bluuebunny/crossref_metadata_2025 huggingface dataset:
Opportunities and challenges of natural killer cell-derived extracellular vesicles
Authors: Qi Yuchen , Zhao Xiang , Dong Yan , Wang Min , Wang Junyi , Fan Zhichao , Weng Qin , Yu Hua , Li Jianjun
Published: March 2023

Extracellular vesicles (EVs) are increasingly recognized as important intermediaries of intercellular communication. They have significant roles in many physiological and pathological processes and show great promise as novel biomarkers of disease, therapeutic agents, and drug delivery tools. Existing studies have shown that natural killer cell-derived EVs (NEVs) can directly kill tumor cells and participate in the crosstalk of immune cells in the tumor microenvironment. NEVs own identical cytotoxic proteins, cytotoxic receptors, and cytokines as NK cells, which is the biological basis for their application in antitumor therapy. The nanoscale size and natural targeting property of NEVs enable precisely killing tumor cells. Moreover, endowing NEVs with a variety of fascinating capabilities via common engineering strategies has become a crucial direction for future research. Thus, here we provide a brief overview of the characteristics and physiological functions of the various types of NEVs, focusing on their production, isolation, functional characterization, and engineering strategies for their promising application as a cell-free modality for tumor immunotherapy.
Probing the conserved roles of cut in the development and function of optically different insect compound eyes
Authors: Rathore Shubham , Meece Michael , Charlton-Perkins Mark , Cook Tiffany A. , Buschbeck Elke K.
Published: March 2023

Astonishing functional diversity exists among arthropod eyes, yet eye development relies on deeply conserved genes. This phenomenon is best understood for early events, whereas fewer investigations have focused on the influence of later transcriptional regulators on diverse eye organizations and the contribution of critical support cells, such as Semper cells (SCs). As SCs in Drosophila melanogaster secrete the lens and function as glia, they are critical components of ommatidia. Here, we perform RNAi-based knockdowns of the transcription factor cut (CUX in vertebrates), a marker of SCs, the function of which has remained untested in these cell types. To probe for the conserved roles of cut, we investigate two optically different compound eyes: the apposition optics of D. melanogaster and the superposition optics of the diving beetle Thermonectus marmoratus. In both cases, we find that multiple aspects of ocular formation are disrupted, including lens facet organization and optics as well as photoreceptor morphogenesis. Together, our findings support the possibility of a generalized role for SCs in arthropod ommatidial form and function and introduces Cut as a central player in mediating this role.
Artemis inhibition as a therapeutic strategy for acute lymphoblastic leukemia
Authors: Ogana Heather A. , Hurwitz Samantha , Hsieh Chih-Lin , Geng Huimin , Müschen Markus , Bhojwani Deepa , Wolf Mark A. , Larocque James , Lieber Michael R. , Kim Yong Mi
Published: March 2023

As effective therapies for relapse and refractory B-cell acute lymphoblastic leukemia (B-ALL) remain problematic, novel therapeutic strategies are needed. Artemis is a key endonuclease in V(D)J recombination and nonhomologous end joining (NHEJ) of DNA double-strand break (DSB) repair. Inhibition of Artemis would cause chromosome breaks during maturation of RAG-expressing T- and B-cells. Though this would block generation of new B- and T-cells temporarily, it could be oncologically beneficial for reducing the proliferation of B-ALL and T-ALL cells by causing chromosome breaks in these RAG-expressing tumor cells. Currently, pharmacological inhibition is not available for Artemis. According to gene expression analyses from 207 children with high-risk pre-B acute lymphoblastic leukemias high Artemis expression is correlated with poor outcome. Therefore, we evaluated four compounds (827171, 827032, 826941, and 825226), previously generated from a large Artemis targeted drug screen. A biochemical assay using a purified Artemis:DNA-PKcs complex shows that the Artemis inhibitors 827171, 827032, 826941, 825226 have nanomolar IC50 values for Artemis inhibition. We compared these 4 compounds to a DNA-PK inhibitor (AZD7648) in three patient-derived B-ALL cell lines (LAX56, BLQ5 and LAX7R) and in two mature B-cell lines (3301015 and 5680001) as controls. We found that pharmacological Artemis inhibition substantially decreases proliferation of B-ALL cell lines while normal mature B-cell lines are not markedly affected. Inhibition of DNA-PKcs (which regulates Artemis) using the DNA-PK inhibitor AZD7648 had minor effects on these same primary patient-derived ALL lines, indicating that inhibition of V(D)J hairpin opening requires direct inhibition of Artemis, rather than indirect suppression of the kinase that regulates Artemis. Our data provides a basis for further evaluation of pharmacological Artemis inhibition of proliferation of B- and T-ALL.
Cervicovaginal mucus barrier properties during pregnancy are impacted by the vaginal microbiome
Authors: Zierden Hannah C. , DeLong Kevin , Zulfiqar Fareeha , Ortiz Jairo Ortiz , Laney Victoria , Bensouda Sabrine , Hernández Nicole , Hoang Thuy M. , Lai Samuel K. , Hanes Justin , Burke Anne E. , Ensign Laura M.
Published: March 2023

Introduction

Mucus in the female reproductive tract acts as a barrier that traps and eliminates pathogens and foreign particles via steric and adhesive interactions. During pregnancy, mucus protects the uterine environment from ascension of pathogens and bacteria from the vagina into the uterus, a potential contributor to intrauterine inflammation and preterm birth. As recent work has demonstrated the benefit of vaginal drug delivery in treating women’s health indications, we sought to define the barrier properties of human cervicovaginal mucus (CVM) during pregnancy to inform the design of vaginally delivered therapeutics during pregnancy.

