bluuebunny/crossref_metadata_2025 huggingface dataset:
The Application Status of Nanoscale Cellulose-Based Hydrogels in Tissue Engineering and Regenerative Biomedicine
Authors: Wang Chenyang , Bai Jin , Tian Pei , Xie Rui , Duan Zifan , Lv Qinqin , Tao Yuqiang
Published: November 2021

As a renewable, biodegradable, and non-toxic material with moderate mechanical and thermal properties, nanocellulose-based hydrogels are receiving immense consideration for various biomedical applications. With the unique properties of excellent skeletal structure (hydrophilic functional groups) and micro-nano size (small size effect), nanocellulose can maintain the three-dimensional structure of the hydrogel to a large extent, providing mechanical strength while ensuring the moisture content. Owing to its unique features, nanocellulose-based hydrogels have made excellent progress in research and development on tissue engineering, drug carriers, wound dressings, development of synthetic organs, 3D printing, and biosensing. This review provides an overview of the synthesis of different types of nanocellulose, including cellulose nanocrystals, cellulose nanofibers, and bacterial nanocellulose, and describes their unique features. It further provides an updated knowledge of the development of nanocellulose-based functional biomaterials for various biomedical applications. Finally, it discusses the future perspective of nanocellulose-based research for its advanced biomedical applications.
Epigenetic Modifications and Therapy in Uveitis
Authors: Zou Yanli , Li Jing Jing , Xue Wei , Kong Xiangbin , Duan Hucheng , Li Yiqun , Wei Lai
Published: November 2021

Uveitis is a sight-threatening intraocular inflammation, and the exact pathogenesis of uveitis is not yet clear. Recent studies, including multiple genome-wide association studies (GWASs), have identified genetic variations associated with the onset and progression of different types of uveitis, such as Vogt–Koyanagi–Harada (VKH) disease and Behcet’s disease (BD). However, epigenetic regulation has been shown to play key roles in the immunoregulation of uveitis, and epigenetic therapies are promising treatments for intraocular inflammation. In this review, we summarize recent advances in identifying epigenetic programs that cooperate with the physiology of intraocular immune responses and the pathology of intraocular inflammation. These attempts to understand the epigenetic mechanisms of uveitis may provide hope for the future development of epigenetic therapies for these devastating intraocular inflammatory conditions.
K-Promoted Ni-Based Catalysts for Gas-Phase CO2 Conversion: Catalysts Design and Process Modelling Validation
Authors: Gandara-Loe J. , Portillo E. , Odriozola J. A. , Reina T. R. , Pastor-Pérez L.
Published: November 2021

The exponential growth of greenhouse gas emissions and their associated climate change problems have motivated the development of strategies to reduce CO2 levels via CO2 capture and conversion. Reverse water gas shift (RWGS) reaction has been targeted as a promising pathway to convert CO2 into syngas which is the primary reactive in several reactions to obtain high-value chemicals. Among the different catalysts reported for RWGS, the nickel-based catalyst has been proposed as an alternative to the expensive noble metal catalyst. However, Ni-based catalysts tend to be less active in RWGS reaction conditions due to preference to CO2 methanation reaction and to the sintering and coke formation. Due to this, the aim of this work is to study the effect of the potassium (K) in Ni/CeO2 catalyst seeking the optimal catalyst for low-temperature RWGS reaction. We synthesised Ni-based catalyst with different amounts of K:Ni ratio (0.5:10, 1:10, and 2:10) and fully characterised using different physicochemical techniques where was observed the modification on the surface characteristics as a function of the amount of K. Furthermore, it was observed an improvement in the CO selectivity at a lower temperature as a result of the K-Ni-support interactions but also a decrease on the CO2 conversion. The 1K catalyst presented the best compromise between CO2 conversion, suppression of CO2 methanation and enhancing CO selectivity. Finally, the experimental results were contrasted with the trends obtained from the thermodynamics process modelling observing that the result follows in good agreement with the modelling trends giving evidence of the promising behaviour of the designed catalysts in CO2 high-scale units.
Effective Prophylaxis of COVID-19 in Rhesus Macaques Using a Combination of Two Parenterally-Administered SARS-CoV-2 Neutralizing Antibodies
Authors: Beddingfield Brandon J. , Maness Nicholas J. , Fears Alyssa C. , Rappaport Jay , Aye Pyone Pyone , Russell-Lodrigue Kasi , Doyle-Meyers Lara A. , Blair Robert V. , Carias Ann M. , Madden Patrick J. , Redondo Ramon Lorenzo , Gao Hongmei , Montefiori David , Hope Thomas J. , Roy Chad J.
Published: November 2021

