bluuebunny/crossref_metadata_2025 huggingface dataset:
Association among smoking, depression, and anxiety: findings from a representative sample of Korean adolescents
Authors: Byeon Haewon
Published: October 2015

This study investigated the relationship between smoking and depression and anxiety using data from a nationwide survey representing Korean adolescents. Subjects were 6,489 adolescents in middle and high school (age 13–18) who had participated in the 2011 Korean Study of Promotion Policies on Children and Adolescents—Mental Health (KSPCAM). Daily smoking number of times for current smokers was classified as 1–2 times, 2–4 times and over 5 times. The odds ratio for the statistical test was presented using hierarchical logistic regression. When adjusted for covariates (gender, age, household economy, type of residing city, type of school, school record, satisfaction with school life, subjective health status, satisfaction with relationship with parents, and drinking experience), smokers more significantly likely to have depression (OR = 1.27, 95% CI [1.02–1.57]), and anxiety (OR = 1.49, 95% CI [1.14–1.96]) than non-smokers (p< 0.05). In addition, adolescents who smoke more than 5 cigarettes a day were 1.5 times more likely to have depression (OR = 1.48, 95% CI [1.13–1.92]) and anxiety (OR = 1.49, 95% CI [1.07–2.08]) than those who do not smoke. Smoking in adolescence was found to be significantly related with depression and anxiety. To promote the mental health of adolescents, effective smoking cessation programs are required.
Investigation into the effects of antioxidant-rich extract ofTamarindus indicaleaf on antioxidant enzyme activities, oxidative stress and gene expression profiles in HepG2 cells
Authors: Razali Nurhanani , Abdul Aziz Azlina , Lim Chor Yin , Mat Junit Sarni
Published: October 2015

The leaf extract ofTamarindus indicaL. (T. indica) had been reported to possess high phenolic content and showed high antioxidant activities. In this study, the effects of the antioxidant-rich leaf extract of theT. indicaon lipid peroxidation, antioxidant enzyme activities, H2O2-induced ROS production and gene expression patterns were investigated in liver HepG2 cells. Lipid peroxidation and ROS production were inhibited and the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase was enhanced when the cells were treated with the antioxidant-rich leaf extract. cDNA microarray analysis revealed that 207 genes were significantly regulated by at least 1.5-fold (p< 0.05) in cells treated with the antioxidant-rich leaf extract. The expression ofKNG1, SERPINC1, SERPIND1, SERPINE1, FGG, FGA, MVK, DHCR24, CYP24A1,ALDH6A1, EPHX1andLEAP2were amongst the highly regulated. When the significantly regulated genes were analyzed using Ingenuity Pathway Analysis software, “Lipid Metabolism, Small Molecule Biochemistry, Hematological Disease” was the top biological network affected by the leaf extract, with a score of 36. The top predicted canonical pathway affected by the leaf extract was the coagulation system (P< 2.80 × 10−6) followed by the superpathway of cholesterol biosynthesis (P< 2.17 × 10−4), intrinsic prothrombin pathway (P< 2.92 × 10−4), Immune Protection/Antimicrobial Response (P< 2.28 × 10−3) and xenobiotic metabolism signaling (P< 2.41 × 10−3). The antioxidant-rich leaf extract ofT. indicaalso altered the expression of proteins that are involved in the Coagulation System and the Intrinsic Prothrombin Activation Pathway (KNG1, SERPINE1, FGG), Superpathway of Cholesterol Biosynthesis (MVK), Immune protection/antimicrobial response (IFNGR1, LEAP2, ANXA3 and MX1) and Xenobiotic Metabolism Signaling (ALDH6A1, ADH6). In conclusion, the antioxidant-rich leaf extract ofT. indicainhibited lipid peroxidation and ROS production, enhanced antioxidant enzyme activities and significantly regulated the expression of genes and proteins involved with consequential impact on the coagulation system, cholesterol biosynthesis, xenobiotic metabolism signaling and antimicrobial response.
Spider crabs of the Western Atlantic with special reference to fossil and some modern Mithracidae
Authors: Klompmaker Adiël A. , Portell Roger W. , Klier Aaron T. , Prueter Vanessa , Tucker Alyssa L.
Published: October 2015

Spider crabs (Majoidea) are well-known from modern oceans and are also common in the western part of the Atlantic Ocean. When spider crabs appeared in the Western Atlantic in deep time, and when they became diverse, hinges on their fossil record. By reviewing their fossil record, we show that (1) spider crabs first appeared in the Western Atlantic in the Late Cretaceous, (2) they became common since the Miocene, and (3) most species and genera are found in the Caribbean region from the Miocene onwards. Furthermore, taxonomic work on some modern and fossil Mithracidae, a family that might have originated in the Western Atlantic, was conducted. Specifically,Maguimithraxgen. nov. is erected to accommodate the extant speciesDamithrax spinosissimus, whileDamithraxcf.pleuracanthusis recognized for the first time from the fossil record (late Pliocene–early Pleistocene, Florida, USA). Furthermore, two new species are described from the lower Miocene coral-associated limestones of Jamaica (Mithrax arawakumsp. nov. andNemausa windsoraesp. nov.). Spurred by a recent revision of the subfamily, two known species from the same deposits are refigured and transferred to new genera:Mithrax donovanitoNemausa, andMithrax unguistoDamithrax. The diverse assemblage of decapods from these coral-associated limestones underlines the importance of reefs for the abundance and diversity of decapods in deep time. Finally, we quantitatively show that these crabs possess allometric growth in that length/width ratios drop as specimens grow, a factor that is not always taken into account while describing and comparing among taxa.
Surgeon and Care Team Network Measures and Timely Breast Cancer Treatment
Authors: Ash Ramsey , Scodari Bruno T. , Schaefer Andrew P. , Cornelius Sarah L. , Brooks Gabriel A. , O’Malley A. James , Onega Tracy , Verhoeven Dana C. , Moen Erika L.
Published: August 2024

Importance

Cancer treatment delay is a recognized marker of worse outcomes. Timely treatment may be associated with physician patient-sharing network characteristics, yet this remains understudied.

