bluuebunny/crossref_metadata_2025 huggingface dataset:
Vertical sleeve gastrectomy associates with airway hyperresponsiveness in a murine model of allergic airway disease and obesity
Authors: Womble Jack T. , Ihrie Mark D. , McQuade Victoria L. , Hegde Akhil , McCravy Matthew S. , Phatak Sanat , Tighe Robert M. , Que Loretta G. , D’Alessio David , Walker Julia K. L. , Ingram Jennifer L.
Published: March 2023

Introduction

Asthma is a chronic airway inflammatory disease marked by airway inflammation, remodeling and hyperresponsiveness to allergens. Allergic asthma is normally well controlled through the use of beta-2-adrenergic agonists and inhaled corticosteroids; however, a subset of patients with comorbid obesity experience resistance to currently available therapeutics. Patients with asthma and comorbid obesity are also at a greater risk for severe disease, contributing to increased risk of hospitalization. Bariatric surgery improves asthma control and airway hyperresponsiveness in patients with asthma and comorbid obesity, however, the underlying mechanisms for these improvements remain to be elucidated. We hypothesized that vertical sleeve gastrectomy (VSG), a model of metabolic surgery in mice, would improve glucose tolerance and airway inflammation, resistance, and fibrosis induced by chronic allergen challenge and obesity.

Methods

Male C57BL/6J mice were fed a high fat diet (HFD) for 13 weeks with intermittent house dust mite (HDM) allergen administration to induce allergic asthma, or saline as control. At week 11, a subset of mice underwent VSG or Sham surgery with one week recovery. A separate group of mice did not undergo surgery. Mice were then challenged with HDM or saline along with concurrent HFD feeding for 1-1.5 weeks before measurement of lung mechanics and harvesting of tissues, both of which occurred 24 hours after the final HDM challenge. Systemic and pulmonary cytokine profiles, lung histology and gene expression were analyzed.

Results

High fat diet contributed to increased body weight, serum leptin levels and development of glucose intolerance for both HDM and saline treatment groups. When compared to saline-treated mice, HDM-challenged mice exhibited greater weight gain. VSG improved glucose tolerance in both saline and HDM-challenged mice. HDM-challenged VSG mice exhibited an increase in airway hyperresponsiveness to methacholine when compared to the non-surgery group.

Discussion

The data presented here indicate increased airway hyperresponsiveness in allergic mice undergoing bariatric surgery.
Serum Irisin level is associated with fall risk, muscle strength, and cortical porosity in postmenopausal women
Authors: Liang Hanting , Qi Wenting , Jiajue Ruizhi , Chi Yue , Liu Wei , Wang Ou , Li Mei , Xing Xiaoping , Yu Wei , Jiang Yan , Xia Weibo
Published: March 2023

Background

Irisin plays a role in bone-muscle crosstalk, but the relationship between the serum irisin level and bone microarchitecture remains unknown.

Objective

This study aimed to investigate the relationships between serum irisin level and fall risk, muscle strength, bone mineral density (BMD), and bone microarchitecture among Chinese postmenopausal women.

Methods

In all 138 postmenopausal women, handgrip strength, short physical performance battery (SPPB), and the timed up-and-go test were performed to evaluate muscle strength, physical performance, and fall risk, respectively. The serum irisin was measured. High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed to acquire volumetric BMD and bone microarchitecture. Bivariate analysis was used to explore relationships between serum irisin level and muscle strength and HR-pQCT parameters. Univariate and multivariate linear regression analyses were performed to determine associations between serum irisin level and vBMD and cortical porosity (Ct.Po).

Results

All participants had a median serum irisin level of 3.91 μg/ml. Participants with high fall risk had significantly lower serum irisin levels than those with low fall risk (2.22 μg/ml vs. 4.16 μg/ml, p=0.024). Irisin level was positively related to handgrip strength (rs=0.185, p=0.030) and SPPB performance. In univariate linear regression, serum irisin level was positively associated with cortical volumetric BMD (Ct.vBMD, radius: standardized β=0.184, p=0.031; tibia: standardized β=0.242, p=0.004), but it had no significant associations with Ct.vBMD after multivariate adjustment. After adjusting by age, height, serum sclerostin level, and body fat ratio, only Ct.Po at the distal radius had a significantly negative association with serum irisin level (standardized β=-0.276, p=0.003).

Conclusion

Postmenopausal women with lower serum irisin levels have a higher fall risk, weaker muscle strength, and higher cortical porosity. Moreover, serum irisin level has a positive association with Ct.vBMD, but it is affected by factors such as age.
Enhanced contrast synchrotron X-ray microtomography for describing skeleton-associated soft tissue defects in zebrafish mutants
Authors: Leyhr Jake , Sanchez Sophie , Dollman Kathleen N. , Tafforeau Paul , Haitina Tatjana
Published: March 2023

