bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypochlorous acid derived from microglial myeloperoxidase could mediate high-mobility group box 1 release from neurons to amplify brain damage in cerebral ischemia–reperfusion injury
Authors: Chen Shuang , Pan Jingrui , Gong Zhe , Wu Meiling , Zhang Xiaoni , Chen Hansen , Yang Dan , Qi Suhua , Peng Ying , Shen Jiangang 
Published: March 2024

AbstractMyeloperoxidase (MPO) plays critical role in the pathology of cerebral ischemia–reperfusion (I/R) injury via producing hypochlorous acid (HOCl) and inducing oxidative modification of proteins. High-mobility group box 1 (HMGB1) oxidation, particularly disulfide HMGB1 formation, facilitates the secretion and release of HMGB1 and activates neuroinflammation, aggravating cerebral I/R injury. However, the cellular sources of MPO/HOCl in ischemic brain injury are unclear yet. Whether HOCl could promote HMGB1 secretion and release remains unknown. In the present study, we investigated the roles of microglia-derived MPO/HOCl in mediating HMGB1 translocation and secretion, and aggravating the brain damage and blood-brain barrier (BBB) disruption in cerebral I/R injury. In vitro, under the co-culture conditions with microglia BV cells but not the single culture conditions, oxygen–glucose deprivation/reoxygenation (OGD/R) significantly increased MPO/HOCl expression in PC12 cells. After the cells were exposed to OGD/R, MPO-containing exosomes derived from BV2 cells were released and transferred to PC12 cells, increasing MPO/HOCl in the PC12 cells. The HOCl promoted disulfide HMGB1 translocation and secretion and aggravated OGD/R-induced apoptosis. In vivo, SD rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus different periods of reperfusion. Increased MPO/HOCl production was observed at the reperfusion stage, accomplished with enlarged infarct volume, aggravated BBB disruption and neurological dysfunctions. Treatment of MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) and HOCl scavenger taurine reversed those changes. HOCl was colocalized with cytoplasm transferred HMGB1, which was blocked by taurine in rat I/R-injured brain. We finally performed a clinical investigation and found that plasma HOCl concentration was positively correlated with infarct volume and neurological deficit scores in ischemic stroke patients. Taken together, we conclude that ischemia/hypoxia could activate microglia to release MPO-containing exosomes that transfer MPO to adjacent cells for HOCl production; Subsequently, the production of HOCl could mediate the translocation and secretion of disulfide HMGB1 that aggravates cerebral I/R injury. Furthermore, plasma HOCl level could be a novel biomarker for indexing brain damage in ischemic stroke patients.
Mechanism of self-recovery of hydrophobicity after surface damage of lotus leaf
Authors: Wang Li , Shu Lichun , Hu Qin , Jiang Xingliang , Yang Hang , Wang Huan , Rao Lipeng 
Published: March 2024

AbstractThe surfaces of lotus leaves with micro- and nano-waxy cuticle structures are superhydrophobic and possess a self-healing ability to regain hydrophobicity after damage. Inspired by this phenomenon, the problem of water-repellent coatings used in natural environments failing to perform after damage can be solved if these coatings are endowed with rapid self-repair and self-growth functions. However, there has been almost no exploration into the hydrophobicity self-repair process in lotus leaves. The changes in surface morphology during the hydrophobicity recovery process are not understood. There is a lack of research on the hydrophobicity recovery in lotus leaves. In this study, the damage and recovery experiments on lotus leaf surfaces were carried out in an artificial climate chamber, and the water repellency recovery process and typical water repellency roughness parameters regained time were obtained. Upon analyzing the differences in the recovery process of different damage types, the recovery mechanism after lotus leaf surface damage was obtained. Finally, it was found that the microscopic roughness determined the static contact angle (WCA) of the lotus leaf surface, and the nanoscopic roughness determined the rolling angle (SA). The dual factors of the recovery of the extruded epidermal tissue and the regeneration of the epidermal wax crystals determined the hydrophobicity recovery process in damaged lotus leaves.
Exploring the support needs of Australian parents of young children with Usher syndrome: a qualitative thematic analysis
Authors: Johansen L. , O’Hare F. , Shepard E. R. , Ayton L. N. , Pelentsov L. J. , Kearns L. S. , Galvin K. L. 
Published: March 2024

Abstract
Background
Advancements in genetic testing have led to Usher syndrome now being diagnosed at a much earlier age than in the past, enabling the provision of early intervention and support to children and families. Despite these developments, anecdotal reports suggest there are substantial gaps in the services and supports provided to parents of children with Usher syndrome. The current study investigated the support needs of parents of children with Usher syndrome Type 1 when their child was aged 0 to 5 years.

