Intrinsic functional connectivity correlates of cognitive deficits involving sustained attention and executive function in bipolar disorder.

BACKGROUND: The neural correlate of cognitive deficits in bipolar disorder (BD) is an issue that warrants further investigation. However, relatively few studies have examined the intrinsic functional connectivity (FC) underlying cognitive deficits involving sustained attention and executive function at both the region and network levels, as well as the different relationships between connectivity patterns and cognitive performance, in BD patients and healthy controls (HCs). METHODS: Patients with BD (n = 59) and HCs (n = 52) underwent structural and resting-state functional magnetic resonance imaging and completed the Wisconsin Card Sorting Test (WCST), the continuous performance test and a clinical assessment. A seed-based approach was used to evaluate the intrinsic FC alterations in three core neurocognitive networks (the default mode network [DMN], the central executive network [CEN] and the salience network [SN]). Finally, we examined the relationship between FC and cognitive performance by using linear regression analyses. RESULTS: Decreased FC was observed within the DMN, in the DMN-SN and DMN-CEN and increased FC was observed in the SN-CEN in BD. The alteration direction of regional FC was consistent with that of FC at the brain network level. Decreased FC between the left posterior cingulate cortex and right anterior cingulate cortex was associated with longer WCST completion time in BD patients (but not in HCs). CONCLUSIONS: These findings emphasize the dominant role of the DMN in the psychopathology of BD and provide evidence that cognitive deficits in BD may be associated with aberrant FC between the anterior and posterior DMN.

Two ACTH analogs exert differential effects on monocytes/macrophages function regulation in ayu (Plecoglossus altivelis).

Adrenocorticotropic hormone (ACTH), a bioactive peptide of the family of melanocortins, is generated from pro-opiomelanocortin (POMC). So far, the research on the specific functions of ACTH in the immune system of teleosts is limited. We determined two complementary DNA (cDNA) sequences of POMC in ayu (Plecoglossus altivelis), termed PaPOMC-A and PaPOMC-B. PaPOMCs transcripts occurred in all examined tissues, and their expression in immune tissues changed following experimental infection with Vibrio anguillarum. PaACTH-B, but not PaACTH-A, suppressed the phagocytosis of monocytes/macrophages (MO/MФ). Two isoforms of PaACTH increased the bactericidal capacity of MO/MФ. PaACTH-A increased anti-inflammatory cytokine expression, while PaACTH-B decreased pro-inflammatory cytokine expression in MO/MФ. Compared with PaACTH-B treatment, the PaACTH-A treatment improved survival rate and reduced the bacterial load in V. anguillarum-infected ayu through interleukin (IL)-10. Our results indicate that the two PaACTH isoforms exert different effects in the host defense against bacterial infection.

Multifunctional lipid-based nanocarriers with antibacterial and anti-inflammatory activities for treating MRSA bacteremia in mice.

BACKGROUND: Bacteremia-induced sepsis is a leading cause of mortality in intensive care units. To control a bacterial infection, an immune response is required, but this response might contribute to organ failure. Kidneys are one of the main organs affected by bacteremia. Combination therapies with antibacterial and anti-inflammatory effects may be beneficial in treating bacteremia. This study aimed to develop nanostructured lipid carriers (NLCs) loaded with ciprofloxacin and rolipram that exert a combination of anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-inflammatory effects. Retinol was incorporated into the nanoparticles to transport retinol-binding protein 4 (RBP4) to the kidneys, which abundantly express RBP receptors. The NLCs were fabricated by high-shear homogenization and sonication, and neutrophils were used as a model to assess their anti-inflammatory effects. Mice were injected with MRSA to establish a model of bacteremia with organ injury. RESULTS: The mean nanoparticle size and zeta potential of the NLCs were 171 nm and - 39 mV, respectively. Ciprofloxacin (0.05%, w/v) and rolipram (0.02%) achieved encapsulation percentages of 88% and 96%, respectively, in the nanosystems. The minimum bactericidal concentration of free ciprofloxacin against MRSA increased from 1.95 to 15.63 µg/ml when combined with rolipram, indicating a possible drug-drug interaction that reduced the antibacterial effect. Nanoparticle inclusion promoted the anti-MRSA activity of ciprofloxacin according to time-kill curves. The NLCs were found to be largely internalized into neutrophils and exhibited superior superoxide anion inhibition than free drugs. Retinol incorporation into the nanocarriers facilitated their efficient targeting to the kidneys. The NLCs significantly mitigated MRSA burden and elastase distribution in the organs of MRSA-infected animals, and the greatest inhibition was observed in the kidneys. Bacterial clearance and neutrophil infiltration suppression attenuated the bacteremia-induced cytokine overexpression, leading to an improvement in the survival rate from 22% to 67%. CONCLUSIONS: The dual role of our NLCs endowed them with greater efficacy in treating MRSA bacteremia than that of free drugs.

