Multi-locus genome-wide association studies reveal the dynamic genetic architecture of flowering time in chrysanthemum.

KEY MESSAGE: The dynamic genetic architecture of flowering time in chrysanthemum was elucidated by GWAS. Thirty-six known genes and 14 candidate genes were identified around the stable QTNs and QEIs, among which ERF-1 was highlighted. Flowering time (FT) adaptation is one of the major breeding goals in chrysanthemum, a multipurpose ornamental plant. In order to reveal the dynamic genetic architecture of FT in chrysanthemum, phenotype investigation of ten FT-related traits was conducted on 169 entries in 2 environments. The broad-sense heritability of five non-conditional FT traits, i.e., budding (FBD), visible coloring (VC), early opening (EO), full-bloom (OF) and decay period (DP), ranged from 56.93 to 84.26%, which were higher than that of the five derived conditional FT traits (38.51-75.13%). The phenotypic variation coefficients of OF_EO and DP_OF were relatively large ranging from 30.59 to 36.17%. Based on 375,865 SNPs, the compressed variance component mixed linear model 3VmrMLM was applied for a multi-locus genome-wide association study (GWAS). As a result, 313 quantitative trait nucleotides (QTNs) were identified for the non-conditional FT traits in single-environment analysis, while 119 QTNs and 67 QTN-by-environment interactions (QEIs) were identified in multi-environment analysis. As for the conditional traits, 343 QTNs were detected in single-environment analysis, and 119 QTNs and 83 QEIs were identified in multi- environment analysis. Among the genes around stable QTNs and QEIs, 36 were orthologs of known FT genes in Arabidopsis and other plants; 14 candidates were mined by combining the transcriptomics data and functional annotation, including ERF-1, ACA10, and FOP1. Furthermore, the haplotype analysis of ERF-1 revealed six elite accessions with extreme FBD. Our findings contribute to the understanding of dynamic genetic architecture of FT and provide valuable resources for future chrysanthemum molecular breeding programs.

HSP90ß regulates EAAT2 expression and participates in ischemia­reperfusion injury in rats.

Cerebrovascular diseases (CVDs) have become a global public health problem and ischemia­reperfusion injury, the major cause of neurological impairment exacerbation, is closely related to excitotoxicity. The present study aimed to investigate the effects of changes in heat shock protein (HSP)90ß expression and verify whether HSP90ß regulates EAAT2 expression in a cerebral ischemia­reperfusion injury model. Healthy adult Sprague­Dawley (SD) male rats were used to establish a control group, sham­operated group, middle cerebral artery occlusion (MCAO) group, empty virus group and lentivirus group. A model of cerebral ischemia­reperfusion was established using the MCAO method. Lentivirus construction and injection were used to interfere with the expression of HSP90ß. The modified neurological severity score was used to assess neurological deficits. Triphenyltetrazolium chloride staining was used to detect infarct areas. Immunofluorescence was used to detect HSP90ß expression localization and the expression levels of HSP90ß and EAAT2 were determined using western blotting and reverse transcription­quantitative PCR. An MCAO model was successfully established and it was found that HSP90ß, but not HSP90α, was upregulated after MCAO. HSP90ß expression coincided with astrocyte markers in the ischemic penumbra area, while no expression was observed in microglia. Inhibition of HSP90ß expression improved neurological deficits and alleviated brain injury by increasing EAAT2 expression. These results suggested that HSP90ß is involved in the process of cerebral ischemia­reperfusion injury in rats and that inhibition of HSP90ß expression increases EAAT2 levels, conferring a neuroprotective effect in MCAO model rats.

Energy-Efficient ReS2-Based Optoelectronic Synapse for 3D Object Reconstruction and Recognition.