SARS-CoV-2 is a respiratory borne pathogenic beta coronavirus that is the source of a worldwide pandemic and the cause of multiple pathologies in man. The rhesus macaque model of COVID-19 was utilized to test the added benefit of combinatory parenteral administration of two high-affinity anti-SARS-CoV-2 monoclonal antibodies (mAbs; C144-LS and C135-LS) expressly developed to neutralize the virus and modified to extend their pharmacokinetics. After completion of kinetics study of mAbs in the primate, combination treatment was administered prophylactically to mucosal viral challenge. Results showed near complete virus neutralization evidenced by no measurable titer in mucosal tissue swabs, muting of cytokine/chemokine response, and lack of any discernable pathologic sequalae. Blocking infection was a dose-related effect, cohorts receiving lower doses (6, 2 mg/kg) resulted in low grade viral infection in various mucosal sites compared to that of a fully protective dose (20 mg/kg). A subset of animals within this cohort whose infectious challenge was delayed 75 days later after mAb administration were still protected from disease. Results indicate this combination mAb effectively blocks development of COVID-19 in the rhesus disease model and accelerates the prospect of clinical studies with this effective antibody combination.
Healthy Sleep Associated With Lower Risk of Hypertension Regardless of Genetic Risk: A Population-Based Cohort Study
Authors: Li Zhi-Hao , Huang Qing-Mei , Gao Xiang , Chung Vincent C. H. , Zhang Pei-Dong , Shen Dong , Zhang Xi-Ru , Zhong Wen-Fang , Liu Dan , Chen Pei-Liang , Chen Qing , Cai Miao-Chun , Cheng Xin , Yang Hai-Lian , Song Wei-Qi , Wu Xian-Bo , Kraus Virginia Byers , Mao Chen
Published: November 2021

Background: Hypertension is a leading contributor to the global burden of disease and to mortality. The combined effects of sleep factors on the risk of hypertension are unclear. We aimed to evaluate the effect of combined sleep factors on the risk of hypertension and to explore whether this association is independent of genetic risk.

Methods: This population-based prospective cohort study included 170,378 participants from the UK Biobank study. We conducted a healthy sleep score based on a combination of major five sleep factors and a genetic risk score based on 118 risk variants. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: A total of 170,378 participants were included. Compared to participants with a healthy sleep score of 0–1, those with healthy sleep scores of 2 (HR, 0.90; 95% CI, 0.83–0.98), 3 (HR, 0.81; 95% CI, 0.75–0.88), 4 (HR, 0.74; 95% CI, 0.68–0.81), or 5 (HR, 0.67; 95% CI, 0.59–0.77) had increasingly lower risks of hypertension (P for trend <0.001). Participants with high genetic risk and an unfavorable sleep pattern had a 1.80-fold greater risk of hypertension than participants with low genetic risk and a favorable sleep pattern. The association between sleep patterns and hypertension persisted in subgroup analysis, stratified by the genetic risk. Nearly 18.2% of hypertension events in this cohort could be attributed to unfavorable sleep pattern.

Conclusions: Favorable sleep pattern was associated with a low risk of hypertension, regardless of genetic risk. These findings highlight the potential of sleep interventions to reduce risk of hypertension across entire populations.
Transcatheter Tricuspid Valve Therapy: From Anatomy to Intervention
Authors: Cammalleri Valeria , Carpenito Myriam , Bono Maria Caterina , Mega Simona , Ussia Gian Paolo , Grigioni Francesco
Published: November 2021

Nowadays, severe symptomatic tricuspid regurgitation (TR) affects millions of persons worldwide. However, the benefit of surgical correction of isolated secondary TR remains controversial because of the increased risk of periprocedural mortality and morbidity. In recent years, novel transcatheter tricuspid valve interventions (TTVI) were developed to treat TR, so that TTVI is currently considered in symptomatic, inoperable, anatomically eligible patients. TTVI can be divided into these five domains: edge-to-edge leaflet repair, tricuspid annuloplasty, caval implants, spacer, and total valve replacement. Each transcatheter intervention needs specific imaging protocols for assessing the anatomical feasibility and consequentially predicting the procedural success. This review summarizes the available multimodality imaging tools for screening patients with TR, and identifies anatomical characteristics to choose the best option for the patient.
Self-Care Experiences of Empty-Nest Elderly Living With Type 2 Diabetes Mellitus: A Qualitative Study From China
Authors: Lv Xiaoyan , Yu Doris S. F. , Cao Yingjuan , Xia Jinghua
Published: November 2021

Background

The number of type 2 diabetes mellitus (T2DM) cases among empty-nest elderly increases with increasing aging in China. Self-care plays an important role in preventing and reducing adverse outcomes of diabetes; however, few studies focus on self-care experiences of empty-nest elderly with T2DM.

Objective

To explore self-care experiences for a chronic disease among empty-nest elderly patients with T2DM in mainland China.

Methods

A descriptive phenomenological design was used in this study. Semi-structured interviews were conducted for 15 empty-nesters with T2DM. Interviews were implemented in department of endocrinology at a tertiary teaching hospital located in Shandong province, east of China.

Results

The participants were poorly adept with monitoring their blood glucose and lacked the ability to deal with abnormal blood glucose levels. Most participants had a good relationship with medication and physical activity. Living without children was perceived as a benefit that improved dietary management and is a disadvantage in terms of economic and emotional support and access to medical resources. Elderly empty-nesters also lacked knowledge about diabetes and paid little attention to potential complications.

Conclusion

Empty-nest elderly patients with T2DM value medication compliance and lifestyle modification more than blood glucose monitoring, complication prevention, and coping with negative emotions. Friends and spouses play indispensable roles in patients’ self-care motivation and maintenance. Diabetes education on self-care, access to medical resources, and social support is needed for better diabetes management.
Ankle-Brachial Index Is Independently Associated With Cardiovascular Outcomes and Foot Ulcers in Asian Patients With Type 2 Diabetes Mellitus
Authors: Yang Ming-Chi , Huang Yu-Yao , Hsieh Sheng-Hwu , Sun Jui-Hung , Wang Chih-Ching , Lin Chia-Hung
Published: November 2021

Background and Aims

The ankle-brachial index (ABI) is an efficient tool for objectively documenting the presence of lower-extremity peripheral arterial disease (PAD). The predictive factors of cardiovascular events and diabetic foot ulcer were not clear from the ABI examination in Taiwanese patients with type 2 diabetes mellitus (DM).