Identification and function of extracellular protein in wastewater treatment using proteomic approaches: A minireview.

Microbial extracellular proteins serve as important functions in wastewater treatment process. Analysis of their compositions and properties is crucial to probe their specific functions. However, conventional analytical techniques cannot obtain interest protein information from complex proteins. Recently, the extracellular proteomics method has been applied to resolve the composition of extracellular proteins. In order to better understand the roles of extracellular protein in wastewater treatment process, this review provides the information on the proteomics methods and their application in investigating extracellular proteins involved in microbial attachment/aggregation, biodegradation of pollutants, and response to environmental stresses. Future work needs to exploit the full capability of the proteome.

Dynamic Dispersal of Surface Layer Biofilm Induced by Nanosized TiO2 Based on Surface Plasmon Resonance and Waveguide.

Pollutant degradation is present mainly in the surface layer of biofilms, and the surface layer is the most vulnerable to impairment by toxic pollutants. In this work, the effects of nanosized TiO2 (n-TiO2) on the average thicknesses of Bacillus subtilis biofilm and on bacterial attachment on different surfaces were investigated. The binding mechanism of n-TiO2 to the cell surface was also probed. The results revealed that n-TiO2 caused biofilm dispersal and the thicknesses decreased by 2.0 to 2.6 µm after several hours of exposure. The attachment abilities of bacteria with extracellular polymeric substances (EPS) on hydrophilic surfaces were significantly reduced by 31% and 81% under 10 and 100 mg/liter of n-TiO2, respectively, whereas those of bacteria without EPS were significantly reduced by 43% and 87%, respectively. The attachment abilities of bacteria with and without EPS on hydrophobic surfaces were significantly reduced by 50% and 56%, respectively, under 100 mg/liter of n-TiO2 The results demonstrated that biofilm dispersal can be attributed to the changes in the cell surface structure and the reduction of microbial attachment ability.IMPORTANCE Nanoparticles can penetrate into the outer layer of biofilm in a relatively short period and can bind onto EPS and bacterial surfaces. The current work probed the effects of nanosized TiO2 (n-TiO2) on biofilm thickness, bacterial migration, and surface properties of the cell in the early stage using the surface plasmon resonance waveguide mode. The results demonstrated that n-TiO2 decreased the adhesive ability of both cell and EPS and induced bacterial migration and biofilm detachment in several hours. The decreased adhesive ability of microbes and EPS worked against microbial aggregation, reducing the effluent quality in the biological wastewater treatment process.

BTLA-expressing CD11c antigen presenting cells in patients with active tuberculosis exhibit low capacity to stimulate T cell proliferation.

Despite past extensive studies on B and T lymphocyte attenuator (BTLA)-mediated negative regulation of T cell activation, the role of BTLA in antigen presenting cells (APCs) in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here, we demonstrate that BTLA expression on CD11c APCs increased in patients with ATB. Particularly, BTLA expression in CD11c APCs was likely associated with the attenuated stimulatory capacity on T cells (especially CD8+ T cell) proliferation. BTLA-expressing CD11c APCs showed lower antigen uptake capacity, lower CD86 expression, higher HLA-DR expression, and enhanced IL-6 secretion, compared to counterpart BTLA negative CD11c APCs in healthy controls (HC). Interestingly, BTLA-expressing CD11c APCs from ATB patients displayed lower expression of HLA-DR and less IL-6 secretion, but higher expression of CD86 than those from HC volunteers. Mixed lymphocyte reaction suggests that BTLA expression is likely associated with positive rather than conventional negative regulation of CD11c APCs stimulatory capacity. This role is impaired in ATB patients manifested by low expression of HLA-DR and low production of IL-6. This previous unappreciated role for BTLA may have implications in the prevention and treatment of patients with ATB.

IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin.

Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP) dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents.

Effective methods for extracting extracellular polymeric substances from Shewanella oneidensis MR-1.

Extracellular polymeric substances (EPS) play crucial roles in bio-aggregate formation and survival of bacterial cells. To develop an effective but harmless method for EPS extraction from Shewanella oneidensis MR-1, five extraction methods, i.e. centrifugation (control), heating (40, 45, 50, and 60 °C), and treatments with H2SO4, ethylenediaminetetraacetic acid (EDTA) and NaOH, were examined, respectively. Results from scanning electron microscope and flow cytometric analyses indicate that MR-1 cells were severely broken by H2SO4, NaOH and heating temperature ≥45 °C. Proteins and polysaccharides in EPS extracted by heating at 40 °C were 7.12 and 1.60 mg g-1 dry cell, respectively. Although EDTA treatment had a relatively lower yield of EPS (proteins and polysaccharides yields of 5.15 and 1.30 mg g-1 dry cell, respectively), cell lysis was barely found after EPS extraction. Three peaks were identified from the three-dimensional excitation-emission matrix spectrum of each EPS sample, suggesting the presence of protein-like substances. Furthermore, the peak intensity was in good accordance with protein concentration measured by the chemical analysis. In short, heating (40 °C) and EDTA treatments were found the most suitable methods for EPS extraction considering the cell lysis and EPS content, composition and functional groups together.

Lipid Carrier Nanostructured Astilbin Ameliorates Rotenone-Induced Neurodegeneration in Mice Brain via Modulation of GSK3ß-Nrf2 Signaling Pathways.

Astilbin is a flavanonol, found in St John's wort (Hypericum perforatum) and many other plants. It has been demonstrated that astilbin contains anti-inflammatory, antioxidant, and immune-suppressive properties. However, the bioavailability of astilbin remains a question for which drug delivery-based nanoparticles can be utilized. We formulated a nanostructured lipid carrier loaded with astilbin (NLC-AS) and tested its effects on the rotenone exposed PC12 cells and in a neurodegenerative mice model of Parkinson's disease (PD) induced by rotenone. Results show that rotenone caused dose-dependent inhibition of PC12 cell growth with about 50% cell death at 2 µM rotenone. Rotenone caused apoptosis in PC12 cells which was reduced to a notable level by NLC-AS through suppression of oxidative stress, especially via elevation of GSH and total antioxidant capacity, and inhibition of monoamine oxidase. Rotenone significantly augmented neurodegeneration in mouse brains by triggering apoptosis and oxidative damage, while NLC-AS treatment halted these processes. Rotenone-exposed mice showed neuronal deficits and impaired neurocognitive functions like loss of memory and learning restrictions which were restored to a remarkable level by NLC-AS administration. The protective effect of NLC-AS was mediated through the inhibition of GSK3ß and induction of Nrf2 genes in the brain tissues. These findings suggest that NLC-AS administration may efficiently regulate the signs of PD in mice and prevent neurodegeneration and neurocognitive dysfunctions.

Striatal Functional Alterations Link to Distinct Symptomatology Across Mood States in Bipolar Disorder.

