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Abstract Background The post COVID-19 health condition of Chinese residents infected with Omicron is not clear after the change of epidemic prevention policies. This study aimed to clarify the epidemiology and associated factors about health status of rehabilitation patients. Methods A quick questionnaire study based on C19-YRSm was conducted in mainland China through internet from May 1, 2023, to May 7, 2023. Chinese native speakers infected with Omicron variant agreed to participate were included. Persisting symptom and living habits were simultaneously inquired. Logistic regression analysis was used to identify the associated factors. Results In this study 753 individuals were included. Of whom 57.90% were males, 89.38% did not seek medical service, 99.47% recovered within less than 120 days. Breathlessness (47.68%), cognitive impairment (44.89%), Anxiety/mood changes (33.20%), pain/discomfort (32.94%), fatigue or tiredness not improved by rest (32.27%) and post-exertional malaise (30.01%) were the top reported key symptoms. Less than 10% respondents reported functional limitations. The prevalence of fever was reported greater than that of other symptoms, with dry eyes at 14.87%, appetite change at 14.34%, and hair loss at 12.22%. Middle age (OR: 2.353, 95%CI: 1.171 ~ 4.729), underlying diseases (OR: 2.293, 95%CI: 1.216 ~ 4.324), severe key symptom (OR: 6.168, 95%CI: 1.376 ~ 27.642) and at least one other symptom (OR: 1.847, 95%CI: 1.225 ~ 2.718)during the recovery were the risk factors of poor overall health after infection (current overall health score

Abstract Artificial visual system empowered by 2D materials-based hardware simulates the functionalities of the human visual system, leading the forefront of artificial intelligence vision. However, retina-mimicked hardware that has not yet fully emulated the neural circuits of visual pathways is restricted from realizing more complex and special functions. In this work, we proposed a human visual pathway-replicated hardware that consists of crossbar arrays with split floating gate 2D tungsten diselenide (WSe2) unit devices that simulate the retina and visual cortex, and related connective peripheral circuits that replicate connectomics between the retina and visual cortex. This hardware experimentally displays advanced multi-functions of red–green color-blindness processing, low-power shape recognition, and self-driven motion tracking, promoting the development of machine vision, driverless technology, brain–computer interfaces, and intelligent robotics.

Renal unilateral ischemia-reperfusion injury (UIRI) constitutes a significant global health challenge, with poor recovery leading to chronic kidney disease and subsequent renal fibrosis. Extracellular vesicles (EVs) present substantial potential benefits for renal diseases. However, the limited yield and efficacy of EVs produced through traditional methodologies (2D-EVs) severely restrict their widespread application. Moreover, the efficient and effective strategies for using EVs in UIRI treatment and their mechanisms remain largely unexplored. In this study, we propose an innovative approach by integrating bioprinted mesenchymal stem cell microfiber extracellular vesicles production technology (3D-EVs) with a tail vein injection method, introducing a novel treatment strategy for UIRI. Our comparison of the biological functions of 2D-EVs and 3D-EVs, both in vitro and in vivo, reveals that 3D-EVs significantly outperform 2D-EVs. Specifically, in vitro, 3D-EVs demonstrate a superior capacity to enhance the proliferation and migration of NRK-52E cells and mitigate hypoxia/reoxygenation (H/R)-induced injuries by reducing epithelial-mesenchymal transformation, extracellular matrix deposition, and ferroptosis. In vivo, 3D-EVs exhibit enhanced therapeutic effects, as evidenced by improved renal function and decreased collagen deposition in UIRI mouse kidneys. We further elucidate the mechanism by which 3D-EVs derived from KLF15 ameliorate UIRI-induced tubular epithelial cells (TECs) ferroptosis through the modulation of SLC7A11 and GPX4 expression. Our findings suggest that bioprinted mesenchymal stem cells microfiber-derived EVs significantly ameliorate renal UIRI, opening new avenues for effective and efficient EV-based therapies in UIRI treatment.

