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Diabetic cardiovascular autonomic neuropathy (DCAN) is a common complication of diabetes mellitus which brings about high mortality, high morbidity, and large economic burden to the society. Compensatory tachycardia after myocardial ischemia caused by DCAN can increase myocardial injury and result in more damage to the cardiac function. The inflammation induced by hyperglycemia can increase P2X7 receptor expression in the superior cervical ganglion (SCG), resulting in nerve damage. It is proved that inhibiting the expression of P2X7 receptor at the superior cervical ganglion can ameliorate the nociceptive signaling dysregulation induced by DCAN. However, the effective drug used for decreasing P2X7 receptor expression has not been found. Schisandrin B is a traditional Chinese medicine, which has anti-inflammatory and antioxidant effects. Whether Schisandrin B can decrease the expression of P2X7 receptor in diabetic rats to protect the cardiovascular system was investigated in this study. After diabetic model rats were made, Schisandrin B and shRNA of P2X7 receptor were given to different groups to verify the impact of Schisandrin B on the expression of P2X7 receptor. Pathological blood pressure, heart rate, heart rate variability, and sympathetic nerve discharge were ameliorated after administration of Schisandrin B. Moreover, the upregulated protein level of P2X7 receptor, NLRP3 inflammasomes, and interleukin-1β in diabetic rats were decreased after treatment, which indicates that Schisandrin B can alleviate the chronic inflammation caused by diabetes and decrease the expression levels of P2X7 via NLRP3. These findings suggest that Schisandrin B can be a potential therapeutical agent for DCAN.

Background: The Chinese medicine punicalagin (Pun), the most important active ingredient in pomegranate peel, has significant bacteriostatic and anti-inflammatory properties. The potential mechanisms of Pun for bacterial enteritis, however, are unknown. Objective: The goal of our research is to investigate the mechanism of Pun in the treatment of bacterial enteritis using computer-aided drug technology, as well as to investigate the intervention effect of Pun on mice with bacterial enteritis using intestinal flora sequencing. Methods: The targets of Pun and Bacterial enteritis were obtained by using the specific database, and cross-targets were screened among these targets, followed by PPI and enrichment analysis of the targets. Furthermore, the degree of binding between Pun and key targets were predicted through molecular docking. After successfully establishing the bacterial enteritis model in vivo, mice were randomly assigned to groups. They were treated for 7 days, the symptoms were observed daily, and the daily DAI and body weight change rate were calculated. Following administration, the intestinal tissue was removed, and the contents were separated. The tight junction protein expression was detected in the small intestine by the immunohistochemical method; ELISA and Western Blot (WB) were performed to detect the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum and intestinal wall of mice. The 16S rRNA sequence was used to determine the composition and diversity of the intestinal flora of mice. Results: In total, 130 intersection targets of Pun and disease were screened by network pharmacology. The enrichment analysis showed cross genes were closely related and enriched in the cancer regulation and the TNF signal pathway. The active components of Pun could specifically bind to the core targets TNF, IL-6, etc., determined from molecular docking results. In vivo experiment results showed that the symptoms in the PUN group mice were alleviated, and the expression levels of TNF-α and IL-6 were significantly reduced. Pun can cause substantial changes in the intestinal flora of mice in terms of structure and function. Conclusion: Pun plays a multi-target role in alleviating bacterial enteritis by regulating intestinal flora.

Spermatogenesis is a cyclical process in which different generations of spermatids undergo a series of developmental steps at a fixed time and finally produce spermatids. Here, we report that overexpression of PD-L1 (B7 homolog1) in the testis causes sperm developmental disorders and infertility in male mice, with severe malformation and sloughing during spermatid development, characterized by disorganized and collapsed seminiferous epithelium structure. PD-L1 needs to be simultaneously expressed on Sertoli cells and spermatogonia to cause spermatogenesis failure. After that, we excluded the influence of factors such as the PD-L1 receptor and humoral regulation, confirming that PD-L1 has an intrinsic function to interact with PD-L1. Studies have shown that PD-L1 not only serves as a ligand but also plays a receptor-like role in signal transduction. PD-L1 interacts with PD-L1 to affect the adhesive function of germ cells, causing malformation and spermatid sloughing. Taken together, these results indicate that PD-L1 can interact with PD-L1 to cause germ cell detachment and male infertility.

