Combination of prostate volume and apparent diffusion coefficient can stratify patients with a PI-RADS score of 3 to reduce unnecessary prostate biopsies.

BACKGROUND: Nowadays, there are many patients who undergo unnecessary prostate biopsies after receiving a prostate imaging reporting and data system (PI-RADS) score of 3. Our purpose is to identify cutoff values of the prostate volume (PV) and minimum apparent diffusion coefficient (ADCmin) to stratify those patients to reduce unnecessary prostate biopsies. METHODS: Data from 224 qualified patients who received prostate biopsies from January 2019 to June 2023 were collected. The Mann-Whitney U test was used to compare non-normal distributed continuous variables, which were recorded as median (interquartile ranges). The correlation coefficients were calculated using Spearman's rank correlation analysis. Categorical variables are recorded by numbers (percentages) and compared by χ2 test. Both univariate and multivariate logistic regression analysis were used to determine the independent predictors. The receiver-operating characteristic curve and the area under the curve (AUC) were used to evaluate the diagnostic performance of clinical variables. RESULTS: Out of a total of 224 patients, 36 patients (16.07%) were diagnosed with clinically significant prostate cancer (csPCa), whereas 72 patients (32.14%) were diagnosed with any grade prostate cancer. The result of multivariate analysis demonstrated that the PV (p < 0.001, odds ratio [OR]: 0.952, 95% confidence interval [95% CI]: 0.927-0.978) and ADCmin (p < 0.01, OR: 0.993, 95% CI: 0.989-0.998) were the independent factors for predicting csPCa. The AUC values of the PV and ADCmin were 0.779 (95% CI: 0.718-0.831) and 0.799 (95% CI: 0.740-0.849), respectively, for diagnosing csPCa. After stratifying patients by PV and ADCmin, 24 patients (47.06%) with "PV < 55 mL and ADCmin < 685 µm2/s" were diagnosed with csPCa. However, only one patient (1.25%) with PV ≥ 55 mL and ADCmin ≥ 685 µm2/s were diagnosed with csPCa. CONCLUSIONS: In this study, we found the combination of PV and ADCmin can stratify patients with a PI-RADS score of 3 to reduce unnecessary prostate biopsies. These patients with "PV ≥ 55 mL and ADCmin ≥ 685 µm2/s" may safely avoid prostate biopsies.

Evidence of a large current of transcranial alternating current stimulation directly to deep brain regions.

Deep brain regions such as hippocampus, insula, and amygdala are involved in neuropsychiatric disorders, including chronic insomnia and depression. Our recent reports showed that transcranial alternating current stimulation (tACS) with a current of 15 mA and a frequency of 77.5 Hz, delivered through a montage of the forehead and both mastoids was safe and effective in intervening chronic insomnia and depression over 8 weeks. However, there is no physical evidence to support whether a large alternating current of 15 mA in tACS can send electrical currents to deep brain tissue in awake humans. Here, we directly recorded local field potentials (LFPs) in the hippocampus, insula and amygdala at different current strengths (1 to 15 mA) in 11 adult patients with drug-resistant epilepsy implanted with stereoelectroencephalography (SEEG) electrodes who received tACS at 77.5 Hz from 1 mA to 15 mA at 77.5 Hz for five minutes at each current for a total of 40 min. For the current of 15 mA at 77.5 Hz, additional 55 min were applied to add up a total of 60 min. Linear regression analysis revealed that the average LFPs for the remaining contacts on both sides of the hippocampus, insula, and amygdala of each patient were statistically associated with the given currents in each patient (p < 0.05-0.01), except for the left insula of one subject (p = 0.053). Alternating currents greater than 7 mA were required to produce significant differences in LFPs in the three brain regions compared to LFPs at 0 mA (p < 0.05). The differences remained significant after adjusting for multiple comparisons (p < 0.05). Our study provides direct evidence that the specific tACS procedures are capable of delivering electrical currents to deep brain tissues, opening a realistic avenue for modulating or treating neuropsychiatric disorders associated with hippocampus, insula, and amygdala.