Methods

We enrolled 482 patients with type 2 DM who regularly visited the outpatient department of Chang Gung Memorial Hospital and received ABI as well as brachial-ankle pulse wave velocity (ba-PWV) examinations from 2010 to 2017. Age, gender, PAD symptoms, comorbidities, family history of chronic diseases, lifestyle (smoking, alcohol consumption, and exercise), height, weight, waist circumference, monofilament testing and foot ulcer status were studied.

Results

There were 104 (22%) patients (mean age, 67.8 years) with the ABI <1.0. These patients with low ABI (ABI<1.0) had a significantly older age (p=0.001), higher delta PWV (p<0.001), higher rates of stroke (p=0.007), myocardial infarction (p=0.016), and foot ulcer (p=0.039). In a multivariable analysis model, the adjusted odds ratio (aOR) for myocardial infarction, stroke, and foot ulcers associated with low ABI were 1.219 (0.397-3.743, p=0.729), 1.204 (0.556-2.610, p=0.638), and 2.712 (1.199-6.133, p=0.017), respectively. The patients with low PWV (PWV<1400 cm/s) were significantly younger (p<0.001) and had a lower rate of hypertension (p<0.001), and higher percentages of stroke (p=0.027) and dialysis (p=0.041) family history.

Conclusions

Low ABI was associated with cardiovascular events and diabetic foot ulcer independently in patients with type 2 DM.
The Risk of Nephropathy, Retinopathy, and Leg Amputation in Patients With Diabetes and Hypertension: A Nationwide, Population-Based Retrospective Cohort Study
Authors: Yen Fu-Shun , Wei James Cheng-Chung , Shih Ying-Hsiu , Hsu Chih-Cheng , Hwu Chii-Min
Published: November 2021

Purpose

To compare the risks of chronic kidney disease (CKD), end-stage renal disease (ESRD), sight-threatening retinopathy, and leg amputation between patients with diabetes or hypertension.

Methods

From January 1, 2000, to December 31, 2015, we identified 28943 matched pairs of patients with diabetes with and without subsequent hypertension, 89102 pairs of patients with hypertension with and without subsequent diabetes, and 145294 pairs of patients with coexisting diabetes and hypertension with a previous history of diabetes or hypertension from Taiwan’s National Health Insurance Research Database. Cox proportional-hazard models were used for calculating the risks of CKD, sight-threatening retinopathy, and leg amputation.

Results

The mean follow-up time of this study in different cohorts was between 3.59 and 4.28 years. In diabetes patients with vs. without subsequent hypertension, hypertension patients with vs. without subsequent diabetes, and comorbid diabetes and hypertension patients with previous diabetes vs. with previous hypertension, the adjusted HRs (95% CIs) for CKD were 2.77 (2.61-2.94), 1.73 (1.68-1.77), and 1.04 (1.02-1.07); for ESRD were 42.38 (22.62-79.4), 2.76 (2.43-3.13), and 0.72 (0.66-0.79); for sight-threatening retinopathy were 2.07 (1.85-2.3), 3.41 (3.14-3.71), and for leg amputation were 1.51 (1.43-1.58); and 4.74 (3.02-7.43), 6.27(4.72-8.31), and 1.19(1.03-1.38).

Conclusions

This study demonstrated that both diabetes and hypertension are risk factors for the development of CKD, retinopathy, and amputation. Tracing subsequent diabetes for patients with hypertension, and hypertension for patients with diabetes are important in clinical settings.
Compelling Evidence Linking CD40 Gene With Graves’ Disease in the Chinese Han Population
Authors: Jiang He , Yuan Fei-Fei , Wang Hai-Ning , Liu Wei , Ye Xiao-Ping , Yang Shao-Ying , Xie Hui-Jun , Yu Sha-Sha , Ma Yu-Ru , Zhang Le-Le , Zhao Shuang-Xia , Song Huai-Dong ,   The China Consortium for the Genetics of Autoimmune Thyroid Disease
Published: November 2021

Mutations in CD40 have been widely reported to be risk factors for Graves’ disease (GD). The gene, along with its cognate ligand CD40L, may regulate pro-inflammatory and immune responses. Rs1883832, located at the -1 position of the Kozak sequence, is the most well-studied single nucleotide polymorphism (SNP) of CD40, and has been confirmed to predispose those with the alteration to GD, regardless of ethnicity. Our genome-wide association study (GWAS) indicated that several SNPs, including rs1883832 located within the vicinity of CD40 were associated with GD in the Han Chinese population. Aiming at identifying the most consequential SNP and its underlying pathogenic mechanism, we performed a two-stage refined study on 8,171 patients with GD and 7,906 controls, and found rs1883832 was the most significantly GD-associated SNP in the CD40 gene region (PCombined = 9.17×10-11, OR = 1.18). Through searching the cis-expression quantitative trait locus database and using quantitative RT-PCR, we further discovered that the rs1883832 genotype can influence CD40 gene transcription. Furthermore, we demonstrated that rs1883832 is a susceptibility locus for pTRAb+ GD patients. In conclusion, the current study provides robust evidence that rs1883832 can regulate CD40 gene expression and affect serum TRAb levels, which ultimately contributes to the development of GD.
Effects of Soil Properties, Temperature and Disturbance on Diversity and Functional Composition of Plant Communities Along a Steep Elevational Gradient on Tenerife
Authors: Ratier Backes Amanda , Frey Larissa , Arévalo José Ramón , Haider Sylvia
Published: November 2021