Method
Purposive sampling was used, and six semi-structured interviews were conducted with Australian parents of children with Usher syndrome, Type 1. Data was analysed using modified reflexive thematic analysis.

Results
Four key themes were identified as being central to the support needs of parents of children with Usher syndrome aged 0 to 5 years. (1) Social Needs referred to parents’ need for various sources of social support, (2) Informational Needs described the lack of information parents received regarding Usher syndrome from treating professionals, (3) Practical Needs included supports needed to assist parents in managing the day-to-day tasks of caring for a child with a disability, and (4) Emotional Needs represented the emotional support (both formal and informal) that parents needed to be a positive support to their child.

Conclusions
Findings provide rich information for relevant support groups, policy makers, individual healthcare professionals, and professional governing bodies regarding the education of stakeholders and the development and implementation of best-practice treatment guidelines.
Effect of an entry-to-care intervention on diabetes distress in individuals with newly diagnosed type 2 diabetes: a study protocol for a cluster-randomized trial
Authors: Hansen Steffan Holst , Jensen Troels Mygind , Petersen Gitte Stentebjerg , Pouwer Francois , Larrabee Sonderlund Anders , Søndergaard Jens 
Published: March 2024

Abstract
Background
Diabetes distress (DD) affects at least 36% of T2DM patients and is often associated with insufficient support and care. This study examines an intervention that targets DD through enhanced cross-sectoral collaboration and treatment during the first 3 months following diagnosis. The intervention aims to improve care and self-management and to reduce DD.

Methods and intervention
The study is designed as a cluster-randomized trial with the intervention focusing on four key elements of diabetes care: effective cross-sectoral communication and information sharing, systematic care, a “one-stop-shop” health screening and start-up conversation at the municipality, and improving patient insights into own care.
This study requires 32 clusters (16/arm) to achieve 80% power and a 5% significance cut-off, with 270 patients required. GP recruitment occurred from May to Dec 2022. Patient recruitment is ongoing from May 2022 to Aug 2023. GPs were randomized 1:1 using computer-generated blocks of six.
Participating GPs are located in Southern Denmark and are not participating in other trials. Patients must be 18 + years of age, have a T2DM diagnosis, and be fluent in spoken and written Danish. DD is the primary outcome and will be measured at baseline, at four months, and again at a 12-month follow-up. Secondary outcomes include quality of care, self-management, quality of life, and clinical factors. Tertiary outcomes comprise depression, stress, resilience, sleep quality, and social network quality.

Conclusion
This study is among the first clinical trials exploring the development of DD from diagnosis to 12 months post-diagnosis. Many previous interventions did not directly target DD as the primary outcome. This research provides new insights into DD progression in patients newly diagnosed with T2DM and examines an intervention designed to lower DD in early diabetes stages, contributing to a better understanding of the development of DD and how this intervention affects patient well-being.

Trial registration
ClinicalTrial.gov NCT05571306. Registered on 07 October 2022.
Structural insights into curdlan degradation via a glycoside hydrolase containing a disruptive carbohydrate-binding module
Authors: Lv Tianhang , Feng Juanjuan , Jia Xiaoyu , Wang Cheng , Li Fudong , Peng Hui , Xiao Yazhong , Liu Lin , He Chao 
Published: March 2024

Abstract
Background
Degradation via enzymatic processes for the production of valuable β-1,3-glucooligosaccharides (GOS) from curdlan has attracted considerable interest. CBM6E functions as a curdlan-specific β-1,3-endoglucanase, composed of a glycoside hydrolase family 128 (GH128) module and a carbohydrate-binding module (CBM) derived from family CBM6.