Objective

To examine the associations of surgeon and care team patient-sharing network measures with breast cancer treatment delay.

Design, Setting, and Participants

This cross-sectional study of Medicare claims in a US population-based setting was conducted from 2017 to 2020. Eligible participants included patients with breast cancer who received surgery and the subset who went on to receive adjuvant therapy. Patient-sharing networks were constructed for treating physicians. Data were analyzed from September 2023 to February 2024.

Exposures

Surgeon linchpin score (a measure of local uniqueness or scarcity) and care density (a measure of physician team familiarity) were assessed. Surgeons were considered linchpins if their linchpin score was in the top 15%. The care density of a patient’s physician team was calculated on preoperative teams for surgically-treated patients and postoperative teams for adjuvant therapy-receiving patients.

Main Outcomes and Measures

The primary outcomes were surgical and adjuvant delay, which were defined as greater than 60 days between biopsy and surgery and greater than 60 days between surgery and adjuvant therapy, respectively.

Results

The study cohort included 56 433 patients (18 004 aged 70-74 years [31.9%]) who were mostly from urban areas (44 931 patients [79.6%]). Among these patients, 8009 (14.2%) experienced surgical delay. Linchpin surgeon status (locally unique surgeon) was not statistically associated with surgical delay; however, patients with high preoperative care density (ie, high team familiarity) had lower odds of surgical delay compared with those with low preoperative care density (odds ratio [OR], 0.58; 95% CI, 0.53-0.63). Of the 29 458 patients who received adjuvant therapy after surgery, 5700 (19.3%) experienced adjuvant delay. Patients with a linchpin surgeon had greater odds of adjuvant delay compared with those with a nonlinchpin surgeon (OR, 1.30; 95% CI, 1.13-1.49). Compared with those with low postoperative care density, there were lower odds of adjuvant delay for patients with high postoperative care density (OR, 0.77; 95% CI, 0.69-0.87) and medium postoperative care density (OR, 0.85; 95% CI, 0.77-0.94).

Conclusions and Relevance

In this cross-sectional study of Medicare claims, network measures capturing physician scarcity and team familiarity were associated with timely treatment. These results may help guide system-level interventions to reduce cancer treatment delays.
Collaboration and term usage dynamics in agricultural buffer strip research: Research weaving
Authors: Young Sarah , Lagisz Malgorzata , Callaghan Max W. , Nakagawa Shinichi , Haddaway Neal R.
Published: August 2024

Systematic maps are used to comprehensively gather and describe the literature on a topic, which is often defined by policy and practice relevance and stakeholder input, identifying trends and gaps in research. Bibliometric methods elucidate the connections between publications, for example, providing information about collaboration in research communities. Research weaving combines these approaches to produce a comprehensive view of research activity on a well‐defined research area.

In this paper, we conduct and describe a bibliometric analysis on a previously published systematic map on the functional roles of buffer strips in agricultural fields. Among other findings, the original systematic map found a paucity of studies addressing multiple functional roles and a huge variation in terminology related to buffer strips. We used research weaving to deepen our understanding of these findings and shed light on collaboration within and among the research communities contributing knowledge to this field.

Of the 1019 papers originally included in the systematic map, 930 were identified in Lens.org and used for subsequent analyses. Co‐authorship and bibliographic coupling networks identified distinct research communities, defined by geography, subdiscipline and characteristic usage of buffer strip terminology. Topic modelling provided further information about these subcommunities and aligned with manually extracted information about the studies' focus on functional roles, indicating potential utility for screening of records in large systematic maps.

Practical Implication: We demonstrate that research weaving methods add insights in support of and in addition to the original systematic map. We provide a methodological approach and discuss limitations related to applying bibliometric analyses to a previously published systematic map. We demonstrate the feasibility of this approach and its ability to enhance and enrich the findings gained from conventional systematic mapping techniques.
Inferring disease course from differential exon usage in the wide titinopathy spectrum
Authors: Di Feo Maria Francesca , Oghabian Ali , Nippala Ella , Gautel Mathias , Jungbluth Heinz , Forzano Francesca , Malfatti Edoardo , Castiglioni Claudia , Krey Ilona , Gomez Andres David , Brady Angela F. , Iascone Maria , Cereda Anna , Pezzani Lidia , Natera De Benito Daniel , Nascimiento Osorio Andres , Estévez Arias Berta , Kurbatov Sergei A. , Attie‐Bitach Tania , Nampoothiri Sheela , Ryan Erin , Morrow Michelle , Gorokhova Svetlana , Chabrol Brigitte , Sinisalo Juha , Tolppanen Heli , Tolva Johanna , Munell Francina , Camacho Soriano Jessica , Sanchez Duran Maria Angeles , Johari Mridul , Tajsharghi Homa , Hackman Peter , Udd Bjarne , Savarese Marco
Published: August 2024

Objective

Biallelic titin truncating variants (TTNtv) have been associated with a wide phenotypic spectrum, ranging from complex prenatal muscle diseases with dysmorphic features to adult‐onset limb‐girdle muscular dystrophy, with or without cardiac involvement. Given the size and complexity of TTN, reaching an unequivocal molecular diagnosis and precise disease prognosis remains challenging.

