bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain-targeted delivery of neuroprotective survival gene minimizing hematopoietic cell contamination: implications for Parkinson’s disease treatment
Authors: Lee Min Hak , Kang Sukyeong , Um Ki-Hwan , Lee Seok Won , Hwang Hyorin , Baek Kyunghwa , Choi Jin Woo 
Published: January 2024

Abstract
Background
Neurodegenerative diseases, including Parkinson's disease, Amyotropic Lateral Sclerosis (ALS) and Alzheimer's disease, present significant challenges for therapeutic development due to drug delivery restrictions and toxicity concerns. Prevailing strategies often employ adeno-associated viral (AAV) vectors to deliver neuroprotective survival genes directly into the central nervous system (CNS). However, these methods have been limited by triggering immunogenic responses and risk of tumorigenicity, resulting from overexpression of survival genes in peripheral blood mononuclear cells (PBMC), thereby increasing the risk of tumorigenicity in specific immune cells. Thus, by coding selectively suppressive microRNA (miRNA) target sequences in AAV genome, we designed CNS-targeted neuroprotective gene expression vector system without leakage to blood cells.

Methods
To minimize the potential for transgene contamination in the blood, we designed a CNS-specific AAV system. Our system utilized a self-complementary AAV (scAAV), encoding a quadruple repeated target sequence of the hematopoietic cell-specific miR142-3p at the 3' untranslated region (UTR). As a representative therapeutic survival gene for Parkinson’s disease treatment, we integrated DX2, an antagonistic splice variant of the apoptotic gene AIMP2, known to be implicated in Parkinson's disease, into the vector.

Results
This configuration ensured that transgene expression was stringently localized to the CNS, even if the vector found its way into the blood cells. A single injection of scAAV-DX2 demonstrated marked improvement in behavior and motor activity in animal models of Parkinson’s disease induced by either Rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Importantly, comprehensive preclinical data adhering to Good Laboratory Practice (GLP) standards revealed no adverse effects in the treated animals.

Conclusions
Our CNS-specific vector system, which encodes a survival transgene DX2, signifies a promising avenue for safe gene therapy, avoiding unintended expression of survival gene in blood cells, applicable to various neurodegenerative diseases.
MicroRNA-93-5p regulates odontogenic differentiation and dentin formation via KDM6B
Authors: Wu Si , Xu Xin , Gao Shiqi , Huo Sibei , Wan Mian , Zhou Xin , Zhou Xuedong , Zheng Liwei , Zhou Yachuan 
Published: January 2024

Abstract
Background
Epigenetic factors influence the odontogenic differentiation of dental pulp stem cells and play indispensable roles during tooth development. Some microRNAs can epigenetically regulate other epigenetic factors like DNA methyltransferases and histone modification enzymes, functioning as epigenetic-microRNAs. In our previous study, microarray analysis suggested microRNA-93-5p (miR-93-5p) was differentially expressed during the bell stage in human tooth germ. Prediction tools indicated that miR-93-5p may target lysine-specific demethylase 6B (KDM6B). Therefore, we explored the role of miR-93-5p as an epi-miRNA in tooth development and further investigated the underlying mechanisms of miR-93-5p in regulating odontogenic differentiation and dentin formation.

Methods
The expression pattern of miR-93-5p and KDM6B of dental pulp stem cells (DPSCs) was examined during tooth development and odontogenic differentiation. Dual luciferase reporter and ChIP-qPCR assay were used to validate the target and downstream regulatory genes of miR-93-5p in human DPSCs (hDPSCs). Histological analyses and qPCR assays were conducted for investigating the effects of miR-93-5p mimic and inhibitor on odontogenic differentiation of hDPSCs. A pulpotomy rat model was further established, microCT and histological analyses were performed to explore the effects of KDM6B-overexpression and miR-93-5p inhibition on the formation of tertiary dentin.

Results
The expression level of miR-93-5p decreased as odontoblast differentiated, in parallel with elevated expression of histone demethylase KDM6B. In hDPSCs, miR-93-5p overexpression inhibited the odontogenic differentiation and vice versa. MiR-93-5p targeted 3′ untranslated region (UTR) of KDM6B, thereby inhibiting its protein translation. Furthermore, KDM6B bound the promoter region of BMP2 to demethylate H3K27me3 marks and thus upregulated BMP2 transcription. In the rat pulpotomy model, KDM6B-overexpression or miR-93-5p inhibition suppressed H3K27me3 level in DPSCs and consequently promoted the formation of tertiary dentin.

