Composite coatings consisting of carbon and polytetrafluoroethylene(PTFE) were prepared on Ti alloy substrate by a simple two-step process of hydrothermal and impregnation. The morphology, composition, hydrophobic and...Composite coatings consisting of carbon and polytetrafluoroethylene(PTFE) were prepared on Ti alloy substrate by a simple two-step process of hydrothermal and impregnation. The morphology, composition, hydrophobic and corrosion properties of the composite coatings were characterized by scanning electron microscopy(SEM), Fourier transform infrared spectroscopy(FTIR), water contact angle method, X-ray photoelectron spectroscopy(XPS) and electrochemical technique, respectively. The effect of PTFE content on the corrosion properties of the composite coatings was studied. It is found that the composite coating film exhibits a full coverage with uniformly distributed PTFE when 0.1 mol/L of glucose is used as carbon source and 20 wt.% PTFE suspension as impregnating solution. The coating with 20 wt.% PTFE has a good bonding strength with Ti plate and exhibits excellent hydrophobic property with a water contact angle of 142.3° as well as superior corrosion resistance with corrosion current density as low as 0.0045 μA/cm^2. With regard to its excellent hydrophobicity and corrosion resistance, the carbon-PTFE composite coating may find potential application in automobiles and metal corrosion industries.展开更多
BACKGROUND In malignant tumors,inflammation plays a vital role in the development,invasion,and metastasis of cancer cells.Diffuse large B-cell lymphoma(DLBCL),the most common malignant proliferative disease of the lym...BACKGROUND In malignant tumors,inflammation plays a vital role in the development,invasion,and metastasis of cancer cells.Diffuse large B-cell lymphoma(DLBCL),the most common malignant proliferative disease of the lymphatic system,is commonly associated with inflammation.The international prognostic index(IPI),which includes age,lactate dehydrogenase(LDH),number of extranodal lesions,Ann Arbor score,and Eastern Cooperative Oncology Group(ECOG)score,can evaluate the prognosis of DLBCL.However,its use in accurately identifying highrisk patients and guiding treatment is poor.Therefore,it is important to find novel immune markers in predicting the prognosis of DLBCL patients.AIM To determine the association between the systemic immune inflammation index(SII),ratio of lymphocytes to monocytes(LMR),ratio of LMR to LDH(LMR/LDH),and prognosis of patients with DLBCL.METHODS A total of 68 patients diagnosed with DLBCL,treated in our hospital between January 2016 and January 2020,were included.χ2 test,Pearson’s R correlation,Kaplan Meier curves,and Cox proportional risk regression analysis were used.The differences in the SII,LMR,and LMR/LDH among patients with different clinicopathological features were analyzed.The differences in progression-free survival time among patients with different SII,LMR,and LMR/LDH expressions and influencing factors affecting the prognosis of DLBCL patients,were also analyzed.RESULTS The LMR and LMR/LDH in patients with Ann Arbor stage III–IV,ECOG score≥2,and SII,IPI score 2–5 were significantly higher than those of patients with Ann Arbor stage I-II and ECOG score<2(P<0.05).Patients with high SII,LMR,and LMR/LDH had progression-free survival times of 34 mo(95%CI:32.52–38.50),35 mo(95%CI:33.42–36.58)and 35 mo(95%CI:33.49–36.51),respectively,which were significantly lower than those with low SII,LMR,and LMR/LDH(P<0.05);the SII,LMR,and LMR/LDH were positively correlated(P<0.05).Cox proportional risk regression analysis showed that the SII,LMR,and LMR/LDH were influencing factors for the prognosis of DLBCL patients(hazard ratio=1.143,1.665,and 1.704,respectively;P<0.05).CONCLUSION The SII,LMR,and LMR/LDH are related to the clinicopathological features of DLCBL,and they also influence the prognosis of patients with the disease.展开更多
