bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐Lactate‐Metabolizing Photosynthetic Bacteria Reprogram Tumor Immune Microenvironment
Authors: Ma Yichuan , Hu Yujing , Liu Huifang , Li Xiaoya , Li Yuanhang , Zhao Yu , Zhang Qi , Zhang Ziyang , Leng Qingqing , Luo Li , Li Lanya , Dai Yunlu , Chen Guojun , Zhang Jinchao , Li Zhenhua
Published: June 2024

The elevated levels of lactate in tumor tissue play a pivotal role in fostering an immunosuppressive microenvironment. Therefore, efficiently reducing lactate levels to reprogram tumor immune microenvironment (TIM) is considered a crucial step for boosted immunotherapy. Here, a high‐lactate‐metabolizing photosynthetic bacteria (LAB‐1) is selectively screened for TIM reprogramming, which then improves the efficacy of tumor immunotherapy. The culture medium for LAB‐1 screening is initially developed through an orthogonal experiment, simulating the tumor microenvironment (TME) and utilizing lactate as the sole organic carbon source. As demonstrated in a murine 4T1 model, LAB‐1 colonizes the TME selectively, resulting in a significant reduction in lactate levels and a subsequent increase in pH values within the tumor tissue. Furthermore, single‐cell RNA sequencing analysis reveals that LAB‐1 effectively reprograms the TIM, thereby enhancing the effectiveness of antitumor immune therapy. This approach of utilizing lactate‐consuming bacteria represents a potent tool for augmenting tumor immunotherapy efficiency.
Indexing Topological Numbers on Images by Transferring Chiral Magnetic Textures
Authors: Park Seong Min , Moon Tae Jung , Yoon Han Gyu , Kwon Hee Young , Won Changyeon
Published: June 2024

Topological analysis is widely adopted in various research fields to unveil intricate features and structural relationships implied in geometrical objects. Especially, in the fields of data analysis, exploring the topological properties of various images offers rich insights into the intrinsic geometrical information within them. In this study, a novel approach is proposed to investigate the topological properties of arbitrary grayscale images by employing a straightforward procedure used in 2D magnetism studies to calculate topological numbers. This method utilizes machine learning techniques to transfer chiral magnetic textures onto the images. Then, the topological number is then computed directly from the converted images by integrating the solid angles formed by adjacent spin vectors. The method successfully identifies the topological numbers of various grayscale images, showing stable performances against small noises. Furthermore, two applications of the method: are demonstrated topological analysis of the Modified National Institute of Standards and Technology (MNIST) dataset and the counting of blood cells in microscopic images.
Large Area Ballistocardiography Enabled by Printed Piezoelectric Sensor Arrays on Elastomeric Substrates
Authors: Zalar Peter , Burghoorn Marieke M. A. , Fijn Joost A. , Rikken Lars F. A. , Rensing Peter A. , van den Brand Jeroen , de Leeuw Dago M. , Smits Edsger C. P.
Published: June 2024

Ballistocardiography (BCG) studies ballistic forces on the body generated during a heartbeat. As it is an unobtrusive detection method, that requires sensors measuring small dynamic forces. Piezoelectric sensors are ideal, but improvements in sensitivity are needed. Here, a universal method is demonstrated to obtain enhanced effective transverse charge constants by utilizing thin and long sensors fabricated upon compliant substrates. This approach is validated using the uniquely printable and patternable piezoelectric polymer, poly(vinylidene fluoride‐co‐trifluoroethylene) (P(VDF‐TrFE). Discrete sensors detect displacements of less than 1 µm, dynamic forces of ∼mN, and accelerations of ≈1 mm−1 s2. Since the sensor is screen‐printable, it is upscaled to a human‐sized array (60 × 90 cm, 255 sensors). High quality spatially resolved BCG measurements of a person is demonstrated in seated and supine positions. The obtained heart rate is verified using photoplethysmography. This development opens the door to ever‐more sensitive piezoelectric sensors, crucial for applications including and beyond healthcare.
Selective and Sensitive Detection of Cu+ in Living Cells Based on Chelator Modified Carbon Dots
Authors: Gao Tian , Deng Peixuan , Guo Shengnan , Zhang Jiaojiao , Cai Yan , Hu Zhicong , Cai Qun , Liu Yi
Published: June 2024

Cuprous ions (Cu+) are essential for various biological activities. However, it is still a great challenge to detect Cu+ efficiently in cells in situ. As emerging 0‐D carbon photoluminescence nanomaterials, carbon dots (CDs) exhibit non‐toxicity and ultra stability, which shows great advantages in biosensing and bioimaging. In this work, CDs are prepared by a one‐step microwave‐assisted hydrothermal method. To enhance the selectivity and efficiency of the CDs‐based sensor, the NS4‐CDs are synthesized by surface modification of CDs using Cu+ chelating molecules. The NS4‐CDs, that carry specific detection molecules, exhibit remarkable selectivity and high sensitivity with an extraordinarily low detection limit (26 nmol L−1). It is noteworthy that the detection response is extremely fast, which only takes 20 s. The PL response mechanism of NS4‐CDs is also thoroughly investigated. In addition, the NS4‐CDs possess great biocompatibility and non‐cytotoxicity, which is vital for advanced cellular imaging applications. Finally, the NS4‐CDs are successfully applied to Cu+ detection in cells in situ. This work paves a new path for the design and efficient construction of CDs‐based biosensors for ion detection in cells, which expands the application area of carbon nanomaterials.
Isl Identifies the Extraembryonic Mesodermal/Allantois Progenitors and is Required for Placenta Morphogenesis and Vasculature Formation
Authors: Zhu Zeyue , Zou Qicheng , Wang Chunxiao , Li Dixi , Yang Yan , Xiao Ying , Jin Yao , Yan Jie , Luo Lina , Sun Yunfu , Liang Xingqun
Published: June 2024