Methods

In this case series, 12 unpublished cases and one already published case with biallelic TTNtv were collected from multiple international medical centers between November 2022 and September 2023. TTN mutations were detected through exome or genome sequencing. Information about familial and personal clinical history was collected in a standardized form. RNA‐sequencing and analysis of TTN exon usage were performed on an internal sample cohort including postnatal skeletal muscles, fetal skeletal muscles, postnatal heart muscles, and fetal heart muscles. In addition, publicly available RNA‐sequencing data was retrieved from ENCODE.

Results

We generated new RNA‐seq data on TTN exons and identified genotype–phenotype correlations with prognostic implications for each titinopathy patient (whether worsening or improving in prenatal and postnatal life) using percentage spliced in (PSI) data for the involved exons. Interestingly, thanks to exon usage, we were also able to rule out a titinopathy diagnosis in one prenatal case.

Interpretation

This study demonstrates that exon usage provides valuable insights for a more exhaustive clinical interpretation of TTNtv; additionally, it may serve as a model for implementing personalized medicine in many other genetic diseases, since most genes undergo alternative splicing.
Clonal hematopoiesis in LGI1‐antibody encephalitis
Authors: Shin Soo Jean , Jang Yoonhyuk , Ahn Soo Hyun , Mon Su Yee , You Ji Hye , An Hong Yul , Sun Choong Hyun , Koh Youngil , Chu Kon , Lee Sang Kun , Lee Soon‐Tae
Published: August 2024

Objective

Leucine‐rich glioma‐inactivated 1 (LGI1)‐antibody encephalitis (LGI1e), the major form of autoimmune encephalitis (AE) presented with memory loss and faciobrachial dystonic seizure, commonly develops in aged population. Hematologic aging is often accompanied by clonal hematopoiesis (CH), a phenomenon in which specific mutations accumulate, potentially leading to autoimmune disorders or malignancies. Our research aimed to investigate the connection between clonal hematopoiesis of indeterminate potential (CHIP) and LGI1e.

Methods

Peripheral blood samples from consecutive LGI1e patients were collected and analyzed for 24 clonal CHIP using targeted gene sequencing. The results were compared to a control dataset from an ethnically matched health care cohort. Patient characteristics were analyzed based on their CHIP status.

Results

A total of 52 LGI1e patients were enrolled for this study. Among them, three patients (5.8%) exhibited functional mutations in the ASXL1 gene, one of the CHIP‐associated genes analyzed by targeted sequencing. This frequency was significantly higher compared to that of the control cohort (1%, p = 0.015). Nevertheless, the patients showed no difference in the clinical characteristics, laboratory results, and immunotherapy outcomes.

Interpretation

LGI1e showed high frequency of ASXL1 functional mutation in the CHIP analysis, which may contribute to the underlying pathogenesis. Further research is needed to determine its direct role in the development of autoimmunity and disease progression.
Effect of Ultrasonic‐Assisted Treatment on Microstructure and Mechanical Properties of Laser Deposition Repairing AlSi7Mg Alloy
Authors: Yi Junzhen , Sun Pengbo , Cui Yanfeng , Ren Yuhang , Wang Chao , Li Changfu , Yang Guang
Published: August 2024

The study focusing on the repairing technology with highly efficient and high quality for aerospace aluminum alloy parts is of great necessity and application significance. Herein, laser deposition repairing (LDR) technology with and without ultrasonic‐assisted treatment is employed to repair the AlSi7Mg alloy. The morphological analysis results show that ultrasonic‐assisted treatment laser deposition repairing (UT‐LDR) can significantly refine the grain, reduce the porosity, and provide dislocation strengthening of repaired zone (RZ). The microhardness of RZ is higher than that of the base material due to the strengthening effect of fine grain. The microhardness of RZ further increases by 27.7% under the action of ultrasound. With the introduction of ultrasound, tensile strength of repaired samples increases from 180.9 to 241.7 MPa, but the elongation decreases from 4.0% to 1.8%. Both LDR and UT‐LDR samples show brittle fracture mechanism with tiny dimples and obvious cleavage planes.
Effect of Trace B on Microstructure and Mechanical Properties of Additive Manufactured Near β Titanium Alloy Ti55531
Authors: Ding Hanlin , Wang Lilin , Yuan Lukai , Lin Xin , Huang Weidong
Published: August 2024

The refinement of β grains is an effective approach to optimize the grain boundary α phase and enhance the mechanical properties for laser‐directed energy deposited (L‐DED) titanium alloys. In this study, the primary β grain size is refined by adding 0.05 and 0.10 wt% boron in Ti55531, respectively. It was found that the addition of trace boron can not only reduce the primary β grain size during molten pool solidification process, but also can suppress the primary β grain coarsening during in‐situ thermal cycling process. The Ti55531 + 0.05B alloy exhibited higher strength and elongation. This is attributed to the enhanced coordinated deformation ability resulting from the refined β grains and little harmful effect resulting from the presence of needle TiB. In contrast, when the boron content increased to 0.10 wt%, the harmful effect of excessive TiB whiskers at the grain boundaries outweighed the favorable effect of the further β grain refinement, which leads to the decrease in plasticity. This study suggests that an appropriate boron content added can refine primary β grain significantly and meanwhile avoid too much TiB precipitation, achieving superior comprehensive mechanical properties for additive manufacturing near β titanium alloy.
Effect of Anodic Oxidation on Antibacterial Properties and Biocompatibility of Ti‐13Nb‐13Zr‐3Cu for Biomedical Application
Authors: Xu Jianwei , Hu Jiali , Liu Shibin , Wang Jing , Ma Zhen , Guo Sijia , Li Muqin , Zhang Erlin
Published: August 2024

