bluuebunny/crossref_metadata_2025 huggingface dataset:
Online Public Relations Communication Strategy by Akar Tuli Malang in Campaigning the Use of Indonesian Sign Languange (BISINDO)
Authors: Hendrawan Jeffrey , Budiana Daniel , Yogatama Astri
Published: July 2023

This study aims to determine the online public relations strategy for Akar Tuli Malang Community in campaigning the use of Indonesian sign language (BISINDO). BISINDO is a sign system used by Deaf in Indonesia to communicate. Akar Tuli Malang is the first Deaf community in East Java which is a place for Deaf and hearing friends to socialize. In carrying out its goals, Akar Tuli Malang has a public relations division that carries out the task of establishing cooperation with various parties, both internal and external. The method used in this research is a case study with a qualitative approach and is a type of descriptive research. The results of the study show that the design of a strategy that refers to the concept of a public relations strategy according to Pinkleton has six stages of strategy and the Malang Deaf Root has carried out five of them. Consists of conceptualization, monitoring, planning, organization and coordination, administration and evaluation. In carrying out the strategy online, PR utilizes social media Instagram as a medium for conveying campaign messages.
Achievement of Ultralow Elastic Modulus through Optimization of Phase Stability and Recrystallization Texture in Ti–Nb–Fe–Sn Alloys
Authors: Ijaz Muhammad Farzik , Tasaki Wataru , Kim Hee Young , Miyazaki Shuichi
Published: July 2023

Ti–Nb–Fe–Sn alloys with relatively low Nb content, located near the phase boundary of (β + ω)/β, are designed on the basis of electron‐to‐atom (e/a) ratio, d‐electron alloy design concept, and Mo equivalent (Moeq) aiming at low Young's modulus comparable to human bone. The effect of Sn content and Nb content on the microstructure and the mechanical properties is investigated in Ti–5Nb–3Fe–(0–6)Sn (at%) and Ti–(3–9)Nb–3Fe–4Sn (at%) alloys. The composition dependence of Young's modulus and tensile strength of Ti–Nb–Fe–Sn alloys is analyzed in terms of the phase stability, ω phase, and recrystallization texture. Both Nb and Sn are effective in suppressing the athermal ω phase and stabilizing the β phase. The recrystallization texture is strongly influenced by the content of Sn and Nb. A strong {110}β<001>β Goss texture is formed in the Ti–5Nb–3Fe–(2–4)Sn and Ti–(3–5)Nb–3Fe–4Sn alloys. The Ti–5Nb–3Fe–4Sn alloy exhibits an exceptionally low Young's modulus of 30 GPa due to the combined effects of low stability of the β phase, a small amount of ω phase, and a strong Goss texture.
Independent directors and environmental innovations: How the visibility of public and private shareholders' environmental activism moderates the influence of board independence
Authors: Ruiz‐Castillo Maria , Aragón‐Correa Juan Alberto , Hurtado‐Torres Nuria Esther
Published: July 2023

While independent directors focus on preserving the shareholders' interests, their individual preferences may differ with regard to how environmental innovations have to be considered. A growing importance of shareholders' environmental activism has sought to influence firms' environmental practices through public proposals and private negotiations with executives. Using a sample of 7111 firms listed in the S&P 1500 index between 2006 and 2019, we examine how the visibility of shareholders' environmental proposals moderates the relationship between board independence and environmental innovations. Our findings show that public and private shareholder activism related to community issues and external reporting reinforces the positive influence of independent directors on firms' environmental innovations. However, private dialogues between executives and environmental activists focused on emissions from company operations diminish the influence of independent directors. Our study sheds light on how the external visibility of the topics involved in the activists' environmental proposals reinforces the interest of independent directors in advancing environmental innovations.
Transcatheter aortic valve‐in‐valve implantation within stentless landing zones: Procedural insights from a single‐center experience
Authors: Lang Frederick M. , Mihatov Nino , Kriegel Jacob , Nazif Tamim M. , Vahl Torsten P. , Ng Vivian G. , Lebehn Mark , Blusztein David , Cahill Thomas J. , Lehenbauer Kyle R. , Hahn Rebecca T. , Leon Martin , Kodali Susheel K. , George Isaac
Published: July 2023

Background

Valve‐in‐valve (VIV) transcatheter aortic valve implantation (TAVI) is a less invasive therapeutic option compared with redo surgical valve replacement for high‐risk patients. Relative to procedures within stented surgical valves, VIV‐TAVI within stentless valves is associated with a higher complication rate due to challenging underlying anatomy and absence of fluoroscopic landmarks.

Aims

We share a single‐center experience with VIV‐TAVI in stentless valves, discussing our procedural insights and associated outcomes.

Methods

Our institutional database was queried, and 25 patients who had undergone VIV‐TAVI within a stentless bioprosthesis, homograft, or valve‐sparing aortic root replacement between 2013 and 2022 were found. Outcome endpoints were based on the Valve Academic Research Consortium‐3 criteria.

Results

The mean age of the cohort was 69.5 ± 13.6 years. VIV implantation was performed within a homograft in 11 patients, a stentless bioprothesis in 10 patients, and a valve‐sparing aortic root replacement in 4 patients. Nineteen (76%) balloon‐expandable valves, 5 (20%) self‐expanding valves, and one mechanically‐expandable (4%) valve were implanted with 100% procedural success, with no instances of significant paravalvular leak, coronary occlusion, or device embolization. There was one (4%) in‐hospitality mortality after an emergency procedure; one (4%) patient experienced a transient ischemic attack; and two (8%) patients required permanent pacemaker implantation. The median length of hospital stay was 2 days. After a median follow‐up time of 16.5 months, valve function was acceptable in all patients with available data.