BACKGROUND: As a central hub in cognitive and emotional brain circuits, the striatum is considered likely to be integrally involved in the psychopathology of bipolar disorder (BD). However, it remains unclear how alterations in striatal function contribute to distinct symptomatology of BD during different mood states. METHODS: Behavioral assessment (i.e., emotional symptoms and cognitive performance) and neuroimaging data were collected from 125 participants comprising 31 (hypo)manic, 31 depressive, and 31 euthymic patients with BD, and 32 healthy control participants. We compared the functional connectivity (FC) of striatal subregions across BD mood states with healthy control participants and then used a multivariate data-driven approach to explore dimensional associations between striatal connectivity and behavioral performance. Finally, we compared the FC and behavioral composite scores, which reflect the individual weighted representation of the associations, among different mood states. RESULTS: Patients in all mood states exhibited increased FC between the bilateral ventral rostral putamen and ventrolateral thalamus. Bipolar (hypo)mania uniquely exhibited increased ventral rostral putamen connectivity and superior ventral striatum connectivity. One latent component was identified, whereby increased FCs of striatal subregions were associated with distinct psychopathological symptomatology (more manic symptoms, elevated positive mood, less depressive symptoms, and worse cognitive performance). Patients with bipolar (hypo)mania had the highest FC and behavioral composite scores while bipolar patients with depression had the lowest scores. CONCLUSIONS: Our data demonstrated both trait features of BD and state features specific to bipolar (hypo)mania. The findings underscored the fundamental role of the striatum in the pathophysiological processes underlying specific symptomatology across all mood states.

Construction and evaluation of China older-adult care service smart supply chain system.

Introduction: As the aging of the population continues to deepen, the pressure on social pensions is gradually increasing, and the issue of assistance has become a problem that must be solved. With the development of science and technology, people's living standard is constantly improving. The older-adult care services expected by the older-adult are wider than meeting the basic daily needs of individuals. The current industry should also consider combining modern science and technology with the older-adult care service industry to serve older-adult better and enable older-adult care service providers to move towards the service needs that make people happier and healthier. This research is about constructing and evaluating China's older-adult care services smart supply chain. Methods: Based on the research results of previous scholars, this paper divides the Sun construction of the smart supply chain of China endowment service into four aspects: policy aspect, economic aspect, social aspect, and technical aspect; the four significant elements are divided into the first-level indicators, and 16 second-level indicators are divided under the first-level indicators. The importance and satisfaction of each evaluation index were obtained by distributing questionnaires to the managers who study the supply chain and the employees who are related to the old-age service. Results and discussion: After the reliability analysis, the importance-performance analysis (IPA) quadrant analysis chart of the evaluation index was constructed using importance-performance analysis. The index of creating a smart supply chain system for China's old-age service is given priority, the supply chain system of China's old-age care service is further improved, and the social security of China's old-age service is enlarged.

Eight-week antidepressant treatment changes intrinsic functional brain topology in first-episode drug-naïve patients with major depressive disorder.

BACKGROUND: A recent study revealed disrupted topological organization of whole-brain networks in patients with major depressive disorder (MDD); however, these results were mostly driven by recurrent MDD patients, rather than first-episode drug-naïve (FEDN) patients. Furthermore, few longitudinal studies have explored the effects of antidepressant therapy on the topological organization of whole-brain networks. METHODS: We collected clinical and neuroimaging data from 159 FEDN MDD patients and 152 normal controls (NCs). A total of 115 MDD patients completed an eight-week antidepressant treatment procedure. Topological features of brain networks were calculated using graph theory-based methods and compared between FEDN MDD patients and NCs, as well as before and after treatment. RESULTS: Decreased global efficiency, local efficiency, small-worldness, and modularity were found in pretreatment FEDN MDD patients compared with NCs. Nodal degrees, betweenness, and efficiency decreased in several networks compared with NCs. After antidepressant treatment, the global efficiency increased, while the local efficiency, the clustering coefficient of the network, the path length, and the normalized characteristic path length decreased. Moreover, the reduction rate of the normalized characteristic path length was positively correlated with the reduction rate of retardation factor scores. LIMITATIONS: The interaction effects of groups and time on the topological features were not explored because of absence of the eighth-week data of NC group. CONCLUSIONS: The topological architecture of functional brain networks is disrupted in FEDN MDD patients. After antidepressant therapy, the global efficiency shifted toward recovery, but the local efficiency deteriorated, suggesting a correlation between recovery of retardation symptoms and global efficiency.

Low-Carbon Travel Motivation and Constraint: Scales Development and Validation.

