Bridging Role Research Articles

Post-transplant relapse in pediatric acute lymphoblastic leukemia in the era of CAR-T cell therapy. A multicenter analysis of Grupo Español de Trasplante Hematopoyetico y Terapia Celular (GETH-TC) Pediatric Committee.

BackgroundThe management of relapsed acute lymphoblastic leukemia (ALL) after hematopoietic stem cell transplantation (HSCT) has evolved significantly. Initially, treatment options were limited to palliative care, salvage chemotherapy, and second HSCT. Currently, the focus has shifted to innovative immunotherapies, particularly CAR T-cell therapy. ObjectivesThis study aims to: 1. Analyze outcomes after relapse following HSCT and identify prognostic factors associated with prolonged survival. 2. To evaluate and compare treatment strategies, including immunotherapy (e.g., CAR T-cell therapy) and second HSCT after achieving a new remission, or both treatments in high-risk cases. Study designThis retrospective, multicenter study will evaluate the outcomes of HSCT relapse in pediatric ALL patients. Key endpoints include disease-free survival (DFS), relapse rate, and NRM. We enrolled 73 children with ALL who relapsed after HSCT in 10 hospitals of the Pediatric Committee of the Spanish Group of Transplantation (GETH-TC) between 2013 and 2021. Among them, 56 patients (77%) had B-cell ALL and 17 (23%) had T-cell ALL. ResultsThe median time to relapse was 6 months after the first HSCT. CAR-T cell therapy was administered to 31 patients, all of whom achieved complete remission with negative MRD. However, two patients died prematurely due to cytokine release syndrome (CRS), resulting in a NRM of 7±4%. Sixteen patients relapsed after CAR-T therapy with a cumulative incidence (CI) of 65±11%. Seven of these patients subsequently underwent a second HSCT. The only significant prognostic factor for DFS was the MRD level prior to CAR-T therapy: DFS was 20±8% with MRD ≥3% compared to 100% with MRD <3% (p=0.002). At a median follow-up of 17 months after CAR-T therapy, DFS was 28±10% and overall survival (OS) was 40±10%. Second allogeneic HSCT was performed in 23 patients, including 7 who had previously received CAR-T therapy. Three patients died from NRM (CI: 19±10%). Eight patients relapsed after the second HSCT (CI: 52±13%), of which 2 were successfully treated with CAR-T therapy. At a median follow-up of 33 months after the second HSCT, DFS was 29±11% and OS was 32±10%. Of 17 patients with T-cell ALL, only 2 survived after a second HSCT with a DFS of 12±9%. Of the 73 patients, 20 are alive with a median follow-up of 4 years (DFS: 20±5%). Time to relapse after HSCT was the strongest predictor of outcome; no patient who relapsed within 6 months after the first HSCT survived. There was a trend towards worse DFS in patients who developed chronic GVHD during the first transplant, with 8 out of 9 relapsing despite rescue therapy (p<0.07). ConclusionsChildren with relapsed ALL after HSCT have a substantial chance of long-term survival if relapse occurs more than 6 months after the first transplant and if chronic GVHD was not present. The treatment paradigm has shifted to immunotherapy, including monoclonal antibodies and CAR-T therapy. The role of bridging to a second allogeneic HSCT after CAR-T therapy to improve long-term survival remains a subject of ongoing debate.

Bibliometric analysis of youth myocardial infarction research (1980-2023).

