bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent pain and numbness in the extremities of an adult due to paraneoplastic peripheral neuropathy caused by olfactory neuroblastoma: A case report
Authors: Liang Wenwen , Wang Yanyan , Sun Wenzhe , Li Dongrui , Zhang Xiaoping , Zhu Pengcheng , Zhu Zhou , Fang Yongkang
Published: January 2023

Background

Paraneoplastic peripheral neuropathy (PPN) caused by olfactory neuroblastoma (ONB) has not yet been reported.

Case report

We present a rare case of an adult who hospitalized repeatedly over the past 9 months for persistent pain and numbness in the limbs. This patient was initially diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) and treated accordingly, but neurological symptoms did not improve significantly. After this admission, FDG-PET/CT showed focal hypermetabolism of a soft-tissue mass in the nasal cavity, and further lesion biopsy suggested ONB. Combined with positive serum anti-Hu antibody, the diagnosis of PPN associated with ONB was eventually made. Furthermore, the patient's neurological symptoms were relieved after removal of the primary tumor, confirming the accuracy of the diagnosis.

Conclusion

Our case not only expanded the clinical characteristics of ONB but also highlighted the importance of early and comprehensive tumor screening for the diagnosis of PPN.
Exploring the role of immune checkpoint inhibitors in the etiology of myasthenia gravis and Lambert-Eaton myasthenic syndrome: A systematic review
Authors: Seligman Carly , Chang Yu-Mei , Luo Jie , Garden Oliver A.
Published: January 2023

Background

While immune checkpoint inhibitors (ICIs) have been revolutionary in the treatment of cancer, their administration has been associated with a variety of immune-related adverse events (irAEs), including myasthenia gravis (MG), and Lambert-Eaton myasthenic syndrome (LEMS).

Objective

To provide a comprehensive synthesis of the evidence supporting an etiological role for ICIs in MG and LEMS in patients with no prior history of autoimmune disease.

Hypothesis

ICIs may trigger MG and LEMS in patients with no prior susceptibility to autoimmune disease.

Methods

Relevant primary research on Medline was interrogated using a series of search algorithms. Search terms were constructed based on the PICOS tool endorsed by the Cochrane Collaboration, which describes population, intervention, comparison, outcomes, and study design. Papers were screened according to inclusion and exclusion criteria. Additional papers were retrieved from the reference lists of screened papers. Each paper included in the qualitative synthesis was assigned an integrated metric of evidence (IME) value, ranging from 0 to 7, based on study design, quality of data, likelihood of a causal link between the immune checkpoint inhibitor(s) and MG/LEMS, confidence of MG/LEMS diagnosis, and the number of patients treated with an ICI prior to MG/LEMS diagnosis.

Results

Ninety-four papers describing at least one patient treated with ICI(s) prior to the onset of MG and/or LEMS were documented. Overall evidence for a causal link between ICI administration and MG/LEMS was low, with a median IME value of 2.88 (range 2.05–6.61).

Conclusions

There is a paucity of evidence in support of an etiological relationship between ICIs and MG/LEMS, due largely to the lack of mechanistic studies and/or prospective clinical trials with relevant study endpoints. The current literature is dominated by case reports and retrospective cohort studies, which inherently yield only low-level evidence, supporting the need for further work in this area. A role of ICIs in the etiology of MG/LEMS remains plausible, arguing for continued vigilance for irAEs in patients treated with these drugs. We argue that there is a need for future mechanistic, high quality, large-scale studies specifically investigating the possible etiological role of ICIs in MG/LEMS.
Impairment of attention network function in posterior circulation ischemia-evidence from the Attention Network Test
Authors: Li Na , Li Chuanjin , Xie Xiaohui , Liu Gang , Wang Kai , Zhang Wendong , Fan Jin
Published: January 2023

Objective

This study aimed to investigate the effect of posterior circulation ischemia (PCI) on attention network function and to determine whether PCI is holistic or selective attention network deficit and which attention network is affected.

Methods

Thirty-six PCI patients aged 30 to 75 were assessed using the Attention Network Test and the Mini-Mental State Examination (MMSE). There were no significant differences in age, sex, and education between PCI group and the control group (n = 32). All data were statistically analyzed by SPSS 23.0 software.

Result

There were no significant difference in the MMSE scores between the two groups. Compared with the control group, the PCI group had significantly shorter response time for alerting and orienting network. The executive control network response time was significantly longer in PCI group than in the control group. The overall mean response time was also significantly longer in PCI group than in normal control group. There was no significant difference in mean accuracy between the two groups.

Conclusion

The alerting, orienting, and executive control networks were significantly less efficient in PCI group than in the control group (P < 0.01). This indicates impaired attention network in PCI patients. Since transient nerve seizures caused by vertebrobasilar ischemia may precede posterior circulation stroke, early assessment of cognitive function in patients with PCI is particularly important, and ANT is an excellent tool for this assessment.
Ethnicity, minority status, and inter-group bias: A systematic meta-analysis on fMRI studies
Authors: Saarinen Aino , Keltikangas-Järvinen Liisa , Ravaja Niklas
Published: January 2023

Introduction

This meta-analysis investigated (1) whether ethnic minority and majority members have a neural inter-group bias toward each other, and (2) whether various ethnic groups (i.e., White, Black, and Asian) are processed in the brain differently by the other respective ethnicities.