Low-carbon travel has emerged as a topic of interest in tourism and academia. Studies have offered reasons tourists may engage in low-carbon travel; however, these explanations are scattered throughout the literature and have yet to be integrated into low-carbon travel motivation and constraint constructs. This study develops a low-carbon travel motivation scale (LCTMS) and a low-carbon travel constraint scale (LCTCS). It performs reliability and validity testing to measure the low-carbon travel motives and obstacles. Items were collected primarily by literature review, and, then, by surveys of 382 tourists from low-carbon travel destinations and 390 from non-low-carbon travel destinations. Through a rigorous scale development process, this study identifies six dimensions of the LCTMS (environmental protection, experience-seeking, escape or social connection, industry pleas and measures for environmental protection, low-carbon products, and green transportation) and four dimensions of the LCTCS (intrapersonal constraints, interpersonal constraints, structural constraints, and the not a travel option).

The impacts of conditions and person-organization fit on alliances performance: And the moderating role of intermediary.

This study expects to provide a reference for the catering industry. The travel industry expands sales channels and turnover tends to choose a strategic alliance with the alliance objects mutually beneficial cooperation to improve their competitiveness. This study examines the effects of alliance conditions and person-organization fit (P-O-fit) on the performance of strategic alliances between travel industries. Furthermore, this study contained the intermediary performance as a moderator to examine the influences of alliance conditions and P-O-fit on the performance of strategic alliances. There were 406 usable questionnaires collected. We verified the hypotheses by the structural equation modeling method. The results suggest that the alliance conditions have positive and significant direct effects on the performance of strategic alliances. Moreover, the P-O-fit also has positive and significant effects on the performance of strategic alliances. Furthermore, the intermediary performance has substantial moderating effects on the influences of P-O-fit on the performance of strategic alliances. The conclusion provides a theoretical and practical basis between performance and the travel industry.

Exploring the Relationship Between Hospital Service Quality, Patient Trust, and Loyalty From a Service Encounter Perspective in Elderly With Chronic Diseases.

Based on the service encounter perspective, this study combines theoretical foundations for such factors as service quality and the characteristics of the hospital service industry to develop a research model scale to investigate whether the quality of hospital services affects patients' perceptions of health service encounters, trust, and loyalty. Nowadays, with the advancement of medical technology, patients pay more attention to the quality of medical services and good service encounters provided by healthcare professionals in order to establish positive patient relationships; hospitals need to improve their own service quality and establish good patient trust relationships so that doctor-patient satisfaction and loyalty can be improved. In a review of related literature, this study found that most past studies focused on issues related of quality of medical services and patient satisfaction, but ignored those related to the relationship between medical service encounters and patient trust and loyalty, as well as the lack of scientific measurement markers for service encounters in the Chinese medical service industry. Therefore, this study uses the Service Encounter Perspective and Service Quality Theory Development Research Scale to collect and analyze data for a typical case of a Chinese tertiary hospital. Finally, this study explores the relationship between the four variables of service quality, service encounter, trust, and loyalty by means of a questionnaire and statistical analysis of the data. Finally, it is concluded that the higher the service quality of the hospital, the higher the customer trust, the higher the service encounter, and in the greater the doctor-patient loyalty.

Diamond Model of Green Commitment and Low-Carbon Travel Motivation, Constraint, and Intention.

Although consumers generally accept and care about environmental issues, consumers have not adjusted their behavior accordingly. Based on the diamond model theory, this study proposes and tests the direct impact of personal green commitments on low-carbon travel motivation and constraint, and the possibility of subsequent low-carbon travel intention. According to the results of 358 valid questionnaire surveys, this study shows that green commitments positively affect the low-carbon travel motivation and intention, while negatively affecting the low-carbon travel constraint. The low-carbon travel motivation has some mediating effects. The research results can be used as a reference by relevant managers of the tourism industry to make changes in the content of travel services that are more suitable for specific populations.

Two paralogs of CXCR4 in the Japanese sea bass (Lateolabrax japonica) are involved in the immune response of B lymphocytes.