Cardiovascular diseases include myocardial infarction, a high mortality disease. Myocardial infarction patients are becoming younger, typically defined as patients under 45 years of age. This study analyzes the relevant papers on myocardial infarction in youth in the Web of Science Core Collection (WoSCC) between 1980 and 2023. It uses bibliometric methods to systematically understand the current status and development trend of research in this field. We searched the WoSCC between 1980 and 2023 for research papers and reviews on myocardial infarction in youth. We set the screening criteria for language as English and used tools such as Citespace, SCImago Graphica, and VOS Viewer to analyze the selected literature exhaustively. This comprehensive approach helped us gain a comprehensive understanding of research hotspots, academic partnerships, and trends in the field. From the WoSCC, we identified 790 publications related to myocardial infarction in youth. First, the United States, Italy, and China are major contributors to international cooperation. The United States plays a vital bridging role. Next, in the scholars' combined contribution power analysis, Krumholz and Donfrio were the key contributors in this field. In addition, popular research directions are based on age. As a result of the literature cluster analysis, we found that myocardial infarction in youth is associated with gender, smoking, coagulation factors, apolipoproteins, and gene polymorphisms. This is the first comprehensive bibliometric study of myocardial infarction in youth. It aims to examine the current status and trends in myocardial infarction in youth. As a result, the study results will provide researchers with an overview of emerging trends.

The spatial impact of high bridges on travel accessibility and economic integration in Guizhou, China: a scenario-based analysis

As crucial fixed links of the transportation systems, high bridges play an essential role in overcoming geographical barriers in mountainous areas. Despite their importance, comprehensive evaluations of the collective spatial-temporal effects of multiple high bridges across broad regions are lacking. This study addresses this gap by analyzing the impact of 295 high bridges in Guizhou, China, on travel accessibility and economic potential through spatial analysis under scenarios with and without these bridges. The aim is to quantify their contributions to accessibility and assess their impacts on regional economic integration from 2000 to 2020. The findings reveal that high bridges significantly improved travel accessibility and economic potential within counties, with the average contributions being the greatest for the period 2010–2015 within the whole study period. High bridge construction promoted accessibility convergence and economic integration, reducing regional disparities. The decline in the coefficient of variation (CV) of accessibility demonstrated a converging effect; while the CV of economic potential showed an initial growth followed by a decline. Economically disadvantaged counties gained the most in accessibility and economic potential, highlighting the role of high bridges in regional integration. This study proposes a framework for accurately measuring the economic benefits of high bridges, providing insights for future transport planning in isolated mountainous counties and supporting economic development in regions with underdeveloped transportation infrastructure.

Bolstering the initiative of construction project members: a self-determination lens combining project social media use

PurposeIn today’s turbulent and complex era, initiative behavior is becoming more drawn to construction projects but challenging to arouse as it is free of the established regulations in project practice. Given the prevalence of social media (SM) in modern workplaces, this study is thereby motivated to investigate whether and how SM use can act to drive initiative behavior of construction project members (PMs) in this context.Design/methodology/approachThis study sharply examines two distinct types of SM use – work-related and social-related – to explore their roles in driving the initiative behavior of construction PMs. Additionally, self-determination theory is employed to explore their underlying translation mechanisms and associated boundary conditions. A survey dataset collected from 229 construction PMs is used to empirically test the proposed theoretical model.FindingsEmpirical results show that role-breadth self-efficacy, psychological safety and project identification, by satisfying basic psychological needs respectively, act as crucial bridging roles in translating SM use into initiative behavior of PMs. Such mediation effects are applied to both work-related and social-related SM use with varied mechanisms. Besides, prevention focus is found to be a contingent moderator on these relationships, with a strengthening role toward role-breadth self-efficacy and a weakening role toward project identification.Originality/valueThis study digs into the nuanced mechanisms of how SM use benefits construction projects, especially in terms of PMs’ initiative. The findings of this research afford new insights into effectively invigorating the initiative behavior of construction PMs under the current digital momentum.

Identification of Veillonella parvula and Streptococcus gordonii adhesins mediating co-aggregation and its impact on physiology and mixed biofilm structure.

