI), borderzone infarct (BZI) and large infarct groups. Among the 4 groups, MSI group had the lowest incidences of ND and poor outcome (13.5% and 16.2%, respectively). In multivariable analyses, for BZI patients, the risks of ND [odds ratio (OR) = 3.90, 95% confidence interval (CI) = 2.10–7.22, p

Abstract We present a versatile platform for label-free magnetic separation of plasma, tailored to accommodate diverse environments. This innovative device utilizes an advanced long-short alternating double Halbach magnetic array, specifically engineered for optimal magnetic separation. The array’s adaptability allows for seamless integration with separation channels of varying sizes, enabling static separation of whole blood. The platform has a highly flexible processing throughput, spanning from 100 μL to 3 mL per separation cycle without sacrificing separation efficiency. A key aspect of this device is its power-free operation throughout the separation process, obviating the complexity of conventional separation devices. Its effectiveness is demonstrated by the extraction of 40 μL of plasma from 100 μL of rat whole blood within 8 min. The separated plasma proved effective for subsequent analysis of antibody concentration and size in the separated plasma for pharmacokinetic investigations, yielding results on par with those obtained via centrifugation. Furthermore, the device’s high-throughput capability was validated using human whole blood, achieving 3 mL of plasma separation in just 1 min. In a follow-up study on COVID-19 IgG antibody detection, the results matched those from centrifugation. The device demonstrates a separation efficiency of 99.9% for cells larger than 1 μm in both rat and human blood samples, with a plasma recovery rate of 72.7%. In summary, our magnetic separation device facilitates rapid plasma extraction from whole blood, with a capacity of up to 3 mL per minute in human blood, without compromising subsequent plasma-based analyses, thereby highlighting its broad applicability across diverse settings.

Six new species of the genus Paederus Fabricius, 1775 from China are described: P. chentangus sp. nov. (Xizang: Chentang), P. mirus sp. nov. (Xizang: Xiayadong), P. songi sp. nov. (Chongqing: Polaoxiang), P. trispinosus sp. nov. (Hubei: Houhe), P. (Harpopaederus) yei sp. nov. (Hubei: Cuijia’ao), and P. zhaoi sp. nov. (Zhejiang: Majian). A key to the micropterous Paederus species of mainland China is given.

It is well known that crossbreds show many advantages over purebreds in improving calf health traits, but the immunological factors responsible for this heterosis remain largely unclear. The objective of this study was to compare the cellular immune responses and antibodies of Holstein (HO) and Montbéliarde-sired × Holstein (MH) F1 generation female calves, and investigate the effects of crossbreeding on the immunity. Fifty three-month-old healthy female calves (25 HO, 25 MH) were selected meticulously in a farm with the same criteria. Subsequently, complete blood count, flow cytometric analysis of T cell subsets and intracellular IFN-γ production, as well as indirect ELISA analysis of antibodies were performed in order to determine the immune profiles of the two groups of calves. We found that MH calves had higher percentage and number of CD4+ and CD8+ T cells than HO calves in the peripheral blood (p

Plant extracts have been widely considered as a feed additive. Rehmannia glutinosa catalpol can promote the growth performance of the host, improve the immune response, and strengthen the intestinal barrier function of the host. The broilers were fed with Rehmannia glutinosa catalpol (0.01%), and the composition of caecum microbiota in broilers was explored by 16S rRNA gene sequencing. Finally, the changes of intestinal mucosa morphology and immune function were analysed by tissue staining and RT-qPCR. The proportion of thick-walled bacteria in the treatment group was higher than that in the control group. At the genus level, the relative abundance of Faecalibacterium, Paraacteroides and Barnesiella increased after the addition of Rehmannia glutinosa catalpol. The function prediction results of PICRUSt2 showed that the microbiota mainly participated in the biosynthesis and degradation/utilization/association pathway. The results of tissue staining and RT-qPCR showed that the caecum tissue morphology and immune barrier function of broilers were significantly improved after the addition of catalpol. The results of this study show that Rehmannia glutinosa catalpol in the diet may be beneficial to the intestinal health of broilers, which may be achieved by regulating the intestinal microbiota and enhancing the immune function of broilers.

