Rapid urbanization and meteorological changes are reshaping the urban vegetation pattern in urban core area: A national 315-city study in China.

Urban vegetation takes on the responsibility of improving the urban environment and human wellbeing. However, the changing pattern and its driving mechanism are still not well understood at the national scale, especially in China under nearly 20 years-long rapid urbanization. In this study, for urban core area in 315 cities, over 18,000 high-resolution remote sensing images across 18 years were used to detect the spatiotemporal changes of urban vegetation and furtherly explore the interaction and independence of rapid urbanization and meteorological change. We found that, urban vegetation coverage decreased from 12.23 % to 5.91 % (-0.35 % per year) in 2003 to 2020. Urban vegetation per capita presented a steeper decline by 68 % (-0.51 m2 per capita per year) from 18.94 m2 in 2003 to 9.83 m2 in 2020. Spatially, the northwest and central-south zone decreased faster at the regional scale, and small cities contribute the higher decreasing rate. From 2003 to 2020, urbanization is the significant negative factor which contribute to 29.6 % of the reduction, and the meteorological factors do not affect urban vegetation change. Also, we found that the temporal pattern of urban vegetation change could be separated into two stages, including a rapid decline stage (2009-2020) and a progressively declining stage (2003-2008), each has its own driving mechanism. From 2003 to 2008, the decline in urban vegetation had insignificant relationship with meteorological changes and rapid urbanization. However, from 2009 to 2020, urbanization became the most critical factor to affect the urban vegetation, the contribution of urbanization rises to 30.3 %, meteorological factors contribute 14.3 % to the variation (r2 = 0.52). A growing crisis awareness of the rapid decline (especially in 2009 to 2020) of urban vegetation should return to the public scene, and these findings may provide some essential suggestions for securing this urban ecological barrier.

Preparation of Gd-doped AuNBP@mSiO2 nanocomposites for the MR imaging, drug delivery and chemo-photothermal synergistic killing of breast cancer cells.

Under near-infrared (NIR) light, gold nanobipyramids (AuNBPs) exhibit a high photothermal conversion rate and photothermal stability, making them ideal mediators for photothermal therapy (PTT). In this study, highly purified AuNBPs are prepared, followed by coating their surfaces with mesoporous silica (mSiO2). The obtained AuNBP@mSiO2 nanocomplex exhibits an ellipsoidal shape with a relatively large specific surface, pore diameter and pore volume. To achieve MRI guided chemo-photothermal therapy of breast cancer cells, the nanocomplex is further coupled with the MRI contrast agent Gd-DTTA and the chemotherapeutic drug doxorubicin (DOX). The results indicated that under NIR light irradiation, AuNBPs exhibited promising PTT effects, while the cumulative release rate of DOX was significantly enhanced to 81.40%. Moreover, the chemo-photothermal therapy approach effectively eradicated 4T1 breast cancer cells. This work successfully confirms that chemo-photothermal synergistic therapy is an effective tumor treatment strategy and demonstrates the potential application of AuNBP@mSiO2 as a nano-drug delivery platform. Additionally, it introduces new ideas for the integrated study of breast cancer diagnosis and treatment.

Weighted gene coexpression network analysis reveals negative regulation of hypertrophic cardiomyopathy by carboxylesterase 1 and cathepsin C.

Hypertrophic cardiomyopathy (HCM) is a primary cardiomyopathy characterized by hypertrophic cardiomyocytes. It is one of the leading causes of sudden death in adolescents. However, the molecular mechanism of HCM is not clear. In our study, ribonucleic acid (RNA) sequence data of myocardial tissue in HCM patients were extracted from the Gene Expression Omnibus (GEO) database (GSE130036) and analyzed by weighted gene coexpression network analysis (WGCNA). A total of 31 coexpression modules were identified. The coexpression black module significantly correlated with maximum left ventricular wall thickness (Maxi LVWT). We screened the differentially expressed mRNAs between normal tissues and HCM tissues using the dplyr and tidyr packages in R3.6.2. The genes in the black module and differentially expressed genes were further intersected. We found that the expression of carboxylesterase 1 (CES1) and cathepsin C (CTSC) was downregulated in HCM tissues and negatively correlated with Maxi LVWT. We further verified the expression of CES1 and CTSC was downregulated in HCM clinical blood and negatively correlated with Maxi LVWT. Finally, we demonstrated that overexpression of CTSC and CES1 could alleviate HCM in an HCM cell model. In summary, the study suggests that CES1 and CTSC negatively regulate the development of HCM and have potential as therapeutic and diagnostic targets for HCM.