Our research explores the mechanisms of bacterial adhesion within the dental plaque, focusing on Veillonella parvula, a key player in the oral microbiome. Dependent on lactate from streptococci, V. parvula plays a crucial bridging role in the formation of dental biofilms by co-aggregating with other bacteria. Despite its importance, the understanding of the underlying mechanisms of co-aggregation remains limited. Our study shows that V. parvula uses different trimeric autotransporters to adhere to oral Streptococci and Actinomyces. We additionally identify a novel adhesin from S. gordonii, VisA (SGO_2004) facilitating this interaction. We found that although co-aggregation does not affect cell-cell communication, it is critical for biofilm structure and species distribution. This research opens up new avenues for exploring microbial interactions in dental health and diseases.

Point-defect-induced electronic polarization to enhance H* generation for removal of bisphenol A

Intrinsic point defects in metal core-shell materials can regulate electron redistribution, thereby reducing catalytic energy barriers and enhancing their ORR activity. However, their specific contributions to electron transfer and mass transport pathways remain unclear. In this study, defect-rich hollow OCo@Co3O4 nanoparticles were successfully synthesized using ZIF-67(Co) as a sacrificial template through controlled annealing and internal electric field substitution reactions. High-resolution electron microscopy analysis and density functional theory (DFT) calculations co-revealed the growth mechanism of Co and O vacancies, as well as antisite defects. The formation of oxygen vacancies significantly lowered the energy barrier for Co vacancy formation, playing a crucial bridging role in the development of antisite defects. The electric field polarization induced by Co-O atomic displacement resulted in asymmetric charge distribution, optimizing the adsorption of active hydrogen (H*) and oxygen atoms and facilitating the generation and release of reactive oxygen species (ROS). Electrocatalytic experiments demonstrated that under the combined action of singlet oxygen (1O2) and H*, bisphenol A (BPA) can be efficiently degraded. This study successfully bridges the knowledge gap between atomic defects and advanced electrocatalysis, providing a new perspective and insight for the in-depth analysis of the structure-performance relationship of electrocatalyst materials in the future.

How Clinician-Scientists Access and Mobilise Social Capital and Thus Contribute to the Professional Development of Their Colleagues in Their Networks

ABSTRACT Clinician-scientists, physicians who conduct research, may fulfil a bridging role in networks of health care researchers and practitioners. Within clinician-scientists’ networks, knowledge sharing is thought to play a vital role in the continuing professional development of themselves and their colleagues. However, little is known about networks of clinician-scientists and how this impacts continuing professional development. Rooted in social capital theory, this study provides a mixed methods exploration of clinician-scientists’ networks. Ego-level social network data were collected via semi-structured interviews on professional interactions about evidence-based practice with 15 clinician-scientists in the area of general practice and elderly care. Quantitative analysis revealed that professional networks of clinician-scientists varied in size, composition, and frequency of interactions depending on appointed research time and experience. Less experienced clinician-scientists interacted most frequently with other clinician-scientists while experienced clinician-scientist experienced more sporadically with clinicians. Clinician-scientists with more research time interacted more frequently with scientists and had a slightly larger professional network than those with less research time. The thematic qualitative analysis revealed different decision-making processes of clinician-scientists on mobilising their social capital and connecting to others in the network: (1) deliberate decision about initiating connections; (2) reactive behaviour without a decision; (3) ad-hoc decision. Clinician-scientists exchange knowledge to enhance their own continuing professional development mainly but also contribute to the professional development of clinicians, scientists, and other clinician-scientists.

Transitory Imaginaries in Central and Eastern Europe: Reconsidering Constitutional Tradition and Constitutional Transition from Symbolic-Imaginary Perspective

Abstract This paper explores the transitory imaginaries in the semi-permanent constitutional polytransition in the Central and Eastern European region. It is centered on the novel concept of transitory imaginaries. This concept serves as a tool for combined socio-legal, comparative, and semiotic approach to constitutional transitions. The paper demonstrates the deep conceptual and pragmatic links between constitutional transitology, memory politics, and identity politics. It exposes the role of the forms of symbolic-imaginary constitutionalism for shaping and understanding of constitutional transitions and polytransitions. The paper shows the importance of constitutional imagination for collective symbolic-imaginary sublimation of constitutional transition and the bridging role of constitutional imaginaries that are stretched between the constitutional past, the constitutional present, and the constitutional future. In that regard, the paper explores the different ways for imagining the constitutional past and constitutional future and offers an outline of the main imaginaries in serving that purpose. More precisely, the paper analyses nationalist transitory imaginaries, universalist transitory imaginaries, and prospective transitional imaginaries.