Conclusion

VIV‐TAVI within stentless valves can be safely performed with methodical procedural technique and can provide clinical benefit in patients at high reoperation risk.
Quantification of root lodging damage in corn using uncrewed aerial vehicle imagery
Authors: Lindsey A. J. , Allred B. , Martinez L. R. , Rouse Greg , Thomison P. R.
Published: July 2023

Accurate quantification of damage associated with root lodging events can help producers assess damage, predict potential yield losses, and help understand potential issues with grain quality that may arise post‐harvest (i.e., kernel weight reductions, premature germination on the ear, or vivipary). The objective of this research was to utilize imagery from an uncrewed aerial vehicle (UAV) to accurately quantify crop canopy height, grain yield, and identify trends in imagery data associated with grain quality after root lodging was imposed at multiple growth stages. Simulated corn (Zea mays L.) root lodging experiments were conducted in 2018 and 2019 with lodging treatments applied at two vegetative or two reproductive growth stages (V10, V14, VT/R1, and R3). At dough stage (R4), visible‐color and multispectral images were collected from each trial. Bare fields were also flown in February to obtain baseline elevation data. Imagery data were used to develop digital surface model (DSM) images and used to calculate indices of normalized difference red edge (NDRE) and normalized difference vegetation index (NDVI). Individual datapoints within each experimental plot were extracted from the imagery files and were compared to ground‐truth measurements. The DSM height values were similar to actual measured heights for most lodging treatments (Adj. R2 = .957). Both NDRE and NDVI exhibited linear trends with height and quality parameters (Adj. R2 = .25–.54), though yield patterns were best described using a quadratic model (Adj. R2 = .42–.60). These procedures hold utility in accurately quantifying canopy height following a root lodging event and hold promise in helping consultants identify yield and grain quality reductions associated with root lodging.
Mapping of corticotropin‐releasing factor, receptors, and binding protein mRNA in the chicken telencephalon throughout development
Authors: Metwalli Alek H. , Pross Alessandra , Desfilis Ester , Abellán Antonio , Medina Loreta
Published: July 2023

Understanding the neural mechanisms that regulate the stress response is critical to know how animals adapt to a changing world and is one of the key factors to be considered for improving animal welfare. Corticotropin‐releasing factor (CRF) is crucial for regulating physiological and endocrine responses, triggering the activation of the sympathetic nervous system and the hypothalamo–pituitary–adrenal axis (HPA) during stress. In mammals, several telencephalic areas, such as the amygdala and the hippocampus, regulate the autonomic system and the HPA responses. These centers include subpopulations of CRF containing neurons that, by way of CRF receptors, play modulatory roles in the emotional and cognitive aspects of stress. CRF binding protein also plays a role, buffering extracellular CRF and regulating its availability. CRF role in activation of the HPA is evolutionary conserved in vertebrates, highlighting the relevance of this system to help animals cope with adversity. However, knowledge on CRF systems in the avian telencephalon is very limited, and no information exists on detailed expression of CRF receptors and binding protein. Knowing that the stress response changes with age, with important variations during the first week posthatching, the aim of this study was to analyze mRNA expression of CRF, CRF receptors 1 and 2, and CRF binding protein in chicken telencephalon throughout embryonic and early posthatching development, using in situ hybridization. Our results demonstrate an early expression of CRF and its receptors in pallial areas regulating sensory processing, sensorimotor integration and cognition, and a late expression in subpallial areas regulating the stress response. However, CRF buffering system develops earlier in the subpallium than in the pallium. These results help to understand the mechanisms underlying the negative effects of noise and light during prehatching stages in chicken, and suggest that stress regulation becomes more sophisticated with age.
A fairness‐aware task offloading method in edge‐enabled IIoT with multi‐constraints using AGE‐MOEA and weighted MMF
Authors: Peng Kai , Ling Chengfang , Zhao Bohai , C. M. Leung Victor
Published: July 2023

By providing distributed and ultra‐low‐latency communication between industrial devices and resource components, the Industrial Internet of Things (IIoT) is at the forefront of a new trend. Such a distributed paradigm is viewed as a collection of autonomous computing resources utilized by multiple heterogeneous devices to achieve higher‐quality interconnection and data exchange. However, stringent requirements of exceptional service and fairness guarantees pose many formidable challenges. To this end, this study investigates the aforementioned concerns in an integrated manner and further proposes a fairness‐aware task offloading method, called FOIMAM. Specifically, the ‐norm is introduced to accommodate the Pareto plane under the non‐Euclidean geometry framework while the evaluation and elimination of low‐quality solutions are completed based on survival scores. Particularly, the fairness requirements are formulated as a multi‐constraint problem and resolved using weighted max‐min fairness. Eventually, numerical results indicate that the proposed method brings substantial improvement in both service efficiency and fairness guarantees.
Clinical Pharmacology Applications of Real‐World Data and Real‐World Evidence in Drug Development and Approval–An Industry Perspective
Authors: Zhu Rui , Vora Bianca , Menon Sujatha , Younis Islam , Dwivedi Gaurav , Meng Zhaoling , Datta‐Mannan Amita , Manchandani Pooja , Nayak Satyaprakash , Tammara Brinda K. , Garhyan Parag , Iqbal Shahed , Dagenais Simon , Chanu Pascal , Mukherjee Arnab , Ghobadi Cyrus ,   International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Real‐World Data Working Group
Published: July 2023