Abstract Purpose To evaluate the diagnostic performance of image-based artificial intelligence (AI) studies in predicting muscle-invasive bladder cancer (MIBC). (2) To assess the reporting quality and methodological quality of these studies by Checklist for Artificial Intelligence in Medical Imaging (CLAIM), Radiomics Quality Score (RQS), and Prediction model Risk of Bias Assessment Tool (PROBAST). Materials and methods We searched Medline, Embase, Web of Science, and The Cochrane Library databases up to October 30, 2023. The eligible studies were evaluated using CLAIM, RQS, and PROBAST. Pooled sensitivity, specificity, and the diagnostic performances of these models for MIBC were also calculated. Results Twenty-one studies containing 4256 patients were included, of which 17 studies were employed for the quantitative statistical analysis. The CLAIM study adherence rate ranged from 52.5% to 75%, with a median of 64.1%. The RQS points of each study ranged from 2.78% to 50% points, with a median of 30.56% points. All models were rated as high overall ROB. The pooled area under the curve was 0.85 (95% confidence interval (CI) 0.81–0.88) for computed tomography, 0.92 (95% CI 0.89–0.94) for MRI, 0.89 (95% CI 0.86–0.92) for radiomics and 0.91 (95% CI 0.88–0.93) for deep learning, respectively. Conclusion Although AI-powered muscle-invasive bladder cancer-predictive models showed promising performance in the meta-analysis, the reporting quality and the methodological quality were generally low, with a high risk of bias. Critical relevance statement Artificial intelligence might improve the management of patients with bladder cancer. Multiple models for muscle-invasive bladder cancer prediction were developed. Quality assessment is needed to promote clinical application. Key Points Image-based artificial intelligence models could aid in the identification of muscle-invasive bladder cancer. Current studies had low reporting quality, low methodological quality, and a high risk of bias. Future studies could focus on larger sample sizes and more transparent reporting of pathological evaluation, model explanation, and failure and sensitivity analyses. Graphical Abstract

Abstract Objective Glioblastoma (GBM) is one of the most aggressive brain tumors and often leads to poor outcomes. Studies have indicated that glycan levels are significantly correlated with the pathogenesis and development of cancers. However, whether glycan levels can serve as diagnostic or prognostic biomarkers in GBM remains unclear. Methods We obtained glycomic profiles in tissue and serum samples from 55 individuals with GBM using a well‐established lectin biochip platform probing with 11 specific lectins. Results Our univariate analysis showed that 5 out of the 11 lectin‐probed glycans (LPGs) were significantly higher in GBM tissues than in peri‐tumoral tissues. After logistic regression analyses, only the Jacalin‐probed T‐antigen difference between the two groups remained significant (p = 0.037). Moreover, survival‐related analyses showed that the level of Jacalin‐probed T‐antigen was significantly associated with the progression‐free survival (p = 0.038) of patients. However, none of the LPG levels were correlated with the overall survival or the chemosensitivity to temozolomide therapy. The correlation coefficient analysis showed a moderate‐to‐strong correlation in the Jacalin‐probed T‐antigen levels between GBM tissues and serum samples, indicating its potential usefulness as a non‐invasive GBM progression biomarker. Interpretation Glycomics analyses can be helpful in the prediction of GBM recurrences and may provide information useful for GBM glycan‐based target therapies or vaccine development.

AimsOur study, employing a multi-omics approach, aimed to delineate the distinct gut microbiota and metabolic characteristics in individuals under 30 with unclassified diabetes, thus shedding light on the underlying pathophysiological mechanismsMethodsThis age- and sex-matched case-control study involved 18 patients with unclassified diabetes, 18 patients with classic type 1 diabetes, 13 patients with type 2 diabetes, and 18 healthy individuals. Metagenomics facilitated the profiling of the gut microbiota, while untargeted liquid chromatography-mass spectrometry was used to quantify the serum lipids and metabolites.ResultsOur findings revealed a unique gut microbiota composition in unclassified diabetes patients, marked by a depletion of Butyrivibrio proteoclasticus and Clostridium and an increase in Ruminococcus torques and Lachnospiraceae bacterium 8_1_57FAA. Comparative analysis identified the combined marker panel of five bacterial species, seven serum biomarkers, and three clinical parameters could differentiate patients with UDM from HCs with an AUC of 0.94 (95% CI 0.85–1). Notably, the gut microbiota structure of patients with unclassified diabetes resembled that of type 2 diabetes patients, especially regarding disrupted lipid and branched-chain amino acid metabolism.ConclusionsDespite sharing certain metabolic features with type 2 diabetes, unclassified diabetes presents unique features. The distinct microbiota and metabolites in unclassified diabetes patients suggest a significant role in modulating glucose, lipid, and amino acid metabolism, potentially influencing disease progression. Further longitudinal studies are essential to explore therapeutic strategies targeting the gut microbiota and metabolites to modify the disease trajectory.