Chronic neuropathic pain is caused by tissue damage or nervous system inflammation and is characterized by sensitivity to painful stimuli. P2X3 receptors play an important role in facilitating pain transmission. Neferine is a bisbenzylisoquinline alkaloid isolated from seed embryos of lotus, which has anti-inflammatory and anti-oxidation pharmacological functions. The present research investigated whether neferine relieves neuropathic pain related to the P2X3 receptor in rat dorsal root ganglia (DRGs). Chronic contraction injury (CCI) in rats was used as a model for neuropathic pain. The results indicated that the expression of P2X3 receptor was significantly increased in the DRGs of CCI rats and that mechanical allodynia and thermal hyperalgesia were also enhanced in CCI rats. Neferine markedly lowered the upregulated P2X3 receptor and interleukin-1beta, inhibited the phosphorylation and activation of ERK1/2 in the DRGs of CCI rats, and relieved neuropathic pain. Therefore, neferine alleviates neuropathic pain by downregulating the expression of P2X3 receptor.

With the fast development of modern industries, scarcity of freshwater resources caused by heavy metal pollution (i.e., Hg

Heavy metal pollution has resulted in numerous environmental challenges. However, classic approaches, involving the use of solid adsorbents are subject to limitations, including the high energy consumption required for processing before and after use. Accordingly, strategies that facilitate the use of metal capture media that extends beyond waste remediation are attractive. Herein, a porous fluorescent aerogel (CPC aerogel) is constructed by immersing amino-based carbon dots (CDs-NH

The shortage of freshwater resources caused by heavy metal pollution is an acute global issue. Herein, a novel nanoplatform was fabricated by hydrothermal deposition of 3D-MoS2 nanospheres onto biocompatible wood sponge (WS) for Hg(ii) removal. Moreover, a secondary water purification strategy was investigated to produce drinkable water using the exhausted wood sponge. The exhausted MoS2-wood sponge (MWS) was used to construct a solar steam generator by wrapping with a hydrophilic polyvinyl alcohol (PVA) layer to prevent heavy metal ion leakage and to enhance the hydrophilicity. The energy conversion efficiency of the evaporator was calculated to be 95.48% under one sun illumination. Remarkably, the treatment of model desulphurization wastewater from power plants with this functional wood sponge could efficiently reduce the mercury concentration below the limit proposed by the World Health Organization for drinking water. These results provide a basis for the application of upcycled hazardous adsorbents for the purification of drinkable water.

Employing fluorescent hydrogels for hazardous Hg(II) detection and removal is an efficient method for water purification. However, it remains challenging to establish a fluorescent system with low detection limit and high adsorption capacity that can readily be upcycled into a valuable material resource. Herein, we report on a fluorescent hydrogel with 0D sulfydryl-based carbon dots that are self-assembled with a 3D hydrogel network. The cellulose-based hydrogel exhibited good sensitivity for the detection of Hg(II) over a range from 0 to 40 µM with a limit detection of 3.0 × 10-6 M. The adsorption experiments confirmed that the cellulose-based hydrogel exhibits good Hg(II) extraction capacity of over 662.25 mg g−1 at room temperature, and can effectively reduce the Hg concentration to attain acceptable levels that comply with industrial water standards (0.05 mg L-1). Subsequently, we used a facile strategy to convert the exhausted waste adsorbent by in-situ sulfurization into a suitable material for solar steam generation. The as-prepared upcycled aerogel evaporators exhibited excellent evaporation rates of ∼ 1.30 kg m−2 h−1 under one sun irradiation. These results not only provide a strategy for heavy metal ion recognition and adsorption, but also provide a route to recycle hazardous waste for seawater desalination.