Methods

A systematic coordinate-based meta-analysis of functional magnetic resonance imaging (fMRI) studies was conducted using Web of Science, PubMed, and PsycINFO (altogether 50 datasets, n = 1211, 50.1% female).

Results

We found that ethnic minority members did not show any signs of neural inter-group bias (e.g., no majority-group derogation). Ethnic majority members, in turn, expressed biased responses toward minority (vs. majority) members in frontal, parietal, temporal, and occipital regions that are known to be involved in e.g., facial processing, attention, and perspective-taking. We also found differences in neural response patterns toward different ethnic groups (White, Black, and Asian); broadest biases in neural response patterns were evident toward Black individuals (in non-Black individuals). Heterogeneity was mostly minor or low.

Discussion:

Overall, the findings increase understanding of neural processes involved in ethnicity perception and cognition as well as ethnic prejudices and discrimination. This meta-analysis provides explanations for previous behavioral reports on ethnic discrimination toward minority groups.
Model-based experimental manipulation of probabilistic behavior in interpretable behavioral latent variable models
Authors: Thome Janine , Pinger Mathieu , Durstewitz Daniel , Sommer Wolfgang H. , Kirsch Peter , Koppe Georgia
Published: January 2023

Introduction

Interpretable latent variable models that probabilistically link behavioral observations to an underlying latent process have increasingly been used to draw inferences on cognition from observed behavior. The latent process usually connects experimental variables to cognitive computation. While such models provide important insights into the latent processes generating behavior, one important aspect has often been overlooked. They may also be used to generate precise and falsifiable behavioral predictions as a function of the modeled experimental variables. In doing so, they pinpoint how experimental conditions must be designed to elicit desired behavior and generate adaptive experiments.

Methods

These ideas are exemplified on the process of delay discounting (DD). After inferring DD models from behavior on a typical DD task, the models are leveraged to generate a second adaptive DD task. Experimental trials in this task are designed to elicit 9 graded behavioral discounting probabilities across participants. Models are then validated and contrasted to competing models in the field by assessing the ouf-of-sample prediction error.

Results

The proposed framework induces discounting probabilities on nine levels. In contrast to several alternative models, the applied model exhibits high validity as indicated by a comparably low prediction error. We also report evidence for inter-individual differences with respect to the most suitable models underlying behavior. Finally, we outline how to adapt the proposed method to the investigation of other cognitive processes including reinforcement learning.

Discussion

Inducing graded behavioral frequencies with the proposed framework may help to highly resolve the underlying cognitive construct and associated neuronal substrates.
An attention-based deep learning network for lung nodule malignancy discrimination
Authors: Liu Gang , Liu Fei , Gu Jun , Mao Xu , Xie XiaoTing , Sang Jingyao
Published: January 2023

Introduction

Effective classification of lung cancers plays a vital role in lung tumor diagnosis and subsequent treatments. However, classification of benign and malignant lung nodules remains inaccurate.

Methods

This study proposes a novel multimodal attention-based 3D convolutional neural network (CNN) which combines computed tomography (CT) imaging features and clinical information to classify benign and malignant nodules.

Results

An average diagnostic sensitivity of 96.2% for malignant nodules and an average accuracy of 81.6% for classification of benign and malignant nodules were achieved in our algorithm, exceeding results achieved from traditional ResNet network (sensitivity of 89% and accuracy of 80%) and VGG network (sensitivity of 78% and accuracy of 73.1%).

Discussion

The proposed deep learning (DL) model could effectively distinguish benign and malignant nodules with higher precision.
Microfluidic cell engineering on high-density microelectrode arrays for assessing structure-function relationships in living neuronal networks
Authors: Sato Yuya , Yamamoto Hideaki , Kato Hideyuki , Tanii Takashi , Sato Shigeo , Hirano-Iwata Ayumi
Published: January 2023

Neuronal networks in dissociated culture combined with cell engineering technology offer a pivotal platform to constructively explore the relationship between structure and function in living neuronal networks. Here, we fabricated defined neuronal networks possessing a modular architecture on high-density microelectrode arrays (HD-MEAs), a state-of-the-art electrophysiological tool for recording neural activity with high spatial and temporal resolutions. We first established a surface coating protocol using a cell-permissive hydrogel to stably attach a polydimethylsiloxane microfluidic film on the HD-MEA. We then recorded the spontaneous neural activity of the engineered neuronal network, which revealed an important portrait of the engineered neuronal network–modular architecture enhances functional complexity by reducing the excessive neural correlation between spatially segregated modules. The results of this study highlight the impact of HD-MEA recordings combined with cell engineering technologies as a novel tool in neuroscience to constructively assess the structure-function relationships in neuronal networks.
Ready-to-eat cereal is an affordable breakfast option associated with better nutrient intake and diet quality in the US population
Authors: Zhu Yong , Jain Neha , Normington James , Holschuh Norton , Sanders Lisa M.
Published: January 2023

Background

Results from observational studies have reported ready-to-eat cereal (RTEC) consumers have higher dietary quality and nutrient intake compared to consumers of non-RTEC breakfasts or those who do not eat breakfast. Yet, there have been few investigations on the relationship of RTEC to meal costs at breakfast and across the day, which may be one reason some consumers choose to not consume breakfast.

Objective

The objective of this study is to evaluate the contribution of RTEC consumed at breakfast to nutrient intake and adequacy, diet quality and meal costs in a nationally representative sample of children and adults in the US.

