Inhibitory Factors Research Articles

Unlocking the genome of the non-sourdough Kazachstania humilis MAW1: insights into inhibitory factors and phenotypic properties

BackgroundAscomycetous budding yeasts are ubiquitous environmental microorganisms important in food production and medicine. Due to recent intensive genomic research, the taxonomy of yeast is becoming more organized based on the identification of monophyletic taxa. This includes genera important to humans, such as Kazachstania. Until now, Kazachstania humilis (previously Candida humilis) was regarded as a sourdough-specific yeast. In addition, any antibacterial activity has not been associated with this species.ResultsPreviously, we isolated a yeast strain that impaired bio-hydrogen production in a dark fermentation bioreactor and inhibited the growth of Gram-positive and Gram-negative bacteria. Here, using next generation sequencing technologies, we sequenced the genome of this strain named K. humilis MAW1. This is the first genome of a K. humilis isolate not originating from a fermented food. We used novel phylogenetic approach employing the 18 S-ITS-D1-D2 region to show the placement of the K. humilis MAW1 among other members of the Kazachstania genus. This strain was examined by global phenotypic profiling, including carbon sources utilized and the influence of stress conditions on growth. Using the well-recognized bacterial model Escherichia coli AB1157, we show that K. humilis MAW1 cultivated in an acidic medium inhibits bacterial growth by the disturbance of cell division, manifested by filament formation. To gain a greater understanding of the inhibitory effect of K. humilis MAW1, we selected 23 yeast proteins with recognized toxic activity against bacteria and used them for Blast searches of the K. humilis MAW1 genome assembly. The resulting panel of genes present in the K. humilis MAW1 genome included those encoding the 1,3-β-glucan glycosidase and the 1,3-β-glucan synthesis inhibitor that might disturb the bacterial cell envelope structures.ConclusionsWe characterized a non-sourdough-derived strain of K. humilis, including its genome sequence and physiological aspects. The MAW1, together with other K. humilis strains, shows the new organization of the mating-type locus. The revealed here pH-dependent ability to inhibit bacterial growth has not been previously recognized in this species. Our study contributes to the building of genome sequence-based classification systems; better understanding of K.humilis as a cell factory in fermentation processes and exploring bacteria-yeast interactions in microbial communities.

‘You are not Sikkimese enough’: Understanding collective action tendencies of old settlers in Sikkim using SIMCA

AbstractThe current study analyses the motivators and inhibitors of collective action tendency using the Social Identity Model of Collective Action (SIMCA). The study was conducted with a minority and state‐based repressed group known as the old settlers in Sikkim, India. The old settlers are a community that have been historically settled in Sikkim prior to the state's merger with India in 1975. They are racially and ethnically different from the majority population of northeasterners in Sikkim and face both institutional and interpersonal discrimination. A qualitative approach using semi‐structured interviews with 11 old settlers was taken to delineate SIMCA variables – moral conviction, identity, injustice and efficacy – within the context of northeast India. Collective action was motivated through moral conviction via principles of equality and unequal treatment and outsider status, identity via politicisation of identity, creation of social movement organisations, injustice via anger and fraternal resentment and efficacy via marches and legal recourses. Collective action was inhibited through moral conviction via denial of violation, identity via acculturation, injustice via fear and efficacy via learned helplessness. These findings indicate that in state‐based repressed groups, collective action tendencies must be understood from a context‐specific lens that attempts to understand both motivating and inhibitory factors.

Combination low-dose cyclophosphamide with check-point blockade and ionizing radiation promote an abscopal effect in mouse models of melanoma.