In recent years, eutectic high entropy alloys have been found to have excellent mechanical properties and corrosion resistance; however, the simultaneous achievement of these mechanical properties and high-temperature oxidation resistance still constitutes a tough challenge. In this study, Ta and Cr elements are added to (FeCoNiNb)98Al2 high-entropy alloy to improve oxidation resistance, and the changes in microstructure and mechanical properties of (FeCoNiNb)98-2x(TaCr)xAl2 as well as the oxidation behaviors at 900 °C are systematically investigated. The results show that the addition of Ta and Cr elements promotes the increase and growth of the Laves phase in the alloy, which improves the oxidation resistance of the alloy and maintains the excellent mechanical properties of (FeCoNiNb)98Al2. The formation of CrTaO4, CrNbO4, and Cr2O3 composite oxide scales can not only prevent the diffusion of O into the alloy, but also inhibit the external diffusion of matrix elements. This result provide experimental data and theoretical support for the optimal design of the high-entropy alloy compositions to improve their antioxidant properties while maintaining excellent mechanical properties.

Abstract Background Trastuzumab, a monoclonal antibody for breast cancer, faces global accessibility challenges, primarily due to high costs. This study examines how changes in medical insurance policies and price adjustments influence Trastuzumab utilization in China, focusing on implementation challenges and their impact on drug accessibility and affordability. Methods This retrospective study investigated Trastuzumab utilization among HER2-positive breast cancer patients at a tertiary hospital from May 2013 to December 2022 in JX, a prefecture-level city in eastern China. Patients were stratified based on their CerbB2 indicator, because those with a 2 + CerbB2 status require further FISH testing to confirm Trastuzumab eligibility. We analyzed the utilization rates of both FISH test and Trastuzumab using logistic regressions, identifying factors that influence their usage. Results 766 patients were included. The utilization rate of Trastuzumab among patients with CerbB2 3+ rose from 40.40 to 77.94% in September 2017 following the expansion of insurance coverage, and further increased to 90.41% after a price reduction in 2020. The FISH test was not covered by health insurance, and it was not available in the local hospital until Trastuzumab became available in JX city. For patients with CerbB2 2+, the proportion undergoing the FISH test increased dramatically from 8.89 to 82.08% after the price reduction in 2020. The mere inclusion into basic medical insurance, regardless of insurance types, significantly increased the utilization of Trastuzumab and the FISH test. However, rural patients in JX city are still facing financial burdens with Trastuzumab's out-of-pocket cost accounting for 62.9% of their annual disposable income in 2020. Conclusions Our findings indicate that insurance coverage and price reduction significantly increased Trastuzumab utilization. However, failure to improve the accessibility of the FISH test can pose challenges in enhancing the uptake of Trastuzumab among eligible patients. With the expiration of Trastuzumab's patent and the development of affordable biosimilars, there are now greater opportunities to enhance treatment access globally. These insights can inform policy makers of implementation guidance about providing financial support for breast cancer patients in other LMICs.

Abstract Background Osteoporosis is a significant concern among individuals with lupus nephritis (LN), with reported prevalence rates exhibiting considerable variation. This study investigates the prevalence and identifies risk factors contributing to osteoporosis in premenopausal and postmenopausal LN patients, addressing the paucity of data specific to the Chinese population. Methods This cross-sectional study enrolled patients with renal biopsy-proven LN, who underwent bone mineral density (BMD) measurements using dual X-ray absorptiometry at the lumbar spine, total hip, and femoral neck. The study was conducted at Tongji hospital from May 2011 to June 2018. Results A total of 130 patients were evaluated, with a mean age of 46.2 ± 12.9 years, including 2 males and 128 females. A significant majority, 52.3% (n = 67) of the female patients, were identified as postmenopausal. BMD measurements revealed that 40.0% of patients had osteoporosis in at least one site. The spearman rank correlation of BMD with clinical characteristics indicated that age at menopause, weight, height, and body mass index were positively correlated with BMD, while age, age at diagnosis of LN, and menopause duration were negatively correlated with BMD in lumbar spine, total hip, and/or femoral neck. Multivariable linear regression analysis demonstrated that body mass index was positively associated with BMD, whereas disease duration and menopause duration were negatively associated with BMD in all and postmenopausal patients. Postmenopausal patients consistently had a higher prevalence of osteoporosis across all measured sites. Factors such as older age, lower weight, and the absence of bisphosphonates therapy were independently associated with an increased risk of osteoporosis in LN patients. Conclusion Our findings underscore a substantial prevalence of osteoporosis in LN patients, especially among postmenopausal individuals. The study identifies older age, lower weight, and absence of bisphosphonates treatment as risk factors for osteoporosis in this patient population.