The neuromorphic vision system (NVS) equipped with optoelectronic synapses integrates perception, storage, and processing and is expected to address the issues of traditional machine vision. However, owing to their lack of stereo vision, existing NVSs focus on 2D image processing, which makes it difficult to solve problems such as spatial cognition errors and low-precision interpretation. Consequently, inspired by the human visual system, an NVS with stereo vision is developed to achieve 3D object recognition, depending on the prepared ReS2 optoelectronic synapse with 12.12 fJ ultralow power consumption. This device exhibits excellent optical synaptic plasticity derived from the persistent photoconductivity effect. As the cornerstone for 3D vision, color planar information is successfully discriminated and stored in situ at the sensor end, benefiting from its wavelength-dependent plasticity in the visible region. Importantly, the dependence of the channel conductance on the target distance is experimentally revealed, implying that the structure information on the object can be directly captured and stored by the synapse. The 3D image of the object is successfully reconstructed via fusion of its planar and depth images. Therefore, the proposed 3D-NVS based on ReS2 synapses for 3D objects achieves a recognition accuracy of 97.0%, which is much higher than that for 2D objects (32.6%), demonstrating its strong ability to prevent 2D-photo spoofing in applications such as face payment, entrance guard systems, and others.

Multi-locus genome-wide association study and genomic prediction for flowering time in chrysanthemum.

MAIN CONCLUSION: Multi-locus GWAS detected several known and candidate genes responsible for flowering time in chrysanthemum. The associations could greatly increase the predictive ability of genome selection that accelerates the possible application of GS in chrysanthemum breeding. Timely flowering is critical for successful reproduction and determines the economic value for ornamental plants. To investigate the genetic architecture of flowering time in chrysanthemum, a multi-locus genome-wide association study (GWAS) was performed using a collection of 200 accessions and 330,710 single-nucleotide polymorphisms (SNPs) via 3VmrMLM method. Five flowering time traits including budding (FBD), visible colouring (VC), early opening (EO), full-bloom (OF) and senescing (SF) stages, plus five derived conditional traits were recorded in two environments. Extensive phenotypic variations were observed for these flowering time traits with coefficients of variation ranging from 6.42 to 38.27%, and their broad-sense heritability ranged from 71.47 to 96.78%. GWAS revealed 88 stable quantitative trait nucleotides (QTNs) and 93 QTN-by-environment interactions (QEIs) associated with flowering time traits, accounting for 0.50-8.01% and 0.30-10.42% of the phenotypic variation, respectively. Amongst the genes around these stable QTNs and QEIs, 21 and 10 were homologous to known flowering genes in Arabidopsis; 20 and 11 candidate genes were mined by combining the functional annotation and transcriptomics data, respectively, such as MYB55, FRIGIDA-like, WRKY75 and ANT. Furthermore, genomic selection (GS) was assessed using three models and seven unique marker datasets. We found the prediction accuracy (PA) using significant SNPs identified by GWAS under SVM model exhibited the best performance with PA ranging from 0.90 to 0.95. Our findings provide new insights into the dynamic genetic architecture of flowering time and the identified significant SNPs and candidate genes will accelerate the future molecular improvement of chrysanthemum.

Green and economic flame retardant prepared by the one-step method for polylactic acid.

Resolving the flammability of poly(L-lactic acid) (PLA) while ensuring its environmental friendliness and preserving key flame retardancy and mechanical properties represents a critical challenge. We have successfully developed a highly efficient and environmentally friendly flame retardant called Hexamethylenediamine tetramethylene phosphonic acid amine (HDME). The flame retardancy of PLA/HDME composites was significantly improved, as indicated by the LOI value of 29.1 % and UL-94 V-0 rating for PLA/3.5 HDME with only 3.5 % HDME addition. The results show a 23.4 % reduction in the total heat release (THR), a 40.0 % increase in the time to ignition (TTI), and a 21.2 % increase in the flame propagation index (FPI) compared to original PLA. Flame retardant mechanism of HDME involves the gas phase, condensed phase, and interrupted heat exchange effects. The HDME also preserved the original mechanical properties of PLA, with the elongation at break and tensile strength retention of PLA/3.5 HDME reaching 93.05 % and 89.65 %. This work provides a simple and efficient method for flame retardant modification of PLA, which can expand its application scope.

