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The AISI M2 coatings were prepared on H13 die steel substrates by laser cladding technology. The effects of MoS2 addition on the microstructure and wear resistance of the coatings were investigated. The results showed that adding MoS2 can reduce the wear rate of M2 coating, enhance the hardness of the coating, and affect the wear mechanism of the coating. The wear rate of the M2 coating is 3.33 × 10−5 mm3/N·m, mainly consisting of oxidative wear and abrasive wear. When the MoS2 addition reached 7 wt%, the wear rate is only 1.88 × 10−5 mm3/N·m, and the wear mechanism is mainly oxidative wear. The microstructure of the coatings was analyzed using X-ray diffraction techniques and scanning electron microscopy techniques, and its mechanism was thoroughly studied. MoS2 can refine grains and promote fine grain hardening. The average grain size of the M2 coating is 3.42 μm, but the average grain size of the coating containing 7 wt% MoS2 decreases to 1.40 μm.

Abstract Background Open fractures are challenging due to susceptibility to Staphylococcus aureus infections. This study examines the impact of Vancomycin-Loaded Calcium Sulfate (VLCS) and negative pressure wound therapy (NPWT) on macrophage behavior in enhancing healing and infection resistance. Both VLCS and NPWT were evaluated individually and in combination to determine their effects on macrophage polarization and infection resistance in open fractures. Methods Through single-cell RNA sequencing, genomic expressions in macrophages from open fracture patients treated with VLCS and NPWT were compared to a control group. The analysis focused on MBD2 gene changes related to macrophage polarization. Results Remarkable modifications in MBD2 expression in the treatment group indicate a shift towards M2 macrophage polarization. Additionally, the combined treatment group exhibited greater improvements in infection resistance and healing compared to the individual treatments. This shift suggests a healing-promoting atmosphere with improved infection resilience. Conclusions VLCS and NPWT demonstrate the ability to alter macrophage behavior toward M2 polarization, which is crucial for infection prevention in open fractures. The synergistic effect of their combined use shows even greater promise in enhancing outcomes in orthopedic trauma care.

Local communities play a crucial role in the entrepreneurship ecosystem. The role and massive influence of the local environment raise several questions. This paper aims to answer the following questions: (1) how and why the local communities affect SMEs’ sustainability, (2) which pillar of sustainability plays a stronger role in this matter, (3) which internal and external motivators drive a firm’s sustainability actions, and (4) whether company and personal characteristics have a significant effect on local patronage.

Tumor-associated macrophages (TAMs) promote tumor advancement in many ways, such as inducing angiogenesis and the formation of new blood vessels that provide tumors with nourishment and oxygen. TAMs also facilitate tumor invasion and metastasis by secreting enzymes that degrade the extracellular matrix and generating pro-inflammatory cytokines that enhance the migration of tumor cells. TAMs also have a role in inhibiting the immune response against malignancies. To accomplish this, they release immunosuppressive cytokines such as IL-10, and TAMs can hinder the function of T cells and natural killer cells, which play crucial roles in the immune system's ability to combat cancer. The role of TAMs in breast cancer advancement is a complex and dynamic field of research. Therefore, TAMs are a highly favorable focus for innovative breast cancer treatments. This review presents an extensive overview of the correlation between TAMs and breast cancer development as well as its role in the tumor microenvironment (TME) shedding light on their impact on tumor advancement and immune evasion mechanisms. Notably, our study provides an innovative approach to employing nanomedicine approaches for targeted TAM therapy in breast cancer, providing an in-depth overview of recent advances in this emerging field.

AbstractIntellectual capital is now recognized as a factor influencing organizational progress. However, many Micro, Small and Medium Enterprises (MSME’s) in Indonesia still need to understand the importance of intellectual capital to support their organizational performance. This study aims to strengthen intellectual capital succession in MSME’s in Indonesia to improve their competitiveness, financial performance, and sustainability. The population of this study is all MSME’s players in Indonesia. At the same time, the research sample selection is carried out using the criteria, namely MSME’s that have been running their business for at least ten years and use technology in business activities. The calculation of the minimum number of samples was determined from this research method using the SEM (Structural Equation Modeling) analysis test by carrying out several tests, namely composite reliability, coefficient determination, and hypothesis testing. Scientific tests found that human capital affects structural capital, relational capital, and the competitiveness of MSME’s in Indonesia. Structural and relational capital mediate the strong relationship between human capital and the competitiveness of MSME’s in Indonesia. Structural and relational capital can also mediate the strong relationship between human capital and the continuity of MSME’s businesses in Indonesia. Meanwhile, the relationship between human capital and the financial performance of MSME’s in Indonesia can only be weakly mediated by structural and relational capital. These findings certainly provide new evidence about the importance of intellectual capital for the sustainability and competitiveness of today’s MSME’s businesses.

The purpose of the current study is to examine the mediating role of organizational pride on the relationship between ethical leadership and employees’ creativity. Using a convenience sample of (130) managers, heads of the department, and their employees from private hospitals in Jordan, the data were gathered by questionnaire. The current study adopted a quantitative approach. Furthermore, structural equation modeling (SEM) was used to test the study hypotheses. The current study reveals that ethical leadership has a significant and positive impact on employees' creativity. On the other side, the results of the study showed that ethical leadership has a significant and positive impact on organizational pride. Additionally, the current study also showed that organizational pride has a significant and positive impact on employees' creativity. Finally, it has been found that there is a mediation impact on the relationship between ethical leadership and employees' creativity. These findings may help the leader to focus heavily on organizational pride to foster the relationship between ethical leadership and employees’ creativity.

Aim/purpose – This pilot study explores the main obstacles hindering the effective implementation of Artificial Intelligence (AI) in small and medium-sized companies (SMEs). By thoroughly understanding these barriers, organizations can develop customized strategies and interventions to overcome them, facilitating smoother and more successful AI adoption. The paper’s primary goal is to help organizations understand the barriers to AI adoption to develop tailored strategies and interventions to overcome these challenges, leading to a more efficient and successful integration of AI. Through a rigorous examination of real-world experiences and perceptions, this paper seeks to elucidate the multifaceted challenges that impede the effective deployment of AI solutions.

A simple method (first-order approximation) to determine the impact of M2 and the Strehl Ratio on the effective focusable spot size avoiding complex propagations of the beam wavefront is proposed. The model is based upon previous models and the definition of M2 and the Strehl Ratio in a simple manner. This work provides qualitative and quantitative estimates for the interplay of M2 and the Strehl Ratio on the effectively focusable spot size.

