bluuebunny/crossref_metadata_2025 huggingface dataset:
Motricidade e qualidade de vida em crianças durante a pandemia por COVID-19
Authors: Santos Luís Eduardo Lima , Ferreira Aline Xavier , Santos Maria Gabriele Rodrigues dos , Lacerda Maria Vitória , Ricarte Kátia Magaly Pires
Published: February 2023

Objetivo: O objetivo do trabalho foi correlacionar o nível de motricidade com a qualidade de vida de crianças na pandemia. Metodologia: Foi realizado um estudo transversal, de caráter quantitativo e natureza descritiva e exploratória que compreendeu uma amostra final de 75 escolares, com idade entre 9 e 10 anos, matriculados em escolas públicas. As crianças responderam um questionário sobre seu perfil sociodemográfico e escolar na pandemia. A avaliação do desempenho motor ocorreu por meio da EDM de Rosa Neto (2002), enquanto a percepção subjetiva de qualidade de vida dos escolares através do questionário AUQEI. Resultados: A grande maioria dos escolares apresentaram um nível de qualidade de vida satisfatório (76%). Ao analisar isoladamente os domínios, constatou-se que o item “autonomia” dos avaliados possui prevalência (92%) de escolares que demostraram insatisfação. Percebeu-se que a grande maioria se mostrou estar dentro dos padrões de normalidade para aos níveis de desenvolvimento motor (62,7%) e ao associar à qualidade de vida, não foi confirmado nenhuma diferença significativa (p<0,001) entre as variáveis. No entanto, observou-se que 33,3% dos avaliados que tiveram um desenvolvimento motor classificado como inferior, apresentaram um nível insatisfatório quanto a análise subjetiva de sua qualidade de vida e ainda que 25% das crianças que se mantiveram no ensino remoto e 37,5% que permaneceram no ensino híbrido apresentaram déficit na idade motora. Conclusão: Concluiu-se que não houve uma associação significativa entre as variáveis de desenvolvimento motor e qualidade de vida. Entretanto, o domínio “autonomia” esteve visivelmente afetado.
Cuidado farmacêutico na farmácia comunitária privada: revisão integrativa
Authors: Souza Emerson Ferreira de , Silva Fernando Pereira da , Marquez Carolinne Oliveira
Published: February 2023

Introdução: A implantação dos serviços clínicos farmacêuticos foi iniciada em ambiente hospitalar e posteriormente expandida para farmácias comunitárias privadas. o objetivo do artigo é a realização de uma síntese de evidências sobre a importância do farmacêutico clínico na farmácia comunitária privada proporcionando aos utentes tratamentos eficientes e com a melhoria da qualidade de vida. Método: Trata-se de uma revisão integrativa fundamentada na pesquisa bibliográfica, método que agrupa a produção científica relevante acerca de um tema preestabelecido. Resultados e discussão: 14 artigos foram selecionados, sendo 08 deles revisões de literatura, 01 estudo transversal, 01 revisão sistemática com síntese narrativa e 04 estudos bibliográficos integrativos, sendo um dele com estudo quantitativo. Os estudos contemplem e sintetizam a importância do farmacêutico clínico na farmácia comunitária privada. Conclusão: As evidências apresentadas neste estudo demonstram a ação do farmacêutico clínico na farmácia comunitária, demonstrando que cabe a este profissional o manejo, dispensação e orientação quanto ao uso de medicamentos.
Adaptation as Arrangement in Three Cornell Woolrich Texts
Authors: Robertson Wojcik Pamela
Published: February 2023

This essay proposes a model of film adaptation as arrangement using three films based on Cornell Woolrich texts, The Window (1949), Rear Window (1954), and The Bride Wore Black (1968). Using Roland Barthes and other theorists, the essay considers the text as a plurality that traverses multiple works. Not only are versions in dialogue with the source material and with each other, but individual texts – the so-called originals – are themselves intertextual and thus plural. In thinking through the ‘stereographic plurality’ of texts and all the intertexts and influences that comprise both source and versions, the essay argues for an understanding of adaptation as an activity that is porous, mediated, and dynamic.
On the Rediscovery of ‘The Fiancée without a Future’ and ‘The Fault-Finder’
Authors: Nevins Francis M.
Published: February 2023

This brief essay serves as introduction to two recently discovered short stories by Cornell Woolrich: ‘The Fiancée without a Future’ and ‘The Fault-Finder’. The circumstances of the stories’ discovery are explained, as well as their place within Woolrich’s corpus. The stories themselves follow.
Mechanical stimulation promotes MSCs healing the lesion of intervertebral disc annulus fibrosus
Authors: Deng Rongrong , Kang Ran , Jin Xiaoyu , Wang Zihan , Liu Xin , Wang Qing , Xie Lin
Published: February 2023

