Integrated GelMA and interleukin 8-loaded liposome composite scaffold for endogenous BMSCs recruitment in bone repair.

Bone repair strategies, based on endogenous stem cell recruitment, can effectively avoid immune rejection and the low utilization of exogenous stem cells. Endogenous stem cells can be recruited to the implantation site by loading chemokines onto bone tissue-engineered scaffolds. However, challenges such as unstable chemokine activity and easy inactivation after implantation remain significant. In the present study, composite fiber scaffolds ((IL8@LIP)-GelMA) consisting of Interleukin 8 (IL8) -loaded liposomes and GelMA were constructed by electrospinning and photocrosslinking, and its ability to recruit bone marrow-derived mesenchymal stem cells (BMSCs) and immunomodulatory effect was investigated. Compared to GelMA loaded directly with IL8, scaffolds of (IL8@LIP)-GelMA demonstrated superior protection of IL8 activity, ensuring a slow and continuous release. Both in vivo and in vitro experiments demonstrated that the (IL8@LIP)-GelMA scaffolds effectively recruited BMSCs to the desired sites. Additionally, the (IL8@LIP)-GelMA scaffolds exhibited the capacity to recruit more macrophages to the implantation site. Importantly, they promoted the polarization of macrophages toward the M2 anti-inflammatory phenotype, facilitating the transition from the inflammatory stage to the tissue repair stage. Therefore, (IL8@LIP)-GelMA scaffolds show great potential for cell-free tissue engineering applications and provide insights into the loading mode of growth factors in scaffolds.

Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies.

Ketamine, a commonly used general anesthetic, can produce rapid and sustained antidepressant effect. However, the efficacy and safety of the perioperative application of ketamine on postoperative depression remains uncertain. We performed a meta-analysis to determine the effect of perioperative intravenous administration of ketamine on postoperative depression. Randomized controlled trials comparing ketamine with placebo in patients were included. Primary outcome was postoperative depression scores. Secondary outcomes included postoperative visual analog scale (VAS) scores for pain and adverse effects associated with ketamine. Fifteen studies with 1697 patients receiving ketamine and 1462 controls were enrolled. Compared with the controls, the ketamine group showed a reduction in postoperative depression scores, by a standardized mean difference (SMD) of -0.97, 95% confidence interval [CI, -1.27, -0.66], P < 0.001, I2 = 72% on postoperative day (POD) 1; SMD-0.65, 95% CI [-1.12, -0.17], P < 0.001, I2 = 94% on POD 3; SMD-0.30, 95% CI [-0.45, -0.14], P < 0.001, I2 = 0% on POD 7; and SMD-0.25, 95% CI [-0.38, -0.11], P < 0.001, I2 = 59% over the long term. Ketamine reduced VAS pain scores on POD 1 (SMD-0.93, 95% CI [-1.58, -0.29], P = 0.005, I2 = 97%), but no significant difference was found between the two groups on PODs 3 and 7 or over the long term. However, ketamine administration distinctly increased the risk of adverse effects, including nausea and vomiting (risk ratio [RR] 1.40, 95% CI [1.12, 1.75], P = 0.003, I2 = 30%), headache (RR 2.47, 95% CI [1.41, 4.32], P = 0.002, I2 = 19%), hallucination (RR 15.35, 95% CI [6.24, 37.34], P < 0.001, I2 = 89%), and dizziness (RR 3.48, 95% CI [2.68, 4.50], P < 0.001, I2 = 89%) compared with the controls. In conclusion, perioperative application of ketamine reduces postoperative depression and pain scores with increased risk of adverse effects.

Feasibility study of ADCs targeting TROP-2, HER2, and CD46 in Ductal Adenocarcinoma and Intraductal Carcinoma of the prostate.