The complex strategy of hypo-fractionated radiotherapy (HFRT) in combination with an immune checkpoint inhibitor (ICI) can stimulate a potential systemic antitumor response; however, the abscopal effect is always precluded by the tumor microenvironment, which may limit sufficient T-cell infiltration of distant nonirradiated tumors for certain kinds of inhibitory factors, such as regulatory T-cells (Tregs). Additionally, low-dose cyclophosphamide (LD-CYC) can specifically kill regulatory Tregs and strongly synergize antigen-specific immune responses, which could promote an abscopal effect. We explored whether a triple regimen consisting of HFRT, ICI, and LD-CYC could achieve a better systemic antitumor response in bilateral mouse tumor models. Our data demonstrate that LD-CYC combined with HFRT and antiprogrammed cell death ligand 1 (PDL-1) therapy could enhance the abscopal effect than only HFRT/antiPDL-1 or HFRT alone. Surprisingly, repeat CYC doses cannot further restrain tumor proliferation but can prolong murine overall survival, as revealed by the major pathologic responses. These results are associated with increased CD8 + effector T-cell infiltration, although LD-CYC did not upregulate PDL-1 expression in the tumor. Compared with traditional strategies, for the first time, we demonstrated that a triple treatment strategy remarkably increased the number of radiation-induced tumor-infiltrating CD8 + T-cells, effectively decreasing infiltrating Tregs, and promoting an abscopal effect. Thus, we describe a novel and effective therapeutic approach by combining multiple strategies to target several tumor-mediated immune inhibitory mechanisms.

Dynamics of urban expansion and form changes impacting carbon emissions in the Guangdong-Hong Kong-Macao Greater Bay Area counties

Cities are the main carriers of social and economic development, and they are also important sources of carbon emissions. Therefore, it is essential to explore the impact of urban expansion and form changes on carbon emissions. Here, we attempted to analyzes the relationship between urban expansion and carbon emissions at the county level in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) from 1997 to 2017. It further decomposes the driving effects of carbon emissions from multiple factors, and considers the spatial heterogeneity between different urban form changes and driving effects. The results show that: The relationship between urban expansion and carbon emissions in the GBA has gone through three stages from 1997 to 2017, with 2012 as a turning point. Optimization of economic development models and strict protection of the ecological environment can effectively control carbon emissions. After 2012, the economic development effect (GE) and population scale effect (PE) are the driving factors of carbon emissions, while the carbon emission intensity effect (CE) and urban land intensity effect (UE) are the inhibitory factors of carbon emissions. The contribution rate of UE to carbon emission reduction can reach 86 %. The impact of urban form changes on carbon emissions has spatial heterogeneity. The changes in urban form have a significant impact on the carbon emissions of counties in Dongguan and Shenzhen. The increase in fragmentation indirectly promotes carbon emissions. In 2007–2012, the increase in centrality significantly weakened the economic development effect, which is conducive to emission reduction. After 2007, the increase in compactness in counties in the eastern part of the GBA, including Zhongshan and Zhuhai, is not conducive to emission reduction.

The main principles of managing patients with Graves’ disease in clinical practice

BACKGROUND: Graves’ disease (GD) is a common cause of persistent thyrotoxicosis. In regions with adequate iodine intake, the incidence is 20–30 cases per 100,000 people. Modern treatment of GD includes antithyroid drugs, radioactive iodine therapy (RAI), and thyroidectomy. The choice of treatment strategy is based on the severity of thyrotoxicosis, the frequency of potential side effects, the availability of treatment options, and the likelihood of achieving sustained remission. Previous studies have demonstrated differences in approaches to diagnosis, treatment, and follow-up between countries and individual specialists.AIM: To conduct a survey on the current clinical practice of treating Graves’ disease in Russia.MATERIALS AND METHODS: An online survey was conducted among physicians in 2022-2023. The questions covered the principles of diagnosis, treatment, and dynamic observation of adult patients with Graves’ disease.RESULTS: The study involved 104 physicians of various specialties who treat patients with Graves’ disease. Approximately 99% of respondents chose the determination of thyroid-stimulating hormone receptor antibodies (TSHR-ab) to clarify the etiology of thyrotoxicosis, while only 60.6% of them chose thyroid scintigraphy. As the first-line treatment method, antithyroid drug therapy is chosen by 88.5%, while 13.5% of physicians use radioactive iodine therapy (RAI), and less than 1% of respondents refer patients to thyroidectomy. Thiamazole is most commonly used (99%), while propylthiouracil (PTU) is used in cases of allergy to thiamazole or during the first trimester of pregnancy. The «block-replace» scheme is preferred over the «block» scheme, with 72.1% compared to 28.8%, respectively. The majority of physicians (95.2%) initiate therapy with moderate doses of thiamazole (20–30 mg) and PTU (200–300 mg). Most physicians conduct dynamic monitoring of liver transaminase levels (57.7%) and complete blood count (78.8%). Conservative therapy is prescribed for a period of 12–18 months (88.5%) or up to 24 months (10.6%). Before discontinuing antithyroid drug therapy, 89.4% of respondents monitor thyroid hormone levels, 82.7% monitor TSHR-Ab levels, and 47.1% perform thyroid ultrasound. Repeat courses of conservative therapy are prescribed for up to 61.5% of respondents. Approximately 63.5% of surveyed physicians reported difficulties in referring patients for radical treatment due to a limited number of specialized institutions. Physicians cited patient unwillingness and the need to postpone pregnancy (81.6% and 24.3% respectively) as the main inhibitory factors for RAI. Thyroidectomy was associated with patient unwillingness (69.2%), as well as physician fear of laryngeal paralysis (48.1%) and postoperative hypoparathyroidism (49%).CONCLUSION: The results of the study demonstrated that physicians in their practice generally adhere to international recommendations for the treatment of Graves’ disease.