Germinal matrix hemorrhage is one of the leading causes of morbidity, mortality, and acquired infantile hydrocephalus in preterm infants in the United States, with little progress made in its clinical management. Blood clots have been shown to elicit secondary brain injury after germinal matrix hemorrhage, by disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage causing post-hemorrhagic hydrocephalus development. Current evidence suggests that rapid hematoma resolution is necessary to improve neurological outcomes after hemorrhagic stroke. Various articles have demonstrated the beneficial effects of stimulating the polarization of microglia cells into the M2 phenotype, as it has been suggested that they play an essential role in the rapid phagocytosis of the blood clot after hemorrhagic models of stroke. N-formyl peptide receptor 2 (FPR2), a G-protein-coupled receptor, has been shown to be neuroprotective after stroke. FPR2 activation has been associated with the upregulation of phagocytic macrophage clearance, yet its mechanism has not been fully explored. Recent literature suggests that FPR2 may play a role in the stimulation of scavenger receptor CD36. Scavenger receptor CD36 plays a vital role in microglia phagocytic blood clot clearance after germinal matrix hemorrhage. FPR2 has been shown to phosphorylate extracellular-signal-regulated kinase 1/2 (ERK1/2), which then promotes the transcription of the dual-specificity protein phosphatase 1 (DUSP1) gene. In this review, we present an intrinsic outline of the main components involved in FPR2 stimulation and hematoma resolution after germinal matrix hemorrhage.

Banks play an essential role in the economy, therefore, their performance must be maintained. Compared to other business sectors, the banking sector has continually achieved the greatest market shares over several periods. When a bank becomes more efficient, it can raise its income and market prices as well as investor confidence. This study examines various factors that influence operational efficiency and the implication for market prices. In 2016 – 2021 years, 28 banking companies were sampled from all banking companies listed on the Indonesia Stock Exchange. Purposive sampling was used for data collection, and linear multiple regression was used for data processing by running tests such as descriptive statistics, determination, regression equations, hypotheses, and implications. The findings reveal a statistically significant relationship between a firm’s size, capital adequacy, loan-to-deposit ratio, net interest, and inflation with operational efficiency, while non-performing loans and exchange rates have no a substantial impact. Additionally, capital adequacy, loan-to-deposit ratio, inflation, and exchange rates had statistically significant effects on market prices, although operational efficiency, non-performing loans, and net interest did not. The mediating analysis reveals that there is no interaction between non-performing loans and net interest with market prices, but it is a mediator for other variables. The research is important for a variety of stakeholders, including managers, investors, and policymakers, who are interested in resolving banking business operations, increasing financial performance, and preserving market prices by establishing mitigation strategies related to specific-internal and external factors.

Extracellular vesicles (EVs) are important cell-to-cell communication mediators. This paper focuses on the regulatory role of tumor-derived EVs on macrophages. It aims to investigate the causes of tumor progression and therapeutic directions. Tumor-derived EVs can cause macrophages to shift to M1 or M2 phenotypes. This indicates they can alter the M1/M2 cell ratio and have pro-tumor and anti-inflammatory effects. This paper discusses several key points: first, the factors that stimulate macrophage polarization and the cytokines released as a result; second, an overview of EVs and the methods used to isolate them; third, how EVs from various cancer cell sources, such as hepatocellular carcinoma, colorectal carcinoma, lung carcinoma, breast carcinoma, and glioblastoma cell sources carcinoma, promote tumor development by inducing M2 polarization in macrophages; and fourth, how EVs from breast carcinoma, pancreatic carcinoma, lungs carcinoma, and glioblastoma cell sources carcinoma also contribute to tumor development by promoting M2 polarization in macrophages. Modified or sourced EVs from breast, pancreatic, and colorectal cancer can repolarize M2 to M1 macrophages. This exhibits anti-tumor activities and offers novel approaches for tumor treatment. Therefore, we discovered that macrophage polarization to either M1 or M2 phenotypes can regulate tumor development. This is based on the description of altering macrophage phenotypes by vesicle contents.

Macrophages are crucial cells in the human body’s innate immunity and are engaged in a variety of non-inflammatory reactions. Macrophages can develop into two kinds when stimulated by distinct internal environments: pro-inflammatory M1-like macrophages and anti-inflammatory M2-type macrophages. During inflammation, the two kinds of macrophages are activated alternatively, and maintaining a reasonably steady ratio is critical for maintaining homeostasis in vivo. M1 macrophages can induce inflammation, but M2 macrophages suppress it. The imbalance between the two kinds of macrophages will have a significant impact on the illness process. As a result, there are an increasing number of research being conducted on relieving or curing illnesses by altering the amount of macrophages. This review summarizes the role of macrophage polarization in various inflammatory diseases, including autoimmune diseases (RA, EAE, MS, AIH, IBD, CD), allergic diseases (allergic rhinitis, allergic dermatitis, allergic asthma), atherosclerosis, obesity and type 2 diabetes, metabolic homeostasis, and the compounds or drugs that have been discovered or applied to the treatment of these diseases by targeting macrophage polarization.

The data provided here relate to the research paper “Assessing the complementarity of TD-NMR, solid-state NMR and Dynamic Vapor Sorption in the characterization of polysaccharide-water interactions”. The original data from TD-NMR, ss-NMR and DVS is provided in .dps, topspin and .xls formats respectively, allowing other authors to repeat our processing protocols using different parameters. We also include results obtained by varying the signal treatments. The analysis of these multimodal data have highlighted a variation in polysaccharide-water interactions depending on the type of assembly. These datasets are very useful for discriminating between water bound to polysaccharides and water absorbed or adsorbed into polysaccharide network, a key element in understanding interactions in these assemblies and an essential approach for developing tailor-made polysaccharides-based products.

This paper estimates the effect of indigenous risk management practices (used by entrepreneurs) on small firm growth amid the current economic crisis in Ghana. The paper hypothesizes that indigenous risk management practices positively affect the growth of informal micro and small agri-food processing firms during the current economic crisis in Ghana. Cross–sectional and limited panel data (covering four years – from the end of 2019 to the end of 2022) have been used in the analysis. Firm Growth has been estimated using sales volume and the number of employees. Findings indicate that apart from savings for business purposes as an indigenous risk management strategy, diversification of economic activities, subscription to formal insurance, forward contracting, cooperative marketing, borrowing, sale of assets, and temporary wage employment outside the business exert a positive influence on small firm growth in terms of sales. Subscription to formal insurance and temporary wages outside the entrepreneur's business positively influence firm growth as related to growth in employee size. We recommend that policymakers design and implement policies that initiate and facilitate the development of marketing cooperatives to negotiate fair prices. This essential tool can help mitigate marketing risks to the agri-food processing entrepreneur. The police should facilitate rolling out skills development programs to increase entrepreneurs' capacities in forward contracting arrangements. Again, entrepreneurs of agri-food processing firms in the wider Ghanaian population should be educated on the need to subscribe to formal insurance to insulate them in times of property loss or personal accidents.

This study examines how blockchain and digital currency have affected the supply of credit and financial stability. It pays particular attention to industry-based analyses and options presented by cryptocurrencies, stablecoins, and digital currencies for the credit supply and financial stability. A positivistic or quantitative research design is employed. The method of data collection is a survey-based questionnaire, as well as the time interval data method, from December 2021 to December 2022. The study sample comprises of five industrial zones of Punjab. The respondents are businessmen, managers, and employees (N = 449). The study finds that the use of various digital currencies quickly transforms business. The study shows that most industries do not require central banks and, instead, concentrate on modern digital currency and blockchain systems for monetary transfers. The private and public models of physical money will likely fail in the future. Rather, central banks should adopt digital currency and blockchain with an online technological payment strategy in order to enhance domestic financial stability and payment systems.