BACKGROUND: Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma of the Prostate (IDC-P) respond poorly to all the currently available conventional therapies. Given their accurate and efficient elimination of cancer cells, Antibody-Drug Conjugates (ADCs) have become one of the most promising anticancer treatments. However, no ADCs have so far been approved for Prostate Cancer (PCa) treatment. This study investigated TROP-2, HER2, and CD46 expression in DAC/IDC-P samples, indirectly analyzing their preliminary feasibility as therapeutic targets for future treatment of the two conditions. PATIENTS AND METHODS: We conducted a retrospective study involving 184 participants (87 DAC/IDC-P patients and 97 Prostatic Acinar Adenocarcinoma (PAC) patients with a Gleason score ≥ 8) without prior treatment between August 2017 and August 2022. Immunohistochemical staining was employed to detect the differential protein expressions of TROP-2, HER2, and CD46 in DAC/IDC-P, PAC, and normal prostate tissues. RESULTS: Compared to pure PAC tissues, TROP-2 expression was significantly higher in DAC/IDC-P and DAC/IDC-P-adjacent PAC tissues (H-score 68.8 vs. 43.8, p < 0.001, and 59.8 vs. 43.8, p = 0.022, respectively). No significant differences in HER2 expression were observed across different cancer tissues. Compared to both DAC/IDC-P-adjacent PAC and pure PAC tissues, CD46 expression was significantly higher in DAC/IDC-P tissues (42.3 vs. 28.6, p = 0.041, and 42.3 vs. 24.3, p = 0.0035, respectively). CONCLUSIONS: Herein, TROP-2 and CD46 expression was higher in DAC/IDC-P tissues than in pure PAC and normal prostate tissues. This finding implies that ADCs targeting the two proteins hold significant promise as potential future treatments for DAC/IDC-P.

Key role of the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve in demyelination of the cuprizone-treated mouse brain.

Multiple sclerosis (MS) is the most common demyelinating disease that attacks the central nervous system. Dietary intake of cuprizone (CPZ) produces demyelination resembling that of patients with MS. Given the role of the vagus nerve in gut-microbiota-brain axis in development of MS, we performed this study to investigate whether subdiaphragmatic vagotomy (SDV) affects demyelination in CPZ-treated mice. SDV significantly ameliorated demyelination and microglial activation in the brain compared with sham-operated CPZ-treated mice. Furthermore, 16S ribosomal RNA analysis revealed that SDV significantly improved the abnormal gut microbiota composition of CPZ-treated mice. An untargeted metabolomic analysis demonstrated that SDV significantly improved abnormal blood levels of metabolites in CPZ-treated mice compared with sham-operated CPZ-treated mice. Notably, there were correlations between demyelination or microglial activation in the brain and the relative abundance of several microbiome populations, suggesting a link between gut microbiota and the brain. There were also correlations between demyelination or microglial activation in the brain and blood levels of metabolites. Together, these data suggest that CPZ produces demyelination in the brain through the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve.

Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase.

Epidemiological studies suggest that exposure to herbicides during pregnancy might increase risk for autism spectrum disorder (ASD) in offspring. However, the precise mechanisms underlying the risk of ASD by herbicides such as glyphosate remain unclear. Soluble epoxide hydrolase (sEH) in the metabolism of polyunsaturated fatty acids is shown to play a key role in the development of ASD in offspring after maternal immune activation. Here, we found ASD-like behavioral abnormalities in juvenile offspring after maternal exposure to high levels of formulated glyphosate. Furthermore, we found higher levels of sEH in the prefrontal cortex (PFC), hippocampus, and striatum of juvenile offspring, and oxylipin analysis showed decreased levels of epoxy-fatty acids such as 8 (9)-EpETrE in the blood, PFC, hippocampus, and striatum of juvenile offspring after maternal glyphosate exposure, supporting increased activity of sEH in the offspring. Moreover, we found abnormal composition of gut microbiota and short-chain fatty acids in fecal samples of juvenile offspring after maternal glyphosate exposure. Interestingly, oral administration of TPPU (an sEH inhibitor) to pregnant mothers from E5 to P21 prevented ASD-like behaviors such as social interaction deficits and increased grooming time in the juvenile offspring after maternal glyphosate exposure. These findings suggest that maternal exposure to high levels of glyphosate causes ASD-like behavioral abnormalities and abnormal composition of gut microbiota in juvenile offspring, and that increased activity of sEH might play a role in ASD-like behaviors in offspring after maternal glyphosate exposure. Therefore, sEH may represent a target for ASD in offspring after maternal stress from occupational exposure to contaminants.