A longitudinal study on the impact of high-altitude hypoxia on perceptual processes.

This study aimed to explore the neural mechanisms underlying high-altitude (HA) adaptation and deadaptation in perceptual processes in lowlanders. Eighteen healthy lowlanders were administered a facial S1-S2 matching task that included incomplete face (S1) and complete face (S2) photographs combined with ERP technology. Participants were tested at four time points: shortly before they departed the HA (Test 1), twenty-five days after entering the HA (Test 2), and one week (Test 3) and one month (Test 4) after returning to the lowlands. Compared with those at sea level (SL), shorter reaction times (RTs), shorter latencies of P1 and N170, and larger amplitudes of complete face N170 were found in HAs. After returning to SL, compared with that of HA, the amplitude of the incomplete face P1 was smaller after one week, and the complete face was smaller after one month. The right hemisphere N170 amplitude was greater after entering HA and one week after returning to SL than at baseline, but it returned to baseline after one month. Taken together, the current findings suggest that HA adaptation increases visual cortex excitation to accelerate perceptual processing. More mental resources are recruited during the configural encoding stage of complete faces after HA exposure. The perceptual processes affected by HA exposure are reversible after returning to SL, but the low-level processing stage differs between incomplete and complete faces due to neural compensation mechanisms. The configural encoding stage in the right hemisphere is affected by HA exposure and requires more than one week but less than one month to recover to baseline.

Cortical and thalamic modulation of auditory gating in the posterior parietal cortex of awake mice.

Auditory gating (AG) is an adaptive mechanism for filtering out redundant acoustic stimuli to protect the brain against information overload. AG deficits have been found in many mental illnesses, including schizophrenia (SZ). However, the neural correlates of AG remain poorly understood. Here, we found that the posterior parietal cortex (PPC) shows an intermediate level of AG in auditory thalamocortical circuits, with a laminar profile in which the strongest AG is in the granular layer. Furthermore, AG of the PPC was decreased and increased by optogenetic inactivation of the medial dorsal thalamic nucleus (MD) and auditory cortex (AC), respectively. Optogenetically activating the axons from the MD and AC drove neural activities in the PPC without an obvious AG. These results indicated that AG in the PPC is determined by the integrated signal streams from the MD and AC in a bottom-up manner. We also found that a mouse model of SZ (postnatal administration of noncompetitive N-methyl-d-aspartate receptor antagonist) presented an AG deficit in the PPC, which may be inherited from the dysfunction of MD. Together, our findings reveal a neural circuit underlying the generation of AG in the PPC and its involvement in the AG deficit of SZ.

A prospective cohort study on perioperative percutaneous balloon compression for trigeminal neuralgia: safety and efficacy analysis.

With the recent emergence of percutaneous balloon compression (PBC) as a promising treatment for trigeminal neuralgia (TN), there is a growing need for research on its safety and efficacy. This study was designed to evaluate the safety and efficacy of PBC in the treatment of TN patients during the perioperative period. This study involved a total of 400 TN patients who were selected and treated with PBC at our institution. The clinical data and short-term outcomes were analyzed based on sex, initial PBC treatment for TN, and subsequent PBC treatment for recurrent TN after previous PBC or microvascular decompression (MVD) or radiofrequency thermocoagulation (RFT). No statistically significant difference was found when comparing postoperative pain relief between male and female patients with TN. Nevertheless, female patients were found to be more vulnerable than male patients to abnormal facial sensations (P = 0.001), diplopia (P = 0.015), postoperative headache (P = 0.012), and hyposmia (P = 0.029). Additionally, it was observed that there was no substantial difference in the postoperative pain relief rate between the first-time PBC group and PBC for recurrent TN patients postoperatively following procedures such as PBC, MVD, and RFT. In conclusion, this study has shown that PBC treatment is effective in managing TN in both males and females, regardless of whether the treatment was administered as a primary intervention or following prior surgical procedures such as PBC, MVD, or RFT. Nonetheless, it is noted that the risk of postoperative complications appears to be higher in female patients compared to male patients.