Detailed histological analyses are desirable for zebrafish mutants that are models for human skeletal diseases, but traditional histological techniques are limited to two-dimensional thin sections with orientations highly dependent on careful sample preparation. On the other hand, techniques that provide three-dimensional (3D) datasets including µCT scanning are typically limited to visualizing the bony skeleton and lack histological resolution. We combined diffusible iodine-based contrast enhancement (DICE) and propagation phase-contrast synchrotron radiation micro-computed tomography (PPC-SRµCT) to image late larval and juvenile zebrafish, obtaining high-quality 3D virtual histology datasets of the mineralized skeleton and surrounding soft tissues. To demonstrate this technique, we used virtual histological thin sections and 3D segmentation to qualitatively and quantitatively compare wild-type zebrafish and nkx3.2-/- mutants to characterize novel soft-tissue phenotypes in the muscles and tendons of the jaw and ligaments of the Weberian apparatus, as well as the sinus perilymphaticus associated with the inner ear. We could observe disrupted fiber organization and tendons of the adductor mandibulae and protractor hyoideus muscles associated with the jaws, and show that despite this, the overall muscle volumes appeared unaffected. Ligaments associated with the malformed Weberian ossicles were mostly absent in nkx3.2-/- mutants, and the sinus perilymphaticus was severely constricted or absent as a result of the fused exoccipital and basioccipital elements. These soft-tissue phenotypes have implications for the physiology of nkx3.2-/- zebrafish, and demonstrate the promise of DICE-PPC-SRµCT for histopathological investigations of bone-associated soft tissues in small-fish skeletal disease models and developmental studies more broadly.
Development and validation of a nomogram model for predicting residue of partially cystic thyroid nodules after ultrasound-guided ethanol and thermal ablation
Authors: Li Di , Zhang Xiaoer , Zhang Yutong , Huang Tongyi , Zhang Rui , Zhou Wenwen , Xie Xiaoyan , Xu Ming
Published: March 2023

Objectives

To develop and validate a nomogram model for predicting residue of partially cystic thyroid nodules (PCTNs) after ethanol and thermal ablation.

Materials and Methods

From July 2015 to August 2022, a total of 97 patients (age 40.78 ± 12.61 years) with 107 treated benign PCTNs receiving ethanol and thermal ablation were enrolled. Pre-ablative laboratory test results and the ultrasound (US) and contrast-enhanced ultrasound (CEUS) features of lesions were collected. They were categorized into non-residue group and residue group according to the CEUS examination assessment after ablation. Univariate and multivariate logistic regression analysis were adopted to build a nomogram. The nomogram was validated by internal stratified fivefold cross-validation. The calibration, discrimination and clinical utility of the nomogram were investigated to assess the performance of the model.

Results

Residue was reported in 30 out of 107nodules (28.0%). Multivariate logistic regression analysis revealed initial volume (OR=1.12, 95%CI 1.06-1.19) and presence of septum (OR=3.19, 95%CI 1.09-9.36) were predictors of residue of PCTNs. The nomogram developed by the above factors showed good calibration and discrimination. The area under the curve (AUC), sensitivity and specificity of this model were 0.832, 86.7% and 68.8%, respectively. When applied to internal validation, the model revealed good generalizability with stratified fivefold cross-validation in the cohort (mean AUC = 0.821).

Conclusions

The nomogram model has good performance for predicting the residue of PCTNs undergoing ethanol and thermal ablation. This could play a role in the decision of treatment and follow-up in clinical practice.
COVID-19 pandemic phases and female precocious puberty: The experience of the past 4 years (2019 through 2022) in an Italian tertiary center
Authors: Chioma Laura , Chiarito Mariangela , Bottaro Giorgia , Paone Laura , Todisco Tommaso , Bizzarri Carla , Cappa Marco
Published: March 2023

Objective

Since the outbreak of COVID-19 pandemic, several centers of pediatric endocrinology worldwide have observed a significant increase in the number of girls presenting with precocious or early puberty. We aimed to compare the incidence rates of female precocious puberty before and during the different phases of COVID-19 pandemic.

Methods

We have retrospectively analyzed all the consultations recorded in the outpatient clinic database of the Endocrinology Unit of Bambino Gesù Children’s Hospital, Rome, Italy, from the lockdown start in March 2020 up to September 2020, in comparison with the consultations recorded in the same months of 2019, 2021 and 2022. Age, height, weight, body mass index, Tanner’s pubertal stage and bone age at presentation, birth weight, ethnicity, family history of central precocious puberty (CPP), maternal age at menarche, history of adoption were retrieved from clinical records. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) both at baseline and after gonadotropin-releasing hormone (GnRH) stimulation, and basal estradiol levels were collected.

Results

In 2019, 78 girls with suspected precocious puberty were referred for endocrinological consultation, compared to 202 girls in 2020, 158 girls in 2021 and 112 girls in 2022. A significant increase in the proportion of girls diagnosed with rapidly progressive CPP was observed in 2020, compared to 2019 (86/202 vs. 18/78, p<0.01). In the following periods of 2021 and 2022, a gradual decrease in the number of cases of progressive CPP was evident, so much that the number of cases was not significantly different from that observed in 2019 (56/158 in 2021 and 35/112 in 2022, p=0.054 and p=0.216 respectively, compared to 2019).