Ti‐13Nb‐13Zr (TNZ), a representative of β‐type titanium alloys, has garnered significant interest in biomedical implant materials recently because of its high strength, and closer elastic modulus to human bone. However, TNZ alloy does not have antibacterial properties and has the potential to cause implant‐related infection, even implantation failure. Herein, TNZ alloy is alloyed by Cu element and the surface is modified by anodic oxidation (AO) to enhance the biocompatibility and antimicrobial qualities. The corrosion resistance, antimicrobial properties, and cytotoxicity of the TNZ‐3Cu alloy before and after anodization are studied by X‐ray diffraction, X‐ray photoelectron spectroscopy, scanning electron microscopy, electrochemical test, mechanical property test, and cell test. The experimental results show that the primary constituents of the TNZ‐3Cu alloy are α″ martensite and β phase after solid solution treatment. The elastic modulus of TNZ‐3Cu alloy is (65 ± 1.33) GPa, 9 GPa lower than that of TNZ alloy. The AO treatment significantly improves the hydrophilicity and antibacterial properties as well as the corrosion resistance by the formation of a dense oxides composites coating. The cell test results show that the coating improves the initial adhesion of cells by the high hydrophilic surface and promotes the proliferation of cells by the release of copper ions.
Analysis of Glucose Responsive Glucagon Therapeutics using Computational Models of the Glucoregulatory System
Authors: Alizadehmojarad Ali A. , Yang Sungyun , Gong Xun , Strano Michael S.
Published: August 2024

Glucose‐responsive glucagon (GRG) therapeutics are a promising technology for reducing the risk of severe hypoglycemia as a complication of diabetes mellitus. Herein, the performance of candidate GRGs in the literature by modeling the kinetics of activation and connecting them as input into physiological glucoregulatory models is evaluated and projected the two distinct GRG designs, experimental results reported in Wu et al. (GRG‐I) and Webber et al. (GRG‐II) is considered. Both are evaluated using a multi‐compartmental glucoregulatory model (IMPACT) and used to compare in‐vivo experimental data of therapeutic performance in rats and mice. For GRG‐I and GRG‐II, the total integrated glucose material balances are overestimated by 41.5% ± 14% and underestimated by 24.8% ± 16% compared to in‐vivo time‐course data, respectively. These large differences to the relatively simple computational descriptions of glucagon dynamics in the model, which underscores the urgent need for improved glucagon models is attributed. Additionally, therapeutic insulin and glucagon infusion pumps are modeled for type 1 diabetes mellitus (T1DM) human subjects to extend the results to additional datasets. These observations suggest that both the representative physiological and non‐physiological models considered in this work require additional refinement to successfully describe clinical data that involve simultaneous, coupled insulin, glucose, and glucagon dynamics.
Implantable Microneedle‐Mediated Eradication of Postoperative Tumor Foci Mitigates Glioblastoma Relapse
Authors: Zhang Yulin , Fang Zezheng , Liu Zejuan , Xi Kaiyan , Zhang Yi , Zhao Dawang , Feng Fan , Geng Humin , Liu Minglu , Lou Jingzhao , Chen Chen , Zhang Yanmin , Wu Zimei , Xu Feng , Jiang Xinyi , Ni Shilei
Published: August 2024

Glioblastoma multiforme (GBM) remains incurable despite multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin (2–3 cm) of the initial resected lesion due to the unreachable residual cancerous cells. Here, a completely biodegradable microneedle for surgical cavity delivery glioblastoma‐associated macrophages (GAMs)‐activating immune nano‐stimulator that mitigates glioblastoma relapse is reported. The residual tumor lesion‐directed biocompatible microneedle releases the nano‐stimulator and toll‐like receptor 9 agonist in a controlled manner until the microneedles completely degrade over 1 week, efferently induce in situ phonotypic shifting of GAMs from anti‐ to pro‐inflammatory and the tumor recurrence is obviously inhibited. The implantable microneedles offer a significant improvement over conventional transdermal ones, as they are 100% degradable, ensuring safe application within surgical cavities. It is also revealed that the T cells are recruited to the tumor niche as the GAMs initiate anti‐tumor response and eradicate residual GBM cells. Taken together, this work provides a potential strategy for immunomodulating the postoperative tumor niche to mitigate tumor relapse in GBM patients, which may have broad applications in other malignancies with surgical intervention.
Regulating Aggregation‐Induced Emission Luminogen for Multimodal Imaging‐Navigated Synergistic Therapy Involving Anti‐Angiogenesis
Authors: Zhang Fei , Cui Jie , Zhang Yao , Yan Miao , Wu Xiaoxiao , Liu Xue , Yan Dingyuan , Zhang Zhijun , Han Ting , Tan Hui , Wang Dong , Tang Ben Zhong
Published: August 2024

As a new avenue for cancer research, phototheranostics has shown inexhaustible and vigorous vitality as it permits real‐time diagnosis and concurrent in situ therapy upon non‐invasive light‐initiation. However, construction of an advanced material, allowing prominent phototheranostic outputs and synchronously surmounting the inherent deficiency of phototheranostics, would be an appealing yet significantly challenging task. Herein, an aggregation‐induced emission (AIE)‐active luminogen (namely DBD‐TM) featured by intensive electron donor‐acceptor strength and twisted architecture with finely modulated intramolecular motion, is tactfully designed and prepared. DBD‐TM simultaneously possessed fluorescence emission in the second near‐infrared (NIR‐II) region and high‐efficiency photothermal conversion. By integrating DBD‐TM with anti‐angiogenic agent sorafenib, a versatile nanomaterial is smoothly fabricated and utilized for trimodal imaging‐navigated synergistic therapy involving photothermal therapy and anti‐angiogenesis toward cancer. This advanced approach is capable of affording accurate tumor diagnosis, complete tumor elimination, and largely restrained tumor recurrence, evidently denoting a prominent theranostic formula beyond phototheranostics. This study will offer a blueprint for exploiting a new generation of cancer theranostics.
Corrosion‐Resistant Ultrathin Cu Film Deposited on N‐Doped Amorphous Carbon Film Substrate and Its Use for Crumpleable Circuit Board
Authors: Shim Chae‐Eun , Lee Sangseob , Kong Minsik , Kim Ik‐Soo , Kwak Jaeik , Jang Woosun , Jeong Se‐Young , Kim Dong Wook , Soon Aloysius , Jeong Unyong
Published: August 2024