Results
Crystallographic analyses were conducted to comprehend the substrate specificity mechanism of CBM6E. This unveiled structures of both apo CBM6E and its GOS-complexed form. The GH128 and CBM6 modules constitute a cohesive unit, binding nine glucoside moieties within the catalytic groove in a singular helical conformation. By extending the substrate-binding groove, we engineered CBM6E variants with heightened hydrolytic activities, generating diverse GOS profiles from curdlan. Molecular docking, followed by mutation validation, unveiled the cooperative recognition of triple-helical β-1,3-glucan by the GH128 and CBM6 modules, along with the identification of a novel sugar-binding residue situated within the CBM6 module. Interestingly, supplementing the CBM6 module into curdlan gel disrupted the gel’s network structure, enhancing the hydrolysis of curdlan by specific β-1,3-glucanases.

Conclusions
This study offers new insights into the recognition mechanism of glycoside hydrolases toward triple-helical β-1,3-glucans, presenting an effective method to enhance endoglucanase activity and manipulate its product profile. Furthermore, it discovered a CBM module capable of disrupting the quaternary structures of curdlan, thereby boosting the hydrolytic activity of curdlan gel when co-incubated with β-1,3-glucanases. These findings hold relevance for developing future enzyme and CBM cocktails useful in GOS production from curdlan degradation.
Attributes of Anopheles gambiae swarms in South Central Uganda
Authors: Birungi Krystal , Mabuka Danspaid P. , Balyesima Victor , Tripet Frederic , Kayondo Jonathan K. 
Published: March 2024

Abstract
Background
Anopheles gambiae continues to be widespread and an important malaria vector species complex in Uganda. New approaches to malaria vector control are being explored including population suppression through swarm reductions and genetic modification involving gene drives. Designing and evaluating these new interventions require good understanding of the biology of the target vectors. Anopheles mosquito swarms have historically been hard to locate in Uganda and therefore have remained poorly characterized. In this study we sought to identify and characterize An. gambiae s.l mosquito swarms in three study sites of high An. gambiae s.l prevalence within Central Uganda.

Methods
Nine sampling visits were made to three villages over a 2-year period. Sampling targeted both wet and dry seasons and was done for 2 days per village during each trip, using sweep nets. All swarm data were analysed using the JMP 14 software (SAS Institute, Inc., Cary, NC, USA), parametrically or non-parametrically as appropriate.

Results
Most of the An. gambiae s.s. swarms sampled during this study were single-species swarms. However, some mixed An. gambiae s.s. and Culex spp. mosquito swarms were also observed. Swarms were larger in the wet season than in the dry season. Mean swarm height ranged from 2.16 m to 3.13 m off the ground and only varied between villages but not by season. Anopheles gambiae mosquitoes were present in all three villages, preferred to swarm over bare ground markers, and could be effectively sampled by field samplers.

Conclusions
This study demonstrated that An. gambiae s.l swarms could be effectively located and sampled in South Central Uganda and provided in-depth descriptions of hitherto poorly understood aspects of An. gambiae local swarm characteristics. Swarms were found close to inhabited households and were greater in size and number during the rainy season. Anopheles gambiae s.s swarms were significantly associated with bare ground markers and were sometimes at heights over 4 m above the ground, showing a necessity to develop tools suitable for swarm sampling at these heights. While mixed species swarms have been reported before elsewhere, this is the first documented instance of mixed genus swarms found in Uganda and should be studied further as it could have implications for swarm sampling explorations where multiple species of mosquitoes exist.

Graphical Abstract
Correlation between time in range and serum uric acid in Chinese patients with type-2 diabetes: an observational cross-sectional study
Authors: Liu Yan , Peng Xiaoren , Qiu Chunjian , Shao Jiaqing 
Published: March 2024

Abstract
Background
At present, the relationship between serum uric acid and blood glucose is controversial, and even opposite conclusions have been reached. We aimed to investigate the relationship between time in range and serum uric acid and estimate the influence of serum uric acid on blood glucose fluctuations in Chinese patients with type-2 diabetes mellitus (T2DM).

