bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulated microRNA-125b-5p in patients with asthma-COPD overlap mediates oxidative stress and late apoptosis via targeting IL6R/TRIAP1 signaling
Authors: Chang Yu-Ping , Tsai Yi-Hsuan , Chen Yu-Mu , Huang Kuo-Tung , Lee Chiu-Ping , Hsu Po-Yuan , Chen Hung-Chen , Lin Meng-Chih , Chen Yung-Che 
Published: February 2024

Abstract
Background
Among patients with chronic obstructive pulmonary disease (COPD), some have features of both asthma and COPD—a condition categorized as asthma-COPD overlap (ACO). Our aim was to determine whether asthma- or COPD-related microRNAs (miRNAs) play a role in the pathogenesis of ACO.

Methods
A total of 22 healthy subjects and 27 patients with ACO were enrolled. We selected 6 miRNAs that were found to correlate with COPD and asthma. The expression of miRNAs and target genes was analyzed using quantitative reverse-transcriptase polymerase chain reaction. Cell apoptosis and intracellular reactive oxygen species production were evaluated using flow cytometry. In vitro human monocytic THP-1 cells and primary normal human bronchial epithelial (NHBE) cells under stimuli with cigarette smoke extract (CSE) or ovalbumin (OVA) allergen or both were used to verify the clinical findings.

Results
We identified the upregulation of miR-125b-5p in patients with ACO and in THP-1 cells stimulated with CSE plus OVA allergen. We selected 16 genes related to the miR-125b-5p pathway and found that IL6R and TRIAP1 were both downregulated in patients with ACO and in THP-1 cells stimulated with CSE plus OVA. The percentage of late apoptotic cells increased in the THP-1 cell culture model when stimulated with CSE plus OVA, and the effect was reversed by transfection with miR-125b-5p small interfering RNA (siRNA). The percentage of reactive oxygen species-producing cells increased in the NHBE cell culture model when stimulated with CSE plus OVA, and the effect was reversed by transfection with miR-125b-5p siRNA. In NHBE cells, siRNA transfection reversed the upregulation of STAT3 under CSE+OVA stimulation.

Conclusions
Our study revealed that upregulation of miR-125b-5p in patients with ACO mediated late apoptosis in THP-1 cells and oxidative stress in NHBE cells via targeting IL6R and TRIAP1. STAT3 expression was also regulated by miR-125b-5p.
Gestational diabetes mellitus and risk of long-term all-cause and cardiac mortality: a prospective cohort study
Authors: Ying Qian , Xu Yao , Zhang Ziyi , Cai Luyi , Zhao Yan , Jin Liping 
Published: February 2024

Background
To investigate the association between gestational diabetes mellitus (GDM) without subsequent overt diabetes and long-term all-cause and cardiac mortality.

Methods
This prospective cohort study included 10,327 women (weighted population: 132,332,187) with a pregnancy history from the National Health and Nutrition Examination Survey (2007 to 2018). Participants were divided into three groups (GDM alone, overt diabetes, and no diabetes). Mortality data was linked from the National Death Index up to December 31, 2019. Multivariable Cox regression analysis was performed to examine the association between GDM alone and overt diabetes with all-cause mortality and cardiac mortality. Data analysis was performed from October 2022 to April 2023.

Results
Among the participants, 510 (weighted 5.3%) had GDM alone and 1862 (weighted 14.1%) had overt diabetes. Over a median follow-up period of 6.7 years (69,063 person-years), there were 758 deaths. The GDM group did not show an increased risk of all-cause mortality (hazard ratio [HR] 0.67; 95% CI, 0.25–1.84), while the overt diabetes group had a significantly higher risk (HR 1.95; 95% CI, 1.62–2.35). Similarly, the GDM group did not exhibit an elevated risk of cardiac mortality (HR 1.48; 95% CI, 0.50–4.39), whereas the overt diabetes group had a significantly higher risk (HR 2.37; 95% CI, 1.69–3.32). Furthermore, sensitivity analysis focusing on women aged 50 or above showed that the HR of GDM history for all-cause mortality was 1.14 (95% CI, 0.33–3.95) and the HR for cardiac mortality was 1.74 (95% CI, 0.49–6.20).