Mesenchymal stem cells (MSCs) and scaffolds offer promising perspectives for annulus fibrosus (AF) repair. The repair effect was linked to features of the local mechanical environment related to the differentiation of MSCs. In this study, we established a Fibrinogen-Thrombin-Genipin (Fib-T-G) gel which is sticky and could transfer strain force from AF tissue to the human mesenchymal stem cells (hMSCs) embedded in the gel. After the Fib-T-G biological gel was injected into the AF fissures, the histology scores of intervertebral disc (IVD) and AF tissue showed that Fib-T-G gel could better repair the AF fissure in caudal IVD of rats, and increase the expression of AF-related proteins including Collagen 1 (COL1), Collagen 2 (COL2) as well as mechanotransduction-related proteins including RhoA and ROCK1. To clarify the mechanism that sticky Fib-T-G gel induces the healing of AF fissures and the differentiation of hMSCs, we further investigated the differentiation of hMSCs under mechanical strain in vitro. It was demonstrated that both AF-specific genes, including Mohawk and SOX-9, and ECM markers (COL1, COL2, aggrecan) of hMSCs were up-regulated in the environment of strain force. Moreover, RhoA/ROCK1 proteins were also found to be significantly up-regulated. In addition, we further -demonstrated that the fibrochondroinductive effect of the mechanical microenvironment process could be significantly blocked or up-regulated by inhibiting the RhoA/ROCK1 pathway or overexpressing RhoA in MSCs, respectively. Summarily, this study will provide a therapeutic alternative to repair AF tears and provide evidence that RhoA/ROCK1 is vital for hMSCs response to mechanical strain and AF-like differentiation.
Utility of atherosclerosis-associated serum antibodies against colony-stimulating factor 2 in predicting the onset of acute ischemic stroke and prognosis of colorectal cancer
Authors: Li Shu-Yang , Yoshida Yoichi , Kubota Masaaki , Zhang Bo-Shi , Matsutani Tomoo , Ito Masaaki , Yajima Satoshi , Yoshida Kimihiko , Mine Seiichiro , Machida Toshio , Hayashi Aiko , Takemoto Minoru , Yokote Koutaro , Ohno Mikiko , Nishi Eiichiro , Kitamura Kenichiro , Kamitsukasa Ikuo , Takizawa Hirotaka , Sata Mizuki , Yamagishi Kazumasa , Iso Hiroyasu , Sawada Norie , Tsugane Shoichiro , Iwase Katsuro , Shimada Hideaki , Iwadate Yasuo , Hiwasa Takaki
Published: February 2023

Introduction

Autoantibodies against inflammatory cytokines may be used for the prevention of atherosclerosis. Preclinical studies consider colony-stimulating factor 2 (CSF2) as an essential cytokine with a causal relationship to atherosclerosis and cancer. We examined the serum anti-CSF2 antibody levels in patients with atherosclerosis or solid cancer.

Methods

We measured the serum anti-CSF2 antibody levels via amplified luminescent proximity homogeneous assay-linked immunosorbent assay based on the recognition of recombinant glutathione S-transferase-fused CSF2 protein or a CSF2-derived peptide as the antigen.

Results

The serum anti-CSF2 antibody (s-CSF2-Ab) levels were significantly higher in patients with acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD) compared with healthy donors (HDs). In addition, the s-CSF2-Ab levels were associated with intima-media thickness and hypertension. The analyzes of samples obtained from a Japan Public Health Center-based prospective study suggested the utility of s-CSF2-Ab as a risk factor for AIS. Furthermore, the s-CSF2-Ab levels were higher in patients with esophageal, colorectal, gastric, and lung cancer than in HDs but not in those with mammary cancer. In addition, the s-CSF2-Ab levels were associated with unfavorable postoperative prognosis in colorectal cancer (CRC). In CRC, the s-CSF2-Ab levels were more closely associated with poor prognosis in patients with p53-Ab-negative CRC despite the lack of significant association of the anti-p53 antibody (p53-Ab) levels with the overall survival.

Conclusion

S-CSF2-Ab was useful for the diagnosis of atherosclerosis-related AIS, AMI, DM, and CKD and could discriminate poor prognosis, especially in p53-Ab-negative CRC.
The impact of biomass burning emissions on aerosol concentrations and depositions in the northern South China Sea region
Authors: Li Jiawei , Zhang Zhisheng , Tao Jun , Pan Yuepeng , Luo Li , Han Zhiwei
Published: February 2023

The impact of biomass burning (BB) emissions on concentrations and depositions of major aerosol components in the northern South China Sea (NSCS) region (105∼115°E and 15∼21°N) from December 2020 to April 2021 has been investigated using the WRF-chem model (weather research and forecasting model coupled with chemistry) in combination with aerosol composition measurement at a mountain site in the Hainan Island of China. Model comparisons with observations in Hainan demonstrated the effectiveness of WRF-chem in simulating aerosol components (PM2.5, black carbon (BC), organic matter (OM), sulfate, nitrate, and ammonium) in the NSCS region. The influences of BB emissions were significant on near-surface PM2.5, BC, and OM but nearly negligible on secondary inorganic components (i.e., sulfate, nitrate, and ammonium). The NSCS regional and period mean PM2.5, BC, and OM concentrations were 17.2 μg/m3, 0.65 μg/m3, and 6.7 μg/m3, in which 20%, 13%, and 35%, respectively, were from BB emissions. The mean PM2.5, BC, and OM deposition fluxes were 73.8 mg/m2/month, 2.9 mg/m2/month, and 29.3 mg/m2/month, respectively, and 22%, 15%, and 38% of these depositions were from BB emissions. Dry deposition dominated the removal of aerosols. For both aerosol concentrations and depositions, the influences of BB emissions exhibited evidently larger contributions in spring (March and April) than those in winter (December to February). Most of the BB emissions were from mainland Southeast Asia (MSEA), in terms of period mean, 79%, 72%, and 81% of the BB PM2.5, BB BC, and BB OM concentrations and 82%, 77%, and 83% of their depositions in the NSCS region were attributed to the MSEA region. The results of this study suggested that BB emissions have strong implications for air quality and biogeochemical cycle of the NSCS region.
Cuticular hydrocarbons of alpine bumble bees (Hymenoptera: Bombus) are species-specific, but show little evidence of elevation-related climate adaptation
Authors: Maihoff Fabienne , Sahler Simone , Schoger Simon , Brenzinger Kristof , Kallnik Katharina , Sauer Nikki , Bofinger Lukas , Schmitt Thomas , Nooten Sabine S. , Classen Alice
Published: February 2023