Copper (Cu) is widely used as an industrial electrode due to its high electrical conductivity, mechanical properties, and cost‐effectiveness. However, Cu is susceptible to corrosion, which degrades device performance over time. Although various methods (alloying, physical passivation, surface treatment, etc.) are introduced to address the corrosion issue, they can cause decreased conductivity or vertical insulation. Here, using the nitrogen‐doped amorphous carbon (a‐C:N) thin film is proposed as a substrate on which Cu is directly deposited. This simple method significantly inhibits corrosion of ultrathin Cu (<20 nm) films in humid conditions, enabling the fabrication of ultrathin electronic circuit boards without corrosion under ambient conditions. This study investigates the origin of corrosion resistance through comprehensive microscopic/spectroscopic characterizations and density‐functional theory (DFT) calculations: i) diffusion of Cu atoms into the a‐C:N driven by stable C‐Cu‐N bond formation, ii) diffusion of N atoms from the a‐C:N to the Cu layer heading the top surface, which is the thermodynamically preferred location for N, and iii) the doped N atoms in Cu layer suppress the inclusion of O into the Cu lattice. By leveraging the ultrathinness and deformability of the circuit board, a transparent electrode and a crumpleable LED lighting device are demonstrated.
Mechanochemistry: Fundamental Principles and Applications
Authors: Dong Liang , Li Luofei , Chen Huiyan , Cao Yi , Lei Hai
Published: August 2024

Mechanochemistry is an emerging research field at the interface of physics, mechanics, materials science, and chemistry. Complementary to traditional activation methods in chemistry, such as heat, electricity, and light, mechanochemistry focuses on the activation of chemical reactions by directly or indirectly applying mechanical forces. It has evolved as a powerful tool for controlling chemical reactions in solid state systems, sensing and responding to stresses in polymer materials, regulating interfacial adhesions, and stimulating biological processes. By combining theoretical approaches, simulations and experimental techniques, researchers have gained intricate insights into the mechanisms underlying mechanochemistry. In this review, the physical chemistry principles underpinning mechanochemistry are elucidated and a comprehensive overview of recent significant achievements in the discovery of mechanically responsive chemical processes is provided, with a particular emphasis on their applications in materials science. Additionally, The perspectives and insights into potential future directions for this exciting research field are offered.
Light‐Activated Anti‐Vascular Combination Therapy against Choroidal Neovascularization
Authors: Xu Shuting , Li Jia , Long Kaiqi , Liang Xiaoling , Wang Weiping
Published: August 2024

Choroidal neovascularization (CNV) underlies the crux of many angiogenic eye disorders. Although medications that target vascular endothelial growth factor (VEGF) are approved for treating CNV, their effectiveness in destroying new blood vessels is limited, and invasive intravitreal administration is required. Additionally, other drugs that destroy established neovessels, such as combretastatin A‐4, may have systemic side effects that limit their therapeutic benefits. To overcome these shortcomings, a two‐pronged anti‐vascular approach is presented for CNV treatment using a photoactivatable nanoparticle system that can release a VEGF receptor inhibitor and a vascular disrupting agent when irradiated with 690 nm light. The nanoparticles can be injected intravenously to enable anti‐angiogenic and vascular disrupting combination therapy for CNV through light irradiation to the eyes. This approach can potentiate therapeutic effects while maintaining a favorable biosafety profile for choroidal vascular diseases.
Mapping Surface‐Defect and Ions Migration in Mixed‐Cation Perovskite Crystals
Authors: Nughays Razan O. , Almasabi Khulud , Nematulloev Sarvarkhodzha , Wang Lijie , Bian Tieyuan , Nadinov Issatay , Irziqat Bahaaeddin , Harrison George T , Fatayer Shadi , Yin Jun , Bakr Osman M. , Mohammed Omar F.
Published: August 2024

Single crystal perovskites have garnered significant attention as potential replacements for existing absorber layer materials. Despite the extensive investigations on their photoinduced charge‐carriers dynamics, most of the time‐resolved techniques focus on bulk properties, neglecting surface characteristic which plays a crucial role for their optoelectronic performance. Herein, 4D ultrafast scanning electron microscopy (4D‐USEM) is utilized to probing the photogenerated carrier transport at the first few nanometers, alongside density functional theory (DFT) to track both defect centers and ions migration. Two compositions of mixed cation are investigated: FA0.6MA0.4PbI3 and FA0.4MA0.6PbI3, interestingly, the former displays a longer lifetime compared to the latter due the presence of a higher surface‐defect centers. DFT calculations fully support that revealing samples with higher FA content have a lower energy barrier for iodide ions to migrate from the bulk to top layer, assisting in passivating surface vacancies, and a higher energy diffusion barrier to escape from surface to vacuum, resulting in fewer vacancies and longer‐lived hole–electron pairs. These findings manifest the influence of cation selection on charge carrier transport and formation of defects, and emphasize the importance of understanding ion migrations role in controlling surface vacancies to assist engineering high‐performance optoelectronic devices based on single crystal perovskites.
Super‐Enhancer Driven LIF/LIFR‐STAT3‐SOX2 Regulatory Feedback Loop Promotes Cancer Stemness in Head and Neck Squamous Cell Carcinoma
Authors: Li Jin , Wang Yuhan , Wang Ziyu , Wei Yuxiang , Diao Pengfei , Wu Yaping , Wang Dongmiao , Jiang Hongbing , Wang Yanling , Cheng Jie
Published: August 2024