Abstract Clinical cases and experimental evidence revealed that electronic cigarettes (ECIG) induce serious adverse health effects, but underlying mechanisms remain to be fully uncovered. Based on recent exploratory evidence, investigating the effects of ECIG on macrophages can broadly define potential mechanisms by focusing on the effect of ECIG exposure with or without nicotine. Here we investigated the effect of ECIG-aerosol exposure on macrophages (MQ) phenotype, inflammatory response, and function of macrophages. MQ were cultured at air liquid interface and exposed to ECIG-aerosol. Oxidative stress was determined by reactive oxygen species (ROS), heat shock protein 60 (HSP60), glutathione peroxidase (GPx) and heme oxygenase1 (HMOX1). Lipid accumulation and lipid peroxidation were defined by lipid staining and level of malondialdehyde (MDA) respectively. MQ polarization was identified by surface expression markers CD86, CD11C and CD206 as well as pro-inflammatory and anti-inflammatory cytokines in gene and protein level. Phagocytosis of E. coli by MQ was investigated by fluorescence-based phagocytosis assay. ECIG-aerosol exposure in presence or absence of nicotine induced oxidative stress evidenced by ROS, HSP60, GPx, GPx4 and HMOX1 upregulation in MQ. ECIG-aerosol exposure induced accumulation of lipids and the lipid peroxidation product MDA in MQ. Pro-inflammatory MQ (M1) markers CD86 and CD11C but not anti-inflammatory MQ (M2) marker CD206 were upregulated in response to ECIG-aerosol exposure. In addition, ECIG induced pro-inflammatory cytokines IL-1beta and IL-8 in gene level and IL-6, IL-8, and IL-1beta in protein level whereas ECIG exposure downregulated anti-inflammatory cytokine IL-10 in protein level. Phagocytosis activity of MQ was downregulated by ECIG exposure. shRNA mediated lipid scavenger receptor ‘CD36’ silencing inhibited ECIG-aerosol-induced pro-inflammatory MQ polarization and recovered phagocytic activity of MQ. ECIG exposure alters lung lipid homeostasis and thus induced inflammation by inducing M1 type MQ and impair phagocytic function, which could be a potential cause of ECIG-induced lung inflammation in healthy and inflammatory exacerbation in disease condition.

The peroxisomal biogenesis factor 19 (PEX19) is necessary for early peroxisomal biogenesis. PEX19 has been implicated in the replication of a variety of viruses, but the details pertaining to the mechanisms of how PEX19 engages in the life cycle of these viruses still need to be elucidated. Here, we demonstrated that the C terminus of PEX19 interacted with the cytoplasmic tail region of the M2 protein of the influenza A virus (IAV) and inhibited the viral growth titers. IAV infection or PEX19 knockdown triggered a reduction in the peroxisome pool and led to the accumulation of ROS and cell damage, thereby creating favorable conditions for IAV replication. Moreover, a reduction in the peroxisome pool led to the attenuation of early antiviral response mediated by peroxisome MAVS and downstream type III interferons. This study also showed that the interaction between IAV M2 and PEX19 affected the binding of PEX19 to the peroxisome-associated protein PEX14 and peroxisome membrane protein 24 (PMP24). Collectively, our data demonstrate that host factor PEX19 suppresses the replication of the IAV, and the IAV employs its M2 protein to mitigate the restricting role of PEX19.

This study tests a framework of business-to-business (B2B) sellers’ sales performance motivations in services firms. An exploratory-descriptive research design was used and data was collected from 389 respondents working in the services-orientated business sector of Norway. The study's results verify that B2B service sales are complex contexts and situations for B2B seller services firms and their B2B customers to handle. Many elements are required to reach a final deal. Therefore, services firms must maintain seller motivation throughout the B2B services sales process, which is usually hard and may involve psychological wear-out. Consequently, this study examines and verifies an important area of sales performance indicators, namely B2B sellers’ motivations in services firms, and explains B2B sellers’ intrinsic and extrinsic motivations.

Human schistosomiasis is caused by helminths of the genus Schistosoma. Macrophages play a crucial role in the immune regulation of this disease. These cells acquire different phenotypes depending on the type of stimulus they receive. M1 macrophages can be ‘classically activated’ and can display a proinflammatory phenotype. M2 or ‘alternatively activated’ macrophages are considered anti-inflammatory cells. Despite the relevance of macrophages in controlling infections, the role of the functional types of these cells in schistosomiasis is unclear. This review highlights different molecules and/or macrophage activation and polarization pathways during Schistosoma mansoni and Schistosoma japonicum infection. This review is based on original and review articles obtained through searches in major databases, including Scopus, Google Scholar, ACS, PubMed, Wiley, Scielo, Web of Science, LILACS and ScienceDirect. Our findings emphasize the importance of S. mansoni and S. japonicum antigens in macrophage polarization, as they exert immunomodulatory effects in different stages of the disease and are therefore important as therapeutic targets for schistosomiasis and in vaccine development. A combination of different antigens can provide greater protection, as it possibly stimulates an adequate immune response for an M1 or M2 profile and leads to host resistance; however, this warrants in vitro and in vivo studies.

Purpose – The study aims at estimating the shadow economy (SE) using the method of demand for currency in Palestine for the period 2008–2018 by studying the relationship between a group of variables that affect the ratio of money traded outside the banking system to the money supply in the broad sense. Design/methodology/approach – The study has adopted analytical and descriptive research methods to estimate SE in Palestinian territories. The data has been obtained from the inflation reports issued by the Palestinian Monetary Authority for ten years, from 2008 to 2018. A standard model was constructed using EViews version 8 for statistical data processing after converting the annual data to quarterly data. Findings – The authors demonstrated that the size of the SE in Palestinian territories has varied over time, and the annual average of its size during the study period reached about $1764.893 (in millions). This amount constitutes about 15.5% of the gross domestic product. The study provides recommendations for reducing the size of the SE in Palestinian territories. Practical implications – The current study shows that shadow economics could significantly matter for economic policy design by policymakers. Originality/value – This study deals directly with Tanzi’s “estimation of shadow economy in Palestinian territories” concept and its impact on economic policies.

Due to increasing pressure from stakeholders, managers face many hurdles in transforming their businesses to advance corporate sustainability. This study explores the relationship between the ability of so-called “change agents for sustainability” with sustainability performance (SP), particularly in the challenging environment of financing constraints. This study also reveals the mechanism by which competent managers alleviate financial constraints in firms. The panel data estimation method is used on a dataset of 4132 Chinese firms from 2010 to 2019. Empirical results reveal that CEO management ability is positively related to SP. Furthermore, the findings contend that competent CEOs alleviate financing constraints in Chinese firms by improving their SP. Moreover, the competent CEOs in financially constrained firms focus more on sustainability than competent CEOs in non-financially constrained firms. The results are robust for alternative estimation techniques. In light of the study's conclusion, the implications and recommendations are also illustrated.