Since the 21st Century Cures Act was signed into law in 2016, real‐world data (RWD) and real‐world evidence (RWE) have attracted great interest from the healthcare ecosystem globally. The potential and capability of RWD/RWE to inform regulatory decisions and clinical drug development have been extensively reviewed and discussed in the literature. However, a comprehensive review of current applications of RWD/RWE in clinical pharmacology, particularly from an industry perspective, is needed to inspire new insights and identify potential future opportunities for clinical pharmacologists to utilize RWD/RWE to address key drug development questions. In this paper, we review the RWD/RWE applications relevant to clinical pharmacology based on recent publications from member companies in the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) RWD Working Group, and discuss the future direction of RWE utilization from a clinical pharmacology perspective. A comprehensive review of RWD/RWE use cases is provided and discussed in the following categories of application: drug–drug interaction assessments, dose recommendation for patients with organ impairment, pediatric plan development and study design, model‐informed drug development (e.g., disease progression modeling), prognostic and predictive biomarkers/factors identification, regulatory decisions support (e.g., label expansion), and synthetic/external control generation for rare diseases. Additionally, we describe and discuss common sources of RWD to help guide appropriate data selection to address questions pertaining to clinical pharmacology in drug development and regulatory decision making.
Institutional pressures and accountability processes in pursuit of sustainable development goals: Insights from Ghanaian indigenous oil companies
Authors: Tetteh Lexis Alexander , Agyenim‐Boateng Cletus , Simpson Samuel Nana Yaw
Published: July 2023

This paper aims at exploring the institutional pressures and accountability processes in pursuit of sustainable development goals (SDGs) in indigenous oil companies in Ghana. Applying a qualitative research strategy, semi‐structured interviews with 20 company managers and other industry stakeholders were used to collect in‐depth and rich empirical data. In pursuit of the SDG agenda, the indigenous oil companies appear to be sensitive to both internal and external stakeholder pressure. However, the coercive pressures from regulators did not always result in the companies implementing actual change. Instead, coercive pressures from non‐governmental actors have taken on the role of ‘regulator’ of organisational practices. Also, internal forces of change were mainly the foreign partner's audit pressure and management commitment to enhance company reputation. Beyond the institutional pressures to incorporate SDGs into business practices, the finding adds fresh perspectives to the three logical steps of SDG accountability processes used by the companies to track their contribution to SDG implementation and reporting, namely: data collection, SDG performance measurement, and communication of SDG outcomes. Finally, the study discovers that the companies are making little progress towards the achievement of the SDGs because of financial limitations, rigid organisational environments that prevent change, and a lack of a standardised institutional framework. The findings suggest that in order for an organisation to gain legitimacy, its SDG agenda must incorporate the concerns of non‐governmental actors and local communities into its corporate decision‐making. Failure to meet the needs of these essential stakeholders may jeopardise the legitimacy of organisation which will threaten its survival.
Adoptive cell therapy for cancer treatment
Authors: Du Shi , Yan Jingyue , Xue Yonger , Zhong Yichen , Dong Yizhou
Published: July 2023

Adoptive cell therapy (ACT) is a rapidly growing anti‐cancer strategy that has shown promise in treating various cancer types. The concept of ACT involves activating patients’ own immune cells ex vivo and then transferring them back to the patients to recognize and eliminate cancer cells. Currently, the commonly used ACT includes tumor‐infiltrating lymphocytes (TILs), genetically engineered immune cells, and dendritic cells (DCs) vaccines. With the advancement of cell culture and genetic engineering techniques, ACT has been used in clinics to treat malignant hematological diseases and many new ACT‐based regimens are in different stages of clinical trials. Here, representative ACT approaches are introduced and the opportunities and challenges for clinical translation of ACT are discussed.
Dynamic regulation of drug biodistribution by turning tumors into decoys for biomimetic nanoplatform to enhance the chemotherapeutic efficacy of breast cancer with bone metastasis
Authors: Zheng Cuixia , Zhang Dandan , Kong Yueyue , Niu Mengya , Zhao Hongjuan , Song Qingling , Feng Qianhua , Li Xingru , Wang Lei
Published: July 2023

Breast cancer with bone metastasis accounts for serious cancer‐associated pain which significantly reduces the quality of life of affected patients and promotes cancer progression. However, effective treatment using nanomedicine remains a formidable challenge owing to poor drug delivery efficiency to multiple cancer lesions and inappropriate management of cancer‐associated pain. In this study, using engineered macrophage membrane (EMM) and drugs loaded nanoparticle, we constructed a biomimetic nanoplatform (EMM@DJHAD) for the concurrent therapy of bone metastatic breast cancer and associated pain. Tumor tropism inherited from EMM provided the targeting ability for both primary and metastatic lesions. Subsequently, the synergistic combination of decitabine and JTC801 boosted the lytic and inflammatory responses accompanied by a tumoricidal effect, which transformed the tumor into an ideal decoy for EMM, resulting in prolonged troop migration toward tumors. EMM@DJHAD exerted significant effects on tumor suppression and a pronounced analgesic effect by inhibiting µ‐opioid receptors in bone metastasis mouse models. Moreover, the nanoplatform significantly reduced the severe toxicity induced by chemotherapy agents. Overall, this biomimetic nanoplatform with good biocompatibility may be used for the effective treatment of breast cancer with bone metastasis.
Green versus conventional growth in the EKC framework of top pollutant footprint countries: Evidence based on advanced panel data techniques
Authors: Usman Ahmed , Ozturk Ilhan , Naqvi Syed Muhammad Muddassir Abbas , Zafar Syeda Maria , Javed Muhammad Imran
Published: July 2023