[Application of iliac vein molding and stent implantation through the ipsilateral great saphenous vein approach in daytime treatment mode].

OBJECTIVE: To explore the feasibility and recent efficacy of iliac vein molding and stenting in daytime treatment mode in patients with iliac vein stenosis. METHODS: Medical records of iliac vein molding and stenting performed in the ipsilateral great saphenous vein approach conducted from February 2017 to March 2022 were retrospective reviewed. There were 21 cases, 6 males and 15 females. Age ranged from 37 to 79 years [(62.5 ± 10.2) years]. The stenosis in the 21 limbs simply involved the common iliac veins in 16 patients, 2 patients had the simple and external iliac veins, and both the total and external iliac veins in 3 patients. Both iliac vein molding and iliac vein stenting were performed through the ipsilateral great saphenous vein approach. The patients with simple iliac vein stenosis with great saphenous vein valve insufficiency also underwent radiofrequency closure of great saphenous vein and flexural vein sclerosis therapy simultaneously. Regular postoperative direct oral anticoagulants therapy and stress therapy were followed. All the patients were hospitalized for less than 24 h. RESULTS: All the 21 patients operations were successful (the success rate was 100%), without any intraoperative complications. Immediate postoperative complications were puncture point bleeding in 1 case. The bandage gauze was completely wet. The bleeding was stopped after 5min of recompression. All the patients were hospitalized for less than 24 h. Follow-up results: The 3-month follow-up rate after operation was 100%. Absolute effective 18 cases (18/21, 85.7%). Relatively effective(postmentation still after surgery, but with less extent) in 3 cases (3/21, 14.3%). The iliac vein stents were unobstructed, and the trunk of the great saphenous vein was well closed in the patients with great saphenous vein radiofrequency treatment. The 6-month follow-up rate after operation was 71.4%(15/21). Of these, 14 cases (14/15, 93.3%) were absolutely effective. Relatively effective(postmentation still after surgery, but with less extent) in 1 case (1/15, 6.7%). The iliac vein stents were no restenosis or obstruction, and the trunk of the great saphenous vein was well closed in the patients with great saphenous vein radiofrequency treatment. CONCLUSION: The interventional treatment technique of iliac vein stenosis is feasible in the daytime treatment mode, with clear advantages and satisfactory recent efficacy.

Allantoin induces pruritus by activating MrgprD in chronic kidney disease.

Chronic kidney disease (CKD) is a disease with decreased, irreversible renal function. Pruritus is the most common skin symptom in patients with CKD, especially in end-stage renal disease. The underlying molecular and neural mechanism of CKD-associated pruritus (CKD-aP) remains obscure. Our data show that the level of allantoin increases in the serum of CKD-aP and CKD model mice. Allantoin could induce scratching behavior in mice and active DRG neurons. The calcium influx and action potential reduced significantly in DRG neurons of MrgprD KO or TRPV1 KO mice. U73122, an antagonist of phospholipase C, could also block calcium influx in DRG neurons induced by allantoin. Thus, our results concluded that allantoin plays an important role in CKD-aP, mediated by MrgprD and TrpV1, in CKD patients.

Utilization of passive visual perception task indetecting patients with major depressive disorder for active health.