Abstract Background Radiotherapy is the primary therapeutic option for glioblastoma. Some studies proved that radiotherapy increased the release of exosomes from cells. The mechanism by which these exosomes modify the phenotype of microglia in the tumor microenvironment to further determine the fate of irradiated glioblastoma cells remains to be elucidated. Methods We erected the co-culture system of glioblastoma cells and microglia. After radiation, we analyzing the immunophenotype of microglia and the proliferation of radiated glioblastoma cells. By whole transcriptome sequencing, we analyzed of circRNAs in exosomes from glioblastoma cells and microglia. We used some methods, which included RT-PCR, dual-luciferase reporter, et al., to identify how circ_0012381 from radiated glioblastoma cell-derived exosomes regulated the immunophenotype of microglia to further affect the proliferation of radiated glioblastoma cells. Results Radiated glioblastoma cell-derived exosomes markedly induced M2 microglia polarization. These M2-polarized microglia promoted the proliferation of irradiated glioblastoma cells. Circ_0012381 expression was increased in the irradiated glioblastoma cells, and circ_0012381 entered the microglia via exosomes. Circ_0012381 induced M2 microglia polarization by sponging with miR-340-5p to increase ARG1 expression. M2-polarized microglia suppressed phagocytosis and promoted the growth of the irradiated glioblastoma cells by CCL2/CCR2 axis. Compared with the effects of radiotherapy alone, the inhibition of exosomes significantly inhibited the growth of irradiated glioblastoma cells in a zebrafish model. Conclusions Our data suggested that the inhibition of exosome secretion might represent a potential therapeutic strategy to increase the efficacy of radiotherapy in patients with glioblastoma.

Rodent premotor cortex (M2) integrates information from sensory and cognitive networks for action planning during goal-directed decision-making. M2 function is regulated by cortical inputs and ascending neuromodulators, including norepinephrine (NE) released from the locus coeruleus (LC). LC-NE has been shown to modulate the signal-to-noise ratio of neural representations in target cortical regions, increasing the salience of relevant stimuli. Using rats performing a two-alternative forced choice task after administration of a β-noradrenergic antagonist (propranolol), we show that β-noradrenergic signaling is necessary for effective action plan signals in anterior M2. Loss of β-noradrenergic signaling results in failure to suppress irrelevant action plans in anterior M2 disrupting decoding of cue-related information, delaying decision times, and increasing trial omissions, particularly in females. Furthermore, we identify a potential mechanism for the sex bias in behavioral and neural changes after propranolol administration via differential expression of β2 noradrenergic receptor RNA across sexes in anterior M2, particularly on local inhibitory neurons. Overall, we show a critical role for β-noradrenergic signaling in anterior M2 during decision-making by suppressing irrelevant information to enable efficient action planning and decision-making.

During development of pancreatic cancer macrophage-mediated inflammatory processes and the formation of cancerous lesions are tightly connected. Based on insight from mouse models we provide an overview on the functions of classically-activated pro-inflammatory and alternatively-activated anti-inflammatory macrophages in the initiation and progression of pancreatic cancer. We highlight their roles in earliest events of tumor initiation such as acinar-to-ductal metaplasia (ADM), organization of the fibrotic lesion microenvironment, and growth of low-grade (LG) lesions. We then discuss their roles as tumor-associated macrophages (TAM) in progression to high-grade (HG) lesions with a cancerous invasive phenotype and an immunosuppressive microenvironment. Another focus is on how targeting these macrophage populations can affect immunosuppression, fibrosis and responses to chemotherapy, and eventually how this knowledge could be used for novel therapy approaches for patients with pancreatic ductal adenocarcinoma (PDA).

Inflammatory dermatosis is characterized by persistent inflammatory infiltration and hard repair of diseased skin. As a member of the human innate immune cells, macrophages usually show different phenotypes in different diseases. The macrophage phenotype (M1/M2) imbalance caused by the increase of M1 macrophages or the decrease of M2 macrophages is common in inflammatory dermatosis. In recent years, with the deepening research on inflammatory skin diseases, more and more natural medicines/traditional Chinese medicines (TCMs), represented by Shikonin and Angelica Dahurica, have shown their therapeutic effects by affecting the polarization of macrophages. This review introduced macrophage polarization in different inflammatory dermatosis, such as psoriasis. Then summarized the natural medicines/TCMs that have potential therapeutic effects so far and introduced their mechanisms of action and the proteins/signal pathways involved. We found that the TCMs with therapeutic effects listed in this review are closely related to the theory of five flavors and four properties of Chinese medicinal, and most of them are bitter, acrid and sweet. Bitter TCMs have antipyretic, anti-inflammatory and antibacterial effects, which may improve the persistent inflammation of M1 macrophage infiltration. Acrid TCMs have the effect of promoting blood circulation, while sweet TCMs have the effect of nourishing. These 2 flavors may accelerate the repair of skin lesions of inflammatory dermatosis by affecting M2 macrophages. In conclusion, we hope to provide sufficient knowledge for natural medicine research and the development of inflammatory dermatosis related to macrophage phenotype imbalance.

BackgroundAlthough the benefits of aspiration thrombectomy for treating acute ischemic stroke caused by proximal large vessel occlusion have been established, fewer data are available for evaluating aspiration thrombectomy of distal occlusion. The objective of this study was to evaluate, by means of prospectively collected data, the safety and efficacy of aspiration thrombectomy in patients with M2 middle cerebral artery (MCA) occlusion.MethodsThis study is a subset analysis of a global prospective multicenter observational registry that included patients who presented with either anterior or posterior large vessel occlusion and were eligible for mechanical thrombectomy using the Penumbra System including the Penumbra 3D Revascularization Device. For this analysis, all patients in the registry with M2 MCA occlusion were included.ResultsOf the 650 patients in the registry, 113 (17.4%) had M2 MCA occlusion. The rate of a modified treatment in cerebral infarction score of 2b to 3 after the procedure was 79.6% (90/113), the rate of a modified Rankin Scale score of 0–2 at 90 days was 72.5% (79/109), and the all-cause mortality rate at 90 days was 8.8% (10/113). Device-related serious adverse events occurred in one patient (0.9%) within 24 h and in two patients (1.8%) overall. Procedure-related serious adverse events occurred in four patients (3.5%) within 24 h and in six patients (5.3%) overall (nine events).ConclusionFor appropriately selected patients, aspiration thrombectomy for acute ischemic stroke due to M2 MCA occlusion was safe and effective, with high rates of technical success and good functional outcome.