Characterization of gut microbiota dynamics in an Alzheimer’s disease mouse model through clade-specific marker-based analysis of shotgun metagenomic data

Alzheimer’s disease (AD) is a complex neurodegenerative disorder significantly impairing cognitive faculties, memory, and physical abilities. To characterize the modulation of the gut microbiota in an in vivo AD model, we performed shotgun metagenomics sequencing on 3xTgAD mice at key time points (i.e., 2, 6, and 12 months) of AD progression. Fecal samples from both 3xTgAD and wild-type mice were collected, DNA extracted, and sequenced. Quantitative taxon abundance assessment using MetaPhlAn 4 ensured precise microbial community representation. The analysis focused on species-level genome bins (SGBs) including both known and unknown SGBs (kSGBs and uSGBs, respectively) and also comprised higher taxonomic categories such as family-level genome bins (FGBs), class-level genome bins (CGBs), and order-level genome bins (OGBs). Our bioinformatic results pinpointed the presence of extensive gut microbial diversity in AD mice and showed that the largest proportion of AD- and aging-associated microbiome changes in 3xTgAD mice concern SGBs that belong to the Bacteroidota and Firmicutes phyla, along with a large set of uncharacterized SGBs. Our findings emphasize the need for further advanced bioinformatic studies for accurate classification and functional analysis of these elusive microbial species in relation to their potential bridging role in the gut-brain axis and AD pathogenesis.

The role of myocardial bridging in athletes with ST-segment depression or T-wave inversion on exercise testing

Abstract Background Myocardial bridging (MB) is a congenital anomaly in which a myocardial band partially or completely covers a coronary artery. It is a common finding in the general population, but it is more frequent in athletes. MB can cause ST-segment depression on exercise testing, which can be misinterpreted as coronary artery disease and generate the prohibition of sports. Aim To evaluate the presence of Myocardial Bridging (MB) through Multi-Slice Tomography Angiography in Moderate to High Intensity Athletes with Electrocardiographic changes and normal parietal motility in Stress Ultrasound with Exercise Methods This study included 159 athletes who had ST-segment depression or T-wave inversion on exercise testing. All participants underwent coronary angiography and/or multislice computed tomography coronary angiography. In addition, follow-up was 36 months (+/- 18 months) to assess the presence of major adverse cardiovascular events (MACE). Results A total of 3790 stress tests were requested from the Cardiology and Sports Clinic: 3631 (95.8%) were completely normal (no ST changes and normal parietal motility) and 159 (4.2%) showed ST segment depression. Of the 159 athletes, 42 (1.11%) had ST depression in the inferior and/or lateral segments and abnormal parietal motility at maximal exercise and were referred for invasive coronary angiography. The remaining 117 (3.09%) had the following ECG changes: 88 (72.21%) inferior and/or lateral ST segment depression and 29 (24.78%) T wave inversion without ST segment depression. Ninety-two (78.64%) of the above 117 athletes were diagnosed with 1 or more MBs in the coronary arteries. One hundred and forty-three MBs were found. The most common location was the anterior descending coronary artery (n=61; 42.6%) in its middle and distal third, followed by findings in the diagonal (n=30; 20.9%), circumflex (n=28; 19.5%) and marginal (n=24; 16.7%) branches. No MACE was recorded during the follow-up period and no further complex diagnostic studies were required. Conclusions Our study suggests that MB is a common cause of ST-segment depression and/or T-wave inversion on exercise testing in athletes. MB is usually benign and does not increase the risk of cardiovascular events. Therefore, athletes with MB should be allowed to continue participating in sports.ECG during maximal exercise stress echocTMSC of athlete