Grain refinement of magnesium alloys is an effective way to improve their tensile strength and ductility to meet industrial application requirements. Herein, a new rheocasting process, internal rapid cooling stirring process (IRCSP), was used to obtain a fully grain-refined spherical semi-solid slurry. Rapid quenching was used to study the microstructure evolution during IRCSP. The experimental results showed that the solid fraction was mainly determined by nucleation, and grain growth played only a minor role. The particle density was determined by a combination of the fragmentation and coalescence of solid particles. Changes in grain size over time followed a 1/3 power law with a ripening coefficient. In addition, the particle distribution was determined using shear stress flow and cooling rates. The microstructural analysis suggested that a fast cooling rate led to grain refinement, and rapid stirring enhanced the interfacial energy and stability of the solid-liquid interface. As a result, fine globular primary α-Mg particles were obtained during IRCSP.

Diabetic neuropathic pain (DNP) is a common complication of diabetes, and its complicated pathogenesis as well as clinical manifestations has brought great troubles to clinical treatment. The spinal cord is an important part of regulating the occurrence and development of DNP. Spinal microglia can regulate the activity of spinal cord neurons and have a regulatory effect on chronic pain. P2Y12 receptor is involved in DNP. P2Y14 and P2Y12 receptor belong to the Gi subtype of P2Y receptors, but there is no report that P2Y14 receptor is involved in DNP. Closely related to many human diseases, the dysregulation of lncRNA has the effect of promoting or inhibiting the occurrence and development of diseases. The aim of this research is to investigate the function of spinal cord P2Y14 receptor in type 2 DNP and to understand the function as well as the possible mechanism of lncRNA-UC.25+ (UC.25+) in rat spinal cord P2Y14 receptor-mediated DNP. Our results showed that P2Y14 shRNA can reduce the expression of P2Y14 in DNP rats, thereby restraining the activation of microglia, decreasing the expression of inflammatory factors and the level of p38 MAPK phosphorylation. At the same time, UC.25+ shRNA can down-regulate the expression of P2Y14 receptor, reduce the release of inflammatory factors, and diminish the p38 MAPK phosphorylation, indicating that UC.25+ can alleviate spinal cord P2Y14 receptor-mediated DNP. The RNA immunoprecipitation result showed that UC.25+ enriched STAT1 and positively regulated its expression. The chromatin immunoprecipitation result indicated that STAT1 combined to the promoter region of P2Y14 receptor and positively regulated the expression of P2Y14 receptor. Therefore, we infer that UC.25+ may alleviate DNP in rats by regulating the expression of P2Y14 receptor in spinal microglia via STAT1.

Diabetic neuropathic pain (DNP) is a common complication of diabetes, and its complicated pathogenesis, as well as clinical manifestations, has brought great trouble to clinical treatment. The spinal cord is an important part of regulating the occurrence and development of DNP. Spinal microglia can regulate the activity of spinal cord neurons and have a regulatory effect on chronic pain. P2Y

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic respiratory symptoms. The respiratory symptoms of patients with acute exacerbation of COPD (AECOPD) worsen rapidly. At present, traditional western medicine treatment can not effectively alleviate the symptoms and attack frequency of patients. Suzi Jiangqi decoction(SZJQ) has a good clinical effect in the treatment of AECOPD. Due to the lack of evidence-based medicine, it can not provide an effective systematic evaluation for the treatment of AECOPD with Suzi Jiangqi decoction. Therefore, it is necessary to provide high-quality evidence evaluation for the clinical efficacy and safety of Suzi Jiangqi Decoction in the treatment of AECOPD. Methods: Two researchers independently retrieved randomized controlled trial (RCT) and quasi-RCTs of SZJQ in the treatment of AECOPD from databases including PubMed, Web of science, the Cochrane Library, CBM, CNKI, Sinomed, VIP and WanFang.The included studies were evaluated for quality according to the RCT quality assessment method provided by Cochrane Reviewer's Handbook 5.3.Review Manager 5.3 software provided by the Cochrane collaboration was used for meta-analysis. Results: This study will provide systematic review on the efficacy and safety of SZJQ as adjuvant therapy in patients with AECOPD by rigorous quality assessment and reasonable data synthesis. Conclusions: This systematic review will provide the good evidence currently on SZJQ as adjuvant therapy in patients with AECOPD.