Patching sulfur vacancies: A versatile approach for achieving ultrasensitive gas sensors based on transition metal dichalcogenides.

Transition metal dichalcogenides (TMDCs) garner significant attention for their potential to create high-performance gas sensors. Despite their favorable properties such as tunable bandgap, high carrier mobility, and large surface-to-volume ratio, the performance of TMDCs devices is compromised by sulfur vacancies, which reduce carrier mobility. To mitigate this issue, we propose a simple and universal approach for patching sulfur vacancies, wherein thiol groups are inserted to repair sulfur vacancies. The sulfur vacancy patching (SVP) approach is applied to fabricate a MoS2-based gas sensor using mechanical exfoliation and all-dry transfer methods, and the resulting 4-nitrothiophenol (4NTP) repaired molybdenum disulfide (4NTP-MoS2) is prepared via a sample solution process. Our results show that 4NTP-MoS2 exhibits higher response (increased by 200 %) to ppb-level NO2 with shorter response/recovery times (61/82 s) and better selectivity at 25 °C compared to pristine MoS2. Notably, the limit of detection (LOD) toward NO2 of 4NTP-MoS2 is 10 ppb. Kelvin probe force microscopy (KPFM) and density functional theory (DFT) reveal that the improved gas sensing performance is mainly attributed to the 4NTP-induced n-doping effect on MoS2 and the corresponding increment of surface absorption energy to NO2. Additionally, our 4NTP-induced SVP approach is universal for enhancing gas sensing properties of other TMDCs, such as MoSe2, WS2, and WSe2.

Germline C1GALT1C1 mutation causes a multisystem chaperonopathy.

Mutations in genes encoding molecular chaperones can lead to chaperonopathies, but none have so far been identified causing congenital disorders of glycosylation. Here we identified two maternal half-brothers with a novel chaperonopathy, causing impaired protein O-glycosylation. The patients have a decreased activity of T-synthase (C1GALT1), an enzyme that exclusively synthesizes the T-antigen, a ubiquitous O-glycan core structure and precursor for all extended O-glycans. The T-synthase function is dependent on its specific molecular chaperone Cosmc, which is encoded by X-chromosomal C1GALT1C1. Both patients carry the hemizygous variant c.59C>A (p.Ala20Asp; A20D-Cosmc) in C1GALT1C1. They exhibit developmental delay, immunodeficiency, short stature, thrombocytopenia, and acute kidney injury (AKI) resembling atypical hemolytic uremic syndrome. Their heterozygous mother and maternal grandmother show an attenuated phenotype with skewed X-inactivation in blood. AKI in the male patients proved fully responsive to treatment with the complement inhibitor Eculizumab. This germline variant occurs within the transmembrane domain of Cosmc, resulting in dramatically reduced expression of the Cosmc protein. Although A20D-Cosmc is functional, its decreased expression, though in a cell or tissue-specific manner, causes a large reduction of T-synthase protein and activity, which accordingly leads to expression of varied amounts of pathological Tn-antigen (GalNAcα1-O-Ser/Thr/Tyr) on multiple glycoproteins. Transient transfection of patient lymphoblastoid cells with wild-type C1GALT1C1 partially rescued the T-synthase and glycosylation defect. Interestingly, all four affected individuals have high levels of galactose-deficient IgA1 in sera. These results demonstrate that the A20D-Cosmc mutation defines a novel O-glycan chaperonopathy and causes the altered O-glycosylation status in these patients.

Targeting altered glycosylation in secreted tumor glycoproteins for broad cancer detection.

There is an urgent need to develop new tumor biomarkers for early cancer detection, but the variability of tumor-derived antigens has been a limitation. Here we demonstrate a novel anti-Tn antibody microarray platform to detect Tn+ glycoproteins, a near universal antigen in carcinoma-derived glycoproteins, for broad detection of cancer. The platform uses a specific recombinant IgG1 to the Tn antigen (CD175) as a capture reagent and a recombinant IgM to the Tn antigen as a detecting reagent. These reagents were validated by immunohistochemistry in recognizing the Tn antigen using hundreds of human tumor specimens. Using this approach, we could detect Tn+ glycoproteins at subnanogram levels using cell lines and culture media, serum, and stool samples from mice engineered to express the Tn antigen in intestinal epithelial cells. The development of a general cancer detection platform using recombinant antibodies for detection of altered tumor glycoproteins expressing a unique antigen could have a significant impact on cancer detection and monitoring.