Phosphate Bufered Saline with 0.4% BSA and M2 medium are one of the most common media used in embryo recovery. The aim of our paper was to investigate if the recovery media used for the recovery of the mouse embryo is influencing in vitro developmental capacity. As biological material we used 10 used were mouse females, age 2 months superovulated with 5UI PMSG (Pregnant Mare Serum Gonadotropine) and 5 UI hCG (human Corionic Gonadotropine). The embryos used were recovered, by oviduct flushing, at 24 hours from the identification of the vaginal plug. The majority of the embryos (78.3%) were in two cells stage. A total of 123, 2 cells embryos were cultivated in M16 medium. The evolution of the embryos was examined at 24, 48 and 72 hours interval. The proportion of hatched blastocyst was higher at the embryos recovered with M2 (53.7%) compared with the embryos recovered with PBS 0.4% BSA. The difference is statistically very significant (p

Excessive alcohol consumption impairs the immune system, induces oxidative stress, and triggers the activation of peripheral blood (PB) monocytes, thereby contributing to alcoholic liver disease (ALD). We analyzed the M1/M2 phenotypes of circulating classical monocytes and macrophage-derived monocytes (MDMs) in excessive alcohol drinkers (EADs). PB samples from 20 EADs and 22 healthy controls were collected for isolation of CD14+ monocytes and short-term culture with LPS/IFNγ, IL4/IL13, or without stimulation. These conditions were also used to polarize MDMs into M1, M2, or M0 phenotypes. Cytokine production was assessed in the blood and culture supernatants. M1/M2-related markers were analyzed using mRNA expression and surface marker detection. Additionally, the miRNA profile of CD14+ monocytes was analyzed. PB samples from EADs exhibited increased levels of pro-inflammatory cytokines. Following short-term culture, unstimulated blood samples from EADs showed higher levels of soluble TNF-α and IL-8, whereas monocytes expressed increased levels of surface TNF-α and elevated mRNA expression of pro-inflammatory cytokines and inducible nitric oxide synthase. MDMs from EADs showed higher levels of TNF-α and CD206 surface markers and increased IL-10 production. LPS/IFNγ induced higher mRNA expression of Nrf2 only in the controls. miRNA analysis revealed a distinctive miRNA profile that is potentially associated with liver carcinogenesis and ALD through inflammation and oxidative stress. This study confirms the predominantly pro-inflammatory profile of PB monocytes among EADs and suggests immune exhaustion features in MDMs.

Abstract Background Macrophages in the peripheral nervous system are key players in the repair of nerve tissue and the development of neuropathic pain due to peripheral nerve injury. However, there is a lack of information on the origin and morphological features of macrophages in sensory ganglia after peripheral nerve injury, unlike those in the brain and spinal cord. We analyzed the origin and morphological features of sensory ganglionic macrophages after nerve ligation or transection using wild-type mice and mice with bone-marrow cell transplants. Methods After protecting the head of C57BL/6J mice with lead caps, they were irradiated and transplanted with bone-marrow-derived cells from GFP transgenic mice. The infraorbital nerve of a branch of the trigeminal nerve of wild-type mice was ligated or the infraorbital nerve of GFP-positive bone-marrow-cell-transplanted mice was transected. After immunostaining the trigeminal ganglion, the structures of the ganglionic macrophages, neurons, and satellite glial cells were analyzed using two-dimensional or three-dimensional images. Results The number of damaged neurons in the trigeminal ganglion increased from day 1 after infraorbital nerve ligation. Ganglionic macrophages proliferated from days 3 to 5. Furthermore, the numbers of macrophages increased from days 3 to 15. Bone-marrow-derived macrophages increased on day 7 after the infraorbital nerve was transected in the trigeminal ganglion of GFP-positive bone-marrow-cell-transplanted mice but most of the ganglionic macrophages were composed of tissue-resident cells. On day 7 after infraorbital nerve ligation, ganglionic macrophages increased in volume, extended their processes between the neurons and satellite glial cells, and contacted these neurons. Most of the ganglionic macrophages showed an M2 phenotype when contact was observed, and little neuronal cell death occurred. Conclusion Most of the macrophages that appear after a nerve injury are tissue-resident, and these make direct contact with damaged neurons that act in a tissue-protective manner in the M2 phenotype. These results imply that tissue-resident macrophages signal to neurons directly through physical contact.

This study aims to investigate the co-movement and Granger causality between Bitcoin prices (BTC) and M2 (cash, demand, and time deposits), inflation, and economic policy uncertainty (EPU) in the U.K. and Japan. It uses monthly data from 31 July 2010 to 30 August 2020 and employs the wavelet coherence method, Toda-Yamamoto, and nonlinear Granger-causality tests. The empirical results show that (i) Bitcoin prices influence M2 and interact with inflation and EPU. In the short term, inflation affects Bitcoin price positively, supporting Bitcoin as an inflation hedged instrument in Japan. Both in Japan and the U.K., the short-term effects of M2 on Bitcoin prices are negative, while EPU's effects on Bitcoin prices are positive, (ii) a bidirectional Toda-Yamamoto Granger causality exists between Bitcoin prices, inflation, and EPU and confirms that M2 affects Bitcoin prices, (iii) a nonlinear bidirectional causality exists between Bitcoin prices and inflation. While Bitcoin prices Granger cause M2 in the U.K. and Japan, inflation shows a nonlinear Granger causality with EPU in Japan. These findings help investors make investment decisions while considering the effects of M2, inflation, and EPU, and monetary authorities and policymakers make policies involving Bitcoin.

Tumor-associated macrophages (TAMs) promote tumor development and metastasis and are categorized into M1-like macrophages, suppressing tumor cells, and M2-like macrophages. M2-like macrophages, occupying a major role in TAMs, can be repolarized into anti-tumoral phenotypes. In this study, outer membrane vesicles (OMVs) secreted by Escherichia coli Nissle 1917 carry perhexiline (OMV@Perhx) to explore the influence of OMVs and perhexiline on TAM repolarization. OMV@Perhx was internalized by macrophages and regulated the phenotype of TAMs from M2-like to M1-like efficiently to increase the level of tumor suppressor accordingly. Re-polarized macrophages promoted apoptosis and inhibited the mobility of tumor, cells including invasion and migration. The results indicate that OMVs improve the efficacy of perhexiline and also represent a promising natural immunomodulator. Combining OMVs with perhexiline treatments shows powerfully synergistic anti-tumor effects through co-culturing with re-polarized macrophages. This work is promising to exploit the extensive applications of OMVs and chemical drugs, therefore developing a meaningful drug carrier and immunomodulator as well as expanding the purposes of traditional chemical drugs.

The Covid-19 pandemic has ushered in a new age in the world. We are still grappling with the implications in various areas of our everyday lives. The impulsive buying habits of consumers, the supply chain, and the whole industry are not exceptions. Consumers and supply chains were both unprepared during the early stages of the novel coronavirus pandemic. The procurement of utilitarian products was referred to as panic buying. The study examined using exploratory studies on several individuals in the eight selected Islamic countries who have been panic buying in coronavirus-affected areas and have faced regional constraints. The data apply on exploratory factor analysis (EFA) in eight selected Islamic countries, three hundred sample finally selected, and a good number of volunteers supported in this study. The results have shown that a drastic financial effect on the economy where purchasing power and remittance inflow declined, inflation goes up and precaution for lockdown, whereas impulsive buying goods tendency increased due to misinformation, and panic buying immensely impact in the economy. The decision-making process has shifted, preventing financial burdening, rising saving patterns, and unwelcoming unhealthy consumption. Moreover, visible psychological distress, depression, anxiety, and post-traumatic stress. These studies concluded with a policy recommendation providing the results.