Observing different types of pores in aluminum alloy from A356 high-pressure die casting by X-ray computerized tomography and scanning electron microscopy, we found that equivalent spherical diameters of pores obeyed the 3-parameter lognormal distribution rather than the 2-parameter one. Statistically, the sphericity of most round gas pores with smooth inner surfaces consisting of oxide films was > 0.58, while the sphericity of shrinkage pores with unfractured dendrites was

BackgroundTriple-negative breast cancer (TNBC) is a significant cause of patient morbidity. The exactly pathobiological features of this condition has yet to be completely elucidated.MethodsBreast cancer data obtained from The Cancer Genome Atlas (TCGA) database were evaluated for lncRNA SNHG6 expression. Normal human breast epithelial cell line (MCF-10A) and other breast cancer cell lines (BT-549, MDA-MB-231, Hs 578t, ZR-75-30, SK-BR-3, MCF-7) were also assessed for lncRNA SNHG6 expressions. Cellular proliferative ability was evaluated with colony formation and CCK-8 assays. The ability of cells to migrate was scrutinized with the wound healing and Boyden chamber cell migration assays. qRT-PCR enabled for detection of lncRNA SNHG6, miR-125b-5p and BMPR1B mRNA expressions. Protein BMPR1B expressions were further assessed using Western Blotting. Direct binding sites between transcripts were determined using dual-luciferase reporter assays. We also constructed a xenograft mouse model to further dissect the vivo implications of lncRNA SNHG6. Ki-67 and c-Caspase-3 expressions were detected using immunohistochemistry staining.ResultsBreast cancer cell lines demonstrated higher lncRNA SNHG6 expressions, particularly TNBC cell lines, in contrast to normal breast epithelial cell lines. This finding coincided with those noted on analysis of TCGA breast cancer data. lncRNA SNHG6 knockdown inhibited TNBC cell proliferation, migration, while promoted cell apoptosis. Furthermore, suppressed lncRNA SNHG6 expressions resulted in lower tumor weights and volumes in a xenograft mouse model, as evidenced by Ki-67 and c-Caspase-3 expression profiles in tumor tissues. miR-125b-5p and lncRNA SNHG6/BMPR1B both possessed direct binding sites for each other which was validated utilizing a dual-luciferase reporter assay. Decreasing lncRNA SNHG6 expression in TNBC cells upregulated miR-125b-5p expression. Another side, inhibiting miR-125b-5p upregulated BMPR1B expression in these cells. Moreover, knocking down lncRNA SNHG6 downregulated BMPR1B expression in TNBC cells, and the finding was rescued in cells which were exposed to miR-125b-5p inhibitor. Downregulating miR-125b-5p mitigated the effect of suppressing lncRNA SNHG6 on TNBC cell proliferation, migration, and apoptosis.ConclusionDownregulation of lncRNA SNHG6 could inhibit TNBC cell proliferative, migratory capabilities and promote apoptosis capability, likely through modulation of the miR-125b-5p/BMPR1B axis. This axis may be targeted in formulating new therapies for TNBC.

