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The evolution of the mammalian brain, particularly the cerebral cortex, is characterized by an increase in size and complexity. Proper development of the cerebral cortex involves several coordinated events such as differentiation and migration, which plays a critical role in establishing a precise six-layered architecture. Our previous study has shown that phosphorylation of JIP1 at T205 by Cdk5 affects the axonal outgrowth. However, the spatiotemporal expression patterns and functions of these three genes in different cell types during cortical development are not well understood. In this study, we interrogated single-cell RNA-sequencing (scRNA-seq) data of mouse embryonic cortex and revealed that Cdk5, Cdk5r1 (p35) and Mapk8ip1 (JIP1) are dynamically expressed in intermediate progenitors (IPs). Pseudotime analysis showed that the expression of these three genes increased simultaneously in IPs during neuronal migration and differentiation. By manipulating the expression of JIP1 and phospho-mimic JIP1 using in utero electroporation, we demonstrated that phosphorylated JIP1 at T205 influenced the temporal migration of neurons. Taken together with previous findings that phospho-JIP1 at T205 regulates axonal growth, our study reveals a mechanism by which Cdk5, p35, and JIP1 coordinate to regulate neuron specification in the developing neocortex.

Our study assesses valproic acid’s effect on NLRP1/3 inflammasome in rats with acute spinal cord injury (SCI). SD rats were clamped by aneurysm clips to establish SCI model followed by analysis of functional recovery by BBB score, degree of inflammatory infiltration, by H&E staining, NLRP1/NLRP3 and P2X7 level by western blot, IL-1β and IL-18 level by ELISA, blood spinal cord barrier by EVANS blue method. After SCI, the lower limb motor function of rats decreased and recovered after valproic acid treatment (P < 0.05). Inflammatory cell infiltration of SCI group increased and decreased after treatment. After SCI, NLRP1/3 level increased and P2X7 protein level elevated which were reversed after valproic acid treatment (P < 0.05). In rats with SCI, IL-1β level in spinal cord was higher than sham operation and lower after treatment (P < 0.05) without difference of IL-18 between injury group and treatment group (P > 0.05). In addition, fluorescence was higher in injury group than sham operation group and lower in valproic acid injection group than injury group. In conclusion, Valproic acid can promote motor function recovery in rats after SCI and inhibit inflammasome 1 and 3 expression, thereby inhibiting the maturation and release of IL-1β, and reducing P2X7 level after SCI.

In the past decade, an increasing number of studies have found a relationship between the occurrence and development of depression and autoimmune diseases, and the high prevalence of depression in patients with connective tissue diseases has also been confirmed. Primary Sjögren's syndrome (pSS) is a chronic autoimmune exocrinopathy characterised by lymphocytic infiltration and exocrine gland destruction. Depression in pSS patients is common, and the factors contributing to this condition are complicated. pSS patients with depression generally have a lower quality of life than pSS patients without depression. Several pathophysiological mechanisms involved in the condition have been proposed in recent years. Thus, in this review, we summarised recent progress on the impact of depression on pSS patients' quality of life, the possible pathogenesis underlying the development of depression in pSS patients and the management of such patients.

Osteoactivin (OA) plays a key role in osteogenic differentiation. miR-26b is elevated in the bone formation process of BMSCs, but whether it is involved in this process is unclear. Bone formation is regulated by FLT3/AXL signaling pathway, which may be a potential target of miR-26b. qRT-PCR detected miR-26b mRNA levels and bone formation-related genes or FLT3/AXL signaling pathway-related genes. Bone formation was analyzed by staining and FLT3/AXL signaling was evaluated along with analysis of miR-26b’s relation with LT3/AXL. miR-26b was significantly elevated in OA-induced bone formation of BMSCs, which can be promoted by miR-26b mimics. When miR-26b was overexpressed, FLT3/AXL signaling pathway was activated. miR-26b can ameliorate Dex-induced osteo-inhibition. miR-26b promotes bone formation of BMSCs by directly targeting FLT3/AXL signaling pathway, suggesting that miR-26b might be a target for inducing osteogenic differentiation.