(R)-ketamine ameliorates demyelination and facilitates remyelination in cuprizone-treated mice: A role of gut-microbiota-brain axis.

Multiple sclerosis (MS) is the most common demyelinating disease that attacks the central nervous system. We recently reported that the new antidepressant (R)-ketamine could ameliorate the disease progression in experimental autoimmune encephalomyelitis model of MS. Cuprizone (CPZ) has been used to produce demyelination which resembles demyelination in MS patients. This study was undertaken to investigate whether (R)-ketamine could affect demyelination in CPZ-treated mice and remyelination after CPZ withdrawal. Repeated treatment with (R)-ketamine (10 mg/kg/day, twice weekly, for 6 weeks) significantly ameliorated demyelination and activated microglia in the brain compared with saline-treated mice. Furthermore, pretreatment with ANA-12 (TrkB antagonist) significantly blocked the beneficial effects of (R)-ketamine on the demyelination and activated microglia in the brain of CPZ-treated mice. The 16S rRNA analysis showed that (R)-ketamine significantly improved abnormal composition of gut-microbiota and decreased levels of lactic acid of CPZ-treated mice. In addition, there were significant correlations between demyelination (or microglial activation) in the brain and the relative abundance of several microbiome, suggesting a link between gut microbiota and brain. Interestingly, (R)-ketamine could facilitate remyelination in the brain after CPZ withdrawal. In conclusion, the study suggests that (R)-ketamine could ameliorate demyelination in the brain of CPZ-treated mice through TrkB activation, and that gut-microbiota-microglia crosstalk may play a role in the demyelination of CPZ-treated mice. Therefore, it is likely that (R)-ketamine could be a new therapeutic drug for MS.

Three-dimensional morphology measurement of underwater objects based on the photoacoustic effect.

Complexities of the underwater environment can seriously affect many underwater detection means, especially the influence of light scattering by water. To solve this problem, a three-dimensional (3D) morphology measurement method is proposed based on the photoacoustic effect. In this method, a measurement object is irradiated with pulsed laser light to produce ultrasonic waves via the photoacoustic effect. A probe collects the ultrasonic signal and subsequent data processing can yield complete object detection. This approach can make full use of the advantages of high precision and good directivity of laser ranging and completely avoid the influence on the laser of backscattering from water. The results yield a displacement measurement accuracy of less than 0.5 mm and an average error of 3D reconstruction of 0.21 mm, demonstrating great application potential.

A role of the subdiaphragmatic vagus nerve in depression-like phenotypes in mice after fecal microbiota transplantation from Chrna7 knock-out mice with depression-like phenotypes.

The α7 subtype of the nicotinic acetylcholine receptor (α7 nAChR: coded by Chrna7) regulates the cholinergic ascending anti-inflammatory pathway involved in depression. We previously reported that Chrna7 knock-out (KO) mice show depression-like phenotypes through systemic inflammation. In this study, we investigated whether fecal microbiota transplantation (FMT) from Chrna7 KO mice causes depression-like phenotypes in mice treated with an antibiotic cocktail (ABX). Chrna7 KO mice with depression-like phenotypes show an abnormal gut microbiota composition, although the alpha diversity and beta diversity were not altered. FMT from Chrna7 KO mice caused depression-like phenotypes, systemic inflammation, and downregulation of synaptic proteins in the prefrontal cortex (PFC) in the ABX-treated mice compared to FMT from the control mice. The Principal component analysis based on the OTU level showed that the FMT group from the KO mice were different from the FMT group from the control mice. We found differences in abundance for several bacteria in the FMT group from the KO mice at the taxonomic level when compared with the other group. Interestingly, subdiaphragmatic vagotomy significantly blocked the development of depression-like phenotypes in the ABX-treated mice after FMT from Chrna7 KO mice. These data suggest that FMT from Chrna7 KO mice produce depression-like phenotypes in ABX-treated mice via the subdiaphragmatic vagus nerve. The brain-gut-microbiota axis association with the subdiaphragmatic vagus nerve plays an important role in the development of depression.