Background Currently, several non-coding RNAs (ncRNAs) were distinguished in polycystic ovarian syndrome (PCOS). This present study aims to explore the potential function of lncRNA HOTAIRM1/miR-433-5p/PIK3CD in ovarian granulosa cells. Methods We analyzed the expression profiles of HOTAIRM1, miR-433-5p and PIK3CD in PCOS samples by enquiring GEO database. GSEA was applied to enrich the pathways related to PCOS. The target association between HOTAIRM1 and miR-433-5p or the binding association between miR-433-5p and PIK3CD were assessed by online prediction tools and a dual luciferase reporter assay. qPCR and western blotting assays were used to detect PIK3CD expression after HOTAIRM1 and miR-433-5p treatment. The proliferation and apoptosis of ovarian granulosa cells were estimated by cell counting kit-8 and flow cytometry assays, respectively. Results The expression profiles of HOTAIRM1 and PIK3CD were increased, whereas miR-433-5p was decreased in PCOS tissues. PIK3CD expression was positively regulated by HOTAIRM1 and negatively modulated by miR-433-5p. Overexpression of HOTAIRM1 reduced the proliferative ability and increased the apoptotic ability of granulosa cells, whereas upregulation of miR-433-5p or downregulation of PIK3CD reversed the effects of HOTAIRM1 on granulosa cells. Moreover, overexpression of miR-433-5 displayed a results with increasing proliferative ability and decreasing apoptotic ability, but upregulation of PIK3CD eliminated the function of miR-433-5p on granulosa cells. Conclusions Our findings illustrated that HOTAIRM1 could sponge miR-433-5p to promote PIK3CD expression, thereby regulating the growth and apoptosis of granulose cells in PCOS.

This paper introduces the doubly-fed induction generator wind turbine running system based on the smart grid laboratory of the Three Gorges University .This system can simulate actual state of the wind, and investigate the operation condition of the generator of different wind strength. It can also control the output voltage and frequency and determine the best working point in different wind conditions.

In many mammals, the eyelids migrate over the eye and fuse during embryogenesis to protect the cornea from damage during birth and early life. Loss-of-function mutations affecting the epidermal growth factor receptor (EGFR) signaling pathway cause an eyes-open-at-birth (EOB) phenotype in rodents. We identified an insertional mutation in Spinster homolog 2 (Spns2) in a strain of transgenic rats exhibiting the EOB phenotype. Spns2, a sphingosine 1-phosphate (S1P) transporter that releases S1P from cells, was enriched at the tip of developing eyelids in wild-type rat embryos. Spns2 expression or treatment with S1P or any one of several EGFR ligands rescued the EOB Spns2 mutant phenotype in vivo and in tissue explants in vitro and rescued the formation of stress fibers in primary keratinocytes from mutants. S1P signaled through the receptors S1PR1, S1PR2, and S1PR3 to activate extracellular signal-regulated kinase (ERK) and EGFR-dependent mitogen-activated protein kinase kinase kinase 1 (MEKK1)-c-Jun signaling. S1P also induced the nuclear translocation of the transcription factor MAL in a manner dependent on EGFR signaling. MAL and c-Jun stimulated the expression of the microRNAs miR-21 and miR-222, both of which target the metalloprotease inhibitor TIMP3, thus promoting metalloprotease activity. The metalloproteases ADAM10 and ADAM17 stimulated EGFR signaling by cleaving a membrane-anchored form of EGF to release the ligand. Our results outline a network by which S1P transactivates EGFR signaling through a complex mechanism involving feedback between several intra- and extracellular molecules to promote eyelid fusion in the developing rat.

