bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular distribution of the Fragile X mental retardation protein in the inner ear: a developmental and comparative study in the mouse, rat, gerbil, and chicken
Authors: Wang Xiaoyu , Fan Qiwei , Yu Xiaoyan , Wang Yuan 
Published: October 2022

AbstractThe Fragile X mental retardation protein (FMRP) is an mRNA binding protein that is essential for neural circuit assembly and synaptic plasticity. Loss of functional FMRP leads to Fragile X syndrome (FXS), a neurodevelopmental disorder characterized by sensory dysfunction including abnormal auditory processing. While the central mechanisms of FMRP regulation have been studied in the brain, whether FMRP is expressed in the auditory periphery and how it develops and functions remains unknown. In this study, we characterized the spatiotemporal distribution pattern of FMRP immunoreactivity in the inner ear of mice, rats, gerbils, and chickens. Across species, FMRP was expressed in hair cells and supporting cells, with a particularly high level in immature hair cells during the prehearing period. Interestingly, the distribution of cytoplasmic FMRP displayed an age‐dependent translocation in hair cells, and this feature was conserved across species. In the auditory ganglion (AG), FMRP immunoreactivity was detected in neuronal cell bodies as well as their peripheral and central processes. Distinct from hair cells, FMRP intensity in AG neurons was high both during development and after maturation. Additionally, FMRP was evident in mature glial cells surrounding AG neurons. Together, these observations demonstrate distinct developmental trajectories across cell types in the auditory periphery. Given the importance of peripheral inputs to the maturation of auditory circuits, these findings implicate involvement of FMRP in inner ear development as well as a potential contribution of periphery FMRP to the generation of auditory dysfunction in FXS.
Automated Supramolecular Polymerization in a Microflow: A Versatile Platform for Multistep Supramolecular Reactions
Authors: Yamashita Kae , Numata Munenori 
Published: October 2022

AbstractThis work reports a basic microflow system capable of performing multistep supramolecular polymerization. In this system, injection of the monomer, directional supramolecular copolymerization, removal of the unreacted monomer, and purification of the product supramolecular diblock copolymers are realized along a three‐stream flow. When injecting a supramolecular polymer into the central stream of the three‐stream flow, the supramolecular polymerization always occurs in the central flow, with the two lateral flows serving as supply and removal lines for the monomer. Employing two kinds of perylene bisimide derivatives as monomers, we confirmed that the reaction occurred selectively at the forward‐facing terminus of the supramolecular polymer, along with recovery of the unreacted monomer, ultimately leading to a high‐purity supramolecular diblock copolymer. Diblock copolymers are basic units for preparing multicomponent supramolecular block copolymers. Thus, connecting the present system in series would, in principle, result in a “microplant” capable of producing supramolecular polymers having desired inner complexity.
Global insect decline is the result of wilful political failure: A battle plan for entomology
Authors: Donkersley Philip , Ashton Louise , Lamarre Greg P. A. , Segar Simon 
Published: October 2022

AbstractThe Millennium Ecosystem Assessment assessed ecosystem change, human wellbeing and scientific evidence for sustainable use of biological systems. Despite intergovernmental acknowledgement of the problem, global ecological decline has continued, including declines in insect biodiversity, which has received much media attention in recent years. Several roadmaps to averting biological declines have failed due to various economic and political factors, and so biodiversity loss continues, driven by several interacting human pressures. Humans are innately linked with nature but tend to take it for granted. The benefits we gain from the insect world are broad, yet aversion or phobias of invertebrates are common, and stand firmly in the path of their successful conservation. Providing an integrated synthesis for policy teams, conservation NGOs, academic researchers and those interested in public engagement, this article considers: (1) The lack of progress to preserve and protect insects. (2) Examples relating to insect decline and contributions insects make to people worldwide, and consequently what we stand to lose. (3) How to engage the public, governmental organizations and researchers through “insect contributions to people” to better address insect declines. International political will has consistently acknowledged the existence of biodiversity decline, but apart from a few narrow cases of charismatic megafauna, little meaningful change has been achieved. Public values are reflected in political willpower, the progress being made across the world, changing views on insects in the public should initiate a much‐needed political sea‐change. Taking both existing activity and required future actions, we outline an entomologist's “battle plan” to enormously expand our efforts and become the champions of insect conservation that the natural world needs.
Discovery of nitrogenous derivatives of dihydromyricetin in cell culture medium
Authors: Zhang Haolin , Wang Minglong , Liang Yuanwei , Lv Xiaomei , Xie Ruiwei , Chen Xiaojia , Xiao Jianbo 
Published: October 2022

