bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asc-2P Sustains Mitochondrial Glycolysis and Promotes Neural Progenitor Cell Activation via Metabotropic Glutamate Receptor 7
Authors: Zhao Jian , Wang Ying , Fang Jing , Hu Ganlu , Tang Kailin , Zeng Xianglu , Wang Changzheng , Yu Yongcun , Zeng Tao , Cao Zhiwei , Fan Guoping 
Published: June 2024

Abstract

Human neural progenitor cells (hNPCs) have been reported to exist in various regions of the central nervous system (CNS) throughout the lifespan and to maintain homeostasis of the CNS. The endogenous NPC pools as well as their function decline during aging, neurodegeneration, or brain damage; therefore, supplementation with hNPCs or enhancement of the potency of endogenous NPCs could lead to potential treatments for these diseases. Here, we showed that 2-phospho-L-ascorbic acid (Asc-2P) promoted hNPC proliferation and differentiation by maintaining mitochondrial glycolysis under growth factor-lacking conditions. Upregulation of metabotropic glutamate receptor 7 (mGluR7) expression by Asc-2P treatment and retention of mGluR7 on the plasma membrane by the specific group III mGluR antagonist alpha-methylserine-O-phosphate (MSOP) promoted the formation of fibroblast growth factor receptor 1 (FGFR1) and mGluR7 complex on the cell membrane, thereby enhanced the phosphorylation and activation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), maintained mitochondrial glycolysis, thus enhanced hNPC proliferation and differentiation in vitro and in vivo. Furthermore, Asc-2P treatment alleviated pathogenesis and related cognitive decline in an Alzheimer’s disease mouse model. Taken together, our findings indicated that modulation of mGluR7 by Asc-2P and/or its antagonists could be promising pharmaceutical and therapeutic options against neurodegeneration and related diseases.
Mental health literacy and the prevalence of depression among college students: a cross- sectional study in Iran
Authors: Panahi Rahman , Moghadam Mohaddeseh Ramezani , Pakdaman Fatemeh , Amjadian Mohiadin 
Published: June 2024

Abstract

Background and objectives:
Considering the high prevalence of depression among students and the fact that the factors that cause depression among students play a significant role in its prevention and control, and also considering the important role of mental health literacy in depression incidence, this study aimed at determining the relationship between mental health literacy and the prevalence of depression among students.
method
In a descriptive-analytical cross-sectional study, 270 students of Qaenat Faculty of Medical Sciences, Iran, were selected to participate in the study in the second semester of 2023–2024 through simple random sampling. The data were collected through demographic and background characteristics, depression (Beck Questionnaire), and mental health literacy questionnaires (MHLQ). The data were analyzed using SPSS 23 software and descriptive statistics and regression.
Results
Mental health literacy was at an average level in the students. Also, the results showed that 67.7% (180 people) were free of depression and the prevalence of mild, moderate, and severe depression was 15% (40 people), 9.8% (26 people), and 7.5% (20 people) respectively among them. The results showed that mental health literacy, having a history of depression, and doing physical activity were effective factors in the prevalence of depression.
Conclusion
The prevalence of depression was higher among students with insufficient levels of mental health literacy, having a history of depression, and those with insufficient physical activity. Therefore, it is suggested to pay more attention to such students in designing educational programs to prevent depression among them.
PD-1 antibody–bound progenitor-exhausted CD8+ T cells in lymph nodes boost PD-1–blockade anti-tumor immunity in gastrointestinal cancer
Authors: Saito Takuro , Nose Yohei , Yasumizu Yoshiaki , Nakamura Yamami , Momose Kota , Yamashita Kotaro , Tanaka Koji , Yamamoto Kazuyoshi , Makino Tomoki , Takahashi Tsuyoshi , Kurokawa Yukinori , Sato Eichi , Ohkura Naganari , Sakaguchi Shimon , Wada Hisashi , Eguchi Hidetoshi , Doki Yuichiro 
Published: June 2024

