bluuebunny/crossref_metadata_2025 huggingface dataset:
An integrated analysis of the rice transcriptome and lipidome reveals lipid metabolism plays a central role in rice cold tolerance
Authors: Liu Hualong , Xin Wei , Wang Yinglin , Zhang Dezhuang , Wang Jingguo , Zheng Hongliang , Yang Luomiao , Nie Shoujun , Zou Detang
Published: March 2022

Background

Rice (Oryza sativaL.) is one of the most widely grown food crops, and its yield and quality are particularly important for a warm-saturated diet. Cold stress restricts rice growth, development, and yield; however, the specific mechanism of cold tolerance in rice remains unknown.

Results

The analysis of leaf physiological and photosynthetic characteristics showed that the two rice varieties were significantly affected by cold stress, but the cold-tolerant variety KY131 had more stable physiological characteristics, maintaining relatively good photosynthetic capacity. To better explore the transcriptional regulation mechanism and biological basis of rice response to cold stress, a comprehensive analysis of the rice transcriptome and lipidome under low temperature and control temperature conditions was carried out. The transcriptomic analysis revealed that lipid metabolism, including membrane lipid and fatty acid metabolism, may be an important factor in rice cold tolerance, and 397 lipid metabolism related genes have been identified. Lipidomics data confirmed the importance of membrane lipid remodeling and fatty acid unsaturation for rice adaptation to cold stress. This indicates that the changes in the fluidity and integrity of the photosynthetic membrane under cold stress lead to the reduction of photosynthetic capacity, which could be relieved by increased levels of monogalactosyldiacylglycerol that mainly caused by markedly increased expression of levels of 1,2-diacylglycerol 3-beta-galactosyltransferase (MGD). The upregulation of phosphatidate phosphatase (PAP2) inhibited the excessive accumulation of phosphatidate (PA) to produce more phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG), thereby preventing of membrane phase transition under cold stress. In addition, fatty acid β-oxidation is worth further study in rice cold tolerance. Finally, we constructed a metabolic model for the regulatory mechanism of cold tolerance in rice, in which the advanced lipid metabolism system plays a central role.

Conclusions

Lipidome analysis showed that membrane lipid composition and unsaturation were significantly affected, especially phospholipids and galactolipids. Our study provides new information to further understand the response of rice to cold stress.
Prenatal exposure to the Dutch famine is associated with more self-perceived cognitive problems at 72 years of age
Authors: Wiegersma Aline Marileen , Boots Amber , Roseboom Tessa J. , de Rooij Susanne R.
Published: March 2022

Background

Undernutrition during critical periods of neurodevelopment can hinder the developing brain with lasting negative consequences for brain size, structure and function. In this study, we describe self-perceived cognitive problems of men and women who were born around the time of the Dutch famine of 1944–45.

Methods

We compared self-perceived cognitive problems between men and women who had been exposed to the 1944–45 Dutch famine in late, mid or early gestation and those who were born before or conceived after the famine (and had thus not been exposed prenatally). We included 595 participants aged 71–74 years.

Results

Women who had been exposed to famine in late gestation more often reported cognitive problems compared to those who had not been exposed (OR 2.2 [95% CI 1.1–4.4]), whereas for men, this was the case for those exposed in early gestation (OR 2.3 [0.9–5.5]). Furthermore, men and women exposed in early gestation more often reported consulting a healthcare practitioner for cognitive problems in the past 12 months (OR 3.2 [1.3–8.1]). Especially men exposed in early gestation reported having consulted a healthcare practitioner more often than unexposed men (OR 4.4 [1.2–16.0]).

Conclusions

These findings suggest that prenatal undernutrition does not only have lasting effects on brain size, but also on its function, with more self-perceived cognitive problems at older age, which also require more medical attention. Also, the effects of undernutrition depend on sex and its timing during gestation.
Effect of GnRH agonist alone or combined with different low-dose hCG on cumulative live birth rate for high responders in GnRH antagonist cycles: a retrospective study
Authors: He Yuxia , Tang Yan , Chen Shiping , Liu Jianqiao , Liu Haiying
Published: March 2022

Background

There is insufficient evidence regarding the impact of dual trigger on oocyte maturity and reproductive outcomes in high responders. Thus, we aimed to explore the effect of gonadotropin-releasing hormone agonist (GnRHa) trigger alone or combined with different low-dose human chorionic gonadotropin (hCG) regimens on rates of oocyte maturation and cumulative live birth in high responders who underwent a freeze-all strategy in GnRH antagonist cycles.

Methods

A total of 1343 cycles were divided into three groups according to different trigger protocols: group A received GnRHa 0.2 mg (n = 577), group B received GnRHa 0.2 mg and hCG 1000 IU (n = 403), and group C received GnRHa 0.2 mg and hCG 2000 IU (n = 363).

Results

There were no significant differences in age, body mass index, and rates of oocyte maturation, fertilization, available embryo, and top-quality embryo among the groups. However, the incidence of moderate to severe ovarian hyperstimulation syndrome (OHSS) was significantly different among the three groups (0% in group A, 1.49% in group B, and 1.38% in group C). For the first frozen embryo transfer (FET) cycle, there were no significant differences in the number of transferred embryos and rates of implantation, clinical pregnancy, live birth, and early miscarriage among the three groups. Additionally, the cumulative ongoing pregnancy rate and cumulative live birth rate were not significantly different among the three groups. Similarly, there were no significant differences in gestational age, birth weight, birth height, and the proportion of low birth weight among subgroups stratified by singleton or twin.

