bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel inhalable quercetin-alginate nanogel as a promising therapy for acute lung injury
Authors: Chen Yi-Bing , Zhang Ya-Bin , Wang Yu-Le , Kaur Prabhleen , Yang Bo-Guang , Zhu Yan , Ye Lei , Cui Yuan-Lu 
Published: June 2022

Abstract
Background
Acute lung injury (ALI), a severe health-threatening disease, has a risk of causing chronic pulmonary fibrosis. Informative and powerful evidence suggests that inflammation and oxidative stress play a central role in the pathogenesis of ALI. Quercetin is well recognized for its excellent antioxidant and anti-inflammatory properties, which showed great potential for ALI treatment. However, the application of quercetin is often hindered by its low solubility and bioavailability. Therefore, to overcome these challenges, an inhalable quercetin-alginate nanogel (QU-Nanogel) was fabricated, and by this special “material-drug” structure, the solubility and bioavailability of quercetin were significantly enhanced, which could further increase the activity of quercetin and provide a promising therapy for ALI.

Results
QU-Nanogel is a novel alginate and quercetin based “material-drug” structural inhalable nanogel, in which quercetin was stabilized by hydrogen bonding to obtain a “co-construct” water-soluble nanogel system, showing antioxidant and anti-inflammatory properties. QU-Nanogel has an even distribution in size of less than 100 nm and good biocompatibility, which shows a stronger protective and antioxidant effect in vitro. Tissue distribution results provided evidence that the QU-Nanogel by ultrasonic aerosol inhalation is a feasible approach to targeted pulmonary drug delivery. Moreover, QU-Nanogel was remarkably reversed ALI rats by relieving oxidative stress damage and acting the down-regulation effects of mRNA and protein expression of inflammation cytokines via ultrasonic aerosol inhalation administration.

Conclusions
In the ALI rat model, this novel nanogel showed an excellent therapeutic effect by ultrasonic aerosol inhalation administration by protecting and reducing pulmonary inflammation, thereby preventing subsequent pulmonary fibrosis. This work demonstrates that this inhalable QU-Nanogel may function as a promising drug delivery strategy in treating ALI.

Graphical Abstract
Development and validation of a PCR-free nucleic acid testing method for RNA viruses based on linear molecular beacon probes
Authors: Du Fuyu , Zhang Weijie , Yao Huimin , Xia Yuqiong , Zhang Xianghan , Yang Peng , Ning Pengbo 
Published: June 2022

Abstract
Background
RNA viruses periodically trigger pandemics of severe human diseases, frequently causing enormous economic losses. Here, a nucleic acid extraction-free and amplification-free RNA virus testing probe was proposed for the sensitive and simple detection of classical swine fever virus (CSFV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), based on a double-stranded molecular beacon method. This RNA virus probe contains two base sequences—a recognition strand that binds to the specific domain of CSFV N2 or SARS-CoV-2 N, with a fluorophore (FAM) labeled at the 5′ end, and a complementary strand (CSFV-Probe B or SARS-CoV-2-Probe B), combined with a quencher (BHQ2) labeled at the 3′ end.

Results
Using linear molecular beacon probe technology, the detection limit of the RNA virus probe corresponding to CSFV and SARS-CoV-2 were as low as 0.28 nM and 0.24 nM, respectively. After CSFV E2 and SARS-CoV-2 N genes were transfected into corresponding host cells, the monitoring of RNA virus probes showed that fluorescence signals were dramatically enhanced in a concentration- and time-dependent manner. These results were supported by those of quantitative (qRT-PCR) and visualization (confocal microscopy) analyses. Furthermore, CSF-positive swine samples and simulated SARS-CoV-2 infected mouse samples were used to demonstrate their applicability for different distributions of viral nucleic acids in series tissues.

Conclusions
The proposed RNA virus probe could be used as a PCR-free, cost-effective, and rapid point-of-care (POC) diagnostic platform for target RNA virus detection, holding great potential for the convenient monitoring of different RNA viruses for early mass virus screening.