Abstract

While progenitor-exhausted T cells (Tpex) expressing TCF1 and PD-1 are crucial for the therapeutic effect of immune checkpoint inhibitors (ICIs; therapeutic anti–PD-1 antibodies), the dynamics of ICI-bound Tpex are not fully understood. In this study, we investigated ICI-bound T cells in detail using combined sequencing analysis at the single cell level. By analyzing samples from gastrointestinal cancer patients with or without ICI treatment, we found that Tpex were enriched in proximal lymph nodes (LNs) and proliferated at a high rate after ICI treatment. Importantly, ICI high–bound Tpex in LNs shared T-cell receptor clonotypes with intratumoral exhausted CD8+ T cells (Tex), suggesting their migration to tumor sites after ICI treatment. These findings indicate that ICIs initially target PD-1+CD8+ Tpex in LNs, prompting their proliferation. Subsequently, these cells migrate to tumors and differentiate into Tex, thereby exerting anti-tumor immunity.
V-notch crack initiation by the coupled criterion considering plasticity
Authors: Doitrand Aurélien , Leguillon Dominique 
Published: June 2024

Abstract

An extension of the coupled criterion (CC) of finite fracture mechanics is proposed in order to assess brittle crack initiation considering plasticity. The main change compared to the classical linear elastic approach consists in considering the plastic strain energy variation due to crack initiation. The proposed approach enables assessing quasi-brittle failure at singularities or stress concentrators in materials exhibiting plastic deformation. It is illustrated on V-notch steel specimens subjected to bending. If plastic deformation is disregarded, the CC underestimates the failure force compared to those measured experimentally. Considering plasticity yields a better representation of failure force variation as a function of the V-notch angle.
Comparative Analysis of Sexual Function and Psychological Health in Infertile Patients with Different Ovarian Dysfunctions
Authors: Dong Meng , Li Yiyang , Li Yining , Wang Yixian , Tan Jichun 
Published: June 2024

Abstract

Objective
This study aims to evaluate and compare sexual function and psychological health among infertile patients with different ovarian dysfunctions, specifically polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), and women with normal ovarian function, to understand the extent of sexual dysfunction associated with these conditions.
Methods
We conducted a cross-sectional analysis involving 340 women, categorized into three groups: PCOS, POI, and normal ovarian function (Control). Sexual function was quantitatively assessed using the Female Sexual Function Index (FSFI), which measures six dimensions of sexual function: desire, arousal, lubrication, orgasm, satisfaction, and pain. Analysis of variance (ANOVA) was employed to compare FSFI scores across the groups, followed by post-hoc tests to identify significant differences between each pair of groups.
Results
The mean FSFI scores were significantly lower in the POI and PCOS groups compared to the Control group (p < 0.05). Women with POI and PCOS exhibited higher incidences of anxiety and depression. Significant differences were observed in arousal ability, vaginal lubricity, and satisfaction scores among the groups, with the Control group generally scoring higher. The incidence of lubrication disorder was highest in the PCOS group (p < 0.05). Multivariable-adjusted analyses identified longer infertility duration and higher Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) scores as significant predictors of sexual dysfunction.
Conclusion
This study highlights the significant impact of reproductive health conditions such as POI and PCOS on sexual and psychological health. The findings underscore the need for integrated care approaches that address both physical and mental health aspects in women with these conditions. By enhancing our understanding of these relationships, we can improve the quality of life for women affected by POI and PCOS. Clinicians should consider both the physiological and psychological dimensions in their treatment plans to ensure comprehensive care that addresses the full spectrum of patient needs.
Evaluation of Techno-Economic Design and Implementation of Solar-Wind Hybrid Microgrid System for a Small Community
Authors: Moomin Ahmed Shabbir Ibrahim , Yousif Muhammad , Kazmi Syed Ali Abbas 
Published: June 2024