Conclusions

Our research suggests that drastic lifestyle changes, such as those imposed by COVID-19 lockdown, and the consequent stress may affect the regulation of pubertal timing. The remarkable increase in CPP cases observed during the 2020 first pandemic wave seems to be reduced in 2021 and 2022, concurrently with the progressive resumption of daily activities. These data seem to support the hypothesis of a direct relationship between profound life-style changes related to the pandemic and the rise in precocious puberty cases.
HCG-responsive aldosteronoma with transient secretion during pregnancy confirmed through HCG-stimulated adrenal venous sampling
Authors: Castinetti Frederic , Guerin Carole , Louiset Estelle , Lacroix André
Published: March 2023

Primary aldosteronism can be regulated by the ectopic expression of G-protein coupled receptors in aldosteronomas or bilateral hyperplasias. We report a rare case of a young woman in whom 2 pregnancies were complicated by pre-eclampsia and 1 miscarriage. The transient primary aldosteronism during pregnancies suggested the possibility of HCG stimulated aberrant adrenal expression of LHCG receptor in her adrenal tissues. This was supported by increased aldosterone and renin suppression during 5-day HCG stimulation test outside of pregnancy. Following a second 5-day HCG stimulation test, bilateral simultaneous adrenal vein sampling identified a lateralized source of aldosterone from an 8 mm right adrenal nodule. A right laparoscopic adrenalectomy resulted in clinical and biochemical cure and allowed a further uneventful pregnancy a few years later. This case illustrates the indication to investigate for potential primary aldosteronism in woman with transient hypertension during pregnancy.
Multigenerational mistimed feeding drives circadian reprogramming with an impaired unfolded protein response
Authors: Huang Kai , Zhang Tao , Zhang Wenjun , Gu Yue , Yu Pan , Sun Lanqing , Liu Zhiwei , Wang Tao , Xu Ying
Published: March 2023

Mistimed food intake in relation to the day/night cycle disrupts the synchrony of circadian rhythms in peripheral tissues and increases the risk of metabolic diseases. However, the health effects over generations have seldom been explored. Here, we established a 10-generation mouse model that was continuously fed with daytime-restricted feeding (DRF). We performed RNA-seq analysis of mouse liver samples obtained every 4 h over a 24 h period from F2, F5 and F10 generations exposed to DRF. Multigenerational DRF programs the diurnal rhythmic transcriptome through a gain or loss of diurnal rhythmicity over generations. Gene ontology (GO) analysis of the differential rhythmic transcriptome revealed that adaptation to persistent DRF is accompanied by impaired endoplasmic reticulum (ER) stress. Consistently, a substantially higher level of folding-deficient proinsulin was observed in F10 liver tissues than in F2 and F5 liver tissues following tail vein injection. Subsequently, tunicamycin induced more hepatocyte death in F10 samples than in F2 and F5 samples. These data demonstrate that mistimed food intake could produce cumulative effects over generations on ER stress sensitivity in mice.
Extracellular vesicles in osteoarthritis of peripheral joint and temporomandibular joint
Authors: Yang Benyi , Li Xin , Fu Chaoran , Cai Wenyi , Meng Bowen , Qu Yan , Kou Xiaoxing , Zhang Qingbin
Published: March 2023

Osteoarthritis (OA) is a disabling disease with significant morbidity worldwide. OA attacks the large synovial joint, including the peripheral joints and temporomandibular joint (TMJ). As a representative of peripheral joint OA, knee OA shares similar symptoms with TMJ OA. However, these two joints also display differences based on their distinct development, anatomy, and physiology. Extracellular vesicles (EVs) are phospholipid bilayer nanoparticles, including exosomes, microvesicles, and apoptotic bodies. EVs contain proteins, lipids, DNA, micro-RNA, and mRNA that regulate tissue homeostasis and cell-to-cell communication, which play an essential role in the progression and treatment of OA. They are likely to partake in mechanical response, extracellular matrix degradation, and inflammatory regulation during OA. More evidence has shown that synovial fluid and synovium-derived EVs may serve as OA biomarkers. More importantly, mesenchymal stem cell-derived EV shows a therapeutic effect on OA. However, the different function of EVs in these two joints is largely unknown based on their distinct biological characteristic. Here, we reviewed the effects of EVs in OA progression and compared the difference between the knee joint and TMJ, and summarized their potential therapeutic role in the treatment of OA.
A mathematical approach to survey electrochemical impedance spectroscopy for aging in lithium-ion batteries
Authors: Chen Bor-Rong , Police Yugandhar R. , Li Meng , Chinnam Paramesh R. , Tanim Tanvir R. , Dufek Eric J.
Published: March 2023

Electrochemical impedance spectroscopy (EIS) is a valuable technique to detect the health status and aging phenomena in lithium-ion batteries (LiB). Equivalent circuit modeling (ECM) is conventionally used when interpreting EIS data and gaining physical insights into the aging mechanisms. However, performing ECM is resource intensive and expert-level of knowledge is usually required to select suitable models and fitting parameters. This article presents a quick and user-friendly data analysis algorithm as an alternative to ECM by mathematically fitting geometric features in Nyquist plots and obtaining the growth trends of the features. The evolving trends in the Nyquist plots, such as chord lengths of the arcs and interception points, are consistent with the growth of resistance components obtained using ECM with R2 values from 0.67 to 0.99, and therefore can be used as indicators of battery aging. Our results show that the quick-fitting approach is suitable for analyzing a series of EIS data acquired during battery cycling and identifying the underlying aging mechanisms.
The influence of dust aerosols on solar radiation and near-surface temperature during a severe duststorm transport episode
Authors: Huang Guan , Zhou Yaman , Guo Zijia , Liu Xin , Chen Yonghang , Liu Qiong , Ta Zhijie , Wang Pengtao , He Qing , Gao Jiacheng , Zhang Ying
Published: March 2023