Elevational variation of vegetation has been of interest for centuries, and a prominent example for such pronounced vegetation changes can be found along the steep elevational gradient on Tenerife, Canary Islands, 200 km off the West-African cost. The 3,718-m ascent to the peak of the island volcano, Teide, offers a unique opportunity to investigate associated changes in vegetation. However, elevation is not a directly acting factor, but represents several natural environmental gradients. While the elevational variation of temperature is globally rather uniform and temperature effects on plant communities are well understood, much less is known about the region-specific elevational change of chemical soil properties and their impact on plant communities along elevational gradients. Because human interference takes place even at high-elevation areas, we considered human-induced disturbance as important third factor acting upon plant community assemblages. In our study, we compared the effects of soil properties, temperature and disturbance on species richness, functional identity and functional diversity of plant communities along the elevational gradient on Tenerife. We used pairs of study plots: directly adjacent to a road and in natural vegetation close by. In each plot, we did vegetation relevées, took soil samples, and installed temperature loggers. Additionally, we collected leaf samples to measure leaf functional traits of 80% of the recorded species. With increasing elevation, soil cation concentrations, cation exchange capacity (CEC) and pH decreased significantly, while the soil carbon to phosphorus ratio slightly peaked at mid-elevations. Temperature had the strongest effects, increasing species richness and favoring communities with fast resource acquisition. Species richness was higher at road verges, indicating the positive effect of reduced competition and artificially generated heterogeneity. However, we did not detect road effects on plant functional characteristics. Vice versa, we did not find soil effects on species richness, but increased concentrations of soil cations favored acquisitive communities. Surprisingly, we could not reveal any influence on community functional diversity. The importance of temperature aligns with findings from large-scale biogeographic studies. However, our results also emphasize that it is necessary to consider the effects of local abiotic drivers, like soil properties and disturbance, to understand variation in plant communities.
An Epigenetic Aging Clock for Cattle Using Portable Sequencing Technology
Authors: Hayes Ben J. , Nguyen Loan T. , Forutan Mehrnush , Engle Bailey N. , Lamb Harrison J. , Copley James P. , Randhawa Imtiaz A. S. , Ross Elizabeth M.
Published: November 2021

Extensively grazed cattle are often mustered only once a year. Therefore, birthdates are typically unknown or inaccurate. Birthdates would be useful for deriving important traits (growth rate; calving interval), breed registrations, and making management decisions. Epigenetic clocks use methylation of DNA to predict an individual’s age. An epigenetic clock for cattle could provide a solution to the challenges of industry birthdate recording. Here we derived the first epigenetic clock for tropically adapted cattle using portable sequencing devices from tail hair, a tissue which is widely used in industry for genotyping. Cattle (n= 66) with ages ranging from 0.35 to 15.7 years were sequenced using Oxford Nanopore Technologies MinION and methylation was called at CpG sites across the genome. Sites were then filtered and used to calculate a covariance relationship matrix based on methylation state. Best linear unbiased prediction was used with 10-fold cross validation to predict age. A second methylation relationship matrix was also calculated that contained sites associated with genes used in the dog and human epigenetic clocks. The correlation between predicted age and actual age was 0.71 for all sites and 0.60 for dog and human gene epigenetic clock sites. The mean absolute deviation was 1.4 years for animals aged less than 3 years of age, and 1.5 years for animals aged 3–10 years. This is the first reported epigenetic clock using industry relevant samples in cattle.
Evaluation of Germline Structural Variant Calling Methods for Nanopore Sequencing Data
Authors: Bolognini Davide , Magi Alberto
Published: November 2021

Structural variants (SVs) are genomic rearrangements that involve at least 50 nucleotides and are known to have a serious impact on human health. While prior short-read sequencing technologies have often proved inadequate for a comprehensive assessment of structural variation, more recent long reads from Oxford Nanopore Technologies have already been proven invaluable for the discovery of large SVs and hold the potential to facilitate the resolution of the full SV spectrum. With many long-read sequencing studies to follow, it is crucial to assess factors affecting current SV calling pipelines for nanopore sequencing data. In this brief research report, we evaluate and compare the performances of five long-read SV callers across four long-read aligners using both real and synthetic nanopore datasets. In particular, we focus on the effects of read alignment, sequencing coverage, and variant allele depth on the detection and genotyping of SVs of different types and size ranges and provide insights into precision and recall of SV callsets generated by integrating the various long-read aligners and SV callers. The computational pipeline we propose is publicly available at https://github.com/davidebolo1993/EViNCe and can be adjusted to further evaluate future nanopore sequencing datasets.
Association of GAK rs1564282 With Susceptibility to Parkinson’s Disease in Chinese Populations
Authors: Li He , Zhang Chen , Ji Yong
Published: November 2021