Conclusions

GnRHa trigger combined with low-dose hCG (1000 IU or 2000 IU) did not improve oocyte maturity and embryo quality and was still associated with an increased risk of moderate to severe OHSS. Therefore, for high responders treated with the freeze-all strategy, the single GnRHa trigger is recommended for final oocyte maturation, which can prevent the occurrence of moderate to severe OHSS and obtain satisfactory pregnancy and neonatal outcomes in subsequent FET cycles.
Association of antimüllerian hormone with polycystic ovarian syndrome phenotypes and pregnancy outcomes of in vitro fertilization cycles with fresh embryo transfer
Authors: Liu Su , Hong Ling , Mo Meilan , Xiao Shan , Wang Xuejin , Fan Xinfeng , Zhang Sainan , Diao Lianghui , Zeng Yong
Published: March 2022

Objective

The current study was undertaken to investigate the relationship between antimüllerian hormone (AMH) and polycystic ovarian syndrome (PCOS) phenotypes and to determine whether AMH is associated with pregnancy outcomes in infertile women undergoing their first in vitro fertilization (IVF) treatment.

Methods

We performed a retrospective cohort study of 2973 infertile women, including 418 women with PCOS undergoing their first IVF treatment at a private fertility center from January 2014 to March 2018. Women were stratified into three groups using cutoffs defined by the 25th and 75th percentiles of the serum AMH level: 746 women had AMH ≤ 2.25 ng/mL; 1486 women had AMH between 2.25 to 5.71 ng/mL; and 741 women had AMH > 5.71 ng/mL. Endocrine characteristics, PCOS phenotypes, stimulation outcomes, pregnancy outcomes were compared among these groups. When there were any statistical differences (P < 0.05) among the three groups, Bonferroni test was performed as post-hoc tests to determine where the statistical differences existed. To assess the relationships between AMH and pregnancy outcomes in total patients and PCOS patients, logistic regression analysis, adjusted for potential confounding covariates, were performed.

Results

Women with high AMH had greater prevalence of hyperandrogenism (HA), polycystic ovarian morphology (PCOM) and amenorrhea than women with low or average AMH. The clinical pregnancy rate were significantly higher in the high-AMH group compared with low- and average-AMH groups (69.9% vs. 58.8% and 64.7% respectively; P < 0.001). The live birth rate was significantly lower in women with AMH ≤ 2.25 ng/mL compared with average- and high-AMH groups (47.6% vs. 55.2 and 59.5% respectively; P < 0.001). However, after controlling for maternal age, oocyte yield, as well as other confounders, AMH was no longer associated with a higher live birth rate (aOR 1.037, 95% CI 0.853–1.261, P = 0.717; aOR 1.099, 95% CI 0.858–1.408, P = 0.455, respectively) and clinical pregnancy rate (aOR 1.064, 95% CI 0.834–1.359, P = 0.617; aOR 1.181, 95% CI 0.875–1.595, P = 0.276, respectively). Moreover, pregnancy outcomes did not differ in PCOS women according to AMH quartiles.

Conclusion

Increased AMH levels associated with PCOS severity and greater ovarian stimulation. However, AMH was not associated with clinical pregnancy rate and live birth rate after controlling for other confounders in women undergoing IVF. Thus, AMH should not be used to alter clinical decisions and exclude patients based on a low or even undetectable AMH value.
ZNF703 promotes triple-negative breast cancer cells through cell-cycle signaling and associated with poor prognosis
Authors: Zhang Xi , Mu Xin , Huang Ou , Wang Zhitang , Chen Jialin , Chen Debo , Wang Gen
Published: March 2022

Background

The oncogenic drivers of triple-negative breast cancer (TNBC), which is characterized by worst prognosis compared with other subtypes, are poorly understood. Although next-generation sequencing technology has facilitated identifying potential targets, few of the findings have been translated into daily clinical practice. The present study is aimed to explore ZNF703 (Zinc finger 703) function and its underlying mechanism in TNBC.

Methods

ZNF703 expressions in tissue microarray were retrospectively examined by immunohistochemistry. The cell proliferation by SRB assay and colony formation assay, as well as cell cycle distribution by flow cytometry were assessed. The protein levels associated with possible underlying molecular mechanisms were evaluated by western blotting. Kaplan-Meier analysis was used to plot survival analysis.

Results

Our data suggest that ZNF703 expressed in 34.2% of triple-negative human breast tumors by immunohistochemistry. In vitro, ZNF703 knockdown had potent inhibitory effects on TNBC cell proliferation and cell cycle, with cyclin D1, CDK4, CDK6, and E2F1 downregulated, while Rb1 upregulated. Moreover, Kaplan-Meier analysis showed that high mRNA expression of ZNF703 was correlated to worse overall survival (HR for high expression was 3.04; 95% CI, 1.22 to 7.57, P = 0.017).