In the west of China, a rarely seen black storm, with a high intensity of dust aerosols and a large area of influence, occurred from April 26–29, 2015, for the first time, after more than 30 years. Based on the regional climate model (RegCM version 4.6), combined with Moderate Resolution Imaging Spectroradiometer (MODIS) satellite retrieval, meteorological, and environmental data, this work presents the pollution situation, weather background, and backward trajectory during the black storm process. In addition, we analyzed the temporal–spatial distribution of aerosol optical depth (AOD) and the impacts of dust aerosols on solar radiation and near-surface temperature under this extreme weather condition. We discovered that this black storm process was caused by the surface cold high pressure and frontal transit under the background of the upper-air circulation of “two troughs and two ridges.” The pollutants primarily from Xinjiang and the Central Asia region, along with the airflow, entered northern Xinjiang almost simultaneously with the southwest airflow, piled up along the Tianshan Mountains, and then crossed the mountains into southern Xinjiang. In addition, the areas with high AOD were mostly in the desert regions and basins, whereas the low-value areas were mountainous areas with relatively high altitudes due to the effect of geographical and climatic conditions. The AOD from RegCM 4.6 was generally lower, unlike the MODIS AOD. Moreover, the dust aerosols from this black storm caused a significant decline in net short-wave radiation (NSR) both at the top of the atmosphere (TOA) and surface. The cooling effect was more significant in the region with high AOD. For the areas where the AOD was higher than 0.7, the net short-wave radiative forcing of dust aerosols (ADRF) at the surface was above −70 W•m−2; on the other hand, the cooling effect at the TOA was not as significant as that at the surface, with the ADRFTOA being only about a quarter of the ADRFSUR. The ADRFSUR could reduce the near-surface temperature, and the region with a large temperature drop corresponded to the high-value areas of ADRFSUR/AOD. During this black storm, the near-surface temperature response to dust aerosols reached 0.40°C–2.9°C with a significant temperature drop because of cold air.
Dynamic variation of non-structural carbohydrates in branches and leaves of temperate broad-leaved tree species over a complete life history
Authors: Wang Kaibo , Jin Guangze , Liu Zhili
Published: March 2023

The composition of non-structural carbohydrates (NSC), one of the photosynthetic products of plants, reflects the survival strategy of a plant. Although several studies have investigated variation of NSC content in woody plants over a set time scale, few studies have considered the dynamic variation of NSC over a continuous life history. In this study, the leaves, new twigs, and old branches of seven temperate broad-leaved tree species (diffuse-porous species:Betula platyphylla,Betula costata,Tilia amurensis,Acer pictumsubsp.mono; ring-porous species:Ulmus davidianavar.japonica,Ulmus laciniata,Fraxinus mandshurica) were observed at three life history stages (seedling, sapling, and mature tree) to measure the dynamic changes of NSC and its influencing factors throughout the entire life cycles of these species. The results showed that life history, wood type, and environmental factors (soil nitrogen and phosphorus content, soil pH) significantly affected the NSC content in leaves and branches (including both new twigs and old branches). As plants grew, the NSC content in the leaves and branches generally showed an upward trend, meaning the total non-structural carbohydrate (TNC) content and soluble sugar (SS) content increased significantly, and the starch (ST) content was relatively stable. Lastly, there was no significant difference in NSC content between the canopy layers of mature trees. This indicates that the influence of life stage on NSC content in leaves and branches of plants may be dominated by genetics instead of being regulated by light factors.
Rhizosphere soil nutrients and bacterial community diversity of four broad-leaved trees planted under Chinese fir stands with different stocking density levels
Authors: Wang Liyan , Sun Yangyang , Li Jing , Tigabu Mulualem , Xu Qingli , Ma Xiangqing , Li Ming
Published: March 2023

Objective

Rhizosphere soil nutrients and bacterial diversity of four broad-leaved tree species underplanted in Chinese fir plantation with different stand density levels were analyzed to reveal characteristics of the rhizosphere soil environment and selection of suitable underplanted tree species.

Methods

Chinese fir plantation with three density levels (900, 1,200, and 1,875 stems ha–1, respectively) were selected and underplanted with Michelia macclurei, Schima superba, Phoebe zhennan, and Tsoongiodendron odorum. The rhizosphere soil nutrients and bacterial community of the broad-leaved tree species were determined after 4 years.

Results

Significant differences in rhizosphere nutrient content were detected among different tree density levels, where the contents of total K, available K and available P in 900 stems ha–1 stands were significantly higher than the other stocking density levels. There were also significant differences in the contents of total C, total N, total K, available K and available P in the rhizosphere soils of the four trees species, while there were no significant differences in pH and total P. Rhizosphere soil nutrient contents were higher under S. superba and M. macclurei than under P. zhennan and T. odorum. The rhizosphere soil nutrient contents and bacterial diversity decreased with the increase of stand density, and the bacterial diversity showed significant differences in the rhizosphere soils of P. zhennan, T. odorum and S. superba when underplanted in different stand densities. The bacterial diversity was positively correlated with the available P content of rhizosphere soils, suggesting that soil available P content plays an important role in shaping the structure of bacterial community.

Conclusion

The nutrient contents and bacterial diversity of rhizosphere soils of underplated broad-leaved species decreased with increasing stand density of Chinese fir plantation. Rhizosphere soils of M. macclurei and S. superba were rich in nutrient contents and bacterial diversity. Thus, low density of Chinese fir plantation (900 stems ha–1) underplanted with M. macclurei and S. superba is suitable for the establishment of mixed forest, which will facilitate better tree growth and maintaining soil fertility to realize sustainable management of forests.
Gene-wide significant association analyses of DNMT1 genetic variants with Parkinson’s disease
Authors: Wang Jian-Yong , Cui Lei , Shi Hong-Yi , Chen Ling-Hao , Jin Ren-Wei , Jiang Xiao-Xia , Chen Zhu-Ling , Zhu Jian-Hong , Zhang Xiong
Published: March 2023

Background: DNA methylation plays an important role in Parkinson’s disease (PD) pathogenesis. DNA methyltransferase 1 (DNMT1) is critical for maintaining DNA methylation in mammals. The link between DNMT1 polymorphisms and PD remains elusive.