Identification of Nonfunctional Alternatively Spliced Isoforms of STING in Human Acute Myeloid Leukemia.

We find that AML acquires resistance to innate immune activation via the STING pathway through aberrant splicing of the STING transcript including two novel forms described herein that act as dominant negatives. These data broaden understanding of how cancers evolve STING resistance, and suggest that the AML tumor microenvironment, not the cancer cell, should be the target of therapeutic interventions to activate STING.

Acod1 expression in cancer cells promotes immune evasion through the generation of inhibitory peptides

Targeting programmed cell death protein 1 (PD-1) is an important component of many immune checkpoint blockade (ICB) therapeutic approaches. However, ICB is not an efficacious strategy in a variety of cancer types, in part due to immunosuppressive metabolites in the tumor microenvironment. Here, we find that αPD-1-resistant cancer cells produce abundant itaconate (ITA) due to enhanced levels of aconitate decarboxylase (Acod1). Acod1 has an important role in the resistance to αPD-1, as decreasing Acod1 levels in αPD-1-resistant cancer cells can sensitize tumors to αPD-1 therapy. Mechanistically, cancer cells with high Acod1 inhibit the proliferation of naive CD8+ Tcells through the secretion of inhibitory factors. Surprisingly, inhibition of CD8+ Tcell proliferation is not dependent on the secretion of ITA but is instead a consequence of the release of small inhibitory peptides. Our study suggests that strategies to counter the activity of Acod1 in cancer cells may sensitize tumors to ICB therapy.

Abstract 346: Trop-2 induces apoptosis via transcriptional activation of TRAIL, FAS-FASL, CD40-TNFRSF5

Abstract Trop-2 is a transmembrane signal transducer that activates cancer growth and metastatic diffusion (1). However, this does not occur in all tumor types, as Trop-2 is associated to better disease outcome in some cancers, e.g. breast and lung tumors. A prototypic pattern of Trop-2 expression in normal multistratified epithelia, e.g. epidermis, esophagus, is that of preferential expression in non-proliferating, terminally differentiated cells. The corresponding expression gradient parallels that of induction of programmed cell death, e.g. in the corneum layer of skin keratinocytes. This led us to explore Trop-2 function as a trigger of apoptosis. We thus assessed NS-0 myeloma Trop-2 transfectants for apoptosis induction by dynamic cell morphometry and quantification of membrane blebbing and cell fragmentation. This was shown to be preceded by phosphatidyl-serine membrane exposure, and was followed by nuclear pyknosis and karyorrhexis. DNA fragmentation was shown by TUNEL and DNA laddering, and was accompanied by a dramatic increase of apoptotic death of Trop-2-expressing cells. Transcriptomic analysis at early time points of apoptosis induction indicated overexpression of TRAIL, FAS/FASL and CD40/TNFRSF5 transmembrane death receptors. This paralleled upregulation of downstream death-inducing signaling complex components and of executioner Caspases 8 and 3, suggesting Trop-2 as a trigger of extrinsic apoptosis pathways. Apoptosis induction translated into diminished tumor growth in vivo, which was shown to be proportional to Trop-2 expression levels. However, apoptosis induction was found to parallel stimulation of NS-0 cell growth and of defence mechanisms from apoptosis, as increased levels of inhibitory transcription factors, Rb-binding protein, survivin, Myd-118. These findings suggest a previously unappreciated balance between stimulation of cell growth and triggering of cell death by Trop-2, and may pave the way for selective anticancer therapy approaches in Trop-2-expressing cancers.(1) Trerotola M. et al., Neoplasia 23: 415-428 (2021). Citation Format: Saverio Alberti, Emanuela Guerra, Antonino Moschella, Martina Ceci, Ludovica Pantalone, Roberta Di Pietro, Marco Trerotola. Trop-2 induces apoptosis via transcriptional activation of TRAIL, FAS-FASL, CD40-TNFRSF5 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 346.