Conclusions

Taken together, the results identified that targeting ZNF703 contributed to the anti-proliferative effects in TNBC cells, due to induced G1-phase arrest. This study is the first to identify ZNF703 as a potentially important protein that is involved in TNBC progression.
Comprehensive analysis of the autophagy-dependent ferroptosis-related gene FANCD2 in lung adenocarcinoma
Authors: Miao Huikai , Ren Qiannan , Li Hongmu , Zeng Mingyue , Chen Dongni , Xu Chunmei , Chen Youfang , Wen Zhesheng
Published: March 2022

Background

The development of lung adenocarcinoma (LUAD) involves the interactions between cell proliferation and death. Autophagy-dependent ferroptosis, a distinctive cell death process, was implicated in a multitude of diseases, whereas no research revealing the relationship between autophagy-dependent ferroptosis and LUAD pathogenesis was reported. Thus, the primary objective was to explore the role and potential function of the autophagy-dependent ferroptosis-related genes in LUAD.

Methods

Clinical information and transcriptome profiling of patients with LUAD were retrieved and downloaded from open-source databases. Autophagy-dependent ferroptosis-related genes were screened by published articles. The critical gene was identified as the intersection between the differentially expressed genes and prognosis-related genes. Patients were divided into high- and low-risk groups using the expression level of the critical gene. The validity of the key gene prognosis model was verified by survival analysis. The correlation between the clinical characteristics of LUAD and the expression level of the key gene was analyzed to explore the clinical significance and prognosis value. And the roles of the key gene in response to chemotherapy, immune microenvironment, and tumor mutation burden were predicted. The validation of key gene expression levels was further performed by quantitative real-time PCR and immunohistochemistry staining.

Results

FANCD2, an essential autophagy-dependent ferroptosis-related gene by searching database, was confirmed as an independent prognostic factor for LUAD occurrence. The high expression level of FANCD2 was associated with an advantaged TNM stage, a less chemotherapy sensitivity, a low ImmuneScore, which indicated a deactivation status in an immune microenvironment, a high tumor mutation burden, and poor survival for LUAD patients. Pathway enrichment analysis showed that FANCD2 responded to oxidative stress and neutrophil-mediated immunity. Quantitative real-time PCR and immunohistochemistry staining showed that the expression level of FANCD2 is higher in LUAD patients than in normal tissue samples, which was in accordance with the database report.

Conclusion

FANCD2, an essential gene related to autophagy-dependent ferroptosis, could work as a biomarker, predicting the survival, chemotherapy sensitivity, tumor immunity, and mutation burden of LUAD. Researching autophagy-dependent ferroptosis and targeting the FANCD2 may offer a new perspective for treating and improving prognosis in LUAD.
The role of alcohol use and adiposity in serum levels of IL-1RA in depressed patients
Authors: Archer Mari , Niemelä Onni , Hämäläinen Mari , Moilanen Eeva , Leinonen Esa , Kampman Olli
Published: March 2022

Background

The role of Interleukin-1 Receptor antagonist (IL-1Ra), an innate antagonist to pro-inflammatory cytokine IL-1, has attracted increasing attention due to its potential pathogenic and therapeutic implications in depression. However, the role of alcohol and adiposity in modulating IL-1Ra cytokine pathway in depressed patients has remainned unknown. The aim of this study was to follow the changes in IL-1Ra serum levels in depressed patients with or without simultaneous alcohol use disorder (AUD) and different degrees of adiposity during 6 months of follow-up.

Materials and methods

A total of 242 patients with depression were followed for 6 months. At baseline 99 patients had simultaneous AUD. Levels of serum IL-1Ra and common mediators of inflammation (IL-6, hs-CRP) were measured. Clinical assessments included Body Mass Index (BMI), Montgomery-Asberg Depression Rating Scale (MADRS) and Alcohol Use Disorders Identification Test (AUDIT) scores.

Results

Significant reductions in clinical symptoms and IL-1Ra were observed during 6-month follow-up. In hierarchical linear regression analysis, the effect of MADRS score, age, gender, and smoking had a combined effect of 2.4% in the model. The effect of AUDIT score increased the effect to 4.2% of variance (p = 0.08), whereas adding BMI increased the effect to 18.5% (p <  0.001).

Conclusion

Adiposity may influence the IL-1Ra anti-inflammatory response in depressed patients, whereas the effect of alcohol consumption in these patients seems insignificant. These findings should be considered in studies on the role of IL-1Ra in depression.

Trial registration

Ostrobothnia Depression Study in ClinicalTrials.gov , Identifier NCT02520271.
Trends of and factors associated with access to residential toilets among the middle-aged and elderly in rural China from 2011 to 2018
Authors: Wang Qun , Cao Huiyuan , Zhang Shuo
Published: March 2022

Background

At the global and country levels, several important sanitation improvement initiatives were launched in the last decade. This study aimed to explore the temporal trend of and factors associated with access to residential toilets among the middle-aged and elderly in rural China from 2011 to 2018.

Methods

This study used the 2011, 2013, 2015, and 2018 data of China Health and Retirement Longitudinal Study (CHARLS). CHARLS was conducted among adults aged ≥ 45 years in 28 provinces of China. We used descriptive statistics and logistic regressions for data analysis.

Results

We found that residential toilet coverage increased by about 6% among population aged ≥ 45 years in rural China from 2011 to 2018. The coverage of flushable toilets and toilets with seats among this sector of the population increased by more than 10% during this period. We also found that being female, higher levels of education, higher annual per capita household consumption, having running water in the residence, larger household size, and better health status were significantly associated with an increased likelihood of residential toilet ownership among population aged ≥ 45 years in rural China.