This paper presents a multi-mode control scheme for a soft-switched flyback converter to achieve high efficiency and excellent load regulation over the entire load range. At heavy load, critical conduction mode with v...This paper presents a multi-mode control scheme for a soft-switched flyback converter to achieve high efficiency and excellent load regulation over the entire load range. At heavy load, critical conduction mode with valley switching (CCMVS) is employed to realize soft switching so as to reduce turn-on loss of power switch as well as conducted electromagnetic interference (EMI). At light load, the converter operates in discontinuous conduction mode (DCM) with valley switching and adaptive off-time control (AOT) to limit the switching frequency range and maintain load regulation. At extremely light load or in standby mode, burst mode operation is adopted to provide low power consumption through reducing both switching frequency and static power dissipation of the controller. The multi-mode control is implemented by an oscillator whose pulse duration is adjusted by output feedback. An accurate valley switching control circuit guarantees the minimum turn-on voltage drop of power switch. The pro-totype of the controller IC was fabricated in a 1.5-μm BiCMOS process and applied to a 310 V/20 V, 90 W flyback DC/DC converter circuitry. Experimental results showed that all expected functions were realized successfully. The flyback converter achieved a high efficiency of over 80% from full load down to 2.5 W, with the maximum reaching 88.8%, while the total power consumption in standby mode was about 300 mW.展开更多
Climate warming is causing rapid permafrost degradation,including thaw-induced subsidence,potentially resulting in heightened carbon release.Nevertheless,our understanding of the levels and variations of carbon compon...Climate warming is causing rapid permafrost degradation,including thaw-induced subsidence,potentially resulting in heightened carbon release.Nevertheless,our understanding of the levels and variations of carbon components in permafrost,particularly during the degradation process,remains limited.The uncertainties arising from this process lead to inaccurate assessments of the climate effects during permafrost degradation.With vast expanses of permafrost in the Tibetan Plateau,there is limited research available on SOC components,particularly in the central Tibetan Plateau.Given remarkable variations in hydrothermal conditions across different areas of the Tibetan Plateau,the existing limited studies make it challenging to assess the overall SOC components in the permafrost across the Tibetan Plateau and simulate their future changes.In this study,we examined the properties of soil organic carbon(SOC)and microbial necromass carbon(MicrobialNC)in a representative permafrost thaw-subsidence area at the southern edge of continuous permafrost in the central Tibetan Plateau.The results indicate that prior to the thaw-subsidence,the permafrost had a SOC content of 72.68±18.53 mg g^(-1),with MicrobialNC accounting for 49.6%.The thaw-subsidence of permafrost led to a 56.4%reduction in SOC,with MicrobialNC accounting for 70.0%of the lost SOC.MicrobialNC constitutes the primary component of permafrost SOC,and it is the main component that is lost during thaw-subsidence formation.Changes in MicrobialNC are primarily correlated with factors pH,plant input,and microbial properties.The present study holds crucial implications for both the ecological and biogeochemical processes associated with carbon release from permafrost,and it furnishes essential data necessary for modeling the global response of permafrost to climate warming.Based on this study and previous research,permafrost thawing in the Tibetan Plateau causes substantial loss of SOC.However,there's remarkable heterogeneity in SOC component changes across different regions,warranting further in-depth investigation.展开更多
Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain la...Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain largely unknown.Our recent study indicated that C-X-C motif chemokine 13(CXCL13)and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation(SNL).Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains unknown.Here,we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after SNL.Knockdown of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic painrelated place avoidance behavior.Furthermore,electrophysiological recording from layer Ⅱ-Ⅲ neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents(sEPSCs),decreased the EPSC paired-pulse ratio,and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio,indicating enhanced glutamatergic synaptic transmission.Finally,superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs.Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmis sion induced by SNL.Collectively,these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.展开更多
Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also con- tribut...Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also con- tributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3-/- mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund's adjuvant-induced chronic inflammatory pain were reduced in Cxcr3-/- mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water (AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Further- more, touch-elicited itch (alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3-/- mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3-/- mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.展开更多
Chemokines and receptors have been implicated in the pathogenesis of chronic pain.Here,we report that spinal nerve ligation(SNL)increased CXCR3 expression in dorsal root ganglion(DRG)neurons,and intra-DRG injection of...Chemokines and receptors have been implicated in the pathogenesis of chronic pain.Here,we report that spinal nerve ligation(SNL)increased CXCR3 expression in dorsal root ganglion(DRG)neurons,and intra-DRG injection of Cxcr3 shRNA attenuated the SNL-induced mechanical allodynia and heat hyperalgesia.SNL also increased the m RNA levels of CXCL9,CXCL10,and CXCL11,whereas only CXCL10 increased the number of action potentials(APs)in DRG neurons.Furthermore,in Cxcr3^(-/-)mice,CXCL10 did not increase the number of APs,and the SNL-induced increase of the numbers of APs in DRG neurons was reduced.Finally,CXCL10 induced the activation of p38 and ERK in ND7-23 neuronal cells and DRG neurons.Pretreatment of DRG neurons with the P38 inhibitor SB203580 decreased the number of APs induced by CXCL10.Our data indicate that CXCR3,activated by CXCL10,mediates p38 and ERK activation in DRG neurons and enhances neuronal excitability,which contributes to the maintenance of neuropathic pain.展开更多
This study was performed to evaluate prostate-specific antigen-age volume (PSA-AV) scores in predicting prostate cancer (PCa) in a Chinese biopsy population. A total of 2355 men who underwent initial prostate biop...This study was performed to evaluate prostate-specific antigen-age volume (PSA-AV) scores in predicting prostate cancer (PCa) in a Chinese biopsy population. A total of 2355 men who underwent initial prostate biopsy from January 2006 to November 2015 in Huashan Hospital were recruited in the current study. The PSA-AV scores were calculated and assessed together with PSA and PSA density (PSAD) retrospectively. Among 2133 patients included in the analysis, 947 (44.4%) were diagnosed with PCa. The mean age, PSA, and positive rates of digital rectal examination result and transrectal ultrasound result were statistically higher in men diagnosed with PCa (all P 〈 0.05). The values of area under the receiver operating characteristic curves (AUCs) of PSAD and PSA-AV were 0.864 and 0.851, respectively, in predicting PCa in the entire population, both performed better than PSA (AUC = 0.805; P 〈 0.05). The superiority of PSAD and PSA-AV was more obvious in subgroup with PSA ranging from 2.0 ng ml^-1 to 20.0 ng ml^-1. A PSA-AV score of 400 had a sensitivity and specificity of 93.7% and 40.0%, respectively. In conclusion, the PSA-AV score performed equally with PSAD and was better than PSA in predicting PCa. This indicated that PSA-AV score could be a useful tool for predicting PCa in Chinese population.展开更多
Storms are usually accompanied by a drop in tempera- ture, and an increase in wind and barometric pressure and rainfall, which have negative impacts on most activ- ities, survival and reproduction in insects (Gillot,...Storms are usually accompanied by a drop in tempera- ture, and an increase in wind and barometric pressure and rainfall, which have negative impacts on most activ- ities, survival and reproduction in insects (Gillot, 2005). The majority of studies have mainly focused on how the flight activity of various flying insects such as honey- bees, bumble bees, horse flies and leafminers were directly influenced by intraday weather changes (Burnett & Hays, 1974; Lundberg, 1980; Casas, 1989; Vicens & Bosch, 2000).展开更多