Macrophage Migration Inhibitory Factor as a Potential Plasma Biomarker of Cognitive Impairment in Cerebral Small Vessel Disease.

As the pathogenesis of cerebral small vessel disease with cognitive impairment (CSVD-CI) remains unclear, identifying effective biomarkers can contribute to the clinical management of CSVD-CI. This study recruited 54 healthy controls (HCs), 60 CSVD-CI patients, and 57 CSVD cognitively normal (CSVD-CN) patients. All participants underwent neuropsychological assessments and multimodal magnetic resonance imaging. Macrophage migration inhibitory factors (MIFs) were assessed in plasma. The least absolute shrinkage and selection operator model was used to determine a composite marker. Compared with HCs or CSVD-CN patients, CSVD-CI patients had significantly increased plasma MIF levels. In CSVD-CI patients, plasma MIF levels were significantly correlated with multiple cognitive assessment scores, plasma levels of blood-brain barrier (BBB)-related indices, white matter hyperintensity Fazekas scores, and the mean amplitude of low-frequency fluctuation in the right superior temporal gyrus. Higher plasma MIF levels were significantly associated with worse global cognition and information processing speed in CSVD-CI patients. The composite marker (including plasma MIF) distinguished CSVD-CI patients from CSVD-CN and HCs with >80% accuracy. Meta-analysis indicated that blood MIF levels were significantly increased in CSVD-CI patients. In conclusion, plasma MIF is a potential biomarker for early identification of CSVD-CI. Plasma MIF may play a role in cognitive decline in CSVD through BBB dysfunction and changes in white matter hyperintensity and brain activity.

Upregulation of Notch Signaling and Cell-Differentiation Inhibitory Transcription Factors in Stable Chronic Obstructive Pulmonary Disease Patients.

Notch signaling is involved in the prevention of cell differentiation and cell fate in various organs, including the lungs. We aimed to determine the transcriptomic and protein expression of Notch receptors, their ligands, and related transcription factors in stable COPD. The expression and localization of Notch receptors, their ligands, and related transcription factors were measured in bronchial biopsies of individuals with stable mild/moderate (MCOPD) (n = 18) or severe/very severe (SCOPD) (n = 16) COPD, control smokers (CSs) (n = 13), and control nonsmokers (CNSs) (n = 11), and in the lung parenchyma of those with MCOPD (n = 13), CSs (n = 10), and CNSs (n = 10) using immunohistochemistry, ELISA tests, and transcriptome analyses. In the bronchial biopsies, Notch4 and HES7 significantly increased in the lamina propria of those with SCOPD compared to those with MCOPD, CSs, and CNSs. In the peripheral lung bronchiolar epithelium, Notch1 significantly increased in those with MCOPD and CSs compared to CNSs. ELISA tests of lung parenchyma homogenates showed significantly increased Notch2 in those with MCOPD compared to CSs and CNSs. Transcriptomic data in lung parenchyma showed increased DLL4 and HES1 mRNA levels in those with MCOPD and CSs compared to CNSs. These data show the increased expression of the Notch pathway in the lungs of those with stable COPD. These alterations may play a role in impairing the regenerative-reparative responses of diseased bronchioles and lung parenchyma.