Alpine bumble bees are the most important pollinators in temperate mountain ecosystems. Although they are used to encounter small-scale successions of very different climates in the mountains, many species respond sensitively to climatic changes, reflected in spatial range shifts and declining populations worldwide. Cuticular hydrocarbons (CHCs) mediate climate adaptation in some insects. However, whether they predict the elevational niche of bumble bees or their responses to climatic changes remains poorly understood. Here, we used three different approaches to study the role of bumble bees’ CHCs in the context of climate adaptation: using a 1,300 m elevational gradient, we first investigated whether the overall composition of CHCs, and two potentially climate-associated chemical traits (proportion of saturated components, mean chain length) on the cuticle of six bumble bee species were linked to the species’ elevational niches. We then analyzed intraspecific variation in CHCs of Bombus pascuorum along the elevational gradient and tested whether these traits respond to temperature. Finally, we used a field translocation experiment to test whether CHCs of Bombus lucorum workers change, when translocated from the foothill of a cool and wet mountain region to (a) higher elevations, and (b) a warm and dry region. Overall, the six species showed distinctive, species-specific CHC profiles. We found inter- and intraspecific variation in the composition of CHCs and in chemical traits along the elevational gradient, but no link to the elevational distribution of species and individuals. According to our expectations, bumble bees translocated to a warm and dry region tended to express longer CHC chains than bumble bees translocated to cool and wet foothills, which could reflect an acclimatization to regional climate. However, chain lengths did not further decrease systematically along the elevational gradient, suggesting that other factors than temperature also shape chain lengths in CHC profiles. We conclude that in alpine bumble bees, CHC profiles and traits respond at best secondarily to the climate conditions tested in this study. While the functional role of species-specific CHC profiles in bumble bees remains elusive, limited plasticity in this trait could restrict species’ ability to adapt to climatic changes.
Evaluation of genetic alterations in hereditary cancer susceptibility genes in the Ashkenazi Jewish women community of Mexico
Authors: Díaz-Velásquez Clara Estela , Gitler Rina , Antoniano Adriana , Kershenovich Sefchovich Ronny , De La Cruz-Montoya Aldo Hugo , Martínez-Gregorio Héctor , Rojas-Jiménez Ernesto Arturo , Cortez Cardoso Penha Ricardo , Terrazas Luis Ignacio , Wegman-Ostrosky Talia , Levi-Lahad Ephrat , Zabaleta Jovanny , Perdomo Sandra , Vaca-Paniagua Felipe
Published: February 2023

Background: Individuals of Ashkenazi Jewish ancestry have been identified as having higher prevalence of specific pathogenic variants associated with susceptibility to specific rare and chronic diseases. In Mexico, the prevalence and composition of rare cancer predisposing germline variants in Ashkenazi Jewish individuals has not been evaluated.

Aim and methods: We aimed to evaluate the prevalence of pathogenic variants by massive parallel sequencing in a panel of 143 cancer-predisposing genes in 341 women from the Ashkenazi Jewish community of Mexico, who were contacted and invited to participate in the study through the ALMA Foundation for Cancer Reconstruction. Pre- and posttest genetic counseling was given and a questionnaire on personal, gyneco-obstetric, demographic and lifestyle variables was conducted. From peripheral blood DNA, the complete coding region, and splicing sites of a panel of 143 cancer susceptibility genes, including 21 clinically relevant genes, were sequenced. The Mexican founder mutation BRCA1 ex9-12del [NC_000017.10(NM_007294):c. (825+1–826-1)_(4,589+1–4,590-1)del] was also evaluated.

Results: Among study participants (mean age ±standard deviation: 47 ± 14) 15% reported a personal history of cancer (50/341). Fourteen percent of participants (48/341) were carriers of pathogenic and likely pathogenic variants distributed among seven high-risk genes (APC, CHEK2, MSH2, BMPR1A, MEN1, MLH1, and MSH6), whereas 18.2% (62/341) had variants of uncertain clinical significance in genes associated with breast and ovarian cancer susceptibility (list of genes with VUS). Pathogenic and likely pathogenic variants in 16 susceptibility genes with ambiguous or non-well-established risk association for cancer were detected in 17.6% (60/341) of participants. Sixty four percent of participants reported current alcohol consumption compared with the 39 percent prevalence of alcohol consumption in Mexican women. None of the participants carried the recurrent Ashkenazi and Mexican founder mutations in BRCA1 or BRCA2, but 2% (7/341) had pathogenic Ashkenazi Jewish founder variants in BLM.