Depression is a common emotional and mental disease. At present, doctors' diagnosis mainly depends on the existing evaluation scales and their accumulated experience, lack of objective electrophysiological quantitative evaluation indicators. This study explores the difference in event-related potential (ERP) between patients with depression and healthy controls under the stimulation of multi-dimensional tasks, extracts the characteristic data, and uses a t-test for statistical analysis to provide an objective evaluation index for the clinical diagnosis of depression. Ninety-nine patients in the major depression group (MDD) and thirty patients in the healthy control group (HC) were used to compare the responses to positive, negative, and neutral stimulation, the results showed that there were significant differences between the left and right occipital lobes and one frontal lobe, and the frontal lobe showed lateralization; There were significant differences between the depression group and the healthy control group under multi-dimensional stimulation (P < 0.01), and the depression patients were significantly lower than the healthy patients. The results showed that emotional information was processed differently in patients with depression in the early stages of visual face processing. Therefore, EEG indices could be used as an objective index for the early detection of depression. Moreover, according to the instructions before the test, the subject is only asked to recognize visual pictures instead report emotional feelings. Stigma about psychiatric disorders could thus be reduced in this way. The explorations above facilitate designing more accurate and implicit active mental health techniques.

The role of the orbitofrontal cortex and insula for prognosis of mesial temporal lobe epilepsy.

OBJECTIVE: We investigated the network between the medial temporal lobe (MTL) and extratemporal structures in patients with mesial temporal lobe epilepsy (MTLE) in order to explain the recurrence of MTLE after surgery. This study contributes to our current understanding of MTLE with stereotactic electroencephalography (SEEG). METHODS: We conducted a retrospective study of SEEG in 20 patients with MTLE in order to observe and analyze the intensity of interictal high-frequency oscillations (HFOs), as well as the dynamic course of coherence connectivity values of the MTL and extratemporal structures during the initial phase of the seizure. The results correlated with the patient prognosis. RESULTS: First, the presence of HFOs was observed during the interictal period in all 20 patients; these were localized to the MTL in 17 patients and the orbitofrontal cortex in seven patients and the insula in six patients. The better the prognosis, the greater the localization of the HFOs concentration in the MTL structures (p < 0.05). Second, significantly enhanced connectivity of MTL structures with the orbitofrontal cortex and insula was observed in most patients with MTLE, before and after the seizure onset (p < 0.05). Finally, the connectivity between extratemporal structures, such as the orbitofrontal cortex and insula, and MTL structures was significantly stronger in patients who had a worse prognosis than in other patients, before and after seizure onset (p < 0.05). INTERPRETATION: The epileptogenic network in recurrent MTLE is not limited to MTL structures but is also associated with the orbitofrontal cortex and insula. This can be used as a potential indicator for predicting the prognosis of patients after surgery, providing an important avenue for future clinical evaluation.

A comparative study on the efficacy and safety of propofol combined with different doses of alfentanil in gastroscopy: a randomized controlled trial.

PURPOSE: Propofol can be used alone or in combination with opioids during gastroscopy. This study aimed to assess the efficacy and safety of intravenous propofol and different doses of alfentanil in patients undergoing gastroscopy. METHODS: A total of 300 patients undergoing sedative gastroscopy were randomly divided into four groups, and 0.9% saline (group A), 2 µg/kg alfentanil (group B), 3 µg/kg alfentanil (group C) or 4 µg/kg alfentanil (group D) were injected intravenously 1 min before the intravenous injection of 1.5 mg/kg propofol. If body movement and coughing occurred during the procedure, 0.5 mg/kg propofol would be administered intravenously. The primary outcome (awakening time) and secondary outcomes were recorded and analyzed, including hemodynamic changes, the incidences of body movement, coughing, hypoxemia, hypotension, hypertension, bradycardia, tachycardia, nausea and vomiting, drowsiness and dizziness. RESULTS: Patients in group C (7.0 [5.0 to 8.0] min) and group D (6.0 [5.0 to 7.0] min) woke up significantly earlier than those in group A (8.0 [6.0 to 10.0] min) (P < 0.001). Patients in group A experienced more body movement (P = 0.001) and coughing (P < 0.001) than the other groups. With the increasing dose of alfentanil, the morbidity of hypotension and bradycardia increased significantly (P = 0.001), while the incidence of dizziness decreased significantly (P = 0.037). The incidences of hypoxemia, tachycardia, drowsiness, nausea and vomiting were similar among the four groups (P > 0.05). CONCLUSIONS: Intravenous 1.5 mg/kg propofol combined with 3 µg/kg alfentanil is more suitable for patients undergoing gastroscopy, and the dose of alfentanil can be reduced according to the patient's actual physical condition.