Conclusions
MiR-93-5p targets epigenetic regulator KDM6B and regulates H3K27me3 marks on BMP2 promoters, thus modulating the odontogenic differentiation of DPSCs and dentin formation.
Metabolic reprogramming based on RNA sequencing of gemcitabine-resistant cells reveals the FASN gene as a therapeutic for bladder cancer
Authors: Zhou Lijie , Du Kaixuan , Dai Yiheng , Zeng Youmiao , Luo Yongbo , Ren Mengda , Pan Wenbang , Liu Yuanhao , Zhang Lailai , Zhu Ronghui , Feng Dapeng , Tian Fengyan , Gu Chaohui 
Published: January 2024

AbstractBladder cancer (BLCA) is the most frequent malignant tumor of the genitourinary system. Postoperative chemotherapy drug perfusion and chemotherapy are important means for the treatment of BLCA. However, once drug resistance occurs, BLCA develops rapidly after recurrence. BLCA cells rely on unique metabolic rewriting to maintain their growth and proliferation. However, the relationship between the metabolic pattern changes and drug resistance in BLCA is unclear. At present, this problem lacks systematic research. In our research, we identified and analyzed resistance- and metabolism-related differentially expressed genes (RM-DEGs) based on RNA sequencing of a gemcitabine-resistant BLCA cell line and metabolic-related genes (MRGs). Then, we established a drug resistance- and metabolism-related model (RM-RM) through regression analysis to predict the overall survival of BLCA. We also confirmed that RM-RM had a significant correlation with tumor metabolism, gene mutations, tumor microenvironment, and adverse drug reactions. Patients with a high drug resistance- and metabolism-related risk score (RM-RS) showed more active lipid synthesis than those with a low RM-RS. Further in vitro and in vivo studies were implemented using Fatty Acid Synthase (FASN), a representative gene, which promotes gemcitabine resistance, and its inhibitor (TVB-3166) that can reverse this resistance effect.
A rare co-existence of histiocytic necrotizing lymphadenitis with metastatic papillary thyroid carcinoma and review of the literature
Authors: Liu Jing , Jiang Lei , Yu Guohua , Qu Guimei , Cai Li 
Published: January 2024

AbstractHistiocytic necrotizing lymphadenitis (HNL) is a benign, self-limiting disease that is rare clinically. The coexistence of HNL and tumor is rarer. We report a male patient who was preoperatively diagnosed with papillary thyroid carcinoma with cervical lymph nodes metastasis, and the postoperative pathological examination showed histiocytic necrotizing lymphadenitis combined with metastatic papillary thyroid carcinoma in the same single lymph node. More interestingly, Epstein‒Barr virus was positive in these lymph nodes by in situ hybridization. This may suggest a trigger for the coexistence of the two diseases.
Supraspinatus extraction from MRI based on attention-dense spatial pyramid UNet network
Authors: Wang Peng , Liu Yang , Zhou Zhong 
Published: January 2024

Abstract
Background
With potential of deep learning in musculoskeletal image interpretation being explored, this paper focuses on the common site of rotator cuff tears, the supraspinatus. It aims to propose and validate a deep learning model to automatically extract the supraspinatus, verifying its superiority through comparison with several classical image segmentation models.

Method
Imaging data were retrospectively collected from 60 patients who underwent inpatient treatment for rotator cuff tears at a hospital between March 2021 and May 2023. A dataset of the supraspinatus from MRI was constructed after collecting, filtering, and manually annotating at the pixel level. This paper proposes a novel A-DAsppUnet network that can automatically extract the supraspinatus after training and optimization. The analysis of model performance is based on three evaluation metrics: precision, intersection over union, and Dice coefficient.

Results
The experimental results demonstrate that the precision, intersection over union, and Dice coefficients of the proposed model are 99.20%, 83.38%, and 90.94%, respectively. Furthermore, the proposed model exhibited significant advantages over the compared models.

