Functional and structural investigation of a broadly neutralizing SARS-CoV-2 antibody.

Since its emergence, SARS-CoV-2 has been continuously evolving, hampering the effectiveness of current vaccines against COVID-19. mAbs can be used to treat patients at risk of severe COVID-19. Thus, the development of broadly protective mAbs and an understanding of the underlying protective mechanisms are of great importance. Here, we isolated mAbs from donors with breakthrough infection with Omicron subvariants using a single-B cell screening platform. We identified a mAb, O5C2, which possesses broad-spectrum neutralization and antibody-dependent cell-mediated cytotoxic activities against SARS-CoV-2 variants, including EG.5.1. Single-particle analysis by cryo-electron microscopy revealed that O5C2 targeted an unusually large epitope within the receptor-binding domain of spike protein that overlapped with the angiotensin-converting enzyme 2 binding interface. Furthermore, O5C2 effectively protected against BA.5 Omicron infection in vivo by mediating changes in transcriptomes enriched in genes involved in apoptosis and interferon responses. Our findings provide insights into the development of pan-protective mAbs against SARS-CoV-2.

Novel IL-4/HB-EGF-dependent crosstalk between eosinophils and macrophages controls liver regeneration after ischaemia and reperfusion injury.

OBJECTIVE: Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair. DESIGN: Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding epidermal growth factor-like growth factor (hb-egf). RESULT: We observed that eosinophils persisted over a week following hepatic IR injury. Their peak accumulation coincided with that of hepatocyte proliferation. Functional studies showed that eosinophil deficiency was associated with a dramatic delay in liver repair, which was normalised by the adoptive transfer of bmEos. Mechanistic studies demonstrated that eosinophil-derived IL-4, but not IL-13, was critically involved in the reparative function of these cells. The data further revealed a selective role of macrophage-dependent IL-4 signalling in liver regeneration. Eosinophil-derived IL-4 stimulated macrophages to produce HB-EGF. Moreover, macrophage-specific hb-egf deletion impaired hepatocyte regeneration after IR injury. CONCLUSION: Together, these studies uncovered an indispensable role of eosinophils in liver repair after acute injury and identified a novel crosstalk between eosinophils and macrophages through the IL-4/HB-EGF axis.

Acute Necrotizing Pancreatitis Complicated with Paroxysmal Nocturnal Haemoglobinuria: A Case Report.

This report presents a unique case of acute necrotizing pancreatitis(ANP) concomitant with paroxysmal nocturnal hemoglobinuria(PNH), a combination that has not been documented in existing literature. The impact of PNH on ANP and its treatment remains uncertain due to the lack of consensus. The case described herein involves a patient who exhibited both ANP and PNH, subsequently experiencing splanchnic vein thrombosis (SVT), resulting in substantial intra-abdominal and gastrointestinal hemorrhaging. We attempted to analyze the role of PNH in the formation of SVT in ANP and propose some new insights and hypotheses for the treatment of such patients.

MPIGAN: An end-to-end deep based generative framework for high-resolution magnetic particle imaging reconstruction.

BACKGROUND: Magnetic particle imaging (MPI) is a recently developed, non-invasive in vivo imaging technique to map the spatial distribution of superparamagnetic iron oxide nanoparticles (SPIONs) in animal tissues with high sensitivity and speed. It is a challenge to reconstruct images directly from the received signals of MPI device due to the complex physical behavior of the nanoparticles. System matrix and X-space are two commonly used MPI reconstruction methods, where the former is extremely time-consuming and the latter usually produces blurry images. PURPOSE: Currently, we proposed an end-to-end machine learning framework to reconstruct high-resolution MPI images from 1-D voltage signals directly and efficiently. METHODS: The proposed framework, which we termed "MPIGAN", was trained on a large MPI simulation dataset containing 291 597 pairs of high-resolution 2-D phantom images and each image's corresponding voltage signals, so that it was able to accurately capture the nonlinear relationship between the spatial distribution of SPIONs and the received voltage signal, and realized high-resolution MPI image reconstruction. RESULTS: Experiment results showed that, MPIGAN exhibited remarkable abilities in high-resolution MPI image reconstruction. MPIGAN outperformed the traditional methods of system matrix and X-space in recovering the fine-scale structure of magnetic nanoparticles' spatial distribution and achieving enhanced reconstruction performance in both visual effects and quantitative assessments. Moreover, even when the received signals were severely contaminated with noise, MPIGAN could still generate high-quality MPI images. CONCLUSION: Our study provides a promising AI solution for end-to-end, efficient, and high-resolution magnetic particle imaging reconstruction.