The analysis of monetary variables and their impact on the economic growth rate has always been in the focus of economic research. In the broadest sense, economic theory distinguishes two basic views defined by the views of monetarists and Keynesians. Although the basic difference is reflected in the determination of price rigidity and money neutrality, specifics of modern economic systems shift the focus towards the positive influence of monetary on real variables. The aim of our research is to identify and quantify the impact of monetary variables on economic growth in Bosnia and Herzegovina. The research was conducted using data from the period 2000-2020. The paper starts with the hypothesis that money supply and inflation ultimately have a positive impact on the real economic growth in BiH. The money supply M2 and the annual inflation rate are taken as explanatory (monetary) variables in the research, while real growth is a dependent variable. The long-term relationship between monetary variables and real growth rates was tested, taking into account the specificity of the BiH monetary arrangement established in the form of a currency board. In order to prove the hypothesis, we applied econometric techniques such as VEC model, cointegration analysis, innovation analysis based on the impulse-responsive function, decomposition variance as well as a causality test. The research results showed the connection between the money supply and the inflation rate with the economic growth in BiH, the relation being positive and statistically significant in the long run. With this, we confirmed the initial hypothesis of the work.

PRRSV infects CD163-positive macrophages and skews their polarization toward an M2 phenotype, followed by T-cell inactivation. In our previous study, we found that recombinant protein A1 antigen derived from PRRSV-2 was a potential vaccine or adjuvant for immunization against PRRSV-2 infection due to its ability to repolarize macrophages into M1 subtype, thereby reducing CD163 expression for viral entry and promoting immunomodulation for Th1-type responses, except for stimulating Toll-like receptor (TLR) activation. The aim of our current study was to evaluate the effects of another two recombinant antigens, A3 (ORF6L5) and A4 (NLNsp10L11), for their ability to trigger innate immune responses including TLR activation. We isolated pulmonary alveolar macrophages (PAMs) from 8- to 12-week-old specific pathogen free (SPF) piglets and stimulated them with PRRSV (0.01 MOI and 0.05 MOI) or antigens. We also investigated the T-cell differentiation by immunological synapse activation of PAMs and CD4+ T-cells in the cocultured system. To confirm the infection of PRRSV in PAMs, we checked the expression of TLR3, 7, 8, and 9. Our results showed that the expression of TLR3, 7, and 9 were significantly upregulated in PAMs by A3 antigen induction, similar to the extent of PRRSV infection. Gene profile results showed that A3 repolarizes macrophages into the M1 subtype potently, in parallel with A1, as indicated by significant upregulation of proinflammatory genes (TNF-α, IL-6, IL-1β and IL-12). Upon immunological synapse activation, A3 potentially differentiated CD4 T cells into Th1 cells, determined by the expression of IL-12 and IFN-γ secretion. On the contrary, antigen A4 promoted regulatory T cell (T-reg) differentiation by significant upregulation of IL-10 expression. Finally, we concluded that the PRRSV-2 recombinant protein A3 provided better protection against PRRSV infection, suggested by its capability to reeducate immunosuppressive M2 macrophages into proinflammatory M1 cells. As M1 macrophages are prone to be functional antigen-presenting cells (APCs), they can call for TLR activation and Th1-type immune response within the immunological synapse.

Background: Vascular fibrosis is a universal phenomenon associated with aging, and oxidative stress plays an important role in the genesis of vascular damage in line with the aging process. However, whether antioxidants can ameliorate vascular fibrosis remains unclear. Objectives: The present study was to determine antioxidant N-acetylcysteine (NAC) could ameliorates aortic fibrosis in aging wild-type C57BL/6 mice. Methods: The aortas were harvested from both 12-week and 60-week wild-type mice. The 60-week mice were treated with and without the NAC for 12 weeks starting at the age of 48 weeks. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining of aortic samples were performed, and the levels of reactive oxygen species (ROS), RNA expression of GAPDH, TNF-α, MCP-1, IL-6, IL-10, IL-4, SIRT-1, SIRT-3, FOXO-1, and macrophage polarization were determined. Results: There is a positive relationship between collagen deposition and the M1/M2 macrophage ratio in the aortic wall of aged wild-type C57BL/6 mice. The higher collagen area percentage in the aortas of 60-week-old mice than in 12-week-old mice was reversed by NAC. NAC could not impact the total number of macrophages, but partly promoted M2 macrophage polarization. By performing qRT-PCR using aortic samples from these mice, we identified that SIRT-1, SIRT-3, FOXO-1 could be somehow responsible for aging-related fibrosis. Conclusions: NAC ameliorates aortic fibrosis in aging wild type mice partly by promoting M2 macrophage polarization.

Parasal değişkenler ve çıktı arasındaki dinamik ilişki makroekonomide en çok çalışılan konulardan biridir. Türkiye Ekonomisine ilişkin olarak yapılan çalışmaların önemli bir kısmının çıkmazı bu çalışmaların birçoğu Granger Nedensellik Testi ve Etki-Tepki fonksiyonu analizi gibi tam örneklem tahmin yöntemlerinin sonuçlarının, göz önünde bulundurduğu örneklem dönemine göre duyarlı görünmesidir. Bu zorluğun üstesinden gelmenin bir yolu olarak, bu çalışmada, Türkiye Ekonomisi için parasal değişkenler ile çıktı değişkeni arasındaki dinamik ilişkiyi vektör otoregresif bir modele dayanan Tarihsel Ayrışma yöntemi kullanılarak incelenmiştir. Çalışmada 1987-2019 dönemi için M1, M2 ve iskonto oranı ile çıktı arasındaki ilişki VAR modeli ile incelenmiş olup enflasyon değişkeninin gecikmeleri bu oluşturulan VAR modeline dışsal değişken olarak eklenmiştir. Tarihsel Ayrıştırma yönteminin avantajlarından faydalanarak değişkenler arasındaki zamanla değişen şoklar uygulanarak daha doğru sonuçlar elde edilmiştir. Bu çalışmadan elde edilen temel sonuç ise çalışmada kullanılan parasal değişkenlerin 1994 ve 2001 Krizlerinde gelir değişkenini negatif olarak güçlü bir şekilde açıkladığı, diğer dönemlerde çoğunlukla güçlü olmamakla beraber pozitif etkilediği şeklindedir.

Abstract Background Pulmonary oedema (PE) is a serious complication of Plasmodium falciparum malaria which can lead to acute lung injury in severe cases. Lung macrophages are activated during malaria infection due to a complex host-immune response. The molecular basis for macrophage polarization is still unclear but understanding the predominant subtypes could lead to new therapeutic strategies where the diseases present with lung involvement. The present study was designed to study the polarization of lung macrophages, as M1 or M2 macrophages, in the lungs of severe P. falciparum malaria patients, with and without evidence of PE. Methods Lung tissue samples, taken from patients who died from severe P. falciparum malaria, were categorized into severe malaria with PE and without PE (non-PE). Expression of surface markers (CD68+, all macrophages; CD40+, M1 macrophage; and CD163+, M2 macrophage) on activated lung macrophages was used to quantify M1/M2 macrophage subtypes. Results Lung injury was demonstrated in malaria patients with PE. The expression of CD40 (M1 macrophage) was prominent in the group of severe P. falciparum malaria patients with PE (63.44 ± 1.98%), compared to non-PE group (53.22 ± 3.85%, p

The main purpose of this study to investigate the impact of the bank rate, budget deficit, FDI and money supply M2 on inflation in the case of Pakistan applying the ARDL model using yearly data from 1974-2016. The Experimental evidence highlight that there is a unique and stable relationship among dependent variable inflation and other different explanatory variables, bank rate, budget deficit, Foreign investment, GDP, Exchange rate and trade openness. After analysis, the result of ARDL indicates that bank rate, exchange rate, and GDP have a negative impact on inflation in the long-run co-efficient. On the other hand, budget deficit, FDI, Money supply M2 and trade openness have a positive impact on inflation. These two tests CUSUM and CUSUMSQ shed light on validates and stability of coefficients in this approach.