The medium spiny neurons(MSNs)in the nucleus accumbens(NAc)integrate excitatory and inhibitory synaptic inputs and gate motivational and emotional behavior output.Here we report that the relative intensity of excitato...The medium spiny neurons(MSNs)in the nucleus accumbens(NAc)integrate excitatory and inhibitory synaptic inputs and gate motivational and emotional behavior output.Here we report that the relative intensity of excitatory and inhibitory synaptic inputs to MSNs of the NAc shell was decreased in mice with neuropathic pain induced by spinal nerve ligation(SNL).SNL increased the frequency,but not the amplitude of spontaneous inhibitory postsynaptic currents(sIPSCs),and decreased both the frequency and amplitude of spontaneous excitatory postsynaptic currents(sEPSCs)in the MSNs.SNL also decreased the paired-pulse ratio(PPR)of evoked IPSCs but increased the PPR of evoked EPSCs.Moreover,acute bath application of C–C motif chemokine ligand 2(CCL2)increased the frequency and amplitude of sIPSCs and sEPSCs in the MSNs,and especially strengthened the amplitude of N-methyl-D-aspartate receptor(NMDAR)-mediated miniature EPSCs.Further Ccl2 overexpression in the NAc in vivo decreased the peak amplitude of the sEPSC/sIPSC ratio.Finally,Ccr2 knock-down improved the impaired induction of NMDAR-dependent long-term depression(LTD)in the NAc after SNL.These results suggest that CCL2/CCR2 signaling plays a role in the integration of excitatory/inhibitory synaptic transmission and leads to an increase of the LTD induction threshold at the synapses of MSNs during neuropathic pain.展开更多
Dear Editor,Itch(pruritus)is an unpleasant somatic sensation that is accompanied by the desire to scratch.While itch provides a warning signal that protects us from potential threats in normal conditions,severe or chr...Dear Editor,Itch(pruritus)is an unpleasant somatic sensation that is accompanied by the desire to scratch.While itch provides a warning signal that protects us from potential threats in normal conditions,severe or chronic itch associated with dermatosis or systemic diseases is often difficult to alleviate and causes severe skin and tissue damage.展开更多
The single locus complementary sex determination (sl-csd) gene is the primary gene determining the gender of honey bees (Apis spp.). While the csd gene has been well studied in the Western honey bee (Apis mellif...The single locus complementary sex determination (sl-csd) gene is the primary gene determining the gender of honey bees (Apis spp.). While the csd gene has been well studied in the Western honey bee (Apis mellifera), and comparable data exist in both the Eastern honey bee (Apis cerana) and the giant honey bee (Apis dorsata), no studies have been conducted in the red dwarf honey bee, Apisflorea. In this study we cloned the genomic region 3 of the A. florea csd gene from 60 workers, and identified 12 csd alleles. Analysis showed that similar to A. mellifera, region 3 of the csd gene contains a RS domain at the N terminal, a proline-rich domain at the C terminal, and a hypervariable region in the middle. However, the A. florea csd gene possessed a much higher level of nucleotide diversity, compared to A. mellifera, A. cerana and Apis dorsata. We also show that similar to the other three Apis species, in A. florea, nonsynonymous mutations in the csd gene are selectively favored in young alleles.展开更多
Trigeminal neuropathic pain(TNP)is a significant health problem but the involved mechanism has not been completely elucidated.Toll-like receptors(TLRs)have recently been demonstrated to be expressed in the dorsal root...Trigeminal neuropathic pain(TNP)is a significant health problem but the involved mechanism has not been completely elucidated.Toll-like receptors(TLRs)have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain.Here,we show that TLR8 was persistently increased in the trigeminal ganglion(TG)neurons in model of TNP induced by partial infraorbital nerve ligation(pIONL).In addition,deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia,reduced the activation of ERK and p38-MAPK,and decreased the expression of pro-inflammatory cytokines in the TG.Furthermore,intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity.VTX-2337 also increased the intracellular Ca^(2+)concentration,induced the activation of ERK and p38,and increased the expression of pro-inflammatory cytokines in the TG.These data indicate that TLR8 contributes to the maintenance of TNP through increasing MAPK-mediated neuroinflammation.Targeting TLR8 signaling may be effective for the treatment of TNP.展开更多