Conclusions
GDM alone was not associated with an increased risk of all-cause and cardiac mortality, while overt diabetes was significantly associated with both types of mortality.
Reprogramming of lipid metabolism in the tumor microenvironment: a strategy for tumor immunotherapy
Authors: Wu Yuting , Pu Xi , Wang Xu , Xu Min 
Published: February 2024

AbstractLipid metabolism in cancer cells has garnered increasing attention in recent decades. Cancer cells thrive in hypoxic conditions, nutrient deficiency, and oxidative stress and cannot be separated from alterations in lipid metabolism. Therefore, cancer cells exhibit increased lipid metabolism, lipid uptake, lipogenesis and storage to adapt to a progressively challenging environment, which contribute to their rapid growth. Lipids aid cancer cell activation. Cancer cells absorb lipids with the help of transporter and translocase proteins to obtain energy. Abnormal levels of a series of lipid synthases contribute to the over-accumulation of lipids in the tumor microenvironment (TME). Lipid reprogramming plays an essential role in the TME. Lipids are closely linked to several immune cells and their phenotypic transformation. The reprogramming of tumor lipid metabolism further promotes immunosuppression, which leads to immune escape. This event significantly affects the progression, treatment, recurrence, and metastasis of cancer. Therefore, the present review describes alterations in the lipid metabolism of immune cells in the TME and examines the connection between lipid metabolism and immunotherapy.
Changes in microbial composition and interaction patterns of female urogenital tract and rectum in response to HPV infection
Authors: Dong Yong-Hong , Luo Yu-Hua , Liu Chen-Jian , Huang Wen-Yu , Feng Lin , Zou Xing-Yuan , Zhou Jin-Yan , Li Xiao-Ran 
Published: February 2024

Abstract
Background
Previous studies have shown that changes in the microbial community of the female urogenital tract are associated with Human papillomavirus (HPV) infection. However, research on this association was mostly focused on a single site, and there are currently few joint studies on HPV infection and multiple sites in the female urogenital tract.

Methods
We selected 102 healthy women from Yunnan Province as the research object, collected cervical exfoliation fluid, vaginal, urethral, and rectal swabs for microbial community analysis, and measured bacterial load, and related cytokine content. The link between HPV, microbiota, and inflammation was comprehensively evaluated using bioinformatics methods.

Findings
The impact of HPV infection on the microbial composition of different parts varies. We have identified several signature bacterial genera that respond to HPV infection in several detection sites, such as Corynebacterium, Lactobacillus, Campylobacter, and Cutibacterium have been detected in multiple sites, reflecting their potential significance in cross body sites HPV infection responses. There was a solid microbial interaction network between the cervix, vagina, and urethra. The interrelationships between inflammatory factors and different bacterial genera might also affect the immune system's response to HPV infection.

Interpretation
It might be an effective strategy to prevent and treat HPV infection by simultaneously understanding the correlation between the microbial changes in multiple parts of the female urogenital tract and rectum and HPV infection, and controlling the microbial network related to HPV infection in different parts.
Herpes simplex virus infection induces necroptosis of neurons and astrocytes in human fetal organotypic brain slice cultures
Authors: Rashidi Ahmad S. , Tran Diana N. , Peelen Caithlin R. , van Gent Michiel , Ouwendijk Werner J. D. , Verjans Georges M. G. M. 
Published: February 2024

Abstract
Background
Herpes simplex virus (HSV) encephalitis (HSE) is a serious and potentially life-threatening disease, affecting both adults and newborns. Progress in understanding the virus and host factors involved in neonatal HSE has been hampered by the limitations of current brain models that do not fully recapitulate the tissue structure and cell composition of the developing human brain in health and disease. Here, we developed a human fetal organotypic brain slice culture (hfOBSC) model and determined its value in mimicking the HSE neuropathology in vitro.

Methods
Cell viability and tissues integrity were determined by lactate dehydrogenase release in supernatant and immunohistological (IHC) analyses. Brain slices were infected with green fluorescent protein (GFP-) expressing HSV-1 and HSV-2. Virus replication and spread were determined by confocal microscopy, PCR and virus culture. Expression of pro-inflammatory cytokines and chemokines were detected by PCR. Cell tropism and HSV-induced neuropathology were determined by IHC analysis. Finally, the in situ data of HSV-infected hfOBSC were compared to the neuropathology detected in human HSE brain sections.