Methods

CVM samples were self-collected by pregnant participants over the course of pregnancy, and barrier properties were quantified using multiple particle tracking. 16S rRNA gene sequencing was performed to analyze the composition of the vaginal microbiome.

Results

Participant demographics differed between term delivery and preterm delivery cohorts, with Black or African American participants being significantly more likely to delivery prematurely. We observed that vaginal microbiota is most predictive of CVM barrier properties and of timing of parturition. Lactobacillus crispatus dominated CVM samples showed increased barrier properties compared to polymicrobial CVM samples.

Discussion

This work informs our understanding of how infections occur during pregnancy, and directs the engineering of targeted drug treatments for indications during pregnancy.
The innate and T-cell mediated immune response during acute and chronic gammaherpesvirus infection
Authors: Rex Viktoria , Zargari Razieh , Stempel Markus , Halle Stephan , Brinkmann Melanie M.
Published: March 2023

Immediately after entry into host cells, viruses are sensed by the innate immune system, leading to the activation of innate antiviral effector mechanisms including the type I interferon (IFN) response and natural killer (NK) cells. This innate immune response helps to shape an effective adaptive T cell immune response mediated by cytotoxic T cells and CD4+ T helper cells and is also critical for the maintenance of protective T cells during chronic infection. The human gammaherpesvirus Epstein-Barr virus (EBV) is a highly prevalent lymphotropic oncovirus that establishes chronic lifelong infections in the vast majority of the adult population. Although acute EBV infection is controlled in an immunocompetent host, chronic EBV infection can lead to severe complications in immunosuppressed patients. Given that EBV is strictly host-specific, its murine homolog murid herpesvirus 4 or MHV68 is a widely used model to obtain in vivo insights into the interaction between gammaherpesviruses and their host. Despite the fact that EBV and MHV68 have developed strategies to evade the innate and adaptive immune response, innate antiviral effector mechanisms still play a vital role in not only controlling the acute infection but also shaping an efficient long-lasting adaptive immune response. Here, we summarize the current knowledge about the innate immune response mediated by the type I IFN system and NK cells, and the adaptive T cell-mediated response during EBV and MHV68 infection. Investigating the fine-tuned interplay between the innate immune and T cell response will provide valuable insights which may be exploited to design better therapeutic strategies to vanquish chronic herpesviral infection.
Hypercapsule is the cornerstone of Klebsiella pneumoniae in inducing pyogenic liver abscess
Authors: Hu Dakang , Chen Wenjie , Wang Weiwen , Tian Dongxing , Fu Pan , Ren Ping , Mu Qing , Li Gang , Jiang Xiaofei
Published: March 2023

Purpose

To investigate the mechanisms of Klebsiella pneumoniae-induced pyogenic liver abscess (PLA).

Methods

Forty-three K. pneumoniae strains from PLAs and 436 from non-PLAs were collected. Their differences were compared for virulence genes and factors, sequence types, and serotypes. Virulence genes wzi, wzy-K1, and wzi+wzy-K1 were deleted in K. pneumoniae NTUH-K2044. Various analyses, such as transmission electron microscopy, neutrophil killing tests, and mouse lethality tests, were used to confirm the consequent changes.

Results

Differences were found between K. pneumoniae strains from PLA and non-PLA samples for virulence genes and factors, including metabolism genes (allS and peg-344), capsular polysaccharide (CPS)-synthesis channel gene (wzy-K1), CPS-regulating genes (p-rmpA, p-rmpA2, and c-rmpA), and siderophore genes (iucA and iroN). When wzy-K1 was positive, the difference between PLA and non-PLA samples was only observed with c-rmpA. Δwzi, Δwzy-K1, and ΔwziΔwzy-K1 strains reverted to hypovirulence. In the Kupffer cell stimulation assay, interleukin (IL)-6, IL-12, IL-10, and transforming growth factor-β secretions were found to be equivalent in NTUH-K2044, Δwzi, Δwzy-K1, and ΔwziΔwzy-K1 groups. Lower IL-1β and higher tumor necrosis factor-α secretions were observed for Δwzi, Δwzy-K1, and ΔwziΔwzy-K1.

Conclusions

Hypercapsule production is the cornerstone of hypervirulence, regardless of exopolysaccharides. K1 K. pneumoniae-induced PLA may decrease core inflammatory cytokines rather than increase anti-inflammatory cytokines. Exopolysaccharides could also attenuate the inflammatory response to aid in the immune escape of K. pneumoniae.
Assessing the effect of dialogue on altruism toward future generations: A preliminary study
Authors: Maalouly Elie , Yamazaki Ryuji , Nishio Shuichi , Nørskov Marco , Kamaga Kohei , Komai Shoji , Chiba Kiyoshi , Atsumi Keiichiro , Akao Ken-Ichi
Published: March 2023

Introduction

Despite the abundance of evidence on climate change and its consequences on future generations, people, in general, are still reluctant to change their actions and behaviors toward the environment that would particularly benefit posterity. In this study, we took a preliminary step in a new research direction to explore humans' altruistic behavior toward future generations of people and whether it can be affected by dialogue.