Conclusion
The designed model in this paper accurately extracts the supraspinatus from MRI, and the extraction results are complete and continuous with clear boundaries. The feasibility of using deep learning methods for musculoskeletal extraction and assisting in clinical decision-making was verified. This research holds practical significance and application value in the field of utilizing artificial intelligence for assisting medical decision-making.
Piloting a one-day parent-only intervention in the treatment of youth with anxiety disorders: child and family-level outcomes
Authors: Cobham Vanessa E. , Radtke Sarah R. , Hawkins Ingrid , Jordan Michele , Ali Nasriah Rizman , Ollendick Thomas H. , Sanders Matthew R. 
Published: January 2024

Abstract
Objective
Parent-only cognitive-behavioural therapy (CBT) interventions have promise for youth with anxiety disorders. Fear-Less Triple P (FLTP) is one such intervention that has been found comparable to child-focused CBT. Although traditionally administered in six sessions, a one-day workshop format of FLTP was developed to improve accessibility. The current study compared the effectiveness of the six-session and one-day workshop formats.

Method
Seventy-three youth (mean age, 8.4 years; 74% male) were randomized to traditional FLTP (6-week group) or the one-day workshop format. Anxiety diagnostic status, self- and parent-reported anxiety symptoms scores, independent evaluator-rated improvement, treatment satisfaction, and measures of family functioning were included to assess treatment outcome. Data were collected prior to treatment, and 1-week, 6-months, and 12-months following treatment.

Results
Both conditions resulted in significant improvement in child anxiety symptom scores per parent report (on both questionnaire and diagnostic interview measures). Furthermore, significant decreases in sibling anxiety were observed in both treatment conditions. There were no statistically significant differences between conditions on any outcome measure.

Conclusions
Results of this study add to the growing evidence that brief, low-intensity, parent-only interventions can effectively target child psychopathology. These brief interventions are ideal for families for whom the resources and time required to commit to a standard multi-week intervention are prohibitive.
Registration of Clinical Trials: This trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN 12615001284550).
Chromatin activity identifies differential gene regulation across human ancestries
Authors: Pettie Kade P. , Mumbach Maxwell , Lea Amanda J. , Ayroles Julien , Chang Howard Y. , Kasowski Maya , Fraser Hunter B. 
Published: January 2024

Abstract
Background
Current evidence suggests that cis-regulatory elements controlling gene expression may be the predominant target of natural selection in humans and other species. Detecting selection acting on these elements is critical to understanding evolution but remains challenging because we do not know which mutations will affect gene regulation.

Results
To address this, we devise an approach to search for lineage-specific selection on three critical steps in transcriptional regulation: chromatin activity, transcription factor binding, and chromosomal looping. Applying this approach to lymphoblastoid cells from 831 individuals of either European or African descent, we find strong signals of differential chromatin activity linked to gene expression differences between ancestries in numerous contexts, but no evidence of functional differences in chromosomal looping. Moreover, we show that enhancers rather than promoters display the strongest signs of selection associated with sites of differential transcription factor binding.

Conclusions
Overall, our study indicates that some cis-regulatory adaptation may be more easily detected at the level of chromatin than DNA sequence. This work provides a vast resource of genomic interaction data from diverse human populations and establishes a novel selection test that will benefit future study of regulatory evolution in humans and other species.
The adc1 knockout with proC overexpression in Synechocystis sp. PCC 6803 induces a diversion of acetyl-CoA to produce more polyhydroxybutyrate
Authors: Utharn Suthira , Jantaro Saowarath 
Published: January 2024

Abstract
Background
Lack of nutrients, in particular nitrogen and phosphorus, has been known in the field to sense glutamate production via 2-oxoglutarate and subsequently accelerate carbon storage, including glycogen and polyhydroxybutyrate (PHB), in cyanobacteria, but a few studies have focused on arginine catabolism. In this study, we first time demonstrated that gene manipulation on proC and adc1, related to proline and polyamine syntheses in arginine catabolism, had a significant impact on enhanced PHB production during late growth phase and nutrient-modified conditions. We constructed Synechocystis sp. PCC 6803 with an overexpressing proC gene, encoding Δ1pyrroline-5-carboxylate reductase in proline production, and adc1 disruption resulted in lower polyamine synthesis.