Cryopreserved cGMP-compliant human pluripotent stem cell-derived hepatic progenitors rescue mice from acute liver failure through rapid paracrine effects on liver cells

BackgroundLiver transplantation remains the only curative treatment for end-stage liver diseases. Unfortunately, there is a drastic organ donor shortage. Hepatocyte transplantation emerged as a viable alternative to liver transplantation. Considering their unique expansion capabilities and their potency to be driven toward a chosen cell fate, pluripotent stem cells are extensively studied as an unlimited cell source of hepatocytes for cell therapy. It has been previously shown that freshly prepared hepatocyte-like cells can cure mice from acute and chronic liver failure and restore liver function.MethodsHuman PSC-derived immature hepatic progenitors (GStemHep) were generated using a new protocol with current good manufacturing practice compliant conditions from PSC amplification and hepatic differentiation to cell cryopreservation. The therapeutic potential of these cryopreserved cells was assessed in two clinically relevant models of acute liver failure, and the mode of action was studied by several analytical methods, including unbiased proteomic analyses.ResultsGStemHep cells present an immature hepatic phenotype (alpha-fetoprotein positive, albumin negative), secrete hepatocyte growth factor and do not express major histocompatibility complex. A single dose of thawed GStemHep rescue mice from sudden death caused by acetaminophen and thioacetamide-induced acute liver failure, both in immunodeficient and immunocompetent animals in the absence of immunosuppression. Therapeutic biological effects were observed as soon as 3 h post-cell transplantation with a reduction in serum transaminases and in liver necrosis. The swiftness of the therapeutic effect suggests a paracrine mechanism of action of GStemHep leading to a rapid reduction of inflammation as well as a rapid cytoprotective effect with as a result a proteome reprograming of the host hepatocytes. The mode of action of GStemHep relie on the alleviation of inhibitory factors of liver regeneration, an increase in proliferation-promoting factors and a decrease in liver inflammation.ConclusionsWe generated cryopreserved and current good manufacturing practice-compliant human pluripotent stem cell-derived immature hepatic progenitors that were highly effective in treating acute liver failure through rapid paracrine effects reprogramming endogenous hepatocytes. This is also the first report highlighting that human allogeneic cells could be used as cryopreserved cells and in the absence of immunosuppression for human PSC-based regenerative medicine for acute liver failure.

Do Pharmacological Treatments Act in Collaboration with Rehabilitation in Spinal Cord Injury Treatment? A Review of Preclinical Studies.

There is no choice other than rehabilitation as a practical medical treatment to restore impairments or improve activities after acute treatment in people with spinal cord injury (SCI); however, the effect is unremarkable. Therefore, researchers have been seeking effective pharmacological treatments. These will, hopefully, exert a greater effect when combined with rehabilitation. However, no review has specifically summarized the combinatorial effects of rehabilitation with various medical agents. In the current review, which included 43 articles, we summarized the combinatorial effects according to the properties of the medical agents, namely neuromodulation, neurotrophic factors, counteraction to inhibitory factors, and others. The recovery processes promoted by rehabilitation include the regeneration of tracts, neuroprotection, scar tissue reorganization, plasticity of spinal circuits, microenvironmental change in the spinal cord, and enforcement of the musculoskeletal system, which are additive, complementary, or even synergistic with medication in many cases. However, there are some cases that lack interaction or even demonstrate competition between medication and rehabilitation. A large fraction of the combinatorial mechanisms remains to be elucidated, and very few studies have investigated complex combinations of these agents or targeted chronically injured spinal cords.