Objectives To evaluate the effect of MTX withdrawal on disease activity and remission rate in patients at target after treatment with biologic DMARDs (bDMARDs)/targeted synthetic DMARDs (tsDMARDs) plus MTX. Material and methods We searched the PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases for all randomized controlled trials (RCTs) on MTX withdrawal in patients with RA at target after combination therapy from inception to 7 March 2022 in order to extract data, including: the change from withdrawal in DAS28 at the endpoint; proportion of low disease activity (LDA) assessed by DAS28, Simplified Disease Activity Index (SDAI) or Clinical Disease Activity Index (CDAI); proportion of remission assessed by DAS28, SDAI CDAI or ACR/EULAR Boolean remission. The Cochrane Q test and I2 test were used to assess heterogeneity, and random-effects models were used for data synthesis. This study is registered with PROSPERO (CRD42022303891). Results Six articles were included for qualitative and quantitative analysis, all of which were noninferior RCTs involving 1430 patients (734 in the withdrawal group and 696 in the continuation group). Compared with continuing combination therapy, tapering off or discontinuing MTX increased DAS28 by 0.20 (95% CI 0.09, 0.32, I2 = 0%) and decreased the percentage of patients with LDA assessed by DAS28 to Conclusions Withdrawing MTX slightly increases the RA disease activity in patients treated at target with bDMARDs/tsDMARDs plus MTX and has limited effects for patients with deep remission.

Paclitaxel (PTX) is a widely used chemotherapeutic drug for treating tumors. However, studies have shown that it can cause cardiac problems such as arrhythmia, myocarditis, chronic cardiomyopathy, and heart failure. Therefore, it is essential to study the mechanism behind the cardiotoxicity of PTX in tumor treatment. In this study, we initially injected PTX into mice to establish a myocardial cell apoptosis model to observe the degree of damage to mouse myocardium caused by PTX. Upon determining the levels of mouse myocardial creatine phosphokinase (CK), myokinase isoenzyme (CK-MB), aspartate transaminase (AST), and lactate dehydrogenase (LDH), we found that all of these levels showed apparent increases in mice treated with PTX. Further analyses of the TNF

It is becoming increasingly clear that robust sex differences exist in the processing of acute and chronic pain in both rodents and humans. However, the underlying mechanism has not been well characterized. The dorsal horn of the lumbar spinal cord is the fundamental building block of ascending and descending pain pathways. It has been shown that numerous neurotransmitter and neuromodulator systems in the spinal cord, including the endocannabinoid system and its main receptor, the cannabinoid 1 receptor (CB

Pink1, Parkin and Fbxo7, three autosomal recessive familial genes of Parkinson's disease (PD), have been implicated in mitophagy pathways for quality control and clearance of damaged mitochondria, but the interplay of these three genes still remains unclear. Here we present that Fbxo7 and Pink1 play a reciprocal role in the regulation of their protein levels. Regardless of the genotypes of Fbxo7, the wild type and the PD familial mutants of Fbxo7 stabilize the processed form of Pink1, supporting the prior study that none of the PD familial mutations in Fbxo7 have an effect on the interaction with Pink1. On the other hand, the interaction of Fbxo7 with Bag2 further facilitates its capability to stabilize Pink1. Intriguingly, the stabilization of Fbxo7 by Pink1 is specifically observed in substantial nigra pars compacta but striatum and cerebral cortex. Taken together, our findings support the notion that Fbxo7 as a scaffold protein has a chaperon activity in the stabilization of proteins.