基金Project(2018YFB1502500) supported by the National Key Research and Development Program of ChinaProject supported by State Key Laboratory of Powder Metallurgy,Central South University,China+1 种基金Projects(21506258,51774127) supported by the National Natural Science Foundation of ChinaProject(2019RS2067) supported by the Science and Technology Planning Project of Hunan Province,China
文摘Composite coatings consisting of carbon and polytetrafluoroethylene(PTFE) were prepared on Ti alloy substrate by a simple two-step process of hydrothermal and impregnation. The morphology, composition, hydrophobic and corrosion properties of the composite coatings were characterized by scanning electron microscopy(SEM), Fourier transform infrared spectroscopy(FTIR), water contact angle method, X-ray photoelectron spectroscopy(XPS) and electrochemical technique, respectively. The effect of PTFE content on the corrosion properties of the composite coatings was studied. It is found that the composite coating film exhibits a full coverage with uniformly distributed PTFE when 0.1 mol/L of glucose is used as carbon source and 20 wt.% PTFE suspension as impregnating solution. The coating with 20 wt.% PTFE has a good bonding strength with Ti plate and exhibits excellent hydrophobic property with a water contact angle of 142.3° as well as superior corrosion resistance with corrosion current density as low as 0.0045 μA/cm^2. With regard to its excellent hydrophobicity and corrosion resistance, the carbon-PTFE composite coating may find potential application in automobiles and metal corrosion industries.
文摘BACKGROUND In malignant tumors,inflammation plays a vital role in the development,invasion,and metastasis of cancer cells.Diffuse large B-cell lymphoma(DLBCL),the most common malignant proliferative disease of the lymphatic system,is commonly associated with inflammation.The international prognostic index(IPI),which includes age,lactate dehydrogenase(LDH),number of extranodal lesions,Ann Arbor score,and Eastern Cooperative Oncology Group(ECOG)score,can evaluate the prognosis of DLBCL.However,its use in accurately identifying highrisk patients and guiding treatment is poor.Therefore,it is important to find novel immune markers in predicting the prognosis of DLBCL patients.AIM To determine the association between the systemic immune inflammation index(SII),ratio of lymphocytes to monocytes(LMR),ratio of LMR to LDH(LMR/LDH),and prognosis of patients with DLBCL.METHODS A total of 68 patients diagnosed with DLBCL,treated in our hospital between January 2016 and January 2020,were included.χ2 test,Pearson’s R correlation,Kaplan Meier curves,and Cox proportional risk regression analysis were used.The differences in the SII,LMR,and LMR/LDH among patients with different clinicopathological features were analyzed.The differences in progression-free survival time among patients with different SII,LMR,and LMR/LDH expressions and influencing factors affecting the prognosis of DLBCL patients,were also analyzed.RESULTS The LMR and LMR/LDH in patients with Ann Arbor stage III–IV,ECOG score≥2,and SII,IPI score 2–5 were significantly higher than those of patients with Ann Arbor stage I-II and ECOG score<2(P<0.05).Patients with high SII,LMR,and LMR/LDH had progression-free survival times of 34 mo(95%CI:32.52–38.50),35 mo(95%CI:33.42–36.58)and 35 mo(95%CI:33.49–36.51),respectively,which were significantly lower than those with low SII,LMR,and LMR/LDH(P<0.05);the SII,LMR,and LMR/LDH were positively correlated(P<0.05).Cox proportional risk regression analysis showed that the SII,LMR,and LMR/LDH were influencing factors for the prognosis of DLBCL patients(hazard ratio=1.143,1.665,and 1.704,respectively;P<0.05).CONCLUSION The SII,LMR,and LMR/LDH are related to the clinicopathological features of DLCBL,and they also influence the prognosis of patients with the disease.