Methods

We used an android robot called Telenoid as a representative of future generations by explaining that the robot is controlled by an Artificial Intelligence (AI) living in a simulation of our world in the future. To measure people's altruistic behavior toward it, we asked the participants to play a round of the Dictator Game with the Telenoid before having an interactive conversation with the Telenoid and then playing another round.

Results

On average, participants gave more money to the Telenoid in the second round (after having an interactive conversation). The average amount of money increased from 20% in the first to about 30% in the second round.

Discussion

The results indicate that the conversation with the robot might have been responsible for the change in altruistic behavior toward the Telenoid. Contrary to our expectations, the personality of the participants did not appear to have an influence on their change of behavior, but other factors might have contributed. We finally discuss the influence of other possible factors such as empathy and the appearance of the robot. However, the preliminary nature of this study should deter us from making any definitive conclusions, but the results are promising for establishing the ground for future experiments.
Causal relationship between type 1 diabetes mellitus and six high-frequency infectious diseases: A two-sample mendelian randomization study
Authors: Chen Xiao-Hong , Liu Hong-Qiong , Nie Qiong , Wang Han , Xiang Tao
Published: March 2023

Purpose

Type 1 diabetes mellitus (T1DM) is associated with different types of infections; however, studies on the causal relationship between T1DM and infectious diseases are lacking. Therefore, our study aimed to explore the causalities between T1DM and six high-frequency infections using a Mendelian randomization (MR) approach.

Methods

Two-sample MR studies were conducted to explore the causalities between T1DM and six high-frequency infections: sepsis, acute lower respiratory infections (ALRIs), intestinal infections (IIs), infections of the genitourinary tract (GUTIs) in pregnancy, infections of the skin and subcutaneous tissues (SSTIs), and urinary tract infections (UTIs). Data on summary statistics for T1DM and infections were obtained from the European Bioinformatics Institute database, the United Kingdom Biobank, FinnGen biobank, and Medical Research Council Integrative Epidemiology Unit. All data obtained for summary statistics were from European countries. The inverse-variance weighted (IVW) method was employed as the main analysis. Considering the multiple comparisons, statistical significance was set at p< 0.008. If univariate MR analyses found a significant causal association, multivariable MR (MVMR) analyses were performed to adjust body mass index (BMI) and glycated hemoglobin (HbA1c). MVMR-IVW was performed as the primary analysis, and the least absolute shrinkage and selection operator (LASSO) regression and MVMR-Robust were performed as complementary analyses.

Results

MR analysis showed that susceptibility to IIs increased in patients with T1DM by 6.09% using the IVW-fixed method [odds ratio (OR)=1.0609; 95% confidence interval (CI): 1.0281–1.0947, p=0.0002]. Results were still significant after multiple testing. Sensitivity analyses did not show any significant horizontal pleiotropy or heterogeneity. After adjusting for BMI and HbA1c, MVMR-IVW (OR=1.0942; 95% CI: 1.0666–1.1224, p<0.0001) showed significant outcomes that were consistent with those of LASSO regression and MVMR-Robust. However, no significant causal relationship was found between T1DM and sepsis susceptibility, ALRI susceptibility, GUTI susceptibility in pregnancy, SSTI susceptibility, and UTI susceptibility.

Conclusions

Our MR analysis genetically predicted increased susceptibility to IIs in T1DM. However, no causality between T1DM and sepsis, ALRIs, GUTIs in pregnancy, SSTIs, or UTIs was found. Larger epidemiological and metagenomic studies are required to further investigate the observed associations between the susceptibility of certain infectious diseases with T1DM.
Clinical characteristics and risk factors of lower extremity amputation in the diabetic inpatients with foot ulcers
Authors: Gong Hongping , Ren Yan , Li Zhenyi , Zha Panpan , Bista Raju , Li Yan , Chen Dawei , Gao Yun , Chen Lihong , Ran Xingwu , Wang Chun
Published: March 2023

Objectives

To analyze clinical characteristics of the diabetic inpatients with foot ulcers and explore the risk factors of lower extremity amputation (LEA) in West China Hospital of Sichuan University.

Methods

A retrospective analysis was performed based on the clinical data of the patients with diabetic foot ulcer (DFU) hospitalized in West China Hospital of Sichuan University from January 1, 2012 to December 31, 2020. The DFU patients were divided into three groups: non-amputation, minor amputation, and major amputation groups. The ordinal logistic regression analysis was used to identify the risk factors for LEA.

Results

992 diabetic patients (622 males and 370 females) with DFU were hospitalized in the Diabetic Foot Care Center of Sichuan University. Among them, 72 (7.3%) (55 minor amputations and 17 major amputations) cases experienced amputation, and 21(2.1%) refused amputation. Excluding the patients who refused amputation, the mean age and duration of diabetes of and HbA1c the 971 patients with DFU, were 65.1 ± 12.3 years old, 11.1 ± 7.6 years, and 8.6 ± 2.3% respectively. The patients in the major amputation group were older and had longer course of diabetes for a longer period of time than those in the non-amputation and minor amputation groups. Compared with the non-amputation patients (55.1%), more patients with amputation (minor amputation (63.5%) and major amputation (88.2%)) suffered from peripheral arterial disease (P=0.019). The amputated patients had statistically lower hemoglobin, serum albumin and ankle brachial index (ABI), but higher white blood cell, platelet counts, fibrinogen and C-reactive protein levels. The patients with amputation had a higher incidence of osteomyelitis (P = 0.006), foot gangrene (P < 0.001), and a history of prior amputations (P < 0.001) than those without amputation. Furthermore, a history of prior amputation (odds ratio 10.194; 95% CI, 2.646-39.279; P=0.001), foot gangrene (odds ratio 6.466; 95% CI, 1.576-26.539; P=0.010) and ABI (odds ratio 0.791; 95% CI, 0.639-0.980; P = 0.032) were significantly associated with LEAs.