Conclusions

China made progress in sanitation improvement in rural areas from 2011 to 2018. However, considering the current coverage levels of residential toilets and the vulnerable subgroups who are more prone to toilet deprivation in rural areas, we suggest to the government to implement further targeted toilet improvement interventions to ensure universal coverage of sanitation facilities for the whole of the Chinese population.
Clinical outcomes of endoscopic synovectomy with adjuvant radiotherapy of pigmented villonodular synovitis of the hip: a case series of single center
Authors: sun Hao , Ju Xiao-Dong , Huang Hong-Jie , Zhang Xin , Wang Jian-Quan
Published: March 2022

Background

Though radiotherapy has been widely used for knee pigmented villonodular synovitis (PVNS), there is few literatures about radiotherapy for the treatment of PVNS hip. Thus, the purpose of this study was to analyze the clinical outcomes of endoscopic synovectomy with/without radiotherapy postoperatively of PVNS hip.

Methods

We performed a retrospective study of patients who underwent endoscopy in our hospital from November 2010 to January 2021. Inclusion criteria was patients with magnetic resonance image (MRI) signs, endoscopic findings and/or histological evidence of PVNS. Exclusion criteria was patients lost follow-up. All patients underwent synovectomy endoscopically and were divided into two groups depending on receiving postoperative radiotherapy or not. The primary outcome measurements were the recurrence of PVNS, receiving revision, and/or converting to total hip arthroplasty (THA). The secondary outcome measurements were the patient-reported outcome (PRO) collected at pre- and post-operation, which consist of Hip Outcome Score Activities of Daily Living (HOS-ADL), modified Harris Hip Score (mHHS), International Hip Outcome Tool-12 (IHOT-12), Non-arthritic Hip Scale (NAHS), and visual analog scale (VAS).

Results

In a case series of 16 patients (8 cases of male, 50%), 4 (25%) cases were localized type and 12 (75%) cases were diffuse type. The average follow-up was 44.8 ± 38.2 months (range,3 to 110). 8 (50%) cases (6 diffuse cases and 2 localized cases) received radiotherapy postoperatively, and the rest (6 diffuse cases and 2 localized cases) received endoscopic treatment alone. At the latest follow-up, 3 (18.75%) cases (2 diffuse cases and 1 localized case) who did not receive radiotherapy converted to arthroplasty. The preoperative HOS-ADL, mHHS, IHOT-12, NAHS, VAS scores of remaining 13 patients were 63.1 ± 19.1 (range,32.0 to 98.8), 54.8 ± 20.1 (range, 10.0 to 77.0), 50.9 ± 15.4 (range, 31.0 to 76.6),51.6 ± 15.9 (range, 20.0 to 84.4), 6.0 ± 1.4 (range,4.0 to 8.0) points, respectively. The latest HOS-ADL, mHHS, IHOT-12, NAHS, VAS scores of the 13 patients were 79.7 ± 10.8 (range, 58.0 to 97.6), 78.6 ± 9.1 (range,55.0 to 87.0), 74.7 ± 9.7 (range, 55.6 to 91.0), 78.9 ± 18.7 (range,20.0 to 92.5), 3.1 ± 1.2 (range,2.0 to 6.0) points respectively.

Conclusion

Endoscopic synovectomy can achieve satisfactory PRO in PVNS hip patients. Besides, postoperative adjuvant radiotherapy can achieve higher hip survivability than synovectomy alone in this present study.
Application of WeChat-based flipped classroom on root canal filling teaching in a preclinical endodontic course
Authors: Zhou Yi , Zhang Denghui , Guan Xiaoxu , Pan Qiaoya , Deng Shuli , Yu Mengfei
Published: March 2022

Background

This study was aimed to evaluate the application of WeChat-based flipped classroom in root canal filling teaching in a preclinical endodontic course.

Methods

A two‐group comparative study was designed. The pre-class test, on-site quiz, and root canal filling on extracted premolars were performed by students from a lecture-based classroom group (LG, n = 30) and a WeChat-based flipped classroom group (WFG, n = 30). Results of the Pre-class test and on-site quiz were analyzed by independent samples t-test. Post-filling radiographs were taken and evaluated by a specialist in oral radiology who was blinded to grouping. Results of root canal fillings were analyzed by the Pearson chi-square test. Student responses in questionnaires were analyzed by Fisher’s exact test.

Results

The students in WFG could get significantly higher scores in the on-site test and make better performances in root canal filling than those in LG. In terms of questionnaires, students from WFG were perceived to be more motivated to learn, better to understand the knowledge, better to improve communication and clinical skills, easier to perform root canal filling but spending more time.

Conclusion

The WeChat-based flipped classroom teaching can have a better effect than lecture-based teaching on root canal filling learning for students with limited endodontic experiences.
Exploring how national educational organizations can promote educational research amongst members: a survey-based study
Authors: Butani Lavjay , Dallaghan Gary L. Beck
Published: March 2022

Background

Engagement of academic faculty in research remains low. While barriers to research have been explored, there are no data on how national organizations can help overcome these barriers. Our study explored faculty satisfaction and motivational drivers for engagement with research opportunities offered by the Council on Medical Student Education in Pediatrics (COMSEP), an organization of pediatric medical educators, and characterize strategies perceived by faculty to promote the use of these opportunities.