Green growth has become the most credible solution to deal with the deterioration of the environment and excessive use of natural resources. Many studies have investigated the relationship between conventional economic growth and environmental degradation in Environmental Kuznets Curve (EKC) framework. However, in this analysis, we have investigated the EKC hypothesis by including green growth instead of conventional growth. Moreover, we have relied on the ecological footprint to represent environmental degradation in this analysis. Hence, the primary focus of the research is to investigate the association between green economic growth and ecological footprint in the EKC framework of top footprint economies for 1991–2017. The study employed the CS‐ARDL model and other advanced panel data techniques to estimate the model. The analysis confirmed the EKC hypothesis in top ecological footprint economies when we use conventional economic growth; however, the estimated coefficients of green growth and its square are negatively significant. The findings imply that green growth can help reduce the environmental burden, and renewable energy, eco‐innovations, and human capital also support the cause.
Safety and efficacy of cerebral embolic protection devices for patients undergoing transcatheter aortic valve replacement: An updated meta‐analysis
Authors: Shrestha Dhan Bahadur , Shtembari Jurgen , Lamichhane Sandesh , Baniya Abinash , Shahi Manoj , Dhungel Swati , Pant Kailash , Sutton Nadia R. , Villablanca Pedro , Mungee Sudhir
Published: July 2023

Background and Aims

Cerebral embolic protection (CEP) devices are employed to capture embolic debris and reduce the risk of stroke during transcatheter aortic valve replacement (TAVR). Evidence is mixed regarding the safety and efficacy of CEP. We aimed to summarize the safety and effectiveness of CEP use during TAVR.

Methods

Electronic databases, including PubMed, PubMed Central, Scopus, Cochrane Library, and Embase, were searched using relevant search terms for articles relating to CEP. All relevant data from 20 studies were extracted into a standardized form. Statistical analyses were performed using Revman 5.4. Odds ratio (OR) or mean differences (MDs) were used to estimate the desired outcome with a 95% confidence interval (CI).

Results

Twenty studies (eight randomized controlled trials [RCTs]) involving 210,871 patients (19,261 in the CEP group and 191,610 in TAVR without the CEP group) were included. The use of CEP was associated with a lower odds of 30‐day mortality by 39% (OR: 0.61, 95% CI: 0.53–0.70) and stroke by 31% (OR: 0.69, 95% CI: 0.52–0.92). Comparing devices, benefit in terms of mortality and stroke was observed with the use of the Sentinel device (Boston Scientific), but not among other devices. No differences were observed in the outcomes of acute kidney injury, major or life‐threatening bleeding events, or major vascular complications between groups. When only RCTs were included, there were no observed differences in the primary or secondary outcomes for CEP versus no CEP use during TAVR.

Conclusions

The totality of evidence suggests a net benefit for the use of CEP, weighted by studies in which the Sentinal device was used. However, given the RCT subanalysis, additional evidence is needed to identify patients at the highest risk of stroke for optimal decision‐making.
Swarming magnetic photonic‐crystal microrobots with on‐the‐fly visual pH detection and self‐regulated drug delivery
Authors: Yu Zheng , Li Luolin , Mou Fangzhi , Yu Shimin , Zhang Di , Yang Manyi , Zhao Qing , Ma Huiru , Luo Wei , Li Tianlong , Guan Jianguo
Published: July 2023

Swarming magnetic micro/nanorobots hold great promise for biomedical applications, but at present suffer from inferior capabilities to perceive and respond to chemical signals in local microenvironments. Here we demonstrate swarming magnetic photonic‐crystal microrobots (PC‐bots) capable of spontaneously performing on‐the‐fly visual pH detection and self‐regulated drug delivery by perceiving local pH changes. The magnetic PC‐bots consist of pH‐responsive hydrogel microspheres with encapsulated one‐dimensional periodic assemblies of Fe3O4 nanoparticles. By programming external rotating magnetic fields, they can self‐organize into large swarms with much‐enhanced collective velocity to actively find targets while shining bright “blinking” structural colors. When approaching the target with abnormal pH conditions (e.g., an ulcerated superficial tumor lesion), the PC‐bots can visualize local pH changes on the fly via pH‐responsive structural colors, and realize self‐regulated release of the loaded drugs by recognizing local pH. This work facilitates the development of intelligent micro/nanorobots for active “motile‐targeting” tumor diagnosis and treatment.

image
Emodin disrupts the Notch1/Nrf2/GPX4 antioxidant system and promotes renal cell ferroptosis
Authors: Xing Miao , Ma Xiaoyu , Wang Xi , Wang Haoze , Xie Minjuan , Zhang Ziwen , Zhou Jie
Published: July 2023