Spinal cord injury (SCI) refers to damage to the spinal cord resulting from trauma, disease or degeneration. Controlling the inflammatory process and restoring neural homeostasis is hypothesized to prevent injury aggravation. S100 calcium-binding protein A9 (S100A9) is a pro-inflammatory alarm protein, which is expressed in and released by activated neutrophils. However, whether S100A9 could serve as an effective target for the treatment of SCI has not been reported to date. In the present study, a T10 spinal cord contusion injury model was established in Sprague-Dawley rats. S100A9 expression level was determined in the serum and injured spinal cord tissue via ELISA, reverse transcription-quantitative PCR (RT-qPCR) and western blotting. The S100A9-specific blocker, ABR-238901 (ABR), was administered during the inflammatory phase of SCI, as a form of treatment. Subsequently, the morphological structure, neuronal viability and inflammatory levels of injured spinal cord were observed by histopathology, immunohistochemistry and RT-qPCR. In the obtained results, S100A9 was found to be highly expressed in the injured spinal cord and serum in the first 3 days after SCI. However, at 28 days after surgery, ABR treatment significantly improved motor function, reduced the cavity formation and neutrophil infiltration in the lesion, which was verified via HE staining and immunohistochemistry for myeloperoxidase. Furthermore, ABR treatment was found to effectively improve the survival and viability of neurons, as shown via Nissl staining and immunofluorescence of the synaptic plasticity markers, microtubule associated protein 2 and neurofilament 200. Moreover, S100A9 blockade effectively upregulated the mRNA expression level of the anti-inflammatory genes, IL-4 and IL-10 and downregulated the mRNA expression level of the pro-inflammatory factors, IL-1β, IL-6 and TNF-α. In addition, S100A9 blockade notably alleviated the apoptosis level of the injured nerve cells. Therefore, the findings of the present study revealed that S100A9 may be a useful target for the treatment of SCI.

The spinal cord is critical to the perception of peripheral information under sensory-guided motor behaviors in health and disease. However, the cellular activity underlie spinal cord function in freely behaving animals is not clear. Here, we developed a new method for imaging the spinal cord at cellular and subcellular resolution over weeks under naturalistic conditions. The method involves an improved surgery to reduce spinal movement, and the installation of a miniaturized two-photon microscope to obtain high-resolution imaging in moving mice. In vivo calcium imaging demonstrated that dorsal horn neurons show a sensorimotor program-dependent synchronization and heterogeneity under distinct cutaneous stimuli in behaving mice. The long-term imaging of sensory neurons revealed that in the spinal cord, healthy mice demonstrated stereotyped responses. However, in a neuropathic pain model, plasticity changes and neuronal sensitization were observed. We provide a practical method to study the function of spinal cord on sensory perception and disorders in freely behaving mice.

Objective. To investigate the correlation between Chinese medicine syndrome and cognitive dysfunction in patients with mild cognitive impairment (MCI). Methods. 121 MCI patients were included for syndrome differentiation and syndrome scoring according to the Chinese medicine syndrome classification standard of senile dementia. The cognitive function and cognitive subitems (including visual space and executive function, naming, attention, language, abstraction, delayed recall, and orientation) of patients with different Chinese medicine syndromes were scored with the Montreal Cognitive Assessment (MoCA). Correlation analysis was made on Chinese medicine syndromes and cognitive domain damage. Results. Chinese medicine syndromes from most to least were kidney deficiency and marrow reduction syndrome, turbid phlegm obstructing orifices syndrome, deficiency of heart and spleen syndrome, qi stagnation and blood stasis syndrome, and yin deficiency of heart and liver syndrome. There were no significant differences in MoCA scores among different Chinese medicine syndromes ( P > 0.05 ).In the kidney deficiency and marrow reduction syndrome, the delayed recall score was 1.74 ± 1.23 and the difference was statistically significant when compared with deficiency of heart and spleen syndrome or the yin deficiency of heart and liver syndrome ( P < 0.05 ). In the turbid phlegm obstructing orifices syndrome, the delayed recall score was 1.81 ± 1.33 and the difference was statistically significant when compared with the yin deficiency of heart and liver syndrome ( P < 0.05 ). There was a significant negative correlation between the kidney deficiency and marrow reduction syndrome’s Chinese medicine syndrome scores and MoCA scores ( P < 0.01 ), and there was a negative correlation between the turbid phlegm obstructing orifices syndrome’s Chinese medicine syndrome scores and MoCA scores ( P < 0.05 ). Correlation analysis showed that the kidney deficiency and marrow reduction syndrome was significantly negatively correlated with delayed recall scores ( P < 0.01 ), and it was also negatively correlated with visual space and executive function scores ( P < 0.05 ). The turbid phlegm obstructing orifices syndrome was significantly negatively correlated with delayed recall scores ( P < 0.01 ). Conclusion. The kidney deficiency and marrow reduction syndrome and the turbid phlegm obstructing orifices syndrome were the most common syndromes in MCI. Patients with kidney deficiency and marrow reduction syndrome might have obvious damage in delayed recall function and have damage in visual space and executive function. Patients with turbid phlegm obstructing orifices syndrome might have obvious damage in delayed recall function.