Methods

In 2021, 5 survey questions were administered to faculty members of COMSEP to explore satisfaction with COMSEP’s research offerings, the perceived value of educational research, and the facilitators, barriers and potential opportunities for COMSEP to promote research. Clark’s Commitment and Necessary Effort model on motivation served as the theoretical framework for our study, which explores motivation, self-efficacy and contextual factors influencing an individual’s pursuit of goals. Chi-square analysis and Wilcoxon Signed Ranks Test were used to compare categorical and scaled variables among groups who did and did not avail of COMSEP’s research offerings.

Results

90 (25%) of 360 recipients responded. 61% expressed satisfaction with COMSEP’s research offerings. 68% indicated research was an expectation of their academic appointment, that education was their primary research focus (74%) and that they did not have other research opportunities that met their needs (58%). Of respondents, 75.7% of females had submitted a proposal compared to 60% of non-responders who were females. The comparison by gender was not statistically significant. Exploration by academic rank revealed that 35% of instructor/assistant professors had submitted a proposal compared to 65% of associate professors/professors (p =.05). Barriers leading to non-submission to any of the offerings included having too much other work, lack of enjoyment in writing and inability to find mentors. Respondents endorsed the importance of several strategies to promote engagement in research-skill building opportunities, personalized consultations and increased funding.

Conclusions

Faculty educators value the importance of educational research and recognize that research opportunities offered by COMSEP address an unmet need, but express ambivalence in the enjoyment of writing (reflecting their mood), and endorse structural barriers, that are amenable to change, affecting their personal agency.
Deep learning radiomics based on contrast-enhanced ultrasound images for assisted diagnosis of pancreatic ductal adenocarcinoma and chronic pancreatitis
Authors: Tong Tong , Gu Jionghui , Xu Dong , Song Ling , Zhao Qiyu , Cheng Fang , Yuan Zhiqiang , Tian Shuyuan , Yang Xin , Tian Jie , Wang Kun , Jiang Tian’an
Published: March 2022

Background

Accurate and non-invasive diagnosis of pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) can avoid unnecessary puncture and surgery. This study aimed to develop a deep learning radiomics (DLR) model based on contrast-enhanced ultrasound (CEUS) images to assist radiologists in identifying PDAC and CP.

Methods

Patients with PDAC or CP were retrospectively enrolled from three hospitals. Detailed clinicopathological data were collected for each patient. Diagnoses were confirmed pathologically using biopsy or surgery in all patients. We developed an end-to-end DLR model for diagnosing PDAC and CP using CEUS images. To verify the clinical application value of the DLR model, two rounds of reader studies were performed.

Results

A total of 558 patients with pancreatic lesions were enrolled and were split into the training cohort (n=351), internal validation cohort (n=109), and external validation cohorts 1 (n=50) and 2 (n=48). The DLR model achieved an area under curve (AUC) of 0.986 (95% CI 0.975–0.994), 0.978 (95% CI 0.950–0.996), 0.967 (95% CI 0.917–1.000), and 0.953 (95% CI 0.877–1.000) in the training, internal validation, and external validation cohorts 1 and 2, respectively. The sensitivity and specificity of the DLR model were higher than or comparable to the diagnoses of the five radiologists in the three validation cohorts. With the aid of the DLR model, the diagnostic sensitivity of all radiologists was further improved at the expense of a small or no decrease in specificity in the three validation cohorts.

Conclusions

The findings of this study suggest that our DLR model can be used as an effective tool to assist radiologists in the diagnosis of PDAC and CP.
Predicting the time to detect moderately virulent African swine fever virus in finisher swine herds using a stochastic disease transmission model
Authors: Malladi Sasidhar , Ssematimba Amos , Bonney Peter J. , St. Charles Kaitlyn M. , Boyer Timothy , Goldsmith Timothy , Walz Emily , Cardona Carol J. , Culhane Marie R.
Published: March 2022

Background

African swine fever (ASF) is a highly contagious and devastating pig disease that has caused extensive global economic losses. Understanding ASF virus (ASFV) transmission dynamics within a herd is necessary in order to prepare for and respond to an outbreak in the United States. Although the transmission parameters for the highly virulent ASF strains have been estimated in several articles, there are relatively few studies focused on moderately virulent strains. Using an approximate Bayesian computation algorithm in conjunction with Monte Carlo simulation, we have estimated the adequate contact rate for moderately virulent ASFV strains and determined the statistical distributions for the durations of mild and severe clinical signs using individual, pig-level data. A discrete individual based disease transmission model was then used to estimate the time to detect ASF infection based on increased mild clinical signs, severe clinical signs, or daily mortality.

Results

Our results indicate that it may take two weeks or longer to detect ASF in a finisher swine herd via mild clinical signs or increased mortality beyond levels expected in routine production. A key factor contributing to the extended time to detect ASF in a herd is the fairly long latently infected period for an individual pig (mean 4.5, 95% P.I., 2.4 - 7.2 days).