Emodin has been demonstrated to possess multiple pharmacological activities. However, emodin has also been reported to induce nephrotoxicity at high doses and with long‐term use, and the underlying mechanism has not been fully disclosed. The current study aimed to investigate the roles of oxidative stress and ferroptosis in emodin‐induced kidney toxicity. Mice were intraperitoneally treated with emodin, and NRK‐52E cells were exposed to emodin in the presence or absence of treatment with Jagged1, SC79, or t‐BHQ. Emodin significantly upregulated the levels of blood urea nitrogen, serum creatinine, malondialdehyde, and Fe2+, reduced the levels of superoxide dismutase and glutathione, and induced pathological changes in the kidneys in vivo. Moreover, the viability of NRK‐52E cells treated with emodin was reduced, and emodin induced iron accumulation, excessive reactive oxygen species production, and lipid peroxidation and depolarized the mitochondrial membrane potential (ΔΨm). In addition, emodin treatment downregulated the activity of neurogenic locus notch homolog protein 1 (Notch1), reduced the nuclear translocation of nuclear factor erythroid‐2 related factor 2 (Nrf2), and decreased glutathione peroxidase 4 protein levels. However, Notch1 activation by Jagged1 pretreatment, Akt activation by SC79 pretreatment, or Nrf2 activation by t‐BHQ pretreatment attenuated the toxic effects of emodin in NRK‐52E cells. Taken together, these results revealed that emodin‐induced ferroptosis triggered kidney toxicity through inhibition of the Notch1/Nrf2/glutathione peroxidase 4 axis.
Circ_0005615 promotes cervical cancer cell growth and metastasis by modulating the miR‐138‐5p/KDM2A axis
Authors: Luo Xiaoning , Liu Jiewen , Wang Xiangcai , Wang Yili , Yuan Jun , Zhang Yu
Published: July 2023

Cervical cancer (CC) is a highly fatal gynecological malignancy due to its high metastasis and recurrence rate. Circular RNA (circRNA) has been regarded as a regulator of CC. However, the underlying molecular mechanism of circ_0005615 in CC remains unclear. The levels of circ_0005615, miR‐138‐5p, and lysine demethylase 2A (KDM2A) were measured using qRT‐PCR or western blot. Cell proliferation was assessed by Cell Counting Kit‐8, 5‐ethynyl‐2′‐deoxyuridine, and colony formation experiments. Cell invasion and migration were tested by transwell assay and wound healing assay. Flow cytometry and Caspase‐Glo 3/7 Assay kit were used to analyze cell apoptosis. The expression of proliferation‐related and apoptosis‐related markers was detected by western blot. The binding relationships among circ_0005615, miR‐138‐5p, and KDM2A were verified by dual‐luciferase reporter assay or RNA immunoprecipitation assay. Xenograft assay was applied to detect the effect of circ_0005615 in vivo. Circ_0005615 and KDM2A were upregulated, while miR‐138‐5p was downregulated in CC tissues and cells. Circ_0005615 knockdown retarded cell proliferation, migration, and invasion, while promoting apoptosis. Besides, circ_0005615 sponged miR‐138‐5p, and miR‐138‐5p could target KDM2A. miR‐138‐5p inhibitor reversed the regulation of circ_0005615 knockdown on CC cell growth and metastasis, and KDM2A overexpression also abolished the inhibitory effect of miR‐138‐5p on CC cell growth and metastasis. In addition, we also discovered that circ_0005615 silencing inhibited CC tumor growth in vivo. Circ_0005615 acted as a tumor promoter in CC by regulating the miR‐138‐5p/KDM2A pathway.
Saikosaponin‐D induces the pyroptosis of lung cancer by increasing ROS and activating the NF‐κB/NLRP3/caspase‐1/GSDMD pathway
Authors: Chen Mengqing , Hu Chunyan , Yang Lei , Guo Qingxi , Liang Yuling , Wang Wenjun
Published: July 2023

Saikosaponin‐D (SSD), an active ingredient in Bupleurum chinense, exerts anticancer effects in various cancers by inhibiting cancer proliferation and inducing apoptosis. However, whether SSD can induce other forms of cell death is unknown. The current study aims to demonstrate that SSD can induce pyroptosis in non‐small‐cell lung cancer. In this study, HCC827 and A549 non‐small‐cell lung cancer cells were treated with different concentrations of SSD for 1.5 h. HE and TUNEL staining were used to verify cell damage caused by SSD. Immunofluorescence and western blotting were performed to verify the effect of SSD on the NF‐κB/NLRP3/caspase‐1/gasdermin D (GSDMD) pathway. Changes in inflammatory factors were detected by ELISAs. Finally, the reactive oxygen species (ROS) scavenger N‐acetylcysteine (NAC) was introduced to verify that SSD induces pyroptosis through the ROS/NF‐κB pathway. The results of the HE and TUNEL staining showed that SSD resulted in balloon‐like swelling of NSCLC cells accompanied by increased DNA damage. Immunofluorescence and western blot assays confirmed that SSD treatment activated the NLRP3/caspase‐1/GSDMD pathway, stimulated an increase in ROS levels and activated NF‐κB in lung cancer cells. The ROS scavenger N‐acetylcysteine significantly attenuated SSD‐induced NF‐κB/NLRP3/caspase‐1/GSDMD pathway activation and inhibited the release of the inflammatory cytokines IL‐1β and IL‐18. In conclusion, SSD induced lung cancer cell pyroptosis by inducing ROS accumulation and activating the NF‐κB/NLRP3/caspase‐1/GSDMD pathway. These experiments lay the foundation for the application of SSD in the treatment of non‐small‐cell lung cancer and regulation of the lung cancer immune microenvironment.
Sinensetin ameliorates high glucose‐induced diabetic nephropathy via enhancing autophagy in vitro and in vivo
Authors: Kong Zili , Lv Wenshan , Wang Yunyang , Huang Yajing , Che Kui , Nan Huiqi , Xin Yu , Wang Jiaxuan , Chen Jintao , Wang Yangang , Chi Jingwei
Published: July 2023