Activation of HCN channels caused by elevated cAMP levels in periaqueductal gray promotes bone cancer pain.

The periaqueductal gray (PAG) is an important relay center for the descending pathways that regulate nociceptive information transduction. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play critical roles in the nerve injury-induced pain hypersensitivity. Previous studies have identified that HCN1 and HCN2 channel protein located in the ventral-lateral periaqueductal gray (vlPAG), a region important for pain regulation. However, it is not clear whether the HCN channel in vlPAG is involved in bone cancer pain (BCP). In this study, we assessed the role of HCN channels in BCP by measuring changes of HCN channel expression and activity in vlPAG neurons in bone cancer rats. In the present study, the BCP model was established by injecting SHZ-88 breast cancer cells into the right tibia bone marrow in rats. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured to evaluate pain behavior in rats. HCN1 and HCN2 channels expression in vlPAG were detected by using Western Blot and immunohistochemistry. In addition, the cAMP level in vlPAG neurons was detected by ELISA, and HCN channel current (Ih) of vlPAG neurons was recorded by whole cell patch-clamp to evaluate HCN channel activity. As a result, decreased MWT and TWL were observed in rats on 7d after SHZ-88 cell inoculation, and the allodynia was sustained until 21d after inoculation. At the same time, HCN1 and HCN2 channels expression and neuronal Ih in vlPAG were significantly increased in BCP rats. In addition, the level of cAMP in vlPAG also increased after SHZ-88 cell inoculation. Furthermore, intravlPAG injection of ZD7288 (HCN channels antagonist) could significantly reduce hyperalgesia and the elevation of cAMP in vlPAG in BCP rats. Our observations suggest that the elevation of cAMP may promote the activation of HCN channels in vlPAG in bone cancer rats, thereby promoting the development of bone cancer pain.

MiR-29c Inhibits TNF-α-Induced ROS Production and Apoptosis in Mouse Hippocampal HT22 Cell Line.

Recent reports have suggested that abnormal miR-29c expression in hippocampus have been implicated in the pathophysiology of some neurodegenerative and neuropsychiatric diseases. However, the underlying effect of miR-29c in regulating hippocampal neuronal function is not clear. In this study, HT22 cells were infected with lentivirus containing miR-29c or miR-29c sponge. Cell counting kit-8 (CCK8) and lactate dehydrogenase (LDH) assay kit were applied to evaluate cell viability and toxicity before and after TNF-α administration. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were measured with fluorescent probes. Hoechst 33258 staining and TUNEL assay were used to evaluate cell apoptosis. The expression of key mRNA/proteins (TNFR1, Bcl-2, Bax, TRADD, FADD, caspase-3, -8 and -9) in the apoptosis pathway was detected by PCR or WB. In addition, the protein expression of microtubule-associated protein-2 (MAP-2), nerve growth-associated protein 43 (GAP-43) and synapsin-1 (SYN-1) was detected by WB. As a result, we found that miR-29c overexpression could improve cell viability, attenuate LDH release, reduce ROS production and inhibit MMP depolarization in TNF-α-treated HT22 cells. Furthermore, miR-29c overexpression was found to decrease apoptotic rate, along with decreased expression of Bax, cleaved caspase-3, cleaved caspase-9, and increased expression of Bcl-2 in TNF-α-treated HT22 cells. However, miR-29c sponge exhibited an opposite effects. In addition, in TNF-α-treated HT22 cells, miR-29c overexpression could decrease the expressions of TNFR1, TRADD, FADD and cleaved caspase-8. However, in HT22 cells transfected with miR-29c sponge, TNF-α-induced the expressions of TNFR1, TRADD, FADD and cleaved caspase-8 was significantly exacerbated. At last, TNF-α-induced the decreased expression of MAP-2, GAP-43 and SYN-1 was reversed by miR-29c but exacerbated by miR-29c sponge. Overall, our study demonstrated that miR-29c protects against TNF-α-induced HT22 cells injury through alleviating ROS production and reduce neuronal apoptosis. Therefore, miR-29c might be a potential therapeutic agent for TNF-α accumulation and toxicity-related brain diseases.