Rapid-acting and long-lasting antidepressant-like action of (R)-ketamine in Nrf2 knock-out mice: a role of TrkB signaling.

The transcription nuclear factor-erythroid factor 2-related factor 2 (Nrf2) plays a key role in inflammation that is involved in depression. We previously reported that Nrf2 knock-out (KO) mice exhibit depression-like phenotypes through systemic inflammation. (R)-ketamine, an enantiomer of ketamine, has rapid-acting and long-lasting antidepressant-like effects in rodents. We investigated whether (R)-ketamine can produce antidepressant-like effects in Nrf2 KO mice. Effects of (R)-ketamine on the depression-like phenotypes in Nrf2 KO mice were examined. Furthermore, the role of TrkB in the antidepressant-like actions of (R)-ketamine was also examined. In the tail-suspension test (TST) and forced swimming test (FST), (R)-ketamine (10 mg/kg) significantly attenuated the increased immobility times of TST and FST in the Nrf2 KO mice. In the sucrose preference test (SPT), (R)-ketamine significantly ameliorated the reduced preference of SPT in Nrf2 KO mice. Decreased expression of synaptic proteins (i.e., GluA1 and PSD-95) in the medial prefrontal cortex (mPFC) of Nrf2 KO mice was significantly ameliorated after a single injection of (R)-ketamine. Furthermore, the pre-treatment with the TrkB antagonist ANA-12 (0.5 mg/kg) significantly blocked the rapid and long-lasting antidepressant-like effects of (R)-ketamine in Nrf2 KO mice. Furthermore, ANA-12 significantly antagonized the beneficial effects of (R)-ketamine on decreased expression of synaptic proteins in the mPFC of Nrf2 KO mice. These findings suggest that (R)-ketamine can produce rapid and long-lasting antidepressant-like actions in Nrf2 KO mice via TrkB signaling.

Splenic NKG2D confers resilience versus susceptibility in mice after chronic social defeat stress: beneficial effects of (R)-ketamine.

The spleen is a large immune organ that plays a key role in the immune system. The precise molecular mechanisms underlying the relationship between the spleen and stress-related psychiatric disorders are unknown. Here we investigated the role of spleen in stress-related psychiatric disorders. FACS analysis was applied to determine the contribution of the spleen to susceptibility and resilience in mice that were subjected to chronic social defeat stress (CSDS). We found a notable increase in splenic volume and weight in CSDS-susceptible mice compared to control (no CSDS) mice and CSDS-resilient mice. The number of granulocytes, but not of T cells and B cells, in the spleen of susceptible mice was higher than in the spleen of both control and resilient mice. Interestingly, NKG2D (natural killer group 2, member D) expression in the spleen of CSDS-susceptible mice was higher than that in control mice and CSDS-resilient mice. In addition, NKG2D expression in the spleen of patients with depression was higher than that in controls. Both increased splenic weight and increased splenic NKG2D expression in CSDS-susceptible mice were ameliorated after a subsequent administration of (R)-ketamine. The present findings indicate a novel role of splenic NKG2D in stress susceptibility versus resilience in mice subjected to CSDS. Furthermore, abnormalities in splenic functions in CSDS-susceptible mice were ameliorated after subsequent injection of (R)-ketamine. Thus, the brain-spleen axis might, at least in part, contribute to the pathogenesis of stress-related psychiatric disorders such as depression.

Effects of bromate on life history parameters, swimming speed and antioxidant biomarkers in Brachionus calyciflorus.