Cationic polymer-mediated interbacterial aggregation: A novel approach for rapid aerobic granules development

This study introduces a novel approach to aerobic granular sludge technology that minimizes the start-up time and guarantees the formation of stable granules. This is achieved by seeding the reactor with a cationic polymer without using inoculated sludge. Three cationic polymers (Hydrofloc C4400SA, C8896, and polyelectrolyte emulsion) were tested to determine the most appropriate polymer for aerobic granular sludge (AGS) startup based on the optimal dose and formation of aerobic granules. Hydrofloc cationic polymer C4400SA has excellent granule-forming properties in the AGS reactor compared to their counterparts. The formation of granules was boosted by adding 15 ppm of polymer, resulting in densely packed aerobic granules after 10 days. This improvement can be due to the more cationic properties of hydrofloc, which play a key role in bridging between cells and particles because the cationic charges of hydrofloc attract negatively charged bacteria in wastewater, thereby promoting aggregation and the formation of initial flocs. These flocs serve as the foundation for the development of granules. After 80 days of operation, 40–50% of particles with an average size range from 0.6 to 0.9 mm were observed. The AGS SBR operation was closely monitored and showed consistent efficiency in removing solids, where TP, TN, NH+4 –N, and the total soluble COD were removed at average efficiencies of 62%, 73%, 97%, 93%, and 79% respectively, during steady-state cycles conducted at room temperature. Overall, this study highlights the potential of hydrofloc cationic polymer C4400SA to enhance the performance and resilience of AGS in wastewater treatment applications.

Locoregional Therapies and Interventional Radiology in Managing Hepatocellular Carcinoma: A Comprehensive Approach to Bridging, Downstaging, and Liver Transplantation

AbstractHepatocellular carcinoma (HCC) remains a significant global health challenge, particularly for patients awaiting liver transplants (LTs) due to the scarcity of donor organs. During the waiting period, a multidisciplinary approach becomes crucial to optimize tumor treatment and preserve liver function. In recent years, interventional radiology has emerged as an integral part of treatment strategies. It has played a pivotal role in bridging and downstaging patients on the path to transplantation. Interventional radiologists administer minimally invasive locoregional therapies to HCC patients on LT waiting lists. Additionally, they address complications such as portal hypertension and portal vein thrombosis, which can lead to clinical deterioration and jeopardize transplant candidacy. This article examines the pivotal role of interventional radiology in the management of HCC, highlighting recent studies and advancements within the field. Additionally, it provides a concise review of the eligibility criteria for LT in patients with HCC, alongside a discussion of the surgical techniques employed in LT for these patients.

Dynamic clustering-based consensus model for large-scale group decision-making considering overlapping communities

Consensus-reaching strategy is crucial in large-scale group decision-making (LSGDM) as it serves as an effective approach to reducing group conflicts. Meanwhile, the common social network relationships in large groups can affect information exchange, thereby influencing the consensus-reaching process (CRP) and decision results. Therefore, how to leverage social network information in LSGDM to obtain an agreed solution has received widespread attention. However, most existing research assumes relative independence between communities in the dimension reduction process of LSGDM and neglects the possibility of different overlaps between them. Moreover, the impact of overlapping communities on CRP has not been adequately explored. Besides, the dynamic variations in clusters and their weights caused by evaluation updates need to be further studied. To address these issues, this paper proposes a dynamic clustering-based consensus-reaching method for LSGDM considering the impact of overlapping communities. First, the LINE-based label propagation algorithm is designed to cluster decision makers (DMs) and detect overlapping communities with social network information. An overlapping community-driven feedback mechanism is then developed to enhance group consensus by utilizing the bridging role of overlapping DMs. During CRP, clusters and their weights are dynamically updated with trust evolution due to the evaluation iteration. Finally, a case study using the Film Trust dataset is conducted to verify the effectiveness of the proposed method. Simulation experiments and comparative analysis demonstrate the capability of our method in modeling practical scenarios and addressing LSGDM problems under social network contexts.