AbstractDihydromyricetin (DMY) is a health‐beneficial flavanonol in the family of flavonoids, extracted from Ampelopsis grossedentata (Hand.‐Mazz.) W. Wang. When investigating the stability of DMY in Dulbecco's modified Eagle's medium (DMEM) solution at 37°C by LC‐MS/MS, four nitrogenous derivatives of DMY were found except for the previously known dimers, oxidized products, and ring‐cleavage products of DMY. Compound 1 (N‐DMY) was identified to be 4′‐amino (NH2)‐DMY based on MS and NMR data. The formation mechanism of N‐DMY was thought to include two steps. First, the pyrogallol moiety on the ring B of DMY was prone to be oxidized to quinone. Second, quinone might further participate in the Strecker degradation of amino acids in DMEM to form N‐DMY and corresponding aldehydes. Correspondingly, compounds 2–4 might be formed by the Strecker degradation reaction of amino acids in DMEM with quinones from the oxidation of DMY dimers and DMY ring‐cleavage products. Consistent with the formation mechanism, it was observed that flavonoids with a catechol or pyrogallol moiety readily form their nitrogenous derivatives during the incubation in DMEM at 37°C, which might be because catechol or pyrogallol are easily oxidized to quinones. In addition, the nitrogenous derivatives of flavonoids may have a potential to participate in the metabolism of flavonoids during in vitro and in vivo experiments. Therefore, flavonoid nitrogenous derivatives may play a significant role in the actual effects of flavonoids, which need to be further investigated in the future.
Computational Insights on Periodicity in Bonding and Lewis Acidity and Basicity of the p‐Block Trispyrazolylborate Complexes
Authors: Prakash Rini , Mohamed Amina , Jemmis Eluvathingal D. , Venugopal Ajay 
Published: October 2022

AbstractHydrotris(pyrazolyl)borate ligands are a popular class of ligands to stabilize both Lewis acidic and Lewis basic main group compounds. In this work we analyze the low‐valent group 13–15 compounds of hydrotris(3,5‐dimethyl‐pyrazolyl)borate ligand, [Tp*E]x, 1–15 (E=group 13 element, x=0; E=group 14 element, x=1+ ; E=group 15 element, x=2+) based on density functional theory. A periodic increment in intrinsic Lewis acidity is observed down the group due to increased E−N bond polarization towards nitrogen, resulting in lower energy secondary binding sites. However, global Lewis acidity measures in terms of FIA and IIA indicate the dependency on the choice of the nucleophile. In general, this study underscores the potential of the Tp* ligand in stabilizing the reactive low‐valent p‐block elements.
The relationship of environmental concern with public and private pro‐environmental behaviours: A pre‐registered meta‐analysis
Authors: Lou Xiaobin , Li Liman Man Wai 
Published: October 2022

AbstractPrevious meta‐analyses identified a gap between environmental concern and pro‐environmental behaviours. However, the failure to differentiate these behaviours and the influence of contextual factors may limit understanding of the gap. This pre‐registered meta‐analysis evaluated the magnitudes of the correlations of environmental concern, as measured by the New Environmental Paradigm of thinking, with public and private pro‐environmental behaviours and investigated the moderating roles of sociocultural contexts. Environmental concern was found positively correlated with public pro‐environmental behaviour (k = 10, N = 4636; r = 0.27) and private pro‐environmental behaviour (k = 31, N = 20,907; r = 0.35). These two pooled correlations did not differ significantly. Institutionalization of environmental protection did not moderate these correlations, while cultural factors, including individualism, long‐term orientation, and external control, did. These findings maintain the utility of environmental concern in facilitating different pro‐environmental behaviours and highlight the lack of research attention on public pro‐environmental behaviour.
Navigating the academic ladder as an early career researcher in earth and environmental sciences
Authors: Alderson Danielle , Clarke Lucy , Schillereff Daniel , Shuttleworth Emma 
Published: October 2022