The placenta links feto‐maternal circulation for exchanges of nutrients, gases, and metabolic wastes between the fetus and mother, being essential for pregnancy process and maintenance. The allantois and mesodermal components of amnion, chorion, and yolk sac are derived from extraembryonic mesoderm (Ex‐Mes), however, the mechanisms contributing to distinct components of the placenta and regulation the interactions between allantois and epithelium during chorioallantoic fusion and labyrinth formation remains unclear. Isl1 is expressed in progenitors of the Ex‐Mes and allantois the Isl1 mut mouse line is analyzed to investigate contribution of Isl1+ Ex‐Mes / allantoic progenitors to cells of the allantois and placenta. This study shows that Isl1 identifies the Ex‐Mes progenitors for endothelial and vascular smooth muscle cells, and most of the mesenchymal cells of the placenta and umbilical cord. Deletion of Isl1 causes defects in allantois growth, chorioallantoic fusion, and placenta vessel morphogenesis. RNA‐seq and CUT&Tag analyses revealed that Isl1 promotes allantoic endothelial, inhibits mesenchymal cell differentiation, and allantoic signals regulated by Isl1 mediating the inductive interactions between the allantois and chorion critical for chorionic epithelium differentiation, villous formation, and labyrinth angiogenesis. This study above reveals that Isl1 plays roles in regulating multiple genetic and epigenetic pathways of vascular morphogenesis, provides the insight into the mechanisms for placental formation, highlighting the necessity of Isl1 for placenta formation/pregnant maintenance.
A Cost‐Effective Hemin‐Based Artificial Enzyme Allows for Practical Applications
Authors: Qiu Dehui , He Fangni , Liu Yuan , Zhou Zhaoxi , Yang Yuqin , Long Zhongwen , Chen Qianqian , Chen Desheng , Wei Shijiong , Mao Xuanxiang , Zhang Xiaobo , Mergny Jean‐Louis , Monchaud David , Ju Huangxian , Zhou Jun
Published: June 2024

Nanomaterials excel in mimicking the structure and function of natural enzymes while being far more interesting in terms of structural stability, functional versatility, recyclability, and large‐scale preparation. Herein, the story assembles hemin, histidine analogs, and G‐quadruplex DNA in a catalytically competent supramolecular assembly referred to as assembly‐activated hemin enzyme (AA‐heminzyme). The catalytic properties of AA‐heminzyme are investigated both in silico (by molecular docking and quantum chemical calculations) and in vitro (notably through a systematic comparison with its natural counterpart horseradish peroxidase, HRP). It is found that this artificial system is not only as efficient as HRP to oxidize various substrates (with a turnover number kcat of 115 s−1) but also more practically convenient (displaying better thermal stability, recoverability, and editability) and more economically viable, with a catalytic cost amounting to <10% of that of HRP. The strategic interest of AA‐heminzyme is further demonstrated for both industrial wastewater remediation and biomarker detection (notably glutathione, for which the cost is decreased by 98% as compared to commercial kits).
Advancements in Ruthenium (Ru)‐Based Heterostructure Catalysts: Overcoming Bottlenecks in Catalysis for Hydrogen Evolution Reaction
Authors: Kuang Yubin , Yang Fulin , Feng Ligang
Published: June 2024

Investigating clean and sustainable hydrogen generation from water splitting requires cost‐effective and highly efficient electrocatalysts for the hydrogen evolution reaction (HER). Ruthenium (Ru)‐based heterostructure catalysts have emerged as promising alternatives to precious Pt, offering significant potential to overcome current bottlenecks. Recent advancements in Ru‐based heterostructure catalysts have focused on achieving a balance between catalytic activity and stability. An overview of these developments provides insights into catalytic mechanisms and facilitates the development of novel catalysts. This review begins with an exploration of the enhanced activity of heterostructure catalysts, followed by a critical summary of synthetic strategies employed to fabricate these catalysts and their catalytic performances for HER. Attention is then directed to experimental endeavors aimed at enhancing the HER performance of Ru‐based heterostructure catalysts. Finally, the opportunities and challenges in developing heterostructure catalysts from the perspectives of material design and synthesis are discussed. Through these discussions, a comprehensive understanding of Ru‐based heterostructure catalysts and inspiring future research directions is the aim to provide.
Low‐pass whole genome sequencing as a cost‐effective alternative to chromosomal microarray analysis for low‐ and middle‐income countries
Authors: Mazzonetto Patricia C. , Villela Darine , Krepischi Ana C. V. , Pierry Paulo M. , Bonaldi Adriano , Almeida Luiz Gustavo D. , Paula Marcelo G. , Bürger Matheus Carvalho , de Oliveira Ana Gabriela , Fonseca Gustavo G. G. , Giugliani Roberto , Riegel‐Giugliani Mariluce , Bertola Débora , Yamamoto Guilherme Lopes , Passos‐Bueno Maria Rita , Campos Gabriele da Silva , Machado Ana Claudia Dantas , Mazzeu Juliana F. , Perrone Eduardo , Zechi‐Ceide Roseli M. , Kokitsu‐Nakata Nancy M. , Vieira Társis Paiva , Steiner Carlos Eduardo , Gil‐da‐Silva‐Lopes Vera Lúcia , Vieira Daniela Koeller Rodrigues , Boy Raquel , de Pina‐Neto João Monteiro , Scapulatempo‐Neto Cristovam , Milanezi Fernanda , Rosenberg Carla
Published: June 2024

Low‐pass whole genome sequencing (LP‐WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing‐based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP‐WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP‐WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%–20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP‐WGS emerges as a cost‐effective alternative for investigating copy number changes in cytogenetics.
Management change following transthoracic echocardiogram in the intensive care unit
Authors: Smith Jeremy A , Mistry Ravi
Published: June 2024

Introduction/Purpose

The optimal utilisation of echocardiography in intensive care units (ICU) is not yet known; however, its use is becoming more frequent. Management change from transthoracic echocardiography (TTE) in ICU is quoted to be from 3% to 50%.