Methods

Dietary data from 2,259 children (2–18 years) and 4,776 adults (≥19 years) in the National Health and Nutrition Examination Survey (NHANES) 2017–2018 were evaluated to compare nutrient intake, adequacy, dietary quality, and food costs in RTEC breakfast consumers, non-RTEC breakfast consumers and those who did not consume breakfast.

Results

RTEC breakfast consumers made up 28% of children and 12% of adults. Children and adults consuming RTEC for breakfast had higher intakes of carbohydrate, dietary fiber, calcium, magnesium, iron, zinc, phosphorus, potassium, B vitamins, vitamins A and D, whole grains, and total dairy compared to consumers of non-RTEC breakfast or no breakfast. There were no differences by breakfast status for sodium, saturated fat, or added sugar, except adults consuming RTEC had lower added sugar intake compared to those who did not consume breakfast. RTEC breakfast consumers were also more likely to meet estimated average requirements (EAR) for intake of several nutrients and had overall higher dietary quality. For children, breakfast meal costs were less for RTEC breakfast compared to non-RTEC breakfast, but total daily meal costs were similar for consumers of RTEC and non-RTEC breakfasts.

Conclusion

RTEC breakfasts may contribute to greater nutrient intake and diet quality in children and adults in the US without increasing total daily meal costs.
Age-period-cohort analysis of gender differential trends in incidence and mortality of non-Hodgkin lymphoma in China, 1990-2019
Authors: Yao Yuanyuan , Liu Hui , Zhao Fei , Zhang Shengli , Liu Xingrong
Published: January 2023

Background

Non-Hodgkin lymphoma (NHL) is one of the dominant malignancies in the hematological system. This study estimated secular trends in NHL incidence and mortality from 1990 to 2019 and provided comprehensive evaluations of potential age, period, and cohort effects.

Methods

Age-period-cohort (APC) model was used to analyze changes in NHL incidence and mortality with age, period, and birth cohort effects based on data from the Global Burden of Disease Study 2019.

Results

The age-standardized incidence rates (ASIR) of NHL rose by 144.6% and age-standardized mortality rate (ASMR) rose by 27.5% from 1990 to 2019. Local drift for incidence was greater than 0 (p< 0.05) for both genders in each age group. Local drift for mortality rates were greater than 0 (p< 0.05) for males aged 20 to 89 years and females aged 60 to 84 years and less than 0 (p< 0.05) for females aged 20 to 50 years. Period rate ratio (RR) and cohort RR of NHL incidence in China showed an increasing trend, while the trend of male and female mortality was not consistent.

Conclusions

NHL incidence and mortality rates have been increasing in China over the past three decades. Males and older individuals were at high risk for NHL. Thus, attention to the prevention and therapy of NHL would be essential to lessen the disease burden of NHL.
Phosphatidyl Inositol 3-Kinase (PI3K)-Inhibitor CDZ173 protects against LPS-induced osteolysis
Authors: Wu Zuoxing , Li Xuedong , Chen Xiaohui , He Xuemei , Chen Yu , Zhang Long , Li Zan , Yang Mengyu , Yuan Guixin , Shi Baohong , Chen Ning , Li Na , Feng Haotian , Zhou Mengyu , Rui Gang , Xu Feng , Xu Ren
Published: January 2023

A major complication of a joint replacement is prosthesis loosening caused by inflammatory osteolysis, leading to the revision of the operation. This is due to the abnormal activation of osteoclast differentiation and function caused by periprosthetic infection. Therefore, targeting abnormally activated osteoclasts is still effective for treating osteolytic inflammatory diseases. CDZ173 is a selective PI3K inhibitor widely used in autoimmune-related diseases and inflammatory diseases and is currently under clinical development. However, the role and mechanism of CDZ173 in osteoclast-related bone metabolism remain unclear. The possibility for treating aseptic prosthesis loosening brought on by inflammatory osteolysis illness can be assessed using an LPS-induced mouse cranial calcium osteolysis model. In this study, we report for the first time that CDZ173 has a protective effect on LPS-induced osteolysis. The data show that this protective effect is due to CDZ173 inhibiting the activation of osteoclasts in vivo. Meanwhile, our result demonstrated that CDZ173 had a significant inhibitory effect on RANKL-induced osteoclasts. Furthermore, using the hydroxyapatite resorption pit assay and podosol actin belt staining, respectively, the inhibitory impact of CDZ173 on bone resorption and osteoclast fusion of pre-OC was determined. In addition, staining with alkaline phosphatase (ALP) and alizarin red (AR) revealed that CDZ173 had no effect on osteoblast development in vitro. Lastly, CDZ173 inhibited the differentiation and function of osteoclasts by weakening the signal axis of PI3K-AKT/MAPK-NFATc1 in osteoclasts. In conclusion, our results highlight the potential pharmacological role of CDZ173 in preventing osteoclast-mediated inflammatory osteolysis and its potential clinical application.
Discovery of a potent olaparib–chlorambucil hybrid inhibitor of PARP1 for the treatment of cancer
Authors: Qin Hongyu , Zhang Jian , Zhao Yilu , Zhang Lihui , Feng Jinhong , Zhang Lei
Published: January 2023

Introduction: Development of Poly (ADP-ribose) polymerase (PARP) inhibitors has been extensively studied in cancer treatment. Olaparib, the first approved PARP inhibitor, showed potency in the inhibition of both BRCA (breast cancer associated)-mutated and BRCA-unmutated cancers.