Abstract

The energy demand and consumption requirements in Pakistan are facing significant challenges due to the recent gradual increase in population; intensifies the critical energy issues confronting the country. Additionally, energy consumption per capita in Pakistan has been steadily rising and is expected to continue increasing in the future. Buyers as a result need to buy such energy in order to produce other features too. The conventional energy globally is the primary energy usage for transforming these machineries function into different kinds of infrastructure methods instead of handmade designs which takes a lot of time duration. Crude oil and petroleum liquids have been the main principal to start these conventional generators and transportation automobiles into production. However, the carbon dioxide gas and other forms from these conventional energy generators has been increasing efficiency which is the main concern for energy generation in Pakistan and the rest of the world. Hence, Renewable Energy Sources (RES) such as solar photovoltaic (PV) and wind farming have been contributing a significant percentage of their daily energy needs. However, these energy has not had such standard rather than conventional energy such as fossil fuels regular. Thus, a microgrid hybrid containing Solar-Wind renewable and conventional generator are in need to produce sustainable Electricity in a small community. On one hand, solar-wind combine can produce energy with specify timing. On the other hand, there are expensive cost. This factor can have prominent issue such as frequent electricity blackouts and imbalanced energy provision across different regions. Therefore, the microgrid hybrid systems can evaluate these incorporating solar PV and wind power renewable energy sources and fossil fuel generators as an optimum feasibility cost. In addition, this optimum feasibility can provide predictable forecasts of these energy production in the future based on economic factors in the small community in Islamabad. This assessment can have HOMER software simulation which faced by challenges in order to explore sustainable solutions through the integration of renewable/conventional energy sources into the existing energy infrastructure.
Neuroinflammation Induces Myelin Damage by Inhibiting Gapdh of Oligodendrocytes in the Hippocampus
Authors: Li Zhongjia , Fu Huiqun , Liu Fangyan , Wu Yan , Wang Tianlong 
Published: June 2024

Abstract

Background Myelin damage has been detected in central nervous system disease accompanied by neuroinflammation and cognitive dysfunction. However, the mechanism of myelin damage associated with neuroinflammation in the aged brain has not been clarified.
Methods We explored the mechanism of myelin damage induced by neuroinflammation in the hippocampus of aged rats through both in vivo and in vitro approaches from the perspective of energy synthesis in oligodendrocytes. We developed a neuroinflammation model by single intraperitoneal injection of LPS and determined cognitive dysfunction and myelin damage in the hippocampus. Single-cell RNA sequencing was employed to exam gene expression changes related to neuroinflammation in oligodendrocytes of the hippocampus and identified Gapdh as a significantly downregulated gene. In vitro, OLN-93 cells were induced to differentiate into mature oligodendrocytes and treated with TNF-α. The effect of Gapdh on TNF-α-induced energy synthesis suppression and MBP reduction in mature oligodendrocytes, and mitochondrial damage, was assessed through Gapdhoverexpression.
Results In aged rats, spatial learning and memory impairments were triggered by LPS, alongside neuroinflammatory responses, as evidenced by elevated levels of TNF-α and IL-1β in the hippocampus. Additionally, there was a reduction in myelin protein expression and disorganization within the myelin structure, which was notably thinner in the hippocampus of the LPS-treated group. The proportion of mature oligodendrocyte clusters related to myelination and remyelination decreased, and the expression level of Gapdh significantly decreased in each oligodendrocyte cluster of the LPS group. In vitro, TNF-α induced mature oligodendrocyte apoptosis and reduced GAPDH and MBP expression. The glycolysis and oxidative phosphorylation ability of cells decreased, accompanied by decreased lactate concentration and ATP content. Mitochondrial oxidative stress and damage were also detected. Overexpression of Gapdh improved damage induced by TNF-α.
Conclusions Neuroinflammation impairs the energy synthesis functions of glycolysis and oxidative phosphorylation, and mitochondria in mature oligodendrocytes, by inhibiting Gapdh expression. Lack of energy support decreases myelin basic protein levels, subsequently resulting in myelin deterioration, which may lead to cognitive dysfunction.
Integrated analysis of physiological and metabolic data uncovers essential dynamic mechanisms involved in the maturation of cigar tobacco leaves
Authors: Liu Haiying , Chi Xinwen , Yang Jinpeng , Ding Guangda , Xu Fangsen , Yang Chunlei , Wang Sheliang 
Published: June 2024