Methods
A total of 458 hospitalized patients with T2DM were selected. According to the SUA level, patients were divided into four groups by quartile: Q1 (≤ 254.5 µmol/L), Q2 (254.5–306.0 µmol/L), Q3 (306.0–385.5 µmol/L) and Q4 (> 385.5 µmol/L). The differences in general data, TIR and other clinical indicators between the four groups were assessed. Multifactor regression was used to analyze the relationship between subgroups of SUA and TIR, TBR, TAR, MAGE, SD, ADRR, MODD and M value. Curve fitting was used to analyze the association between TIR and SUA and to identify the inflection point.

Results
TIR showed an overall increasing trend with increasing SUA, while HbA1c, TAR, MAGE, SD, ADRR, MODD and M value showed an overall decreasing trend with increasing SUA. Multivariate regression analysis showed that, compared with Q1, there was no correlation between SUA and TIR, TAR, ADRR, SD, or MODD in all models of Q2. In the Q3 and Q4 groups, SUA was correlated with SD, MODD, and MAGE in all models. In the Q4 group, SUA was correlated with TIR, TAR, ADRR, and the M value in all models. When SUA > 306 µmol/L (Q3 and Q4), TIR and SUA have a curve-like relationship, and the inflection point of the fitted curve was SUA = 460 mmol/L. Before the inflection point, β was 0.1, indicating that when SUA increases by 10 mmol/L, the corresponding TIR increases by 1%. After the inflection point, there was no significant difference in the correlation between TIR and SUA (P > 0.05).

Conclusions
There is a close relationship between TIR and SUA in T2DM patients, it is speculated that SUA in a certain range had a positive protective effect on blood glucose control.
Comment on "Effectiveness and safety of stem cell therapy for diabetic foot: a meta-analysis update"
Authors: Bai Yan , Zhang Fan 
Published: March 2024

AbstractIn the study published by Sun et al., a systematic review and meta-analysis illustrated the advantageous of stem cell therapy in diabetic foot and can improve the quality of life of patients. Nevertheless, the authors had a lack of knowledge regarding the methodology of the meta-analysis, which had four main aspects: (1) The textual report is inconsistent with the forest plot results, i.e., the authors have insufficient knowledge of RevMan. (2) The "zero event" needs to be corrected for summary analysis. (3) Lack of aesthetics in the forest plots. (4) Registration is recommended for systematic reviews and meta-analyses.
Pocket Crafter: a 3D generative modeling based workflow for the rapid generation of hit molecules in drug discovery
Authors: Shen Lingling , Fang Jian , Liu Lulu , Yang Fei , Jenkins Jeremy L. , Kutchukian Peter S. , Wang He 
Published: March 2024

AbstractWe present a user-friendly molecular generative pipeline called Pocket Crafter, specifically designed to facilitate hit finding activity in the drug discovery process. This workflow utilized a three-dimensional (3D) generative modeling method Pocket2Mol, for the de novo design of molecules in spatial perspective for the targeted protein structures, followed by filters for chemical-physical properties and drug-likeness, structure–activity relationship analysis, and clustering to generate top virtual hit scaffolds. In our WDR5 case study, we acquired a focused set of 2029 compounds after a targeted searching within Novartis archived library based on the virtual scaffolds. Subsequently, we experimentally profiled these compounds, resulting in a novel chemical scaffold series that demonstrated activity in biochemical and biophysical assays. Pocket Crafter successfully prototyped an effective end-to-end 3D generative chemistry-based workflow for the exploration of new chemical scaffolds, which represents a promising approach in early drug discovery for hit identification.
Therapeutic and immunomodulatory potentials of mesenchymal stromal/stem cells and immune checkpoints related molecules
Authors: Hazrati Ali , Malekpour Kosar , Khorramdelazad Hossein , Rajaei Samira , Hashemi Seyed Mahmoud 
Published: March 2024