Conclusion: Our findings show a diverse pathogenic variant composition among the recruited individuals of Ashkenazi Jewish ancestry in Mexico consistent with being a high-risk population for genetic diseases, which warrants further investigation to adequately assess the burden of hereditary breast cancer in this group and implement appropriate preventative programs.
Identification of three metabolic subtypes in gastric cancer and the construction of a metabolic pathway-based risk model that predicts the overall survival of GC patients
Authors: Chen Tongzuan , zhao Liqian , Chen Junbo , Jin Gaowei , Huang Qianying , Zhu Ming , Dai Ruixia , Yuan Zhengxi , Chen Junshuo , Tang Mosheng , Chen Tongke , Lin Xiaokun , Ai Weiming , Wu Liang , Chen Xiangjian , Qin Le
Published: February 2023

Gastric cancer (GC) is highly heterogeneous and GC patients have low overall survival rates. It is also challenging to predict the prognosis of GC patients. This is partly because little is known about the prognosis-related metabolic pathways in this disease. Hence, our objective was to identify GC subtypes and genes related to prognosis, based on changes in the activity of core metabolic pathways in GC tumor samples. Differences in the activity of metabolic pathways in GC patients were analyzed using Gene Set Variation Analysis (GSVA), leading to the identification of three clinical subtypes by non-negative matrix factorization (NMF). Based on our analysis, subtype 1 showed the best prognosis while subtype 3 exhibited the worst prognosis. Interestingly, we observed marked differences in gene expression between the three subtypes, through which we identified a new evolutionary driver gene, CNBD1. Furthermore, we used 11 metabolism-associated genes identified by LASSO and random forest algorithms to construct a prognostic model and verified our results using qRT-PCR (five matched clinical tissues of GC patients). This model was found to be both effective and robust in the GSE84437 and GSE26253 cohorts, and the results from multivariate Cox regression analyses confirmed that the 11-gene signature was an independent prognostic predictor (p < 0.0001, HR = 2.8, 95% CI 2.1–3.7). The signature was found to be relevant to the infiltration of tumor-associated immune cells. In conclusion, our work identified significant GC prognosis-related metabolic pathways in different GC subtypes and provided new insights into GC-subtype prognostic assessment.
Dysfunction of the noradrenergic system drives inflammation, α-synucleinopathy, and neuronal loss in mouse colon
Authors: Song Sheng , Tu Dezhen , Meng Chengbo , Liu Jie , Wilson Belinda , Wang Qingshan , Shih Yen-Yu Ian , Gao Hui-Ming , Hong Jau-Shyong
Published: February 2023

Clinical and pathological evidence revealed that α-synuclein (α-syn) pathology seen in PD patients starts in the gut and spreads via anatomically connected structures from the gut to the brain. Our previous study demonstrated that depletion of central norepinephrine (NE) disrupted brain immune homeostasis, producing a spatiotemporal order of neurodegeneration in the mouse brain. The purpose of this study was 1) to determine the role of peripheral noradrenergic system in the maintenance of gut immune homeostasis and in the pathogenesis of PD and 2) to investigate whether NE-depletion induced PD-like α-syn pathological changes starts from the gut. For these purposes, we investigated time-dependent changes of α-synucleinopathy and neuronal loss in the gut following a single injection of DSP-4 (a selective noradrenergic neurotoxin) to A53T-SNCA (human mutant α-syn) over-expression mice. We found DPS-4 significantly reduced the tissue level of NE and increased immune activities in gut, characterized by increased number of phagocytes and proinflammatory gene expression. Furthermore, a rapid-onset of α-syn pathology was observed in enteric neurons after 2 weeks and delayed dopaminergic neurodegeneration in the substantia nigra was detected after 3-5 months, associated with the appearance of constipation and impaired motor function, respectively. The increased α-syn pathology was only observed in large, but not in the small, intestine, which is similar to what was observed in PD patients. Mechanistic studies reveal that DSP-4-elicited upregulation of NADPH oxidase (NOX2) initially occurred only in immune cells during the acute intestinal inflammation stage, and then spread to enteric neurons and mucosal epithelial cells during the chronic inflammation stage. The upregulation of neuronal NOX2 correlated well with the extent of α-syn aggregation and subsequent enteric neuronal loss, suggesting that NOX2-generated reactive oxygen species play a key role in α-synucleinopathy. Moreover, inhibiting NOX2 by diphenyleneiodonium or restoring NE function by salmeterol (a β2-receptor agonist) significantly attenuated colon inflammation, α-syn aggregation/propagation, and enteric neurodegeneration in the colon and ameliorated subsequent behavioral deficits. Taken together, our model of PD shows a progressive pattern of pathological changes from the gut to the brain and suggests a potential role of the noradrenergic dysfunction in the pathogenesis of PD.
Preclinical evaluation of CD70-specific CAR T cells targeting acute myeloid leukemia
Authors: Wu Gongqiang , Guo Shanshan , Luo Qian , Wang Xiaoxia , Deng Wenhai , Ouyang Guifang , Pu Jeffrey J. , Lei Wen , Qian Wenbin
Published: February 2023

Backgrounds

Chimeric antigen receptor (CAR)-T cell therapy has achieved unprecedented success in treating hematopoietic malignancies. However, this cell therapy is hampered in treating acute myeloid leukemia (AML) due to lack of ideal cell surface targets that only express on AML blasts and leukemia stem cells (LSCs) but not on normal hematopoietic stem cells (HSCs).