The baking industries and disinfection of tap water released a considerable amount of bromate into surface water, which has been reported as a carcinogenic compound to mammals. Rotifers play an important role in freshwater ecosystems and are model organisms to assess environmental contamination. In the present study, the effects of different concentrations (0.001, 0.01, 0.1, 1, 10, 100 and 200 mg/L) of bromate on the life-table and population growth parameters were investigated in the rotifer Brachionus calyciflorus. The results showed that the 24-h LC50 of bromate to B. calyciflorus was 365.29 mg/L (95%Cl: 290.37-480.24). Treatments with 0.01, 10 and 200 mg/L bromate shorten the reproductive period. High levels of bromate (100 and 200 mg/L) significantly decreased net reproductive rate, intrinsic rate of population increase, life span, mictic rate of B. calyciflorus. To investigate the underlying mechanisms, swimming speed and antioxidative biomarkers were compared between bromate treatments and the control. The results showed that glutathione (GSH) and malondialdehyde (MDA) contents, total superoxide dismutase (T-SOD) and peroxidase (POD) activities decreased significantly in response to bromate exposure and the reasons required further investigation. Treatments with 0.001-200 mg/L bromate all significantly reduced swimming linear speed to rotifer larvae and treatments with 100-200 mg/L bromate significantly suppressed the swimming linear speed of adult rotifer. These changes would reduce filtration of algal food and could explain the decreased survival and reproduction. Overall, bromate may not show acute toxicity to rotifers, but still have potential adverse effects on rotifer behavior, which may then influence the community structure in aquatic ecosystems.

A complete atmospheric emission inventory of F, As, Se, Cd, Sb, Hg, Pb, and U from coal-fired power plants in Anhui Province, eastern China.

Anhui Province is the most important energy production base for eastern China. Many large pithead coal-fired power plants are being operated in the coal-rich Huainan and Huaibei coalfields in northern Anhui. To assess the environmental risks of local coal-fired power plants, a complete atmospheric emission inventory of F, As, Se, Cd, Sb, Hg, Pb, and U from coal-fired power plants in Anhui was compiled by a simple mass-balance-based method. The results indicated that the atmospheric emissions of F, As, Se, Cd, Sb, Hg, Pb, and U in 2017 from the Anhui coal-fired power plants were 578 t, 2.01 t, 15.3 t, 0.57 t, 0.18 t, 2.80 t, 23.7 t, and 0.099 t, respectively. The emission factor is the major contributor to the uncertainties in this inventory. With increasing energy demand by the more developed eastern China region, the atmospheric emissions of volatile hazardous elements will continue to increase in the near future.

Ingestion of Lactobacillus intestinalis and Lactobacillus reuteri causes depression- and anhedonia-like phenotypes in antibiotic-treated mice via the vagus nerve.

BACKGROUND: The brain-gut-microbiota axis plays a role in the pathogenesis of stress-related disorders such as depression. In this study, we examined the effects of fecal microbiota transplantation (FMT) in mice with antibiotic-treated microbiota depletion. METHODS: The fecal microbiota was obtained from mice subjected to chronic social defeat stress (CSDS) and control (no CSDS) mice. FMT from these two groups was performed to antibiotic-treated mice. 16S rRNA analysis was performed to examine the composition of gut microbiota. Furthermore, the effects of subdiaphragmatic vagotomy in depression-like phenotypes after ingestion of microbes were examined. RESULTS: The ingestion of fecal microbiota from CSDS-susceptible mice resulted in an anhedonia-like phenotype, higher plasma levels of interleukin-6 (IL-6), and decreased expression of synaptic proteins in the prefrontal cortex (PFC) in antibiotic-treated mice but not in water-treated mice. 16S rRNA analysis suggested that two microbes (Lactobacillus intestinalis and Lactobacillus reuteri) may be responsible for the anhedonia-like phenotype in antibiotic-treated mice after FMT. Ingestion of these two microbes for 14 days led to depression- and anhedonia-like phenotypes, higher plasma IL-6 levels, and decreased expression of synaptic proteins in the PFC of antibiotic-treated mice. Interestingly, subdiaphragmatic vagotomy significantly blocked the development of behavioral abnormalities, elevation of plasma IL-6 levels, and downregulation of synaptic proteins in the PFC after ingestion of these two microbes. CONCLUSIONS: These findings suggest that microbiota depletion using an antibiotic cocktail is essential for the development of FMT-induced behavioral changes and that the vagus nerve plays a key role in behavioral abnormalities in antibiotic-treated mice after the ingestion of L. intestinalis and L. reuteri. Therefore, it is likely that the brain-gut-microbiota axis participates in the pathogenesis of depression via the vagus nerve.