Background General anesthesia (GA), which is routinely applied in patients who undergo percutaneous endoscopic interlaminar lumbar discectomy (PEILD) of L5-S1 disc herniation, is closely associated with postoperative cognitive dysfunction (POCD) in the elderly. Local anesthesia (LA) is an alternative pain control protocol that has not yet been fully evaluated. Objectives To evaluate the feasibility of LA in PEILD compared with GA. Study design A retrospective study. Setting This study took place at the First Affiliated Hospital of Harbin Medical University. Methods A total of 120 patients (aged 60-85 years) diagnosed with L5-S1 disc herniation and with American Society of Anesthesiologists fitness grade I or II between March 2016 and August 2017 were enrolled in the current study. Patients were randomly divided into LA group and GA group. For LA, 0.25% lidocaine was injected layer-by-layer into skin, subcutaneous tissue, fasciae, lumbar facet joint, muscle, and ligamentum flavum followed by injection of 1.33% lidocaine into epidural space; for GA, propofol, sufentanil, and cisatracurium were infused intravenously at 1 to 2 mg/kg, 0.3 µg/kg, and 0.15 mg/kg, respectively. Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and MacNab Criteria (MNC) evaluated the feasibility of LA as pain control protocol in comparison to GA before and after operation. The development of POCD was assessed by the Mini-Mental State Examination 1 and 7 days postsurgery. Feasibility of LA as a pain control protocol was also evaluated by patient's willingness to receive the same surgical procedure immediately and 24 hours after the surgery, and intraoperative fluoroscopy use, blood loss, surgery duration, postoperative bed confinement, and duration and cost of hospital stay were also evaluated. Results Patients in both LA and GA groups had comparable VAS grade, ODI, and MNC pre- and post-PEILD, with significant pain reduction after operation. However, POCD developed only in GA group but not in LA group. In addition, compared with GA, LA group did not require postoperative bed confinement, had significantly shorter hospital stay, and lower hospital cost. Low intraoperative VAS grade and willingness to receive the same procedure reflected the acceptance of LA by patients. Limitations The development of POCD was examined only 7 days after operation. The follow-up should be extended to 3 months and 2 years postoperation. Conclusions LA has satisfactory pain control and low-risk of POCD in PEILD and is well accepted by patients. The benefits of LA are no postoperative bed confinement, faster recovery, shorter hospital stay, and lower hospital cost. Key words L5-S1 disc herniation, older patients, percutaneous endoscopic interlaminar lumbar discectomy, local anesthesia, general anesthesia, postoperative cognitive dysfunction, American Society of Anesthesiologists grade, Oswestry Disability Index, MacNab Criteria, Mini-Mental State Examination.

In order to improve the capability of monitoring and predicting strong convective weather of Zhaoqing area, monitoring and early-warning system of strong convective weather is developed. Graphic and image technology is applied in the development of the system. The region growing method is used in image segmentation. The map of all towns of Zhaoqing area is drawn by coordinate transformation and graphics technologies. The processed radar image and the map of Zhaoqing area have been overlapped. By using improved arc-length method, the system can judge which areas are affected by strong convective echo.

The regulation of glucose-stimulated insulin secretion and glucose excursion has a sensory component that operates in a sex-dependent manner. Objective Here, we aim to dissect the basis of the sexually dimorphic interaction between sensory neurons and pancreatic β cells and its overall impact on insulin release and glucose homeostasis. Methods We used viral retrograde tracing techniques, surgical and chemodenervation models, and primary cell-based co-culture systems to uncover the biology underlying sex differences in sensory modulation of pancreatic β-cell activity. Results Retrograde transsynaptic labeling revealed a sex difference in the density of sensory innervation in the pancreas. The number of sensory neurons emanating from the dorsal root and nodose ganglia that project in the pancreas is higher in male than in female mice. Immunostaining and confocal laser scanning microscopy confirmed the higher abundance of peri-islet sensory axonal tracts in the male pancreas. Capsaicin-induced sensory chemodenervation concomitantly enhanced glucose-stimulated insulin secretion and glucose clearance in male mice. These metabolic benefits were blunted when mice were orchidectomized prior to the ablation of sensory nerves. Interestingly, orchidectomy also lowered the density of peri-islet sensory neurons. In female mice, capsaicin treatment did not affect glucose-induced insulin secretion nor glucose excursion and ovariectomy did not modify these outcomes. Interestingly, same- and opposite-sex sensory-islet co-culture paradigms unmasked the existence of potential gonadal hormone-independent mechanisms mediating the male-female difference in sensory modulation of islet β-cell activity. Conclusion Taken together, these data suggest that the sex-biased nature of the sensory control of islet β-cell activity is a result of a combination of neurodevelopmental inputs, sex hormone-dependent mechanisms and the potential action of somatic molecules encoded by the sex chromosome complement., Highlights • Pancreas-projecting sensory neurons are more abundant in males than in females. • Male sex hormones regulate the density of peri-islet sensory innervation in adulthood. • Male sex hormones regulate sensory modulation of β-cell activity and glucose clearance. • Sex chromosome mechanisms regulate sensory modulation of islet β-cell activity.