Abstract Blockchain after several years of hustle, bustle, precipitation, and sublimation, with the landing application step by step towards maturity and development, gradually spawned the outreach needs of interacting with other applications. At this stage, only the mobility cross-chain interoperability technology is the infrastructure system that can perfectly solve such needs. To achieve a cross-chain system that defines and realizes user-free liquidity interoperability according to the cross-chain environment and cross-chain requirements, this paper designs a convex optimization-based liquidity contract pair cross-chain model. This model can realize a uniform distributed NFT ID construction identification method for the whole chain, and at the same time use the convex optimization model to obtain liquidity contract pairs that have and only have the global optimal matching, and in this way lock the shortest cross-chain time required, with AMM bonding curve management to achieve immediate liquidity effect, and realize the interconnection and interoperability of users’ assets with free liquidity. Finally, the time-consumption, robustness, and radius of convergence of the models are tested by comparing the model experiments and the proposed model’s proposed cross-chain incentive experiments yield results that verify that the proposed convex optimization-based liquidity contract is efficient, applicable, and secure for cross-chain models.

Abstract Background Alcohol drinking and gut microbiota are related to hepatocellular carcinoma (HCC), but the specific relationship between them remains unclear. Aims We aimed to establish the alcohol drinking-gut microbiota-liver axis and develop machine learning (ML) models in predicting the occurrence of early-stage HCC. Methods Two hundred sixty-nine patients with early-stage HCC and 278 controls were recruited. Alcohol drinking-gut microbiota-liver axis was established through the mediation/moderation effect analyses. Eight ML algorithms including Classification and Regression Tree (CART), Gradient Boosting Machine (GBM), K-Nearest Neighbor (KNN), Logistic Regression (LR), Neural Network (NN), Random Forest (RF), Support Vector Machine (SVM), and eXtreme Gradient Boosting (XGBoost) were applied. Results A total of 160 pairs of individuals were included for analyses. The mediation effects of Genus_Catenibacterium (P = 0.024), Genus_Tyzzerella_4 (P

Abstract Density wave (DW) order is believed to be correlated with superconductivity in the recently discovered high-temperature superconductor La3Ni2O7. However, experimental investigations of its evolution under high pressure are still lacking. Here, we explore the quasiparticle dynamics in bilayer nickelate La3Ni2O7 single crystals using ultrafast optical pump-probe spectroscopy under high pressures up to 34.2 GPa. At ambient pressure, the temperature-dependent relaxation dynamics demonstrate a phonon bottleneck effect due to the opening of an energy gap around 151 K. The energy scale of the DW-like gap is determined to be 66 meV by the Rothwarf-Taylor model. Combined with recent experiential results, we propose that this DW-like transition at ambient pressure and low temperature is spin density wave (SDW). With increasing pressure, this SDW order is significantly suppressed up to 13.3 GPa before it completely disappears around 26 GPa. Remarkably, at pressures above 29.4 GPa, we observe the emergence of another DW-like order with a transition temperature of approximately 135 K, which is probably related to the predicted charge density wave (CDW) order. Our study provides the experimental evidences of the evolution of the DW-like gap under high pressure, offering critical insights into the correlation between DW order and superconductivity in La3Ni2O7.