Graphical Abstract
Reciprocal regulation of NRF2 by autophagy and ubiquitin–proteasome modulates vascular endothelial injury induced by copper oxide nanoparticles
Authors: Li Na , Du Hang , Mao Lejiao , Xu Ge , Zhang Mengling , Fan Yinzhen , Dong Xiaomei , Zheng Lijun , Wang Bin , Qin Xia , Jiang Xuejun , Chen Chengzhi , Zou Zhen , Zhang Jun 
Published: June 2022

AbstractNRF2 is the key antioxidant molecule to maintain redox homeostasis, however the intrinsic mechanisms of NRF2 activation in the context of nanoparticles (NPs) exposure remain unclear. In this study, we revealed that copper oxide NPs (CuONPs) exposure activated NRF2 pathway in vascular endothelial cells.NRF2knockout remarkably aggravated oxidative stress, which were remarkably mitigated by ROS scavenger. We also demonstrated that KEAP1 (the negative regulator of NRF2) was not primarily involved in NRF2 activation in thatKEAP1knockdown did not significantly affect CuONPs-induced NRF2 activation. Notably, we demonstrated that autophagy promoted NRF2 activation as evidenced by thatATG5knockout or autophagy inhibitors significantly blocked NRF2 pathway. Mechanically, CuONPs disturbed ubiquitin–proteasome pathway and consequently inhibited the proteasome-dependent degradation of NRF2. However, autophagy deficiency reciprocally promoted proteasome activity, leading to the acceleration of degradation of NRF2 via ubiquitin–proteasome pathway. In addition, the notion that the reciprocal regulation of NRF2 by autophagy and ubiquitin–proteasome was further proven in a CuONPs pulmonary exposure mice model. Together, this study uncovers a novel regulatory mechanism of NRF2 activation by protein degradation machineries in response to CuONPs exposure, which opens a novel intriguing scenario to uncover therapeutic strategies against NPs-induced vascular injury and disease.Graphical Abstract
Association of single nucleotide polymorphisms (SNPs) with gastric cancer susceptibility and prognosis in population in Wuwei, Gansu, China
Authors: Fan Ping , Zhang Zhiyi , Lu Linzhi , Guo Xingcai , Hao Zhicheng , Wang Xinghua , Ye Yancheng 
Published: June 2022

Abstract
Background
Gastric cancer (GC) is the sixth most common cancer. China is one of the most frequent GC occurred countries, and Wuwei, Gansu, is one of the highest incidence area in China. Possible biomarkers of GC susceptibility and prognosis among the population in Wuwei are urgently needed.

Methods
All participants in this study were recruited from the Wuwei Cancer Hospital in Gansu, including 303 patients diagnosed with GC and 200 non-cancer controls. DNA was extracted for further single nucleotide polymorphisms (SNP) genotyping. All SNPs were firstly screened by additive logistic regression model then selected SNPs were subjected to univariate Cox regression analysis and multivariate Cox regression analysis for their associations with GC occurrence.

Results
The results showed that 31 SNPs were significantly related to the incidence of GC in Wuwei, Gansu, China. Genotype rs4823921 was significantly related to the overall survival of GC patients and AC/AA genotype of rs4823921 polymorphism was significantly associated with an increased risk of GC in Wuwei population.

Conclusions
Thirty-one SNPs were significantly related to the incidence of GC in Wuwei and rs4823921 genotype AC/AA was significantly associated with poor prognosis of GC patients in Wuwei, Gansu.
Diagnostic potential of a circulating miRNA model associated with therapeutic effect in heart failure
Authors: Qian Lu , Zhao Qian , Yu Ping , Lü Jinhui , Guo Yuefan , Gong Xin , Ding Yuanyuan , Yu Shanshan , Fan Lieying , Fan Huimin , Zhang Yuzhen , Liu Zhongmin , Sheng Hongzhuan , Yu Zuoren 
Published: June 2022