Results
Slicing and serum-free culture conditions were optimized to maintain the viability and tissue architecture of ex vivo human fetal brain slices for at least 14 days at 37 °C in a CO2 incubator. The hfOBSC supported productive HSV-1 and HSV-2 infection, involving predominantly infection of neurons and astrocytes, leading to expression of pro-inflammatory cytokines and chemokines. Both viruses induced programmed cell death—especially necroptosis—in infected brain slices at later time points after infection. The virus spread, cell tropism and role of programmed cell death in HSV-induced cell death resembled the neuropathology of HSE.

Conclusions
We developed a novel human brain culture model in which the viability of the major brain-resident cells—including neurons, microglia, astrocytes and oligodendrocytes—and the tissue architecture is maintained for at least 2 weeks in vitro under serum-free culture conditions. The close resemblance of cell tropism, spread and neurovirulence of HSV-1 and HSV-2 in the hfOBSC model with the neuropathological features of human HSE cases underscores its potential to detail the pathophysiology of other neurotropic viruses and as preclinical model to test novel therapeutic interventions.
Predictive value of systemic immune-inflammation index in the high-grade subtypes components of small-sized lung adenocarcinoma
Authors: Wei BoHua , Zhang Yi , Shi Kejian , Jin Xin , Qian Kun , Zhang Peilong , Zhao Teng 
Published: February 2024

Abstract
Background
Identification of micropapillary and solid subtypes components in small-sized (≤ 2 cm) lung adenocarcinoma plays a crucial role in determining optimal surgical procedures. This study aims to propose a straightforward prediction method utilizing preoperative available indicators.

Methods
From January 2019 to July 2022, 341 consecutive patients with small-sized lung adenocarcinoma who underwent curative resection in thoracic surgery department of Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The patients were divided into two groups based on whether solid or micropapillary components ≥ 5% or not (S/MP5+ and S/MP5-). Univariate analysis and multivariate logistic regression analysis were utilized to identify independent predictors of S/MP5+. Then a nomogram was constructed to intuitively show the results. Finally, the calibration curve with a 1000 bootstrap resampling and the receiver operating characteristic (ROC) curve were depicted to evaluate its performance.

Results
According to postoperative pathological results, 79 (23.2%) patients were confirmed as S/MP5+ while 262 (76.8%) patients were S/MP5-. Based on multivariate analysis, maximum diameter (p = 0.010), consolidation tumor ratio (CTR) (p < 0.001) and systemic immune-inflammation index (SII) (p < 0.001) were identified as three independent risk factors and incorporated into the nomogram. The calibration curve showed good concordance between the predicted and actual probability of S/MP5+. Besides, the model showed certain discrimination, with an area under ROC curve of 0.893.

Conclusions
The model constructed based on SII is a practical tool to predict high-grade subtypes components of small-sized lung adenocarcinoma preoperatively and contribute to determine the optimal surgical approach.
Sestrin1, 2, and 3 are dispensable for female fertility in mice
Authors: Wang Mengchen , Chen Wenhui , Zeng Xinxin , Wang Taojun , Sun Yingpu , Yang Qingling 
Published: February 2024

Abstract
Background
Sestrins have been implicated in regulating aging in various organs through multiple pathways. However, their roles in ovarian aging remain unrevealed.

Methods
Female Sestrin1−/−, Sestrin2−/−, and Sestrin3−/− mice were generated using the CRISPR-Cas9 system. Body weights, little sizes, ovarian weights, estrous cyclicity, and follicle number in female mice were observed. ELISA was utilized to measure serum anti-Müllerian hormone (AMH) levels. Real time PCR, western blot, immunofluorescence, and Masson trichrome staining were employed for assessment of aging-related change.

Results
The deletion of Sestrin 1, 2, or 3 had no discernible impact on body weights,or serum AMH levels in female mice at the age of 12 months. And there were no discernible differences in litter sizes or estrous cyclicity which were assessed at the age of 8 months. At the age of 12 months, no significant differences were observed in ovarian weights or follicle numbers among the knockout mice. Consistently, the extent of fibrosis within the ovaries remained comparable across all experimental groups at this age. Additionally, autophagy, apoptosis, DNA damage, and inflammation within the ovaries were also found to be comparable to those in wild-type mice of the same age.