Methods: Aiming to the discovery of olaparib analogs for the treatment of cancer, structural modifications were performed based on the scaffold of olaparib. In the first series, reduction of carbonyl group to CH2 led to decrease of PARP1 inhibitory activity. Preserving the original carbonyl group, molecules with potent PARP1 inhibitory activities were derived by introduction of hydrazide and aromatic nitrogen mustard groups. The synthesized compounds were evaluated in the in the PARP1 enzyme inhibitory screening, cancer cell based antiproliferative assay, cell cycle arrest and apoptosis studies.

Results: It is remarkable that, molecule C2 with chlorambucil substitution, exhibited potent PARP1 inhibitory activity and a broad-spectrum of anticancer potency in the in vitro antiproliferative assay. Compared with olaparib and chlorambucil, molecule C2 also showed significant potency in inhibition of a variety of BRCA-unmutated cell lines. Further analysis revealed the effects of C2 in induction of G2/M phase cell cycle arrest and promotion of apoptosis.

Discussion: Collectively, the olaparib-chlorambucil hybrid molecule (C2) could be utilized as a lead compound for further drug design.
Kidney tonifying traditional Chinese medicine: Potential implications for the prevention and treatment of osteoporosis
Authors: Duan Yan , Su Yu-Ting , Ren Jie , Zhou Qun , Tang Min , Li Juan , Li Shun-Xiang
Published: January 2023

The aging global population is increasingly affected by osteoporosis (OP), which is one of the most significant threats to the elderly. Moreover, its prevention and treatment situations have become increasingly severe. Therefore, it is imperative to develop alternatives or complementary drugs for preventing and treating osteoporosis. Kidney tonifying traditional Chinese medicine (KTTCM) has been used for the treatment of osteoporosis for a long time. Pharmacological studies have shown that kidney tonifying traditional Chinese medicine can promote osteoblasts, inhibit osteoclasts, and regulate the level of estrogen and plays vital roles in stimulating osteogenesis, restraining adipogenesis of marrow mesenchymal stem cells (MSCs), regulating the metabolism of calcium and phosphorus, and inhibiting oxidative stress. These effects are mediated by OPG/RANKL/RANK, BMP/Smads, MAPKs, and Wnt/β-catenin systems. To develop a safe, synergistic, effective, and homogenized TCM formula with robust scientific evidence to provide faster and more economical alternatives, the anti-osteoporosis ingredients and pharmacological mechanisms of kidney tonifying traditional Chinese medicine are recapitulated from the perspective of molecular and cell biology, and the safety and toxicity of kidney tonifying traditional Chinese medicine have also been reviewed in this paper.
Advancements in lead therapeutic phytochemicals polycystic ovary syndrome: A review
Authors: Luo Er-Dan , Jiang Hai-Mei , Chen Wei , Wang Yao , Tang Mi , Guo Wen-Mei , Diao Hao-Yang , Cai Ning-Yuan , Yang Xiao , Bian Ying , Xing Sha-Sha
Published: January 2023

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women of reproductive age and features complex pathological symptoms and mechanisms. Existing medical treatments have, to some extent, alleviated the deterioration of PCOS. However, these strategies only temporarily control symptoms, with a few side effects and no preventive effect. Phytochemicals extracted from medicinal herbs and plants are vital for discovering novel drugs. In recent years, many kinds of research have proven that phytochemicals isolated from traditional Chinese medicine (TCM) and medicinal plants show significant potential in preventing, alleviating, and treating PCOS. Nevertheless, compared to the abundance of experimental literature and minimal specific-topic reviews related to PCOS, there is a lack of systematic reviews to summarize these advancements in this promising field. Under this background, we systematically document the progress of bioactive phytochemicals from TCM and medicinal plants in treating PCOS, including flavonoids, polyphenols, and alkaloids. According to the literature, these valuable phytochemicals demonstrated therapeutic effects on PCOS supported by in vivo and in vitro experiments, mainly depending on anti-inflammatory, antioxidation, improvement of hormone disorder and insulin resistance (IR), and alleviation of hyperinsulinemia. Based on the current progress, future research directions should emphasize 1) exploring bioactive phytochemicals that potentially mediate bone metabolism for the treatment of PCOS; 2) improving unsatisfactory bioavailability by using advanced drug delivery systems such as nanoparticles and antibody-conjugated drugs, as well as a chemical modification; 3) conducting in-depth research on the pathogenesis of PCOS to potentially impact the gut microbiota and its metabolites in the evolution of PCOS; 4) revealing the pharmacological effects of these bioactive phytochemicals on PCOS at the genetic level; and 5) exploring the hypothetical and unprecedented functions in regulating PCOS by serving as proteolysis-targeting chimeras and molecular glues compared with traditional small molecule drugs. In brief, this review aims to provide detailed mechanisms of these bioactive phytochemicals and hopefully practical and reliable insight into clinical applications concerning PCOS.
Pharmacological activities and mechanisms of action of hypophyllanthin: A review
Authors: Wan Saidin Wan Azmira , Jantan Ibrahim , Abdul Wahab Siti Mariam , Jalil Juriyati , Mohd Said Mazlina , Yusoff Syaratul Dalina , Husain Khairana
Published: January 2023