Methods

A retrospective review of clinical practice was performed over a 2‐month period in a tertiary adult ICU, to explore the utilisation of formal TTEs and the findings of these. The rate of management change and critical findings were investigated, along with the indication for TTE and the patient cohort.

Results

Sixty‐three TTEs were performed in 54 patients. A change in management occurred in 25.4% (16/63) of TTEs, with critical findings being found in 47.6% (30/63) of all TTEs. The most common indications for formal TTEs were incompletely differentiated or further evaluation of shock, and post arrest cardiac function.

Discussion

Almost half of the TTEs performed had critical findings, with common critical findings being severe LV dysfunction, severe RV dysfunction and regional wall motion abnormalities. Despite critical findings being seen frequently, there was only management change in 25%, suggesting that several of the critical findings were already suspected, clinically confirmed or had anticipatory management prior to TTE.

Conclusion

Critical findings are common in critically ill patients. However, not all critical findings will lead to a change in management. Formal TTEs in the ICU should be focussed to the clinical question being asked and a screening intensivist performed bedside TTE may be appropriate in certain situations to decrease workload of cardiology department.
An ethically guided preclinical device for phenotyping H2 production in laboratory rodents
Authors: Pascal‐Moussellard Victor , Boucher Emilie , Tanguy Stéphane , Cinquin Philippe , Barraud Pierre‐Alain , Davin Chloé , Salomez‐Ihl Cordélia , Hannani Dalil , Boucher François , Alcaraz Jean‐Pierre
Published: June 2024

Background

Dihydrogen (H2) is produced endogenously by the intestinal microbiota through the fermentation of diet carbohydrates. Over the past few years, numerous studies have demonstrated the significant therapeutic potential of H2 in various pathophysiological contexts, making the characterization of its production in laboratory species of major preclinical importance.

Methods

This study proposes an innovative solution to accurately monitor H2 production in free‐moving rodents while respecting animal welfare standards. The developed device consisted of a wire rodent cage placed inside an airtight chamber in which the air quality was maintained, and the H2 concentration was continuously analyzed. After the airtightness and efficiency of the systems used to control and maintain air quality in the chamber were checked, tests were carried out on rats and mice with different metabolic phenotypes, over 12 min to 1‐h experiments and repeatedly. H2 production rates (HPR) were obtained using an easy calculation algorithm based on a first‐order moving average.

Results

HPR in hyperphagic Zucker rats was found to be twice as high as in control Wistar rats, respectively, 2.64 and 1.27 nmol.s−1 per animal. In addition, the ingestion of inulin, a dietary fiber, stimulated H2 production in mice. HPRs were 0.46 nmol.s−1 for animals under control diet and 1.99 nmol.s−1 for animals under inulin diet.

Conclusions

The proposed device coupled with our algorithm enables fine analysis of the metabolic phenotype of laboratory rats or mice with regard to their endogenous H2 production.
Preliminary study of metabonomic changes during the progression of atherosclerosis in miniature pigs
Authors: Jia Yunxiao , Zhao Yuqiong , Niu Miaomiao , Zhao Changqi , Li Xuezhuang , Chen Hua
Published: June 2024

Background

To explore potential biomarkers for early diagnosis of atherosclerosis (AS) and provide basic data for further research on AS, the characteristics of serum metabolomics during the progression of AS in mini‐pigs were observed dynamically.

Methods

An AS model in Bama miniature pigs was established by a high‐cholesterol and high‐fat diet. Fasting serum samples were collected monthly for metabolomics and serum lipid detection. At the end of the treatment period, pathological analysis of the abdominal aorta and coronary artery was performed to evaluate the lesions of AS, thereby distinguishing the susceptibility of mini‐pigs to AS. The metabolomics was detected using a high‐resolution untargeted metabolomic approach. Statistical analysis was used to identify metabolites associated with AS susceptibility.

Results

Based on pathological analysis, mini‐pigs were divided into two groups: a susceptible group (n = 3) and a non‐susceptible group (n = 6). A total of 1318 metabolites were identified, with significant shifting of metabolic profiles over time in both groups. Dynamic monitoring analysis highlighted 57 metabolites that exhibited an obvious trend of differential changes between two groups with the advance of time. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis indicated significant disorders in cholesterol metabolism, primary bile acid metabolism, histidine metabolism, as well as taurine and hypotaurine metabolism.