Evaluation of dentinal tubule occlusion and pulp tissue response after using 980-nm diode laser for dentin hypersensitivity treatment.

OBJECTIVES: To evaluate the effectiveness of the 980-nm diode laser for dentinal tubule occlusion, measure the intrapulpal temperature, and investigate the dental pulp response. MATERIALS AND METHODS: The dentinal samples were randomly divided into G1-G7 groups: control; 980-nm laser irradiation (0.5 W, 10 s; 0.5 W, 10 s × 2; 0.8 W, 10 s; 0.8 W, 10 s × 2; 1.0 W, 10 s; 1.0 W, 10 s × 2). The dentin discs were applied for laser irradiation and analyzed by scanning electron microscopy (SEM). The intrapulpal temperature was measured on the 1.0-mm and 2.0-mm thickness samples, and then divided into G2-G7 groups according to laser irradiation. Moreover, forty Sprague Dawley rats were randomly divided into the laser-irradiated group (euthanized at 1, 7, and 14 days after irradiation) and the control group (non-irradiated). qRT-PCR, histomorphology, and immunohistochemistry analysis were employed to evaluate the response of dental pulp. RESULTS: SEM indicated the occluding ratio of dentinal tubules in the G5 (0.8 W, 10 s × 2) and G7 (1.0 W, 10 s × 2) were significantly higher than the other groups (p < 0.05). The maximum intrapulpal temperature rises in the G5 were lower than the standard line (5.5 ℃). qRT-PCR showed that the mRNA expression level of TNF-α and HSP-70 upregulated significantly at 1 day (p < 0.05). Histomorphology and immunohistochemistry analysis showed that, compared with the control group, the inflammatory reaction was slightly higher at the 1 and 7 days (p < 0.05) and decreased to the normal levels at 14 days (p > 0.05). CONCLUSIONS: A 980-nm laser at a power of 0.8 W with 10 s × 2 defines the best treatment for dentin hypersensitivity in terms of compromise between the efficacy of the treatment and the safety of the pulp. CLINICAL RELEVANCE: The 980-nm laser is an effective option for treating dentin sensitivity. However, we need to ensure the safety of the pulp during laser irradiation.

Central medial thalamic nucleus dynamically participates in acute itch sensation and chronic itch-induced anxiety-like behavior in male mice.

Itch is an annoying sensation consisting of both sensory and emotional components. It is known to involve the parabrachial nucleus (PBN), but the following transmission nodes remain elusive. The present study identified that the PBN-central medial thalamic nucleus (CM)-medial prefrontal cortex (mPFC) pathway is essential for itch signal transmission at the supraspinal level in male mice. Chemogenetic inhibition of the CM-mPFC pathway attenuates scratching behavior or chronic itch-related affective responses. CM input to mPFC pyramidal neurons is enhanced in acute and chronic itch models. Specifically chronic itch stimuli also alter mPFC interneuron involvement, resulting in enhanced feedforward inhibition and a distorted excitatory/inhibitory balance in mPFC pyramidal neurons. The present work underscores CM as a transmit node of the itch signal in the thalamus, which is dynamically engaged in both the sensory and affective dimensions of itch with different stimulus salience.

Collateral projections from the ventral tegmental area/substantia nigra pars compacta to the nucleus accumbens and insular cortex in the rat.

Midbrain dopaminergic (DAergic) regions including ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) are involved in diverse brain functions. Previous studies demonstrated that the VTA/SNc to nucleus accumbens (NAc) pathway is critical in reward and motivation. Moreover, DAergic innervations within the insular cortex (IC) are reported to play important roles in pain regulation. To investigate whether VTA/SNc sends collateral projections to NAc and IC, we injected retrograde tracer Fluoro-Gold (FG) into the NAc and Fluorescent retrograde tracer beads (RetroBeads) into the ipsilateral IC in rats. Then, to detect whether collateral projection neurons participate in neuropathic pain, parts of the rats received the spare nerve injury (SNI) surgery. The immunofluorescence staining results showed that FG, RetroBeads, and FG/RetroBeads double-labeled neurons were distributed in the VTA/SNc bilaterally with an ipsilateral predominance. The proportion of FG/RetroBeads double-labeled neurons to the total number of FG and RetroBeads-labeled neurons was 16.7% and 30.3%, respectively. About 90.3% of FG/RetroBeads double-labeled neurons showed DAergic neuron marker tyrosine hydroxylase (TH)-immunoreactive (IR), whereas, only 7.5% exhibited a subset of GABAergic inhibitory projection neuron marker parvalbumin (PV)-IR. One week after SNI, about 53.1% and 33.6% of FG- and RetroBeads-labeled neurons were FG/Fos- and RetroBeads/Fos-IR neurons, respectively. Finally, about 35.9% of the FG/RetroBeads double-labeled neurons showed Fos-IR. The present study indicates that parts of DAergic and PV-IR GABAergic neurons in the VTA/SNc send collateral projections to both NAc and IC, which are activated under SNI-induced neuropathic pain, and probably contribute to the regulation of nociception.