Abstract Background Thoracic epidural anesthesia (TEA) is associated with a knowledge gap regarding its mechanisms in lung protection and reduction of postoperative pulmonary complications (PPCs). Driving pressure (ΔP), an alternative indicator of alveolar strain, is closely linked to reduced PPCs with lower ΔP values. We aim to investigate whether TEA contributes to lung protection by lowering ΔP during mechanical ventilation. Methods In this prospective, randomized, patient and evaluator-blinded parallel study, adult patients scheduled for elective major upper abdominal surgery were assigned to either the TEA group with combined thoracic epidural anesthesia and general anesthesia (TEA-GA) (n = 30) or the control group with only general anesthesia (GA) (n = 30). Measurements The primary outcome was the minimum ΔP determined based on positive end-expiratory pressure (PEEP) after intubation. Secondary outcomes included the incidence of PPCs within seven days, the minimum ΔP at various time points, blood gas analysis, intensive care unit (ICU) admission rates, length of hospital stay, and 30-day mortality rate. Results The TEA group had a significantly lower minimum ΔP titrated based on PEEP compared to the control group (11.23 ± 2.19 cmH2O vs. 12.67 ± 2.70 cmH2O; P = 0.028). Multivariate linear regression analysis showed that intraoperative TEA application (compared with its absence; unstandardized beta coefficient (B) = -1.289; P = 0.008) significantly correlated with ΔP. The incidence of PPCs did not differ significantly between the two groups (8 of 30 [26.7%] vs. 12 of 30 [40%]; P = 0.273), but the incidence of atelectasis in the TEA group was significantly lower than in the control group (5 of 30 [16.7%] vs. 12 of 30 [40.7%]; P = 0.012). Multivariate logistic regression analysis indicated that ΔP was the only variable significantly associated with PPCs (Adjusted Odds Ratio [OR] = 2.190; 95% Confidence Interval [CI]: 1.300 to 3.689; P = 0.003). Conclusion Compared to GA, TEA-GA can reduce intraoperative ΔP in patients undergoing major upper abdominal surgery, especially those undergoing laparoscopic surgery. However, compared to GA combined with ΔP-guided ventilation, TEA-GA combined with ΔP-guided ventilation does not reduce the risk of PPCs. There was no significant difference in the total use of various vasoactive drugs between the two groups. Trial registration This study was registered in the Chinese Clinical Trial Registry (registration number ChiCTR2300068778 date of registration February 28, 2023).

Abstract Background Blood-brain barrier (BBB) disruption after stroke is closely associated with brain tissue edema and neuronal injury, which requires accurate assessment. However, there is a lack of appropriate BBB imaging modality in vivo. As albumin in the blood could cross the damaged BBB into brain tissue after stroke, it serves as a biomarker for BBB disruption. Therefore, we aimed to develop an albumin-seeking near-infrared (NIR) probe to assess BBB disruption in stroke. Results We proposed a chemoselective strategy for seeking albumin with NIR dyes and identified an optimal probe to evaluate BBB disruption in stroke. The probe combined a NIR fluorescent dye with inherent albumin-targeting moieties and exhibited high affinity and selectivity for binding to albumin. Using a mouse stroke model, the probe displayed a high-resolution visualization of the location and extent of BBB disruption in vivo and correlated well with BBB leakage measured by Evans blue ex vivo. A dual-channel NIR-II imaging was successfully used to simultaneously assess BBB disruption and cerebral perfusion after stroke. Furthermore, we applied this method to dynamically evaluate the BBB disruption process and reperfusion of thrombolytic therapy in a stroke model in real time, which showed excellent application value. Conclusions We developed an albumin-seeking NIR probe that accurately evaluated BBB disruption in a safe, non-invasive and real-time manner in various stroke models, and has a great potential guiding stroke treatment in a real-time manner. Graphical Abstract