Methods

We detected the CD70 expression on the surfaces of AML cell lines, primary AML cells, HSC, and peripheral blood cells and generated a second-generation CD70-specific CAR-T cells using a construct containing a humanized 41D12-based scFv and a 41BB-CD3ζ intracellular signaling domain. Cytotoxicity, cytokine release, and proliferation in antigen stimulation, CD107a assay, and CFSE assays were used to demonstrate the potent anti-leukemia activity in vitro. A Molm-13 xenograft mouse model was established to evaluate the anti-leukemic activity of CD70 CAR-T in vivo. CFU assay was explored to assess the safety of CD70 CAR-T on HSC.

Results

CD70 heterogeneously expressed on AML primary cells, including leukemia blasts, leukemic progenitor, and stem cells, but not expressed on normal HSCs and majority of blood cells. Anti-CD70 CAR-T cells exhibited potent cytotoxicity, cytokines production, and proliferation when incubated with CD70+ AML cell lines. It also displayed robust anti-leukemia activity and prolonged survival in Molm-13 xenograft mouse model. However, such CAR-T cell therapy did not completely eliminate leukemia in vivo.

Discussion

Our study reveals that anti-CD70 CAR-T cells are a new potential treatment for AML. However, such CAR-T cell therapy did not completely eliminate leukemia in vivo, suggesting that future studies aiming to generate innovative combinatorial CAR constructs or to increase CD70 expression density on leukemia cell surface to prolong the life-span of CAR-T cells in the circulation will be needed in order to optimize CAR-T cell responses for AML.
Design of a multi-epitope vaccine against six Nocardia species based on reverse vaccinology combined with immunoinformatics
Authors: Zhu Fei , Tan Caixia , Li Chunhui , Ma Shiyang , Wen Haicheng , Yang Hang , Rao Mingjun , Zhang Peipei , Peng Wenzhong , Cui Yanhui , Chen Jie , Pan Pinhua
Published: February 2023

Background

Nocardia genus, a complex group of species classified to be aerobic actinomycete, can lead to severe concurrent infection as well as disseminated infection, typically in immunocompromised patients. With the expansion of the susceptible population, the incidence of Nocardia has been gradually growing, accompanied by increased resistance of the pathogen to existing therapeutics. However, there is no effective vaccine against this pathogen yet. In this study, a multi-epitope vaccine was designed against the Nocardia infection using reverse vaccinology combined with immunoinformatics approaches.

Methods

First, the proteomes of 6 Nocardia subspecies Nocardia subspecies (Nocardia farcinica, Nocardia cyriacigeorgica, Nocardia abscessus, Nocardia otitidiscaviarum, Nocardia brasiliensis and Nocardia nova) were download NCBI (National Center for Biotechnology Information) database on May 1st, 2022 for the target proteins selection. The essential, virulent-associated or resistant-associated, surface-exposed, antigenic, non-toxic, and non-homologous with the human proteome proteins were selected for epitope identification. The shortlisted T-cell and B-cell epitopes were fused with appropriate adjuvants and linkers to construct vaccines. The physicochemical properties of the designed vaccine were predicted using multiple online servers. The Molecular docking and molecular dynamics (MD) simulation were performed to understand the binding pattern and binding stability between the vaccine candidate and Toll-like receptors (TLRs). The immunogenicity of the designed vaccines was evaluated via immune simulation.

Results

3 proteins that are essential, virulent-associated or resistant-associated, surface-exposed, antigenic, non-toxic, and non-homologous with the human proteome were selected from 218 complete proteome sequences of the 6 Nocardia subspecies epitope identification. After screening, only 4 cytotoxic T lymphocyte (CTL) epitopes, 6 helper T lymphocyte (HTL) epitopes, and 8 B cell epitopes that were antigenic, non-allergenic, and non-toxic were included in the final vaccine construct. The results of molecular docking and MD simulation showed that the vaccine candidate has a strong affinity for TLR2 and TLR4 of the host and the vaccine-TLR complexes were dynamically stable in the natural environment. The results of the immune simulation indicated that the designed vaccine had the potential to induce strong protective immune responses in the host. The codon optimization and cloned analysis showed that the vaccine was available for mass production.

Conclusion

The designed vaccine has the potential to stimulate long-lasting immunity in the host, but further studies are required to validate its safety and efficacy.
Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma
Authors: Chen Chen , Wang Zehua , Ding Yi , Qin Yanru
Published: February 2023

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the third leading cause of tumor-related mortality worldwide. In recent years, the emergency of immune checkpoint inhibitor (ICI) has revolutionized the management of HCC. Especially, the combination of atezolizumab (anti-PD1) and bevacizumab (anti-VEGF) has been approved by the FDA as the first-line treatment for advanced HCC. Despite great breakthrough in systemic therapy, HCC continues to portend a poor prognosis owing to drug resistance and frequent recurrence. The tumor microenvironment (TME) of HCC is a complex and structured mixture characterized by abnormal angiogenesis, chronic inflammation, and dysregulated extracellular matrix (ECM) remodeling, collectively contributing to the immunosuppressive milieu that in turn prompts HCC proliferation, invasion, and metastasis. The tumor microenvironment coexists and interacts with various immune cells to maintain the development of HCC. It is widely accepted that a dysfunctional tumor-immune ecosystem can lead to the failure of immune surveillance. The immunosuppressive TME is an external cause for immune evasion in HCC consisting of 1) immunosuppressive cells; 2) co-inhibitory signals; 3) soluble cytokines and signaling cascades; 4) metabolically hostile tumor microenvironment; 5) the gut microbiota that affects the immune microenvironment. Importantly, the effectiveness of immunotherapy largely depends on the tumor immune microenvironment (TIME). Also, the gut microbiota and metabolism profoundly affect the immune microenvironment. Understanding how TME affects HCC development and progression will contribute to better preventing HCC-specific immune evasion and overcoming resistance to already developed therapies. In this review, we mainly introduce immune evasion of HCC underlying the role of immune microenvironment, describe the dynamic interaction of immune microenvironment with dysfunctional metabolism and the gut microbiome, and propose therapeutic strategies to manipulate the TME in favor of more effective immunotherapy.
Density regulation of aquaculture production and its effects on commercial profit and quality as food in the cosmopolitan edible seaweed Undaria pinnatifida
Authors: Sato Yoichi , Fujiwara Takayuki , Endo Hikaru
Published: February 2023