Diabetic nephropathy (DN) affects around 40% of people with diabetes, the final outcome of which is end‐stage renal disease. The deficiency of autophagy and excessive oxidative stress have been found to participate in the pathogenesis of DN. Sinensetin (SIN) has been proven to have strong antioxidant capability. However, the effect of SIN on DN has not been studied. We examined the effect of SIN on cell viability and autophagy in the podocyte cell line, MPC5 cells, treated with high glucose (HG). For in vivo studies, DN mice models were established by intraperitoneal injected with streptozotocin (40 mg/kg) for 5 consecutive days and fed with a 60% high‐fat diet, and SIN was given (10, 20, and 40 mg/kg) for 8 weeks via intraperitoneal injection. The results showed that SIN could protect MPC5 cells against HG‐induced damage and significantly improve the renal function of DN mice. Moreover, SIN remarkably restored the autophagy activity of MPC5 cells which was inhibited under HG conditions. Consistent with this, SIN efficiently improved autophagy in the kidney tissue of DN mice. In brief, our findings demonstrated the protective effect of SIN on DN via restoring the autophagic function, which might provide a basis for drug development.
Sanguinarine targets BRD4 to suppress cell proliferation and migration in clear cell renal cell carcinoma
Authors: Wen Yibo , Song Yue , Ma Yuan , Wen Jianguo , Yang Jinghua
Published: July 2023

Sanguinarine is an alkaloid with diverse biological activities, nevertheless, whether it can target epigenetic modifiers remains unknown. In this study, sanguinarine was characterized as a strong BRD4 inhibitor with IC50 = 361.3 nM against BRD4 (BD1) and IC50 = 302.7 nM against BRD4 (BD2) that can inactivate BRD4 reversibly. Additional cellular assays suggested that sanguinarine can bind BRD4 in human clear cell renal cell carcinoma (ccRCC) cell line 786‐O and inhibit cell growth with IC50 (24 h) = 0.6752 μM and IC50 (48 h) = 0.5959 μM in a BRD4 dependent manner partially. Meanwhile, sanguinarine can inhibit the migration of 786‐O cells in vitro and in vivo, and reverse epithelial−mesenchymal transition. Moreover, it can inhibit 786‐O cells proliferation in vivo in a BRD4 dependent manner partially. In sum, our study identified BRD4 as a new target of sanguinarine, and sanguinarine may serve as a potential therapeutic agent against ccRCC.
PPARγ agonist inhibits c‐Myc‐mediated colorectal cancer tumor immune escape
Authors: Xu Liuqian , Che Suning , Chen Huiqing , Liu Qian , Shi Juanjuan , Jin Jianhua , Hou Yongzhong
Published: July 2023

As a master transcription factor, c‐Myc plays an important role in promoting tumor immune escape. In addition, PPARγ (peroxisome proliferator‐activated receptor γ) regulates cell metabolism, inflammation, and tumor progression, while the effect of PPARγ on c‐Myc‐mediated tumor immune escape is still unclear. Here we found that cells treated with PPARγ agonist pioglitazone (PIOG) reduced c‐Myc protein expression in a PPARγ‐dependent manner. qPCR analysis showed that PIOG had no significant effect on c‐Myc gene levels. Further analysis showed that PIOG decreased c‐Myc protein half‐life. Moreover, PIOG increased the binding of c‐Myc to PPARγ, and induced c‐Myc ubiquitination and degradation. Importantly, c‐Myc increased PD‐L1 and CD47 immune checkpoint protein expression and promoted tumor immune escape, while PIOG inhibited this event. These findings suggest that PPARγ agonist inhibited c‐Myc‐mediated tumor immune escape by inducing its ubiquitination and degradation.
The role of GPLD1 in chronic diseases
Authors: Cao Jing , Zhou Anni , Zhou Zhuoyang , Liu Hui , Jia Shaohui
Published: July 2023

Glycosylphosphatidylinositol‐specific phospholipase D (GPLD1) is a specific enzyme for glycosylphosphatidylinositol (GPI) anchors, thereby exerting its biological functions by cleaving membrane‐associated GPI molecules. GPLD1 is abundant in serum, with a concentration of approximately 5−10 µg/mL. Previous studies have demonstrated that GPLD1 plays a crucial role in the pathogenesis of numerous chronic diseases including disorders of lipid and glucose metabolism, cancer, and neurological disorders. In the present study, we reviewed the structure, functions, and localization of GPLD1 in chronic diseases, as well as exercise‐mediated regulation of GPLD1, thus providing a theoretical support to develop GPLD1 as a new therapeutic target for chronic diseases.
Plant anthraquinones: Classification, distribution, biosynthesis, and regulation
Authors: Wang Peng , Wei Jia , Hua Xin , Dong Gangqiang , Dziedzic Krzysztof , Wahab Atia‐tul , Efferth Thomas , Sun Wei , Ma Pengda
Published: July 2023