Conclusions

The DFU inpatients with amputation were older with long duration of diabetes, poorly glycemic control, malnutrition, PAD, severe foot ulcers with infection. A history of prior amputation, foot gangrene and a low ABI level were the independent predictors of LEA. Multidisciplinary intervention for DFU is essential to avoid amputation of the diabetic patients with foot ulcer.
Laughter yoga as an enjoyable therapeutic approach for glycemic control in individuals with type 2 diabetes: A randomized controlled trial
Authors: Hirosaki Mayumi , Ohira Tetsuya , Wu Yawei , Eguchi Eri , Shirai Kokoro , Imano Hironori , Funakubo Narumi , Nishizawa Hitoshi , Katakami Naoto , Shimomura Iichiro , Iso Hiroyasu
Published: March 2023

Background

Laughter has been reported to have various health benefits. However, data on the long-term effects of laughter interventions on diabetes are limited. This study aimed to investigate whether laughter yoga can improve glycemic control among individuals with type 2 diabetes.

Methods

In a single-center, randomized controlled trial, 42 participants with type 2 diabetes were randomly assigned to either the intervention or the control group. The intervention consisted of a 12-week laughter yoga program. Hemoglobin A1c (HbA1c), body weight, waist circumference, psychological factors, and sleep duration were evaluated at baseline and week 12.

Results

Intention-to-treat analysis showed that participants in the laughter yoga group experienced significant improvements in HbA1c levels (between-group difference: −0.31%; 95% CI −0.54, −0.09) and positive affect scores (between-group difference: 0.62 points; 95% CI 0.003, 1.23). Sleep duration tended to increase in the laughter yoga group with a between-group difference of 0.4 hours (95% CI −0.05, 0.86; P = 0.080). The mean attendance rate for laughter yoga program was high (92.9%).

Conclusions

A 12-week laughter yoga program is feasible for individuals with type 2 diabetes and improves glycemic control. These findings suggest that having fun could be a self-care intervention. Further studies with larger numbers of participants are warranted to better evaluate the effects of laughter yoga.

Clinical trial registration

http://www.chinadrugtrials.org.cn, identifier UMIN000047164.
Thirty synchronous medullary and papillary thyroid carcinomas
Authors: Zhang Daqi , Yang Mingyu , Zhang Xin , Wang Cheng , Li Kunlin , Wang Hongbo , Chi Hao , Sui Chengqiu , Dionigi Gianlorenzo , Sun Hui
Published: March 2023

Synopsis for table of contents

An exceptional number of synchronous MTC/PTC in the same thyroid gland is presented. This may be the most numerous case series reported in the literature. Synchronous PTC/MTC in the same thyroid gland were classified into 4 subtypes and the clinical and pathological aspects as well as the results are presented.

Background and objectives

The synchronous occurrence of multiple neoplastic processes in the thyroid gland is unusual. We investigated the clinicopathological features of 30 medullary thyroid carcinomas (MTC) in association with papillary (PTC).

Method

Retrospective analysis of operated patients for thyroid tumors. Synchronous PTC/MTC in the same thyroid gland were classified into 4 subtypes: (type I) True mixed MTC/PTC, MTC and PTC closely intermingled. (Type II) Collision MTC/PTC, i.e. tumors that meet at the same site, invade each other and appear as a single mass in the thyroid gland, i.e. MTC and PTC merge. (Type III) Synchronous anatomically separate tumors in the same thyroid lobe, i.e. separated from each other by non-tumorous thyroid parenchyma. (Type IV) Synchronous tumors occurring in separate anatomical lobes or in the isthmus. Clinical and pathological data were reviewed. Location: Department of thyroid surgery, China-Japan Union Hospital, Jilin University. Time frame: 14 years (June 2008-November 2022).

Results

Thirty patients were identified with an overall prevalence of 28621 (0.1%). 17 (56.7%) were male, 13 (43.3%) female, mean age 51.3 ± 11.0 years, mean BMI 23.6 ± 3.6kg/m2. Mean duration of symptoms was 11.2 ± 18.4 months. Mean calcitonin level was 133.7 ± 196.4 pg/ml. Fine needle aspiration (FNA) was offered in 21 cases: 9 (42.9%) were suspected carcinoma, 9 (42.9%) PTC, 1 (4.8%) MTC, 2 (9.4%) MTC/PTC. Pathology revealed type I 4 (13.3%), type II 2 (6.7%), type III 14 (46.7%), type IV 10 (33.3%). The mean diameter of MTC was 1.6 ± 2.0cm, 18 (60%) were micro-MTC. The mean diameter of PTC was 0.9 ± 1.9 cm, 26 (86.7%) were micro-PTC. In 16 (53.3%) micro-PTC/-MTC occurred in synchronous sequence. Four patients had a recurrence: 2 had to be re-operated due to MTC recurrence, 2 died due to distant metastases (bone, liver).