Abstract Background Emerging evidence suggests that circadian rhythms play a role in the regulation of cardiovascular diseases (CVDs). We aim to examine the relationship between the 24-hour behavior rhythms (activity-rest and feeding-fasting rhythms) and stroke. Methods The study included 3201 adult participants with prediabetes/diabetes from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. The 24-hour behavior rhythm indices were calculated using data from accelerometer wearable device and dietary recall for two nonconsecutive days. Six indices were calculated including interdaily stability (IS), intradaily variability (IV), relative amplitude (RA), average activity during the least active continuous 5-hour period (L5), Average activity during the most active continuous 10-hour period (M10) which reflects the activity-rest rhythm, and feeding rhythm score which reflects the feeding-fasting rhythm. These continuous variables were divided into quintiles for logistic regression models. Results Comparing participants in quintile 1, those in quintile 5 of IS and RA exhibited a lower odds of stroke. Conversely, participants in quintile 5 of IV, L5, and L5 start time demonstrated a higher odds of stroke. Furthermore, participants in quintile 5 of feeding rhythm score had a significantly lower odds of stroke. The associations of IV and feeding rhythm score with stroke were more pronounced in participants with diabetes compared to those with prediabetes/diabetes. No significant associations were observed between other 24-hour behavior rhythms and stroke. Conclusions Overall, this study highlights a significant association between 24-hour behavior rhythm and stroke in American adults with prediabetes/diabetes.

Abstract Background Rapid diagnosis of pulmonary tuberculosis (PTB) is urgently needed. We aimed to improve diagnosis rates by combining tuberculosis-interferon (IFN)-γ release assays (TB-IGRA) with metagenomic next-generation sequencing (mNGS) for PTB diagnosis. Methods A retrospective study of 29 PTB and 32 non-TB patients from our hospital was conducted between October 2022 and June 2023. Samples were processed for TB-IGRA and mNGS tests according to the manufacturer’s protocol. Results The levels of IFN-γ release in PTB patients were significantly higher than those in non-TB patients (604.15 ± 112.18 pg/mL, and 1.04 ± 0.38 pg/mL, respectively; p

Abstract Background The efficacy of immune checkpoint blockade therapy in patients with hepatocellular carcinoma (HCC) remains poor. Although serine‐ and arginine‐rich splicing factor (SRSF) family members play crucial roles in tumors, their impact on tumor immunology remains unclear. This study aimed to elucidate the role of SRSF10 in HCC immunotherapy. Methods To identify the key genes associated with immunotherapy resistance, we conducted single‐nuclear RNA sequencing, multiplex immunofluorescence, and The Cancer Genome Atlas and Gene Expression Omnibus database analyses. We investigated the biological functions of SRSF10 in immune evasion using in vitro co‐culture systems, flow cytometry, various tumor‐bearing mouse models, and patient‐derived organotypic tumor spheroids. Results SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8+ T cell activity. Mechanistically, SRSF10 interacted with the 3′‐untranslated region of MYB, enhancing MYB RNA stability, and subsequently upregulating key glycolysis‐related enzymes including glucose transporter 1 (GLUT1), hexokinase 1 (HK1), lactate dehydrogenase A (LDHA), resulting in elevated intracellular and extracellular lactate levels. Lactate accumulation induced histone lactylation, which further upregulated SRSF10 expression. Additionally, lactate produced by tumors induced lactylation of the histone H3K18la site upon transport into macrophages, thereby activating transcription and enhancing pro‐tumor macrophage activity. M2 macrophages, in turn, inhibited the enrichment of CD8+ T cells and the proportion of interferon‐γ+CD8+ T cells in the tumor microenvironment (TME), thus creating an immunosuppressive TME. Clinically, SRSF10 could serve as a biomarker for assessing immunotherapy resistance in various solid tumors. Pharmacological targeting of SRSF10 with a selective inhibitor 1C8 enhanced the efficacy of programmed cell death 1 (PD‐1) monoclonal antibodies (mAbs) in both murine and human preclinical models. Conclusions The SRSF10/MYB/glycolysis/lactate axis is critical for triggering immune evasion and anti‐PD‐1 resistance. Inhibiting SRSF10 by 1C8 may overcome anti‐PD‐1 tolerance in HCC.