Conclusion

These transmission model parameter estimates and estimated time to detection via clinical signs provide valuable information that can be used not only to support emergency preparedness but also to inform other simulation models of evaluating regional disease spread.
Short-term intermittent cigarette smoke exposure enhances alveolar type 2 cell stemness via fatty acid oxidation
Authors: Irie Hidehiro , Ozaki Mari , Chubachi Shotaro , Hegab Ahmed E. , Tsutsumi Akihiro , Kameyama Naofumi , Sakurai Kaori , Nakayama Shingo , Kagawa Shizuko , Wada Sachika , Ishii Makoto , Betsuyaku Tomoko , Fukunaga Koichi
Published: March 2022

Background

Cigarette smoke (CS) is associated with chronic obstructive pulmonary disease (COPD) and cancer. However, the underlying pathological mechanisms are not well understood. We recently reported that mice exposed to long-term intermittent CS for 3 months developed more severe emphysema and higher incidence of adenocarcinoma than mice exposed to long-term continuous CS for 3 months and long-term continuous CS exposure activated alveolar stem cell proliferation. However, the influence of variations in the CS exposure pattern in alveolar stem cell in unknown. Here, we exposed mice to 3 weeks of continuous or intermittent CS to identify whether different CS exposure patterns would result in differential effects on stem cells and the mechanisms underlying these potential differences.

Methods

Female mice expressing GFP in alveolar type 2 (AT2) cells, which are stem cells of the alveolar compartment, were exposed to mainstream CS via nasal inhalation. AT2 cells were collected based on their GFP expression by flow cytometry and co-cultured with fibroblasts in stem cell 3D organoid/colony-forming assays. We compared gene expression profiles of continuous and intermittent CS-exposed AT2 cells using microarray analysis and performed a functional assessment of a differentially expressed gene to confirm its involvement in the process using activator and inhibitor studies.

Results

AT2 cells sorted from intermittent CS-exposed mice formed significantly more colonies compared to those from continuous CS-exposed mice, and both CS-exposed groups formed significantly more colonies when compared to air-exposed cells. Comparative microarray analysis revealed the upregulation of genes related to fatty acid oxidation (FAO) pathways in AT2 cells from intermittent CS-exposed mice. Treatment of intermittent CS-exposed mice with etomoxir, an inhibitor of the FAO regulator Cpt1a, for 5 weeks resulted in a significant suppression of the efficiency of AT2 cell colony formation. In vitro treatment of naïve AT2 cells with a FAO activator and inhibitor further confirmed the relationship between FAO and AT2 stem cell function.

Conclusions

Alveolar stem cell function was more strongly activated by intermittent CS exposure than by continuous CS exposure. We provide evidence that AT2 stem cells respond to intermittent CS exposure by activating stem cell proliferation via the activation of FAO.
IR792-MCN@ZIF-8-PD-L1 siRNA drug delivery system enhances photothermal immunotherapy for triple-negative breast cancer under near-infrared laser irradiation
Authors: Wang Yongmei , Wang Haibo , Song Yuhua , Lv Meng , Mao Yan , Song Hongming , Wang Yuanyuan , Nie Gang , Liu Xiaoyi , Cui Jian , Zou Xueqing
Published: March 2022

Background

Despite extensive investigations on photothermal therapy, the clinical application is restricted due to poor stability, low therapeutic efficacy of photothermal therapy agents and its affinity loss in the multistep synthesis of delivery carriers. To address this, we designed an IR792-MCN@ZIF-8-PD-L1 siRNA (IM@ZP) nanoparticle drug delivery system. IM@ZP was prepared by in situ synthesis and physical adsorption, followed by characterization. Photothermal conversion ability of IM@ZP was assessed by irradiation of near-infrared (NIR) laser, followed by analysis of its effect on 4T1 cell viability, maturation of dendritic cells (DCs) and the secretion of related cytokines in vitro, and the changes of tumor infiltrating T cells and natural killer (NK) cells in vivo. Subcutaneous 4T1 tumor-bearing mouse and lung metastasis models were established to investigate the role of IM@ZP in killing tumor and inhibiting metastasis in vivo.

Results

IM@ZP was uniform nanoparticles of 81.67 nm with the characteristic UV absorption peak of IR792, and could effectively adsorb PD-L1 siRNA. Under the irradiation of 808 nm laser, IM@ZP exhibited excellent photothermal performance. IM@ZP could be efficiently uptaken by 4T1 cells, and had high transfection efficiency of PD-L1 siRNA. Upon NIR laser irradiation, IM@ZP effectively killed 4T1 cells, upregulated HSP70 expression, induced DC maturation and increased secretion of TNF-α and IL-6 in vitro. Moreover, in vivo experimental results revealed that IM@ZP enhanced photothermal immunotherapy as shown by promoted tumor infiltrating CD8 +  and CD4 +  T cells and NK cells, and inhibited tumor growth and lung metastasis.

Conclusion

Together, biocompatible IM@ZP nanoparticles result in high photothermal immunotherapy efficiency and may have a great potential as a delivery system for sustained cancer therapy.

Graphical Abstract
Effects of iron oxide nanoparticles as T2-MRI contrast agents on reproductive system in male mice
Authors: Yang Heyu , Wang Hui , Wen Chenghao , Bai Shun , Wei Pengfei , Xu Bo , Xu Yunjun , Liang Chaozhao , Zhang Yunjiao , Zhang Guilong , Wen Huiqin , Zhang Li
Published: March 2022