AbstractHeart failure (HF), as the leading cause of death, is continuing to increase along with the aging of the general population all over the world. Identification of diagnostic biomarkers for early detection of HF is considered as the most effective way to reduce the risk and mortality. Herein, we collected plasma samples from HF patients (n = 40) before and after medical therapy to determine the change of circulating miRNAs through a quantitative real-time PCR (QRT-PCR)-based miRNA screening analysis. miR-30a-5p and miR-654-5p were identified as the most significantly changed miRNAs in the plasma of patients upon treatment. In consistence, miR-30a-5p showed upregulation and miR-654-5p showed downregulation in the circulation of 30 HF patients, compared to 15 normal controls in the training phase, from which a two-circulating miRNA model was developed for HF diagnosis. Next, we performed the model validation using an independent cohort including 50 HF patients and 30 controls. As high as 98.75% of sensitivity and 95.00% of specificity were achieved. A comparison between the miRNA model and NT-pro BNP in diagnostic accuracy of HF indicated an upward trend of the miRNA model. Moreover, change of the two miRNAs was further verified in association with the therapeutic effect of HF patients, in which miR-30a-5p showed decrease while miR-654-5p showed increase in the plasma of patients after LVAD implantation. In conclusion, the current study not only identified circulating miR-654-5p for the first time as a novel biomarker of HF, but also developed a novel 2-circulating miRNA model with promising potentials for diagnosis and prognosis of HF patients, and in association with therapeutic effects as well.
Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats
Authors: Zhao Yu-Ting , Deng Jie , Liu He-Ming , Wei Jia-You , Fan Hai-Ting , Liu Meng , Xu Ting , Chen Ting-Feng , He Jing-Yi , Sun Wei-Ming , Jia Tao-Yu , Zhang Xue-Qin , Xin Wen-Jun 
Published: June 2022

AbstractBackgroundThe adaption of brain region is fundamental to the development and maintenance of nervous system disorders. The prelimbic cortex (PrL) participates in the affective components of the pain sensation. However, whether and how the adaptation of PrL contributes to the comorbidity of neuropathic pain and depression are unknown.MethodsUsing resting-state functional magnetic resonance imaging (rs-fMRI), genetic knockdown or overexpression, we systematically investigated the activity of PrL region in the pathogenesis of neuropathic pain/depression comorbid using the combined approaches of immunohistochemistry, electrophysiology, and behavior.ResultsThe activity of PrL and the excitability of pyramidal neurons were decreased, and the osteoclastic tartrate-resistant acid phosphatase 5 (Acp5) expression in PrL neurons was upregulated following the acquisition of spared nerve injury (SNI)-induced comorbidity. Genetic knockdown of Acp5 in pyramidal neurons, but not parvalbumin (PV) neurons or somatostatin (SST) neurons, attenuated the decrease of spike number, depression-like behavior and mechanical allodynia in comorbidity rats. Overexpression of Acp5 in PrL pyramidal neurons decreased the spike number and induced the comorbid-like behavior in naïve rats. Moreover, the expression of interleukin-6 (IL-6), phosphorylated STAT3 (p-STAT3) and acetylated histone H3 (Ac-H3) were significantly increased following the acquisition of comorbidity in rats. Increased binding of STAT3 to the Acp5 gene promoter and the interaction between STAT3 and p300 enhanced acetylation of histone H3 and facilitated the transcription of Acp5 in PrL in the modeled rodents. Inhibition of IL-6/STAT3 pathway prevented the Acp5 upregulation and attenuated the comorbid-like behaviors in rats.ConclusionsThese data suggest that the adaptation of PrL mediated by IL-6/STAT3/Acp5 pathway contributed to the comorbidity of neuropathic pain/depression induced by SNI.
Professionalism, stigma, and willingness to provide patient-centered safe abortion counseling and care: a mixed methods study of Ethiopian midwives
Authors: Fekadu Addisu , Berhe Aster , Belgu Belete , Yimer Ibrahim , Tesfaye Yeshitila , Holcombe Sarah Jane , Burrowes Sahai 
Published: June 2022

Abstract
Background
Midwives are a large proportion of Ethiopia’s health care workforce, and their attitudes and practices shape the quality of reproductive health care, including safe abortion care (SAC) services. This study examines how midwives’ conceptions of their professional roles and views on women who have abortions relate to their willingness to provide respectful SAC.

Methods
This study uses a cross-sectional, mixed methods design to conduct a regionally representative survey of midwives in Ethiopia’s five largest regions (Oromia; Amhara; Southern Nations, Nationalities, and Peoples [SNNP]; Tigray; and Addis Ababa) with a multistage, cluster sampling design (n = 944). The study reports survey-weighted population estimates and the results of multivariate logistic regression analyzing factors associated with midwives’ willingness to provide SAC. Survey data were triangulated with results from seven focus group discussions (FGDs) held with midwives in the five study regions. Deductive and inductive codes were used to thematically analyze these data.