The susceptibility of the GAK rs1564282 variant in Parkinson’s disease (PD) in Europeans was identified using a series of published genome-wide association studies. Recently, some studies focused on the association between rs1564282 and PD risk in Chinese populations but with inconsistent results. Thus, we conducted an updated meta-analysis with a total of 7,881 samples (4,055 PD cases and 3,826 controls) from eligible studies. After excluding significant heterogeneity, we showed that the rs1564282 variant was significantly associated with PD in Chinese populations (p = 1.00E-04, odds ratio = 1.28 and 95% confidence interval = 1.16–1.42). The sensitivity analysis showed that the association between rs1564282 and PD was not greatly influenced, and there was no significant publication bias among the included studies. Consequently, this meta-analysis indicates that the GAK rs1564282 variant is significantly associated with susceptibility to PD in Chinese populations.
Gut–Lung Axis: Microbial Crosstalk in Pediatric Respiratory Tract Infections
Authors: Zhu Wenxia , Wu Yilin , Liu Hui , Jiang Caini , Huo Lili
Published: November 2021

The gut microbiota is an important regulator for maintaining the organ microenvironment through effects on the gut-vital organs axis. Respiratory tract infections are one of the most widespread and harmful diseases, especially in the last 2 years. Many lines of evidence indicate that the gut microbiota and its metabolites can be considered in therapeutic strategies to effectively prevent and treat respiratory diseases. However, due to the different gut microbiota composition in children compared to adults and the dynamic development of the immature immune system, studies on the interaction between children’s intestinal flora and respiratory infections are still lacking. Here, we describe the changes in the gut microbiota of children with respiratory tract infections and explain the relationship between the microbiota of children with their immune function and disease development. In addition, we will provide perspectives on the direct manipulation of intestinal microbes to prevent or treat pediatric respiratory infections.
Polyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience
Authors: Balcerek Joanna , Shy Brian R. , Putnam Amy L. , Masiello Lisa M. , Lares Angela , Dekovic Florinna , Acevedo Luis , Lee Michael R. , Nguyen Vinh , Liu Weihong , Paruthiyil Sreenivasan , Xu Jingying , Leinbach Ashley S. , Bluestone Jeffrey A. , Tang Qizhi , Esensten Jonathan H.
Published: November 2021

We report on manufacturing outcomes for 41 autologous polyclonal regulatory T cell (PolyTreg) products for 7 different Phase 1 clinical trials over a 10-year period (2011-2020). Data on patient characteristics, manufacturing parameters, and manufacturing outcomes were collected from manufacturing batch records and entered into a secure database. Overall, 88% (36/41) of PolyTreg products met release criteria and 83% (34/41) of products were successfully infused into patients. Of the 7 not infused, 5 failed release criteria, and 2 were not infused because the patient became ineligible due to a change in clinical status. The median fold expansion over the 14-day manufacturing process was 434.8 -fold (range 29.8-2,232), resulting in a median post-expansion cell count of 1,841 x 106 (range 56.9-16,179 x 106). The main correlate of post-expansion cell number was starting cell number, which positively correlates with absolute circulating Treg cell count. Other parameters, including date of PolyTreg production, patient sex, and patient age did not significantly correlate with fold expansion of Treg during product manufacturing. In conclusion, PolyTreg manufacturing outcomes are consistent across trials and dates of production.
Tumor Necrosis Factor Family Member Profile Predicts Prognosis and Adjuvant Chemotherapy Benefit for Patients With Small-Cell Lung Cancer
Authors: Zhang Zhihui , Wu Peng , Zhang Chaoqi , Luo Yuejun , Zhang Guochao , Zeng Qingpeng , Wang Lide , Yang Zhaoyang , Sun Nan , He Jie
Published: November 2021

Tumor necrosis factor (TNF) family members participate in the body’s antitumor immunity response and influence tumor prognosis and treatment response. However, little is known about the roles of TNF family members in small cell lung cancer (SCLC). Therefore, we conducted the first comprehensive investigation of TNF family members in patients with SCLC, with the goal of using them to predict prognosis and chemotherapy benefit. Abnormal genetic alterations and expression of TNF family members were found to be widespread in SCLC patients. Using LASSO Cox regression analysis, we constructed a TNF family-based signature that separated SCLC patients in the training set (n=77) into high- and low-risk groups with distinct survival and chemotherapy benefit, and the signature was well-validated in the validation set (n=137) by RT-qPCR. Importantly, the signature exhibited superior predictive performance and was identified as a novel independent prognostic factor. Additionally, different immune phenotypes were found between the low-risk and high-risk groups, and high-risk patients had higher CMTM6 expression, suggesting that these patients could benefit from therapeutic methods targeting CMTM6. We constructed the first clinically applicable TNF family-based signature for predicting prognosis and chemotherapy benefit for patients with SCLC. The findings reported here provide a new method for predicting the prognosis of SCLC patients and optimizing clinical management.
Neuro-Immunity and Gut Dysbiosis Drive Parkinson’s Disease-Induced Pain
Authors: Roversi Katiane , Callai-Silva Natalia , Roversi Karine , Griffith May , Boutopoulos Christos , Prediger Rui Daniel , Talbot Sébastien
Published: November 2021