Iron oxide nanoparticles (IONPs)-based contrast agents are widely used for T2-weighted magnetic resonance imaging (MRI) in clinical diagnosis, highlighting the necessity and importance to evaluate their potential systematic toxicities. Although a few previous studies have documented the toxicity concerns of IONPs to major organs, limited data are available on the potential reproductive toxicity caused by IONPs, especially when administrated via intravenous injection to mimic clinical use of MRI contrast agents. Our study aimed to determine whether exposure to IONPs would affect male reproductive system and cause other related health concerns in ICR mice. The mice were intravenously injected with different concentrations IONPs once followed by routine toxicity tests of major organs and a series of reproductive function-related analyses at different timepoints. As a result, most of the contrast agents were captured by reticuloendothelial system (RES) organs such as liver and spleen, while IONPs have not presented adverse effects on the normal function of these major organs. In contrast, although IONPs were not able to enter testis through the blood testicular barrier (BTB), and they have not obviously impaired the overall testicular function or altered the serum sex hormones levels, IONPs exposure could damage Sertoli cells in BTB especially at a relative high concentration. Moreover, IONPs administration led to a short-term reduction in the quantity and quality of sperms in a dose-dependent manner, which might be attributed to the increase of oxidative stress and apoptotic activity in epididymis. However, the semen parameters have gradually returned to the normal range within 14 days after the initial injection of IONPs. Collectively, these results demonstrated that IONPs could cause reversible damage to the reproductive system of male mice without affecting the main organs, providing new guidance for the clinical application of IONPs as T2-MRI contrast agents.

Graphical Abstract
All-in-one theranostic nano-platform based on polymer nanoparticles for BRET/FRET-initiated bioluminescence imaging and synergistically anti-inflammatory therapy for ulcerative colitis
Authors: Yan Xiangji , Yang Chunhua , Yang Mei , Ma Yana , Zhang Yuanyuan , Zhang Yujie , Liu Cui , Xu Qiuran , Tu Kangsheng , Zhang Mingzhen
Published: March 2022

Background

Ulcerative colitis (UC), a subtype of inflammatory bowel disease (IBD), has evolved into a global burden given its high incidence. There is a clinical need to create better diagnostic and therapeutic approaches to UC.

Results

We fabricated P-selectin binding peptide-decorated poly lactic-co-glycolic acid (PBP-PLGA-NP) doped with two lipophilic dyes, DiL and DiD. Meanwhile, two low-toxic anti-inflammatory natural products (betulinic acid [BA] and resveratrol [Res]) were co-loaded in the PBP-PLGA-NP system. The BA/Res-loaded NPs had an average size of around 164.18 nm with a negative zeta potential (− 25.46 mV). Entrapment efficiencies of BA and Res were 74.54% and 52.33%, respectively, and presented a sustained drug release profile. Further, the resulting PBP-PLGA-NP could be internalized by RAW 264.7 cells and Colon-26 cells efficiently in vitro and preferentially localized to the inflamed colon. When intravenously injected with luminol, MPO-dependent bioluminescence imaging to visualize tissue inflammation was activated by the bioluminescence and fluorescence resonance energy transfer (BRET-FRET) effect. Importantly, injected NPs could remarkably alleviate UC symptoms yet maintain intestinal microbiota homeostasis without inducing organ injuries in the mice models of colitis.

Conclusions

This theranostic nano-platform not only serves as a therapeutic system for UC but also as a non-invasive and highly-sensitive approach for accurately visualizing inflammation.

Graphical Abstract
QR code model: a new possibility for GPCR phosphorylation recognition
Authors: Chen Hao , Zhang Suli , Zhang Xi , Liu Huirong
Published: March 2022

G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in the human body and are responsible for accurately transmitting extracellular information to cells. Arrestin is an important member of the GPCR signaling pathway. The main function of arrestin is to assist receptor desensitization, endocytosis and signal transduction. In these processes, the recognition and binding of arrestin to phosphorylated GPCRs is fundamental. However, the mechanism by which arrestin recognizes phosphorylated GPCRs is not fully understood. The GPCR phosphorylation recognition “bar code model” and “flute” model describe the basic process of receptor phosphorylation recognition in terms of receptor phosphorylation sites, arrestin structural changes and downstream signaling. These two models suggest that GPCR phosphorylation recognition is a process involving multiple factors. This process can be described by a “QR code” model in which ligands, GPCRs, G protein-coupled receptor kinase, arrestin, and phosphorylation sites work together to determine the biological functions of phosphorylated receptors.

Graphical Abstract
A descriptive assessment of a broad range of food-related parenting practices in a diverse cohort of parents of preschoolers using the novel Real-Time Parent Feeding Practices Survey
Authors: Loth K. A. , Ji Z. , Wolfson J. , Neumark-Sztainer D. , Berge J. M. , Fisher J. O.
Published: March 2022

Background

Much of the research to-date on food parenting has evaluated typical use of various parent feeding practices via questionnaire. The Real-Time Parent Feeding Practices Measurement survey was developed for use within an Ecological Momentary Assessment (EMA) protocol to capture momentary use of parent feeding practices in real-time.

Methods

This manuscript describes the development of the EMA-based Real-Time Parent Feeding Practices survey and highlights initial descriptive data on the real-time use of 22 individual parent feeding practices (e.g., pressure-to-eat, guided choices, etc.) as reported via EMA by parents of preschool-aged children (n = 116) over a 10-day data collection time period. A total of 3382 eating occasions were reported, with an average of 29.2 reported eating occasions per participant.