Methods: The DNMT1 gene contained a total of 28 single nucleotide polymorphisms (SNPs). Four representing tag-SNPs (rs16999593, rs2162560, rs11880553, and rs9305012) were identified and genotyped in a Han Chinese population comprising 712 PD patients and 696 controls. Association analyses were performed at gene-wide significance (p < 1.8 × 10−3).

Results: Rs9305012, but not the other 3 tag-SNPs, was gene-wide significantly associated with PD risk (p = 0.8 × 10−3). The rs9305012/C was a protective allele against PD (p = 1.5 × 10−3, OR 0.786, 95% CI 0.677–0.912). No significant association was observed in individual genders or PD subtypes. Haplotypes of the 4 tag-SNPs showed a significant overall distribution difference between PD patients and controls (p < 1 × 10−4). The 3-allele ACC module in the order of rs2162560, rs11880553, and rs9305012 was the highest-risk haplotype associated with PD (p < 1 × 10−4, OR 2.439, 95% CI 1.563–3.704). Rs9305012 displayed certain probability to affect transcription factor binding and target gene expression based on functional annotation analyses.

Conclusion: The DNMT1 variant rs9305012 together with its haplotypes may gene-wide significantly modulate PD susceptibility. Our results support a role of DNMT1 in PD pathogenesis and provide novel insights into the genetic connection in between.
Immune checkpoint inhibitor-associated toxicity in advanced non-small cell lung cancer: An updated understanding of risk factors
Authors: Hu Xiangxiao , Wang Lina , Shang Bin , Wang Junren , Sun Jian , Liang Bin , Su Lili , You Wenjie , Jiang Shujuan
Published: March 2023

Immune checkpoint inhibitors (ICIs), such as programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, etc, have revolutionized cancer treatment strategies, including non-small cell lung cancer (NSCLC). While these immunotherapy agents have achieved durable clinical benefits in a subset of NSCLC patients, they bring in a variety of immune-related adverse events (irAEs), which involve cardiac, pulmonary, gastrointestinal, endocrine and dermatologic system damage, ranging from mild to life-threatening. Thus, there is an urgent need to better understand the occurrence of irAEs and predict patients who are susceptible to those toxicities. Herein, we provide a comprehensive review of what is updated about the clinical manifestations, mechanisms, predictive biomarkers and management of ICI-associated toxicity in NSCLC. In addition, this review also provides perspective directions for future research of NSCLC-related irAEs.
COVID-19 spike polypeptide vaccine reduces the pathogenesis and viral infection in a mouse model of SARS-CoV-2
Authors: Hisham Yasmin , Seo Sun-Min , Kim Sinae , Shim Saerok , Hwang Jihyeong , Yoo Eun-Seon , Kim Na-Won , Song Chang-Seon , Jhun Hyunjhung , Park Ho-Young , Lee Youngmin , Shin Kyeong-Cheol , Han Sun-Young , Seong Je Kyung , Choi Yang-Kyu , Kim Soohyun
Published: March 2023

The SARS-CoV-2 coronavirus, which causes a respiratory disease called COVID-19, has been declared a pandemic by the World Health Organization (WHO) and is still ongoing. Vaccination is the most important strategy to end the pandemic. Several vaccines have been approved, as evidenced by the ongoing global pandemic, but the pandemic is far from over and no fully effective vaccine is yet available. One of the most critical steps in vaccine development is the selection of appropriate antigens and their proper introduction into the immune system. Therefore, in this study, we developed and evaluated two proposed vaccines composed of single and multiple SARS-CoV-2 polypeptides derived from the spike protein, namely, vaccine A and vaccine B, respectively. The polypeptides were validated by the sera of COVID-19-vaccinated individuals and/or naturally infected COVID-19 patients to shortlist the starting pool of antigens followed by in vivo vaccination to hACE2 transgenic mice. The spike multiple polypeptide vaccine (vaccine B) was more potent to reduce the pathogenesis of organs, resulting in higher protection against the SARS-CoV-2 infection.
Characterization of a mutant samhd1 zebrafish model implicates dysregulation of cholesterol biosynthesis in Aicardi-Goutières syndrome
Authors: Withers Sarah E. , Rowlands Charlie F. , Tapia Victor S. , Hedley Frances , Mosneag Ioana-Emilia , Crilly Siobhan , Rice Gillian I. , Badrock Andrew P. , Hayes Andrew , Allan Stuart M. , Briggs Tracy A. , Kasher Paul R.
Published: March 2023