A novel series of cyclane-aminol 10-hydroxycamptothecin (HCPT) analogs was designed and synthesized through the Mannich reaction using HCPT as the lead compound, such as 10-hydroxyl-9-L-prolinol (+) methylcamptothecin (PRPT), 10-hydroxyl-9-(4'-hydroxy) piperidinylmethylcamptothecin (PPPT), and 10-hydroxy-9-(4'-hydroxyethyl)-piperazinylmethycamptothecin (QPPT). Three kinds of new cyclane-aminols were introduced into the structure of HCPT, which modified strong cytotoxic HCPT into cyclane-aminol HCPT analogs with moderate cytotoxicity and improved selectivity toward DNA topoisomerase I inhibition in tumor cells. Special metabolic pathways for cyclane-aminol HCPT analogs in rats were discovered, which differed from other HCPT analogs. Cyclane-aminol HCPT analogs can capture O2 and cause an increase in intracellular hydrogen peroxide levels with selective induction of apoptosis in tumor cells rather than in normal peripheral blood mononuclear cells. Among them, PPPT has a much better druggability than topotecan (TPT) and has the potential to be developed into an antitumor agent.

The desired starting material for semi-solid processing is the semi-solid slurry in which the solid phase is present as fine and globular particles. A modified solid–liquid mixing (SLM) is reported wherein semi-solid slurry can be produced by mixing a solid alloy block into a liquid alloy, and mechanical vibration is utilized to enhance the mixing. Effects such as liquid alloy temperature, mass ratio, and mixing intensity on the microstructure and the cooling curves during SLM were evaluated. 2D and 3D microstructure analysis of treated A356 aluminum alloy shows that microstructure can be refined significantly with a considerable morphology change in primary Al phase. It is critical that the temperature of mixture after mixing is lower than its liquidus temperature to obtain a valid SLM process. Specially, mixing intensity is identified as a primary factor for a favorable microstructure of semi-solid slurry.

In this study, the formation of nondendritic structures in the primary phase of magnesium alloy solidified under oscillation and ultrasonic vibration was investigated by numerical simulation and experimentally. The growth and motion of a dendrite during solidification was simulated by a combination of the lattice Boltzmann method and the phase-field method. The simulation and experimental results indicated that higher oscillation amplitudes and acoustic streaming made the microstructures change from dendritic to nondendritic in the α-Mg primary phases. A sufficient shear stress and an appropriate flow time in the barrel should be satisfied when a given inclined angle is selected. The effects of the flow and the thermal field on the nucleation behavior, the constitutional undercooling, and the growth morphology are also discussed. It was found that a high shear rate and high turbulence can help homogenize the temperature and the concentration fields and collide and rotate the α-Mg primary phases.

The inhibitory co-receptor programmed death 1 (PD-1, encoded by pdcd1) and its two ligands PD-L1 and PD-L2 comprise an important immune inhibitory signaling pathway for defense against microbes and for self-tolerance. Unlike other members of the B7-CD28 family, expression of PD-L1 and PD-L2 is not limited to the immune system. In this study, we determined that a polyclonal antibody (pAb) (R&D Systems) against extracellular domains of mouse PD-L2 (mPD-L2) could recognize antigen(s) in diverse mouse tissues, including the anterior and intermediate pituitary gland, olfactory bulbs and olfactory epithelium, tongue epithelium, keratinized epithelial cells and skin and whisker hair follicles. These findings differed from previous reports of mPD-L2 localization. Reverse transcription PCR and Western blot analyses, however, were unable to detect any mPD-L2 transcripts or proteins of the 25-kD predicted molecular weight in RNA and protein extracts, respectively, from the above tissues, suggesting that the anti-mPD-L2 pAb cross-reacts with certain novel antigen(s). Developmental studies revealed that the earliest expression of mPD-L2-like antigen was in the olfactory epithelium at embryonic day 12.5 (E12.5). At E14.5, mPD-L2-like antigen was present in the skin, tongue and follicles of the skin and whiskers. The distribution patterns of mPD-L2-like antigen remained similar from E18.5 to adulthood. The results of bioinformatic analysis and other experiments suggested neural cell adhesion molecule and hemicentin-1 as candidate proteins with cross-reactivity to the anti-mPD-L2 pAb. These results demonstrate that care is required in interpreting staining patterns generated when anti-PD-L2 pAb is used to locate PD-L2-expressing cells in the central nervous system and epithelial tissues, such as the olfactory epithelium. In addition, this anti-PD-L2 pAb may be used as an alternative antibody for labeling the olfactory epithelium during embryonic development in mice.