CXC chemokine receptor 4 (CXCR4), a member of the G-protein-coupled receptor family, plays an important role in host immune responses. Within the teleost lineage, there are two paralogs of CXCR4; however, the role of CXCR4 in teleost B cells is poorly understood. In this study, we determined the cDNA sequences of the two CXCR4 paralogs from the Japanese sea bass (Lateolabrax japonica; LjCXCR4a and LjCXCR4b). Sequence and phylogenetic tree analyses revealed that LjCXCR4a and LjCXCR4b are most closely related to CXCR4a and CXCR4b, respectively, in the large yellow croaker (Larimichthys crocea). CXCR4 transcripts were mainly expressed in the gills, and their expression in different tissues was altered upon infection with Vibrio harveyi. LjCXCR4a and LjCXCR4b protein levels were upregulated in infected B cells. Knockdown of LjCXCR4a and LjCXCR4b in B cells by RNA interference, the phagocytic activity of B cells was not affected. Furthermore, knockdown of LjCXCR4a, not of LjCXCR4b, was observed to inhibit LjIgM expression in lipopolysaccharide-stimulated B cells. In addition, knockdown of LjCXCR4a, not of LjCXCR4b, was found to reduce reactive oxygen species levels in B cells. Our results indicate that LjCXCR4a and LjCXCR4b modulate the immune response of Japanese sea bass B cells against bacterial infection, albeit via different pathways.

Nanocrystalline chloroxine possesses broad-spectrum antimicrobial activities and excellent skin tolerability in mice.

Background: Antimicrobial submicrometer particles are being studied as promising interventions against a wide range of skin conditions, such as fungal or bacterial infections. Aims: To submicronize chloroxine, the crystalline compound 5,7-dichloro-8-hydroxyquinoline, by nanoprecipitation and characterize the resulting assemblies. Methods: The chloroxine particles were stabilized by a nonionic surfactant and were studied by a broth microdilution assay against 20 medically important bacteria and fungi. The intervention was studied using a murine model of skin irritation. Results & conclusion: Chloroxine nanoparticles with a diameter of 600-800 nm exhibit good tolerability in terms of skin irritation in vivo and good antimicrobial activity. Thus, the fabricated formulation shows great promise for interventions for both cutaneous infection control and prophylaxis.

Matrix metalloproteinase-25 from Japanese sea bass (Lateolabrax japonicus) is involved in pro-inflammatory responses.

Matrix metalloproteinases (MMPs) are highly expressed in leukocytes and macrophages, which play a role in the innate immune response. Here, the cDNA sequence of MMP25 from Japanese sea bass (Lateolabrax japonicus) (LjMMP25) was identified. Phylogenetic analysis revealed that LjMMP25 was most closely related to large yellow croaker MMP25. Multiple sequence alignment of LjMMP25 with MMP25 sequences from other teleosts revealed that regions of known functional importance were highly conserved. Expression analysis revealed that LjMMP25 was highly expressed in the head kidney and widely expressed in other tissues including gill, spleen, and liver. LjMMP25 was found to regulate inflammatory cytokine production and promote phagocytosis and bacterial killing in monocytes/macrophages (MO/MФ). Furthermore, LjMMP25 regulated the inflammatory response by modulating NF-κB signaling. These findings reveal new information about the role of LjMMP25 in regulating pro-inflammatory responses in this species.

Meteorin links the bone marrow hypoxic state to hematopoietic stem/progenitor cell mobilization.

Hematopoietic stem/progenitor cells (HSPCs) are supported and regulated by niche cells in the bone marrow with an important characterization of physiological hypoxia. However, how hypoxia regulates HSPCs is still unclear. Here, we find that meteorin (Metrn) from hypoxic macrophages restrains HSPC mobilization. Hypoxia-induced factor 1α and Yin Yang 1 induce the high expression of Metrn in macrophages, and macrophage-specific Metrn knockout increases HSPC mobilization through modulating HSPC proliferation and migration. Mechanistically, Metrn interacts with its receptor 5-hydroxytryptamine receptor 2b (Htr2b) to regulate the reactive oxygen species levels in HSPCs through targeting phospholipase C signaling. The reactive oxygen species levels are reduced in HSPCs of macrophage-specific Metrn knockout mice with activated phospholipase C signaling. Targeting the Metrn/Htr2b axis could therefore be a potential strategy to improve HSPC mobilization for stem cell-based therapy.