Brain Region- and Age-Dependent 5-Hydroxymethylcytosine Activity in the Non-Human Primate.

Because of the difficulty in collecting fresh brains of humans at different ages, it remains unknown how epigenetic regulation occurs in the primate brains during aging. In the present study, we examined the genomic distribution of 5hmC, an indicator of DNA methylation, in the brain regions of non-human primates (rhesus monkey) at the ages of 2 (juvenile), 8 (young adult), and 17 (old) years. We found that genomic 5hmC distribution was accumulated in the monkey brain as age increased and displayed unique patterns in the cerebellum and striatum in an age-dependent manner. We also observed a correlation between differentially hydroxymethylated regions (DhMRs) and genes that contribute to brain region-related functions and diseases. Our studies revealed, for the first time, the brain-region and age-dependent 5hmC modifications in the non-human primate and the association of these 5hmC modifications with brain region-specific function and potentially aging-related brain diseases.

NF-κB and AP-1 are required for the lipopolysaccharide-induced expression of MCP-1, CXCL1, and Cx43 in cultured rat dorsal spinal cord astrocytes.

TLR4 and Cx43 signaling in dorsal spinal cord has been shown to be involved in the development of neuropathic pain. However, it is not clear whether TLR4 signaling is associated with the expression of MCP-1, CXCL1, and Cx43 in LPS (lipopolysaccharide)-treated rat dorsal spinal cord astrocytes under in vitro condition. In the present study, we found that TLR4 antagonist TAK-242 significantly inhibited LPS-induced MCP-1, CXCL1, and Cx43 expression, suggesting the role of TLR4 in response to LPS in cultured dorsal spinal cord astrocytes. Application of TAK-242 significantly blocked LPS-induced NF-κB and AP-1 activity and the expression of MCP-1, CXCL1 and Cx43. Furthermore, NF-κB inhibitor PDTC and AP-1 inhibitor SR11302 significantly blocked LPS-induced MCP-1, CXCL1, and Cx43 expression. DNA-binding activity of NF-κB, its effect on MCP-1 expression was suppressed by PDTC and SR11302. On the other hand, DNA-binding activity of AP-1, its effect on CXCL1 or Cx43 expression was also suppressed by PDTC and SR11302. In addition, PDTC was found to inhibit the nuclear translocation of AP-1 and the expression of c-Jun induced by LPS, which suggested that NF-κBp65 is essential for the AP-1 activity. Similarly, SR11302 significantly blocked LPS-induced the nuclear translocation of NF-κBp65 and the expression of NF-κBp65 induced by LPS. Pretreatment with CBX, Gap26, or Gap19 (Cx43 blockers) significantly inhibited abnormal astrocytic hemichannel opening and chemokines (MCP-1 and CXCL1) release in LPS-stimulated astrocytes. In summary, cell culture experiments revealed that LPS stimulation could evoke TLR4 signaling with the subsequent activation of NF-κB and AP-1, resulting in the expression of MCP-1, CXCL1, and Cx43. TLR4 activation increased Cx43 hemichannel, but not gap-junction activities and induced the release of the MCP-1 and CXCL1 from astrocytes via Cx43 hemichannel. These findings may help us to understand the role of astrocytic signaling in inflammatory response within dorsal spinal cord tissue.

Blockage of HCN Channels Inhibits the Function of P2X Receptors in Rat Dorsal Root Ganglion Neurons.