AbstractThere is growing concern in Higher Education around job security, work–life balance and inequalities, and early career researchers (ECRs) must make difficult trade‐offs and life choices. Literature confirms that women navigating academia face additional challenges compared to their male counterparts. Few studies connected contractual circumstances, employment priorities and their impacts on the life choices of individual academics. We report results from a survey exploring the experiences of 37 ECRs who completed PhDs in the United Kingdom (UK) navigating the academic ladder in geomorphology and earth/environmental science, and contextualize these findings by drawing on personal experiences and wider literature. We find evidence of multi‐directional pressures that have materially negative effects on individuals' life choices, including concern that academic employment is a barrier to living where and with whom one may want to. The level of precarity amongst survey respondents is stark in terms of number of years they have held fixed‐term contracts (maximum 10 years), the number of individual contracts held (maximum 14) and number of different institutions worked at (maximum six). Women respondents were less prepared to be employed on precarious contracts and put more emphasis on job security when applying for academic posts, with men being generally more satisfied by financial aspects of university employment; which will amplify the leaky pipeline and gender gaps at more senior levels. We also find that perceived institutional prestige was a surprisingly low priority for the majority of respondents, and there were notable divergences between career advice given by more senior colleagues and the priorities of ECRs seeking guidance. We put forward a set of key considerations: improving policies on parental leave and flexible working; formalizing and improving mentorship; more considerate recruitment procedures; reducing contract precarity; and, transparency on pay and promotion. We believe these are within the scope of action by departments, laboratories and research groups.
The purification and identification of antioxidants and dipeptidyl peptidase IV inhibitory peptides from whey protein hydrolysates
Authors: Yuanrong Zheng , Jiakun Pang , Zhenmin Liu 
Published: October 2022

AbstractIn the present study, whey protein was enzymatically hydrolyzed using an ultrahigh‐pressure synergistic enzymolysis method. The antioxidant activities and DPP‐IV inhibitory activities of the enzymatic hydrolysates were measured. Three‐layer isolation and purification were conducted on the enzymatic hydrolysates with antioxidant activity and DPP‐IV inhibitory activity by gel filtration chromatography and RP‐HPLC. The amino acid sequences were determined by LC‐MS/MS. The identified amino acid sequences were then synthesized, and their antioxidants and DPP‐IV inhibitory activities were determined. The results showed that 3 of the 14 polypeptides of N3‐8 exhibited high antioxidant activity. Among them, peptide DDQNPHSSN had both high antioxidant activity and DPP‐IV inhibitory activity. When the concentration was 1 mg/mL, then the ABTS radical scavenging rate, DPPH radical scavenging rate and reducing power were prominent, reaching 91.42%, 88.76%, and 0.637%, respectively, and DPP‐IV inhibitory activity reached 66.28%. Whey protease hydrolysates are expected to be commercially developed as functional peptides.
Liver Metastasis Modulate Responses of Suppressive Macrophages and Exhausted T Cells to Immunotherapy Revealed by Single Cell Sequencing
Authors: Zhang Qiming , Liu Siyuan , Liu Yedan , Bhatt Dev , Estrada Juan , Belmontes Brian , Ren Xianwen , Canon Jude , Ouyang Wenjun 
Published: October 2022

AbstractLiver metastasis is associated with immunotherapy resistance, although the underlying mechanisms remain incompletely understood. By applying single cell RNA‐sequencing to a concurrent subcutaneous and liver tumor murine model to recapitulate liver metastases, it is identified that subsets within tumor‐infiltrating exhausted CD8+ T (Tex) cells and immunosuppressive tumor‐associated macrophages (TAMs) display opposite responses to concurrent liver tumors and anti‐PD‐1 treatment, suggesting a complex immune regulating network. Both angiogenic and interferon‐reactive TAMs show increased frequencies in implanted liver tumors, and anti‐PD‐1 treatment further elevates the frequencies of angiogenic TAMs. Such TAMs frequencies negatively correlate with the proportions of cytotoxic T cell subsets. Further, expression of interferon‐stimulated genes in TAMs is dramatically reduced under effective anti‐PD‐1 treatment, while such tendencies are diminished in mice with implanted liver tumors. Therefore, the study indicates that liver metastases could increase immunosuppressive TAMs frequencies and inhibit Tex responses to PD‐1 blockade, resulting in compromised systemic antitumor immunity and limited immunotherapy efficacy.
Endocannabinoid signaling in microglia
Authors: Marinelli Sara , Marrone Maria Cristina , Di Domenico Marina , Marinelli Silvia 
Published: October 2022