Aicardi-Goutières syndrome (AGS1-9) is a genetically determined encephalopathy that falls under the type I interferonopathy disease class, characterized by excessive type I interferon (IFN-I) activity, coupled with upregulation of IFN-stimulated genes (ISGs), which can be explained by the vital role these proteins play in self-non-self-discrimination. To date, few mouse models fully replicate the vast clinical phenotypes observed in AGS patients. Therefore, we investigated the use of zebrafish as an alternative species for generating a clinically relevant model of AGS. Using CRISPR-cas9 technology, we generated a stable mutant zebrafish line recapitulating AGS5, which arises from recessive mutations in SAMHD1. The resulting homozygous mutant zebrafish larvae possess a number of neurological phenotypes, exemplified by variable, but increased expression of several ISGs in the head region, a significant increase in brain cell death, microcephaly and locomotion deficits. A link between IFN-I signaling and cholesterol biosynthesis has been highlighted by others, but not previously implicated in the type I interferonopathies. Through assessment of neurovascular integrity and qPCR analysis we identified a significant dysregulation of cholesterol biosynthesis in the zebrafish model. Furthermore, dysregulation of cholesterol biosynthesis gene expression was also observed through RNA sequencing analysis of AGS patient whole blood. From this novel finding, we hypothesize that cholesterol dysregulation may play a role in AGS disease pathophysiology. Further experimentation will lend critical insight into the molecular pathophysiology of AGS and the potential links involving aberrant type I IFN signaling and cholesterol dysregulation.
Immune checkpoint inhibitors related respiratory disorders in patients with lung cancer: A meta-analysis of randomized controlled trials
Authors: Liu Han , Luo Sean X. , Jie Jing , Peng Liping , Wang Shuai , Song Lei
Published: March 2023

Background

In recent years, immune checkpoint inhibitors (ICIs) had extremely rapid growth in anti-cancer and improved outcomes of many malignancies, specifically lung cancer. However, the incidence of ICIs-related adverse events also raised. Using this meta-analysis, ICIs-related respiratory disorders were investigated in lung cancer patients.

Methods

Using Cochrane Library, Embase, and PubMed databases, we performed an integrated search for randomized controlled trials (RCTs) to compare respiratory disorders among different regimens. The data was prepared with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline, and the quality of included studies was evaluated based on the Cochrane manual.

Results

In total, 22 RCTs were involved in this meta-analysis. Compared with ICIs, chemotherapy reduced the risk of interstitial lung disease (p = 0.03; SMD: 2.81; 95% CI: 1.08, 7.27), pleural effusion (p = 0.002; SMD: 2.12; 95% CI: 1.32, 3.42), and pneumonitis (p < 0.00001; SMD: 9.23; 95% CI: 4.57, 18.64). ICIs plus chemotherapy could provide a higher probability for patients to suffer pneumonitis than chemotherapy (p = 0.01; SMD: 1.96; 95% CI: 1.17, 3.28). In addition, single ICI brought a lower likelihood for patients suffering pneumonitis than double ICIs (p = 0.004; SMD: 2.17; 95% CI: 1.27, 3.69).

Conclusion

ICIs-based treatment, such as ICIs alone, ICIs plus chemotherapy and double ICIs, can raise the incidences of some respiratory disorders in patients with lung cancer. It suggests that ICIs should be conducted based on a comprehensive consideration to prevent ICIs-related respiratory disorders. To a certain degree, this study might be provided to the clinician as a reference for ICIs practice.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022378901, identifier (CRD42022378901).
Hypothermic machine perfusion alleviates ischemia-reperfusion injury of intestinal transplantation in pigs
Authors: Hou Wen , Yang Shuang , Lu Jiansen , Shi Yuan , Chen Jing , Chen Decheng , Wang Fei , Liu Lei
Published: March 2023

Background

Intestinal transplantation (IT) has become an important procedure for the treatment of irreversible intestinal failure. However, IT is extremely vulnerable to ischemia–reperfusion injury (IRI). Due to the limitations of static cold storage (SCS), hypothermic machine perfusion (HMP) is rapidly gaining popularity. In this study, the intestinal HMP system is established and HMP is compared with SCS.

Methods

An intestinal HMP system was built. Ten miniature pigs were randomly divided into the HMP and SCS groups, and their intestines were perfused using the HMP device and SCS, respectively, followed by orthotopic auto-transplantation. Analysis was done on the grafts between the two groups.

Results

Operation success rates of the surgery were 100% in both groups. The 7-day survival rate was 100% in the HMP group, which was significantly higher than that of the SCS group (20%, P< 0.05). The pathological results showed that fewer injuries of grafts were in the HMP group. Endotoxin (ET), IL-1, IL-6, IFN-γ and TNF-α levels in the HMP group were significantly lower than in the SCS group (P<0.05), whereas IL-10 levels were significantly higher (P<0.05).The intestinal expression levels of ZO-1 and Occludin were higher in the HMP group compared to the SCS group, whereas Toll-like receptor 4 (TLR4), nuclear factor kappa B (NFκB), and caspase-3 were lower.

Conclusions

In this study, we established a stable intestinal HMP system and demonstrated that HMP could significantly alleviate intestinal IRI and improve the outcome after IT.
Immunomodulatory activity of manganese dioxide nanoparticles: Promising for novel vaccines and immunotherapeutics
Authors: Huang Yuhe , Ruan Yongdui , Ma Yuhe , Chen Dongsheng , Zhang Tangxin , Fan Shuhao , Lin Wensen , Huang Yifan , Lu Hongmei , Xu Jun-Fa , Pi Jiang , Zheng Biying
Published: March 2023