Conclusions
The loss of Sestrin 1, 2, or 3 does not exert a noticeable influence on ovarian function during the aging process. Sestrin1, 2, and 3 are not essential for female fertility in mice.
Exploring preliminary dietary intake results using a novel dietary assessment tool with pregnant participants enrolled in a birth cohort
Authors: Santarossa Sara , Redding Ashley , Connell Mackenzie , Kao Karissa , Susick Laura , Kerver Jean M. 
Published: February 2024

Abstract
Objective
We aimed to describe preliminary dietary intake results using DietID™ for dietary assessment during pregnancy. A sub-sample of participants in the Research Enterprise to Advance Children’s Health (REACH) prospective birth cohort from Detroit, MI received a unique web link to complete the DietID™ assessment multiple times during pregnancy. We present results for the first dietary assessment completed during pregnancy by each participant. DietID™ uses an image-based algorithm to estimate nutrient intake, dietary patterns, and diet quality and provides immediate results to participants. Descriptive statistics were used to summarize participant characteristics, nutrient intakes, dietary patterns, diet quality, and participant-rated accuracy of individual dietary assessment results. Differences in diet parameters were assessed by participant race with an independent t-test.

Results
Participants (n = 84) identified as majority Black (n = 47; 56%), reflective of the source population. Mean (SD) maternal age and gestational age at dietary assessment were 32 (5.6) years and 14.3 (4.8) weeks, respectively. Mean dietary quality, as reported in the DietID™ data output as the Healthy Eating Index (HEI), was 68 (range 12–98; higher scores indicate higher diet quality) and varied significantly between Black (mean [SD] 61 [23]) and White (mean [SD] 81 [19]) race (p < 0.01). Mean participant-rated accuracy of individual dietary assessment results was high at 87% on a scale of 0-100% (“not quite right” to “perfect”; range 47–100%).
DLM-DTI: a dual language model for the prediction of drug-target interaction with hint-based learning
Authors: Lee Jonghyun , Jun Dae Won , Song Ildae , Kim Yun 
Published: February 2024

AbstractThe drug discovery process is demanding and time-consuming, and machine learning-based research is increasingly proposed to enhance efficiency. A significant challenge in this field is predicting whether a drug molecule’s structure will interact with a target protein. A recent study attempted to address this challenge by utilizing an encoder that leverages prior knowledge of molecular and protein structures, resulting in notable improvements in the prediction performance of the drug-target interactions task. Nonetheless, the target encoders employed in previous studies exhibit computational complexity that increases quadratically with the input length, thereby limiting their practical utility. To overcome this challenge, we adopt a hint-based learning strategy to develop a compact and efficient target encoder. With the adaptation parameter, our model can blend general knowledge and target-oriented knowledge to build features of the protein sequences. This approach yielded considerable performance enhancements and improved learning efficiency on three benchmark datasets: BIOSNAP, DAVIS, and Binding DB. Furthermore, our methodology boasts the merit of necessitating only a minimal Video RAM (VRAM) allocation, specifically 7.7GB, during the training phase (16.24% of the previous state-of-the-art model). This ensures the feasibility of training and inference even with constrained computational resources.
Enhancing protein production and growth in chinese hamster ovary cells through miR-107 overexpression
Authors: Jari Maryam , Abdoli Shahriyar , Bazi Zahra , Shamsabadi Fatemeh Tash , Roshanmehr Farnaz , Shahbazi Majid 
Published: February 2024

AbstractChinese Hamster Ovary (CHO) cells are widely employed as host cells for biopharmaceutical production. The manufacturing of biopharmaceuticals poses several challenges, including restricted growth potential and inadequate productivity of the host cells. MicroRNAs play a crucial role in regulating gene expression and are considered highly promising tools for cell engineering to enhance protein production. Our study aimed to evaluate the effects of miR-107, which is recognized as an onco-miR, on erythropoietin-producing CHO cells (CHO-hEPO). To assess the impact of miR-107 on CHO cells, a DNA plasmid containing miR-107 was introduced to CHO-hEPO cells through transfection. Cell proliferation and viability were assessed using the trypan blue dye exclusion method. Cell cycle analysis was conducted by utilizing propidium iodide (PI) staining. The quantification of EPO was determined using an immunoassay test. Moreover, the impact of miR-107 on the expression of downstream target genes was evaluated using qRT-PCR. Our findings highlight and underscore the substantial impact of transient miR-107 overexpression, which led to a remarkable 2.7-fold increase in EPO titers and a significant 1.6-fold increase in the specific productivity of CHO cells (p < 0.01). Furthermore, this intervention resulted in significant enhancements in cell viability and growth rate (p < 0.05). Intriguingly, the overexpression of miR‑107 was linked to the downregulation of LATS2, PTEN, and TSC1 genes while concurrently driving upregulation in transcript levels of MYC, YAP, mTOR, and S6K genes within transgenic CHO cells. In conclusion, this study collectively underscores the feasibility of utilizing cancer-associated miRNAs as a powerful tool for CHO cell engineering. However, more in-depth exploration is warranted to unravel the precise molecular intricacies of miR-107's effects in the context of CHO cells.
Promoting higher-valent pediatric combination vaccines in China: challenges and recommendations for action
Authors: Li Jiuling , Chen Shu , Asturias Edwin , Tang Shenglan , Cui Fuqiang 
Published: February 2024