ABSTRACT Background Abnormal glycosylation is associated with tumors. The clinical value of serum glycans in assessing progression of hepatocellular carcinoma (HCC) patients remains a challenge. Methods A study dynamically comparing levels of fifteen lectin‐specific glycans between preoperative and postoperative serum of 65 HCC patients was conducted via lectin biochip technology. Multivariable logistic regression analysis was used to address associations between serum glycan levels and clinicopathological characteristics. Kaplan–Meier analysis was used to evaluate the impacts of serum glycan levels on overall survival (OS) and progression‐free survival (PFS) of the HCC patients. Results HCC patients presented significantly higher levels of the lectin‐specific glycans in preoperative serum than disease‐free individuals (p

This study synthesized biochar adsorbents from chemically activated sugarcane bagasse using ZnCl 2 at pyrolysis temperatures of 400, 500, and 600°C. The modified bagasse biochar was used to remove methylene blue (MB) and acid red (AR) dyes. The surface characteristics of the modified bagasse biochars were analyzed using Scanning Electron Microscope (SEM), Fourier Transform infrared spectroscopy (FTIR), and Brunauer-Emmett-Teller (BET) analysis. Batch adsorption experiments were conducted to assess the impact of various parameters on adsorption performance. Among the different bagasse biochar samples, Zn-BC-600 exhibited superior adsorption capacities for MB and AR with values of 182.225 and 43.324 mg/g, respectively. The adsorption efficiency was significantly influenced by pH, with optimal conditions at pH = 6.0 for MB and pH = 2.0 and 10.0 for AR. The adsorption process for MB and AR on Zn-BCs followed a pseudo-second-order kinetic model, indicating chemisorption as the primary mechanism. Adsorption isotherm studies revealed that Zn-BCs conform to the Freundlich model, proposing a multilayer adsorption due to the heterogeneity of the biochar surface. Regeneration experiments indicated that Zn-BCs could be reused for multiple adsorption cycles. In conclusion, the modified bagasse biochar showed strong adsorption affinity for both MB and AR, particularly for MB, making it a promising adsorbent for treating printing and dyeing wastewater.

Identification of potential cerebrovascular disorder in the patient with traumatic subarachnoid hemorrhage (tSAH) is a key element to decrease the complication occurrence and mortality rate. In this study, we aim to compare the diagnostic values between dual-source computed tomography angiography (DSCTA) and traditional tomography angiography (CTA) in identification of potential cerebrovascular disorder among tSAH patients. A total of 113 tSAH patients with the hemorrhage involving more than 2 cisterns were recruited. Among that, 42 patients received DSCTA scans, and another 71 patients received traditional CTA scans. Subsequently, all patients received digital subtraction angiography (DSA) tests to confirm the presence of the cerebrovascular disorder. In DSCTA scan group, 21.4 % (9/42) patients were reported to have cerebrovascular disorders: seven patients had intracranial aneurysms; a patient had pseudoaneurysm with carotid artery cavernous sinus fistula; and a patient had Moyamoya disease. DSA tests had the same results with that with DSCTA scans. In the cohort receiving CTA scans, 19.7 % (14/71) patients were reported to had intracranial aneurysms. However, the positive results of DSA tests for this cohort were 22.5 % (16/71). Two inconsistent results between the CTA scan and DSA test were found, including an arteriovenous malformation and an arteriovenous fistula. In summary, DSCTA and CTA had similar positive rates but differ in diagnostic accuracy for identification of cerebrovascular disorders in tSAH patients.

Abstract Background Olfactory dysfunction occurs frequently in Parkinson’s disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. Methods MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Next, prok2R overexpression (prok2R+) and knockdown (prok2R−) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP+ were evaluated in prok2R overexpression (prok2R+) HEK293T cell lines. Results Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R+ and prok2R− HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R+ HEK293T cells were resistant to MPP+-induced apoptosis. Conclusions This study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients.

Abstract The commercialization of intellectual property has become a fundamental avenue for universities to improve regional competitiveness. However, large-scale empirical studies on patent transfers, reflecting technology and knowledge sharing, remain limited. This study used social network analysis to investigate university technology flows in China based on patent assignments from technological, organizational, and regional perspectives. The results firstly revealed clear stage characteristics in the number of university patent assignments with the improvement of the Chinese version of the Bayh-Dole Act. Secondly, popular technologies in university technology flows mainly concentrated on measurement, testing, digital transmission, and other areas in which enterprises lack international competitive advantage. Thirdly, central actors comprised prestigious universities focusing on science, engineering, and comprehensive disciplines, along with intellectual property-focused enterprises. Finally, university technology flows gradually delocalized, and varied regional patterns exist owing to a spatial mismatch between university knowledge supply and regional demand. These findings have several practical and policy implications for government and university management in terms of promoting emerging technologies and clarifying universities’ functions in regional and national innovation systems. This study contributes to the economic geography literature on regional innovation.