Hypophyllanthin is a major lignan present in various Phyllanthus species and has been used as one of the bioactive chemical markers for quality control purposes as it contributes to their diverse pharmacological activities. The objective of this study is to compile up-to-date data on the pharmacological actions and mechanisms of hypophyllanthin. This review also includes the extracts of Phyllanthus species whose pharmacological actions have been partially attributed to hypophyllanthin. The scientific findings on the compound are critically analyzed and its potential as a lead molecule for the discovery of drug candidates for the development of therapeutics to treat diverse diseases is highlighted. Data collection was mainly through the exploration of Ovid-MEDLINE, Scopus, Science Direct, and Elsevier databases. Studies conducted in vitro and in vivo showed that hypophyllanthin had potent immunomodulating properties as well as a variety of other pharmacological properties, including anti-inflammatory, hepatoprotective, anti-tumor, anti-allergic, anti-hypertensive, and phytoestrogenic properties. Several mechanisms of action on the effects of hypophyllanthin on the immune system, in cancer and other disease states, were presented to provide some insights into its pharmacological effects. Before being submitted to clinical investigations, additional animal studies utilising different animal models are necessary to analyse its bioavailability, pharmacokinetics, and pharmacodynamic properties, as well as its toxicity, to determine its efficacy and safety. Understanding its potential as a lead molecule for the discovery of therapeutic candidates, particularly for the development of therapies for inflammatory and immune-related disorders, requires an understanding of its pharmacological activities and mechanisms of action. An insight into its pharmacological activities and mechanisms of action will provide an understanding of its potential as a lead compound for the discovery of drug candidates, especially for the development of therapies for inflammatory and immune related diseases.
Research progress of treatment of functional dyspepsia with traditional Chinese medicine compound based on cell signal pathway
Authors: Song Yujiao , Yin Defei , Zhang Zhenyi , Chi Lili
Published: January 2023

Functional dyspepsia (FD) is the most common clinical gastrointestinal disease, with complex and prolonged clinical symptoms. The prevalence of FD is increasing year by year, seriously affecting the quality of life of patients. The main causes of FD are related to abnormal gastrointestinal dynamics, increased visceral sensitivity, Helicobacter pylori (HP) infection, intestinal flora disturbance and psychological factors. A review of the relevant literature reveals that the mechanisms of traditional Chinese medicine (TCM) in the treatment of FD mainly involve the following pathways:5-HT signal pathway, AMPK signal pathway,C-kit signal pathway, CRF signal pathway, PERK signal pathway,NF-κB signal pathway. Based on a holistic concept, TCM promotes gastrointestinal motility, regulates visceral sensitivity and alleviates gastrointestinal inflammation through multiple signal pathways, reflecting the advantages of multi-level, multi-pathway and multi-targeted treatment of FD.
Astragalus propinquus schischkin and Salvia miltiorrhiza bunge promote angiogenesis to treat myocardial ischemia via Ang-1/Tie-2/FAK pathway
Authors: Zhang Mu-Xin , Huang Xue-Ying , Song Yu , Xu Wan-Li , Li Yun-Lun , Li Chao
Published: January 2023

Astragalus propinquus Schischkin and Salvia miltiorrhiza Bunge (AS) have been clinically used as adjunctive drugs in the treatment of myocardial ischemia (MI). However, the effect and mechanism of AS on MI have yet to be fully recognized. Here, we explored the cardioprotective effect of their combined use, and the mechanism of promoting angiogenesis through pericyte recruitment. Our data revealed that AS reduced MI and protects cardiac function. AS-treated MI mice exhibited reduced ST-segment displacement and repolarization time, increased ejection fraction, and less BNP and NT-proBNP expression. Pathological studies showed that, AS reduced the area of infarcted myocardium and slowed down the progress of cardiac remodelling and fibrosis. In addition, AS increased the content of platelet-derived growth factor receptors β (PDGFR-β), platelet endothelial cell adhesion molecule-1 (CD31) and angiogenesis-related proteins including vascular endothelial cadherin (VE-cadherin), Vascular Endothelial Growth Factor (VEGF) and transforming growth factor β (TGF-β). Moreover, these botanical drugs upregulated the expression of Angiopoietin-1 (Ang-1), phosphorylated angiopoietin-1 receptor (p-Tie-2), focal adhesion kinase (FAK) and growth factor receptor bound protein 7 (GRB7), indicating that the cardioprotection-related angiogenesis effect was related to pericyte recruitment, which may be through Ang-1/Tie-2/FAK pathway. In summary, AS can treat MI by protecting cardiac function, attenuating cardiac pathological changes, and hindering the progression of heart failure, which is related to angiogenesis after pericyte recruitment. Therefore, AS at a certain dose can be a promising treatment for MI with broad application prospects.
Engineered elastin-like polypeptides: An efficient platform for enhanced cancer treatment
Authors: Jiang Aiguo , Guan Xinqiang , He Lianping , Guan Xingang
Published: January 2023