Exploration on the mechanism of enhancing flotation of long-flame coal by diesel modification via oxidation

Low-rank coal is naturally hydrophilic, and the traditional hydrocarbon collectors often have poor performance in its flotation. In this study, the modification of diesel was conducted using an instantaneous gasification-oxidation-condensation device for the expected improvement of collector’s performance. Experimental analyses and interfacial interaction calculation were performed to explore the mechanism of enhancing flotation of long-flame coal by diesel modification. It indicated that the flotation of coal sample can be greatly enhanced by the modified diesel, and a combustible matter recovery of 90.52 % could be attained only consuming 6 kg/t of modified diesel which was far better than the flotation effect consuming 100 kg/t of common diesel. The improved flotation effect of the coal sample could be attributed to the increased polarity of collector from 0.48 % to 9.76 % resulted from the newly added oxygenated functional groups after the oxidation of diesel, which significantly enhanced the adsorption capacity of the collector on the long-flame coal surface reflected by the FTIR and XPS analyses. Furthermore, the calculated results of interfacial interaction between the coal sample and the common/modified diesel suggested that the efficient adsorption of modified diesel on the coal sample was achieved through the bridging role acted by water molecules. This research may give some insight into enhancing flotation of low-rank coal.

Pyrazine Dicarboxylic Acid and Phosphite-Bridging Lanthanide-Incorporated Tellurotungstates and Their Fluorescence Performances.

Two pyrazine dicarboxylic acid and phosphite-bridging lanthanide-incorporated tellurotungstates [H2N(CH3)2]12 Na4[Ln4(H2O)2(H2PDBA)2(HPO3)2W6O10][B-α-TeW8O31]4 · 70H2O [Ln = Eu3+ (1), Tb3+ (2); H2PDBA = 2,5-pyrazine dicarboxylic acid) were prepared, which contain four [B-α-TeW8O31]10- subunits and a deca-nuclear heterometallic [Ln(H2O)2(HPO3)2 (H2PDBA)2(W3O5)2]24+ cluster. Strikingly, two H2PDBA ligands connect two equivalent {W3Eu2O5(H2O)(B-α-TeW8O31)2(HPIIIO3)}8- moieties to form the polyanion skeleton, while the phosphite plays a bridging role in joining two lanthanide centers in the {W3Eu2O5(H2O)(B-α-TeW8O31)2(HPIIIO3)}8- moiety. In addition to the fluorescence (FL) properties of 1 and 2 at room temperature, their temperature-dependent FL properties were also investigated. In 80-298 K, FL intensities of 1 and 2 decrease as temperature increases, and their maximum relative sensitivities (Sr) are 3.70 and 1.99% K-1, whereas the minimum temperature uncertainties (δT) are 1.25 and 1.18 K for 1 and 2. In 298-973 K, upon increasing temperature, FL intensities of 1 and 2 initially rise to their maxima at 373 K and subsequently decrease. This is because samples of 1 and 2 undergo dehydration together with amorphization below 473 K and decomposition above this temperature. This work lays a foundation for the development for luminescent thermometers based on lanthanide-incorporated polyoxometalates.