Abstract

The timing of maturity significantly impacts the quality of cigar tobacco leaves, with both premature and delayed maturation leading to quality degradation. Despite the known association between maturity and physiological metabolic activities, there is a paucity of concrete evidence detailing the physiological behavior of cigar leaves harvested at varying times. This research involved a comprehensive physiological and metabolomic examination of the cigar tobacco variety CX-014, cultivated in Danjiangkou City, Hubei Province. The study focused on leaves picked at 35 (T1), 42 (T2), 49 (T3), and 56 (T4) days following the removal of the apical inflorescence. As the harvest period progressed, the leaves’ hue transitioned from green to yellow, displaying white mature spots. Between T1 and T2, there was an uptick in pigment indices (like chlorophyll a and b) and photosynthetic traits (such as stomatal conductance), which then diminished in the T3 and T4 samples. Optimal levels of sugar-to-nicotine and potassium-to-chlorine ratios—key indicators of smoking quality and tobacco combustibility—were observed at T3, suggesting a more balanced chemical composition in the leaves harvested at this stage. Metabolomic analysis revealed 2,153 distinct metabolites, with the most significant changes occurring between T2 and T3, highlighting critical physiological transformations during this interval. Pathway enrichment analysis via KEGG pinpointed notable shifts in amino acid synthesis pathways, particularly those involving tryptophan, alanine, and aspartate. Tryptophan metabolism and zeatin biosynthesis were substantially altered, with compounds like indolepyruvic acid, N-formylpurine nucleotide, isopentenyladenine nucleotide, and dihydrozeatin showing marked reductions at T3. This study also explored how the timing of lower leaf harvest influences the physiological processes of middle leaves, finding that a plethora of metabolites associated with the breakdown of arachidonic acid—a primitive metazoan signaler implicated in plant stress and defense networks—were abundant in T3 leaves when lower leaves were harvested 43 to 38 days prior. These findings suggest that the harvest timing of lower leaves may sway the maturation physiology and environmental adaptability of middle leaves. Overall, this investigation sheds light on the intricate physiological dynamics of cigar leaves throughout maturation and pinpoints crucial metabolites that signify pivotal metabolic pathways.
Determining the Challenges and Satisfaction of faculty with the use of Electronic Test Management System at Riphah International University
Authors: Iqbal Sana , Sabqat Mashaal , Ain Noor ul , Khan Rehan Ahmed , Kazmi Fatima Ali , Ashraf Javed 
Published: June 2024

Abstract

Aim: The study aimed to identify challenges faced by faculty in the item banking process at Riphah International University and to assess faculty satisfaction with Electronic Test Management System (ETMS)—Schoolhouse testing software.
Methodology: The study used quasi-experimental design and data was collected in two phases: pre-intervention and post-intervention. A purposive sampling was used in order to select faculty members who were involved in item banking practices at the medical college of Riphah International University (RIU). The questionnaires with 5-point Likert scales were used to measure challenges associated with current item banking, and a faculty satisfaction survey was conducted using Schoolhouse testing software. Both the questionnaires were validated for content, response process validity, and reliability.
Result: The faculty of Riphah International University encountered slight challenges in item security (71%), alignment of assessment items and high-quality assessments (42%,56%), time intensiveness (58%), and sorting questions according to different categories (60%). The adoption of ETMS Schoolhouse addressed these challenges, leading to increased satisfaction among faculty members. The faculty expressed satisfaction with user-friendliness (35%), user interface and the process of storing (29%) and retrieving test items (33%) in the software. However, aspects such as the improvement in the search function, and security of test items, displayed comparatively lower satisfaction levels, which was 22% each.
Conclusion: The study found that item banking at Riphah International University poses challenges for faculty. Schoolhouse testing software can help with these challenges, making the process more convenient and efficient. However, further research is needed to explore the impact of item banking software on faculty satisfaction.
Qingxiong Ointment and its Active Ingredient, Shikonin Treat Psoriasis
through HIF-1 Signaling Pathway
Authors: Zhang Bin , Yan Ge , Li Fei , Tang Ye , Xu Guangyao , Zhang Yanan , Ze Kan 
Published: June 2024

Background:
Psoriasis is a common chronic inflammatory skin disorder. Qingxiong ointment (QX)
is a natural medicinal combination frequently employed in clinical treatment of psoriasis. However, the active
ingredients of QX and its precise mechanisms of improving psoriasis remain unclear. This study elucidated the
effects of QX on an Imiquimod (IMQ)-induced mouse model of psoriasis while also exploring the regulation
of the active ingredient of QX, shikonin, on the HIF-1 signaling pathway in HaCaT cells.