Anthraquinones are polycyclic compounds with an unsaturated diketone structure (quinoid moiety). As important secondary metabolites of plants, anthraquinones play an important role in the response of many biological processes and environmental factors. Anthraquinones are common in the human diet and have a variety of biological activities including anticancer, antibacterial, and antioxidant activities that reduce disease risk. The biological activity of anthraquinones depends on the substitution pattern of their hydroxyl groups on the anthraquinone ring structure. However, there is still a lack of systematic summary on the distribution, classification, and biosynthesis of plant anthraquinones. Therefore, this paper systematically reviews the research progress of the distribution, classification, biosynthesis, and regulation of plant anthraquinones. Additionally, we discuss future opportunities in anthraquinone research, including biotechnology, therapeutic products, and dietary anthraquinones.
Trastuzumab Deruxtecan Dosing in Human Epidermal Growth Factor Receptor 2‐Positive Gastric Cancer: Population Pharmacokinetic Modeling and Exposure–Response Analysis
Authors: Yoshihara Kazutaka , Kobayashi Yoshimasa , Endo Seiko , Fukae Masato , Hennig Stefanie , Kastrissios Helen , Kamiyama Emi , Garimella Tushar , Abutarif Malaz
Published: July 2023

This study evaluated the benefit/risk of trastuzumab deruxtecan (T‐DXd) 6.4 mg/kg in patients with human epidermal growth factor receptor 2 (HER2)‐positive gastric cancer using pharmacometrics. A population pharmacokinetic (PopPK) model was developed using data from patients with gastric cancer, breast cancer, or other tumors in T‐DXd clinical trials, primarily conducted in Asia. Post hoc model‐estimated pharmacokinetic metrics were used in exposure–efficacy (objective response rates, ORRs) and exposure–safety analyses. The PopPK analysis included 808 patients (217 with gastric cancer, 512 with breast cancer, and 79 with other cancers). In gastric cancer, the T‐DXd 6.4 mg/kg steady‐state exposure metrics were lower compared with 6.4 mg/kg in breast cancer, but were similar to 5.4 mg/kg in breast cancer. Tumor type was selected as a significant covariate on T‐DXd clearance. In exposure–efficacy analysis among 160 patients with gastric cancer, the T‐DXd steady‐state minimum concentration was associated with a confirmed ORR in univariate logistic regression analysis (P = .023). The model‐predicted confirmed ORRs in gastric cancer were 36.0% (90%CI 29.3% to 43.7%) with 5.4 mg/kg and 40.0% (90%CI 33.1% to 47.6%) with 6.4 mg/kg. Among 808 patients in the exposure–safety analyses, the model‐predicted estimates for the rates of any‐grade interstitial lung disease (ILD) over a period of 180 days were 10.2% (90%CI 8.7% to 12.8%) with 6.4 mg/kg in gastric cancer and 9.7% (90%CI 8.2% to 11.8%) with 5.4 mg/kg in breast cancer. In gastric cancer, the efficacy of T‐DXd was higher at 6.4 mg/kg than at 5.4 mg/kg. Exposure and ILD rates were comparable between 6.4 mg/kg in gastric cancer and 5.4 mg/kg in breast cancer. This study identified T‐DXd 6.4 mg/kg as the recommended dose in HER2‐positive gastric cancer.
Electronic periodontal tool integration to enrich clinical diagnosis
Authors: Garcia M. Nathalia , Whitener Sara J. , Miley Douglas , Hildebolt Charles F.
Published: July 2023

Purpose/objectives

The objective of this study was to evaluate the effectiveness of an Electronic‐Periodontal‐Diagnosis‐Tool (EPDT) to facilitate the formulation of a correct periodontal diagnosis and analyze students’ perceptions of the use of the EPDT.

Methods

Fifty Year‐3 students who recently started their clinical training, were randomly assigned to two groups. Two clinical scenarios involving challenging periodontal diagnoses, each one with unique components, variables, and categories were distributed with specific instructions. The cases were analyzed to determine the correct periodontal diagnosis–half without the use of the EPDT and half with the use of the EPDT. A post‐exercise discussion conducted by the faculty explained the answer rationales. The students completed an anonymous/voluntary survey to evaluate their perceptions. Statistical analysis using likelihood ratio chi‐square tests and a generalized linear model evaluated whether the use of the EPDT resulted in higher percentages of correct diagnoses.

Results

EPDT use resulted in a three times higher percentage of correct classifications than no tool use (48% versus 16%), which the investigators considered an important effect of the EPDT. The generalized‐linear‐model assessment confirmed that EPDT resulted in better classifications (p < 0.0001). The feedback about the perceptions of the EPDT was favorable.

Conclusion

Students using the EPDT resulted in higher percentages of correct diagnoses. The EPDT provided students with a useful framework to determine the correct periodontal diagnoses, which is essential in providing appropriate treatments.
Skeletal anatomy of the pectoral fin in mudskipper species from terrestrial and aquatic habitats
Authors: Zhou Haodong , Donatelli Cassandra M. , Laneuville Odette , Standen Emily M.
Published: July 2023