Results

Results revealed that most participants used a variety of food-related parenting practices day-to-day that span four higher-order domains: structure, autonomy support, coercive control and indulgence. Supportive feeding practices, defined as those from the structure and autonomy support domains, were reported most frequently, with one or more structure behavior (e.g., specific mealtime rules/routines) was used at 88.9% of reported eating occasions and one or more autonomy support behavior (e.g., involvement of the child in meal preparation) was used at 87.3% of eating occasions. While unsupportive feeding practices, defined as practices from within the coercive control (e.g., pressure-to-eat) and indulgent (e.g., anticipatory catering) feeding domains, were reported less frequently, one or more behaviors from each of these domains were still reported at over 25% of all eating occasions.

Conclusions

Results of the current study take a next step towards deepening our understanding of the use of a broad range of food-related parenting practices in real-time. Findings revealed that the vast majority of practices used by parents fall within the structure and autonomy support domains. However, most parents did not exclusively use supportive or unsupportive practices, rather they used a combination of food-related parenting practices across all domains. Future research should continue to explore a broad range of food-related parenting practices and seek to understand how parent approaches to feeding are associated with long-term child outcomes, including dietary intake, food preferences, and eating patterns.
Treatment regimens for neuromyelitis optica spectrum disorder attacks: a retrospective cohort study
Authors: Demuth Stanislas , Guillaume Maxime , Bourre Bertrand , Ciron Jonathan , Zephir Hélène , Sirejacob Yoann , Kerbrat Anne , Lebrun-Frenay Christine , Papeix Caroline , Michel Laure , Laplaud David , Vukusic Sandra , Maillart Elisabeth , Cohen Mikael , Audoin Bertrand , Marignier Romain , Collongues Nicolas ,   for the NOMADMUS Study Group
Published: March 2022

Background

Neuromyelitis optica spectrum disorder (NMOSD) attacks require an urgent probabilistic anti-inflammatory therapeutic strategy. As inadequately treated attacks result in disability, there is a need to identify the optimal attack-treatment regimen. Our study aimed to identify predictors of outcome after a first attack in patients with an NMOSD presentation and propose the best treatment strategy.

Methods

We performed a retrospective cohort study on the French national NMOSD registry (NOMADMUS), a nested cohort of the French multiple sclerosis observatory (OFSEP) recruiting patients with NMOSD presentations in France. We studied the first attack for any independent locations of clinical core characteristic of NMOSD, in treatment-naïve patients. The primary outcome was the evolution of the Expanded Disability Status Scale (EDSS) score at 6 months, stratified in two ways to account for recovery (return to baseline EDSS score) and treatment response (classified as “good” if the EDSS score decreased by ≥ 1 point after a nadir EDSS score ≤ 3, or by ≥ 2 points after a nadir EDSS score > 3). We used ordinal logistic regression to infer statistical associations with the outcome.

Results

We included 211 attacks among 183 patients (104 with anti-AQP4 antibodies, 60 with anti-MOG antibodies, and 19 double seronegative). Attack treatment regimens comprised corticosteroids (n = 196), plasma exchanges (PE; n = 72) and intravenous immunoglobulins (n = 6). Complete recovery was reached in 40 attacks (19%) at 6 months. The treatment response was “good” in 134 attacks (63.5%). There was no improvement in EDSS score in 50 attacks (23.7%). MOG-antibody seropositivity and short delays to PE were significantly and independently associated with better recovery and treatment response.

Conclusions

We identified two prognostic factors: serostatus (with better outcomes among MOG-Ab-positive patients) and the delay to PE. We, therefore, argue for a more aggressive anti-inflammatory management of the first attacks suggesting an NMOSD presentation, with the early combination of PE with corticosteroids.
The comparative anti-cancer effects of krill oil and oxaliplatin in an orthotopic mouse model of colorectal cancer
Authors: Jayathilake Abilasha Gayani , Hassanzadeganroudsari Majid , Jovanovska Valentina , Luwor Rodney Brain , Nurgali Kulmira , Su Xiao Qun
Published: March 2022

Background

Our in vitro studies demonstrated that krill oil (KO) has anti-cancer potential. This study aimed to compare the anti-cancer effects of KO with a commonly used chemotherapeutic drug, oxaliplatin and to identify the molecular mechanisms associated with KO supplementation in a mouse model of colorectal cancer (CRC).

Methods

Thirty-six male Balb/c mice were randomly divided into six groups. Five groups received standard chow diet supplemented with KO (150 g/kg)), corn oil (150 g/kg), KO combined with ½ dose of oxaliplatin (1.5 mg/kg body weight/3 times per week), corn oil combined with ½ dose of oxaliplatin (1.5 mg/kg body weight/3 times per week), or a full dose of oxaliplatin (3 mg/kg body weight/3 times per week). The control (sham) group received a standard chow diet. Treatments started three weeks before and continued for three weeks after orthotopic CRC induction. The number of metastases, tumour weight and volume were quantified ex-vivo. The expression of cytochrome c, cleaved caspase-9 and -3, DNA damage, PD-L1, PD-L2 and HSP-70 were determined.

Results

A significant reductions in the weight and volume of tumours were observed in mice treated with KO and KO plus a ½ dose of oxaliplatin compared to the sham group, similar to oxaliplatin-treated mice. KO, and KO plus ½ dose of oxaliplatin significantly increased the expression of cytochrome c, cleaved caspase-9 and -3, and DNA damage and decreased expression of PD-L1, PD-L2 and HSP-70 in tumour tissues compared to the sham group.

Conclusions

The in vivo anti-cancer effects of KO are comparable with oxaliplatin. Thus, dietary KO supplementation has a great potential as a therapeutic/adjunctive agent for CRC treatment.