Sequential Scan-Based Single-Dimension Multi-Voxel System Matrix Calibration for Open-Sided Magnetic Particle Imaging.

Open-sided magnetic particle imaging (OS-MPI) has garnered significant interest due to its potential for interventional applications. However, the system matrix calibration in OS-MPI using sequential scans is a time-consuming task and susceptible to the low signal-to-noise ratio (SNR) resulting from the small calibration sample size. These challenges have hindered the practical implementation of system matrix-based reconstruction for sequentially scanned OS-MPI. To address these issues, we propose a novel calibration method, named sequential scan-based single-dimension multi-voxel calibration (SS-SDMVC), to efficiently obtain a high-SNR system matrix. This method was implemented in a cylindrical field of view (FOV), where a bar calibration sample parallel to the field-free line (FFL) was shifted along a fixed radial direction. A standard image reconstruction process was also introduced to verify the feasibility of SS-SDMVC. Through simulations, we analyzed the effects of noise levels and scanner imperfections on the SS-SDMVC-based reconstruction and demonstrated its robustness. In experiments, we compared the imaging performance of SS-SDMVC and the sequential scan-based traditional cubic-FOV SMC. The results showed that SS-SDMVC reduced the number of measurements by a factor of 210.94 and achieved higher reconstruction quality. Therefore, SS-SDMVC is expected to improve the reconstruction quality of human-scale or high-gradient FFL MPI scanners.

Live and pasteurized Akkermansia muciniphila ameliorates diabetic cognitive impairment by modulating gut microbiota and metabolites in db/db mice.

The established role of disturbances in the microbiota-gut-brain axis in the development of diabetic cognitive impairment (DCI) has long been recognized. It has shown the potential of Akkermansia muciniphila (A. muciniphila) in improving metabolic disorders and exerting anti-inflammatory effects. However, there remains a lack of comprehensive understanding regarding the specific effects and mechanisms underlying the treatment of DCI with A. muciniphila. This study aimed to evaluate the potential of A. muciniphila in alleviating DCI in db/db mice. Eleven-week-old db/db mice were administered either live or pasteurized A. muciniphila (5 × 109 CFU/200 µL) for a duration of eight weeks. Administering live A. muciniphila significantly ameliorated cognitive impairments, improved the synaptic ultrastructure, and inhibited hippocampal neuron loss in the CA1 and CA3 subregions in db/db mice. Both live and pasteurized A. muciniphila effectively mitigated neuroinflammation. Moreover, live A. muciniphila increased the relative abundance of Lactococcus and Staphylococcus, whereas pasteurized A. muciniphila increased the relative abundance of Lactobacillus, Prevotellaceae_UCG_001, and Alistipes. Supplementation of A. muciniphila also induced alterations in serum and brain metabolites, with a particular enrichment observed in tryptophan metabolism, glyoxylate and dicarboxylate metabolism, nitrogen metabolism, and pentose and glucuronate interconversions. Correlation analysis further demonstrated a direct and substantial correlation between the altered gut microbiota and the metabolites in the serum and brain tissue. In conclusion, the results indicate that live A. muciniphila demonstrated greater efficacy compared to pasteurized A. muciniphila. The observed protective effects of A. muciniphila against DCI are likely mediated through the neuroinflammation and microbiota-metabolites-brain axis.

Space-Specific Mixing Excitation for High-SNR Spatial Encoding in Magnetic Particle Imaging.