AbstractMicroglia, the innate immune cells of the central nervous system (CNS), execute their sentinel, housekeeping and defense functions through a panoply of genes, receptors and released cytokines, chemokines and neurotrophic factors. Moreover, microglia functions are closely linked to the constant communication with other cell types, among them neurons. Depending on the signaling pathway and type of stimuli involved, the outcome of microglia operation can be neuroprotective or neurodegenerative. Accordingly, microglia are increasingly becoming considered cellular targets for therapeutic intervention. Among signals controlling microglia activity, the endocannabinoid (EC) system has been shown to exert a neuroprotective role in many neurological diseases. Like neurons, microglia express functional EC receptors and can produce and degrade ECs. Interestingly, boosting EC signaling leads to an anti‐inflammatory and neuroprotective microglia phenotype. Nonetheless, little evidence is available on the microglia‐mediated therapeutic effects of EC compounds. This review focuses on the EC signals acting on the CNS microglia in physiological and pathological conditions, namely on the CB1R, CB2R and TRPV1‐mediated regulation of microglia properties. It also provides new evidence, which strengthens the understanding of mechanisms underlying the control of microglia functions by ECs. Given the broad expression of the EC system in glial and neuronal cells, the resulting picture is the need for in vivo studies in transgenic mouse models to dissect the contribution of EC microglia signaling in the neuroprotective effects of EC‐derived compounds.
Xenotransplantation—reflections on the bioethics
Authors: Zhai Xiaomei 
Published: October 2022

AbstractBackgroundSimilar to most countries in the world, China has a severe shortage of human organs, and this is one of the main issues restricting the application of organ transplantation technology. In 2019 alone, only 19,454 (23.90%) of the 81,410 people waiting were able to receive organ transplants. There is an increasing focus from both the medical profession and society on how to fill the gap between supply and demand.MethodsXenotransplantation using animal organs is being considered as one option to make up for the shortage of human organs for transplantation. For some years now, the international medical community has been examining the possibility of using animal organs for human transplant. However, the research has faced two important types of challenges: scientific and ethical issues.ResultsIn January 2021, the first clinical trial of transgenic pig heart transplantation into a human recipient was completed by the Medical Center of the University of Maryland in the United States. This has stimulated enthusiasm and interest in xenotransplantation.ConclusionsThe trend towards xenotransplantation has highlighted global problems such as the severe shortage of organ transplant donors and the high cost of organ transplantation. China needs to consider how to cope with the scientific, public health, and social ethics challenges of xenotransplantation clinical trials.
Role of immune‐inflamed phenotype in the prognosis of hypopharyngeal carcinoma following primary surgery
Authors: Chen Renhui , Cai Qian , Lin Peiliang , Liang Faya , Han Ping , Zhang Long , Song Pan , Zhang Tingzhen , Huang Xiaoming 
Published: October 2022

AbstractBackgroundThe immune profile in primary resected hypopharyngeal squamous cell carcinoma (HPSCC) and its prognostic value remain to be defined.MethodsWe enrolled 100 patients with HPSCC underwent primary surgical resection at our department. HPSCC samples were examined using immunohistochemistry for the expressions of CD8, Foxp3, CD163, CD66B, programmed death ligand‐1 (PD‐L1), and interferon (IFN)‐γ. The immune pattern of the tumor microenvironment (TME) was discriminated into inflamed and non‐inflamed tumors based on the presence or absence of parenchymal CD8+ T cells.ResultsWe found that 74% of HPSCC cases in our cohort were characterized by an immune‐inflamed TME. Immune‐inflamed patterns demonstrated an inferior survival with a significantly increased density of CD163+ tumor‐associated macrophages and Foxp3+ regulatory T cells. Additionally, the inflamed tumor showed increased expression of PD‐L1, without IFN‐γ upregulation.ConclusionsThe immune‐inflamed pattern is the predominant preexisting immune phenotype in HPSCC and demonstrates immunosuppressive immune cell recruitment.
Adenoid cystic carcinoma of the head and neck: Patterns of recurrence and implications for intensity‐modulated radiotherapy
Authors: Gao Robert W. , Routman David M. , Harmsen William S. , Ebrahimi Sasha , Foote Robert L. , Ma Daniel J. , Neben‐Wittich Michelle , McGee Lisa A. , Patel Samir H. , Moore Eric J. , Choby Garret W. , Tasche Kendall K. , Price Katharine A. , Gamez Mauricio E. , Lester Scott C. 
Published: October 2022