Results
Three engineered Synechocystis sp. PCC 6803 strains, including a ProC-overexpressing strain (OXP), adc1 mutant, and an OXP strain lacking the adc1 gene (OXP/Δadc1), certainly increased the PHB accumulation under nitrogen and phosphorus deficiency. The possible advantages of single proC overexpression include improved PHB and glycogen storage in late phase of growth and long-term stress situations. However, on day 7 of treatment, the synergistic impact created by OXP/Δadc1 increased PHB synthesis by approximately 48.9% of dry cell weight, resulting in a shorter response to nutrient stress than the OXP strain. Notably, changes in proline and glutamate contents in engineered strains, in particular OXP and OXP/Δadc1, not only partially balanced the intracellular C/N metabolism but also helped cells acclimate under nitrogen (N) and phosphorus (P) stress with higher chlorophyll a content in comparison with wild-type control.

Conclusions
In Synechocystis sp. PCC 6803, overexpression of proC resulted in a striking signal to PHB and glycogen accumulation after prolonged nutrient deprivation. When combined with the adc1 disruption, there was a notable increase in PHB production, particularly in situations where there was a strong C supply and a lack of N and P.
Impaired immune tolerance mediated by reduced Tfr cells in rheumatoid arthritis linked to gut microbiota dysbiosis and altered metabolites
Authors: Wu Ruihe , Wang Dongming , Cheng Liyun , Su Rui , Li Baochen , Fan Chunxue , Gao Chong , Wang Caihong 
Published: January 2024

Abstract
Background
Patients with rheumatoid arthritis (RA) showed impaired immune tolerance characterized by reduced follicular regulatory T (Tfr) cells, and they also exhibited altered gut microbiotas and their metabolites in RA. However, the association of gut microbiotas and their metabolites with the immune tolerance mediated by Tfr cells in RA remains unclear.

Methods
Peripheral blood and stool samples were collected from 32 new-onset RA patients and 17 healthy controls (HCs) in the Second Hospital of Shanxi Medical University between January 2022 and June 2022. The peripheral blood was used to detect the circulating regulatory T (Treg), helper T(Th)17, Tfr, and follicular helper T (Tfh) cells by modified flow cytometry. The stool samples were used to analyze the gut microbiotas and their metabolites via 16S rDNA sequencing and metabolomic profiling. We aimed to characterize the gut microbiotas and their metabolites in RA and identified their association with Tfr cell-mediated immune tolerance.

Results
The new-onset RA demonstrated reduced Treg and Tfr cells, associated with the disease activity and autoantibodies. There were significant differences in gut microbiotas between the two groups as the results of β diversity analysis (P = 0.039) including 21 differential gut microbiotas from the phylum to genus levels. In which, Ruminococcus 2 was associated with the disease activity and autoantibodies of RA, and it was identified as the potential biomarker of RA [area under curve (AUC) = 0.782, 95% confidence interval (CI) = 0.636–0.929, P = 0.001]. Eleven differential metabolites were identified and participated in four main pathways related to RA. Arachidonic acid might be the potential biomarker of RA (AUC = 0.724, 95% CI = 0.595–0.909, P = 0.038), and it was the core metabolite as the positive association with six gut microbiotas enriched in RA. The reduced Tfr cells were associated with the altered gut microbiotas and their metabolites including the Ruminococcus 2, the arachidonic acid involved in the biosynthesis of unsaturated fatty acid pathway and the 3-methyldioxyindole involved in the tryptophan metabolism pathway.

Conclusion
The breakdown of immune tolerance mediated by reduced Tfr cells was associated with the altered gut microbiotas and their metabolites implying the possible mechanism of RA pathogenesis from the perspective of microecology-metabolism-immune.
The association between gestational weight trajectories in women with gestational diabetes and their offspring's weight from birth to 40 months
Authors: Zheng Wei , Wang Jia , Li Yichen , Shang Xiaorui , Ma Kaiwen , Yuan Xianxian , Zhang Kexin , Yang Ruihua , Ma Yuru , Li Guanghui 
Published: January 2024

Abstract
Aims
To identify the gestational weight gain (GWG) patterns in women with gestational diabetes mellitus (GDM) and evaluate their association with offspring weight status from birth to 40 months.