Aquaculture of marine macroalgae (i.e. seaweeds) such as the kelp Undaria pinnatifida is expected to contribute to future food and biomass production. Although macroalgal survival, biomass, and morphology are strongly affected by the density of individual plants in natural environments, little is known about the cultivation density (individuals per 1 m of cultivation rope) of macroalgae required to optimize aquaculture production, commercial profit (sales – labor expenses for processing), and quality as food. The present study examined the effect of increasing the cultivation density of U. pinnatifida from 10 to 200 individuals m-1 on survival rate, biomass production, profit, and morphological features related to quality as food. Survival rate was almost 100% in all treatments, indicating self-thinning did not occur. Biomass production increased with increasing density, suggesting that the maximum density possible is in excess of 200 individuals m-1. However, although profit rose with increasing density from 10 to 120 individuals m-1, it did not rise further if density was further increased. Moreover, some morphological features related to quality increased or decreased with increasing density. On balance, these results suggest that 80-120 individuals m-1 is an appropriate density range to optimize production of this species in terms of both profit and quality as food. However, only 10-30 individuals m-1 was the density best suited to enhance production of the sporophyll form, which is known to be a nutritious food both for humans and sea urchins.
Spatio-temporal changes and driving forces of reclamation based on remote sensing: A case study of the Guangxi Beibu Gulf
Authors: Lu Jingfang , Zhang Yibo , Shi Honghua , Lv Xianqing
Published: February 2023

Since 2000, coastal reclamation projects have been implemented in the Guangxi Beibu Gulf to alleviate the shortage of coastal land resources. As a result, the reclamation area has increased significantly. In this study, based on the Landsat program, we tracked coastal reclamation in the coastal waters of Guangxi in the 21st century. An indicator system was proposed to assess the driving forces of reclamation synthetically. Our results showed that 98.6 km2 of coastal waters of the Guangxi Beibu Gulf was reclaimed from 1997 to 2017, in which three regions underwent great changes: Fangcheng Bay, Tieshan Bay, and Qiznhou Bay. Furthermore, spatio-temporal changes of reclamation were affected by the combination of population growth, economic development, and marine industry development in coastal cities. These results provide an important historical reference for tracking the human development processes of the Guangxi Beibu Gulf, and also offer some suggestions for the rational allocation of reclamation resources.
Bacterial microbiome variation across symbiotic states and clonal lines in a cnidarian model
Authors: Curtis Ezra , Moseley Joanne , Racicot Riccardo , Wright Rachel M.
Published: February 2023

Introduction

Exaiptasia diaphana is a popular model organism for exploring the symbiotic relationship observed between cnidarians and their microsymbionts. While physiological roles of algal photosymbionts (Symbiodinaceae) are well studied, the contributions of bacterial communities are less defined in this system.

Methods

We investigated microbial variation between distinct parts of the body and symbiotic state across four genets held in identical environmental conditions using 16s rRNA gene amplicon sequencing.

Results

We found differentially abundant taxa between body part and symbiotic state that highlight the roles these bacteria may play in holobiont heterotrophy and nutrient cycling. Beta-diversity analysis revealed distinct communities between symbiotic states consistent with previous studies; however, we did not observe the presence of previously reported core microbiota. We also found community differences across clonal lines, despite years of identical rearing conditions.

Conclusion

These findings suggest the Exaiptasia bacterial microbiome is greatly influenced by host genetics and unpredictable environmental influences.
Increasing in situ bioremediation effectiveness through field-scale application of molecular biological tools
Authors: Madison Andrew S. , Sorsby Skyler J. , Wang Yingnan , Key Trent A.
Published: February 2023