AbstractMany countries have adopted higher-valent pediatric combination vaccines to simplify vaccination schedules and minimize health expenditures and social costs. However, China is conservative in the use of pediatric combination vaccines. By reviewing and synthesizing quantitative and qualitative data, in this commentary we identify gaps and challenges to combination vaccine use and make recommendations for promoting use of higher-valent pediatric combination vaccines in China. Challenges are in four dimensions: (1) legislation and regulation, (2) immunization schedule design, (3) vaccine awareness and price, and (4) research and development capacity. To optimize the use of combination vaccines to reduce vaccine-preventable disease burden, we make recommendations that address key challenges: (1) develop policies and regulations to strengthen enforcement of the Vaccine Administration Law and remove regulatory hurdles that hinder combination vaccine research and development, (2) establish an evidence-informed policy-making mechanism for combination vaccines, (3) resolve immunization schedule conflicts between monovalent and combination vaccines, and (4) implement effective interventions to increase vaccine awareness and reduce price.
Graphical Abstract
Features of optical coherence tomography angiography in age-related macular degeneration with residual fluid after three loading doses of aflibercept
Authors: Song Yong-Yeon , Seong Hyun-Je , Kim Jung-Tae , Lee Sung-Chul , Lee Min-Woo 
Published: February 2024

Abstract
Background
To identify the macular neovascularization (MNV) features in exudative age-related macular degeneration (AMD) patients who exhibited residual fluid after receiving three loading doses of aflibercept.

Methods
Patients were classified into two groups: Group 1, which did not exhibit intraretinal fluid (IRF) and subretinal fluid (SRF), and Group 2, which did exhibit IRF and/or SRF. Optical coherence tomography angiography (OCTA) features were assessed and compared between the groups.

Results
A total of 101 eyes were enrolled; 65 for Group 1 and 36 for Group 2. No significant differences were found in baseline MNV size (2.94 ± 2.51 µm2 vs. 2.22 ± 2.26 µm2, P = 0.178) or vessel density (47.1 ± 15.4 % vs. 41.3 ± 10.5%, P = 0.052) between Groups 1 and 2. There were significant differences in the presence of loops (52.3% vs. 75%, P = 0.026) and peripheral arcades (29.2% vs. 55.6%, P < 0.001) at baseline between the two groups. In Group 1, there was a significant reduction in the presence of branching (P < 0.001) and loops (P = 0.016) after treatment. In Group 2, only the presence of branching decreased significantly (P < 0.001) after treatment. Multivariable analysis revealed that the presence of a peripheral arcade (B = 4.77, P = 0.001) was significantly associated with residual fluid.

Conclusions
Although responding to treatment, the presence of loops and peripheral arcades in exudative AMD patients may contribute to residual fluid following the three loading doses of aflibercept. The peripheral arcade, in particular, may play a more significant role in the presence of residual fluid.
Housing differentiation from the spatial opportunity structure perspective: an empirical study on new-generation migrants in China
Authors: Mu Xueying , Cui Can , Cui Junru 
Published: February 2024

AbstractUsing data from the 2017 China Migrants Dynamics Survey, this study employs generalized structural equation modeling to examine the effects of migrants' places of origin and socioeconomic status on their destination choice and access to homeownership in the destination city. The analyses reveal significant disparities in access to homeownership among migrants from different places of origin. Furthermore, the position of the destination city in the urban hierarchy not only has a direct impact on migrants' access to homeownership but also plays an important mediating role. This study highlights the spatial foundations of housing inequality and builds an analytical framework that links spatial mobility with social mobility. Our findings have significant implications for housing policies and practices aimed at improving the housing conditions of new-generation migrants.