OBJECTIVE: Magnetic Particle Imaging (MPI) is a radiation-free tracer-based imaging technology that visualizes the spatial distribution of superparamagnetic iron oxide nanoparticles. Conventional spatial encoding methods in MPI rely on a gradient magnetic field with a constant gradient strength to generate a field-free point or line for spatial scanning. However, increasing the gradient strength can enhance theoretical spatial resolution but also lead to a decrease in the Signal-to-Noise Ratio (SNR) and sensitivity of the imaging system. This poses a technical challenge in balancing spatial resolution and sensitivity, necessitating intricate hardware design. METHODS: To address this, we present a Space-Specific Mixing Excitation (SSME) technique for achieving high-SNR spatial encoding in MPI. By utilizing a dual-frequency excitation magnetic field with a non-homogeneous field strength, magnetic particles at each position generate unique intermodulation responses. By performing multi-channel acquisitions across the entire field of view, high SNR MPI signals can be acquired. When combined with reconstruction techniques based on system matrix, multi-dimensional SSME-MPI can be achieved. RESULTS: The effectiveness of the proposed method was validated through phantom and in vivo imaging experiments. The results demonstrate significant improvements in sensitivity (3.6-fold improvement) and spatial resolution (better than 1 mm) without any hardware modifications. CONCLUSION: These findings demonstrate the capability of SSME to enhance both the spatial resolution and sensitivity of MPI. SIGNIFICANCE: This method provides a solution to the ongoing challenge of balancing spatial resolution and sensitivity in MPI, potentially facilitating the implementation of MPI in a wider range of medical applications.

Caffeinated Chewing Gum Improves Basketball Shooting Accuracy and Physical Performance Indicators of Trained Basketball Players: A Double-Blind Crossover Trial.

(1) Background: This study investigated the effects of caffeinated chewing gum on the basketball-specific performance of trained basketball players. A double-blind, randomized crossover design was employed. (2) Methods: Fifteen participants (age: 20.9 ± 1.0 years; height: 180.9 ± 5.4 cm; mass: 77.2 ± 7.5 kg; training age: 8.2 ± 0.3 years) were recruited and divided into a caffeine trial (CAF) and placebo trial (PL). The participants in the CAF trial chewed gum containing 3 mg/kg of caffeine for 10 min, while those in the PL trial chewed a placebo gum without caffeine. Following a 15 min rest, all the participants completed basketball-specific performance tests. (3) Results: The free throw accuracy for the CAF trial was significantly higher than that for the PL trial (CAF: 79.0 ± 4.31%; PL: 73.0 ± 9.16%; p = 0.012; Cohen's d = 0.94). Additionally, the CAF trial demonstrated significantly better performance in the 20 m segmented dash (CAF: 2.94 ± 1.12 s; PL: 3.13 ± 0.10 s; p < 0.001; Cohen's d =1.8) and squats (p < 0.05), and exhibited lower fatigue indexes (CAF: 3.6 ± 1.6%; PL: 5.2 ± 1.6%; p = 0.009; Cohen's d =1.0). (4) Conclusions: These findings suggest that chewing gum containing 3 mg/kg of caffeine offers moderate-to-large improvements in key performance aspects relevant to professionally trained basketball players.

Serum urate levels and neurodegenerative outcomes: a prospective cohort study and mendelian randomization analysis of the UK Biobank.

BACKGROUND: Previous studies on the associations between serum urate levels and neurodegenerative outcomes have yielded inconclusive results, and the causality remains unclear. This study aimed to investigate whether urate levels are associated with the risks of Alzheimer's disease and related dementias (ADRD), Parkinson's disease (PD), and neurodegenerative deaths. METHODS: This prospective study included 382,182 participants (45.7% men) from the UK Biobank cohort. Cox proportional hazards models were used to assess the associations between urate levels and risk of neurodegenerative outcomes. In the Mendelian randomization (MR) analysis, urate-related single-nucleotide polymorphisms were identified through a genome-wide association study. Both linear and non-linear MR approaches were utilized to investigate the potential causal associations. RESULTS: During a median follow-up period of 12 years, we documented 5,400 ADRD cases, 2,553 PD cases, and 1,531 neurodegenerative deaths. Observational data revealed that a higher urate level was associated with a decreased risk of ADRD (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90, 0.96), PD (HR: 0.87, 95% CI: 0.82, 0.91), and neurodegenerative death (HR: 0.88, 95% CI: 0.83, 0.94). Negative linear associations between urate levels and neurodegenerative events were observed (all P-values for overall < 0.001 and all P-values for non-linearity > 0.05). However, MR analyses yielded no evidence of either linear or non-linear associations between genetically predicted urate levels and the risk of the aforementioned neurodegenerative events. CONCLUSION: Although the prospective cohort study demonstrated that elevated urate levels were associated with a reduced risk of neurodegenerative outcomes, MR analyses found no evidence of causality.