Leveraging the capabilities of microorganisms to reduce (degrade or transform) concentrations of pollutants in soil and groundwater can be a cost-effective, natural remedial approach to manage contaminated sites. Traditional design and implementation of bioremediation strategies consist of lab-scale biodegradation studies or collection of field-scale geochemical data to infer associated biological processes. While both lab-scale biodegradation studies and field-scale geochemical data are useful for remedial decision-making, additional insights can be gained through the application of Molecular Biological Tools (MBTs) to directly measure contaminant-degrading microorganisms and associated bioremediation processes. Field-scale application of a standardized framework pairing MBTs with traditional contaminant and geochemical analyses was successfully performed at two contaminated sites. At a site with trichloroethene (TCE) impacted groundwater, framework application informed design of an enhanced bioremediation approach. Baseline abundances of 16S rRNA genes for a genus of obligate organohalide-respiring bacteria (i.e., Dehalococcoides) were measured at low abundances (101–102 cells/mL) within the TCE source and plume areas. In combination with geochemical analyses, these data suggested that intrinsic biodegradation (i.e., reductive dechlorination) may be occurring, but activities were limited by electron donor availability. The framework was utilized to support development of a full-scale enhanced bioremediation design (i.e., electron donor addition) and to monitor remedial performance. Additionally, the framework was applied at a second site with residual petroleum hydrocarbon (PHC) impacted soils and groundwater. MBTs, specifically qPCR and 16S gene amplicon rRNA sequencing, were used to characterize intrinsic bioremediation mechanisms. Functional genes associated with anaerobic biodegradation of diesel components (e.g., naphthyl-2-methyl-succinate synthase, naphthalene carboxylase, alkylsuccinate synthase, and benzoyl coenzyme A reductase) were measured to be 2–3 orders of magnitude greater than unimpacted, background samples. Intrinsic bioremediation mechanisms were determined to be sufficient to achieve groundwater remediation objectives. Nonetheless, the framework was further utilized to assess that an enhanced bioremediation could be a successful remedial alternative or complement to source area treatment. While bioremediation of chlorinated solvents, PHCs, and other contaminants has been demonstrated to successfully reduce environmental risk and reach site goals, the application of field-scale MBT data in combination with contaminant and geochemical data analyses to design, implement, and monitor a site-specific bioremediation approach can result in more consistent remedy effectiveness.
Urogenital tract and rectal microbiota composition and its influence on reproductive outcomes in infertile patients
Authors: Dong Yong-Hong , Fu Zhong , Zhang Ning-Nan , Shao Jing-Yi , Shen Jie , Yang En , Sun Shi-Yi , Zhao Zhi-Min , Xiao An , Liu Chen-Jian , Li Xiao-Ran
Published: February 2023

Introduction

Microbiota in the human body are closely related to human diseases. Female urogenital tract and rectal microbes have been considered as important factors affecting female pregnancy, but the mechanism is unknown.

Methods

Cervical, vaginal, urethral, and rectal swabs were collected from 22 infertile patients and 10 controls, and follicular fluid was extracted from 22 infertile patients. The microbial composition of different sampling sites of infertile patients was examined. By comparing the microbial composition difference between infertile patients and controls and combining bioinformatics methods to analyze the potential impact of the female urogenital tract (cervical, vaginal and urethral) and rectal microbial diversity on female infertility and pregnancy outcomes.

Results

Lactobacillus predominated in the female urogenital tract, but its abundance decreased in infertile patients, whereas the abundance of Gardnerella and Atopobium increased. The microbial changes in the urethra had the same trend as that in the vagina. Compared with healthy controls, the cervical and rectal microbial diversity of infertile patients were significantly increased and decreased, respectively. There might be interactions between microbes in different parts of female. Geobacillus thermogeniticans was enriched in the urogenital tract and rectum of infertile patients, and has a good predictive effect on infertility. Compared with infertile patients, L. johnsonii was enriched in the vagina, urethra, and intestine of the control group. L. acidophilus in follicular fluid might be associated with Non-pregnancy.

Conclusion

This study found that the microbial composition of infertile patients was changed compared with that of healthy people. The translocation of Lactobacillus between the rectum and urogenital tract might play a protective barrier role. The changes of Lactobacillus and Geobacillus might be related to female infertility or pregnancy outcome. The study provided a theoretical basis for the future treatment of female infertility from the perspective of microorganisms by detecting the microbial changes associated with female infertility.
Microbial community succession patterns and drivers of Luxiang-flavor Jiupei during long fermentation
Authors: Liu Xiaogang , Ma Dongna , Yang Chen , Yin Qianqian , Liu Shuangping , Shen Caihong , Mao Jian
Published: February 2023

Luxiang-flavor Baijiu is the mainstream of Baijiu production and consumption in China, and the microbial composition has a great influence on the flavor and quality of Baijiu. In this study, we combined multi-omics sequencing technology to explore the microbial composition, dynamics and metabolite changes of Luxiang-flavor Jiupei during long fermentation periods. The results showed that based on the interaction between environmental constraints and microorganisms, Jiupei microorganisms formed different ecological niches and functional differentiation, which led to the formation of Jiupei stable core microorganisms. The bacteria were mainly Lactobacillus and Acetobacter, and the fungi were mainly Kazachstani and Issatchenkia. Most bacteria were negatively correlated with temperature, alcohol and acidity, and for the fungi, starch content, reducing sugar content and temperature had the most significant effects on community succession. Macroproteomic analysis revealed that Lactobacillus jinshani had the highest relative content; microbial composition, growth changes and functions were more similar in the pre-fermentation period (0–18 days); microorganisms stabilized in the late fermentation period (24–220 days). The metabolome analysis revealed that the metabolites of the Jiupei changed rapidly from 18 to 32 days of fermentation, with a significant increase in the relative content of amino acids, peptides and analogs and a significant decrease in the relative content of sugars; the metabolites of the Jiupei changed slowly from 32 to 220 days of fermentation, with a stabilization of the content of amino acids, peptides and analogs. This work provides insights into the microbial succession and microbial drivers during the long-term fermentation of Jiupei, which have potential implications for optimizing production and improving the flavor of Baijiu.
The effect of a methyl group on structure and function: Serine vs. threonine glycosylation and phosphorylation
Authors: Barchi Joseph J. , Strain Caitlin N.
Published: February 2023