Symptom Network and Clusters of the Multidimensional Symptom Experience in Patients With Atrial Fibrillation

Background The symptom network can provide a visual insight into the symptom mechanisms. However, few study authors have explored the multidimensional symptom network of patients with atrial fibrillation (AF). Objectives We aimed to identify the core symptom and symptom clusters of patients with AF by generating a symptom network. Furthermore, we wanted to identify multiple characteristics related to symptom clusters. Methods This is a cross-sectional study. A total of 384 patients with AF at Tianjin Medical University General Hospital were enrolled. The University of Toronto Atrial Fibrillation Severity Scale was used to assess AF symptoms. Network analysis was used to explore the core symptom and symptom cluster. Results Shortness of breath at rest (r s = 1.189, r c = 0.024), exercise intolerance (r s = 1.116), shortness of breath during physical activity (r s = 1.055, r c = 0.022), and fatigue at rest (r c = 0.020) have the top centrality for strength and closeness. The top 3 symptoms of bridge strength were shortness of breath at rest (r s = 0.264), dizziness (r s = 0.208), and palpitations (r s = 0.207). Atrial fibrillation symptoms could be clustered into the breathless cluster and the cardiac cluster. We have identified multiple factors such as mental health status, left ventricular ejection fraction, heart failure, sex, B-type natriuretic peptide, and chronic obstructive pulmonary disease as significant contributors within the breathless cluster, whereas sex, mental health status, and history of radiofrequency ablation were strongly associated with the cardiac cluster, holding promise in elucidating the underlying mechanisms of these symptoms. Conclusion Special attention should be given to shortness of breath at rest as its core and bridging role in patients' symptoms. Furthermore, both the breathless and cardiac clusters are common among patients. Network analysis reveals direct connections between symptoms, symptom clusters, and their influencing factors, providing a foundation for clinicians to effectively manage patients' symptoms.

A Simple Analysis of the Second (Extra) Disulfide Bridge of VHHs.

Camelids produce a special type of antibody, known as VHHs, that has lost the VL domain, providing a more optimised VH domain. This particular highly stable antibody domain has interesting properties for biotechnological development. Ordinarily, those molecules possess only one disulphide bridge, but surprisingly, at least a quarter of these VHHs have a second one. Curiously, this does not seem to be essential for the stability and the function of this domain. In an attempt to characterise precisely the role and impact of this disulphide bridge at the molecular level, several in silico mutants of a VHH were created to disrupt this second disulphide bridge and those systems were submitted to molecular dynamics simulation. The loss of the second disulphide bridge leads to an increase in the flexibility of CDR1 and CDR3 and an unexpected rigidification of CDR2. Local conformational analysis shows local differences in the observed protein conformations. However, in fact, there is no exploration of new conformations but a change in the equilibrium between the different observed conformations. This explains why the interaction of VHHs is not really affected by the presence or absence of this second bridge, but their rigidity is slightly reduced. Therefore, the additional disulphide bridge does not seem to be an essential part of VHHs function.

Evaluation of Boundary Layer Characteristics at Mount Si’e Based on UAV and Lidar Data

The atmospheric boundary layer is a crucial transitional region connecting the surface with the free atmosphere, playing a bridging role in land-sea-air interactions and the interactions between different atmospheric layers. This study utilizes rotary-wing UAVs, high-resolution lidar, and WRF simulation data to analyze the vertical distribution characteristics of temperature, humidity, wind speed, and wind direction boundary layer over the Mount Si’e region in 4–6 April 2024. The results indicate that the boundary layer temperature decreases with increasing altitude, reaching up to 18°C, while humidity decreases with height, dropping to as low as 35%. Daytime wind speeds range from 4 to 8 m/s, decreasing to 2 to 4 m/s at night. The boundary layer height can reach up to 900 m during the day and drops to 100–200 m at night, showing distinct diurnal variation characteristics. UAV observations are in good agreement with lidar and WRF simulation results, highlighting the application value of UAVs in high temporal and spatial resolution boundary layer studies. The study also reveals the significant impact of complex terrain on boundary layer characteristics, providing scientific insights into the dynamic and thermal processes of the boundary layer and offering reference value for improving regional weather forecasting and numerical simulations.