AbstractMesenchymal stromal/stem cells (MSCs) are used in many studies due to their therapeutic potential, including their differentiative ability and immunomodulatory properties. These cells perform their therapeutic functions by using various mechanisms, such as the production of anti-inflammatory cytokines, growth factors, direct cell-to-cell contact, extracellular vesicles (EVs) production, and mitochondrial transfer. However, mechanisms related to immune checkpoints (ICPs) and their effect on the immunomodulatory ability of MSCs are less discussed. The main function of ICPs is to prevent the initiation of unwanted responses and to regulate the immune system responses to maintain the homeostasis of these responses. ICPs are produced by various types of immune system regulatory cells, and defects in their expression and function may be associated with excessive responses that can ultimately lead to autoimmunity. Also, by expressing different types of ICPs and their ligands (ICPLs), tumor cells prevent the formation and durability of immune responses, which leads to tumors' immune escape. ICPs and ICPLs can be produced by MSCs and affect immune cell responses both through their secretion into the microenvironment or direct cell-to-cell interaction. Pre-treatment of MSCs in inflammatory conditions leads to an increase in their therapeutic potential. In addition to the effect that inflammatory environments have on the production of anti-inflammatory cytokines by MSCs, they can increase the expression of various types of ICPLs. In this review, we discuss different types of ICPLs and ICPs expressed by MSCs and their effect on their immunomodulatory and therapeutic potential.
Sensitive and reliable miRNA analysis based on cyclic reverse transcription and CRISPR-Cas12a-assisted signal cycle
Authors: Yang Xiaoqing , Gao Jie 
Published: March 2024

AbstractMicroRNAs (miRNAs), a category of small molecules that possess significant regulatory capabilities, have been extensively employed as biomarkers in the domain of biosensing to facilitate the early detection of diverse ailments. However, sensitive and accurate miRNA detection remains a huge challenge due to the high similarity between the homologous sequences and low abundance. Therefore, it is essential to develop methods with high sensitivity and specificity for miRNA detection. In this study, we present the development of a signal cycle-based platform that utilizes cyclic reverse transcription (CRT) and CRISPR-Cas12a to enable the precise and sensitive detection of microRNAs. The CRT mechanism facilitates precise target recognition in the presence of target miRNA, thereby converting miRNA signals to DNA signals. The trans-cleavage activity of the Cas12a protein is triggered by the formation of complete hairpin-shaped CRT products; this results in the cleavage of the DNA section contained in the H probe, while the RNA section (“4”@MBs) remains loaded onto the surface of magnetic beads (MB). By binding with the “reporter” sensor, the “4” sequences create an RNA/DNA duplex that the duplex-specific nuclease (DSN) can recognize. The “reporter” probe is thus metabolized, leading to the reappearance of the fluorescence signal. By capitalizing on the exceptional fidelity and selectivity of CRISPR/Cas12a, as well as the substantial impact of triggered enzymatic cycle amplification, this approach demonstrated remarkable sensitivity and specificity in miRNA detection, even in a complex environment containing 10% fetal bovine serum (FBS) and a serum sample. In contrast, a detection limit of 3.2 fM is conceivable. Furthermore, this approach maintained a notable degree of stability, which was anticipated to result in the detection of miRNAs in an effective and sensitive manner.
Direct and indirect instruction in educational robotics: a comparative study of task performance per cognitive level and student perception
Authors: Anđić Branko , Maričić Mirjana , Mumcu Filiz , Prodromou Theodosia , Leoste Janika , Saimon Musa , Lavicza Zsolt 
Published: March 2024

AbstractEducational Robotics (ER) has emerged as one of the tools to improve STEM learning in primary education if students are properly instructed. However, there is a lack of studies that guide teachers on which type of instruction should be used for ER in STEM between direct (DI) and indirect instruction (II). As a result, the present study aims to compare the two types of instructions in terms of their effect on learning outcomes, students’ perceptions, and students’ gender differences. We adopted a quasi-experiment comparative research design involving 100 ninth-grade students (13–14 years old). We collected data through achievement tests and perception questionnaires and analyzed them using Cochran’s Q-test, Mann–Whitney U-test, and independent samples t-test. Results show that the group in which II was used performed better than those from the group where DI was used. Also, the results show that girls performed better with DI than boys. Furthermore, students perceived ER as useful for developing collaboration and interest in STEM. Therefore, teachers should be supported in learning how to use II and DI strategically in ER to enhance STEM learning.