Conclusion

We report an exceptional number of MTC/PTC in the same thyroid gland. This may be the most numerous case series reported in the literature. The clinical and pathological aspects as well as the results are presented.
Electrohydrodynamic air amplifier for low-energy airflow generation—An experimental proof-of-concept
Authors: Rubinetti Donato , Iranshahi Kamran , Onwude Daniel , Nicolaï Bart , Xie Lei , Defraeye Thijs
Published: March 2023

With electrohydrodynamics (EHD), we can propel air in a low-energy fashion. EHD airflow, or ionic wind, arises when a high voltage gradient is applied to a set of electrodes. The air ionizes between electrodes via corona discharge and accelerates in an electric field, exchanging momentum with the surrounding air. While the ionization process is energy-efficient, reaching competitive flow rates remains challenging from a high-voltage engineering perspective. To increase EHD-generated flow rates, this study experimentally investigates a novel concept called EHD air amplification. The concept uses ionic wind as bleed flow to induce a more significant bulk flow by the air-amplifying Coanda effect. Due to the complex interactions between EHD and dielectric structures for air amplification, the conceptual EHD air amplifier device is designed stage-wise, starting with a simple emitter-collector electrode configuration. First, regular EHD flow was studied in a 150 × 150 × 500 mm3 channel. Then, a dielectric material was added to determine its influence on the electric field. The impact of a converging nozzle on the EHD-generated airflow was subsequently studied. Lastly, the converged nozzle airflow was used to create a bleed flow on a plate to facilitate air amplification of the surrounding air. We show the proof-of-concept for an EHD air amplification system. After a voltage threshold of 14 kV, amplified airstreams up to an amplification factor of 3 were measured. Maximum airflow rates of about 15 m3 h−1 were obtained shortly before electric breakdown at 22 kV. Compared to regular EHD, we achieved a higher aerodynamic performance for the same electric energy invested. The flow rate to electric power ratio increased to 66% in EHD air amplification compared to regular EHD. The proposed EHD air amplifier operates at atmospheric pressure. It lays the groundwork for further optimization studies to position EHD air amplification as a low-energy, low-maintenance, motor- and noiseless airflow generation technology.
Development and demonstration of concentric-type HTS power cable for distribution grid in Shenzhen urban
Authors: Tang Shouquan , Li Minhong , Xie Hong , Wang Zhenzi , Yu Peng , Li Zhonghang , Wang Zhe , Chen Tengbiao , Wang Bangzhu
Published: March 2023

High-temperature superconducting (HTS) cable can transmit massive power with little dissipation in a limited corridor, which is an attractive solution for future power transmission. Shenzhen Power Supply energized a 400 m/10 kV/2.5 kA concentric HTS cable system on 28 September 2021 to power Ping’an Financial Centre, a Shenzhen’s landmark building, which was the debut of concentric HTS cable made of YBCO in the urban area of a megacity. For more than 1 year, the HTS cable system has been operating well and will continue to operate for a long time. This paper systematically reviews the system specification, cable and its accessories design, cryogenic cooling system design, type and exploratory test, project construction, pre-commissioning test, and operation of the demonstration cable system. Based on our R&D practice, we identify that cost, long-term reliability, and operational simplicity are the main hinders factors that need to be addressed to advance the large-scale application and we propose a set of solution ideas meanwhile.
How does corporate ESG performance affect sustainable development: A green innovation perspective
Authors: Lian Yonghui , Li Yaqi , Cao Hong
Published: March 2023

This study examines the influence of corporate ESG performance on green innovation based on the data of 2024 A-share listed firms in China from 2009 to 2020. We find that ESG performance has a significantly positive impact on green innovation. Mechanism analysis reveals that excellent ESG performance contributes to relieving financing constraints, enhancing the level of corporate human capital, and improving management myopia, thus positively influencing corporate green innovation. Heterogeneity analysis shows that the positive effect of ESG performance on green innovation is more pronounced in firms with strong innovation capacity, non-state enterprises, firms in non-polluting industries, firms located in areas with high marketization, and firms in poor macroeconomic environments. Further analyses prove that good ESG performance also helps to enhance the quality of green innovation, the efficiency of green innovation, and the proportion of collaborative green innovation. These results offer important implications for improving firm ESG performance and promoting corporate green innovation.
Heterogeneity in the isolation of patches may be essential for the action of metacommunity mechanisms
Authors: Borthagaray Ana I. , Cunillera-Montcusí David , Bou Jordi , Tornero Irene , Boix Dani , Anton-Pardo Maria , Ortiz Esteban , Mehner Thomas , Quintana Xavier D. , Gascón Stéphanie , Arim Matías
Published: March 2023