Prediction of hematologic toxicity in luminal type breast cancer patients receiving neoadjuvant chemotherapy using CT L1 level skeletal muscle index.

This study aims to explore the correlation between the CT-L1 and L3 body composition parameters and analyze the relationship between L1 body composition and hematologic toxicity in luminal-type breast cancer patients undergoing neoadjuvant chemotherapy. Data from 140 luminal-type breast cancer patients who underwent surgical treatment after neoadjuvant chemotherapy were analyzed retrospectively. Spearman analysis was used to assess the correlation between CT-L1 and CT-L3 body composition parameters pre-neoadjuvant chemotherapy. Additionally, univariate and multivariate logistic regression analyses were performed to identify factors influencing hematologic toxicity. CT-L1 body composition parameters were positively correlated with CT-L3 body composition parameters in 34 patients. Severe hematological toxicity occurred in 46 cases among the patient cohort. A skeletal muscle index (SMI) of < 32.91 cm2/m2, initial tumor size ≥ 3.335 cm, and a glucose-to-neutrophil ratio (GLR) ≥ 2.88 were identified as independent risk factors for severe hematologic toxicity during neoadjuvant chemotherapy in luminal-type breast cancer patients. The sample size in this study is small, and the predictive capacity of GLR in hematologic toxicity requires further research for comprehensive validation. CT-L1 analysis represents a viable alternative to CT-L3 analysis for body composition assessment. Patients with a low skeletal muscle index were more prone to experiencing severe hematologic toxicity during neoadjuvant chemotherapy.

Survival Analysis of Patients Undergoing Intraoperative Contrast-enhanced Ultrasound in the Surgical Treatment of Malignant Glioma.

OBJECTIVE: Complete resection of malignant gliomas is often challenging. Our previous study indicated that intraoperative contrast-enhanced ultrasound (ICEUS) could aid in the detection of residual tumor remnants and the total removal of brain lesions. This study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant glioma. METHODS: A total of 64 patients diagnosed with malignant glioma (WHO grade HI and IV) who underwent surgery between 2012 and 2018 were included. Among them, 29 patients received ICEUS. The effects of ICEUS on overall survival (OS) and progression-free survival (PFS) of patients were evaluated. A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding tissues. RESULTS: The ICEUS group showed better survival rates both in OS and PFS than the control group. The univariate analysis revealed that age, pathology and ICEUS were significant prognostic factors for PFS, with only age being a significant prognostic factor for OS. In multivariate analysis, age and ICEUS were significant prognostic factors for both OS and PFS. The quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding tissue. CONCLUSION: ICEUS facilitates the identification of residual tumors. Age and ICEUS are prognostic factors for malignant glioma surgery, and use of ICEUS offers a better prognosis for patients with malignant glioma.

BF3 complexing phosphate/phosphonate ionic liquids: synthesis, characterization and thermophysical properties.

A new group of BF3 complexing phosphate/phosphonate ionic liquids (ILs) [Emim][X(BF3)2] (X = dimethyl phosphate, diethyl phosphate, methyl phosphonate, and ethyl phosphonate) were synthesized and characterized. Key thermophysical properties of the new complex ionic liquids, including density, viscosity, conductivity, surface tension, solid-liquid phase transition, and thermal stability were determined and compared with those of [Emim][X]. Some other important thermophysical properties such as isobaric thermal expansion coefficient, molecular volume, standard molar entropy, and lattice potential energy were obtained from measured density data, and the free volume was estimated by a linear equation presented in this article, while critical temperature, normal boiling temperature, and enthalpy of vaporization were estimated from measured surface tension and density data. Furthermore, Fragility study shows that [Emim][X(BF3)2] could be considered as metallic glass-forming liquids, while [Emim][X] could be considered as extremely fragile liquids. The ionicity of [Emim][X(BF3)2] was predicted by Walden rule, and the result shows that these ILs fit well with Walden law. The key features of these complex ILs are their extremely low glass transition (-95.33~-98.46 ℃) without melting, considerably low viscosities (33.876~58.117 mPa·s), and high values of free volume fraction (comparable to [Omim][BF4], [Emim][NTf2], and [Emim][TCB]).