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting 1–2% of the population aged 65 and over. Additionally, non-motor symptoms such as pain and gastrointestinal dysregulation are also common in PD. These impairments might stem from a dysregulation within the gut-brain axis that alters immunity and the inflammatory state and subsequently drives neurodegeneration. There is increasing evidence linking gut dysbiosis to the severity of PD’s motor symptoms as well as to somatosensory hypersensitivities. Altogether, these interdependent features highlight the urgency of reviewing the links between the onset of PD’s non-motor symptoms and gut immunity and whether such interplays drive the progression of PD. This review will shed light on maladaptive neuro-immune crosstalk in the context of gut dysbiosis and will posit that such deleterious interplays lead to PD-induced pain hypersensitivity.
The Immune Landscape of Human Primary Lung Tumors Is Th2 Skewed
Authors: Frafjord Astri , Buer Linn , Hammarström Clara , Aamodt Henrik , Woldbæk Per Reidar , Brustugun Odd Terje , Helland Åslaug , Øynebråten Inger , Corthay Alexandre
Published: November 2021

Tumor-specific T helper (Th) cells have a central role in the immune response against cancer. However, there exist distinct Th cell subsets with very different and antagonizing properties. Some Th subsets such as Th1 protect against cancer, while others (Th2, T regulatory/Treg) are considered detrimental or of unknown significance (T follicular helper/Tfh, Th17). The Th composition of human solid tumors remains poorly characterized. Therefore, we established a four-color multiplex chromogenic immunohistochemical assay for detection of Th1, Th2, Th17, Tfh and Treg cells in human tumor sections. The method was used to analyze resected primary lung tumors from 11 patients with non-small cell lung cancer (NSCLC). Four microanatomical regions were investigated: tumor epithelium, tumor stroma, peritumoral tertiary lymphoid structures (TLS) and non-cancerous distal lung tissue. In tumor epithelium and stroma, most CD4+T cells identified had either a Th2 (GATA-3+CD3+CD8-) or Treg (FOXP3+CD3+CD8-) phenotype, whereas only low numbers of Th1, Th17, and Tfh cells were observed. Similarly, Th2 was the most abundant Th subset in TLS, followed by Treg cells. In sharp contrast, Th1 was the most frequently detected Th subset in non-cancerous lung tissue from the same patients. A higher Th1:Th2 ratio in tumor stroma was found to be associated with increased numbers of intratumoral CD8+T cells. The predominance of Th2 and Treg cells in both tumor stroma and tumor epithelium was consistent for all the 11 patients investigated. We conclude that human primary NSCLC tumors are Th2-skewed and contain numerous Treg cells. If human tumors are Th2-skewed, as our data in NSCLC suggest, reprogramming the type of immune response from a detrimental Th2 to a beneficial Th1 may be critical to increase the response rate of immunotherapy.
Histone H2A Nuclear/Cytoplasmic Trafficking Is Essential for Negative Regulation of Antiviral Immune Response and Lysosomal Degradation of TBK1 and IRF3
Authors: Wu Xiao Man , Fang Hong , Zhang Jie , Bi Yong Hong , Chang Ming Xian
Published: November 2021

Histone H2A is a nuclear molecule tightly associated in the form of the nucleosome. Our previous studies have demonstrated the antibacterial property of piscine H2A variants against gram-negative bacteria Edwardsiella piscicida and Gram-positive bacteria Streptococcus agalactiae. In this study, we show the function and mechanism of piscine H2A in the negative regulation of RLR signaling pathway and host innate immune response against spring viremia of carp virus (SVCV) infection. SVCV infection significantly inhibits the expression of histone H2A during an early stage of infection, but induces the expression of histone H2A during the late stage of infection such as at 48 and 72 hpi. Under normal physiological conditions, histone H2A is nuclear-localized. However, SVCV infection promotes the migration of histone H2A from the nucleus to the cytoplasm. The in vivo studies revealed that histone H2A overexpression led to the increased expression of SVCV gene and decreased survival rate. The overexpression of histone H2A also significantly impaired the expression levels of those genes involved in RLR antiviral signaling pathway. Furthermore, histone H2A targeted TBK1 and IRF3 to promote their protein degradation via the lysosomal pathway and impair the formation of TBK1-IRF3 functional complex. Importantly, histone H2A completely abolished TBK1-mediated antiviral activity and enormously impaired the protein expression of IRF3, especially nuclear IRF3. Further analysis demonstrated that the inhibition of histone H2A nuclear/cytoplasmic trafficking could relieve the protein degradation of TBK1 and IRF3, and blocked the negative regulation of histone H2A on the SVCV infection. Collectively, our results suggest that histone H2A nuclear/cytoplasmic trafficking is essential for negative regulation of RLR signaling pathway and antiviral immune response in response to SVCV infection.
Pushing Past the Blockade: Advancements in T Cell-Based Cancer Immunotherapies
Authors: Waibl Polania Jessica , Lerner Emily C. , Wilkinson Daniel S. , Hoyt-Miggelbrink Alexandra , Fecci Peter E.
Published: November 2021