The effect of music intervention on sedation in elderly patients undergoing transurethral resection of prostate under spinal anesthesia: a prospective randomized controlled clinical trial.

PURPOSE: Music intervention is commonly used as a non-pharmacologic therapeutic modality to alleviate anxiety in perioperative patients. This study aimed to assess the sedative and anxiolytic effects of music on elderly patients receiving transurethral resection of prostate (TURP) under spinal anesthesia. METHODS: This was a prospective randomized controlled trial on patients who aged over 60 and received TURP under spinal anesthesia. Participants were randomized to the music group or the control group (no music). The primary outcome was perioperative BIS values, and the secondary outcomes were patient's perioperative anxiety levels, heart rate (HR), blood pressure, and patient satisfaction score. RESULTS: A total of 82 patients were analyzed. The perioperative BIS values in the music group were significantly lower than those of the control group at almost all time points (P < 0.001), as well as showed a significant reduction compared with baseline (P < 0.001), whereas the control group did not. In comparison with the control group, systolic blood pressure (SBP) significantly decreased in the music group at the beginning (mean difference, - 8.0 mmHg; 95% CI - 15.70 to 0.35; P = 0.041) and the 60th minute (mean difference, - 7.9 mmHg; 95% CI - 15.30 to 0.51; P = 0.037) of TURP. Furthermore, compared with baseline within the music group, diastolic blood pressure (DBP) and HR significant reduced at whole time points (P < 0.05), yet the control group not. CONCLUSION: Music intervention effectively provided slight sedation for elderly patients when undergoing TURP under spinal anesthesia without sedatives.

LncRNA NEAT1-associated aerobic glycolysis blunts tumor immunosurveillance by T cells in prostate cancer.

Long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) is nuclear-located and transcribed from chromatin 11. To date, little is known about the cellular functions and regulatory mechanisms of NEAT1 in prostate cancer (PCa). In this study, whole-genome RNA sequencing data were downloaded from TCGA and GEO databases. Biological information was used to analyze the different expressions of NEAT1. In situ hybridization (ISH) was performed to detect the expression of NEAT1 in PCa and paracarcinoma clinical samples. Then, NEAT1 was knocked down in PC3 cells through lentiviral infection with a plasmid construct. Bioinformatics and integrative analytical approaches were utilized to identify the relationships of NEAT1 with specific cancer-related gene sets. Cell proliferation assay and colony formation assay were performed to evaluate the cell proliferative ability. Glycolysis stress test, metabolism assay, and infiltrating T-cell function analysis were implemented to assess the changes in metabolism and immune microenvironment of PCa. We found that the expression of NEAT1 was higher in PCa than in non-neoplastic tissues. The cell proliferative capability of PCa cells was significantly reduced in the NEAT1 knockdown group. PCR array and bioinformatics analysis revealed that the enrichment of acidic substance-related gene sets was associated with NEAT1 expression. NEAT1 depletion inhibited PCa cell aerobic glycolysis accompanied by the reduction of lactate levels in the medium. Further, we found that lactate dehydrogenase A (LDHA) expression was positively regulated by NEAT1. At last, co-culture systems indicated that NEAT1 or LDHA knockdown promoted the secretion of CD8+ T-lymphocyte factors, including TNF-α, IFN-γ, and Granzyme B, and enhanced the antitumor effects.

mMrgprA3/mMrgprC11/hMrgprX1: Potential therapeutic targets for allergic contact dermatitis-induced pruritus in mice and humans.