Health risk assessment of potentially harmful elements in subsidence water bodies using a Monte Carlo approach: An example from the Huainan coal mining area, China.

Enrichment of potentially harmful elements in surface water results in ecological risk to the surrounding environment. Assessing the environmental risk of these elements is of great importance. In this study, surface water samples from 6 different subsidence water bodies in the Huainan coal mining area were collected. The concentrations of Cu, Ni, Pb, Cd, Co, Cr, V, Fe, Mn and Zn were measured by atomic absorption spectrophotometry, and those of As and Hg were analyzed by atomic fluorescence spectrometry. Then, human health risks through the ingestion and dermal contact pathways were assessed and analyzed on the basis of a Monte Carlo simulation. The mean and 95th percentile risks were reported. The results showed that the total carcinogenic risk values in every subsidence water body summed for Cr, Ni and As via two exposure pathways were greater than the maximum acceptable level (1 × 10-4), and Xinji'er water body had the highest carcinogenic risk. Among three elements, Ni was the highest contributor to carcinogenic risk. All non-carcinogenic health risk (hazard quotients) values except for one water area of Co (Xinji'er) were less than 1; however, the total non-carcinogenic health risks of two water bodies (Xinji'er, Xinjiyi) summed for all the elements based on mean concentrations were higher than 1. Xinji'er had the highest hazard index. The extent of the impacts of the total hazard quotients followed the order of Co > As > Cd > Hg > Pb > V >Fe > Ni > Mn > Zn > Cr. Furthermore, the total hazard quotients of Co and As via ingestion pathway summed for the six subsidence water areas were greater than 1, which should be a concern.

Cellular prion protein is involved in decidualization of mouse uterus.

Prion protein (PrP) is encoded by a single copy gene Prnp in many cell and tissue types. PrP is very famous for its infectious conformers (PrPSC) resulting in transmissible spongiform encephalopathies. At present, physiological functions of its cellular isoform (PrPC) remain ambiguous. Although PrPC expression has been found in uterus, whether it functions in maternal-fetal dialogue during early pregnant is unknown. In this study, we examined PrPC mRNA and protein in the uterus of peri-implantation mice, and found that they were expressed with a spatiotemporal dynamic pattern. Interestingly, PrPC was significantly increased in the decidual zones around the implanting embryos at the implantation window stage. To further demonstrate that PrPC is involved in the decidualization of mouse uterus during embryo implantation, we constructed the artificial decidualization models and the delayed implantation models. Once the pseudopregnant mice were artificially induced to decidualization, the PrPC expression then increased significantly in the decidua zone. And also, if the delayed implantation embryos were allowed to implant, PrPC protein was also simultaneously improved in stromal cells surrounding the implanting embryos. Moreover, PrPC expression can be inhibited by progesterone but upregulated by estrogen in mouse uterus. These results suggest that PrPC may play an important role in embryo implantation and decidualization.

Effects of coal spoil amendment on heavy metal accumulation and physiological aspects of ryegrass (Lolium perenne L.) growing in copper mine tailings.