Hyperpolarization-activated cyclic nucleotide-gated channels and purinergic P2X receptors play critical roles in the nerve injury-induced pain hypersensitivity. Both HCN channels and P2XR are expressed in dorsal root ganglia sensory neurons. However, it is not clear whether the expression and function of P2X2 and P2X3 receptors can be modulated by HCN channel activity. For this reason, in rats with chronic constriction injury of sciatic nerve, we evaluated the effect of intrathecal administration of HCN channel blocker ZD7288 on nociceptive behavior and the expression of P2X2 and P2X3 in rat DRG. The mechanical withdrawal threshold was measured to evaluate pain behavior in rats. The protein expression of P2X2 and P2X3 receptor in rat DRG was observed by using Western Blot. The level of cAMP in rat DRG was measured by ELISA. As a result, decreased MWT was observed in CCI rats on 1 d after surgery, and the allodynia was sustained throughout the experimental period. In addition, CCI rats presented increased expression of P2X2 and P2X3 receptor in the ipsilateral DRG at 7 d and 14 d after CCI operation. Intrathecal injection of ZD7288 significantly reversed CCI-induced mechanical hyperalgesia, and attenuated the increased expression of P2X2 and P2X3 receptor in rat DRG, which open up the possibility that the expression of P2X2 and P2X3 receptor in DRG is down-regulated by HCN channel blocker ZD7288 in CCI rats. Furthermore, the level of cAMP in rat DRG significantly increased after nerve injury. Intrathecal administration of ZD7288 attenuated the increase of cAMP in DRG caused by nerve injury. Subsequently, effects of HCN channel activity on ATP-induced current (IATP) in rat DRG neurons were explored by using whole-cell patch-clamp techniques. ATP (100 µM) elicited three types of currents (fast, slow and mixed IATP) in cultured DRG neurons. Pretreatment with ZD7288 concentration-dependently inhibited three types of ATP-activated currents. On the other hand, pretreatment with 8-Br-cAMP (a cell-permeable cAMP analog, also known as an activator of PKA) significantly increased the amplitude of fast, slow and mixed IATP in DRG neurons. The enhanced effect of 8-Br-cAMP on ATP-activated currents could be reversed by ZD7288. In a summary, our observations suggest that the opening of HCN channels could enhance the expression and function of P2X2 and P2X3 receptor via the cAMP-PKA signaling pathway. This may be important for pathophysiological events occurring within the DRG, for where it is implicated in nerve injury-induced pain hypersensitivity.

Charge transfer driven by redox dye molecules on graphene nanosheets for room-temperature gas sensing.

Special functional groups to modify the surface of graphene have received much attention since they enable the charge transfer enhancement, thus realizing gas-sensing at room temperature. In this work, three typical redox dye molecules, methylene blue (MB), indigo carmine (IC) and anthraquinone-2-sulfonate (AQS), were selected to be supramolecularly assembled with reduced graphene oxide (rGO), respectively. Remarkably, three graphene-based materials AQS-rGO (response = 3.2, response time = 400 s), IC-rGO (response = 4.3, response time = 300 s) and MB-rGO (response = 7.1, response time = 100 s) exhibited excellent sensitivity and short response time toward 10 ppm NO2 at room temperature. The corresponding NO2 sensing mechanism of the obtained materials was further investigated by cyclic voltammetry (CV) measurements. CV was conducted to measure the anodic peak potential (Epa) of three redox dyes. Interestingly, it is obvious that the Epa values were positively correlated with the gas sensitivity and response time of the three materials. To explore the mechanism, UV-vis spectroscopy was adopted to analyze the lowest unoccupied molecular orbitals (LUMOs) of three redox dye molecules. The results show that the oxidation abilities of three redox dyes were also positively correlated with the gas sensitivity and response time of three corresponding graphene-based materials.

Cosmc deficiency causes spontaneous autoimmunity by breaking B cell tolerance.