BACKGROUND: Although the Mas-related G-protein-coupled receptors (Mrgprs) play essential roles in itch detection, their contribution to allergic contact dermatitis (ACD)-associated itch remains unclear. OBJECTIVES: To investigate whether Mrgprs are involved in ACD and whether Mrgprs can be identified as potential therapeutic targets. METHODS: Mrgpr-clusterΔ-/- mice and human MrgprX1 (hMrgprX1) transgenic mice were used to evaluate the function of Mrgprs in oxazolone-induced ACD. RESULTS: Utilizing an ACD model, we found that Mrgpr-clusterΔ-/- mice display significantly reduced pruritus. Among 12 Mrgprs deleted in Mrgpr-clusterΔ-/- mice, the expression of MrgprC11 and MrgprA3 was significantly increased in the ACD model, which also innervated the skin and spinal cord at higher-than-normal densities. The proportions of dorsal root ganglia neurons responding to bovine adrenal medulla peptide 8-22 and chloroquine were also remarkably increased in the ACD model, resulting in enhanced itch behaviour. To study the function of human Mrgprs in ACD-induced itch, we used hMrgprX1 transgenic mice, which rescued the severe itch defect of Mrgpr-clusterΔ-/- mice in the ACD model. Remarkably, pharmacological blockade of hMrgprX1 significantly attenuates ACD itch in hMrgprX1 transgenic mouse. CONCLUSIONS: Our study provides the first evidence that Mrgprs are involved in ACD-induced chronic itch, which provides new avenues for itch management in ACD.

Binaural processing deficit and cognitive impairment in Alzheimer's disease.

Speech comprehension in noisy environments depends on central auditory functions, which are vulnerable in Alzheimer's disease (AD). Binaural processing exploits two ear sounds to optimally process degraded sound information; its characteristics are poorly understood in AD. We studied behavioral and electrophysiological alterations in binaural processing among 121 participants (AD = 27; amnestic mild cognitive impairment [aMCI] = 33; subjective cognitive decline [SCD] = 30; cognitively normal [CN] = 31). We observed impairment of binaural processing in AD and aMCI, and detected a U-shaped curve change in phase synchrony (declining from CN to SCD and to aMCI, but increasing from aMCI to AD). This improvement in phase synchrony accompanying more severe cognitive stages could reflect neural adaptation for binaural processing. Moreover, increased phase synchrony is associated with worse memory during the stages when neural adaptation apparently occurs. These findings support a hypothesis that neural adaptation for binaural processing deficit may exacerbate cognitive impairment, which could help identify biomarkers and therapeutic targets in AD.

A lightweight automatic sleep staging method for children using single-channel EEG based on edge artificial intelligence.

With the development of telemedicine and edge computing, edge artificial intelligence (AI) will become a new development trend for smart medicine. On the other hand, nearly one-third of children suffer from sleep disorders. However, all existing sleep staging methods are for adults. Therefore, we adapted edge AI to develop a lightweight automatic sleep staging method for children using single-channel EEG. The trained sleep staging model will be deployed to edge smart devices so that the sleep staging can be implemented on edge devices which will greatly save network resources and improving the performance and privacy of sleep staging application. Then the results and hypnogram will be uploaded to the cloud server for further analysis by the physicians to get sleep disease diagnosis reports and treatment opinions. We utilized 1D convolutional neural networks (1D-CNN) and long short term memory (LSTM) to build our sleep staging model, named CSleepNet. We tested the model on our childrens sleep (CS) dataset and sleep-EDFX dataset. For the CS dataset, we experimented with F4-M1 channel EEG using four different loss functions, and the logcosh performed best with overall accuracy of 83.06% and F1-score of 76.50%. We used Fpz-Cz and Pz-Oz channel EEG to train our model in Sleep-EDFX dataset, and achieved an accuracy of 86.41% without manual feature extraction. The experimental results show that our method has great potential. It not only plays an important role in sleep-related research, but also can be widely used in the classification of other time sequences physiological signals.

EEG-Based Anxious States Classification Using Affective BCI-Based Closed Neurofeedback System.