Conclusions

During the progression of AS in mini‐pigs induced by high‐cholesterol/high‐fat diet, the alterations in serum metabolic profile exhibited a time‐dependent pattern, accompanied by notable disturbances in lipid metabolism, cholesterol metabolism, and amino acid metabolism. These metabolites may become potential biomarkers for early diagnosis of AS.
Chitosan‐based pH‐sensitive antibacterial bionanocomposites with laponite immobilized silver nanoparticles for delivery of sunitinib maleate to breast cancers
Authors: Labib Parisa , Mahdavinia Gholam Reza , Dehghani Arezoo , Nobarzad Raoofeh Sattari , Sayyar Zahra , Jafari Hessam , Najafzadeh Khashayar , Akinay Yüksel , Akbari Ali
Published: June 2024

In this work, new pH‐sensitive and antibacterial drug carrier systems based on silver nanoparticles (AgNPs) embedded in the interlayer of laponite (Lap) in the presence of chitosan (CTS) for the controllable release of sunitinib maleate (STM) were developed. Silver ions and sunitinib maleate were first loaded into Lap, and the CTS‐based hybrid bionanocomposite carrier (Lap@CTS@AgNPs@STM) was obtained in the presence of citric acid as a cross‐linker agent. The successful preparation of nanocarrier and Ag NPs formation was thoroughly confirmed using techniques such as FTIR, XRD, TGA, SEM, and TEM. TEM images illustrated the excellent distribution of Ag NPs in the structure of Lap@CTS@AgNPs. The as‐prepared samples showed a pH‐sensitive anticancer drug release behavior. The STM release mechanism was studied using Korsmeyer–Peppas and Higuchi kinetic models. Furthermore, the in vitro cytotoxicity and antibacterial tests were carried out against both bacteria S. aureus and E. coli and MCF‐7 cell lines, respectively, to prove the effectiveness of synthesized samples as multifunctional carrier systems for biomedical applications.
Effect of lubricant functional groups on tribological properties of epoxy/graphene composites
Authors: Zheng Wenxuan , Zhang Guoliang , Qi Jian , Lu Shichao , Li Yang
Published: June 2024

The functional group in the molecular chain of lubricants is a key factor for a boundary lubricating film, which can further enhance the friction performance by interfacial tribochemistry. In this paper, the tribological behavior of epoxy/graphene (EP/Gra) composites was investigated through varying lubrication conditions, including dry friction, or different lubricants (such as water, hexadecane, oleylamine, and oleic acid). The porosity and Shore hardness (SHD) of the EP composites were significantly improved by the addition of graphene. Results showed that the porosity of the EP/0.75 wt.% Gra composites was reduced by 75.6% and their SHD increased by 5.4 compared with the EP/0.05 wt.% Gra composites. The average coefficient of friction (COF) of the composites was reduced by at least 27.3% under dry friction conditions. For water as lubricant, the EP/0.5 wt.% Gra composite exhibited the lowest COF (0.0455). The EP/0.75 wt.% Gra composite displayed the lowest COF (0.0466) when hexadecane acted as lubricant. By contrast, EP/0.05 wt.% Gra showed the lowest COF (0.0389) with oleylamine as lubricant, and the EP/0.25 wt.% Gra composites gave the lowest COF (0.0433) under oleic acid. The amine group of oleylamine reacted with the EP group to form a hydroxyl group, resulting in a polymer with low friction adhered to the friction interface. Simultaneously, the EP group reacted with the carboxyl group, forming a network of hydrogen bonds with graphene, which reduced the shear stress on the friction interface. Therefore, the functional groups of lubricants have a vital influence on the tribological properties of frictional composites, which may provide a new approach to solving the problem of wear.
Synthesis of polyesters derived from glycerol and phthalic anhydride and its application for bitumen modification
Authors: Joshi Vedant , Kumar Kamal , Nandu Krishna K. , Senthilkumar Thangaraj
Published: June 2024

This study introduces phthalic anhydride (P) and glycerol (G)‐based polyester as an additive for upgrading lower‐grade bitumen to higher‐grade bitumen. The different colorless polyesters were synthesized using polycondensation of P and G as a monomer in the ratio of 1:1 and polymerization time of 1, 3, 5, and 7 h. A rheological analysis was performed on all the synthesized polyesters to check their performance with respect to their use in bitumen modification. The polyesters were blended with base bitumens (VG10) to obtain the modified bitumens that were tested for the rheological and physicochemical properties and to assess the performance based on the grade quality test. The quality test of the modified bitumens includes softening point (SP), penetration (PEN), kinematic viscosity (KV), dynamic viscosity (DV), and rheological properties as per standard ASTM test methods. Based on the performance evaluation, P1G1H3 polyester was found suitable for blending with bitumen, and further study was carried out with blending of P1G1H3 with 3, 6, 10, and 15 wt%. The finding illustrates that 6.0 wt% of polyester‐modified bitumen show an enhanced SP, KV, and DV by 23.6, 86, and 30%, respectively, while decreasing the PEN by 49% with respect to VG10. Polyester blending also improved the rheological parameters in terms of deformation resistance, load‐bearing capacity, and the viscoelastic nature of bitumen. The investigation concluded that 6 wt% P1G1H3 polyester on blending in VG10 meets VG30 bitumen specification as per IS:73:2013.
Engineering Nanobelt Structure via Sulphur and Oxygen Doping: Synthesis, Structural Characterization, and Complexation with Fullerenes
Authors: Liu Yandie , Wang Shenghua , Xie Jialin , Du Zhenglin , Chen Qing , Li Xia , Zhu Kelong
Published: June 2024