Abstract Microgrid can realize energy saving and emission reduction and multi‐energy complementation, but the fluctuation of renewable energy output and the error of day‐ahead scheduling will threaten the stability of microgrid operation. For this reason, this article proposes a microgrid multi‐timescale optimal scheduling method based on new energy output scenario generation. First, the microgrid framework of this article is introduced, and an energy cycle emission reduction model taking into account electricity‐to‐gas conversion is designed; second, a new energy prediction error model is established based on the prediction box and Gaussian hybrid model, and the scenario of wind and photovoltaic power generation is generated by correcting the sampling intervals for error sampling; and then, based on the day‐ahead scheduling plan, an intraday cooling, heating and electricity two‐layer rolling optimization model is established to correct the day‐ahead scenario. Finally, the example analysis shows that the cyclic emission reduction model can realize the recycling of resources, reduce the fuel cost and carbon emission, and the generation of scenarios for wind power can smooth out the fluctuation of new energy power, which, together with the intra‐day two‐layer rolling optimization, can reduce the day‐ahead scheduling error and improve the stability of microgrid operation.

Abstract In this research, we present PerceptHashing, a technique designed to categorize million-scale agricultural scenic images by incorporating human gaze shifting paths (GSPs) into a hashing framework. For each agricultural image, we identify visually and semantically significant object patches, such as fields, crops, and water bodies. These patches are linked to form a graphlet, establishing a network of spatially adjacent patches, and a GSP is then extracted using an active learning algorithm. The GSP reflects the distribution of human gaze across different regions of each agricultural scene, typically involving fewer than 12 regions, as validated by cross-validation. We then design a binary hashing framework that effectively leverages the semantics encoded in these GSPs. This framework integrates three key elements: (i) refinement of noisy labels, (ii) incorporation of deep image-level agricultural semantics, and (iii) updates to the adaptive data graph. The resulting hash codes from each GSP are converted into a kernelized visual descriptor for classification. To evaluate the influence of GSPs on agricultural image classification both qualitatively and quantitatively, we conducted an extensive user study comparing GSPs from typical observers with those from Alzheimer’s patients. The results demonstrate that: (1) the classification accuracy of 1.22 million agricultural aerial images using our approach is significantly higher than those processed by other methods, and (2) GSPs from 33 Alzheimer’s patients differ markedly from those of 37 normal observers, leading to notable differences in classification accuracy ( $$acc_{normal}=0.694$$ a c c normal = 0.694 versus $$acc_{patient}=0.322$$ a c c patient = 0.322 ).

Abstract Background This study aimed to develop a predictive model utilizing radiomics and body composition features derived from 18F-FDG PET/CT scans to forecast progression-free survival (PFS) and overall survival (OS) outcomes in patients with esophageal squamous cell carcinoma (ESCC). Methods We analyzed data from 91 patients who underwent baseline 18F-FDG PET/CT imaging. Radiomic features extracted from PET and CT images and subsequent radiomics scores (Rad-scores) were calculated. Body composition metrics were also quantified, including muscle and fat distribution at the L3 level from CT scans. Multiparametric survival models were constructed using Cox regression analysis, and their performance was assessed using the area under the time-dependent receiver operating characteristic (ROC) curve (AUC) and concordance index (C-index). Results Multivariate analysis identified Rad-scorePFS (P = 0.003), sarcopenia (P

Abstract SNF2L encodes an ISWI chromatin remodeling factor that promotes gene transcription and is consistently elevated in cancers. Previous studies have shown that inhibiting SNF2L expression in cancer cells leads to significant growth suppression, DNA damage, and cell death. However, the underlying mechanisms remain poorly understood. In this study, we demonstrated that cancer cells lacking SNF2L show significantly decreased glutathione (GSH) levels, leading to elevated reactive oxygen species (ROS) and increased oxidative stress. SNF2L deficiency also heightened the sensitivity of cancer cells to APR-246, a drug that depletes GSH and induces oxidative stress, consequently decreasing cell viability and increasing ROS levels, regardless of p53 status. Mechanistically, we found that NRF2 recruits SNF2L to the SLC7A11 promoter, leading to increased chromatin accessibility and facilitating SLC7A11 transcription. This results in decreased cystine uptake and impaired GSH biosynthesis. These findings suggest that targeting the SNF2L/SLC7A11 axis could enhance the effectiveness of APR-246 by depleting GSH and increasing ROS level in cancer cells, highlighting SNF2L as a promising therapeutic target.