Abstract Background Most oral squamous cell carcinomas (OSCC) occur on the basis of oral leukoplakias (OLP). The histologic degree of dysplasia is insufficient for the prediction of OLP malignant transformation. Immunologic parameters are gaining importance for prognostic assessment and therapy of cancer. M2 polarized macrophages were shown to be associated with OSCC progression and inferior prognosis. The current study aims to answer the question if OLP with malignant transformation into OSCC within 5 years differ from OLP without transformation regarding macrophage infiltration and polarization. Methods 201 specimens (50 transforming OLP, 53 non-transforming OLP, 49 corresponding OSCC and 49 healthy oral mucosa controls) were processed for immunohistochemistry. Samples were stained for CD68, CD163 and CD11c expression, completely digitalized and computer-assisted cell counting was performed. Epithelial and subepithelial compartments were differentially assessed. Groups were statistically compared using the Mann–Whitney U-test. A cut-off point for the discrimination of transforming and non-transforming OLP was determined and the association between macrophage infiltration and malignant transformation was calculated using the Chi-square test (χ2 test). Results Macrophage infiltration and M2 polarization in OLP with malignant transformation within 5 years was significantly increased compared to OLP without malignant transformation (p

BackgroundGlioma is the most common primary brain tumor with a poor prognosis. Key genes that are negatively related to prognosis may provide the therapy targets to cure glioma. To clarify the role of CD44 in glioma, we explored its function at bulk-transcriptome, spatial and single-cell transcriptome levels.MethodsIn total, expression profiles with survival data of whole-grade glioma from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), RNA-seq data with anatomic information of glioblastoma (GBM) from the Ivy Glioblastoma Atlas Project, RNA-sequencing (RNA-seq) data from recurrent GBM receiving adjuvant anti-PD-1 immunotherapy accessed through GSE121810, and single-cell RNA-seq data of GBM under accession GSE103224 were enrolled in this study. CD44-specific findings were further analyzed by R language.ResultsCD44 is positively correlated with WHO grade of malignancy and is negatively related to prognosis in glioma. Meanwhile, CD44 predominantly expresses in GBM mesenchymal subtype, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses reveal that CD44 positively coexpressed genes are closely related to glioma immunity. Moreover, CD44+ cells mainly distribute in perinecrotic region with high expression of immune factors. At single-cell resolution, only malignant tumor cells, tumor-associated macrophages (TAMs), and T cells express CD44 in GBM. CD44+ malignant tumor cells are in mesenchymal-1-like (MES1-like) cellular state, and CD44+ TAMs are in M2 phenotype. CD44+ T cells have high expression of both PD-1 and PD-L1. CD44 and its directly interacted inhibitory immunomodulators are upregulated in patients with nonresponder recurrent GBM treated with PD-1 blockade therapy.ConclusionOur work demonstrates that CD44, a new M2 TAM biomarker, is involved in immune suppressor and promote glioma progression in glioma microenvironment. These results expand our understanding of CD44-specific clinical and immune features in glioma.

This paper argues that provision of industrial commons (IC), might be considered as a crucial factor of a cluster’s attractiveness in digital transformation, e.g. in Industry 4.0 (I4.0) time. By drawing on the qualitative case study method of Hamburg Aviation cluster (HAv), it aims at exploring the nature of IC in the leading German I4.0 cluster. Proximity emerges, even if sometimes not explicitly, as the recurring topic facilitating the provision of IC, along with the advancement of I4.0. As Industry 4.0 stipulates much uncertainty, the closeness featuring in clusters, seems to bring various benefits, which can help address challenges associated with I4.0, and faced mainly by small and medium firms (SMEs). The vicinity to key actors and the gains of networking, reflect the importance of (un)articulated proximity.3

The purpose of this paper is to explore the relationship between market orientation, innovation resources and companies’ financial performance. Focus is put on the mediator role of proactive market orientation (PMO) in the relationship between reactive market orientation (RMO), innovation resources and financial performance in the context of Central and Eastern European (CEE) countries. Research builds on reliable scales. Four hundred and fifteen usable questionnaires were collected from companies in Slovenia with more than 20 employees. The results show a strong and positive relationship between RMO and PMO. The impact of RMO on innovativeness as an element of organisational culture is both positive and stronger than the impact of PMO. PMO proved to have a significant positive influence on the capacity to innovate. While innovativeness alone does not directly influence financial performance, the results do confirm the positive impact of an organisational capacity to innovate on financial performance. The finding of our paper is that when PMO was included as a mediator between RMO and the capacity to innovate, the result was that this indirect impact proved to be one of the strongest in the model. Also, it proves that in CEE countries, it is important to stress the influence of market and market orientation in building innovation resources and consequently financial performance. The limitation of the current study is that we considered the relationship only among few marketing resources and organisational performance. In future research, additional measures of market performance may be introduced as mediators between innovation resources and financial performance.

Diabetes mellitus type II and obesity are two important causes of death in modern society. They are characterized by low-grade chronic inflammation and metabolic dysfunction (meta-inflammation), which is observed in all tissues involved in energy homeostasis. A substantial body of evidence has established an important role for macrophages in these tissues during the development of diabetes mellitus type II and obesity. Macrophages can activate into specialized subsets by cues from their microenvironment to handle a variety of tasks. Many different subsets have been described and in diabetes/obesity literature two main classifications are widely used that are also defined by differential metabolic reprogramming taking place to fuel their main functions. Classically activated, pro-inflammatory macrophages (often referred to as M1) favor glycolysis, produce lactate instead of metabolizing pyruvate to acetyl-CoA, and have a tricarboxylic acid cycle that is interrupted at two points. Alternatively activated macrophages (often referred to as M2) mainly use beta-oxidation of fatty acids and oxidative phosphorylation to create energy-rich molecules such as ATP and are involved in tissue repair and downregulation of inflammation. Since diabetes type II and obesity are characterized by metabolic alterations at the organism level, these alterations may also induce changes in macrophage metabolism resulting in unique macrophage activation patterns in diabetes and obesity. This review describes the interactions between metabolic reprogramming of macrophages and conditions of metabolic dysfunction like diabetes and obesity. We also focus on different possibilities of measuring a range of metabolites intra-and extracellularly in a precise and comprehensive manner to better identify the subsets of polarized macrophages that are unique to diabetes and obesity. Advantages and disadvantages of the currently most widely used metabolite analysis approaches are highlighted. We further describe how their combined use may serve to provide a comprehensive overview of the metabolic changes that take place intracellularly during macrophage activation in conditions like diabetes and obesity.