This study explores the synthesis, structural characterization, and host‐guest interactions of heteroatom bridged nanobelts, focusing on a cyclothianthrene nanobelt and a fused nanobelt incorporating thianthrene and phenoxathiin. Utilizing a cyclization‐followed‐by‐bridging synthetic approach, both molecular belts were successfully synthesized, and their structures confirmed through NMR and MALDI‐TOF‐MS analysis. Crystallographic studies revealed that the cyclothianthrene nanobelt adopts an octagonal column‐like conformation, while the hybrid belt forms an oval tub‐shaped shape, both exhibiting distinct assembly motifs. The host‐guest chemistry of these nanobelts was investigated with fullerenes (C60, C70, and PC61BM). The cyclothianthrene belt showed no interaction with these fullerenes, whereas the other belt demonstrated adaptive binding capabilities, forming stable complexes with C60 and C70 through π–π interactions and C−H⋅⋅⋅S hydrogen bonds. The binding constants indicated that the hybrid belt has a stronger affinity for C70 due to better size complementarity. Additionally, its interaction with PC61BM showcased a specific 1 : 1 binding mode despite exhibiting a smaller binding constant. This study underscores the impact of heteroatom incorporation on the structural and functional properties of nanobelts, offering insights for future molecular design strategies.
Probabilistischer Nachweis einer Spannbetonbrücke – Teil 2
Authors: Özlü Caner , Küttenbaum Stefan , Kainz Christian , Braml Thomas , Taffe Alexander
Published: June 2024

Im zweiten Teil dieses Beitrags werden die Grenzzustandsfunktionen für die Nachweise im Grenzzustand der Tragfähigkeit für Biegung mit Normalkraft, Querkraft mit Querkraftbewehrung und Torsion vorgestellt. Die Eingangsgrößen der mechanischen Widerstandsmodelle werden durch zahlreiche Abbildungen illustriert. Auf Grundlage der probabilistischen Modelle aus dem ersten Teil dieses Aufsatzes und der mechanischen Modelle aus diesem zweiten Teil werden die probabilistischen Nachweise geführt. Die Ergebnisse aus der Zuverlässigkeitsanalyse werden mit den semiprobabilistischen Berechnungsergebnissen verglichen. Mittels Parameterstudien wird gezeigt, welche Eingangsgrößen im Standsicherheitsnachweis die größten Einflüsse auf die Bauwerkszuverlässigkeit haben. Die Messung dieser Parameter ist entsprechend besonders nützlich. Auf dieser Basis wird abschließend gezeigt, welche Chancen sich aus der Durchführung von zerstörungsfreien Bauwerksprüfungen für die Nachrechnung ergeben.
Balancing act: BRCA2's elaborate management of telomere replication through control of G‐quadruplex dynamicity
Authors: Joo So Young , Sung Keewon , Lee Hyunsook
Published: June 2024

In billion years of evolution, eukaryotes preserved the chromosome ends with arrays of guanine repeats surrounded by thymines and adenines, which can form stacks of four‐stranded planar structure known as G‐quadruplex (G4). The rationale behind the evolutionary conservation of the G4 structure at the telomere remained elusive. Our recent study has shed light on this matter by revealing that telomere G4 undergoes oscillation between at least two distinct folded conformations. Additionally, tumor suppressor BRCA2 exhibits a unique mode of interaction with telomere G4. To elaborate, BRCA2 directly interacts with G‐triplex (G3)‐derived intermediates that form during the interconversion of the two different G4 states. In doing so, BRCA2 remodels the G4, facilitating the restart of stalled replication forks. In this review, we succinctly summarize the findings regarding the dynamicity of telomeric G4, emphasize its importance in maintaining telomere replication homeostasis, and the physiological consequences of losing G4 dynamicity at the telomere.
iPS cell therapy 2.0: Preparing for next‐generation regenerative medicine
Authors: Hui Kelvin K. , Yamanaka Shinya
Published: June 2024

This year marks the tenth anniversary of the world's first transplantation of tissue generated from induced pluripotent stem cells (iPSCs). There is now a growing number of clinical trials worldwide examining the efficacy and safety of autologous and allogeneic iPSC‐derived products for treating various pathologic conditions. As we patiently wait for the results from these and future clinical trials, it is imperative to strategize for the next generation of iPSC‐based therapies. This review examines the lessons learned from the development of another advanced cell therapy, chimeric antigen receptor (CAR) T cells, and the possibility of incorporating various new bioengineering technologies in development, from RNA engineering to tissue fabrication, to apply iPSCs not only as a means to achieve personalized medicine but also as designer medical applications.
Feasible and economic DIY procedures of a hand‐held fluorescence detector set—FluorDetector to assist laboratory course development
Authors: Ding Bo , Wang Ju , Mao Yaxin , Meng Tian , Luo Yumei , Xu Xiaomei , Lv Zhanqing , Zhou Mian , Yang Qiuying
Published: June 2024

Fluorescence‐related experimental techniques play an important role in biochemistry, molecular biology, and cell biology. However, fluorescence‐related experiments are rarely included in the laboratory courses of most Chinese universities. This is mainly due to the conflict between large class size (50–60 students in one room) and funding/space limitations to purchase and accommodate enough fluorescence detection equipment. Here, we proposed feasible and economical Do It Yourself (DIY) procedures of a hand‐held fluorescence detector set—FluorDetector to support the development of laboratory courses. Tested on several samples, clear fluorescence signals could be directly observed by FluorDetector and photographed with a smartphone. In addition, FluorDetector was able to turn a conventional stereomicroscope into a fluorescence stereomicroscope, detecting fluorescence signals with clean background. FluorDetector is easy to make with a 3D printer, with an extremely low cost ($200 each) when compared with a commercial fluorescence microscope or fluorescence stereomicroscope, and almost as sensitive as a microplate reader in measuring fluorescence. Therefore, FluorDetector is a possible strategy to solve the problem and help to integrate fluorescence‐related experimental modules in laboratory courses.
Nanomedicine hitchhiking on bacteria for treating tumors
Authors: Zheng Shujing , Li Xingwei , Guo Shutao
Published: June 2024