基金the National Natural Science Foundation of China (No. 90707002)the Natural Science Foundation of Zheji-ang Province, China (No. Z104441)
文摘This paper presents a multi-mode control scheme for a soft-switched flyback converter to achieve high efficiency and excellent load regulation over the entire load range. At heavy load, critical conduction mode with valley switching (CCMVS) is employed to realize soft switching so as to reduce turn-on loss of power switch as well as conducted electromagnetic interference (EMI). At light load, the converter operates in discontinuous conduction mode (DCM) with valley switching and adaptive off-time control (AOT) to limit the switching frequency range and maintain load regulation. At extremely light load or in standby mode, burst mode operation is adopted to provide low power consumption through reducing both switching frequency and static power dissipation of the controller. The multi-mode control is implemented by an oscillator whose pulse duration is adjusted by output feedback. An accurate valley switching control circuit guarantees the minimum turn-on voltage drop of power switch. The pro-totype of the controller IC was fabricated in a 1.5-μm BiCMOS process and applied to a 310 V/20 V, 90 W flyback DC/DC converter circuitry. Experimental results showed that all expected functions were realized successfully. The flyback converter achieved a high efficiency of over 80% from full load down to 2.5 W, with the maximum reaching 88.8%, while the total power consumption in standby mode was about 300 mW.
基金This study was supported by the National Natural Science Foundation of China(U23A2062,32361133551)State Key Laboratory of Cryospheric Science(SKLCS-ZZ-2023)+1 种基金Second Tibetan Plateau Scientific Expedition and Research Program_(STEP,2019QZKK0605)NaturalScience FoundationoGf ansuProvince(21JR7RA500 and 22ZD6FA005).
文摘Climate warming is causing rapid permafrost degradation,including thaw-induced subsidence,potentially resulting in heightened carbon release.Nevertheless,our understanding of the levels and variations of carbon components in permafrost,particularly during the degradation process,remains limited.The uncertainties arising from this process lead to inaccurate assessments of the climate effects during permafrost degradation.With vast expanses of permafrost in the Tibetan Plateau,there is limited research available on SOC components,particularly in the central Tibetan Plateau.Given remarkable variations in hydrothermal conditions across different areas of the Tibetan Plateau,the existing limited studies make it challenging to assess the overall SOC components in the permafrost across the Tibetan Plateau and simulate their future changes.In this study,we examined the properties of soil organic carbon(SOC)and microbial necromass carbon(MicrobialNC)in a representative permafrost thaw-subsidence area at the southern edge of continuous permafrost in the central Tibetan Plateau.The results indicate that prior to the thaw-subsidence,the permafrost had a SOC content of 72.68±18.53 mg g^(-1),with MicrobialNC accounting for 49.6%.The thaw-subsidence of permafrost led to a 56.4%reduction in SOC,with MicrobialNC accounting for 70.0%of the lost SOC.MicrobialNC constitutes the primary component of permafrost SOC,and it is the main component that is lost during thaw-subsidence formation.Changes in MicrobialNC are primarily correlated with factors pH,plant input,and microbial properties.The present study holds crucial implications for both the ecological and biogeochemical processes associated with carbon release from permafrost,and it furnishes essential data necessary for modeling the global response of permafrost to climate warming.Based on this study and previous research,permafrost thawing in the Tibetan Plateau causes substantial loss of SOC.However,there's remarkable heterogeneity in SOC component changes across different regions,warranting further in-depth investigation.
基金supported by grants from the National Natural Science Foundation of China (31671091 and 81771197)the Natural Science Foundation of Jiangsu Province, China (BK20171255)the Science and Technology Planning Project of Nantong Municipality, China (MS12017023-9)
文摘Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain largely unknown.Our recent study indicated that C-X-C motif chemokine 13(CXCL13)and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation(SNL).Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains unknown.Here,we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after SNL.Knockdown of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic painrelated place avoidance behavior.Furthermore,electrophysiological recording from layer Ⅱ-Ⅲ neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents(sEPSCs),decreased the EPSC paired-pulse ratio,and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio,indicating enhanced glutamatergic synaptic transmission.Finally,superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs.Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmis sion induced by SNL.Collectively,these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.