Manganese (Mn), a nutrient inorganic trace element, is necessary for a variety of physiological processes of animal body due to their important roles in oxidative regulation effects and other aspects of activities. Moreover, manganese ion (Mn2+) has widely reported to be crucial for the regulations of different immunological responses, thus showing promising application as potential adjuvants and immunotherapeutics. Taking the advantages of Mn-based biological and immunological activities, Manganese dioxide nanoparticles (MnO2 NPs) are a new type of inorganic nanomaterials with numerous advantages, including simple preparation, low cost, environmental friendliness, low toxicity, biodegradable metabolism and high bioavailability. MnO2 NPs, as a kind of drug carrier, have also shown the ability to catalyze hydrogen peroxide (H2O2) to produce oxygen (O2) under acidic conditions, which can enhance the efficacy of radiotherapy, chemotherapy and other therapeutics for tumor treatment by remodeling the tumor microenvironment. More importantly, MnO2 NPs also play important roles in immune regulations both in innate and adaptive immunity. In this review, we summarize the biological activities of Manganese, followed by the introduction for the biological and medical functions and mechanisms of MnO2 NPs. What’s more, we emphatically discussed the immunological regulation effects and mechanisms of MnO2 NPs, as well as their potentials to serve as adjuvants and immunomodulators, which might benefit the development of novel vaccines and immunotherapies for more effective disease control.
Mass cytometry identifies characteristic immune cell subsets in bronchoalveolar lavage fluid from interstitial lung diseases
Authors: Hata Kentaro , Yanagihara Toyoshi , Matsubara Keisuke , Kunimura Kazufumi , Suzuki Kunihiro , Tsubouchi Kazuya , Eto Daisuke , Ando Hiroyuki , Uehara Maki , Ikegame Satoshi , Baba Yoshihiro , Fukui Yoshinori , Okamoto Isamu
Published: March 2023

Immune cells have been implicated in interstitial lung diseases (ILDs), although their phenotypes and effector mechanisms remain poorly understood. To better understand these cells, we conducted an exploratory mass cytometry analysis of immune cell subsets in bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF), connective-tissue disease (CTD)-related ILD, and sarcoidosis, using two panels including 64 markers. Among myeloid cells, we observed the expansion of CD14+ CD36hi CD84hiCCR2– monocyte populations in IPF. These CD14+ CD36hi CD84hi CCR2– subsets were also increased in ILDs with a progressive phenotype, particularly in a case of acute exacerbation (AEx) of IPF. Analysis of B cells revealed the presence of cells at various stages of differentiation in BALF, with a higher percentage of IgG memory B cells in CTD-ILDs and a trend toward more FCRL5+ B cells. These FCRL5+ B cells were also present in the patient with AEx-IPF and sarcoidosis with advanced lung lesions. Among T cells, we found increased levels of IL-2R+ TIGIT+ LAG3+ CD4+ T cells in IPF, increased levels of CXCR3+ CD226+ CD4+ T cells in sarcoidosis, and increased levels of PD1+ TIGIT+ CD57+ CD8+ T cells in CTD-ILDs. Together, these findings underscore the diverse immunopathogenesis of ILDs.
Population genetics of zig-zag eel (Mastacembelus armatus) uncover gene flow between an isolated island and the mainland China
Authors: Yang Yexin , Wang Yuanyuan , Wu Yuli , Liu Yi , Liu Chao , Jiang Zhiyong , Mu Xidong
Published: March 2023

Introduction

Mastacembelus armatus is a commercially valuable fish, normally distributed in southern China and Southeast Asia. The natural population size of M. armatus is shrinking in recent years because of overfishing and habitat loss. In order to clarify the genetic diversity and differentiation of M. armatus populations, we collected 114 samples from eight populations in southern China and Vietnam and analyzed their population structure using nuclear ribosomal DNA sequences, the concatenated 18S and ITS2 regions.

Methods

Genomic DNA from the fin clip was extracted and sequenced on an Illumina novaseq 6000 (Illumina, USA) high-throughput sequencing platform in accordance with the manufacturer’s instructions. After assembly and annotation, haplotype diversity, TCS network analysis, AMOVA analysis, population pairwise genetic distances, and UPGMA tree construction were conducted based on the concatenated sequences of 18S and ITS2.

Results and discussion

In total, eleven nrDNA haplotypes were detected based on the concatenated sequences of 18S and ITS2. Amongst, three haplotypes were the main haplotypes, as representatives of three corresponding Clusters. There were two major Clusters in China, however, the Cluster in Vietnam was significantly divergent from the other two in China, likely due to the lack of river connection between China and Vietnam. Interestingly, based on low FST value, we found that gene flow occurred between the isolated island, Hainan Province, and the mainland China of Guangxi Province, probably as a result of exposed continental shelf connected them during glacial periods. In general, combing our data and literature data, genetic diversity and differentiation of M. armatus populations are relatively high regardless of spatial scale, although their natural population size is declining. This suggests that it is not too late to adopt measures to protect M. armatus, which benefits not only species itself but also the whole ecosystem.
WASH and NTDs: Outcomes and lessons learned from the implementation of a formative research study in NTD skin co-endemic communities in Benin
Authors: Salou Bachirou Zoulkifl , Mignanwande Zinsou Franck , Bokossa Hervé , Degnonvi Horace , Djossou Parfait , Hondjrebo Flora , Amoukpo Hermione , Anagonou Esai Gimatal , Agbo Inès , Toffa Damien , Ba Rafiatou , Gine Anna , Diez Gabriel , Johnson Roch Christian
Published: March 2023