Sensitive and reliable analysis of telomerase activity is important for clinical diagnosis, therapy, and prognosis of osteosarcoma. Telomerase activity is a complicated concept including both the amount of active telomerases and the length of the telomerases extension product. Still, few of the strategies formerly proposed distinguish the two aspects of telomerase activity. Herein, we propose a novel CRISPR-Cas12a-based fluorescent sensing platform that can output signals of both the amounts of telomerase and length of telomerase extension products with the assistance of an elegantly designed stem-loop probe and CRISPR-Cas12a system. On this basis, we induced a novel index, average telomerase activity, for accurate cancer reporting. Through systematic laboratory and clinical experiments, we have demonstrated that average telomerase activity can accurately distinguish cancer cells and has the potential for osteosarcoma staging.

Background: Groin pain can be induced by high-level (L1-L2 or L2-L3) lumbar disc herniation. However, 4.1% of patients with lower-level (L4-L5 or L5-S1) lumbar disc herniation also complained of groin pain. The pathomechanism of groin pain occurring due to lumbar disc herniation at and below the L4-5 levels is still unclear. Objective: To investigate the afferent pathways of lower-level lumbar disc herniation induced groin pain. And evaluate the clinical results of transforaminal endoscopic discectomy treatment for discogenic groin pain. Study Design: This retrospective observational study used an experimental design (institutional review board: HROH 201-C2-100). Setting: The research took place in the Laboratory Research Center and spine center at The First Affiliated Hospital of Harbin Medical University. Methods: Firstly, 14 adult Wistar rats were randomly divided into 2 groups: control group (the paravertebral sympathetic trunks were preserved) and experimental group (the paravertebral sympathetic trunks were resected). All Wistar rats were intraperitoneally anesthetized, and then 1 μL of fast blue was injected into the dorsal rami of L2 spinal nerves on the right side. Forty hours later, 2 μL of nuclear yellow was injected into the right posterior portion of the L5-L6 intervertebral disc. The L1 and L2 spinal ganglia were sectioned 8 hours later to observe fluorescently double-labeled cells and the effect of paravertebral sympathetic trunk resection. Secondly, 14 adult Wistar rats were anesthetized, and the right posterior portion of the L5- L6 intervertebral disc was electrostimulated to observe potential changes in the genitocrural nerve in the ipsilateral inguinal region. To evaluate the clinical outcomes of transforaminal endoscopic discectomy for the treatment of discogenic groin pain, between September 2015 and May 2017, transforaminal endoscopic discectomy was performed on 30 patients with lower-level discogenic groin pain. Outcomes were analyzed utilizing the visual analog scale, Oswestry disability index, and MacNab Criteria. Results: The total proportion of cells in the right L1 and L2 spinal ganglia with fast blue/nuclear yellow double labeling was 3.33% and 3.41% (48 and 56), respectively. The number of fluorescently doublelabeled cells in the resected paravertebral sympathetic trunk group was significantly less (P < 0.01). Electrical stimulation of the right posterior portion of the L5-L6 intervertebral disc could elicit action potentials in the ipsilateral genitofemoral nerve. All patients were followed for 12 months, and the visual analog scale score at 1 week, 1 month, 3 months, 6 months, and 12 months after the operation was 0.79 ± 0.55, 0.54 ± 0.55, 0.47 ± 0.65, 0.51 ± 0.65, and 0.69 ± 0.55, respectively, showing a significant decrease compared with the preoperative visual analog scale score (P < 0.01). Based on the MacNab scoring system, the effective rate was 100%, and the rate of good and excellent results was 93.3%. Limitations: A relatively small number of patients and a short follow-up period. Conclusions: Discogenic groin pain is transmitted by sympathetic nerves and appears in the area segmentally innervated by the anterior rami of the L1 and L2 spinal nerves. Posterolateral percutaneous transforaminal endoscopic discectomy and radiofrequency thermal annuloplasty are effective minimally invasive alternative treatments for discogenic groin pain. Key Words: Discogenic groin pain, percutaneous transforaminal endoscopic discectomy, radiofrequency thermal annuloplasty