Abstract Background Developmental and epileptic encephalopathy-50 (DEE-50) is a rare clinical condition believed to be caused by a mutation in the CAD gene and is associated with a bleak prognosis. CAD-related diseases have a wide range of clinical manifestations and other symptoms that may be easily overlooked. Like other rare diseases, the clinical manifestations and the treatment of DEE-50 necessitate further investigation. Case presentation A 1-year-old male patient presented with developmental delay, seizures, and anaemia at 3 months of age. He further developed refractory status epilepticus (SE), rapid deterioration of cognitive and motor function, and even became comatose at 5 months of age. Whole-exome sequencing of trios (WES-trios) revealed a compound heterozygous variant in the CAD gene, with one locus inherited from his father (c.1252C>T: p.Q418* nonsense mutation) and one from his mother (c.6628G>A: p.G2210S, missense mutation). This compound heterozygous CAD variant was unreported in the Human Gene Mutation Database. After uridine treatment, his cognitive faculties dramatically improved and he remained seizure-free. Forty two cases with CAD gene mutation reported in the literatures were reviewed. Among them, 90% had onset before 3 years of age, with average of 1.6±1.8 years old. The average age of diagnosis was 7.7 ± 10 years. The mortality rate was approximately 9.5%, with all reported deaths occurring in patients without uridine treatment. The clinical entity could be improved dramatically when the patient treated with uridine. Conclusions We present a boy with DEE 50 caused by novel CAD gene mutations and reviewed the clinical features of 42 patients reported previously. DEE 50 has early onset, refractory seizures, even status epilepticus leading to death, with favorable response to treatment with oral uridine. Early uridine treatment is recommended if CAD defect is suspected or genetically diagnosed. This study enhances the knowledge of DEE 50 and expands the spectrum of CAD gene mutations.

BackgroundThe WFS1 gene encodes the protein wolframin, which is crucial for maintaining endoplasmic reticulum homeostasis. Variants in this gene are predominantly associated with Wolfram syndrome and have been implicated in other disorders such as diabetes mellitus and psychiatric diseases, which increases the rate of clinical misdiagnosis.MethodsPatients were diagnosed with early-onset unclassified diabetes according to their clinical and laboratory data. We performed whole-exome sequencing (WES) in 165 patients, interpreting variants according to the American College of Medical Genetics/Association for Molecular Pathology (ACMG/AMP) 2015 guidelines. Variant verification was done by Sanger sequencing. In vitro experiments were conducted to evaluate the effects of WFS1 compound heterozygous variants.ResultsWe identified WFS1 compound heterozygous variants (p.A214fs*74/p.F329I and p.I427S/p.I304T) in two patients with Wolfram Syndrome-Like disorders (WSLD). Both WFS1 compound heterozygous variants were associated with increased ER stress, reduced cell viability, and decreased SERCA2b mRNA levels. Additionally, pathogenic or likely pathogenic WFS1 heterozygous variants were identified in the other three patients.ConclusionOur results underscore the importance of early genetic testing for diagnosing young-onset diabetes and highlight the clinical relevance of WFS1 variants in increasing ER stress and reducing cell viability. Incorporating these genetic insights into clinical practice can reduce misdiagnoses and improve treatment strategies for related disorders.

Abstract Neural stem cells (NSCs) transplantation is an attractive and promising treatment strategy for spinal cord injury (SCI). Various pathological processes including the severe inflammatory cascade and difficulty in stable proliferation and differentiation of NSCs limit its application and translation. Here, a novel physico‐chemical bifunctional neural stem cells delivery system containing magnetic nanoparticles (MNPs and methylprednisolone (MP) is designed to repair SCI, the former regulates NSCs differentiation through magnetic mechanical stimulation in the chronic phase, while the latter alleviates inflammatory response in the acute phase. The delivery system releases MP to promote microglial M2 polarization, inhibit M1 polarization, and reduce neuronal apoptosis. Meanwhile, NSCs tend to differentiate into functional neurons with magnetic mechanical stimulation generated by MNPs in the static magnetic field, which is related to the activation of the PI3K/AKT/mTOR pathway. SCI mice achieve better functional recovery after receiving NSCs transplantation via physico‐chemical bifunctional delivery system, which has milder inflammation, higher number of M2 microglia, more functional neurons, and axonal regeneration. Together, this bifunctional NSCs delivery system combined physical mechanical stimulation and chemical drug therapy is demonstrated to be effective, which provides new treatment insights into clinical transformation of SCI repair.

Transparent conductive oxide (TCO) films, known for their role as carrier transport layers in solar cells, can be adversely affected by hydrolysis products from encapsulants. In this study, we explored the morphology, optical-electrical properties, and deterioration mechanisms of In2O3-based TCO films under acetic acid stress. A reduction in film thickness and carrier concentration due to acid-induced corrosion was observed. X-ray photoelectron spectroscopy and inductively coupled plasma emission spectrometry analyses revealed that TCOs doped with less-reactive metals exhibited enhanced corrosion resistance. The efficiency of silicon heterojunction (SHJ) solar cells with tin-doped indium oxide, titanium-doped indium oxide, and zinc-doped indium oxide films decreased by 10%, 26%, and 100%, respectively, after 200 ​h of corrosion. We also found that tungsten-doped indium oxide could effectively safeguard SHJ solar cells against acetic acid corrosion, which offers a potential option for achieving long-term stability and lower levelized cost of solar cell systems. This research provides essential insights into selecting TCO films for solar cells and highlights the implications of ethylene-vinyl acetate hydrolysis for photovoltaic modules.

Abstract Background Patients with Alzheimer’s disease (AD) are often co-morbid with unprovoked seizures, making clinical diagnosis and management difficult. Although it has an important role in both AD and epilepsy, abnormal γ-aminobutyric acid (GABA)ergic transmission is recognized only as a compensative change for glutamatergic damage. Neuregulin 1 (NRG1)-ErbB4 signaling can promote GABA release and suppress epileptogenesis, but its effects on cognition in AD are still controversial. Methods Four-month-old APPswe/PS1dE9 mice (APP mice) were used as animal models in the early stage of AD in this study. Acute/chronic chemical-kindling epilepsy models were established with pentylenetetrazol. Electroencephalogram and Racine scores were performed to assess seizures. Behavioral tests were used to assess cognition and emotion. Electrophysiology, western blot and immunofluorescence were performed to detect the alterations in synapses, GABAergic system components and NRG1-ErbB4 signaling. Furthermore, NRG1 was administrated intracerebroventricularly into APP mice and then its antiepileptic and cognitive effects were evaluated. Results APP mice had increased susceptibility to epilepsy and resulting hippocampal synaptic damage and cognitive impairment. Electrophysiological analysis revealed decreased GABAergic transmission in the hippocampus. This abnormal GABAergic transmission involved a reduction in the number of parvalbumin interneurons (PV+ Ins) and decreased levels of GABA synthesis and transport. We also found impaired NRG1-ErbB4 signaling which mediated by PV+ Ins loss. And NRG1 administration could effectively reduce seizures and improve cognition in four-month-old APP mice. Conclusion Our results indicated that abnormal GABAergic transmission mediated hippocampal hyperexcitability, further excitation/inhibition imbalance, and promoted epileptogenesis in the early stage of AD. Appropriate NRG1 administration could down-regulate seizure susceptibility and rescue cognitive function. Our study provided a potential direction for intervening in the co-morbidity of AD and epilepsy.

Abstract Rechargeable calcium (Ca) metal batteries are promising candidates for sustainable energy storage due to the abundance of Ca in Earth’s crust and the advantageous theoretical capacity and voltage of these batteries. However, the development of practical Ca metal batteries has been severely hampered by the current cathode chemistries, which limit the available energy and power densities, as well as their insufficient capacity retention and low-temperature capability. Here, we describe the rechargeable Ca/Cl2 battery based on a reversible cathode redox reaction between CaCl2 and Cl2, which is enabled by the use of lithium difluoro(oxalate)borate as a key electrolyte mediator to facilitate the dissociation and distribution of Cl-based species and Ca2+. Our rechargeable Ca/Cl2 battery can deliver discharge voltages of 3 V and exhibits remarkable specific capacity (1000 mAh g−1) and rate capability (500 mA g−1). In addition, the excellent capacity retention (96.5% after 30 days) and low-temperature capability (down to 0 °C) allow us to overcome the long-standing bottleneck of rechargeable Ca metal batteries.

Accurate measurement of interferometer arm-length difference is very important in the application fields such as fiber optic hydrophones. However, the interferometer is very sensitive to the environmental vibration and noise, which affects the accuracy of the interferometer measurement. A novel environmental random phase noise separation (ERPNS) technology is proposed to effectively reduce optical frequency domain reflectometer (OFDR)’s sensitivity to environmental vibration for the measurement of the fiber interferometer. A set of optical paths based on dual-laser coherent detection technology and the related ERPNS algorithm was developed to extract the environmental phase noise from the measurement data. The OFDR's sensitivity to vibration is decreased by ∼60 dB in theory and a measurement accuracy better than 0.05 mm for the static arm length difference of 74.51902 m in different dynamic environment is achieved experimentally, with 56 μm of spatial resolution in the maximum detectable distance of about 75 m.

Abstract Background Moyamoya disease (MMD) is a cerebrovascular disorder characterized by progressive unilateral or bilateral stenosis of the distal internal carotid artery. As hemodynamic features in MMD patients alter, the comorbidity of intracranial aneurysm (IA) is sometimes observed clinically. We aim to investigate clinical characteristics and therapeutic strategies for the comorbidity of Moyamoya disease with intracranial aneurysms (MMD-IA). Methods A total of 13 MMD-IA patients were recruited in this study and were manifested to be intracranial hemorrhage. We reviewed the surgical technique notes for all patients. Results According to the locations of an aneurysm, MMD-IA could be divided into several categories: (1) MMD-IA at a circle of Willis—aneurysms usually located at the trunk of Willis circle; (2) MMD-IA at collateral anastomosis—aneurysms located at the distal end of collateral anastomosis; and (3) MMA-IA at basal ganglia region. In this report, aneurysms in 10 patients located at Willis circle, 2 at the pericallosal artery, and 1 at the basal ganglia region. Among them, endovascular embolism was performed among 5 patients. Aneurysm clipping was conducted among 7 patients. A patient with an aneurysm at the basal ganglia region just accepted revascularization treatment. All the treatments were successful. Follow-up studies, ranging from 6 to 24 months, demonstrated all patients received satisfactory curative effects. Conclusion Diverse clinical presentations could be observed among MMD-IA patients. Individualized neurosurgical treatments should be chosen according to the locations of the aneurysm.

As the commercialisation of Intelligent Connected Vehicles (ICVs) accelerates, Vehicle-to-Everything (V2X)-based general testing and assessment systems have emerged at the forefront of the research. Current field testing schemes mostly follow the norms of traditional vehicle tests. In contrast, Original Equipment Manufacturers (OEMs) have increasingly focused on the potential influence of V2X communication performance on the application response characteristics. Our previous work resulted in a C-V2X (Cellular-V2X) large-scale testing system (LSTS) for communication performance testing. However, when addressing the need to combine application and communication, the system software faces confronts heightened technical challenges. This paper proposes a layered software architecture for the automated C-V2X LSTS, which is tailored to combined scenarios. This architecture integrates scenario encapsulation technology with a large-scale node array deployment strategy, enabling communication and application testing under diversified scenarios. The experimental results demonstrate the scalability of the system, and a case study of Forward Collision Warning (FCW) validates the effectiveness and reliability of the system.

Among the pathogens that cause infectious diarrhea in China, Shigella is the most prominent. Shigellosis affects both adults and children, particularly those in developing nations, with nearly 190 million annual cases and a third resulting in fatalities. The recently emerged CRISPR/Cas system has also been increasingly applied for the detection of different biological targets. The lateral flow assay (LFA) has the advantages of short detection time, simple operation, high sensitivity, and low cost, and it provides an ideal platform for on-site detection. In this study, a recombinase polymerase amplification–CRISPR/Cas12a–LFA test for Shigella flexneri was constructed. The established method had good specificity and sensitivity, and the qualitative accuracy of 32 tested strains reached 100%. The detection limit of genomic DNA reached 8.3 copies/μL. With the advantages of high accuracy and portability, this diagnostic apparatus represents a novel method of identification and detection of Shigella flexneri, particularly in settings that lack complex laboratory infrastructure.

Numerical experiments using the WRF model were conducted to analyze the sensitivity of Typhoon Mangkhut intensification simulations to seven widely used planetary boundary layer (PBL) parameterization schemes, including YSU, MYJ, QNSE, MYNN2, MYNN3, ACM2, and BouLac. The results showed that all simulations generally reproduced the tropical cyclone (TC) track and intensity, with YSU, QNSE, and BouLac schemes better capturing intensification processes and closely matching observed TC intensity. In terms of surface layer parameterization, the QNSE scheme produced the highest Ck/Cd ratio, resulting in stronger TC intensity based on Emanuel’s potential intensity theory. In terms of PBL parameterization, the YSU and BouLac schemes, with the same revised MM5 surface layer scheme, simulated weaker turbulent diffusivity Km and shallower mixing height, leading to stronger TC intensity. During the intensification period, the BouLac, YSU, and QNSE PBL schemes exhibited stronger tangential wind, radial inflow within the boundary layer, and updraft around the eye wall, consistent with TC intensity results. Both PBL and surface layer parameterization significantly influenced simulated TC intensity. The QNSE scheme, with the largest Ck/Cd ratio, and the YSU and BouLac schemes, with weaker turbulent diffusivity, generated stronger radial inflow, updraft, and warm core structures, contributing to higher storm intensity.