Neglected Tropical Diseases (NTDs) are a diverse group of bacterial, viral, parasitic and fungal diseases affecting people, most of whom live below the poverty threshold. Several control strategies are defined against these diseases, including chemotherapy and Water, Hygiene and Sanitation (WASH). This study assesses the effect of promoting hygiene and sanitation on soil-transmitted helminthiasis s and NTDs of the skin. It took place in the communes of Ze, Lalo, and Zangnanado, three municipalities located in the south of Benin. This is a formative research that took place in three phases. The first phase entailed a baseline informations and situational analysis of the state of hygiene and health, using soil-transmitted helminthiasis and wound hygiene practices as cases studies. In the second phase, interventions to promote improved hygiene and sanitation were implemented. The third phase was devoted to post-intervention evaluation. The situation analysis showed that the prevalence of soil-transmitted helminthiasis was 6.43 and 7.10% in the municipalities of Ze and Lalo, respectively. In the communes of Zangnanado, the most common wound management practices identified were: putting sand or ashes in the wounds to keep flies away, the use of medicinal plants and the application of powder from antibiotic capsules for wound dressing. The post-intervention evaluation showed a decrease in the prevalence of soil-transmitted helminthiasis from 6.43 to 1.19% in the municipality of Lalo and from 7.10 to 1.75% in the municipality of Ze. In the commune of Zangnanado, a significant shift in wound management practices was noted, which led to the healing of several chronic wounds. This research supports the evidence that WASH-based interventions are very important to tackle neglected tropical diseases NTDs in addition to specific diseases based interventions.
Biopriming of seed with plant growth-promoting bacteria for improved germination and seedling growth
Authors: Fiodor Angelika , Ajijah Nur , Dziewit Lukasz , Pranaw Kumar
Published: March 2023

Several seed priming methods can be used to improve seed germination, seedling vigor, and to overcome abiotic stress. In addition to these benefits, only the biopriming method provides the additional benefit of biotic stress management, earning it special attention. Seed biopriming is useful in almost all crops around the world and is an environmentally friendly alternative to chemical fungicides. Biopriming usually refers to use of beneficial microorganisms, in particular plant growth-promoting bacteria (PGPB) able to survive under various harsh environmental conditions. In this study, various bacterial strains were isolated from samples of different origins, i.e., rhizospheric soil, desert sand, and sea mud. Preliminary screening of 156 bacterial isolates was conducted on the basis of their potassium (K), phosphorus (P) solubilization ability, and production of plant growth hormone, i.e., indole acetic acid (IAA). The most efficient bacteria were identified by 16S rRNA gene nucleotide sequences and further examined for their ACC deaminase activity, ammonia production, and biocontrol activity (defined via chitinolytic activity, HCN, and siderophores production). Finally, carrot seed germination assay was conducted with 10 shortlisted most potent isolates. 68.6, 58.3, and 66.7% of tested bacterial isolates were capable of P, K, and Zn solubilization, respectively. Klebsiella aerogenes AF3II1 showed the highest P and K solubilization, while isolate AF4II5, AF7II3, and PC3 showed the highest IAA synthesis ability. Serratia plymuthica EDC15 and Pseudomonas putida AF1I1 showed the strongest chitinolytic and siderophore production activity, respectively. Seven isolates demonstrated strong HCN production ability. Five isolates improved carrot seed germination. Only selected isolates with plant growth-promoting properties can improve carrot germination. The results of this study demonstrate that mainly auxins are involved in seed germination. Furthermore, the data suggest that phosphate solubilization ability may play an additional role in seed germination.
Community response of soil microorganisms to combined contamination of polycyclic aromatic hydrocarbons and potentially toxic elements in a typical coking plant
Authors: Shen Qihui , Fu Wei , Chen Baodong , Zhang Xuemeng , Xing Shuping , Ji Chuning , Zhang Xin
Published: March 2023

Both polycyclic aromatic hydrocarbons (PAHs) and potentially toxic elements (PTEs) of coking industries impose negative effects on the stability of soil ecosystem. Soil microbes are regarded as an essential moderator of biochemical processes and soil remediation, while their responses to PAHs-PTEs combined contamination are largely unknown. In the present study, soil microbial diversity and community composition in the typical coking plant under the chronic co-exposure of PAHs and PTEs were investigated and microbial interaction networks were built to reveal microbial co-occurrence patterns. The results indicated that the concentrations of PAHs in the soil inside the coking plant were significantly higher than those outside the plant. The mean concentration of ∑16PAHs was 2894.4 ng·g−1, which is 5.58 times higher than that outside the plant. The average Hg concentration inside the coking plant was 22 times higher than the background value of Hebei province. The soil fungal community inside the coking plant showed lower richness compared with that of outside community, and there are significant difference in the bacterial and fungal community composition between inside and outside of coking plant (p < 0.01). Predicted contribution of different environmental factors to each dominant species based on random forest identified 20 and 25 biomarkers in bacteria and fungi, respectively, that were highly sensitive to coking plant soil in operation, such as Betaproteobacteria，Sordariomycetes and Dothideomycetes. Bacterial and fungal communities were shaped by the soil chemical properties (pH), PTEs (Hg), and PAHs together in the coking plant soils. Furthermore, the bacterial and fungal interaction patterns were investigated separately or jointly by intradomain and interdomain networks. Competition is the main strategy based on the co-exclusion pattern in fungal community, and the competitive relationship inside the coking plant is more complex than that outside the plant. In contrast, cooperation is the dominant strategy in bacterial networks based on the co-occurrence pattern. The present study provided insights into microbial response strategies and the interactions between bacteria and fungi under long-term combined contamination.