The spatial isolation gradient of communities and the gradient in the species dispersal ability are recognized as determinants of biodiversity in metacommunities. In spite of this, mean field models, spatially explicit models, and experiments were mainly focused on idealized spatial arrangements of communities leaving aside the combining role of dispersal and isolation gradients in metacommunity processes. Consequently, we have an incipient understanding of the role of the real spatial arrangement of communities on biodiversity patterns. We focus on six metacommunities for which confident information about the spatial arrangement of water bodies is available. Using coalescent metacommunity models and null models that randomize the location of water bodies, we estimated the potential effect of the landscape on biodiversity and its dependence on species dispersal ability. At extremely low or high dispersal abilities, the location of ponds does not influence diversity because different communities are equally affected by the low or high incoming dispersal. At intermediate dispersal abilities, peripheral communities present a much lower richness and higher beta diversity than central communities. Moreover, metacommunities from real landscapes host more biodiversity than randomized landscapes, a result that is determined by the heterogeneity in the geographic isolation of communities. In a dispersal gradient, mass effects systematically increase the local richness and decrease beta diversity. However, the spatial arrangement of patches only has a large importance in metacommunity processes at intermediate dispersal abilities, which ensures access to central locations but limits dispersal in isolated communities. The ongoing reduction in spatial extent and simplification of the landscape may consequently undermine the metacommunity processes that support biodiversity, something that should be explicitly considered in preserving and restoring strategies.
Assessment of fire hazard in Southwestern Amazon
Authors: Ferreira Igor J. M. , Campanharo Wesley A. , Barbosa Maria L. F. , Silva Sonaira S. da , Selaya Galia , Aragão Luiz E. O. C. , Anderson Liana O.
Published: March 2023

Fires are among the main drivers of forest degradation in Amazonia, causing multiple socioeconomic and environmental damages. Although human-ignited sources account for most of the fire events in Amazonia, extended droughts may magnify their occurrence and propagation. The southwestern Amazonia, a transnational region shared by Brazil, Peru, and Bolivia and known as the MAP region, has been articulating coordinated actions to prevent disasters, including fire, to reduce their negative impacts. Therefore, to understand the fire patterns in the MAP region, we investigated their main drivers and the changes in the suitability of fire occurrence for the years 2005, 2010, 2016, and 2020. We used a maximum entropy (MaxEnt) model approach based on active fire data from satellites, climatic data, and land use and land cover mapping to spatially quantify the suitability of fire occurrence and its drivers. We used the year 2015 to calibrate the models. For climatic data and active fire count, we only considered grid cells with active fire count over the third quartile. All our models had a satisfactory performance, with values of the area under the curve (AUC) above 0.75 and p < 0.05. Additionally, all models showed sensitivity rates higher than 0.8 and false positive rates below 0.25. We estimated that, on average, 38.5% of the study region had suitable conditions for fire occurrence during the study period. Most of the fire-prone areas belong to Acre, representing approximately 74% of the entire MAP region. The percentage of deforested areas, productive lands, forest edges, and high temperatures were the main drivers of fire occurrence in southwestern Amazonia, indicating the high vulnerability of fragmented landscapes extreme climatic conditions to fire occurrence. We observed that the modeling approach based on Maxint is useful for useful for evaluating the implications of climatic and anthropogenic variables on fire distribution. Furthermore, because the model can be easily employed to predict suitable and non-suitable locations for fire occurrence, it can to prevent potential impacts associated with large-scale wildfire in the future at regional levels.
Climate and forest properties explain wildfire impact on microbial community and nutrient mobilization in boreal soil
Authors: Eckdahl Johan A. , Kristensen Jeppe A. , Metcalfe Daniel B.
Published: March 2023

The boreal landscape stores an estimated 40% of the earth's carbon (C) found in terrestrial vegetation and soils, with a large portion collected in thick organic soil layers. These ground stores are subject to substantial removals due to the centurial return of wildfire, which has strong impacts on the soil microbial community and nutrient cycling, which in turn can control ecosystem recovery patterns and process rates, such as C turnover. Currently, predictive knowledge used in assessing fire impacts is largely focused on ecosystems that experience only superficial burning and few robust observations exist regarding the effect that smoldering combustion in deeper active soil layers has on post-fire soil activity. This study provided a highly replicated and regionally extensive survey of wildfire impact on microbial community structure (using fatty acid biomarkers) and nutrient cycling (using in situ ionic resin capsules) across broad gradients of climate, forest properties and fire conditions within 50 separate burn scars and 50 additional matched unburnt boreal forest soils. The results suggest a strong metabolic shift in burnt soils due to heat impact on their structure and a decoupling from aboveground processes, releasing ecosystem N limitation and increasing mobilization of N, P, K, and S as excess in conjunction with an altered, C-starved microbial community structure and reduced root uptake due to vegetation mortality. An additional observed climatic control over burnt soil properties has implications for altered boreal forest function in future climate and fire regimes deserving of further attention.
Case report: Optical genome mapping revealed double rearrangements in a male undergoing preimplantation genetic testing
Authors: Ren Jun , Keqie Yuezhi , Li Yutong , Li Lingping , Luo Min , Gao Meng , Peng Cuiting , Chen Han , Hu Ting , Chen Xinlian , Liu Shanling
Published: March 2023