Successful cancer immunotherapies rely on a replete and functional immune compartment. Within the immune compartment, T cells are often the effector arm of immune-based strategies due to their potent cytotoxic capabilities. However, many tumors have evolved a variety of mechanisms to evade T cell-mediated killing. Thus, while many T cell-based immunotherapies, such as immune checkpoint inhibition (ICI) and chimeric antigen receptor (CAR) T cells, have achieved considerable success in some solid cancers and hematological malignancies, these therapies often fail in solid tumors due to tumor-imposed T cell dysfunctions. These dysfunctional mechanisms broadly include reduced T cell access into and identification of tumors, as well as an overall immunosuppressive tumor microenvironment that elicits T cell exhaustion. Therefore, novel, rational approaches are necessary to overcome the barriers to T cell function elicited by solid tumors. In this review, we will provide an overview of conventional immunotherapeutic strategies and the various barriers to T cell anti-tumor function encountered in solid tumors that lead to resistance. We will also explore a sampling of emerging strategies specifically aimed to bypass these tumor-imposed boundaries to T cell-based immunotherapies.
Low-Dose Acetylsalicylic Acid Reduces T Cell Immune Activation: Potential Implications for HIV Prevention
Authors: Lajoie Julie , Kowatsch Monika M. , Mwangi Lucy W. , Boily-Larouche Geneviève , Oyugi Julius , Chen Yufei , Kimani Makobu , Ho Emmanuel A. , Kimani Joshua , Fowke Keith R.
Published: November 2021

Introduction

Acetylsalicylic acid (ASA) is a well-known and safe anti-inflammatory. At low-dose, it is prescribed to prevent secondary cardiovascular events in those with pre-existing conditions and to prevent preeclampsia. Little is known about how low-dose ASA affects the immune response. In this study, we followed women to assess how ASA use modifies T cells immune phenotypes in the blood and at the genital tract.

Methods

HIV uninfected women from Kenya were enrolled in this study and followed for one month to assess baseline responses including systemic/mucosal baseline immune activation. Participants then received 81mg of ASA daily for 6 weeks to assess changes to T cell immune activation (systemic and mucosal) relative to baseline levels.

Results

The concentration of ASA measured in the blood was 58% higher than the level measured at the female genital tract. In the blood, the level of ASA was inversely correlated with the following: the proportion of Th17 expressing HLA-DR (p=0.04), the proportion of effector CD4+ T cells expressing CCR5 (p=0.03) and the proportion of CD8+Tc17 expressing CCR5 (p=0.04). At the genital tract, ASA use correlated with a decreased of activated CD4+T cells [CD4+CCR5+CD161+ (p=0.02) and CD4+CCR5+CD95+ (p=0.001)].

Conclusion

This study shows that ASA use impacts the immune response in both the systemic and genital tract compartments. This could have major implications for the prevention of infectious diseases such as HIV, in which the virus targets activated T cells to establish an infection. This could inform guidelines on ASA use in women.

Clinical Trial Registration

ClinicalTrials.gov, identifier NCT02079077.
Role of CXCL5 in Regulating Chemotaxis of Innate and Adaptive Leukocytes in Infected Lungs Upon Pulmonary Influenza Infection
Authors: Guo Lei , Li Nan , Yang Zening , Li Heng , Zheng Huiwen , Yang Jinxi , Chen Yanli , Zhao Xin , Mei Junjie , Shi Haijing , Worthen G. Scott , Liu Longding
Published: November 2021

Respirovirus such as influenza virus infection induces pulmonary anti-viral immune response, orchestration of innate and adaptive immunity restrain viral infection, otherwise causes severe diseases such as pneumonia. Chemokines regulate leukocyte recruitment to the inflammation site. One chemokine CXCL5, plays a scavenging role to regulate pulmonary host defense against bacterial infection, but its role in pulmonary influenza virus infection is underdetermined. Here, using an influenza (H1N1) infected CXCL5-/- mouse model, we found that CXCL5 not only responds to neutrophil infiltration into infected lungs at the innate immunity stage, but also affects B lymphocyte accumulation in the lungs by regulating the expression of the B cell chemokine CXCL13. Inhibition of CXCL5-CXCR2 axis markedly induces CXCL13 expression in CD64+CD44hiCD274hi macrophages/monocytes in infected lungs, and in vitro administration of CXCL5 to CD64+ alveolar macrophages suppresses CXCL13 expression via the CXCL5-CXCR2 axis upon influenza challenge. CXCL5 deficiency leads to increased B lymphocyte accumulation in infected lungs, contributing to an enhanced B cell immune response and facilitating induced bronchus-associated lymphoid tissue formation in the infected lungs during the late infection and recovery stages. These data highlight multiple regulatory roles of CXCL5 in leukocyte chemotaxis during pulmonary influenza infection.
Complementary Roles of Short and Long Pentraxins in the Complement-Mediated Immune Response to Aspergillus fumigatus Infections
Authors: Parente Raffaella , Possetti Valentina , Erreni Marco , D’Autilia Francesca , Bottazzi Barbara , Garlanda Cecilia , Mantovani Alberto , Inforzato Antonio , Doni Andrea
Published: November 2021