Copper mine tailings pose many threats to the surrounding environment and human health, and thus, their remediation is fundamental. Coal spoil is the waste by-product of coal mining and characterized by low levels of metals, high content of organic matter, and many essential microelements. This study was designed to evaluate the role of coal spoil on heavy uptake and physiological responses of Lolium perenne L. grown in copper mine tailings amended with coal spoil at rates of 0, 0.5, 1, 5, 10, and 20%. The results showed that applying coal spoil to copper mine tailings decreased the diethylenetriaminepentaacetic acid (DTPA)-extractable Cd, Cu, Pb, and Zn contents in tailings and reduced those metal contents in both roots and shoots of the plant. However, application of coal spoil increased the DTPA-extractable Cr concentration in tailings and also increased Cr uptake and accumulation by Lolium perenne L. The statistical analysis of physiological parameters indicated that chlorophyll and carotenoid increased at the lower amendments of coal spoil followed by a decrease compared to their respective controls. Protein content was enhanced at all the coal spoil amendments. When treated with coal spoil, the activities of superoxide dismutases (SOD), peroxidase (POD), and catalase (CAT) responded differently. CAT activity was inhibited, but POD activity was increased with increasing amendment ratio of coal spoil. SOD activity increased up to 1% coal spoil followed by a decrease. Overall, the addition of coal spoil decreased the oxidative stress in Lolium perenne L., reflected by the reduction in malondialdehyde (MDA) contents in the plant. It is concluded that coal spoil has the potential to stabilize most metals studied in copper mine tailings and ameliorate the harmful effects in Lolium perenne L. through changing the physiological attributes of the plant grown in copper mine tailings.

[Role of cannabinoid receptor 1-mediated synaptic plasticity in neuropathic pain and associated depression].

Neuropathic pain is a class of pain caused by an injury or diseases of the somatosensory system and characterized by spontaneous pain, allodynia, and hyperalgesia. It is well established that central sensitization is one of the key mechanisms underlying the development and maintenance of neuropathic pain. Cannabinoid receptor 1 (CB1R) of endocannabinoid system modulates synaptic transmission, regulates synaptic plasticity, inhibits central sensitization, and thus attenuates neuropathic pain. Recent studies have shown that activation of CB1R also involves in the relief of neuropathic pain-induced depression.

Spectroscopic studies on the interaction mechanisms of safranin T with herring sperm DNA using acridine orange as a fluorescence probe.

Under the condition of physiological pH environment (pH = 7.40), the interactions of safranin T (ST) with herring sperm DNA were studied by means of spectral methods using acridine orange (AO) as a fluorescence probe. The spectroscopic characteristics of DNA-AO in the case of ST (along with the increase of concentration) were observed in an aqueous medium. The binding constants for ST stranded DNA and competitive bindings of ST interacting with DNA-AO systems were examined by fluorescence spectra, and the binding mechanism of ST with DNA was researched via viscosity measurements. All the testimony manifested that bonding modes between ST and DNA were evidenced to be intercalative binding and electrostatic binding, and the combining constant of ST with DNA was obtained. The binding of ST to DNA was driven by entropy and enthalpy through the calculated thermodynamic parameters (Δr Hm (Ó¨), Δr Sm and Δr Gm (Ó¨)).

UBE2J1 promotes ALV-A proviral DNA synthesis through the STAT3/IRF1 signaling pathway.

The ubiquitin-binding enzyme E2J1 is located on the endoplasmic reticulum membrane. It plays a role in transport throughout the process of ubiquitination. In mammals, UBE2J1 can promote RNA virus replication. However, the biological function of chicken UBE2J1 is unclear. In this study, chicken UBE2J1 was cloned for the first time, and UBE2J1 overexpression and shRNA knockdown plasmids were constructed. In chicken embryo fibroblasts, overexpression of UBE2J1 promoted the replication of subtype A avian leukosis virus, while knockdown of UBE2J1 inhibited the replication of ALV-A virus. In addition, we divided virus replication into virus adsorption and invasion into DF-1 cells, synthesis of proviral DNA, and release of viral particles. UBE2J1 promoted the replication of ALV-A virus by promoting the synthesis of proviral DNA. This result was caused by UBE2J1 inhibiting the production of interferon by inhibiting the STAT3/IRF1 pathway. We mutated ser at position 184 of UBE2J1 to Gly and found that this site plays a role as the phosphorylation site of UBE2J1. We confirmed that UBE2J1 promotes ALV-A replication in chicken embryo fibroblasts by inhibiting the STAT3/IRF1 pathway. This study provides new ideas and insights into ubiquitin-related proteins and antiviral immunity.