Methods:
A mouse model of psoriasis was established through topical application of IMQ, and the local therapeutic
effect of QX was evaluated using dorsal skin tissue with mouse psoriatic lesion and Psoriasis Area
Severity Index (PASI) scores, hematoxylin-eosin (HE) staining, and immunohistochemical staining. Elisa and
qPCR were employed to identify changes in the expression of inflammation-related factors in the mouse dorsal
skin. Immunofluorescence was used to assess changes in the expression of T cell subsets before and after
treatment with various doses of QX. HPLC was used to analyze the content of shikonin, and network pharmacology
was employed to analyze the main targets of shikonin. Immunofluorescence was used to identify the effects
of shikonin on the HIF-1 signaling pathway in IL6-induced psoriasis HaCaT cells. Finally, qPCR was
used to identify the differential expression of the HIF-1 signaling pathway in skin tissues.

Results:
QX significantly reduces PASI scores on the backs of IMQ-induced psoriasis mice. HE staining reveals
alleviated epidermal thickness in the QX group. Immunohistochemical analysis shows a significant reduction
in ICAM, KI67, and IL17 expression levels in the QX group. Immunofluorescence results indicate
that QX can notably decrease the proportions of CD4+ T cells, γδ T cells, and CD8+ T cells while increasing
the proportion of Treg cells. Network pharmacology analysis demonstrates that the main targets of shikonin
are concentrated in the HIF-1 signaling pathway. Molecular docking results show favorable binding affinity between
shikonin and key genes of the HIF-1 signaling pathway. Immunofluorescence results reveal that
shikonin significantly reduces p-STAT3, SLC2A1, HIF1α, and NOS2 expression levels. qPCR results show
significant downregulation of the HIF-1 signaling pathway at cellular and tissue levels.

Conclusion:
Our study revealed that QX can significantly reduce the dorsal inflammatory response in the
IMQ-induced psoriasis mouse model. Furthermore, we discovered that its main component, shikonin, exerts
its therapeutic effect by diminishing the HIF-1 signaling pathway in HaCaT cells.
Protective Effect and Related Mechanism of Modified Danggui Buxue
Decoction on Retinal Oxidative Damage in Mice based on Network
Pharmacology
Authors: Hu Xiangka , Liu Feifei , Yang He , Qi Mushuang , Ren Ying , Zhu Wanjun , Dai Chunmei 
Published: June 2024

Introduction:
Age-related macular degeneration (AMD) is one of the common diseases that cause
vision loss in the elderly, and oxidative stress has been considered a major pathogenic factor for AMD. Modified
Danggui Buxue Decoction (RRP) has a good therapeutic effect on non-proliferatic diabetic retinopathy
and can improve the clinical symptoms of patients. Aim: This study aimed to predict and verify the protective
effect and mechanism of RRP on retinal oxidative damage in mice based on network pharmacology and animal
experiments.

Methods:
The key ingredients and core targets of RRP protecting retinal oxidative damage were obtained by
Network pharmacology analysis. A mouse retinal oxidative damage model induced by tail vein injection of
1% NaIO3 solution (25 mg/kg) was treated with RRP for 4 weeks and used to verify the pharmacodynamics
and related mechanism.

Aim:
This study aimed to predict and verify the protective effect and mechanism of RRP on retinal oxidative
damage in mice based on network pharmacology and animal experiments

Results:
A total of 15 key active components included in RRP interacted with 57 core targets related to retinal
oxidative damage (such as AKT1, NFE2L2, HMOX1), mainly involved in the AGE-RAGE signaling pathway
in diabetic complications, PI3K-AKT signaling pathway and so on. Further studies in vivo found that RRP improved
the retinal oxidative damage, increased the content of SOD and GSH, decreased the content of MDA in
mouse serum, promoted the expression of p-PI3K, p-AKT, Nrf2, HO-1 and NQO1 proteins in the mouse retina,
and inhibited the expression of Nrf2 in the cytoplasm.

Conclusion:
This study revealed that RRP had a protective effect on oxidative damage of the retina in mice,
and might exert anti-oxidative effect by activating the PI3K/Akt/Nrf2 signal pathway. This study provided scientific
data for the further development of hospital preparations of RRP, and a good theoretical basis for the
clinical application of RRP.