Factors regulating the induction and development of B cell­mediated autoimmunity are not well understood. Here, we report that targeted deletion in murine B cells of X-linked Cosmc, encoding the chaperone required for expression of core 1 O-glycans, causes the spontaneous development of autoimmune pathologies due to a breakdown of B cell tolerance. BC-CosmcKO mice display multiple phenotypic abnormalities, including severe weight loss, ocular manifestations, lymphadenopathy, and increased female-associated mortality. Disruption of B cell tolerance in BC-CosmcKO mice is manifested as elevated self-reactive IgM and IgG autoantibodies. Cosmc-deficient B cells exhibit enhanced basal activation and responsiveness to stimuli. There is also an elevated frequency of spontaneous germinal center B cells in BC-CosmcKO mice. Mechanistically, loss of Cosmc confers enhanced B cell receptor (BCR) signaling through diminished BCR internalization. The results demonstrate that Cosmc, through control of core 1 O-glycans, is a previously unidentified immune checkpoint gene in maintaining B cell tolerance.

Altered Neurovascular Coupling in Patients with Chronic Myofascial Pain.

BACKGROUND: Despite previous reports on cerebral structures and functional connectivity in patients with myofascial pain (MFP), it is not clear whether alterations in neurovascular coupling occur in these patients. OBJECTIVES: We analyzed the coupling between resting-state cerebral blood flow (CBF) and functional connectivity strength (FCS) for observation of neurovascular coupling in patients with chronic MFP. STUDY DESIGN: Observational study. SETTING: University hospital. METHODS: Resting-state functional magnetic resonance imaging and arterial spin labeling were performed in 23 patients with chronic MFP and 23 healthy controls (HC) for the calculation of FCS and CBF. The whole-brain gray matter CBF-FCS correlations and CBF/FCS ratios of the various voxels of the 2 groups were subsequently compared. RESULTS: Compared with the HC, the patients with MFP experienced a decrease in whole-brain gray matter CBF-FCS coupling. In patients with MFP, a decrease in CBF/FCS was found in the bilateral superior temporal gyri, right parahippocampal gyrus, right hippocampus, caudate nucleus, right medial prefrontal cortex, and the periaqueductal gray matter (PAG), whereas an increase in CBF/FCS was found in the bilateral lingual gyri, posterior cingulate cortex, and bilateral inferior parietal lobules. In addition, the CBF/FCS of the PAG in patients with MFP was significantly negatively correlated with the pain visual analog scale score and pain duration. LIMITATIONS: Alterations in neurovascular coupling in patients with MFP were observed only before treatment. Therefore, there is a lack of data on the alterations that occurred after treatment. CONCLUSION: This study demonstrated for the first time that impairment of neurovascular coupling in the brain may be a potential neuropathological mechanism of chronic MFP.

A Photovoltaic Self-Powered Gas Sensor Based on All-Dry Transferred MoS2 /GaSe Heterojunction for ppb-Level NO2 Sensing at Room Temperature.

Traditional gas sensors are facing the challenge of low power consumption for future application in smart phones and wireless sensor platforms. To solve this problem, self-powered gas sensors are rapidly developed in recent years. However, all reported self-powered gas sensors are suffering from high limit of detection (LOD) toward NO2 gas. In this work, a photovoltaic self-powered NO2 gas sensor based on n-MoS2 /p-GaSe heterojunction is successfully prepared by mechanical exfoliation and all-dry transfer method. Under 405 nm visible light illumination, the fabricated photovoltaic self-powered gas sensors show a significant response toward ppb-level NO2 with short response and recovery time and high selectivity at room temperature (25 °C). It is worth mentioning that the LOD toward NO2 of this device is 20 ppb, which is the lowest of the reported self-powered room-temperature gas sensors so far. The discussed devices can be used as building blocks to fabricate more functional Internet of things devices.

cAMP-PKA signaling is involved in regulation of spinal HCN channels function in diabetic neuropathic pain.

The cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signaling acts a pivotal part in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels-mediated neuropathic and inflammatory pain. However, there has been no evidence of cAMP-PKA signaling is involved in regulation of spinal HCN channels function in the occurrence of diabetic neuropathic pain (DNP). The study aimed to elucidate the impact of HCN channels on neuropathic pain in a rat model of diabetes induced by streptozotocin, and whether cAMP-PKA signaling is involved in regulation of HCN channels function. In this report, we evaluated the effect of intrathecal administration of HCN channel blockers ZD7288, cAMP inhibitor SQ22536 and PKA inhibitor H-89 on nociceptive behavior in DNP rats. The mechanical withdrawal threshold (MWT) was measured to evaluate pain behavior in rats. Protein expression levels of HCN2, HCN4 channels and PKA in the spinal dorsal horn of rats were assessed. Furthermore, the levels of cAMP in rat spinal dorsal horn was analyzed. We discovered that DNP rats showed significant mechanical allodynia and are related to the increased HCN2 and HCN4 channels expression, enhanced cAMP production and elevated the expression of PKA protein in the spinal dorsal horn, which were attenuated by intrathecal ZD7288. Furthermore, intrathecal injection of SQ22536 and H-89 significantly reduced the HCN2 and HCN4 channels expression in the spinal dorsal horn of DNP rats. Our findings indicate that HCN channels of the spinal dorsal horn participate in the pathogenesis of allodynia in rats with DNP, which could be regulated by cAMP-PKA signaling. Therefore, HCN channels and cAMP-PKA signaling are potential targets for hyperalgesia treatment in DNP patients.

Inhibition of p38 MAPK regulates epileptic severity by decreasing expression levels of A1R and ENT1.

Epilepsy is a chronic nervous system disease. Excessive increase of the excitatory neurotransmitter glutamate in the body results in an imbalance of neurotransmitters and excessive excitation of neurons, leading to epileptic seizures. Long­term recurrent seizures lead to behavior and cognitive changes, and even increase the risk of death by 2­ to 3­fold relative to the general population. Adenosine A1 receptor (A1R), a member of the adenosine system, has notable anticonvulsant effects, and adenosine levels are controlled by the type 1 equilibrative nucleoside transporter (ENT1); in addition the p38 MAPK signaling pathway is involved in the regulation of ENT1, although the effect of its inhibitors on the expression levels of A1R and ENT1 is unclear. Therefore, in the present study, SB203580 was used to inhibit the p38 MAPK signaling pathway in rats, and the expression levels of A1R and ENT1 in the brain tissue of rats with acute LiCl­pilocarpine­induced status epilepticus was detected. SB203580 decreased pathological damage of hippocampal neurons, prolonged seizure latency, reduced the frequency of seizures, and decreased levels of A1R and ENT1 protein in rats.

All-Dry Transferred ReS2 Nanosheets for Ultrasensitive Room-Temperature NO2 Sensing under Visible Light Illumination.

For gas sensing applications, most of the reported two-dimensional (2D) materials are suffering from relatively low sensitivity and high limit of detection (LOD) at room temperature. In this work, we selected rhenium disulfide (ReS2) nanosheets to fabricate ReS2 transistor-based gas sensors (RTGSs) with ultrahigh sensitivity and low LOD toward nitrogen dioxide (NO2). The ReS2 nanosheets with different thicknesses were prepared via mechanical exfoliation and all-dry transfer method. Under 405 nm light illumination at room temperature (25 °C), the fabricated gas sensors showed a significant enhancement of the response with full reversibility toward ppb level NO2 (response of 9.07 at 500 ppb, a LOD of 50 ppb). In particular, the total response and recovery time of the RTGS was revealed to be less than 4 minutes (55 and 180 s, respectively), which is one of the top three shortest response and recovery times toward ppb level NO2 of the reported 2D material-based room-temperature gas sensors so far. Via Raman spectrometry, Kelvin probe force microscopy (KPFM), and X-ray photoelectron spectrometry (XPS), the structure and gas sensing mechanism of the materials were systematically investigated. It was confirmed that the electrons transfer from the ReS2 surface to NO2 molecules, inducing the hole doping of ReS2, which consequently increased the sensor resistance. Moreover, the concentration of the photogenerated carriers in ReS2 would accordingly be promoted by light illumination, which accounts for the substantial light enhancement of the gas sensing performance of RTGSs.