Lactate and the associated H+ ions are still introduced in many biochemistry and general biology textbooks and courses as a metabolic by-product within fast or oxygen-independent glycolysis. However, the role of lactate as a fuel source has been well-appreciated in the field of physiology, and the role of lactate as a metabolic feedback regulator and distinct signaling molecule is beginning to gain traction in the field of immunology. We now know that while lactate and the associated H+ ions are generally immunosuppressive negative regulators, there are cell, receptor, mediator, and microenvironment-specific effects that augment T helper (Th)17, macrophage (M)2, tumor-associated macrophage, and neutrophil functions. Moreover, we are beginning to uncover how lactate and H+ utilize different transporters and signaling cascades in various immune cell types. These immunomodulatory effects may have a substantial impact in cancer, sepsis, autoimmunity, wound healing, and other immunomodulatory conditions with elevated lactate levels. In this article, we summarize the known effects of lactate and H+ on immune cells to hypothesize potential explanations for the divergent inflammatory vs. anti-inflammatory effects.

Cutaneous leishmaniasis is a zoonotic infectious disease broadly distributed worldwide, causing a range of diseases with clinical outcomes ranging from self-healing infections to chronic disfiguring disease. The effective immune response to this infection is yet to be more comprehensively understood and is fundamental for developing drugs and vaccines. Thus, we used experimental models of susceptibility (BALB/c) and partial resistance (C57BL/6) to Leishmania amazonensis infection to investigate the local profile of mediators involved in the development of cutaneous leishmaniasis. We found worse disease outcome in BALB/c mice than in C57BL/6 mice, with almost 15 times higher parasitic load, ulcerated lesion formation, and higher levels of IL-6 in infected paws. In contrast, C57BL/6 presented higher levels of IFN-γ and superoxide anion (•O2−) after 11 weeks of infection and no lesion ulcerations. A peak of local macrophages appeared after 24 h of infection in both of the studied mice strains, followed by another increase after 240 h, detected only in C57BL/6 mice. Regarding M1 and M2 macrophage phenotype markers [iNOS, MHC-II, CD206, and arginase-1 (Arg-1)], we found a pronounced increase in Arg-1 levels in BALB/c after 11 weeks of infection, whereas C57BL/6 showed an initial predomination of markers from both profiles, followed by an M2 predominance, coinciding with the second peak of macrophage infiltration, 240 h after the infection. Greater deposition of type III collagen and lesion resolution was also observed in C57BL/6 mice. The adoptive transfer of macrophages from C57BL/6 to infected BALB/c at the 11th week showed a reduction in both edema and the number of parasites at the lesion site, in addition to lower levels of Arg-1. Thus, C57BL/6 mice have a more effective response against L. amazonensis, based on a balance between inflammation and tissue repair, while BALB/c mice have an excessive Arg-1 production at late infection. The worst evolution seems to be influenced by recruitment of Arg-1 related macrophages, since the adoptive transfer of macrophages from C57BL/6 mice to BALB/c resulted in better outcomes, with lower levels of Arg-1.

Gross margin, as a measure of profitability has been associated with an enterprise and for a single product. The determinants of the gross margin have also been investigated using multiple regression. Whilst attempts have been made to model joint production, this has not been the case for gross margin for joint production. Further, multiple regression analysis is inadequate in modelling the gross margins of joint production. In this paper, we contribute to the literature by estimating gross margin for a joint product, decomposed the gross margin into the respective joint products and investigated the drivers (and constraints) of the joint product gross margins by use of multivariate multiple regression. Using data on smallholder palm fruit processing in Ghana, collected using a pretested questionnaire, we have shown that, attention must not be on the gross margin of the major product alone, in a joint production environment. Gender (being female), number of years of formal education, experience in palm oil processing and credit explained the joint product gross margin. Government, NGOs and other development partners should encourage females to stay longer in the formal school system and enhance credit opportunities to smallholder palm oil processors. The gross margin of the complete set of the joint product must be considered. We showed that failure to account for the minor product would underestimate the gross margin. The outcome is useful for computing profit margins in a joint production environment. Also, it assists the manager in identifying what factors to tweak to increase the profit margin for the joint product.

A good prediction model is useful to accurately predict patient prognosis. Tumor–node–metastasis (TNM) staging often cannot accurately predict prognosis when used alone. Some researchers have shown that the infiltration of M2 macrophages in many tumors indicates poor prognosis. This approach has the potential to predict prognosis more accurately when used in combination with TNM staging, but there is less research in gastric cancer. A multivariate analysis demonstrated that CD163 expression, TNM staging, age, and gender were independent risk factors for overall survival. Thus, these parameters were assessed to develop the nomogram in the training data set, which was tested in the validation and whole data sets. The model showed a high degree of discrimination, calibration, and good clinical benefit in the training, validation, and whole data sets. In conclusion, we combined CD163 expression in macrophages, TNM staging, age, and gender to develop a nomogram to predict 3- and 5-year overall survivals after curative resection for gastric cancer. This model has the potential to provide further diagnostic and prognostic value for patients with gastric cancer.

Macrophage activation refers to the enhanced functionality of macrophages in response to endogenous or exogenous stimuli. Due to the existence of limitless stimuli and a multitude of receptors on macrophage surfaces, the nature of activation (or acquired functioning) can be specific to the encountering stimulus. This article describes a macrophage-activation screening platform in a 96-well format. The methodology involves the generation of bone marrow-derived macrophages, their activation into two extreme activation states, and screening of activated macrophages for expression of bonafide protein biomarkers. A high-throughput and stringent assay to determine macrophage activation markers developed in this article can be adapted for biomarker determination in pathological conditions and toxicant/drug safety screening.

This work aimed to validate the potential use of dental pulp-derived stem cells (DPSCs) for the treatment of inflammation by defining their mechanisms of action. We planned to investigate whether priming of DPSC with proinflammatory molecules had any impact on their behavior and function. In the first step of our validation in vitro, we showed that priming of DPSCs with the bioactive agents LPS, TNF-α, or IFN-γ altered DPSCs’ immunologic properties by increasing their expression levels of IL-10, HGF, IDO, and IL-4 and by decreasing their mitochondrial functions. Moreover, DPSCs induced accelerated wound healing irrespective of priming, as determined by using a gut epithelial cell line in a scratch wound assay. Wound healing of gut epithelial cells was mediated by regulating the expressions of AKT, NF-κB, and ERK1/2 proteins compared to the control epithelial cells. In addition, primed DPSCs altered monocyte polarization toward an immuno-suppressive phenotype (M2), where monocytes expressed higher levels of IL-4R, IL-6, Arg1, and YM-1 compared to monocytes cultured with control DPSCs. In silico analysis revealed that this was accomplished in part by the interaction between kynurenine and PPARγ, which regulated the expression of M2 differentiation-related genes. Collectively, these data provided evidence that the DPSCs reduced inflammation, induced M2 polarization of myeloid cells, and healed damaged gut epithelial cells through inactivation of inflammation and modulating constitutively active signaling pathways.