Spatial difference on nitrogen removal in the water based on different resolutions for Sanhuanpao wetland, Northeast China.

The research on the deviations caused by different resolutions is relevant to the study of spatial scale effects. In 2018, spatial interpolations were performed using the removal ratios of the TN, NH4-N, and NO3-N of the layers of different resolutions, respectively. Based on the mean and the standard deviation, the area, shape, and position were obtained for four levels related to the removal ratios of the three nitrogen forms. The linear and 6th function fitting methods were used to reveal the differences in nitrogen removal in wetland water at different spatial resolutions. The results showed that a resolution of 25 times the original was the key scale of the spatial effects. Due to the fact that 52 of the 72 functions did not reach a significant level (P < 0.05), the spatial scale effect of the nitrogen removal was mainly characterized by disorderly fluctuations. The results have a certain extrapolation value for the analysis of spatial scale effects. PRACTITIONER POINTS: The resolution difference was not sufficient to change the spatial pattern of the geographic phenomena. The resolution of 25 times the original was the important scale for determining spatial effects. When studying the spatial scale effects caused by differences in resolution, it was necessary to comprehensively consider various resolutions.

Relationship between fatty acid intake and aging: a Mendelian randomization study.

BACKGROUND: Observational studies have previously shown a possible link between fatty acids and aging-related diseases, raising questions about its health implications. However, the causal relationship between the two remains uncertain. METHODS: Univariable and multivariable Mendelian randomization (MR) was used to analyze the relationship between five types of fatty acids-polyunsaturated fatty acid (PUFA), monounsaturated fatty acid (MUFA), saturated fatty acid (SFA), Omega-6 fatty acid (Omega-6 FA), and Omega-3 fatty acid (Omega-3 FA) and three markers of aging: telomere length (TL), frailty index (FI), and facial aging (FclAg). The primary approach for Mendelian randomization (MR) analysis involved utilizing the inverse variance weighted (IVW) method, with additional supplementary methods employed. RESULTS: Univariate MR analysis revealed that MUFA, PUFA, SFA, and Omega-6 fatty acids were positively associated with TL (MUFA OR: 1.019, 95% CI: 1.006-1.033; PUFA OR: 1.014, 95% CI: 1.002-1.026; SFA OR: 1.016, 95% CI: 1.002-1.031; Omega-6 FAs OR=1.031, 95% CI: 1.006-1.058). PUFA was also associated with a higher FI (OR: 1.033, 95% CI: 1.009-1.057). In multivariate MR analysis, after adjusting for mutual influences among the five fatty acids, MUFA and PUFA were positively independently associated with TL (MUFA OR: 1.1508, 95% CI = 1.0724-1.2350; PUFA OR: 1.1670, 95% CI = 1.0497-1.2973, while SFA was negatively correlated (OR: 0.8005, 95% CI: 0.7045-0.9096). CONCLUSIONS: Our research presents compelling evidence of a causal association between certain fatty acids and indicators of the aging process. In particular, MUFA and PUFA may play a role in slowing down the aging process, while SFAs may contribute to accelerated aging. These findings could have significant implications for dietary recommendations aimed at promoting healthy aging.

Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. METHODS: Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS: A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. CONCLUSIONS: The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.

The BMAL1/HIF2A heterodimer modulates circadian variations of myocardial injury.

Acute myocardial infarction stands as a prominent cause of morbidity and mortality worldwide1-6. Clinical studies have demonstrated that the severity of cardiac injury following myocardial infarction exhibits a circadian pattern, with larger infarct sizes and poorer outcomes in patients experiencing morning onset myocardial infarctions7-14. However, the molecular mechanisms that govern circadian variations of myocardial injury remain unclear. Here, we show that BMAL114-20, a core circadian transcription factor, orchestrates diurnal variability in myocardial injury. Unexpectedly, BMAL1 modulates circadian-dependent cardiac injury by forming a transcriptionally active heterodimer with a non-canonical partner, hypoxia-inducible factor 2 alpha (HIF2A)6,21-23, in a diurnal manner. Substantiating this finding, we determined the cryo-EM structure of the BMAL1/HIF2A/DNA complex, revealing a previously unknown capacity for structural rearrangement within BMAL1, which enables the crosstalk between circadian rhythms and hypoxia signaling. Furthermore, we identified amphiregulin (AREG) as a rhythmic transcriptional target of the BMAL1/HIF2A heterodimer, critical for regulating circadian variations of myocardial injury. Finally, pharmacologically targeting the BMAL1/HIF2A-AREG pathway provides effective cardioprotection, with maximum efficacy when aligned with the pathway's circadian trough. Our findings not only uncover a novel mechanism governing the circadian variations of myocardial injury but also pave the way for innovative circadian-based treatment strategies, potentially shifting current treatment paradigms for myocardial infarction.