Materials and methods
This study included 2,723 GDM-mother–child pairs from the Beijing Birth Cohort Study. The association between GWG trajectories identified by the latent class model and offspring weight outcomes from birth to 40 months were evaluated, after adjustment for maternal age, parity, pre-pregnancy body mass index, maternal height, and blood glucose levels.

Results
Three GWG rate groups, including the non-excessive GWG group (1,994/2,732), excessive GWG group (598 /2,732), and excessive early GWG group (140/2,732), were identified in women with GDM, respectively. Compared to the non-excessive GWG group, the adjusted OR (aOR) and 95% CI were 1.83 (1.35–2.47) and 1.79 (1.06–3.01) for macrosomia, 1.33 (1.07–1.66) and 1.48 (1.01–2.17) for large for gestational age (LGA) in the excessive GWG group and excessive early GWG group. Excessive GWG was also associated with an increased risk of BMI-for-age at 40 months (aOR = 1.66, 95% CI 1.14–2.42).

Conclusions
Both excessive GWG and excessive early GWG increased the risk of macrosomia and LGA in women with GDM, but only the excessive GWG was associated with childhood overweight/obesity. The results suggest the long-term impact of GWG on offspring weight status in women with GDM and the potential benefits of GWG restriction after GDM diagnosis.
Activation of γ-globin expression by LncRNA-mediated ERF promoter hypermethylation in β-thalassemia
Authors: Bao Xiuqin , Gao Yuanyi , Wang Zhongju , Ye Yuhua , Chen Diyu , Zuo Yangjin , Zhao Cunyou , Xu Xiangmin 
Published: January 2024

AbstractThe mechanism that drives the switch from fetal to adult hemoglobin (Hb) provides a therapeutic target for β-thalassemia. We have previously identified that hypermethylation of transcription factor ERF promoter reactivated γ-globin expression. To uncover the mechanism underlying the hypermethylation of ERF promoter, we performed RNA sequencing in β0/β0-thalassemia patients and identified an upregulated long noncoding RNA (RP11-196G18.23) associated with HbF production. RP11-196G18.23 bound to the ERF promoter and recruited DNA methyltransferase 3A to promote DNA hypermethylation-mediated ERF downregulation, thereby ameliorating ERF-induced γ-globin inactivation. The identification of RP11-196G18.23 provides an epigenetic mechanism for the reactivation of fetal γ-globin expression for β-hemoglobinopathies.
Remediation of copper-contaminated soils and growth enhancement of Pakchoi (B. chinensis L.) via biofertilizers composed of new Bacillus amyloliquefaciens SYNU1
Authors: He Haisheng , Bao Sijia , Wu Yannan , Tong Deli 
Published: January 2024

Abstract
Background
Excessive copper contaminants are harmful to soil, microbes, plants and humans and can be remediated by biosorption. Applying biofertilizers to remediate copper-contaminated soil is an environmentally friendly way.

Results
In this study, we identified a new strain, Bacillus amyloliquefaciens SYNU1, based on morphological, biochemical, physiological and phylogenetic analyses. It has been cultured on Luria–Bertani (LB) medium and absorbs soluble Cu2+ from pH 3.5–5 and 25–40 °C at Cu2+ concentrations of 100 mg L−1. The results showed that the maximum adsorption capacity of copper by strain SYNU1 is 53.09% w/w. Furthermore, microbe fertilizers were made based on strain SYNU1, these fertilizers were allowed to ferment for 15 days, and they were used for remediation of copper-contaminated soil and growth tests of Pakchoi (B. chinensis L) in pot experiments. The results showed that the growth of Pakchoi planted in copper-contaminated soil at concentrations ranging from 50 to 200 mg kg−1 was inhibited, and its growth indices, such as plant height, fresh weight and dry weight, decreased significantly with increasing copper concentration. Compared with the control, the increases in plant height, fresh weight and dry weight of Pakchoi treated with biofertilizer were 10.37, 65.3 and 67.78%, respectively, indicating that biofertilizer could significantly promote the growth of Pakchoi.

Conclusions
Bacillus amyloliquefaciens SYNU1 is useful for the bioremediation of Cu2+-contaminated soil in Northeast China.