Development in hemoglobin-based oxygen carriers (HBOCs) that may be used as alternatives to donated blood requires an extensive supply of highly pure hemoglobin (Hb) preparations. Therefore, it is essential to fabricate inexpensive, stable and highly selective absorbents for Hb purification. Molecular imprinting is an attractive technology for preparing such materials for targeted molecular recognition and rapid separations. In this case study, we developed human fetal hemoglobin (HbF)-imprinted polymer beads through the fusion of surface imprinting and Pickering emulsion polymerization. HbF was firstly covalently coupled to silica nanoparticles through its surface-exposed amino groups. The particle-supported HbF molecules were subsequently employed as templates for the synthesis of molecularly imprinted polymers (MIPs) with high selectivity for Hb. After removing the silica support and HbF, the resulting MIPs underwent equilibrium and kinetic binding experiments with both adult Hb (HbA) and HbF. These surface-imprinted MIPs exhibited excellent selectivity for both HbA and HbF, facilitating the one-step isolation of recombinant Hb from crude biological samples. The saturation capacities of HbA and HbF were found to be 15.4 and 17.1 mg/g polymer, respectively. The present study opens new possibilities for designed resins for tailored protein purification, separation and analysis.

Hemozoin (Hz) is a heme crystal produced during malaria infection that stimulates immune cells, leading to the production of cytokines and chemokines. The immunostimulatory action of Hz has previously been applied in the development of alternative adjuvants. Crystallization of hemin is a chemical approach for producing Hz. Here, we focused on an enzymatic production method for Hz using the heme detoxification protein (HDP), which catalyzes heme dimer formation from hemin in Plasmodium. We examined the immunostimulatory effects of an enzymatically synthesized analog of Hz (esHz) produced by recombinant Plasmodium falciparum HDP. Enzymatically synthesized Hz stimulates a macrophage cell line and human peripheral mononuclear cells, leading to the production of interleukin (IL)-6 and IL-12p40. In mice, subcutaneous administration of esHz together with an antigen, ovalbumin (OVA), increased the OVA-specific immunoglobulin (Ig) G2c isotype level in the serum, whereas OVA-specific IgG1 was not induced. Our findings suggest that esHz is a useful Th-1 cell adjuvant.

Efficient obstacle-avoidance path planning is critical for orchards with numerous irregular obstacles. This paper presents a continuous bidirectional Quick-RRT* (CBQ-RRT*) algorithm based on the bidirectional RRT (Bi-RRT) and Quick-RRT* algorithms and proposes an expansion cost function that evaluates path smoothness and length to overcome the limitations of the Quick-RRT* algorithm for non-holonomic mobile robot applications. To improve the zigzag between dual trees caused by the dual-tree expansion of the Bi-RRT algorithm, CBQ-RRT* proposes the CreateConnectNode optimization method, which effectively solves the path smoothness problem at the junction of dual trees. Simulations conducted on the ROS platform showed that the CBQ-RRT* outperformed the unidirectional Quick-RRT* in terms of efficiency for various orchard layouts and terrain conditions. Compared to Bi-RRT*, CBQ-RRT* reduced the average path length and maximum heading angle by 8.5% and 21.7%, respectively. In addition, field tests confirmed the superior performance of the CBQ-RRT*, as evidenced by an average maximum path lateral error of 0.334 m, a significant improvement over Bi-RRT* and Quick-RRT*. These improvements demonstrate the effectiveness of the CBQ-RRT* in complex orchard environments.

BackgroundAdrenocortical carcinoma (ACC) is an aggressive endocrine malignancy with limited therapeutic options. Treating advanced ACC with mitotane, the cornerstone therapy, remains challenging, thus underscoring the significance to predict mitotane response prior to treatment and seek other effective therapeutic strategies.ObjectiveWe aimed to determine the efficacy of mitotane via an in vitro assay using patient-derived ACC cells (PDCs), identify molecular biomarkers associated with mitotane response and preliminarily explore potential agents for ACC.MethodsIn vitro mitotane sensitivity testing was performed in 17 PDCs and high-throughput screening against 40 compounds was conducted in 8 PDCs. Genetic features were evaluated in 9 samples using exomic and transcriptomic sequencing.ResultsPDCs exhibited variable sensitivity to mitotane treatment. The median cell viability inhibition rate was 48.4% (IQR: 39.3-59.3%) and -1.2% (IQR: -26.4-22.1%) in responders (n=8) and non-responders (n=9), respectively. Median IC50 and AUC were remarkably lower in responders (IC50: 53.4 µM vs 74.7 µM, P