Results
The study surveyed 960 respondents. An estimated half of midwives believed that providing SAC was a professional duty. Slightly more than half were willing to provide SAC. A belief in right of refusal was common: two-thirds of respondents said that midwives should be able to refuse SAC provision on moral or religious grounds. Modifiable factors positively associated with willingness to provide SAC were SAC training (AOR 4.02; 95% CI 2.60, 6.20), agreeing that SAC refusal risked women’s lives (AOR 1.69; 95% CI 1.20, 2.37), and viewing SAC provision as a professional duty (AOR 1.72; 95% CI 1.23, 2.39). In line with survey findings, a substantial number of FGD participants stated they had the right to refuse SAC. Responses to client scenarios revealed “directive counseling” to be common: many midwives indicated that they would actively attempt to persuade clients to act as they (the midwives) thought was best, rather than support clients in making their own decisions.

Conclusion
Findings suggest a need for new guidelines to clarify procedures surrounding conscientious objection and refusal to provide SAC, as well as initiatives to equip midwives to provide rights-based, patient-centered counseling and avoid directive counseling.
Signs of a turning tide in social norms and attitudes toward abortion in Ethiopia: Findings from a qualitative study in four regions
Authors: O’Connell Kathryn A. , Kebede Addisalem T. , Menna Bereket M. , Woldetensay Mengistu T. , Fischer Sara E. , Samandari Ghazaleh , Kassaw Jemal K. 
Published: June 2022

AbstractBackgroundDespite the 2005 expansion in abortion legal indications in Ethiopia, which provided for abortions in cases of rape, incest, or fetal impairment and other circumstances, nearly half of abortions occurred outside health facilities in 2014. The purpose of this study is to explore and understand the social barriers women face in seeking and obtaining quality safe abortion care, as a means to generate evidence that could be used to improve access to and quality of abortion services.MethodsThirty-two focus group discussions with both men and women were held in four different regions of Ethiopia: Addis Ababa; Amhara; Oromia; and the Southern Nations, Nationalities, and Peoples’ Region. The study team recruited participants (n = 193) aged 18–55 in each region using a purposive sample with snowball recruitment techniques. We conducted discussions in Amharic or Afaan Oromo using a semi-structured guide and transcribed and translated them into English for analysis. We used deductive coding and analysis to categorize findings into emergent themes around stigma, barriers, and the changing nature of attitudes around abortion.ResultsDespite changes in abortion law, findings show that women with unwanted pregnancies and those seeking abortions are still heavily stigmatized and sanctioned in a number of communities across Ethiopia. Abortion was deemed unacceptable in most cases, though respondents were more tolerant in cases of risk to the mother’s life and of rape. We saw promising indications that changes are taking place in Ethiopian society’s view of abortion, and several participants indicated progress toward a more supportive environment overall for women seeking abortion care. Still, this progress may be limited by variable knowledge of abortion laws and tightly held gender-based social norms, particularly in rural areas. Most participants noted the importance of education and outreach to improve abortion attitudes and norms.ConclusionPolicymakers should create further awareness in Ethiopia on the availability of quality abortion services in public health facilities and the indications for legal abortion. Such efforts should be based on principles of gender equality, as a means of ensuring enduring changes for women’s reproductive choice throughout the country.
If fear of infertility restricts contraception use, what do we know about this fear? An examination in rural Ethiopia
Authors: Sedlander Erica , Yilma Hagere , Emaway Dessalew , Rimal Rajiv N. 
Published: June 2022

Abstract
Background
Ethiopia has made great progress toward reducing unmet need for family planning and increasing contraception use over the last decade. However, almost one-quarter of women still have an unmet need. The primary reason for non-use is “method-related health concerns” and, within this broad category, the belief that using contraception will cause infertility is common. This belief extends beyond Ethiopia to low-, middle-, and high-income countries across the world. The objective of this paper is to examine associations with the belief that contraception use causes infertility and to subsequently suggest potential strategies to address this misperception.

Methods
We collected data from women of reproductive age (between 15 and 49 years old) in 115 rural districts of Ethiopia (n = 706). Our main outcome variable was the belief that contraception causes infertility. We analyzed data, both individual-level factors and interpersonal factors, using nested logistic regression models.