The experiment of the rheocasting-rolling for semi-solid magnesium was carried out on the equipment made by ourselves in our laboratory. Semi-solid AZ91D magnesium slurry was prepared by cooling slope and mchanical sirring The evolution of microstructure under different technological parameters were studied. The results show that the technological parameters have great influence on the microstructure of the semi-solid magnesium slurry. The results show that the optimum parameters of slope method were: pouring temperature 630 degrees�� angle of slope 60°�� length of slope 0.570m. the optimum parameters of slope method were: stirring rate 500r/min ; holding time 10min; stirring time 15min; casting temperature 560 degrees.

Cyclin-dependent kinase 1 (CDK1) is the only necessary CDK in the cell proliferation process and a new target in the research and development of anti-cancer drugs. Natural flavones are selective CDK1 inhibitors which can suppress the proliferation of cancer cells. However, their bioavailability is poor. To solve these problems, 6 Scutellaria flavones were isolated from hydrolyzed products of Scutellaria baicalensis and used as lead compounds, 18 Scutellaria flavones cyclane-aminol Mannich base derivatives were semi-synthesized and their biological activity as novel CDK1 inhibitors was evaluated. Results indicated that the biological activity of 8-Hydroxypiperidinemethyl-baicalein (BA-j) is the highest among these compounds. BA-j is a selective CDK1 inhibitor, and has broad-spectrum anti-proliferative activity in human cancer cells (IC50 12.3μM). BA-j can capture oxygen free radicals (.O2(-)) and selectively increase intracellular H2O2 level in cancer cells and activated lymphocytes, thus inducing their apoptosis rather than in normal cells. These findings suggest that BA-j selectively induces apoptosis in cancer and activated lymphocyte by controlling intracellular H2O2 level, and can be developed into a novel anti-proliferative agent for the treatment of cancer, AIDS, and some immune diseases.

The inflammatory response following spinal cord injury (SCI) involves the activation of resident microglia and the infiltration of macrophages. Macrophages and microglia can be polarized into the classically activated proinflammatory M1 phenotype or the alternatively activated anti-inflammatory M2 phenotype. Programmed cell death 1 (PD-1) is a critical immune inhibitory receptor involved in innate and adaptive immune responses. However, whether PD-1 is involved in the modulation of macrophage/microglial polarization is unknown. In this study, the mRNA levels of pd1 gradually increased after SCI, and PD-1 protein was found in macrophages/microglia in injured spinal cord sections. PD-1 knockout (KO) mice showed poor locomotor recovery after spinal cord crushing compared with wild-type mice. M1-type macrophages/microglia accumulated in greater numbers in the injured spinal cord of PD-1-KO mice. Under polarized stimulation, induced expression of PD-1 occurred in cultured macrophages and microglia. PD-1 suppressed M1 polarization by reducing the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and promoted M2 polarization by increasing STAT6 phosphorylation. In PD-1-KO mice, the M1 response was enhanced via the activation of STAT1 and nuclear factor-kappa B. Furthermore, PD-1 played various roles in phagocytosis in macrophages and microglia. Therefore, our results suggest that PD-1 signaling plays an important role in the regulation of macrophage/microglial polarization. Thus, deregulated PD-1 signaling may induce the polarization of macrophages/microglia toward the M1 phenotype. Overall, our results provide new insights into the modulatory mechanisms of macrophage/microglial polarization, thereby possibly facilitating the development of new therapies for SCI via the regulation of macrophage/microglial polarization through PD-1 signaling. Electronic supplementary material The online version of this article (doi:10.1007/s13311-013-0254-x) contains supplementary material, which is available to authorized users.