A variety of glycan structures cover the surface of all cells and are involved in myriad biological processes, including but not limited to, cell adhesion and communication, protein quality control, signal transduction and metabolism, while also being intimately involved in innate and adaptive immune functions. Immune surveillance and responses to foreign carbohydrate antigens, such as capsular polysaccharides on bacteria and surface protein glycosylation of viruses, are the basis of microbial clearance, and most antimicrobial vaccines target these structures. In addition, aberrant glycans on tumors called Tumor-Associated Carbohydrate Antigens (TACAs) elicit immune responses to cancer, and TACAs have been used in the design of many antitumor vaccine constructs. A majority of mammalian TACAs are derived from what are referred to as mucin-type O-linked glycans on cell-surface proteins and are linked to the protein backbone through the hydroxyl group of either serine or threonine residues. A small group of structural studies that have compared mono- and oligosaccharides attached to each of these residues have shown that there are distinct differences in conformational preferences assumed by glycans attached to either “unmethylated” serine or ß-methylated threonine. This suggests that the linkage point of antigenic glycans will affect their presentation to the immune system as well as to various carbohydrate binding molecules (e.g., lectins). This short review, followed by our hypothesis, will examine this possibility and extend the concept to the presentation of glycans on surfaces and in assay systems where recognition of glycans by proteins and other binding partners can be defined by different attachment points that allow for a range of conformational presentations.
The contradictory roles of macrophages in non-alcoholic fatty liver disease and primary liver cancer—Challenges and opportunities
Authors: Kohlhepp Marlene Sophia , Liu Hanyang , Tacke Frank , Guillot Adrien
Published: February 2023

Chronic liver diseases from varying etiologies generally lead to liver fibrosis and cirrhosis. Among them, non-alcoholic fatty liver disease (NAFLD) affects roughly one-quarter of the world population, thus representing a major and increasing public health burden. Chronic hepatocyte injury, inflammation (non-alcoholic steatohepatitis, NASH) and liver fibrosis are recognized soils for primary liver cancer, particularly hepatocellular carcinoma (HCC), being the third most common cause for cancer-related deaths worldwide. Despite recent advances in liver disease understanding, therapeutic options on pre-malignant and malignant stages remain limited. Thus, there is an urgent need to identify targetable liver disease-driving mechanisms for the development of novel therapeutics. Monocytes and macrophages comprise a central, yet versatile component of the inflammatory response, fueling chronic liver disease initiation and progression. Recent proteomic and transcriptomic studies performed at singular cell levels revealed a previously overlooked diversity of macrophage subpopulations and functions. Indeed, liver macrophages that encompass liver resident macrophages (also named Kupffer cells) and monocyte-derived macrophages, can acquire a variety of phenotypes depending on microenvironmental cues, and thus exert manifold and sometimes contradictory functions. Those functions range from modulating and exacerbating tissue inflammation to promoting and exaggerating tissue repair mechanisms (i.e., parenchymal regeneration, cancer cell proliferation, angiogenesis, fibrosis). Due to these central functions, liver macrophages represent an attractive target for the treatment of liver diseases. In this review, we discuss the multifaceted and contrary roles of macrophages in chronic liver diseases, with a particular focus on NAFLD/NASH and HCC. Moreover, we discuss potential therapeutic approaches targeting liver macrophages.
Deletion of histone demethylase Lsd1 (Kdm1a) during retinal development leads to defects in retinal function and structure
Authors: Ferdous Salma , Shelton Debresha A. , Getz Tatiana E. , Chrenek Micah A. , L’Hernault Nancy , Sellers Jana T. , Summers Vivian R. , Iuvone P. Michael , Boss Jeremy M. , Boatright Jeffrey H. , Nickerson John M.
Published: February 2023

Purpose

The purpose of this study was to investigate the role of Lysine specific demethylase 1 (Lsd1) in murine retinal development. LSD1 is a histone demethylase that can demethylate mono- and di-methyl groups on H3K4 and H3K9. Using Chx10-Cre and Rho-iCre75 driver lines, we generated novel transgenic mouse lines to delete Lsd1 in most retinal progenitor cells or specifically in rod photoreceptors. We hypothesize that Lsd1 deletion will cause global morphological and functional defects due to its importance in neuronal development.

Methods

We tested the retinal function of young adult mice by electroretinogram (ERG) and assessed retinal morphology by in vivo imaging by fundus photography and SD-OCT. Afterward, eyes were enucleated, fixed, and sectioned for subsequent hematoxylin and eosin (H&E) or immunofluorescence staining. Other eyes were plastic fixed and sectioned for electron microscopy.

Results

In adult Chx10-Cre Lsd1fl/fl mice, we observed a marked reduction in a-, b-, and c-wave amplitudes in scotopic conditions compared to age-matched control mice. Photopic and flicker ERG waveforms were even more sharply reduced. Modest reductions in total retinal thickness and outer nuclear layer (ONL) thickness were observed in SD-OCT and H&E images. Lastly, electron microscopy revealed significantly shorter inner and outer segments and immunofluorescence showed modest reductions in specific cell type populations. We did not observe any obvious functional or morphological defects in the adult Rho-iCre75 Lsd1fl/fl animals.

Conclusion

Lsd1 is necessary for neuronal development in the retina. Adult Chx10-Cre Lsd1fl/fl mice show impaired retinal function and morphology. These effects were fully manifested in young adults (P30), suggesting that Lsd1 affects early retinal development in mice.