Nanomedicine has shown promising therapeutic potential in cancer treatment, with clinically approved formulations such as Doxil® and Abraxane® already providing tangible benefits to patients. However, challenges such as low targeting efficiency and poor tumor penetration limit its application. Bacteria have emerged as promising drug delivery carriers due to their capacity for autonomous navigation and deep penetration into hypoxic tumor parenchyma. Therefore, utilizing bacteria as carriers for nanomedicine can partially overcome the limitations of anti‐tumor nanomedicine. Moreover, some bacteria, like Salmonella typhimurium and Escherichia coli, exhibit immunostimulatory and oncolytic effects and can synergistically enhance the anti‐tumor effects of nanomedicine. This article summarizes common types of bacteria and nanomedicines and their respective advantages and challenges in cancer treatment. It elaborates on various strategies for combining bacteria and nanomedicine under different administration routes, outlining the clinical progress and challenges of bacterial anti‐tumor therapy and outlooking for future applications of utilizing bacteria as carriers for nanomedicine in cancer treatment.
Multiparameter neuroimaging study of neurovascular coupling changes in patients with end‐stage renal disease
Authors: Sun Wei , Li Chen , Jiao Zhuqing , Liu Tongqiang , Shi Haifeng
Published: June 2024

Purpose

To assess changes in neurovascular coupling (NVC) by evaluating the relationship between cerebral perfusion and brain connectivity in patients with end‐stage renal disease (ESRD) undergoing hemodialysis versus in healthy control participants. And by exploring brain regions with abnormal NVC associated with cognitive deficits in patients, we aim to provide new insights into potential preventive and therapeutic interventions.

Materials and methods

A total of 45 patients and 40 matched healthy controls were prospectively enrolled in our study. Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. Arterial spin labeling (ASL) was used to calculate cerebral blood flow (CBF), and graph theory–based analysis of results from resting‐state functional magnetic resonance imaging (rs‐fMRI) was used to calculate brain network topological parameters (node betweenness centrality [BC], node efficiency [Ne], and node degree centrality [DC]). Three NVC biomarkers (CBF‐BC, CBF‐Ne, and CBF‐DC coefficients) at the whole brain level and 3 NVC biomarkers (CBF/BC, CBF/Ne, and CBF/DC ratios) at the local brain region level were used to assess NVC. Mann–Whitney U tests were used to compare the intergroup differences in NVC parameters. Spearman's correlation analysis was used to evaluate the relationship among NVC dysfunctional pattern, cognitive impairment, and clinical characteristics multiple comparisons were corrected using a voxel‐wise false‐discovery rate (FDR) method (p < .05).

Results

Patients showed significantly reduced global coupling coefficients for CBF‐Ne (p = .023) and CBF‐BC (p = .035) compared to healthy controls. Coupling ratios at the local brain region level were significantly higher in patients in 33 brain regions (all p values < .05). Coupling ratio changes alone or accompanied by changes in CBF, node properties, or both CBF and node properties were identified. In patients, negative correlations were seen between coupling ratios and MoCA scores in many brain regions, including the left dorsolateral superior frontal gyrus, the bilateral median cingulate and paracingulate gyri, and the right superior parietal gyrus. The correlations remained even after adjusting for hemoglobin and hematocrit levels.

Conclusion

Disrupted NVC may be one mechanism underlying cognitive impairment in dialysis patients.
A perspective on neurodivergent‐affirming relational practice: Exploration of identity and the healing process
Authors: Fuld Samantha , McKelvie M. R.
Published: June 2024

Background

This commentary examines the historic primacy of behavioural interventions in psychotherapeutic work with neurodivergent people. Such interventions have been increasingly criticised as failing to affirm aspects of neurodivergence as significant for one's identity and positive sense of self, instead emphasising conformity to socially and academically determined norms, which may not always be the goals of the individual engaging with therapy.

Findings

Relational therapeutic interventions, which have not traditionally been centred in clinical approaches with this group of people, have great potential to address the inadequacies of more behaviourally oriented modalities as they were designed to address experiences of internalised stigma and invalidation, enhance a cohesive sense of self, affirm intersectional identity, tune into emotional experiences, and engage in healing through relationships and connection.

Discussion

While further research is needed to support the efficacy of relational approaches in work alongside neurodivergent people, their application is promising and aligned with the expressed needs of this community.
Synthesis and Cytotoxic Activity of Friedelinyl Esters
Authors: Oliveira Leila R. , Vidal Diogo M. , Freitas Túlio R. , de P. Sabino Adriano , Duarte Lucienir P. , de Sousa Grasiely F.
Published: June 2024

Commonly isolated from plants of Celastraceae family, pentacyclic triterpenoids have a broad spectrum of biological activities, such as antitumor, anti‐inflammatory, antinociceptive properties, among others. Structural modifications in these triterpenoids can enhance their biological activity, as well as their selectivity, while improving their physicochemical and pharmacokinetic aspects. In this study, eight novel esters were synthesized: four derivatives of 3α‐friedelinol (friedelan‐3α‐yl p‐bromobenzoate (1a); friedelan‐3α‐yl naproxenate (1b); friedelan‐3α‐yl pent‐4‐ynoate (1c); friedelan‐3α‐yl undec‐10‐ynoate (1d)) and four derivatives of 3β‐friedelinol (friedelan‐3β‐yl p‐bromobenzoate (2a); friedelan‐3β‐yl naproxenate (2b); friedelan‐3β‐yl pent‐4‐ynoate (2c); friedelan‐3β‐yl undec‐10‐ynoate (2d)). Overall, 3α‐friedelinol showed greater reactivity when compared to the β‐epimer. The esters 1b–d and 2b–c were tested for antileukemic activity against THP‐1 and K‐562 cells but showed low cytotoxicity for both cell lines. The most active against THP‐1 cells was friedelan‐3β‐yl naproxenate (2b, IC50=266±6 μM), and the most active against K‐562 cells was friedelan‐3α‐yl pent‐4‐ynoate (1c, IC50=267±5 μM).
Chemical Composition and Phytotoxic Activity of Mentha vagans Boriss. Essential Oil
Authors: Ma Yonghui , Shah Muddaser , Shi Kai , Chen Hongyang , Golkar Pooran , Mehmood Abbasi Arshad , Shao Hua
Published: June 2024