Drug delivery systems (DDSs) have recently gained widespread attention for improving drug loading and delivery efficiency in treating many cancers. Elastin-like polypeptides (ELPs) are synthetic peptides derived from a precursor of elastin (tropoelastin), reserving similar structural and physicochemical properties. ELPs have gained a variety of applications in tissue engineering and cancer therapy due to their excellent biocompatibility, complete degradability, temperature-responsive property, controllable sequence and length, and precisely tuned structure and function. ELPs-based drug delivery systems can improve the pharmacokinetics and biodistribution of therapeutic reagents, leading to enhanced antitumor efficacy. In this review, we summarize the recent application of ELPs in cancer treatment, focusing on the delivery of functional peptides, therapeutic proteins, small molecule drugs, and photosensitizers.
Quercetin 7-rhamnoside protects against alpha-naphthylisothiocyanate (ANIT)-induced in cholestatic hepatitis rats by improving biliary excretion and inhibiting inflammatory responses
Authors: Jin Hong-Liu , Liu Xiao-Jia , Feng Xiao-Ying , Zhu Wen-Ting , Feng Sen-Ling , Cao Li-Ping , Yuan Zhong-Wen
Published: January 2023

Objective: To explore the pharmacological effects and molecular mechanism of quercetin 7-rhamnoside (Q7R) in the treatment of cholestatic hepatitis induced by alpha-naphthylisothiocyanate (ANIT).

Methods: ANIT-induced cholestatic hepatitis rat model was used to investigate the hepatoprotective effects of three different doses of Q7R (1.25 mg/kg; 2.5 mg/kg; 5 mg/kg). Serum biochemical indices were detected using commercial kits. H&E and masson staining were used to observe hepatic tissue damage and collagen deposition in hepatocytes. The metabolism of bile acid-related substances was detected via HPLC-MS/MS by 5-(diisopropylamino) amylamine (DIAAA) derivative method. Hepatocyte injury, cholestasis, and inflammation were detected at the mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, respectively.

Results: Q7R can decrease the level of CYP7A1, and increase FXR, CYP27A1 so then improving abnormal bile acid secretion. Furthermore, Q7R can also ameliorating inflammation by reduce TNF-α, IL-1β, PTGS1, PTGS2, NCOA2, NF-κB level. Therefore, Q7R had an effective therapeutic effect on ANIT-induced cholestatic hepatitis, improving abnormal bile acid secretion, and inhibiting inflammatory responses.

Conclusion: The results demonstrated that Q7R treat cholestatic hepatitis by regulating bile acid secretion and alleviating inflammation.
Effects of Kalimeris indica (L.) Sch Bip on colitis-associated colorectal cancer
Authors: Wang Mo-Fei , Li Hao , Cui Jian , Chen Yu-Han , Cui Yong
Published: January 2023

Kalimeris indica (L.) Sch Bip (K. indica) is a plant of the genus Kalimeris in Asteraceae, and its whole herb can be used as medicine for the treatment of intestinal inflammatory diseases. But the mechanism is not clear. Therefore, this study was designed to explore the mechanism of K. indica (KI) in colitis-associated colorectal cancer. The expression levels of miR-31-5p and proinflammatory factors were detected using THP-1 and Caco2 cells in vitro. KI could rescue the upregulation of miR-31-5p induced by IL-6 and TNF-α in Caco2 and THP-1 cells. In LPS-stimulated PMA-differentiated THP-1 cells, KI restored miR-31-5p expression by downregulating the expression of IL-6 and TNF-α. C57BL/6 mice were used to construct CAC model through the induction of azoxymethane/dextran sulfate sodium. The successfully established CAC mice were treated with water extract of KI through intragastric administration for 5 weeks. The result showed that KI could significantly reduce the atypical hyperplasia in colon tissue, and inhibit the expression of proinflammatory factors such as IL-6, TNF, IL-11, IL-7, etc. At the same time, KI could restore the level of miR-31-5p in mice, and therefore the downstream LATS2 to inhibit the development of CAC. These above results indicate that KI is a potentially effective herb medicine to prevent CAC.
Eda controls the size of the enamel knot during incisor development
Authors: Horakova Lucie , Dalecka Linda , Zahradnicek Oldrich , Lochovska Katerina , Lesot Herve , Peterkova Renata , Tucker Abigail S. , Hovorakova Maria
Published: January 2023

Ectodysplasin (Eda) plays important roles in both shaping the developing tooth and establishing the number of teeth within the tooth row. Sonic hedgehog (Shh) has been shown to act downstream of Eda and is involved in the initiation of tooth development. Eda−/− mice possess hypoplastic and hypomineralized incisors and show changes in tooth number in the molar region. In the present study we used 3D reconstruction combined with expression analysis, cell lineage tracing experiments, and western blot analysis in order to investigate the formation of the incisor germs in Eda−/− mice. We show that a lack of functional Eda protein during early stages of incisor tooth germ development had minimal impact on development of the early expression of Shh in the incisor, a region proposed to mark formation of a rudimental incisor placode and act as an initiating signalling centre. In contrast, deficiency of Eda protein had a later impact on expression of Shh in the primary enamel knot of the functional tooth. Eda−/− mice had a smaller region where Shh was expressed, and a reduced contribution from Shh descendant cells. The reduction in the enamel knot led to the formation of an abnormal enamel organ creating a hypoplastic functional incisor. Eda therefore appears to influence the spatial formation of the successional signalling centres during odontogenesis.
Purinoreceptors and ectonucleotidases control ATP-induced calcium waveforms and calcium-dependent responses in microglia: Roles of P2 receptors and CD39 in ATP-stimulated microglia
Authors: Chun Byeong J. , Aryal Surya P. , Varughese Peter , Sun Bin , Bruno Joshua A. , Richards Chris I. , Bachstetter Adam D. , Kekenes-Huskey Peter M.
Published: January 2023