Dry needling on latent and active myofascial trigger points versus oral diclofenac in patients with knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Latent and active myofascial trigger points (MTrPs) in knee-associated muscles may play a key role in pain management among patients with knee osteoarthritis (KOA). The aim of this study was to investigate the effect of dry needling treatment on pain intensity, disability, and range of motion (ROM) in patients with KOA. METHODS: This randomized, single-blinded, clinical trial was carried out for 6 weeks of treatment and 6-month follow-up. A total of 98 patients met the entry criteria and were randomly assigned to the dry needling latent and active myofascial trigger point (MTrPs) with the stretching group or the oral diclofenacwith the stretching group. Numeric Pain Rating Scale (NPRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and ROM were statistically analyzed before and after treatment and at the 6-month follow-up. RESULTS: A total of 42 patients in the dry needling group (DNG) and 35 patients in the diclofenac group (DG), respectively, completed the study, and there was no significant difference in the general data between the two groups. After treatments, both the groups showed a good effect in knee pain, function, and ROM, However, the DNG showed a significantly better result than the DG. Especially in the results of the 6-month follow-up, the DNG showed much better results than the DG. CONCLUSIONS: Dry needling on latent and active MTrPs combined with stretching and oral diclofenac combined with stretching can effectively relieve pain, improve function, and restore knee ROM affected by KOA. However, the effects of dry needling and stretching are better and longer lasting than those of oral diclofenac and stretching for at least 6 months. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ) in 17/11/2017 with the following code: ChiCTR-INR-17013432.

Morphological investigations of endomorphin-2 and spinoparabrachial projection neurons in the spinal dorsal horn of the rat.

It has been proved that endomorphin-2 (EM2) produced obvious analgesic effects in the spinal dorsal horn (SDH), which existed in our human bodies with remarkable affinity and selectivity for the µ-opioid receptor (MOR). Our previous study has demonstrated that EM2 made synapses with the spinoparabrachial projection neurons (PNs) in the SDH and inhibited their activities by reducing presynaptic glutamate release. However, the morphological features of EM2 and the spinoparabrachial PNs in the SDH have not been completely investigated. Here, we examined the morphological features of EM2 and the spinoparabrachial PNs by using triple fluorescence and electron microscopic immunohistochemistry. EM2-immunoreactive (-ir) afferents directly contacted with the spinoparabrachial PNs in lamina I of the SDH. Immunoelectron microscopy (IEM) were used to confirm that these contacts were synaptic connections. It was also observed that EM2-ir axon terminals contacting with spinoparabrachial PNs in lamina I contained MOR, substance P (SP) and vesicular glutamate transporter 2 (VGLUT2). In lamina II, MOR-ir neurons were observed to receive direct contacts from EM2-ir varicosities. The synaptic connections among EM2, MOR, SP, VGLUT2, and the spinoparabrachial PNs were also confirmed by IEM. In sum, our results supply morphological evidences for the analgesic effects of EM2 on the spinoparabrachial PNs in the SDH.

Exercise for Stroke Rehabilitation: A Bibliometric Analysis of Global Research From 2001 to 2021.

Objective: To make a bibliometric analysis of global trends in research into exercise interventions for stroke between 2001 and 2021. Method: This study did the systematic literature from 2001 to 2021 in Web of Science Core Collection. CiteSpace software was used to analyze the relationship of publications with countries, journals, authors, references, and keywords. Results: A total of 3,484 publications were obtained in the bibliometric analysis. The number of publications increased gradually over the period. The United States have the most number of publications. The journal stroke had the most citations per paper (106.95) and the highest impact factor (IF 2020, 7.194). The most high frequency keywords are "stroke," "rehabilitation," and "recovery," the top of burst key words are "health," "speed," and "aerobic exercise". Conclusion: These findings provide the trends of exercise for stroke s and provided the potential research frontiers in the past 20 years. It will be a useful basis for further research into focus issues, cooperators, development trends.

Effects of urbanization intensity on glomalin-related soil protein in Nanchang, China: Influencing factors and implications for greenspace soil improvement.