Super‐enhancers (SEs) have been recognized as key epigenetic regulators underlying cancer stemness and malignant traits by aberrant transcriptional control and promising therapeutic targets against human cancers. However, the SE landscape and their roles during head and neck squamous cell carcinoma (HNSCC) development especially in cancer stem cells (CSCs) maintenance remain underexplored yet. Here, we identify leukemia inhibitory factor (LIF)‐SE as a representative oncogenic SE to activate LIF transcription in HNSCC. LIF secreted from cancer cells and cancer‐associated fibroblasts promotes cancer stemness by driving SOX2 transcription in an autocrine/paracrine manner, respectively. Mechanistically, enhancer elements E1, 2, 4 within LIF‐SE recruit SOX2/SMAD3/BRD4/EP300 to facilitate LIF transcription; LIF activates downstream LIFR‐STAT3 signaling to drive SOX2 transcription, thus forming a previously unknown regulatory feedback loop (LIF‐SE‐LIF/LIFR‐STAT3‐SOX2) to maintain LIF overexpression and CSCs stemness. Clinically, increased LIF abundance in clinical samples correlate with malignant clinicopathological features and patient prognosis; higher LIF concentrations in presurgical plasma dramatically diminish following cancer eradication. Therapeutically, pharmacological targeting LIF‐SE‐LIF/LIFR‐STAT3 significantly impairs tumor growth and reduces CSC subpopulations in xenograft and PDX models. Our findings reveal a hitherto uncharacterized LIF‐SE‐mediated auto‐regulatory loop in regulating HNSCC stemness and highlight LIF as a novel noninvasive biomarker and potential therapeutic target for HNSCC.
Syneresis‐Driven Self‐Refilling Printing of Geometry/Component‐Controlled Nano/Microstructures
Authors: Shiba Kota , Saito Kayoko , Minami Kosuke , Arai Shunto , Yoshikawa Genki , Sun Luyi , Tenjimbayashi Mizuki
Published: August 2024

Nano/microfabrication is of fundamental importance both in scientific and industrial situations. There are, therefore, many attempts at realizing easier, quicker, and more precise fabrication of various structures; however, achieving this aim without a bulky and costly setup is still challenging. Here, we introduce a facile and versatile means of printing an ordered structure consisting of nanoscale stripes and more complicated geometries including pillars and wavy form with a lateral resolution of single micrometers. To this end, we prepare a polydimethylsiloxane (PDMS) slab with an oxygen plasma‐induced wrinkled surface where liquid PDMS exudes by syneresis. Since this liquid PDMS is automatically loaded, the printing is repeatable without inking. A substrate moderately wettable to the liquid PDMS as well as amount/property‐controlled syneresis is primarily important for the creation of well‐defined structures. Precisely controlling these conditions will make this method universally applicable to diverse substrates and liquids including suspensions.
Myeloid Cells and Sensory Nerves Mediate Peritendinous Adhesion Formation via Prostaglandin E2
Authors: Zhang Xinshu , Xiao Yao , Tao Zaijin , Zhang Yizhe , Cheng Xuan , Liu Xuanzhe , Li Yanhao , Yin Weiguang , Tian Jian , Wang Shuo , Zhang Tianyi , Yang Xiao , Liu Shen
Published: August 2024

Peritendinous adhesion that forms after tendon injury substantially limits daily life. The pathology of adhesion involves inflammation and the associated proliferation. However, the current studies on this condition are lacking, previous studies reveal that cyclooxygenase‐2 (COX2) gene inhibitors have anti‐adhesion effects through reducing prostaglandin E2 (PGE2) and the proliferation of fibroblasts, are contrary to the failure in anti‐adhesion through deletion of EP4 (prostaglandin E receptor 4) gene in fibroblasts in mice of another study. In this study, single‐cell RNA sequencing analysis of human and mouse specimens are combined with eight types of conditional knockout mice and further reveal that deletion of COX2 in myeloid cells and deletion of EP4 gene in sensory nerves decrease adhesion and impair the biomechanical properties of repaired tendons. Furthermore, the COX2 inhibitor parecoxib reduces PGE2 but impairs the biomechanical properties of repaired tendons. Interestingly, PGE2 local treatment improves the biomechanical properties of the repaired tendons. These findings clarify the complex role of PGE2 in peritendinous adhesion formation (PAF) and tendon repair.
A Novel Antigen Design Strategy to Isolate Single‐Domain Antibodies that Target Human Nav1.7 and Reduce Pain in Animal Models
Authors: Martina Marzia , Banderali Umberto , Yogi Alvaro , Arbabi Ghahroudi Mehdi , Liu Hong , Sulea Traian , Durocher Yves , Hussack Greg , van Faassen Henk , Chakravarty Balu , Liu Qing Yan , Iqbal Umar , Ling Binbing , Lessard Etienne , Sheff Joey , Robotham Anna , Callaghan Debbie , Moreno Maria , Comas Tanya , Ly Dao , Stanimirovic Danica
Published: August 2024