SMURF1 mediates damaged lysosomal homeostasis by ubiquitinating PPP3CB to promote the activation of TFEB

ABSTRACT The calcium-activated phosphatase PPP3/calcineurin dephosphorylates TFEB (transcription factor EB) to trigger its nuclear translocation and the activation of macroautophagic/autophagic targets. However, the detailed molecular mechanism regulating TFEB activation remains poorly understood. Here, we highlighted the importance of SMURF1 (SMAD specific E3 ubiquitin protein ligase 1) in the activation of TFEB for lysosomal homeostasis. SMURF1 deficiency prevents the calcium-triggered ubiquitination of the catalytic subunit of PPP3/calcineurin in a manner consistent with defective autophagic degradation of damaged lysosomes. Mechanically, PPP3CB/CNA2 plays a bridging role in the recruitment of SMURF1 by LGALS3 (galectin 3) upon lysosome damage. Importantly, PPP3CB increases the dissociation of the N-terminal tail (NT) and C-terminal carbohydrate-recognition domain (CRD) of LGALS3, which may promote the formation of open conformers in a PPP3CB dephosphorylation activity-dependent manner. In addition, PPP3CB is ubiquitinated at lysine 146 by the recruited SMURF1 in response to intracellular calcium stimulation. The K63-linked ubiquitination of PPP3CB enhances the recruitment of TFEB. Moreover, TFEB directly interacts with both PPP3CB and the regulatory subunit PPP3R1 which facilitate the conformational correction of TFEB for its activation for the transcription of TFEB-targeted genes. Altogether, our results highlighted a critical mechanism for the regulation of PPP3/calcineurin activity via its ubiquitin ligase SMURF1 in response to lysosomal membrane damage, which may account for a potential target for the treatment of stress-related diseases.Abbreviation AID: autoinhibitory domain; ATG: autophagy related; CD: catalytic domain; CRD: carbohydrate-recognition domain; CsA: cyclosporin A; DMSO: dimethyl sulfoxide; ESCRT: endosomal sorting complexes required for transport; GSK3B: glycogen synthase kinase 3 beta; LAMP1: lysosomal associated membrane protein 1; LGALS3: galectin 3; LLOMe: L-leucyl-L-leucine methyl ester; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; ML-SA1: mucolipin synthetic agonist 1; MTORC1: mechanistic target of rapamycin kinase complex 1; NT: N-terminal tail; PPP3CB: protein phosphatase 3 catalytic subunit beta; PPP3R1: protein phosphatase 3 regulatory subunit B, alpha; SMURF1: SMAD specific E3 ubiquitin protein ligase 1; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; VCP/p97: valosin containing protein; YWHA/14-3-3: tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein.

A nanoscale natural drug delivery system for targeted drug delivery against ovarian cancer: action mechanism, application enlightenment and future potential.

Ovarian cancer (OC) is one of the deadliest gynecological malignancies in the world and is the leading cause of cancer-related death in women. The complexity and difficult-to-treat nature of OC pose a huge challenge to the treatment of the disease, Therefore, it is critical to find green and sustainable drug treatment options. Natural drugs have wide sources, many targets, and high safety, and are currently recognized as ideal drugs for tumor treatment, has previously been found to have a good effect on controlling tumor progression and reducing the burden of metastasis. However, its clinical transformation is often hindered by structural stability, bioavailability, and bioactivity. Emerging technologies for the treatment of OC, such as photodynamic therapy, immunotherapy, targeted therapy, gene therapy, molecular therapy, and nanotherapy, are developing rapidly, particularly, nanotechnology can play a bridging role between different therapies, synergistically drive the complementary role of differentiated treatment schemes, and has a wide range of clinical application prospects. In this review, nanoscale natural drug delivery systems (NNDDS) for targeted drug delivery against OC were extensively explored. We reviewed the mechanism of action of natural drugs against OC, reviewed the morphological composition and delivery potential of drug nanocarriers based on the application of nanotechnology in the treatment of OC, and discussed the limitations of current NNDDS research. After elucidating these problems, it will provide a theoretical basis for future exploration of novel NNDDS for anti-OC therapy.