AbstractBackgroundWe seek to inform radiotherapy (RT) delivery for adenoid cystic carcinoma of the head and neck (ACC) by evaluating RT techniques and recurrence patterns.MethodsWe identified patients with ACC treated with curative‐intent RT from 2005 to 2021. Imaging was reviewed to determine local recurrence (LR).ResultsNinety‐one patients were included. The 5‐year LR risk was 12.2% (6.6–22.7). One patient each experienced a marginal and out‐of‐field recurrence. Patients receiving >60 Gy postoperatively had a 5‐year LR risk of 0% compared to 10.7% (4.2–27.2) with ≤60 Gy. Those receiving 70 and <70 Gy definitively had a 5‐year LR risk of 15.2% (2.5–91.6) and 33.3% (6.7–100.0), respectively. No patients had regional nodal failure.ConclusionsModern, conformal RT for ACC results in low rates of LR. Doses >60 and 70 Gy may improve control in the postoperative and definitive settings, respectively. Elective nodal treatment can be omitted in well‐selected patients.
HCV direct acting antiviral treatment leads to highly durable rates of ALT and AST lower than 30/19 criteria and improved APRI and FIB‐4 scores
Authors: Huynh Tung , Ma Stephanie , Hu Ke‐Qin 
Published: October 2022

Abstract
Direct acting antiviral treatment (DAA) has been the standard of care for hepatitis C virus (HCV) infection, but its long‐term benefits in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) improvement and hepatic fibrosis assessed by aspartate aminotransferase–to–platelet ratio index (APRI) and Fibrosis‐4 index (FIB‐4) scores remain unknown. The purpose of the present study was to assess DAA's long‐term benefits, including frequencies of posttreatment week 96 ALT/AST < 30 (males)/19 (females) (<30/19), improvement of APRI and FIB‐4 scores, and the associated factors. This was a single‐center, retrospective study on 157 patients with HCV with DAA‐mediated sustained virological response (SVR) 12. At posttreatment week (post‐Rx wk) 96, 75.4% had ALT < 30/19; 62.7%, AST < 30/19; and 60.1%, both ALT/AST < 30/19. ALT/AST < 30/19 at post‐Rx wk 96 was associated with ALT/AST < 30/19 at post‐Rx wk 12 (p = 0.026), independently of Child‐Turcotte‐Pugh < 6 (p = 0.862), platelets ≤ 120 × 109/L (p = 0.343). Improvement rates of APRI < 0.5 and FIB‐4 < 1.45 from baseline to post‐Rx wk 96 were from 30.9% to 80.5%, and from 23% to 37.8%, respectively. Both APRI and FIB‐4 improvement was associated with both ALT/AST < 30 (males)/19 (females) at post‐Rx wk 12 (p = 0.012 and 0.011, respectively). Conclusion: The present study showed that DAA‐mediated SVR12 in patients with HCV resulted in (1) high and durable rates of ALT (75.4%), AST (62.7%), and both ALT/AST (60.1%) < 30/19, and (2) high rates of APRI < 0.5 (80.5%) and FIB‐4 < 1.45 (37.8%) at post‐Rx wk 96, demonstrated clinical value of ALT/AST < 30/19 and excellent long‐term outcomes of DAA‐mediated SVR12 in these patients.
Performance of first‐trimester ultrasound in detection of structural abnormalities in Indian women: A prospective observational study
Authors: Singh Chanchal , Shahnaz Gazala , Dagar Savita , Shastri Aditi , Kurana Deeksha , Thakur Seema 
Published: October 2022

SynopsisFirst‐trimester screening is an invaluable opportunity for early identification of fetal structural defects irrespective of maternal body mass index.