Genetic studies have identified the voltage‐gated sodium channel 1.7 (Nav1.7) as pain target. Due to the ineffectiveness of small molecules and monoclonal antibodies as therapeutics for pain, single‐domain antibodies (VHHs) are developed against the human Nav1.7 (hNav1.7) using a novel antigen presentation strategy. A 70 amino‐acid peptide from the hNav1.7 protein is identified as a target antigen. A recombinant version of this peptide is grafted into the complementarity determining region 3 (CDR3) loop of an inert VHH in order to maintain the native 3D conformation of the peptide. This antigen is used to isolate one VHH able to i) bind hNav1.7, ii) slow the deactivation of hNav1.7, iii) reduce the ability of eliciting action potentials in nociceptors, and iv) reverse hyperalgesia in in vivo rat and mouse models. This VHH exhibits the potential to be developed as a therapeutic capable of suppressing pain. This novel antigen presentation strategy can be applied to develop biologics against other difficult targets such as ion channels, transporters and GPCRs.
Spin‐Flip‐Restricted Multiple‐Resonance Emitters for Extended Device Lifetime in Indolocarbazole‐Based Blue Organic Light‐Emitting Diodes
Authors: Kang Jihoon , Lee Ha Lim , Jeon Soon Ok , Bae Hye Jin , Kim Seung Chan , Han Seungwon , Lee Jun Yeob
Published: August 2024

In this study, a multiple‐resonance (MR) core structure is developed with a spin‐flip‐restricted emission mechanism based on a fused indolo[3,2,1‐jk]carbazole (ICz) framework as emitters to improve the lifetime of blue organic light‐emitting diodes. The molecular skeleton modulation approach applied to the conjugated π‐system effectively stabilizes the triplet energy of the fused ICz emitters and narrows the full‐width‐at‐half maximum (<20 nm). In addition, the emitters exhibit higher exciton stability than conventional boron‐based MR emitters. The fused ICz‐based blue fluorescent device exhibits a high external quantum efficiency of 7.2%, a blue index of 68.6 cd A−1 at a Commission internationale de l'éclairage y coordinate (CIEy) of 0.075, and a device lifetime 1.8 times longer than that of a boron‐based emitter. In addition, a phosphor‐sensitized fluorescent device based on the ICz emitter exhibited an improved external quantum efficiency of 20.6% with a CIEy coordinate of 0.076.
A Spatiotemporally Controlled Gene‐Regulation Strategy for Combined Tumor Therapy Based on Upconversion Hybrid Nanosystem
Authors: Wang Fang , Liu Zechao , Liu Yuechen , Zhang Jiayi , Xu Weizhe , Liu Bei , Sun Zhaogang , Chu Hongqian
Published: August 2024

The lack of precise spatiotemporal gene modulation and therapy impedes progress in medical applications. Herein, a 980 nm near‐infrared (NIR) light‐controlled nanoplatform, namely URMT, is developed, which can allow spatiotemporally controlled photodynamic therapy and trigger the enzyme‐activated gene expression regulation in tumors. URMT is constructed by engineering an enzyme‐activatable antisense oligonucleotide, which combined with an upconversion nanoparticle (UCNP)‐based photodynamic nanosystem, followed by the surface functionalization of triphenylphosphine (TPP), a mitochondria‐targeting ligand. URMT allows for the 980 nm NIR light‐activated generation of reactive oxygen species, which can induce the translocation of a DNA repair enzyme (namely apurinic/apyrimidinic endonuclease 1, APE1) from the nucleus to mitochondria. APE1 can recognize the basic apurinic/apyrimidinic (AP) sites in DNA double‐strands and perform cleavage, thereby releasing the functional single‐strands for gene regulation. Overall, an augmented antitumor effect is observed due to NIR light‐controlled mitochondrial damage and enzyme‐activated gene regulation. Altogether, the approach reported in this study offers high spatiotemporal precision and shows the potential to achieve precise and specific gene regulation for targeted tumor treatment.
Unraveling Nanomaterials in Biomimetic Mineralization of Dental Hard Tissue: Focusing on Advantages, Mechanisms, and Prospects
Authors: Dai Danni , Li Dan , Zhang Chao
Published: August 2024

The demineralization of dental hard tissue imposes considerable health and economic burdens worldwide, but an optimal method that can repair both the chemical composition and complex structures has not been developed. The continuous development of nanotechnology has created new opportunities for the regeneration and repair of dental hard tissue. Increasingly studies have reported that nanomaterials (NMs) can induce and regulate the biomimetic mineralization of dental hard tissue, but few studies have examined how they are involved in the different stages, let alone the relevant mechanisms of action. Besides their nanoscale dimensions and excellent designability, NMs play a corresponding role in the function of the raw materials for mineralization, mineralized microenvironment, mineralization guidance, and the function of mineralized products. This review comprehensively summarizes the advantages of NMs and examines the specific mineralization mechanisms. Design strategies to promote regeneration and repair are summarized according to the application purpose of NMs in the oral cavity, and limitations and development directions in dental hard tissue remineralization are proposed. This review can provide a theoretical basis to understand the interaction between NMs and the remineralization of dental hard tissue, thereby optimizing design strategy, rational development, and clinical application of NMs in the field of remineralization.
Label‐Free Microfluidic Apheresis of Circulating Tumor Cell Clusters
Authors: Zhan Li , Edd Jon , Mishra Avanish , Toner Mehmet
Published: August 2024