基金supported by Grants from the National Natural Science Foundation of China(31371121,81300954,and 31671091)the Priority Academic Program Development of Jiangsu Higher Education Institutions,China
文摘Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also con- tributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3-/- mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund's adjuvant-induced chronic inflammatory pain were reduced in Cxcr3-/- mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water (AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Further- more, touch-elicited itch (alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3-/- mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3-/- mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.
基金supported by the National Natural Science Foundation of China(31871064 and 32030048)the Natural Science Research Program of Jiangsu Province,China(BK20171255)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(KYCX192088)。
文摘Chemokines and receptors have been implicated in the pathogenesis of chronic pain.Here,we report that spinal nerve ligation(SNL)increased CXCR3 expression in dorsal root ganglion(DRG)neurons,and intra-DRG injection of Cxcr3 shRNA attenuated the SNL-induced mechanical allodynia and heat hyperalgesia.SNL also increased the m RNA levels of CXCL9,CXCL10,and CXCL11,whereas only CXCL10 increased the number of action potentials(APs)in DRG neurons.Furthermore,in Cxcr3^(-/-)mice,CXCL10 did not increase the number of APs,and the SNL-induced increase of the numbers of APs in DRG neurons was reduced.Finally,CXCL10 induced the activation of p38 and ERK in ND7-23 neuronal cells and DRG neurons.Pretreatment of DRG neurons with the P38 inhibitor SB203580 decreased the number of APs induced by CXCL10.Our data indicate that CXCR3,activated by CXCL10,mediates p38 and ERK activation in DRG neurons and enhances neuronal excitability,which contributes to the maintenance of neuropathic pain.
文摘This study was performed to evaluate prostate-specific antigen-age volume (PSA-AV) scores in predicting prostate cancer (PCa) in a Chinese biopsy population. A total of 2355 men who underwent initial prostate biopsy from January 2006 to November 2015 in Huashan Hospital were recruited in the current study. The PSA-AV scores were calculated and assessed together with PSA and PSA density (PSAD) retrospectively. Among 2133 patients included in the analysis, 947 (44.4%) were diagnosed with PCa. The mean age, PSA, and positive rates of digital rectal examination result and transrectal ultrasound result were statistically higher in men diagnosed with PCa (all P 〈 0.05). The values of area under the receiver operating characteristic curves (AUCs) of PSAD and PSA-AV were 0.864 and 0.851, respectively, in predicting PCa in the entire population, both performed better than PSA (AUC = 0.805; P 〈 0.05). The superiority of PSAD and PSA-AV was more obvious in subgroup with PSA ranging from 2.0 ng ml^-1 to 20.0 ng ml^-1. A PSA-AV score of 400 had a sensitivity and specificity of 93.7% and 40.0%, respectively. In conclusion, the PSA-AV score performed equally with PSAD and was better than PSA in predicting PCa. This indicated that PSA-AV score could be a useful tool for predicting PCa in Chinese population.
基金Acknowledgments This work was supported by the earmarked fund for China Agriculture Research System (No. CARS-45-KXJ 12) and the National Natural Science Foundation of China (No. 31360587). We thank Prof. Dr. Zachary Y. Huang and Dr. Qiang Huang for revising the paper, and we thank Hao Liu and Hai-Yan Gan for helping with the experiment.
文摘Storms are usually accompanied by a drop in tempera- ture, and an increase in wind and barometric pressure and rainfall, which have negative impacts on most activ- ities, survival and reproduction in insects (Gillot, 2005). The majority of studies have mainly focused on how the flight activity of various flying insects such as honey- bees, bumble bees, horse flies and leafminers were directly influenced by intraday weather changes (Burnett & Hays, 1974; Lundberg, 1980; Casas, 1989; Vicens & Bosch, 2000).
基金Grants from the National Natural Science Foundation of China(32030048,31871064,and 31671091).