The ubiquitous moldAspergillus fumigatusis the major etiologic agent of invasive aspergillosis, a life-threatening infection amongst immune compromised individuals. An increasing body of evidence indicates that effective disposal ofA. fumigatusrequires the coordinate action of both cellular and humoral components of the innate immune system. Early recognition of the fungal pathogen, in particular, is mediated by a set of diverse soluble pattern recognition molecules (PRMs) that act as “ancestral antibodies” inasmuch as they are endowed with opsonic, pro-phagocytic and killing properties. Pivotal is, in this respect, the contribution of the complement system, which functionally cooperates with cell-borne pattern recognition receptors (PRRs) and other soluble PRMs, including pentraxins. Indeed, complement and pentraxins form an integrated system with crosstalk, synergism, and regulation, which stands as a paradigm of the interplay between PRMs in the mounting and orchestration of antifungal immunity. Following upon our past experience with the long pentraxin PTX3, a well-established immune effector in the host response toA. fumigatus, we recently reported that this fungal pathogen is targetedin vitroandin vivoby the short pentraxin Serum Amyloid P component (SAP) too. Similar to PTX3, SAP promotes phagocytosis and disposal of the fungal pathogenviacomplement-dependent pathways. However, the two proteins exploit different mechanisms of complement activation and receptor-mediated phagocytosis, which further extends complexity and integration of the complement-pentraxin crosstalk in the immune response toA. fumigatus. Here we revisit this crosstalk in light of the emerging roles of SAP as a novel PRM with antifungal activity.
Spatio-Temporal Variability in White Shark (Carcharodon carcharias) Movement Ecology During Residency and Migration Phases in the Western North Atlantic
Authors: Franks Bryan R. , Tyminski John P. , Hussey Nigel E. , Braun Camrin D. , Newton Alisa L. , Thorrold Simon R. , Fischer George C. , McBride Brett , Hueter Robert E.
Published: November 2021

Understanding how mobile, marine predators use three-dimensional space over time is central to inform management and conservation actions. Combining tracking technologies can yield powerful datasets over multiple spatio-temporal scales to provide critical information for these purposes. For the white shark (Carcharodon carcharias), detailed movement and migration information over ontogeny, including inter- and intra-annual variation in timing of movement phases, is largely unknown in the western North Atlantic (WNA), a relatively understudied area for this species. To address this need, we tracked 48 large juvenile to adult white sharks between 2012 and 2020, using a combination of satellite-linked and acoustic telemetry. Overall, WNA white sharks showed repeatable and predictable patterns in horizontal movements, although there was variation in these movements related to sex and size. While most sharks undertook an annual migratory cycle with the majority of time spent over the continental shelf, some individuals, particularly adult females, made extensive forays into the open ocean as far east as beyond the Mid-Atlantic Ridge. Moreover, increased off-shelf use occurred with body size even though migration and residency phases were conserved. Summer residency areas included coastal Massachusetts and portions of Atlantic Canada, with individuals showing fidelity to specific regions over multiple years. An autumn/winter migration occurred with sharks moving rapidly south to overwintering residency areas in the southeastern United States Atlantic and Gulf of Mexico, where they remained until the following spring/summer. While broad residency and migration periods were consistent, migratory timing varied among years and among individuals within years. White sharks monitored with pop-up satellite-linked archival tags made extensive use of the water column (0–872 m) and experienced a broad range of temperatures (−0.9 – 30.5°C), with evidence for differential vertical use based on migration and residency phases. Overall, results show dynamic inter- and intra-annual three-dimensional patterns of movements conserved within discrete phases. These results demonstrate the value of using multiple tag types to track long-term movements of large mobile species. Our findings expand knowledge of the movements and migration of the WNA white shark population and comprise critically important information to inform sound management strategies for the species.
Effects of Different Plastic Mulching Film on Soil Hydrothermal Status and Water Utilization by Spring Maize in Northwest China
Authors: Liu Ruhua , Wang Zhenhua , Ye Hanchun , Li Wenhao , Zong Rui , Tian Xulang
Published: November 2021

The problem of residual film pollution in farmland caused by polyethylene mulching films is serious. The application effects of different mulching films combined with drip irrigation on maize planting in the Ili area, Xinjiang, China, were explored. In this study, four types of mulching films and non-mulching treatment were used to study the degradation properties of different plastic mulching and their effects on the dynamic changes of soil moisture, heat, and crop yields of maize under drip irrigation. The results showed that after 160 days of mulching film, only small cracks appeared in polyethylene mulching films. The degradation performance of white oxo-biodegradable film treatment was optimal than the black oxo-biodegradable film treatment. The quality loss rate of the two biodegradable films were 52.26 and 48.48%, respectively. Various mulching film treatments could increase soil moisture in the early stage of maize growth. At the 0–60 cm soil layer, the soil moisture under the white oxo-biodegradable mulching film and black oxo-biodegradable mulching film treatments were lower by 2.75 and 2.66% (p < 0.05) than the white polyethylene mulching film and black polyethylene mulching film treatments. The soil water consumption was highest in the non-mulching treatment, followed by biodegradable film, and the small least value was observed in the polyethylene film treatment. The average soil temperature at depth of 0–15 cm in white polyethylene mulching film, black polyethylene mulching film, white oxo-biodegradable mulching film, and black oxo-biodegradable mulching film treatments were 1.43, 1.16, 0.72 and 0.64°C higher than the non-mulching treatment, respectively. Mulching films treatment played a critical role in increasing production and improving water use efficiency. The black polyethylene mulching film treatment had the highest yield and the best water use efficiency. The black oxo-biodegradable mulching film treatment only reduces the yield by 0.33% compared to the black polyethylene mulching film treatment, and the water use efficiency was only reduced by 0.90% (p > 0.05). Comprehensive analysis showed that black oxo-biodegradable mulching film could be used as a substitute for polyethylene mulching film and can be applied to the production practice of drip irrigation maize in the Ili area.