Healthcare professionals’ attitudes towards the termination of pregnancy: a qualitative analysis of survey data in Northern Ireland

Abortion was decriminalised in Northern Ireland in October 2019. Following decriminalisation, the new regulations set out legal provision for abortion up until 12 weeks, with conditions thereafter. This cross-sectional descriptive survey, conducted in late 2019 in Northern Ireland, gathered the views of health professionals on decriminalisation, and their willingness to provide abortion services. This article provides a thematic analysis of answers to narrative questions from the online survey, and identifies priority areas of engagement with healthcare professionals. We assess how healthcare professional roles and responsibilities, abortion procedures, the foetus, and women and pregnant people were discursively constructed by respondents who are willing or unwilling to provide abortion services in Northern Ireland. We identify a narrow understanding of ‘harm’, and gendered norms of women as irresponsible or duplicitous, as inhibitory factors to the normalisation of abortion services in Northern Ireland.

Investigating the immune mechanism of natural products in the treatment of lung cancer.

With the deepening of people's understanding of lung cancer, the research of lung cancer immunotherapy has gradually become the focus of attention. As we all know, the treatment of many diseases relies on the rich sources, complex and varied compositions and wide range of unique biological properties of natural products. Studies have shown that natural products can exert anticancer effects by inducing tumor cell death, inhibiting tumor cell proliferation, and enhancing tumor cell autophagy. More notably, natural products can adjust and strengthen the body's immune response, which includes enhancing the function of NK cells and promoting the differentiation and proliferation of T lymphocytes. In addition, these natural products may enhance their anticancer effects by affecting inhibitory factors in the immune system, hormone levels, enzymes involved in biotransformation, and modulating other factors in the tumor microenvironment. The importance of natural products in lung cancer immunotherapy should not be underestimated. However, the specific links and correlations between natural products and lung cancer immunity are not clear enough, and further studies are urgently needed to clarify the relationship between the two. In this paper, we will focus on the correlation between natural products and lung cancer immune responses, with a view to providing new research perspectives for immunotherapy of lung cancer.

The implementation of lean management in reducing waste in the emergency department

Emergency Department (ED) is the frontliner unit of the hospital which becomes the entry door for emergency patients who need quick and efficient treatment. Prolonged doctor’s response time results in complaints, patients feel neglected, and affect the quality of service in the emergency room. This study aims to identify waste in emergency department services and to formulate recommendations for improvement. Methods used in this study is action research. , n=10; emergency room patients/caretakers, n=10. Data were taken through in-depth interviews, data was recorded, transcribed verbatim, and content analysis was carried out. The results of this study found 4 themes; literacy and expectations of health service of waste; complexity of inhibitory factors of services; as well as potential service improvements from supporting factors. There are four types of waste including waiting time, overprocessing, motion, unnecessary inventory, and the trial carried out was shown that it can shortened the doctor’s response time by average of 1 minute 29 seconds 82 . Lean implementation is able to found waste that can be eliminated. It takes commitment from hospital staff and management to always improving and continuously evaluating the service system.

An examination of criminal offenders with dementia in Australian courts

This study aims to characterize people with dementia who were charged with criminal offences between 1995 and 2020 and describe their offending. Court cases were derived from Australian legal databases and descriptive data were manually extracted from case reports. Of 62 people variously charged with homicide, assault, child sexual assault, breach of conditions, property and larceny offences, driving offences, perverting the course of justice and arson, 46 were identified as having executive dysfunction, either as stated by medical expert witnesses or implicitly, due to conditions like Huntington’s disease and frontotemporal dementia. Offending history was found to differ depending on offence type and dementia type. Executive dysfunction appears to underly offending in the sample; furthermore, some disease factors may combine to ‘inhibit’ or ‘permit’ offending. Permitting factors include executive dysfunction and younger age at time of offending; inhibitory factors include dementia-related impacts on mobility, memory and reaction speed.

Meningkatkan Kemampuan Membaca Cepat

The era of globalization demands the ability to read quickly as a crucial skill in facing the rapid growth of information. Speed reading is not just about speed, but also maintaining understanding of the reading content. This journal reviews the concept of speed reading, inhibiting factors, benefits, and strategies for increasing reading speed. The research method used is a qualitative approach with a focus on data collection and analysis. The results show that speed reading involves speed without compromising content understanding. Inhibitory factors involve vocalization, lip movements, head movements, finger pointing, regression, and subvocalization. Strategies to overcome inhibition include reducing physical movements, minimizing vocalizations, and strengthening self-confidence. The goals of speed reading involve efficiency in getting a general impression, finding specific information, and saving time. Increasing reading speed can be achieved through applying methods, focusing on relevant aspects, and avoiding inhibiting habits. This journal presents a comprehensive view to help individuals optimize their speed reading skills.