Retinal degeneration diseases (RDDs) are common and devastating eye diseases characterized by the degeneration of photoreceptors, which are highly associated with oxidative stress. Previous studies reported that mitochondrial dysfunction is associated with various neurodegenerative diseases. However, the role of mitochondrial proteostasis mainly regulated by mitophagy and mitochondrial unfolded protein response (mtUPR) in RDDs is unclear. We hypothesized that the mitochondrial proteostasis is neuroprotective against oxidative injury in RDDs. In this study, the data from our hydrogen peroxide (H2O2)-treated mouse retinal cone cell line (661w) model of RDDs showed that nicotinamide riboside (NR)-activated mitophagy increased the expression of LC3B II and PINK1, and promoted the co-localization of LC3 and mitochondria, as well as PINK1 and Parkin in the H2O2-treated 661w cells. However, the NR-induced mitophagy was remarkably reversed by chloroquine (CQ) and cyclosporine A (CsA), mitophagic inhibitors. In addition, doxycycline (DOX), an inducer of mtUPR, up-regulated the expression of HSP60 and CHOP, the key proteins of mtUPR. Activation of both mitophagy and mtUPR increased the cell viability and reduced the level of apoptosis and oxidative damage in the H2O2-treated 661w cells. Furthermore, both mitophagy and mtUPR played a protective effect on mitochondria by increasing mitochondrial membrane potential and maintaining mitochondrial mass. By contrast, the inhibition of mitophagy by CQ or CsA reversed the beneficial effect of mitophagy in the H2O2-treated 661w cells. Together, our study suggests that the mitophagy and mtUPR pathways may serve as new therapeutic targets to delay the progression of RDDs through enhancing mitochondrial proteostasis.

Using historical data, a machine learning model is usually built to forecast the future meteorological elements such as temperature, precipitation, etc. However, for numerous small and medium-sized cities, it is a challenging task because the maintained data of these cities are usually very limited due to historical or infrastructural reasons. So it is difficult to build an accurate forecast model in small and medium-sized cities. Aiming at this problem, a forecast method based on transfer learning method is proposed. Using instance-based transfer learning, this method extends the data of the target city by transferring the data from related cities and then builds a forecast model based on the extended dataset, so that the problem of insufficient samples in machine learning is solved. As a case study, the proposed technique is applied in Zhaoqing City, China. In the experiments, the data of temperature sequence and the precipitation sequence of Gaoyao weather station in Zhaoqing district are extended according to the data of related cities. The transferred temperature data and precipitation data are collected from 1884 to 1997 in Hong Kong and 1908 to 2016 in Guangzhou, respectively. Then temperature and precipitation forecasting models are built based on least square method and autoregressive integrated moving average. The experimental results have been verified by the actual situation. The results justify the effectiveness of the proposed method in building accurate meteorological forecasting model with limited data, and the superiority over existing techniques.

Voice-over IP (VoIP) technology is a kind of digital transmission technology based on IP network. It is one of the important methods to use voice service in VoIP as steganographic carrier to ensure secure transmission. However, the traditional steganographic code has some problems, such as low embedding efficiency and weak concealment, which cannot meet the requirements of VoIP streaming media information hiding for the security of secret information. Therefore, a steganographic algorithm combining F5 and simplified wet paper code (SWPC) algorithm is proposed. The main idea is to embed secret messages in each row of the carrier matrix using the F5 algorithm, and then the SWPC algorithm is used to embed the columns according to the wet and dry characteristics of the wet paper code without affecting the results before row embedding. We use the VoIP streams encoded by the ITU-T G.729a codec as a carrier to verify the proposed scheme. The experimental results demonstrate that the proposed scheme can achieve relatively better IP speech data steganographic transparency and that it can outperform F5-WPC and SWPC approaches.