文摘The medium spiny neurons(MSNs)in the nucleus accumbens(NAc)integrate excitatory and inhibitory synaptic inputs and gate motivational and emotional behavior output.Here we report that the relative intensity of excitatory and inhibitory synaptic inputs to MSNs of the NAc shell was decreased in mice with neuropathic pain induced by spinal nerve ligation(SNL).SNL increased the frequency,but not the amplitude of spontaneous inhibitory postsynaptic currents(sIPSCs),and decreased both the frequency and amplitude of spontaneous excitatory postsynaptic currents(sEPSCs)in the MSNs.SNL also decreased the paired-pulse ratio(PPR)of evoked IPSCs but increased the PPR of evoked EPSCs.Moreover,acute bath application of C–C motif chemokine ligand 2(CCL2)increased the frequency and amplitude of sIPSCs and sEPSCs in the MSNs,and especially strengthened the amplitude of N-methyl-D-aspartate receptor(NMDAR)-mediated miniature EPSCs.Further Ccl2 overexpression in the NAc in vivo decreased the peak amplitude of the sEPSC/sIPSC ratio.Finally,Ccr2 knock-down improved the impaired induction of NMDAR-dependent long-term depression(LTD)in the NAc after SNL.These results suggest that CCL2/CCR2 signaling plays a role in the integration of excitatory/inhibitory synaptic transmission and leads to an increase of the LTD induction threshold at the synapses of MSNs during neuropathic pain.
基金This work was supported by grants from the National Natural Science Foundation of China(32030048,31970938,and 31871064)the Natural Science Foundation of Jiangsu Province(BK20191448).
文摘Dear Editor,Itch(pruritus)is an unpleasant somatic sensation that is accompanied by the desire to scratch.While itch provides a warning signal that protects us from potential threats in normal conditions,severe or chronic itch associated with dermatosis or systemic diseases is often difficult to alleviate and causes severe skin and tissue damage.
文摘The single locus complementary sex determination (sl-csd) gene is the primary gene determining the gender of honey bees (Apis spp.). While the csd gene has been well studied in the Western honey bee (Apis mellifera), and comparable data exist in both the Eastern honey bee (Apis cerana) and the giant honey bee (Apis dorsata), no studies have been conducted in the red dwarf honey bee, Apisflorea. In this study we cloned the genomic region 3 of the A. florea csd gene from 60 workers, and identified 12 csd alleles. Analysis showed that similar to A. mellifera, region 3 of the csd gene contains a RS domain at the N terminal, a proline-rich domain at the C terminal, and a hypervariable region in the middle. However, the A. florea csd gene possessed a much higher level of nucleotide diversity, compared to A. mellifera, A. cerana and Apis dorsata. We also show that similar to the other three Apis species, in A. florea, nonsynonymous mutations in the csd gene are selectively favored in young alleles.
基金the National Natural Science Foundation of China(31970938,31671091,31871064,81571070,and 31700899)the Natural Science Research Program of Jiangsu Province,China(BK20171255 and BK20191448)+1 种基金the Qing Lan Projectthe Innovation and Entrepreneurship Training Program for College Students in Jiangsu Province,China(201810304029Z)。
文摘Trigeminal neuropathic pain(TNP)is a significant health problem but the involved mechanism has not been completely elucidated.Toll-like receptors(TLRs)have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain.Here,we show that TLR8 was persistently increased in the trigeminal ganglion(TG)neurons in model of TNP induced by partial infraorbital nerve ligation(pIONL).In addition,deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia,reduced the activation of ERK and p38-MAPK,and decreased the expression of pro-inflammatory cytokines in the TG.Furthermore,intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity.VTX-2337 also increased the intracellular Ca^(2+)concentration,induced the activation of ERK and p38,and increased the expression of pro-inflammatory cytokines in the TG.These data indicate that TLR8 contributes to the maintenance of TNP through increasing MAPK-mediated neuroinflammation.Targeting TLR8 signaling may be effective for the treatment of TNP.