Adenosine triphosphate (ATP) and its metabolites drive microglia migration and cytokine production by activating P2X- and P2Y- class purinergic receptors. Purinergic receptor activation gives rise to diverse intracellular calcium (Ca2+ signals, or waveforms, that differ in amplitude, duration, and frequency. Whether and how these characteristics of diverse waveforms influence microglia function is not well-established. We developed a computational model trained with data from published primary murine microglia studies. We simulate how purinoreceptors influence Ca2+ signaling and migration, as well as, how purinoreceptor expression modifies these processes. Our simulation confirmed that P2 receptors encode the amplitude and duration of the ATP-induced Ca2+ waveforms. Our simulations also implicate CD39, an ectonucleotidase that rapidly degrades ATP, as a regulator of purinergic receptor-induced Ca2+ responses. Namely, it was necessary to account for CD39 metabolism of ATP to align the model’s predicted purinoreceptor responses with published experimental data. In addition, our modeling results indicate that small Ca2+ transients accompany migration, while large and sustained transients are needed for cytokine responses. Lastly, as a proof-of-principal, we predict Ca2+ transients and cell membrane displacements in a BV2 microglia cell line using published P2 receptor mRNA data to illustrate how our computer model may be extrapolated to other microglia subtypes. These findings provide important insights into how differences in purinergic receptor expression influence microglial responses to ATP.
The return from underperformance to sustainable world-class level: A case study of a male cross-country skier
Authors: Talsnes Rune Kjøsen , Moxnes Einar Flaktveit , Nystad Trond , Sandbakk Øyvind
Published: January 2023

Purpose: To determine the main factors associated with unexpected underperformance and prospectively describe the holistic process of returning to sustainable world-class level in a male cross-country skier.

Methods: Longitudinal training data was retrospectively analyzed across nine seasons (2012-2013 to 2020-2021), and categorized into training forms (endurance, strength, and speed), intensities [low- (LIT), moderate- (MIT), and high-intensity training (HIT)], and modes (specific and non-specific). Performance data was obtained from the International Ski and Snowboard Federation. Following two seasons of unexpected underperformance (2019-2020 and 2020-2021), the participant was prospectively followed in the process of returning to sustainable world-class level (2021-2022). Day-to-day training data and physiological tests were analyzed, and interviews with the participant and the head coach conducted.

Results: Longitudinal training data from 2012-2013 to 2018-2019 demonstrated a non-linear 30% increase in total training volume (from 772 to 1,002 h), mainly caused by increased volume of ski-specific endurance training without changes in intensity distribution. Coincidingly, the participant gradually reached a world-class performance level. After two seasons of unexpected underperformance with relatively similar training volumes and intensity distributions as in the preceding seasons, the possible contributing factors were identified: lack of training periodization, limited monitoring and intensity control, particularly in connection with a “extreme” regime of training with low carbohydrate availability and days including two MIT sessions, as well as lack of systematic technique training and follow-up by coaches on a daily basis. Consequently, the return to world-class level included the introduction of a clear micro-cycle periodization, more systematic physiological monitoring and testing, more accurate intensity control, increased carbohydrate intake during and between sessions, as well as increased emphasize on technique training and an assistant coach present during day-to-day training.

Conclusion: These longitudinal data describe the main factors leading to unexpected underperformance, in addition to providing unique insights into the corresponding process of returning to sustainable world-class level in a male cross-country skier. The holistic approach described in this case study may serve as a theoretical framework for future studies and practical work with underperforming endurance athletes.
Pedigree-based analysis in multi-parental diploid rose populations reveals QTLs for cercospora leaf spot disease resistance
Authors: Rawandoozi Zena J. , Young Ellen L. , Kang Stella , Yan Muqing , Noyan Seza , Fu Qiuyi , Hochhaus Tessa , Rawandoozi Maad Y. , Klein Patricia E. , Byrne David H. , Riera-Lizarazu Oscar
Published: January 2023

Cercospora leaf spot (CLS) (Cercospora rosicola) is a major fungal disease of roses (Rosa sp.) in the southeastern U.S. Developing CLS-resistant cultivars offers a potential solution to reduce pesticide use. Yet, no work has been performed on CLS resistance. This study aimed to identify QTLs and to characterize alleles for resistance to CLS. The study used pedigree-based QTL analysis to dissect the genetic basis of CLS resistance using two multi-parental diploid rose populations (TX2WOB and TX2WSE) evaluated across five years in two Texas locations. A total 38 QTLs were identified across both populations and distributed over all linkage groups. Three QTLs on LG3, LG4, and LG6 were consistently mapped over multiple environments. The LG3 QTL was mapped in a region between 18.9 and 27.8 Mbp on the Rosa chinensis genome assembly. This QTL explained 13 to 25% of phenotypic variance. The LG4 QTL detected in the TX2WOB population spanned a 35.2 to 39.7 Mbp region with phenotypic variance explained (PVE) up to 48%. The LG6 QTL detected in the TX2WSE population was localized to 17.9 to 33.6 Mbp interval with PVE up to 36%. Also, this study found multiple degrees of favorable allele effects (q-allele) associated with decreasing CLS at major loci. Ancestors ‘OB’, ‘Violette’, and PP-M4-4 were sources of resistance q-alleles. These results will aid breeders in parental selection to develop CLS-resistant rose cultivars. Ultimately, high throughput DNA tests that target major loci for CLS could be developed for routine use in a DNA-informed breeding program.
Genome-Wide Identification of 14-3-3 gene family reveals their diverse responses to abiotic stress by interacting with StABI5 in Potato (Solanum tuberosum L.)
Authors: Wang Qianqian , Yan Chongchong , Fu Yuying , Wang Yu , Jiang Pengfei , Ding Yinyuan , Liao Huajun
Published: January 2023