This study explored the composition of essential oil (EO) and the first phytotoxic screening of EO obtained from the stems and leaves of Mentha vagans Boriss (MVEO) via hydro‐distillation technique. The EO ingredients were detected through Gas Chromatography‐Mass Spectrometry (GC‐MS). GC‐MS analysis revealed that MVEO contained 49 constituents, constituting 93.95 % of the total oil. Among MVEO constituents, dihydrocarvone was observed as the dominant constituent (24.14 %), followed by D‐carvone (16.28 %) and piperitone (18.14 %). The phytotoxic effects of MVEO and its dominant compounds were examined against Amaranthus retroflexus, Lolium perenne, and Poa annua. Significant inhibition was observed by MVEO in comparison with the major constituents and their mixture, suppressing the seedling growth of tested species at the lowest dosage (0.01 mg/mL); in general, seedling growth of all tested species was markedly inhibited when applied concentration of the EO and its constituents reached 0.05 mg/mL. Our results also indicated that constituents other than the dominant compounds of MVEO possessed considerable phytotoxic effects because the EO's activity was stronger than its major constituents and their mixture. Thus, additional studies are required to investigate MVEO and its constituents and commercialize them as environment‐friendly bio‐herbicides.
Allosteric Effects of EF‐G Domain I Mutations Inducing Ribosome Frameshifting Revealed by Multiplexed Force Spectroscopy
Authors: Chen Yanjun , Gavriliuc Miriam , Zeng Yi , Xu Shoujun , Wang Yuhong
Published: June 2024

Ribosome translocation catalyzed by elongation factor G (EF‐G) is a critical step in protein synthesis where the ribosome typically moves along the mRNA by three nucleotides at each step. To investigate the mechanism of EF‐G catalysis, it is essential to precisely resolve the ribosome motion at both ends of the mRNA, which, to our best knowledge, is only achieved with the magnetic‐based force spectroscopy developed by our groups. Here, we introduce a novel multiplexed force spectroscopy technique that, for the first time, offers single‐nucleotide resolution for multiple samples. This technique combines multiple acoustic force generators with the smallest atomic magnetometer designed for biological research. Utilizing this technique, we demonstrate that mutating EF‐G at the GTP binding pocket results in the ribosome moving only two nucleotides on both ends of the mRNA, thereby compromising ribosome translocation. This finding suggests a direct link between GTP hydrolysis and ribosome translocation. Our results not only provide mechanistic insights into the role of GTP binding pocket but also illuminate how allosteric mutations can manipulate translocation. We anticipate broader applications of our technique in the ribosome field, leveraging its high efficiency and single‐nucleotide resolution.
Biosynthesis and Assembly Logic of Fungal Hybrid Terpenoid Natural Products
Authors: Yuan Guan‐Yin , Zhang Jin‐Mei , Xu Yan‐Qiu , Zou Yi
Published: June 2024

In recent decades, fungi have emerged as significant sources of diverse hybrid terpenoid natural products, and their biosynthetic pathways are increasingly unveiled. This review mainly focuses on elucidating the various strategies underlying the biosynthesis and assembly logic of these compounds. These pathways combine terpenoid moieties with diverse building blocks including polyketides, nonribosomal peptides, amino acids, p‐hydroxybenzoic acid, saccharides, and adenine, resulting in the formation of plenty of hybrid terpenoid natural products via C−O, C−C, or C−N bond linkages. Subsequent tailoring steps, such as oxidation, cyclization, and rearrangement, further enhance the biological diversity and structural complexity of these hybrid terpenoid natural products. Understanding these biosynthetic mechanisms holds promise for the discovery of novel hybrid terpenoid natural products from fungi, which will promote the development of potential drug candidates in the future.
Laparoscopy versus endovascular aneurysm repair for abdominal aortic aneurysm: A systematic review
Authors: Duric Bea , Hadjihannas Ioannis , Sugumaran Sveta , Jagic Karlo , Patel Bijendra
Published: June 2024