In insects, the number and specificity of antennal lobe glomeruli often reflect the number and diversity of expressed chemosensory genes, which are linked to its ecological niche and specific olfactory needs. The oriental armyworm, Mythimna separata, is an important and common lepidopteran pest of cereal crops. Given its reliance on the olfactory system for crucial behaviors, understanding the evolutionary potential of this system requires a thorough characterization of the anatomical structure of the primary olfactory center. Here, we systematically identified all antennal lobe glomeruli of M. separata based on synaptic antibody immunostaining and mass staining of the olfactory sensory neurons. A total of 69 glomeruli were identified in females and 65 in males, and an intuitive nomenclature based on glomerular positions was applied. Our findings uncovered some sex-specific glomeruli in this species. There were ten female-specific glomeruli and three male-specific glomeruli, except for the macroglomerular complex (MGC) units, with a notable observation that the female labial pit organ glomerulus was larger than its male counterpart. Additionally, we identified four antennal-lobe tracts (ALTs) and retrograde labeling from the calyx revealed that all glomeruli were innervated by the medial ALT projection neurons. The comparison of the olfactory system structures between M. separata and sympatric moths supports their evolutionary convergence in noctuid moths. These results collectively lay the foundation for future studies on olfactory processing in M. separata.

Abstract Fabricated ballastless track has witnessed increasingly wide application in large-span bridges of municipal railways. The current ballastless track standard is applicable to bridges with a main span of 200 m to 400 m. For the main span is longer than 400 m, it is necessary to ensure the travelling safety and comfort on the fabricated tracks. In this study, static and dynamic analysis models of train-track-bridge are established to explore the influence of complex ambient temperature changes and concrete shrinkage and creep on bridge deformation, followed by the analysis of the deformation coordination between long-span bridge and fabricated ballastless tracks, thereby revealing the dynamic response of the train-track-bridge system under the complex influence of temperature. The results show that when a train runs at a speed of 160 km/h, the existing ballastless track design standard is still applicable to a bridge span of 688 m. Compared with CRTS type III track, the adoption of the novel prefabricated ballastless track on long-span urban bridges provides higher safety and greater comfort, with comprehensive power performance improved by more than 10%. This design comprehensively takes into account the deformation coordination and dynamic performance of the rail bridge, providing a basis for the design and application of fabricated ballastless tracks on long-span bridges of urban railways.

Abstract The digitization of operation and maintenance in the intelligent power grid equipment relies on a diverse array of information for smart decision-making. In the domain of intelligent decision generation, proficiency is contingent upon extensive learning from copious amounts of text. This necessitates not only robust processing capabilities but also a high level of specialization. In addressing situations where authorization is lacking, pre-trained language models (PLMs) have already provided ideas when confronted with specialized domains or tasks. In consideration of the complexity of textual content in the field of the power grid, which encompasses a multitude of specialized knowledge and involves an abundance of proprietary terminology, we have undertaken an exploration of pre-trained model specialization using the power grid domain as an example, specifically for the task of generating maintenance strategies. A two-stage fine-tuning approach (P2FT) is employed, utilizing a large-scale pre-training model specifically designed for natural language processing. The efficacy and practical value of this method were evaluated through multiple metrics, juxtaposed with other advanced approaches involving low-parameter or parameter-free fine-tuning methods. Through a meticulous analysis and validation of experimental outcomes, we have corroborated the feasibility and practical application value of employing this approach for pre-trained model specialization. Additionally, it has furnished valuable guidance for text generation within both the Chinese language domain and the power grid domain.