PURPOSE: Anxiety disorder is one of the psychiatric disorders that involves extreme fear or worry, which can change the balance of chemicals in the brain. To the best of our knowledge, the evaluation of anxiety state is still based on some subjective questionnaires and there is no objective standard assessment yet. Unlike other methods, our approach focuses on study the neural changes to identify and classify the anxiety state using electroencephalography (EEG) signals. METHODS: We designed a closed neurofeedback experiment that contains three experimental stages to adjust subjects' mental state. The EEG resting state signal was recorded from thirty-four subjects in the first and third stages while EEG-based mindfulness recording was recorded in the second stage. At the end of each stage, the subjects were asked to fill a Visual Analogue Scale (VAS). According to their VAS score, the subjects were classified into three groups: non-anxiety, moderate or severe anxiety groups. RESULTS: After processing the EEG data of each group, support vector machine (SVM) classifiers were able to classify and identify two mental states (non-anxiety and anxiety) using the Power Spectral Density (PSD) as patterns. The highest classification accuracies using Gaussian kernel function and polynomial kernel function are 92.48 ±  1.20% and 88.60  ±  1.32%, respectively. The highest average of the classification accuracies for healthy subjects is 95.31 ±  1.97% and for anxiety subjects is 87.18 ±  3.51%. CONCLUSIONS: The results suggest that our proposed EEG neurofeedback-based classification approach is efficient for developing affective BCI system for detection and evaluation of anxiety disorder states.

Facilitation of MrgprD by TRP-A1 promotes neuropathic pain.

Neuropathic pain remains a therapeutic challenge because of its complicated mechanisms. Mas-related GPCR D (MrgprD) is specifically expressed in small-diameter, nociceptive neurons of dorsal root ganglia (DRGs) and is implicated in pain modulation. However, the underlying mechanism of MrgprD involved in neuropathic pain remains elusive. In this study, we used behavioral experiments and physiologic examination methods to investigate the role of MrgprD in chronic constriction injury (CCI)-induced neuropathic pain. We found that MrgprD is necessary for the initiation of mechanical hypersensitivity and cold allodynia, but not for heat allodynia. Moreover, we demonstrated that transient receptor potential cation channel (TRP)-A1 was the ion channel downstream of MrgprD, and the ß-alanine-induced calcium signal was attributed mostly to TRP-A1 function. We further showed that PKA serves as a downstream mediator of ß-alanine-activated MrgprD signaling to activate TRP-A1 in DRG neurons and in human embryonic kidney 293 cells, to coexpress MrgprD and TRP-A1 plasmids. Finally, we found that the ß-alanine-induced pain behavior was increased, whereas the itching behavior was unchanged in CCI models compared with sham-injured animals. Knockout of TRPA1 also attenuated the ß-alanine-induced pain behavior in CCI models. In conclusion, MrgprD is essential in cold allodynia in CCI-induced neuropathic pain through the PKA-TRP-A1 pathway. TRP-A1 facilitates MrgprD to development of neuropathic pain. Our findings reveal a novel mechanism of neuropathic pain formation and highlight MrgprD as a promising drug target for the treatment of neuropathic pain.-Wang, C., Gu, L., Ruan, Y., Geng, X., Xu, M., Yang, N., Yu, L., Jiang, Y., Zhu, C., Yang, Y., Zhou, Y., Guan, X., Luo, W., Liu, Q., Dong, X., Yu, G., Lan, L., Tang, Z. Facilitation of MrgprD by TRP-A1 promotes neuropathic pain.

Sucrose and starch metabolism during Fargesia yunnanensis shoot growth.