Aiming at many problems of school multimedia classroom management, a remote control system for multimedia classroom based on cloud computing is developed. The system includes cloud computing management platform, network switch, single-chip microcomputer and equipment in the multimedia classrooms. It uses VMware desktop virtualization technology to deploy virtual machine templates of different courses in each classroom through the campus network. It controls all multimedia equipment in each classroom by single-chip microcomputer remote control. In terms of software and hardware, key problems such as multithreading, socket communication and remote control are solved and a single-chip microcomputer is developed to control the classroom equipment through the serial ports automatically. Compared with the traditional system, the system based on cloud computing has the advantages of rapid deployment and unified management. It improves the teaching effects of multimedia course and it reduces the construction and maintenance of multimedia classrooms.

Animals and humans display two types of response to noxious stimuli. The first includes reflexive defensive responses that prevent or limit injury; a well-known example of these responses is the quick withdrawal of one's hand upon touching a hot object. When the first-line response fails to prevent tissue damage (for example, a finger is burnt), the resulting pain invokes a second-line coping response-such as licking the injured area to soothe suffering. However, the underlying neural circuits that drive these two strings of behaviour remain poorly understood. Here we show in mice that spinal neurons marked by coexpression of TAC1Cre and LBX1Flpo drive coping responses associated with pain. Ablation of these spinal neurons led to the loss of both persistent licking and conditioned aversion evoked by stimuli (including skin pinching and burn injury) that-in humans-produce sustained pain, without affecting any of the reflexive defensive reactions that we tested. This selective indifference to sustained pain resembles the phenotype seen in humans with lesions of medial thalamic nuclei1-3. Consistently, spinal TAC1-lineage neurons are connected to medial thalamic nuclei by direct projections and via indirect routes through the superior lateral parabrachial nuclei. Furthermore, the anatomical and functional segregation observed at the spinal level also applies to primary sensory neurons. For example, in response to noxious mechanical stimuli, MRGPRD- and TRPV1-positive nociceptors are required to elicit reflexive and coping responses, respectively. Our study therefore reveals a fundamental subdivision within the cutaneous somatosensory system, and challenges the validity of using reflexive defensive responses to measure sustained pain.

There is emerging evidence to support an important role for the transient receptor potential vanilloid type 1 (TRPV1) sensory innervation in glucose homeostasis. However, it remains unknown whether the glucoregulatory action of these afferent neurons is sex-biased and whether it is pancreatic β-cell-mediated. Objective We investigated in male and female mice whether denervation of whole-body or pancreas-projecting TRPV1 sensory neurons regulates adult functional β-cell mass and alters systemic glucose homeostasis. Methods We used a combination of pharmacological and surgical approaches to ablate whole-body or pancreatic TRPV1 sensory neurons and assessed islet β-cell function and mass, aspects of glucose and insulin homeostasis, and energy expenditure. Results Capsaicin-induced chemodenervation of whole-body TRPV1 sensory neurons improved glucose clearance and enhanced glucose-stimulated insulin secretion without alterations in β-cell proliferation and mass, systemic insulin sensitivity, body composition, and energy expenditure. Similarly, denervation of intrapancreatic TRPV1 afferents by pancreas intraductal injection of capsaicin or surgical removal of the dorsal root ganglia projecting into the pancreas lowered post-absorptive glucose levels and increased insulin release upon glucose stimulation. The beneficial effects of TRPV1 sensory denervation on glucose tolerance and β-cell function were observed in male but not female mice. Conclusion Collectively, these findings suggest that TRPV1 neurons regulate glucose homeostasis, at least partly, through direct modulation of glucose-induced insulin secretion and that this regulation operates in a sex-dependent manner., Highlights • Whole-body ablation of TRPV1 neurons increases insulin secretion and glucose clearance in male but not female mice. • Pancreas-selective ablation of TRPV1 neurons enhances insulin secretion and glucose clearance in male but not female mice. • Surgical removal of lower thoracic DRGs improves insulin secretion and glucose clearance in male but not female mice.