A Novel Local Magnetic Fluid Hyperthermia Based on High Gradient Field Guided by Magnetic Particle Imaging.

Magnetic Particle Imaging (MPI)-guided Magnetic Fluid Hyperthermia (MFH) has the potential for widespread utilization, as it allows for the prediction of magnetothermal dosage, real-time visualization of the thermal therapy process, and precise localization of the lesion area. However, the existing MPI-guided MFH (MPI-MFH) method is insensitive to concentration gradients of magnetic nanoparticles (MNPs) and is susceptible to causing damage to normal tissues with high MNP concentrations during MFH treatment, while inadequately heating tumor tissues with lower MNP concentrations. In this work, we established a relationship between MNP concentration and heating efficiency through simulations and phantom measurements, enabling the optimal selection of MFH parameters guided by MPI. Based on these findings, we developed a high-gradient field MPI-MFH method using a fieldfree point (FFP) approach to achieve precise local heating. Phantom experiments and in vivo glioma model experiments were conducted to validate this proposed method. The results demonstrated that the proposed method of MPIMFH can improve the MNP concentration gradient sensitivity to ±1 mg/ml, thereby enabling more effective lesion-site heating without damaging normal tissues. This method not only reduced glioma size effectively but also holds promise for application in various other types of cancers.

In Situ Detection of Nucleic Acids in Extracellular Vesicles via Membrane Fusion.

Extracellular vesicles (EVs) carry diverse biomolecules (e. g., nucleic acids, proteins) for intercellular communication, serving as important markers for diseases. Analyzing nucleic acids derived from EVs enables non-invasive disease diagnosis and prognosis evaluation. Membrane fusion, a fundamental cellular process wherein two lipid membranes merge, facilitates cell communication and cargo transport. Building on this natural phenomenon, recent years have witnessed the emergence of membrane fusion-based strategies for the detection of nucleic acids within EVs. These strategies entail the encapsulation of detection probes within either artificial or natural vesicles, followed by the induction of membrane fusion with EVs to deliver probes. This innovative approach not only enables in situ detection of nucleic acids within EVs but also ensures the maintenance of structural integrity of EVs, thus preventing nucleic acid degradation and minimizing the interference from free nucleic acids. This concept categorizes approaches into universal and targeted membrane fusion strategies, and discusses their application potential, and challenges and future prospects.

Spatio-temporal evolution and driving factors of new urbanization in central China based on multi-source data.

Urbanization is an inevitable outcome of the development of human society to a certain stage, and it is also an irreversible pattern of the concentration degree of human society. Based on multi-source data such as remote sensing images, ecological environment and socio-economic data, the evaluation index system of new urbanization is constructed from multi-dimensions of population, economy, society, space and ecology. To explore the spatio temporal evolution and driving factors of urbanization in 80 prefecture-level cities in central China from 2013 to 2021 by using entropy method, spatial autocorrelation model and geographic detector. The results show that: (1) The level of new urbanization continues to grow, with the average value rising from 0.1562 in 2013 to 0.2557 in 2021, and the regional differences are obvious, forming a circle structure with Wuhan, Zhengzhou and other provincial capitals as the center and weakening radiation to surrounding cities. (2) The agglomeration of ecological urbanization is significant, and the agglomeration trend is gradually enhanced. The high-high agglomeration areas tend to Xinzhou City, most prefecture-level cities in Hubei Province and some prefecture-level cities in Southern Hunan Province, while the low-low agglomeration areas tend to Changzhi City, most prefecture level cities in Henan Province and some prefecture-level cities in Northern Anhui Province. (3) The night light index, total retail sales of consumer goods, investment in fixed assets, proportion of built-up areas and urban economic density are the main driving factors affecting the level of new urbanization. (4) The interaction of driving factors shows double factor enhancement and nonlinear enhancement effects.