Bamboo is one of the fastest growing plants in the world, but their shoot buds develop very slowly. Information about the sugar storage and metabolism during the shoot growth is lacking. In the present study, we determined the activity of sucrose and starch metabolizing enzymes during the developmental period of Fargesia yunnanensis from shoot buds to the young culms that have achieved their full height. The soluble sugars and starch contents were also determined and analyzed in shoot buds and shoots at different developmental stages. The results showed that there were higher sucrose contents in shoot buds than shoots, which coincides with the sweeter taste of shoot buds. As the shoot buds sprouted out of the ground, the starch and sucrose were depleted sharply. Coupled with this, the activity of soluble acid invertase (SAI), cell wall-bound invertase (CWI), sucrose synthase at cleavage direction (SUSYC) and starch phosphorylase (STP) increased significantly in the rapidly elongating internodes. These enzymes dominated the rapid elongation of internodes. The activities of SAI, CWI, SUSYC and STP and adenosine diphosphate-glucose pyrophosphorylase were higher as compared to other enzymes in the shoot buds, but were far lower than those in the developing shoots. The slow growth of shoot buds was correlated with the low activity of these enzymes. These results complement our understanding of the physiological differences between shoot buds and elongating shoots and ascertain the physiological mechanism for the rapid growth of bamboo shoots.

Diminished stimulator of interferon genes production with cigarette smoke-exposure contributes to weakened anti-adenovirus vectors response and destruction of lung in chronic obstructive pulmonary disease model.

Cigarette smoke (CS) is the primary risk factor for chronic obstructive pulmonary disease (COPD) and dampens antiviral response, which increases viral infections and leads to COPD acute exacerbation (AECOPD). Adenovirus, a nonenveloped DNA virus, is linked with AECOPD, whose DNAs trigger innate immune response via interacting with pattern recognition receptors (PRRs). Stimulator of interferon genes (STING), as a cytosolic DNA sensor, participates in adenovirus-induced interferon ß (IFNß)-dependent antiviral response. STING is involved in various pulmonary diseases, but role of STING in pathogenesis of AECOPD is not well documented. In the present study, we explored relationship between STING and AECOPD induced by recombinant adenovirus vectors (rAdVs) and CS in wild type (WT) and STING-/- mice; and also characterized the inhibition of STING- IFNß pathway in pulmonary epithelium exposed to cigarette smoke extract (CSE). We found that CS or CSE exposure alone dramatically inhibited STING expression, but not significantly effected IFNß production. Moreover, CS or CSE-exposed significantly suppressed activation of STING-IFNß pathway induced by rAdVs and suppressed clearance of rAdVs DNA. Inflammation, fibrosis and emphysema of lung tissues were exaggerated when treated with CS plus rAdVs, which further deteriorate in absences of STING. In A549 cells with knockdown of STING, we also observed enhancing apoptosis related to emphysema, especially CSE and adenovirus vectors in combination. Therefore, STING may play a protective role in preventing the progress of COPD.

Responses of the proteome in testis of mice exposed chronically to environmentally relevant concentrations of Microcystin-LR.

Microcystin-LR (MC-LR), a widespread environmental contaminant, has been shown to have potent acute testicular toxicity. However, magnitudes of toxic effects, induced by MCs, depend on route and magnitude of exposure to the toxin. In the present study, male mice were orally exposed 1, 10 or 100 µg/L MC-LR for 90 or 180 days, and pathological approach and the isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics were employed with testes. Proteomics revealed that a number of differentially altered proteins may be involved in MC-LR-induced chronic testicular toxicity. The biological process analysis indicated the altered proteins played an important role in biological adhesion, cellular process, response to stimulus or rhythmic process. The cellular component analysis revealed that most of the proteins with altered expression associated with cell part, extracellular region, extracellular region part, membrane, membrane part, organelle or organelle part. The molecular function showed that these proteins were critical in molecular transducer activity. Integrity analyses provide first compelling evidence that MC-LR significantly cause dysfunction of blood-testis barrier (BTB) through affecting tight junctions and gap junctions. Moreover, phosphatidylinositol 3-kinase (PI3K)/AKT eventually contributed to injury result from chronic low-level MC-LR treatment. Identification of proteins in testis responsive to MC-LR provides insights into molecular mechanisms of chronic toxicity of MCs.