Chromosome rearrangement is one of the main causes of abortion. In individuals with double chromosomal rearrangements, the abortion rate and the risk of producing abnormal chromosomal embryos are increased. In our study, preimplantation genetic testing for structural rearrangement (PGT-SR) was performed for a couple because of recurrent abortion and the karyotype of the male was 45, XY der (14; 15)(q10; q10). The PGT-SR result of the embryo in this in vitro fertilization (IVF) cycle showed microduplication and microdeletion at the terminals of chromosomes 3 and 11, respectively. Therefore, we speculated whether the couple might have a cryptic reciprocal translocation which was not detected by karyotyping. Then, optical genome mapping (OGM) was performed for this couple, and cryptic balanced chromosomal rearrangements were detected in the male. The OGM data were consistent with our hypothesis according to previous PGT results. Subsequently, this result was verified by fluorescence in situ hybridization (FISH) in metaphase. In conclusion, the male’s karyotype was 45, XY, t(3; 11)(q28; p15.4), der(14; 15)(q10; q10). Compared with traditional karyotyping, chromosomal microarray, CNV-seq and FISH, OGM has significant advantages in detecting cryptic and balanced chromosomal rearrangements.
Functional genomic effects of indels using Bayesian genome-phenome wide association studies in sorghum
Authors: Boatwright J. Lucas , Sapkota Sirjan , Kresovich Stephen
Published: March 2023

High-throughput genomic and phenomic data have enhanced the ability to detect genotype-to-phenotype associations that can resolve broad pleiotropic effects of mutations on plant phenotypes. As the scale of genotyping and phenotyping has advanced, rigorous methodologies have been developed to accommodate larger datasets and maintain statistical precision. However, determining the functional effects of associated genes/loci is expensive and limited due to the complexity associated with cloning and subsequent characterization. Here, we utilized phenomic imputation of a multi-year, multi-environment dataset using PHENIX which imputes missing data using kinship and correlated traits, and we screened insertions and deletions (InDels) from the recently whole-genome sequenced Sorghum Association Panel for putative loss-of-function effects. Candidate loci from genome-wide association results were screened for potential loss of function using a Bayesian Genome-Phenome Wide Association Study (BGPWAS) model across both functionally characterized and uncharacterized loci. Our approach is designed to facilitate in silico validation of associations beyond traditional candidate gene and literature-search approaches and to facilitate the identification of putative variants for functional analysis and reduce the incidence of false-positive candidates in current functional validation methods. Using this Bayesian GPWAS model, we identified associations for previously characterized genes with known loss-of-function alleles, specific genes falling within known quantitative trait loci, and genes without any previous genome-wide associations while additionally detecting putative pleiotropic effects. In particular, we were able to identify the major tannin haplotypes at the Tan1 locus and effects of InDels on the protein folding. Depending on the haplotype present, heterodimer formation with Tan2 was significantly affected. We also identified major effect InDels in Dw2 and Ma1, where proteins were truncated due to frameshift mutations that resulted in early stop codons. These truncated proteins also lost most of their functional domains, suggesting that these indels likely result in loss of function. Here, we show that the Bayesian GPWAS model is able to identify loss-of-function alleles that can have significant effects upon protein structure and folding as well as multimer formation. Our approach to characterize loss-of-function mutations and their functional repercussions will facilitate precision genomics and breeding by identifying key targets for gene editing and trait integration.
Development of severe colitis is associated with lung inflammation and pathology
Authors: Raftery April L. , O’Brien Caitlin A. , Harris Nicola L. , Tsantikos Evelyn , Hibbs Margaret L.
Published: March 2023

Inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis are chronic relapsing diseases that affect the gastrointestinal tract, most commonly the colon. A link between the gut and the lung is suggested since patients with IBD have an increased susceptibility for chronic inflammatory lung disease. Furthermore, in the absence of overt lung disease, IBD patients have worsened lung function and more leukocytes in sputum than healthy individuals, highlighting a conduit between the gut and lung in disease. To study the gut-lung axis in the context of IBD, we used TCRδ-/- mice, which are highly susceptible to dextran sulfate sodium (DSS) due to the importance of γδ T cells in maintenance of barrier integrity. After induction of experimental colitis using DSS, the lungs of TCRδ-/- mice exhibited signs of inflammation and mild emphysema, which was not observed in DSS-treated C57BL/6 mice. Damage to the lung tissue was accompanied by a large expansion of neutrophils in the lung parenchyma and an increase in alveolar macrophages in the lung wash. Gene expression analyses showed a significant increase in Csf3, Cxcl2, Tnfa, and Il17a in lung tissue in keeping with neutrophil infiltration. Expression of genes encoding reactive oxygen species enzymes and elastolytic enzymes were enhanced in the lungs of both C57BL/6 and TCRδ-/- mice with colitis. Similarly, surfactant gene expression was also enhanced, which may represent a protective mechanism. These data demonstrate that severe colitis in a susceptible genetic background is sufficient to induce lung inflammation and tissue damage, providing the research community with an important tool for the development of novel therapeutics aimed at reducing co-morbidities in IBD patients.
ILC2 require cell-intrinsic ST2 signals to promote type 2 immune responses
Authors: Topczewska Patrycja M. , Rompe Zoe A. , Jakob Manuel O. , Stamm Anton , Leclère Pierre S. , Preußer Alexandra , Duerr Claudia U. , Thole Linda Marie Laura , Kotsch Katja , Artis David , Klose Christoph S. N.
Published: March 2023