Results
Almost half of women in our sample (48.2%) believed that contraceptive use causes infertility. In the final model that included factors from both levels, self-efficacy to use contraception (AOR = 0.81, p < 0.05), visiting a health center and speaking to a provider about family planning in the last 12 months (AOR = 0.78, p < 0.05), and husband support of contraception (AOR = 0.77, p < 0.01) were associated with a reduction in the odds of believing that contraception causes infertility. The belief that infertility will result in abandonment from one’s husband (AOR = 3.06, p < 0.001) was associated with an increase in the odds of holding the belief that contraception causes infertility. A home visit in the last 12 months from a health worker who discussed family planning was not associated with the belief that contraceptive use causes infertility.

Conclusions
Given that this belief is both salient and positively associated with other fears such as abandonment from one’s husband, it is critical for family planning programs to address it. Communication campaigns or interventions that address this misperception among couples may diminish this belief, thereby increasing contraception use and reducing unmet need in rural Ethiopia.
Generation and characterization of genome-modified chondrocyte-like cells from the zebra finch cell line immortalized by c-MYC expression
Authors: Jung Kyung Min , Kim Young Min , Yoo Eunhui , Han Jae Yong 
Published: June 2022

Abstract
Background
Due to their cost effectiveness, ease of use, and unlimited supply, immortalized cell lines are used in place of primary cells for a wide range of research purposes, including gene function studies, CRISPR-based gene editing, drug metabolism tests, and vaccine or therapeutic protein production. Although immortalized cell lines have been established for a range of animal species, there is still a need to develop such cell lines for wild species. The zebra finch, which is used widely as a model species to study the neurobiological basis of human speech disorders, has been employed in several functional studies involving gene knockdown or the introduction of exogenous transgenes in vivo; however, the lack of an immortalized zebra finch cell line has hampered precise genome editing studies.

Results
Here, we established an immortalized cell line by a single genetic event, expression of the c-MYC oncogene, in zebra finch embryonic fibroblasts and examined its potential suitability for gene targeting investigations. Retroviral vector-mediated transduction of c-MYC was used to immortalize zebra finch primary fibroblasts; the transformed cells proliferated stably over several passages, resulting in the expression of chondrocyte-specific genes. The transfection efficiency of the immortalized cells was much higher than that of the primary cells. Targeted knockout of the SOX9 gene, which plays a role in the differentiation of mesenchymal progenitor cells into chondrocytes, was conducted in vitro and both apoptosis and decreased expression levels of chondrogenic marker genes were observed in edited cells.

Conclusions
The c-MYC induced immortalized chondrocyte-like cell line described here broadens the available options for establishing zebra finch cell lines, paves the way for in-depth biological researches, and provides convenient approaches for biotechnology studies, particularly genomic modification research.
Dihydromyricetin ameliorates diet-induced obesity and promotes browning of white adipose tissue by upregulating IRF4/PGC-1α
Authors: Leng Qingyang , Zhou Jianhua , Li Chang , Xu Yanhong , Liu Lu , Zhu Yi , Yang Ying , Zhang Hongli , Li Xiaohua 
Published: June 2022

AbstractBackgroundPromoting the browning of white adipose tissue (WAT) is a promising approach for the treatment of obesity and related comorbidities because it increases energy expenditure. In this study, we investigated whether Dihydromyricetin (DHM), a flavonoid component, could ameliorate diet-induced obesity through promoting the browning of WAT.MethodsMale C57BL/6 J mice were received a high-fat diet (HFD) to induce obesity and subsequently were treated with DHM (100 mg/kg/day) or vehicle for 4 weeks. The effects of DHM on weight reduction and metabolic phenotype improvement were observed in the mice. The expression of genes and protein involved in browning of WAT were assessed in inguinal WAT (iWAT) of the mice. Then, the effect of DHM on the inducing browning program was verified in adipocytes differentiated from stromal vascular fraction (SVF) cells of mouse iWAT. Finally, the mechanism by which DHM improves the browning of WAT was explored using RNA-seq and luciferase reporter assay.ResultsWe find that DHM reduces body weight, decreases WAT mass, improves glucose and lipid metabolic disorders, and ameliorates hepatic steatosis in diet-induced obese (DIO) mice. Further studies show that DHM induces WAT browning, which is manifested by increased expression of uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and enhanced mitochondrial activity in iWAT and primary adipocytes. In addition, we also find that DHM enhances interferon regulatory factor 4 (IRF4) expression, which is a key transcriptional regulator of PGC-1α.ConclusionOur findings identify that DHM prevents obesity by inducing the browning of WAT through the upregulation of IRF4/PGC-1α, which may have potential therapeutic implications for the treatment of obesity.