Minimally invasive surgery is a useful alternative to open repair for patients with nonruptured abdominal aortic aneurysms (AAA). We aim to compare the clinical outcomes for three different minimally invasive techniques: hand‐assisted laparoscopic surgery (HALS), total laparoscopic surgery (TLS), and endovascular aneurysm repair (EVAR). The electronic databases MEDLINE, Embase, Web of Science, Google Scholar, and the Cochrane Library were searched between January and March 2023. Cohort studies and randomized controlled trials (RCTs) comparing two minimally invasive techniques were eligible for inclusion. Primary outcomes were mortality (in‐hospital, 30‐day, or 1‐year) and reintervention rates (30‐day or 1‐year). Length of surgery, blood loss, transfusion volume, conversion to open surgery, major complication rates, length of hospital stay, and length of intensive care unit (ICU) stay were also evaluated. Eight cohort studies and one RCT were included comparing patients undergoing HALS (n = 500), TLS (n = 263), and EVAR (n = 438) for elective AAA repair. The TLS group had the highest rate of 30‐day postoperative reinterventions (p = 0.00056), the longest surgical duration (p = 0.0311), and the highest rate of conversion to open surgery (p < 0.001). TLS was also associated with the most blood loss during surgery, the highest blood transfusion volumes, and the longest length of ICU stay, although these results did not reach statistical significance. Subgroup analysis revealed superior contemporary EVAR outcomes compared to TLS. Laparoscopic surgery (LAS) and EVAR have comparable mortality rates. However, LAS, particularly TLS, is significantly less efficacious than EVAR in terms of intraoperative conversions to open surgery and 30‐day reintervention rates. Further controlled trials with larger sample sizes are needed to confirm the evidence.
Covalently Linked 5,6,11,12‐Tetraazanaphthacene Dimer and Its Triptycene‐Capped Derivatives as Electron Acceptors
Authors: Kamebuchi Hajime , Makino Rintaro , Hiruma Koji , Tomura Kazumasa , Tadokoro Makoto
Published: June 2024

The development of electron transport and n‐type materials is still largely dominated by a limited number of organic semiconductors, with fullerenes at the forefront. In contrast, substantial progress has been made in developing hole transport and p‐type materials. Therefore, expanding the range of electron acceptors, making them solution‐processable, and elucidating their structural arrangement by X‐ray crystallography is essential. We synthesised 2,2’‐bi‐(5,6,11,12‐tetraazanaphthacene) (bi‐TANC) and its triptycene end‐capped derivative, 2,2′‐bi(8,13‐dihydro‐8,13‐[1,2]benzenonaphtho‐5,6,15,16‐tetraazanaphthacene) (bi‐TpTANC), as electron acceptors. Bi‐TANC exhibits a herringbone‐like crystal packing with intermolecular π–π overlap, which is observed in typical organic n‐type semiconductors. However, it showed poor solubility, similar to larger acenes. In contrast, bi‐TpTANC exhibited favourable solubility, and its electrochemistry in solution was investigated. In the cyclic voltammogram of bi‐TpTANC, reversible redox waves corresponding to 3‐step/4‐electron transfer were observed at −0.795 V (1e−), −0.927 V (1e−), and −1.44 V (2e−) as half‐wave potentials. The redox wave associated with the two‐electron transfer on the negative low‐potential side indicates the presence of through‐bond charge delocalisation in the monoanionic state. Furthermore, the LUMO level of bi‐TpTANC is −4.1 eV, which indicates its potential as a promising air‐stable n‐type material.
Research progress of electrocatalysts for hydrogen oxidation reaction in alkaline media
Authors: Zeng Youze , Wang Xue , Hu Yang , Qi Wei , Wang Zhuoqi , Xiao Meiling , Liu Changpeng , Xing Wei , Zhu Jianbing
Published: June 2024

Anion exchange membrane fuel cells (AEMFCs) have been hailed as a promising hydrogen energy technology due to high energy conversion efficiency, zero carbon emission and the potential independence on scare and expensive noble metal electrocatalysts. A variety of platinum group metal (PGM)‐free catalysts has been developed with superior catalytic performance to noble metal benchmarks toward cathodic oxygen reduction reactions (ORR). However, PGM electrocatalysts still dominate the anodic catalyst research because the kinetics of hydrogen oxidation reaction (HOR) are two or three orders of magnitude slower than in that acidic media. Therefore, it is urgently desirable to improve noble metal utilization efficiency and/or develop high‐performance PGM‐free electrocatalysts for HOR, thus promoting the real‐world implementation of AEMFCs. In this review, the current research progress of electrocatalysts for HOR in alkaline media is summarized. We start with the discussion on the current HOR reaction mechanisms and existing controversies. Then, methodologies to improve the HOR performance are reviewed. Following these principles, the recently developed HOR electrocatalysts including PGM and PGM‐free HOR electrocatalysts in alkaline media are systematically introduced. Finally, we put forward the challenges and prospects in the field of HOR catalysis.
A Randomized, Cross‐Over Study Investigating the Comparability of Somatrogon‐ghla in 2 Different Drug Product Presentations
Authors: Manners Allison , Korth‐Bradley Joan , Wajnrajch Michael P.
Published: June 2024

Somatrogon‐ghla is a long‐acting, recombinant human growth hormone approved for the treatment of pediatric patients with growth hormone deficiency. Forty‐nine healthy, adult males were enrolled in a randomized, crossover study to compare somatrogon exposure after subcutaneous doses administered using a frozen vial presentation or a prefilled, multiple dose pen. Somatrogon, insulin‐like growth factor‐I, and IGF‐1 binding protein‐3 concentrations were collected for up to 240 hours post dose to assess pharmacokinetic and pharmacodynamic responses. There was a 2‐week washout between administration of the doses. Seven participants did not complete the study due to withdrawal of consent (n = 2) or loss to follow‐up. Two treatment‐emergent adverse events, headaches, were judged by the investigator as possibly related to study drug administration. Both were mild. Injection site reactions were observed in 6/48 participants after administration with the pen and 12/46 after administration using the vial. Drug and biomarker concentrations were assessed using validated assays and noncompartmental methods were used to determine pharmacokinetic and pharmacodynamic parameters. Bioequivalence was demonstrated for somatrogon area under the concentration‐time curve, but not for the peak somatrogon concentration, where the lower limit of the 90% confidence interval for the ratio of pen/vial was 74.2%, which is less than the lower limit, 80.0%, dictated by bioequivalence criteria. The IGF‐1 responses were largely within bioequivalence limits. It was concluded that the 2 formulations are comparable.