The initiation of type 2 immune responses at mucosal barriers is regulated by rapidly secreted cytokines called alarmins. The alarmins IL-33, IL-25 and TSLP are mainly secreted by stromal and epithelial cells in tissues and were linked to chronic inflammatory diseases, such as allergic lung inflammation, or to resistance against worm infections. Receptors for alarmins are expressed by a variety of immune cells, including group 2 innate lymphoid cells (ILC2s), an early source of the type 2 cytokines, such as IL-5 and IL-13, which have been linked to atopic diseases and anti-worm immunity as well. However, the precise contribution of the IL-33 receptor signals for ILC2 activation still needs to be completed due to limitations in targeting genes in ILC2. Using the newly established Nmur1iCre-eGFP mouse model, we obtained specific conditional genetic ablation of the IL-33 receptor subunit ST2 in ILC2s. ST2-deficient ILC2s were unresponsive to IL-33 but not to stimulation with the alarmin IL-25. As a result of defective ST2 signals, ILC2s produced limited amounts of IL-5 and IL-13 and failed to support eosinophil homeostasis. Further, ST2-deficient ILC2s were unable to expand and promote the recruitment of eosinophils during allergic lung inflammation provoked by papain administration. During infection with Nippostrongylus brasiliensis, ILC2-intrinsic ST2 signals were required to mount an effective type 2 immune response against the parasite leading to higher susceptibility against worm infection in conditional knockout mice. Therefore, this study argues for a non-redundant role of cell-intrinsic ST2 signals triggering proper activation of ILC2 for initiation of type 2 immunity.
Linking dysbiosis to precancerous stomach through inflammation: Deeper than and beyond imaging
Authors: Lopes Catarina , Almeida Tatiana C. , Pimentel-Nunes Pedro , Dinis-Ribeiro Mário , Pereira Carina
Published: March 2023

Upper gastrointestinal endoscopy is considered the gold standard for gastric lesions detection and surveillance, but it is still associated with a non-negligible rate of missing conditions. In the Era of Personalized Medicine, biomarkers could be the key to overcome missed lesions or to better predict recurrence, pushing the frontier of endoscopy to functional endoscopy. In the last decade, microbiota in gastric cancer has been extensively explored, with gastric carcinogenesis being associated with progressive dysbiosis. Helicobacter pylori infection has been considered the main causative agent of gastritis due to its interference in disrupting the acidic environment of the stomach through inflammatory mediators. Thus, does inflammation bridge the gap between gastric dysbiosis and the gastric carcinogenesis cascade and could the microbiota-inflammation axis-derived biomarkers be the answer to the unmet challenge of functional upper endoscopy? To address this question, in this review, the available evidence on the role of gastric dysbiosis and chronic inflammation in precancerous conditions of the stomach is summarized, particularly targeting the nuclear factor-κB (NF-κB), toll-like receptors (TLRs) and cyclooxygenase-2 (COX-2) pathways. Additionally, the potential of liquid biopsies as a non-invasive source and the clinical utility of studied biomarkers is also explored. Overall, and although most studies offer a mechanistic perspective linking a strong proinflammatory Th1 cell response associated with, but not limited to, chronic infection with Helicobacter pylori, promising data recently published highlights not only the diagnostic value of microbial biomarkers but also the potential of gastric juice as a liquid biopsy pushing forward the concept of functional endoscopy and personalized care in gastric cancer early diagnosis and surveillance.
A close look at current γδ T-cell immunotherapy
Authors: Ma Ling , Feng Yanmin , Zhou Zishan
Published: March 2023

Owing to their antitumor and major histocompatibility complex (MHC)-independent capacities, γδ T cells have gained popularity in adoptive T-cell immunotherapy in recent years. However, many unknowns still exist regarding γδ T cells, and few clinical data have been collected. Therefore, this review aims to describe all the main features of the applications of γδ T cells and provide a systematic view of current γδ T-cell immunotherapy. Specifically, this review will focus on how γδ T cells performed in treating cancers in clinics, on the γδ T-cell clinical trials that have been conducted to date, and the role of γδ T cells in the pharmaceutical industry.
Deep characterization of human γδ T cell subsets defines shared and lineage-specific traits
Authors: Sanz Marta , Mann Brendan T. , Ryan Paul L. , Bosque Alberto , Pennington Daniel J. , Hackstein Holger , Soriano-Sarabia Natalia
Published: March 2023

Under non-pathological conditions, human γδ T cells represent a small fraction of CD3+ T cells in peripheral blood (1-10%). They constitute a unique subset of T lymphocytes that recognize stress ligands or non-peptide antigens through MHC-independent presentation. Major human γδ T cell subsets, Vδ1 and Vδ2, expand in response to microbial infection or malignancy, but possess distinct tissue localization, antigen recognition, and effector responses. We hypothesized that differences at the gene, phenotypic, and functional level would provide evidence that γδ T cell subpopulations belong to distinct lineages. Comparisons between each subset and the identification of the molecular determinants that underpin their differences has been hampered by experimental challenges in obtaining sufficient numbers of purified cells. By utilizing a stringent FACS-based isolation method, we compared highly purified human Vδ1 and Vδ2 cells in terms of phenotype, gene expression profile, and functional responses. We found distinct genetic and phenotypic signatures that define functional differences in γδ T cell populations. Differences in TCR components, repertoire, and responses to calcium-dependent pathways suggest that Vδ1 and Vδ2 T cells are different lineages. These findings will facilitate further investigation into the ligand specificity and unique role of Vδ1 and Vδ2 cells in early immune responses.