AimsTo determine the roles of matrix metallopeptidase-9 (MMP9) on human coronary artery smooth muscle cells (HCASMCs) in vitro, early beginning of atherosclerosis in vivo in diabetic mice, and drug naïve patients with diabetes.MethodsActive human MMP9 (act-hMMP9) was added to HCASMCs and the expressions of MCP-1, ICAM-1, and VCAM-1 were measured. Act-hMMP9 (n=16) or placebo (n=15) was administered to diabetic KK.Cg-Ay/J (KK) mice. Carotid artery inflammation and atherosclerosis measurements were made at 2 and 10 weeks after treatment. An observational study of newly diagnosed drug naïve patients with type 2 diabetes mellitus (T2DM n=234) and healthy matched controls (n=41) was performed and patients had ultrasound of carotid arteries and some had coronary computed tomography angiogram for the assessment of atherosclerosis. Serum MMP9 was measured and its correlation with carotid artery or coronary artery plaques was determined.ResultsIn vitro, act-hMMP9 increased gene and protein expressions of MCP-1, ICAM-1, VCAM-1, and enhanced macrophage adhesion. Exogenous act-hMMP9 increased inflammation and initiated atherosclerosis in KK mice at 2 and 10 weeks: increased vessel wall thickness, lipid accumulation, and Galectin-3+ macrophage infiltration into the carotid arteries. In newly diagnosed T2DM patients, serum MMP9 correlated with carotid artery plaque size with a possible threshold cutoff point. In addition, serum MMP9 correlated with number of mixed plaques and grade of lumen stenosis in coronary arteries of patients with drug naïve T2DM.ConclusionMMP9 may contribute to the initiation of atherosclerosis and may be a potential biomarker for the early identification of atherosclerosis in patients with diabetes.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT04424706.

Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

Mycorrhizal fungi, a category of fungi that form symbiotic relationships with plant roots, can participate in the induction of plant disease resistance by secreting phosphatase enzymes. While extensive research exists on the mechanisms by which mycorrhizal fungi induce resistance, the specific contributions of phosphatases to these processes require further elucidation. This article reviews the spectrum of mycorrhizal fungi-induced resistance mechanisms and synthesizes a current understanding of how phosphatases mediate these effects, such as the induction of defense structures in plants, the negative regulation of plant immune responses, and the limitation of pathogen invasion and spread. It explores the role of phosphatases in the resistance induced by mycorrhizal fungi and provides prospective future research directions in this field.

Previous studies have demonstrated that when the cyclin D2 (CCND2), a cell-cycle regulatory protein, is overexpressed in human-induced pluripotent stem cells (hiPSCs), cardiomyocytes (CMs) differentiated from these CCND2-overexpressing hiPSCs can proliferate after transplantation into infarcted hearts, which significantly improves the cells’ potency for myocardial regeneration. However, persistent CM proliferation could lead to tumor growth or the development of arrhythmogenic complications; thus, the goal of the current study was to generate a line of hiPSCs in which CCND2 overexpression could be tightly controlled. First, we transfected hiPSCs with vectors coding for a doxycycline-inducible Tet-On transactivator and S. pyogenes dCas9 fused to the VPR activation domain; then, the same hiPSCs were engineered to express guide RNAs targeting the CCND2 promotor. Thus, treatment with doxycycline (dox) activated dCas9-VPR expression, and the guide RNAs directed dCas9-VPR to the CCND2 promoter, which activated CCND2 expression. Subsequent experiments confirmed that CCND2 expression was dox-dependent in this newly engineered line of hiPSCs (doxCCND2-hiPSCs): CCND2 protein was abundantly expressed after 48 h of treatment with dox and declined to near baseline level ~96 h after dox treatment was discontinued.

Ultrasound is widely applied in diverse domains, such as medical imaging, non-destructive evaluation, and acoustic communication. Piezoelectric micromachined ultrasonic transducers (PMUTs) capable of generating and receiving ultrasonic signals at the micrometer level have become a prominent technology in the field of ultrasound. It is important to enrich the models of the PMUTs to meet the varied applications. In this study, a series of PMUT devices featured with various top electrode configurations, square, circular, and doughnut, were designed to assess the influence of shape on the emission efficacy. It was demonstrated that the PMUTs with a circular top electrode were outperformed, which was calculated from the external acoustic pressure produced by the PMUTs operating in the fundamental resonant mode at a specified distance. Furthermore, the superior performance of PMUT arrays were exhibited through computational simulations for the circular top electrode geometries. Conventional microelectromechanical systems (MEMS) techniques were used to fabricate an array of PMUTs based on aluminum nitride (AlN) films. These findings make great contributions for enhancing the signal transmission sensitivity and bandwidth of PMUTs, which have significant potential in non-destructive testing and medical imaging applications.