The 14-3-3 genes are widely present in plants and participate in a wide range of cellular and physiological processes. In the current study, twelve 14-3-3s were identified from potato genome. According to phylogenetic evolutionary analysis, potato 14-3-3s were divided into ϵ and non-ϵ groups. Conserved motif and gene structure analysis displayed a distinct class-specific divergence between the ϵ group and non-ϵ group. Multiple sequence alignments and three-dimensional structure analysis of 14-3-3 proteins indicated all the members contained nine conservative antiparallel α-helices. The majority of 14-3-3s had transcript accumulation in each detected potato tissue, implying their regulatory roles across all stages of potato growth and development. Numerous cis-acting elements related to plant hormones and abiotic stress response were identified in the promoter region of potato 14-3-3s, and the transcription levels of these genes fluctuated to different degrees under exogenous ABA, salt and drought stress, indicating that potato 14-3-3s may be involved in different hormone signaling pathways and abiotic stress responses. In addition, eight potato 14-3-3s were shown to interact with StABI5, which further demonstrated that potato 14-3-3s were involved in the ABA-dependent signaling pathway. This study provides a reference for the identification of the 14-3-3 gene family in other plants, and provides important clues for cloning potential candidates in response to abiotic stresses in potato.
Learning to detect sexism: An evaluation of the effects of a brief video-based intervention using ROC analysis
Authors: König Regina , Heine Angela
Published: January 2023

Empirical evidence for the effectiveness of interventions teaching lay people how to recognize sexism is scarce. The purpose of the present study was, thus, twofold: The first aim was to evaluate a brief intervention using a lecture-like educational video on how to recognize subtle sexism. The second aim was to demonstrate the usefulness of signal detection theory (SDT) for evaluating the participants’ ability to discriminate between subtle sexist and non-sexist statements. Participants (N = 73) were randomly assigned to a subtle sexism treatment group (SSG), an overt sexism treatment group (OSG), or a control group (CG). After the intervention phase, the participants were asked to rate statements in vignettes with respect to how sexist they perceived them to be. The participants in the SSG were significantly better in correctly identifying subtle sexist content than the participants in the OSG and CG. However, they were not more accurate overall. This was because they claimed sexism more often, irrespective of whether it was present or not. We conclude that while our intervention increased participants’ sensitivity in detecting sexist content, it did so at the cost of specificity. Our results make clear that practitioners teaching people how to recognize sexism should control intervention outcomes for unintended effects of biased decision criteria, given that erroneous allegations of sexism could have grave consequences. To this effect, the value of SDT, which allows for fine-grained and, consequently, more accurate insight than standard approaches to the analysis of intervention effects, was demonstrated.
The nonlinear effect of time pressure on innovation performance: New insights from a meta-analysis and an empirical study
Authors: Song Haojie , Gao Renjing , Zhang Qiang , Li Yongxin
Published: January 2023

As competition grows, when employees are required to accelerate innovation, they also face increasing time pressure. In order to shed light on how time pressure affects employees’ innovation performance, two studies were conducted to examine the effect of time pressure on innovation performance. In Study 1, based on 50 effect sizes from 50 independent samples (N = 15,751) in 40 articles, a meta-analysis was conducted to examine the J-shaped effect of time pressure on innovation performance. In Study 2, based on a two-wave survey of 645 employees, the mechanism underlying the J-shaped effect of time pressure on innovation performance was explored. Results from Study 1 revealed that time pressure had a J-shaped effect on innovation performance, such that high levels of time pressure had a more positive effect on innovation performance. Results from Study 2 showed that learning behavior significantly mediated the J-shaped effect of time pressure on innovation performance, and that supervisor developmental feedback moderated the intermediary process. These results deepen the understanding of the relationship between time pressure and innovation performance, and provide practical advice on how to manage innovation performance under time pressure.
How and when leader narcissism links to employees’ objective career success: The roles of ingratiation and careerist orientation
Authors: Ding Zhihui , Liu Mingwei , Quan Lei , Wang Huaqiang , Zhang Pengcheng , Liu Wenxing
Published: January 2023

Previous researches have emphasized the value of leader narcissism on employees’ career success, whereas we still know little about how and when this relationship will materialize. By integrating dramaturgical theory and leader narcissism literatures, we propose a theoretical model to explain the mechanism and boundary of leader narcissism in promoting employees’ objective career success (e.g., salary increases and promotions). To test our hypotheses, we carried out a multi-wave research design and collected data from 299 employees in Chinese manufacturing firms. The results of multiple regression analysis showed that leader narcissism motivates employees’ ingratiation, which in turn facilitates employees’ objective career success, especially when those employees are high in careerist orientation. Theoretical and practical implications of the findings are discussed.