Mudskippers are a group of amphibious fishes in the family Oxudercidae, whose species inhabit a range of habitats from mostly aquatic to mostly terrestrial. Most of our understanding about habitat preference comes from natural history observations, particularly where they are collected (i.e., low intertidal vs. high intertidal regions). Mudskippers have undergone several morphological changes to accommodate a terrestrial life, including major changes to the pectoral and pelvic girdles. These changes result in a novel crutching gait, which mudskippers use to move over land. Though the appendicular morphology and crutching gait of mudskippers have been described in some species, few studies have compared skeletal structures across the family. In our study, we use microcomputed tomography (µCT) scans to compare the skeletal anatomy of 16 species of aquatic and terrestrial mudskippers. Linear discriminant analysis is used to analyze measurements obtained through geometric morphometrics (landmarks). We found bone structures of the pectoral region in the terrestrial group were significantly longer and wider than those in the aquatic group. Furthermore, a significant difference in anatomy is shown between terrestrial and aquatic genera with both axial and appendicular elements contributing to the separation between groups. This work describes the differences in skeletal morphology associated with terrestriality in mudskippers and provides valuable insights into specific anatomical characteristics contributing to their adaptation to novel environments.
A protospacer adjacent motif‐free, multiplexed, and quantitative nucleic acid detection platform with barcode‐based Cas12a activity
Authors: Zhou Miaojin , Zhang Chunhua , Chen Miaomiao , Hu Zhiqing , Li Menglin , Li Zhuo , Wu Lingqian , Liang Desheng
Published: July 2023

Clustered regularly interspaced short palindromic repeat (CRISPR)‐based biosensors have been developed to facilitate the rapid and sensitive detection of nucleic acids. However, most approaches using CRISPR‐based detection have disadvantages associated with the limitations of CRISPR RNA (crRNA), protospacer adjacent motif (PAM) or protospacer flanking sequence restriction, single channel detection, and difficulty in quantitative detection resulting in only some target sites being detected qualitatively. Here, we aimed to develop a barcode‐based Cas12a‐mediated DNA detection (BCDetection) strategy, which overcomes the aforementioned drawbacks and enables (1) detection with a universal PAM and crRNA without PAM or crRNA restriction, (2) simultaneous detection of multiple targets in a single reaction, and (3) quantitative detection, which can significantly distinguish copy number differences up to as low as a two‐fold limit. We could efficiently and simultaneously detect three β‐thalassemia mutations in a single reaction using BCDetection. Notably, samples from normal individuals, spinal muscular atrophy (SMA) carriers, and SMA patients were significantly and accurately distinguished using the quantitative detection ability of BCDetection, indicating its potential application in β‐thalassemia and SMA carrier screening. Therefore, our findings demonstrate that BCDetection provides a new platform for accurate and efficient quantitative detection using CRISPR/Cas12a, highlighting its bioanalytical applications.
Modulation of the immunity and inflammation by autophagy
Authors: Gan Ting , Qu Shu , Zhang Hong , Zhou Xu‐jie
Published: July 2023

Autophagy, a highly conserved cellular self‐degradation pathway, has emerged with novel roles in the realms of immunity and inflammation. Genome‐wide association studies have unveiled a correlation between genetic variations in autophagy‐related genes and heightened susceptibility to autoimmune and inflammatory diseases. Subsequently, substantial progress has been made in unraveling the intricate involvement of autophagy in immunity and inflammation through functional studies. The autophagy pathway plays a crucial role in both innate and adaptive immunity, encompassing various key functions such as pathogen clearance, antigen processing and presentation, cytokine production, and lymphocyte differentiation and survival. Recent research has identified novel approaches in which the autophagy pathway and its associated proteins modulate the immune response, including noncanonical autophagy. This review provides an overview of the latest advancements in understanding the regulation of immunity and inflammation through autophagy. It summarizes the genetic associations between variants in autophagy‐related genes and a range of autoimmune and inflammatory diseases, while also examining studies utilizing transgenic animal models to uncover the in vivo functions of autophagy. Furthermore, the review delves into the mechanisms by which autophagy dysregulation contributes to the development of three common autoimmune and inflammatory diseases and highlights the potential for autophagy‐targeted therapies.
Low‐profile omnidirectional antenna with broad bandwidth and high gain
Authors: Guo Yao , Zhao Jing , Hui Weihua , Xie Kunlun , Hou Quanwen , Zhao Xiaopeng
Published: July 2023

In this study, a novel low profile wideband omnidirectional antenna is proposed. Horizontal dimension is utilized by introducing annular patches and near‐zero‐index metamaterials, instead of enhancing horizontal gain through increasing the profile of antenna. Measured results illustrate that horizontal gain of this antenna is enhanced to more than 2.5 dBi with 9.81% relative bandwidth (4.97−5.49 GHz) and low profile (0.034λ). Compared with other works, this novel antenna has obvious advantages in electromagnetic characteristics and physical structure, which has great potential in vehicular communications.
Impact of undernutrition on the pharmacokinetics of chemotherapy in children with cancer: A systematic review
Authors: Schoon Sterre , Makamo Nthongase , Uittenboogaard Aniek , Bernhardt Melanie B. , Ozuah Nmazuo W. , Kaspers Gertjan J. L. , Huibers Minke H. W.
Published: July 2023

Objectives

This systematic review provides an overview of the effect of undernutrition on the pharmacokinetics of chemotherapy in children with cancer.

Methods

PubMed, Embase, and Cochrane were searched to identify eligible studies. This study uses the definition for undernutrition from the World Health Organization and the Gomez classification.

Results

Four studies with a total of 668 children with cancer were included and n = 121 (18%) were undernourished. Significant decreased clearance rates were found for vincristine in undernourished children compared to children with a normal nutritional status.

Conclusion

Presenting outcomes only show significant changes in the pharmacokinetics of vincristine in undernourished children with cancer. However, data are scarce, groups were small, and none of the studies included severely undernourished children. In order to improve outcomes for (severely) undernourished children with cancer, more pharmacokinetic research is needed. The ultimate goal would be to develop subgroups, and ultimately individualized drug dosing in order to improve outcomes for children with cancer worldwide.