Microalgae cultivation with recycled harvesting water achieved economic and sustainable production of biomass and lipid: Feasibility assessment and inhibitory factors analysis

This study was conducted to achieve economic and sustainable production of biomass and lipids from Chlorella sorokiniana by recirculating cultivation with recycled harvesting water, to identify the major inhibitory factors in recirculating culture, and to analyze accordingly economic benefits. The results showed that recirculating microalgae cultivation (RMC) could obtain 0.20–0.32 g/L biomass and lipid content increased by 23.1 %-38.5 %. Correlation analysis showed that the extracellular polysaccharide (PSext), chemical oxygen demand (COD) and chromaticity of recirculating water inhibited photosynthesis and induced oxidative stress, thus inhibiting the growth of C. sorokiniana. In addition, the economic benefits analysis found that circulating the medium twice could save about 30 % of production cost, which is the most economical RMC solution. In conclusion, this study verified the feasibility and economy of RMC, and provided a better understanding of inhibitory factors identification in culture.

Proposing a Model to Enhance Social Intelligence among Faculty Members of Farhangian University in Tehran

The primary aim of this article is to propose a model for enhancing social intelligence among faculty members of Farhangian University in Tehran. The research method employed is a mixed-method approach (qualitative-quantitative). In addition to documentary studies, the technique of thematic analysis using MAXQDA12 software was utilized to identify the dimensions and components. The statistical population in this research includes all experts in educational management, cultural management, human resource management, as well as experts in social psychology. Theoretical saturation was reached after conducting 20 interviews, each lasting between 75 to 120 minutes. In the end, basic, organizing, and overarching themes were extracted. In the quantitative section, to determine the current status and the contribution of dimensions and components, a developmental method using structural equation modeling (PLS software) was employed. Based on the semi-structured interviews, 55 indicators, 9 components, and 3 dimensions were identified for constitutive factors; 3 dimensions, 7 components, and 42 indicators for facilitating factors; and 3 dimensions, 6 components, and 17 indicators for inhibitory factors for enhancing social intelligence among the faculty members of Farhangian University in Tehran. According to the coefficients obtained from the structural equation modeling, the facilitating factors ranked first with a coefficient of 0.837, inhibitory factors ranked second with a coefficient of 0.808, and constitutive factors ranked third with a coefficient of 0.778. Finally, through internal validation using four dimensions (philosophy and objectives, theoretical foundations, evaluation system, executive mechanism), the model was confirmed by experts.

CD39 expression defines exhausted CD4+ Tcells associatedwith poor survival and immune evasion in human gastric cancer.

CD4+ Tcell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor-infiltrating CD4+ Tcell exhaustion and how it contributes to the immune response and disease progression in human gastriccancer (GC) remain largely unknown. A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD-1 on CD4+ Tcells in the different samples was analysed by flow cytometry. GC-infiltrating CD4+ Tcell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC-infiltrating Tcells was investigated by inhibiting CD39 enzymatic activity. In comparison with CD4+ Tcells from the non-tumor tissues, significantly more GC-infiltrating CD4+ Tcells expressed CD39. Most GC-infiltrating CD39+CD4+ Tcells exhibited CD45RA-CCR7- effector-memory phenotype expressing more exhaustion-associated inhibitory molecules and transcription factors and produced less TNF-α, IFN-γ and cytolytic molecules than their CD39-CD4+ counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF-α and IFN-γ production. Finally, increased percentages of GC-infiltrating CD39+CD4+ Tcells were positively associated with disease progression and patients' poorer overall survival. Our study demonstrates that CD39 expression defines GC-infiltrating CD4+ Tcell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients.