bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bitter taste receptors in the reproductive system: Function and therapeutic implications
Authors: Lu Ping , Moore Simas Tiffany A. , Delpapa Ellen , ZhuGe Ronghua 
Published: January 2024

AbstractType 2 taste receptors (TAS2Rs), traditionally known for their role in bitter taste perception, are present in diverse reproductive tissues of both sexes. This review explores our current understanding of TAS2R functions with a particular focus on reproductive health. In males, TAS2Rs are believed to play potential roles in processes such as sperm chemotaxis and male fertility. Genetic insights from mouse models and human polymorphism studies provide some evidence for their contribution to male infertility. In female reproduction, it is speculated that TAS2Rs influence the ovarian milieu, shaping the functions of granulosa and cumulus cells and their interactions with oocytes. In the uterus, TAS2Rs contribute to uterine relaxation and hold potential as therapeutic targets for preventing preterm birth. In the placenta, they are proposed to function as vigilant sentinels, responding to infection and potentially modulating mechanisms of fetal protection. In the cervix and vagina, their analogous functions to those in other extraoral tissues suggest a potential role in infection defense. In addition, TAS2Rs exhibit altered expression patterns that profoundly affect cancer cell proliferation and apoptosis in reproductive cancers. Notably, TAS2R agonists show promise in inducing apoptosis and overcoming chemoresistance in these malignancies. Despite these advances, challenges remain, including a lack of genetic and functional studies. The application of techniques such as single‐cell RNA sequencing and clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR‐associated endonuclease 9 gene editing could provide deeper insights into TAS2Rs in reproduction, paving the way for novel therapeutic strategies for reproductive disorders.
Role of the ubiquitin–proteasome system on macrophages in the tumor microenvironment
Authors: Xiao Yue , Liu Ruiqian , Li Na , Li Yong , Huang Xuan 
Published: January 2024

AbstractTumor‐associated macrophages (TAMs) are key components of the tumor microenvironment, and their different polarization states play multiple roles in tumors by secreting cytokines, chemokines, and so on, which are closely related to tumor development. In addition, the enrichment of TAMs is often associated with poor prognosis of tumors. Thus, targeting TAMs is a potential tumor treatment strategy, in which therapeutic approaches such as reducing TAMs numbers, remodeling TAMs phenotypes, and altering their functions are being extensively investigated. Meanwhile, the ubiquitin–proteasome system (UPS), an important mechanism of protein hydrolysis in eukaryotic cells, participates in cellular processes by regulating the activity and stability of key proteins. Interestingly, UPS plays a dual role in the process of tumor development, and its role in TAMs deserve to be investigated in depth. This review builds on this foundation to further explore the multiple roles of UPS on TAMs and identifies a promising approach to treat tumors by targeting TAMs with UPS.
M1 polarization of macrophages promotes stress‐induced hair loss via interleukin‐18 and interleukin‐1β
Authors: Xiao Xing , Gao Ying , Yan Lingchen , Deng Cuncan , Wu Wang , Lu Xiaofang , Lu Qiumei , Zhong Wenwei , Xu Yunsheng , Zhang Changhua , Chen Wei , Huang Bihui 
Published: January 2024

AbstractStress‐induced hair loss is a prevalent health concern, with mechanisms that remain unclear, and effective treatment options are not yet available. In this study, we investigated whether stress‐induced hair loss was related to an imbalanced immune microenvironment. Screening the skin‐infiltrated immune cells in a stressed mouse model, we discovered a significant increase in macrophages upon stress induction. Clearance of macrophages rescues mice from stress‐induced hair shedding and depletion of hair follicle stem cells (HFSCs) in the skin, demonstrating the role of macrophages in triggering hair loss in response to stress. Further flow cytometry analysis revealed a significant increase in M1 phenotype macrophages in mice under stressed conditions. In searching for humoral factors mediating stress‐induced macrophage polarization, we found that the hormone Norepinephrine (NE) was elevated in the blood of stressed mice. In addition, in‐vivo and in‐vitro studies confirm that NE can induce macrophage polarization toward M1 through the β‐adrenergic receptor, Adrb2. Transcriptome, enzyme‐linked immunosorbent assay (ELISA), and western blot analyses reveal that the NLRP3/caspase‐1 inflammasome signaling and its downstream effector interleukin 18 (IL‐18) and interleukin 1 beta (IL‐1β) were significantly upregulated in the NE‐treated macrophages. However, inhibition of the NE receptor Adrb2 with ICI118551 reversed the upregulation of NLRP3/caspase‐1, IL‐18, and IL‐1β. Indeed, IL‐18 and IL‐1β treatments lead to apoptosis of HFSCs. More importantly, blocking IL‐18 and IL‐1β signals reversed HFSCs depletion in skin organoid models and attenuated stress‐induced hair shedding in mice. Taken together, this study demonstrates the role of the neural (stress)‐endocrine (NE)‐immune (M1 macrophages) axis in stress‐induced hair shedding and suggestes that IL‐18 or IL‐1β may be promising therapeutic targets.
Angiogenic activity of mitochondria; beyond the sole bioenergetic organelle
Authors: Sadeghsoltani Fatemeh , Hassanpour Parisa , Safari Mir‑Meghdad , Haiaty Sanya , Rahbarghazi Reza , Rahmati Mohamad , Mota Ali 
Published: January 2024

AbstractAngiogenesis is a complex process that involves the expansion of the pre‐existing vascular plexus to enhance oxygen and nutrient delivery and is stimulated by various factors, including hypoxia. Since the process of angiogenesis requires a lot of energy, mitochondria play an important role in regulating and promoting this phenomenon. Besides their roles as an oxidative metabolism base, mitochondria are potential bioenergetics organelles to maintain cellular homeostasis via sensing alteration in oxygen levels. Under hypoxic conditions, mitochondria can regulate angiogenesis through different factors. It has been indicated that unidirectional and bidirectional exchange of mitochondria or their related byproducts between the cells is orchestrated via different intercellular mechanisms such as tunneling nanotubes, extracellular vesicles, and gap junctions to maintain the cell homeostasis. Even though, the transfer of mitochondria is one possible mechanism by which cells can promote and regulate the process of angiogenesis under reperfusion/ischemia injury. Despite the existence of a close relationship between mitochondrial donation and angiogenic response in different cell types, the precise molecular mechanisms associated with this phenomenon remain unclear. Here, we aimed to highlight the possible role of mitochondria concerning angiogenesis, especially the role of mitochondrial transport and the possible relation of this transfer with autophagy, the housekeeping phenomenon of cells, and angiogenesis.
The role of DNA damage in neural stem cells ageing
Authors: Zhong Yiming , Wang Guangming , Yang Shangzhi , Zhang Yang , Wang Xianli 
Published: January 2024

AbstractNeural stem cells (NSCs) are pluripotent stem cells with the potential to differentiate into a variety of nerve cells. NSCs are susceptible to both intracellular and extracellular insults, thus causing DNA damage. Extracellular insults include ultraviolet, ionizing radiation, base analogs, modifiers, alkyl agents and others, while intracellular factors include Reactive oxygen species (ROS) radicals produced by mitochondria, mismatches that occur during DNA replication, deamination of bases, loss of bases, and more. When encountered with DNA damage, cells typically employ three coping strategies: DNA repair, damage tolerance, and apoptosis. NSCs, like many other stem cells, have the ability to divide, differentiate, and repair DNA damage to prevent mutations from being passed down to the next generation. However, when DNA damage accumulates over time, it will lead to a series of alterations in the metabolism of cells, which will cause cellular ageing. The ageing and exhaustion of neural stem cell will have serious effects on the body, such as neurodegenerative diseases. The purpose of this review is to examine the processes by which DNA damage leads to NSCs ageing and the mechanisms of DNA repair in NSCs.
Novel compound heterozygous variants in ARL13B lead to Joubert syndrome
Authors: Lin Zaisheng , Shen Yue , Li Yan , Lu Chao , Zhu Ying , He Ruida , Cao Zongfu , Yin Zhe , Gao Huafang , Guo Bin , Ma Xu , Cao Muqing , Luo Minna 
Published: January 2024

AbstractJoubert syndrome (JBTS) is a systematic developmental disorder mainly characterized by a pathognomonic mid‐hindbrain malformation. All known JBTS‐associated genes encode proteins involved in the function of antenna‐like cellular organelle, primary cilium, which plays essential roles in cellular signal transduction and development. Here, we identified four unreported variants in ARL13B in two patients with the classical features of JBTS. ARL13B is a member of the Ras GTPase family and functions in ciliogenesis and cilia‐related signaling. The two missense variants in ARL13B harbored the substitutions of amino acids at evolutionarily conserved positions. Using model cell lines, we found that the accumulations of the missense variants in cilia were impaired and the variants showed attenuated functions in ciliogenesis or the trafficking of INPP5E. Overall, these findings expanded the ARL13B pathogenetic variant spectrum of JBTS.
By regulating the IP3R/GRP75/VDAC1 complex to restore mitochondrial dynamic balance, selenomethionine reduces lipopolysaccharide‐induced neuronal apoptosis
Authors: Xu Anqi , Wang Yixuan , Luo Dongliu , Xia Yu , Xue Hua , Yao Haidong , Li Shu 
Published: January 2024

AbstractSelenium (Se), as one of the essential trace elements, plays an anti‐inflammatory, antioxidation, and immune‐enhancing effect in the body. In addition, Se can also improve nervous system damage induced by various factors. Earlier studies have described the important role of mitochondrial dynamic imbalance in lipopolysaccharide (LPS)‐induced nerve injury. The inositol 1,4,5‐triphosphate receptor (IP3R)/glucose‐regulated protein 75 (GRP75)/voltage‐dependent anion channel 1 (VDAC1) complex is considered to be the key to regulating mitochondrial dynamics. However, it is not clear whether Selenomethionine (SeMet) has any influence on the IP3R/GRP75/VDAC1 complex. Therefore, the aim of this investigation was to determine whether SeMet can alleviate LPS‐induced brain damage and to elucidate the function of the IP3R/GRP75/VDAC1 complex in it. We established SeMet and/or LPS exposure models in vivo and in vitro using laying hens and primary chicken nerve cells. We noticed that SeMet reversed endoplasmic reticulum stress (ERS) and the imbalance in mitochondrial dynamics and significantly prevented the occurrence of neuronal apoptosis. We made this finding by morphological observation of the brain tissue of laying hens and the detection of related genes such as ERS, the IP3R/GRP75/VDAC1 complex, calcium signal (Ca2+), mitochondrial dynamics, and apoptosis. Other than that, we also discovered that the IP3R/GRP75/VDAC1 complex was crucial in controlling Ca2+ transport between the endoplasmic reticulum and the mitochondrion when SeMet functions as a neuroprotective agent. In summary, our results revealed the specific mechanism by which SeMet alleviated LPS‐induced neuronal apoptosis for the first time. As a consequence, SeMet has great potential in the treatment and prevention of neurological illnesses (like neurodegenerative diseases).
Transplantation of beige adipose organoids fabricated using adipose acellular matrix hydrogel improves metabolic dysfunction in high‐fat diet‐induced obesity and type 2 diabetes mice
Authors: Quan Yuping , Li Jian , Cai Junrong , Liao Yunjun , Zhang Yuteng , Lu Feng 
Published: January 2024

AbstractTransplantation of brown adipose tissue (BAT) is a promising approach for treating obesity and metabolic disorders. However, obtaining sufficient amounts of functional BAT or brown adipocytes for transplantation remains a major challenge. In this study, we developed a hydrogel that combining adipose acellular matrix (AAM) and GelMA and HAMA that can be adjusted for stiffness by modulating the duration of light‐crosslinking. We used human white adipose tissue‐derived microvascular fragments to create beige adipose organoids (BAO) that were encapsulated in either a soft or stiff AAM hydrogel. We found that BAOs cultivated in AAM hydrogels with high stiffness demonstrated increased metabolic activity and upregulation of thermogenesis‐related genes. When transplanted into obese and type 2 diabetes mice, the HFD + BAO group showed sustained improvements in metabolic rate, resulting in significant weight loss and decreased blood glucose levels. Furthermore, the mice showed a marked reduction in nonalcoholic liver steatosis, indicating improved liver function. In contrast, transplantation of 2D‐cultured beige adipocytes failed to produce these beneficial effects. Our findings demonstrate the feasibility of fabricating beige adipose organoids in vitro and administering them by injection, which may represent a promising therapeutic approach for obesity and diabetes.
Appropriateness of conducting and reporting random‐effects meta‐analysis in oncology
Authors: Ren Jinma , Ma Jia , Cappelleri Joseph C. 
Published: January 2024

AbstractA random‐effects model is often applied in meta‐analysis when considerable heterogeneity among studies is observed due to the differences in patient characteristics, timeframe, treatment regimens, and other study characteristics. Since 2014, the journals Research Synthesis Methods and the Annals of Internal Medicine have published a few noteworthy papers that explained why the most widely used method for pooling heterogeneous studies—the DerSimonian–Laird (DL) estimator—can produce biased estimates with falsely high precision and recommended to use other several alternative methods. Nevertheless, more than half of studies (55.7%) published in top oncology‐specific journals during 2015–2022 did not report any detailed method in the random‐effects meta‐analysis. Of the studies that did report the methodology used, the DL method was still the dominant one reported. Thus, while the authors recommend that Research Synthesis Methods and the Annals of Internal Medicine continue to increase the publication of its articles that report on specific methods for handling heterogeneity and use random‐effects estimates that provide more accurate confidence limits than the DL estimator, other journals that publish meta‐analyses in oncology (and presumably in other disease areas) are urged to do the same on a much larger scale than currently documented.
Assisting refugee survivors of torture and trauma: An existential perspective
Authors: Fernandes Pearl , Rhodes Paul , Buus Niels 
Published: January 2024

AbstractConsistent exposure to refugee narratives of trauma and torture can profoundly impact trauma therapists. This secondary analysis reanalyzed data from a narrative inquiry investigating the lived experiences of refugee trauma therapists. We aimed to explore emergent concerns through an existential lens to enrich understanding and provide additional insights into the lived experiences of these individuals. Participants in this purposive sample (N = 19) were therapists who had provided interventions to refugees for 2–34 years. Narrative construction, theory‐guided data analysis, and memo writing were used to reanalyze data generated by semistructured interviews augmented by photo elicitation. The findings indicate that being forced to reevaluate familiar beliefs consequent to one's professional roles induced intense existential moments, described as “a dark night of the soul,” “the paradox of life and death,” “uncanny feelings of not being at home,” and “a falling.” Acknowledging the complexities of the field, an existential framework to assist refugee trauma therapists in metabolizing and living with the professional challenges they encounter instead of focusing on alleviating decontextualized symptoms of distress is recommended. Research to inform requirements of the space to enable refugee trauma therapists to share their concerns and facilitate transitions toward more authentic, nonevasive sense of “being‐in‐the‐world” is suggested.
The Delaware‐Oslo ACL Cohort treatment algorithm yields superior outcomes to usual care 9–12 years after anterior cruciate ligament reconstruction
Authors: Urhausen Anouk P. , Grindem Hege , Engebretsen Lars , Grävare Silbernagel Karin , Axe Michael J. , Snyder‐Mackler Lynn , Risberg May Arna 
Published: January 2024

AbstractPurposePatient‐reported outcomes were compared between participants who followed the treatment algorithm of the Delaware‐Oslo ACL Cohort, consisting of progressive preoperative and postoperative rehabilitation, patient education, clinical testing and shared decision‐making about treatment choice, and those who followed usual care 9–12 years after anterior cruciate ligament reconstruction (ACLR).MethodsParticipants with primary ACLR were included from the Norwegian arm of the Delaware‐Oslo ACL Cohort and the Norwegian Knee Ligament Registry (usual care). The Knee Injury and Osteoarthritis Outcome Score (KOOS) subscale scores and the International Knee Documentation Committee‐Subjective Knee Form (IKDC‐SKF) scores were compared. KOOS scores for the usual care group were converted to IKDC‐SKF scores with recently published validated crosswalk. The percentages of participants with scores above predefined thresholds for patient acceptable symptom state (PASS) were also calculated.ResultsEighty of 100 (80%) participants from the Delaware‐Oslo ACL Cohort and 1588 of 3248 (49%) from the usual care group participated in the follow‐up. Participants from the Delaware‐Oslo ACL Cohort had higher KOOS subscale (p < 0.001) and IKDC‐SKF scores (p < 0.001), and a higher percentage reached PASS (84%–96% vs. 62%–76%, p ≤ 0.002) for KOOS Pain, symptoms, activities of daily living and sports compared to the usual care group. No significant differences were found for KOOS quality of life scores (not significant [n.s.]) or PASS percentages (80% vs. 74%, n.s.).ConclusionParticipants with ACLR who followed the Delaware‐Oslo ACL Cohort treatment algorithm had reduced knee symptoms, superior function and higher percentages of satisfactory outcomes than participants who followed usual care.Level of EvidenceLevel II.
To buy or not to buy? The impulse buying dilemma in livestream shopping
Authors: Miranda Sandra , Borges‐Tiago Maria Teresa , Tiago Flávio , Tu Xiangjin 
Published: January 2024

AbstractLivestream shopping can potentially contribute to impulse buying because this format's immediacy and interactive nature may induce viewers to make unplanned purchases. As a relatively new concept, livestream shopping is still being explored by retailers and consumers alike. Given its rapid rise in recent years, understanding this phenomenon and its potential is crucial. We applied a two‐study strategy to understand the influencer and environmental characteristics that may affect users' impulse‐buying behavior, adopting a stimulus–organism–response framework in both studies. We applied a partial least squares structural equation model to the gathered data (671 questionnaires), revealing that perceived usefulness influences impulse buying more than perceived enjoyment. This difference is more vivid for more experienced livestream shoppers, who tend to value perceived usefulness under the influence of streamer characteristics. With a qualitative approach, the second study evaluated the performance of a top‐streaming influencer in China to determine whether the survey's most influential variables were adopted during the most successful sale ever. Our findings suggest that endorser style and promotion strategies (scarcity and sales promotions) affect consumer behavior. This study thus provides firms with insights into effectively influencing consumers' impulse‐buying behavior in livestreaming commerce.
Bundling and horizontally differentiated innovation
Authors: Chung Hui‐Ling , Lin Yan‐Shu , Shih Pei‐Cyuan 
Published: January 2024

AbstractThis research builds a three‐stage (bundling, horizontally differentiated innovations [HDIs], and outputs) game in which only one multi‐product firm undertakes a bundling strategy in order to analyze the impacts of bundling on HDIs and competes with a single‐product firm. It is found that no matter what the degree of initial product substitution is, bundling will definitely amplify the degree of horizontal product differentiation. When the initial degree of product substitution is large, the bundling strategy subdues the firm's HDI while increasing the competitor's HDI. However, when the initial degree of product substitution is small, the bundling increases both firms' HDIs, resulting in higher competitor's profit, consumer surplus, and social welfare. An important policy implication of our results is that antitrust regulation that allows bundling may contribute to the multi‐product firm's HDI.
Decoding the systemic risk implications of corporate innovation: Evidence from a three‐period game model and a panel data regression
Authors: Huang Xiulu , Zhu Rui , Tang Chuxiong 
Published: January 2024

AbstractHow to understand the implications of corporate innovation in integrating economic development and financial stability is of great importance to the academia and the authority. Based on data from Chinese A‐share listed firms during 2007–2021, this study constructs a three‐period game model and a two‐way fixed effects panel regression model to examine the impact of corporate innovation on systemic risk theoretically and empirically. It is found that innovation measured by quantity and investment significantly pushes up corporate systemic risk, and such an effect is stronger in firms facing a more severe principal‐agent issue and in firms with weaker internal governance and external supervision. The effect pertains to the fact that innovation features high innovation risk and low innovation information robustness. Nevertheless, innovation quality manifested by R&D capitalization has a significant depressing effect on firm systemic risk. Additional tests show that inventive innovation strategies have a significant pushing‐up effect on firm systemic risk. Contrarily, non‐inventive innovation strategies are not necessarily related to a lower failure risk and higher innovation information robustness, and impact firm systemic importance and systemic vulnerability inconsistently, causing an undefined effect on firm systemic risk. The study highlights that the authority should scientifically guide enterprises to innovate and focus on improving innovation quality for structuring a balanced system of stabilizing growth and resolving risks.
Gig work: Does it get you more happiness?
Authors: Klein Galit , Klunover Doron , Shavit Tal 
Published: January 2024

AbstractGig work is one of the fastest‐growing trends in the labor market, one that accelerated during the COVID‐19 pandemic. It is therefore important to understand its impact on individual happiness. A simple theoretical framework is constructed to analyze aspects of gig work and their effect on happiness. In particular, we model happiness as being dependent on various characteristics of work, such as income, work flexibility, job stability and job security, employee benefits, and non‐pecuniary benefits. We demonstrate that merging salaried work and gig work can be an effective way to increase happiness. The proposed framework identifies the characteristics of an individual who will achieve greater happiness in gig work. These insights may help to understand the effect of recent changes in the labor market on workers' happiness.