Glomalin-related soil protein (GRSP) is a stable and persistent glycoprotein secreted by arbuscular mycorrhizal fungi that plays an important role in sequestering soil organic carbon (SOC) and improving soil quality. Rapid urbanization disturbs and degrades the soil quality in the greenspace. However, few studies have investigated the effects of urbanization on GRSP and its influencing factors. This study selected impervious surface area as a measure of urbanization intensity. A total of 184 soil samples were collected from the 0-20 cm soil layer in the greenspace of Nanchang, China (505 km2). The GRSP content, soil properties, urban forest characteristics, and land-use configuration were determined. The total GRSP (TG) and easily extractable GRSP (EEG) contents were 2.38 and 0.57 mg g-1, respectively. TG and EEG decreased by 16.22% and 19.35%, respectively, from low to heavy urbanized areas. Moreover, SOC decreased from 39.9 to 1.4 mg g-1, while EEG/SOC and TG/SOC increased by approximately 17% and 34%, respectively, indicating the significant contribution of GRSP to the SOC pool. Pearson and redundancy analysis showed that GRSP was positively correlated with SOC, phosphorus, nitrogen, vegetation richness, and tree height, but negatively correlated with pH, bulk density, and impervious area. The partial least squares path model demonstrated that urbanization affected soil properties, forest characteristics, and land use factors, resulting in GRSP changes. This study clarifies the key factors of urbanization that affect GRSP and provides insight for urban greenspace soil improvement from the new perspective of enhancing the GRSP content.

NADH dehydrogenase subunit 1/4/5 promotes survival of acute myeloid leukemia by mediating specific oxidative phosphorylation.

Acute myeloid leukemia (AML) is a type of hematological malignancy caused by uncontrolled clonal proliferation of hematopoietic stem cells. The special energy metabolism mode of AML relying on oxidative phosphorylation is different from the traditional 'Warburg effect'. However, its mechanism is not clear. In the present study, it was demonstrated that the mRNA expression levels of NADH dehydrogenase subunit 1, 4 and 5 (ND1, ND4 and ND5) were upregulated in AML samples from The Cancer Genome Atlas database using the limma package in the R programming language. Reverse transcription­quantitative PCR and ELISA were used to verify the upregulation of ND1, ND4 and ND5 in clinical samples. Pan­cancer analysis revealed that the expression of ND1 was upregulated only in AML, ND2 was upregulated only in AML and thymoma, and ND4 was upregulated only in AML and kidney chromophobe. In the present study, it was demonstrated that silencing of ND1/4/5 could inhibit the proliferation of AML cells in transplanted tumor of nude mice. Additionally, it was found that oxidative phosphorylation and energy metabolism of AML cells were decreased after silencing of ND1/4/5. In conclusion, the present study suggested that ND1/4/5 may be involved in the regulation of oxidative phosphorylation metabolism in AML as a potential cancer­promoting factor.

Decrease in the residents' accessibility of summer cooling services due to green space loss in Chinese cities.

Urban green spaces (UGSs) reduce the surrounding temperature and create cooling areas as a buffer between people and high temperatures, thus helping residents adapt to the warming climate. However, the accessibility of UGS cooling services to the residents of cities remains largely unknown, which hinders decision-making regarding the formulation of climate adaptation and urban greening schemes. In the present study, we estimated the number of residents who accessed UGSs for cooling by analyzing the annual changes in such cooling areas during summer across 315 Chinese cities from 2003 to 2015. Approximately 93.3% of the cities showed significant decreasing trends (p < 0.05) of the total UGS area; as such the UGS coverage dropped from 12.23 ± 0.32% in 2003 to 7.69 ± 0.22% in 2015. Consequently, with the prevalent loss of UGS, the coverage of cooling spaces decreased from 32.55 ± 0.76% in 2003 to 24.39 ± 0.60% in 2015. This has formed a spatial mismatch between the growing urban population and the remaining UGSs. Accordingly, the number of residents of areas outside these cooling spaces increased by 4.23 million per year. In particular, the shortage of cooling services was more significant in cities with < 20,000 USD gross domestic product per capita and < 5 million residents than in the rest of the cities. To minimize the adverse impacts of increasing temperatures, focused greening plans are warranted, specifically in underdeveloped cities.

Ultrasensitive electrochemical sensor for mercury ion detection based on molybdenum selenide and Au nanoparticles via thymine-Hg2+-thymine coordination.