Screening liters of blood (i.e., apheresis) represents a generalized approach to promote the reliable access to circulating tumor cell clusters (CTCCs), which are known to be highly metastasis‐competent, yet ultrarare. However, no existing CTCC sorting technology has demonstrated high throughput, high yield, low shear stress, and minimal blood dilution simultaneously as required in apheresis. Here, a label‐free method is introduced termed Precision Apheresis for Non‐invasive Debulking of cell Aggregates (PANDA) to continuously isolate CTCCs from undiluted blood to clean buffer through size sorting, processing 1.4 billion cells per second. The cell focusing is optimized within whole blood leveraging secondary transverse flow and margination. The PANDA chip recovers >90% of spiked ≈24 rare HeLa cell clusters from 100 mL undiluted blood samples (equivalent to ≈500 billion blood cells) at 1 L h−1 throughput, with ≤20s device residence time, ≤15 Pa shear stress, and >99.9% return of blood components. The technology lays the groundwork for future routine isolation to increase the recovery of these ultrarare yet clinically significant tumor cell populations from large volumes of blood to advance cancer research, early detection, and treatment.
Unveiling the Influence of Linkers on Conformations of Oligomeric Acceptors for High‐Performance Polymer Solar Cells
Authors: Wu Jingnan , Sun Fengbo , Wang Xunchang , Chen Qiaonan , Franco Leandro R. , Zheng Xufan , Araujo C. Moyses , Yang Renqiang , Yu Donghong , Wang Ergang
Published: August 2024

Conformational isomerism of organic photovoltaic materials has a profound impact on their molecular packing and therefore performance of polymer solar cells (PSCs). However, the conformations of oligomeric acceptors (OAs) are mostly predicted by simulations rather than experimental determinations. Herein, the stereochemical S‐shaped structure of two dimeric‐type acceptor molecules, V‐DYIC and V‐DYIC‐4F, is first confirmed with different end groups (IC for V‐DYIC and IC‐2F for V‐DYIC‐4F), incorporating vinylene linkage for connecting the distinct state‐of‐the‐art small molecule acceptor Y‐segments. Through the synthetic control of fluorination sites adjacent to the vinyl‐linker, S‐shaped the conformation by NMR experiments is validated. Compared to the O‐shaped dimer, S‐shaped conformation results in enhanced lamellar order and reduced nonradiative recombination losses. The optimal acceptor, V‐DYIC‐4F, achieved a champion efficiency of 18.10% with the lowest energy loss of 0.556 eV in its devices paired with PM6 due to their efficient carrier transport, and suppressed recombination compared to other devices, being attributed to the synergistic effect of conformation and end group fluorination. The insights gained in this work contribute valuable knowledge of both synthetic control and structural determination of OAs, providing strategic design guidelines for the future development of dimeric acceptors toward high‐efficiency PSCs.
miR‐30d Attenuates Pulmonary Arterial Hypertension via Targeting MTDH and PDE5A and Modulates the Beneficial Effect of Sildenafil
Authors: Liang Xuchun , Zhou Jingwen , Wang Hongyun , Zhang Ziyi , Yin Mingming , Zhu Yujiao , Li Lin , Chen Chen , Wei Meng , Hu Meiyu , Zhao Cuimei , Yao Jianhua , Li Guoping , Dinh‐Xuan Anh‐Tuan , Xiao Junjie , Bei Yihua
Published: August 2024

Pulmonary arterial hypertension (PAH) is associated with aberrant pulmonary vascular smooth muscle cell (PASMC) function and vascular remodeling. MiR‐30d plays an important role in the pathogenesis of several cardiovascular disorders. However, the function of miR‐30d in PAH progression remained unknown. Our study shows that circulating miR‐30d level is significantly reduced in the plasma from PAH patients. In miR‐30d transgenic (TG) rats, overexpressing miR‐30d attenuates monocrotaline (MCT)‐induced pulmonary hypertension (PH) and pulmonary vascular remodeling. Increasing miR‐30d also inhibits platelet‐derived growth factor‐bb (PDGF‐bb)‐induced proliferation and migration of human PASMC. Metadherin (MTDH) and phosphodiesterase 5A (PDE5A) are identified as direct target genes of miR‐30d. Meanwhile, nuclear respiratory factor 1 (NRF1) acts as a positive upstream regulator of miR‐30d. Using miR‐30d knockout (KO) rats treated with sildenafil, a PDE5A inhibitor that is used in clinical PAH therapies, it is further found that suppressing miR‐30d partially attenuates the beneficial effect of sildenafil against MCT‐induced PH and vascular remodeling. The present study shows a protective effect of miR‐30d against PAH and pulmonary vascular remodeling through targeting MTDH and PDE5A and reveals that miR‐30d modulates the beneficial effect of sildenafil in treating PAH. MiR‐30d should be a prospective target to treat PAH and pulmonary vascular remodeling.
A Cable‐Actuated Soft Manipulator for Dexterous Grasping Based on Deep Reinforcement Learning
Authors: Zhou Kunyu , Mao Baijin , Zhang Yuzhu , Chen Yaozhen , Xiang Yuyaocen , Yu Zhenping , Hao Hongwei , Tang Wei , Li Yanwen , Liu Houde , Wang Xueqian , Wang Xiaohao , Qu Juntian
Published: August 2024

The growing interest in the flexibility and operational capabilities of soft manipulators in confined spaces emphasizes the need for precise modeling and accurate motion control. Conventional control methods encounter difficulties in modeling and involve intricate computations. This work introduces a novel deep reinforcement learning (DRL) control algorithm based on neural network modeling. Using the Whale Optimization Algorithm, an approximate dynamic model for the soft manipulator is established. The twin delayed deterministic policy gradient is employed for DRL control. Domain randomization is applied during pretraining in a simulated environment. The algorithm addresses issues related to dependency on measurement data quality and redundant mappings, outperforming other methods by 8–15 mm in control accuracy. The trained DRL controller achieves precise trajectory tracking within the soft manipulator's task space, enabling successful grasping tasks in various complex environments, including pipelines and other narrow spaces. Experimental results confirm the autonomy of our controller in performing these tasks without human intervention.