An ultrasensitive and specific-selection electrochemical sensor was constructed for Hg2+ detection based on Au nanoparticles and molybdenum selenide (Au NPs@MoSe2) as well as the thymine-Hg2+-thymine (T-Hg2+-T) coordination. Herein, Au NPs@MoSe2 not only could improve the sensitivity due to the large surface area and good electrical conductivity but also offered more sites to immobilize thiol-labeled T-rich hairpin DNA probes (P-1), which has a specific recognition for Hg2+ and methylene blue-labeled T-rich DNA probes (MB-P). When Hg2+ and MB-P exist, P-1 and MB-P can form a stable T-Hg2+-T complex. Then, methylene blue can be close to the electrode and detectable via differential pulse voltammetry (DPV). Benefiting from the specific recognition of T-Hg2+-T and the merits of Au NPs and MoSe2, the fabricated biosensor presented an ultrasensitive and highly selective performance. The DPV responses had a positive linear relationship with Hg2+ concentrations over ten orders of magnitude from 1.0 × 10-16 to 1.0 × 10-7 mol L-1. The detection limit was down to 1.1 × 10-17 mol L-1. Moreover, the developed sensor exhibited a promising application for trace Hg2+determination in water samples.

A sandwich-type photoelectrochemical aptasensor using Au/BiVO4 and CdS quantum dots for carcinoembryonic antigen assay.

A novel sandwich-type photoelectrochemical (PEC) aptasensor for the carcinoembryonic antigen (CEA) assay was fabricated using the CEA aptamer, Au/BiVO4 and CdS quantum dots (CdS QDs). In virtue of the localized surface plasmon resonance effect of Au nanoparticles, Au/BiVO4 showed an effective utilization of visible light and excellent photoactivity, and was employed as the photoanode. After CdS QDs were conjugated to Au/BiVO4 through the sandwich structure based on the hybridization of the CEA aptamer with two partially complementary single-stranded DNA molecules, the photocurrents were further enhanced by a resonance energy transfer between CdS QDs and Au nanoparticles. Meanwhile, the consumption of the photo-induced holes by ascorbic acid could also retard the combination of the electron-hole pairs and cause an increase of the photocurrents. However, the specific recognition of CEA by the CEA aptamer could destroy the sandwich structure and remarkably weaken the photocurrent response. Thus, the quantitative detection of CEA was connected with the decrease of the photocurrent. Benefitting from the above methods for signal enhancement, the PEC aptasensor showed a wide sensing range of 0.0001-10 ng mL-1 and a low detection limit of 0.047 pg mL-1 for CEA detection. The specificity, stability and recoveries of the PEC aptasensor were also excellent. Therefore, the construction of the present PEC aptasensor provides a universal and practical method for sensing other substances.

Projecting neurons in spinal dorsal horn send collateral projections to dorsal midline/intralaminar thalamic complex and parabrachial nucleus.

Itch is an annoying sensation that always triggers scratching behavior, yet little is known about its transmission pathway in the central nervous system. Parabrachial nucleus (PBN), an essential transmission nucleus in the brainstem, has been proved to be the first relay station in itch sensation. Meanwhile, dorsal midline/intralaminar thalamic complex (dMITC) is proved to be activated with nociceptive stimuli. However, whether the PBN-projecting neurons in spinal dorsal horn (SDH) send collateral projections to dMITC, and whether these projections involve in itch remain unknown. In the present study, a double retrograde tracing method was applied when the tetramethylrhodamine-dextran (TMR) was injected into the dMITC and Fluoro-gold (FG) was injected into the PBN, respectively. Immunofluorescent staining for NeuN, substance P receptor (SPR), substance P (SP), or FOS induced by itch or pain stimulations with TMR and FG were conducted to provide morphological evidence. The results revealed that TMR/FG double-labeled neurons could be predominately observed in superficial laminae and lateral spinal nucleus (LSN) of SDH; Meanwhile, most of the collateral projection neurons expressed SPR and some of them expressed FOS in acute itch model induced by histamine. The present results implicated that some of the SPR-expressing neurons in SDH send collateral projections to the dMITC and PBN in itch transmission, which might be involved in itch related complex affective/emotional processing to the higher brain centers.

Projections from the lateral parabrachial nucleus to the lateral and ventral lateral periaqueductal gray subregions mediate the itching sensation.

ABSTRACT: Lateral and ventral lateral subregions of the periaqueductal gray (l/vlPAG) have been proved to be pivotal components in descending circuitry of itch processing, and their effects are related to the subclassification of neurons that were meditated. In this study, lateral parabrachial nucleus (LPB), one of the most crucial relay stations in the ascending pathway, was taken as the input nucleus to examine the modulatory effect of l/vlPAG neurons that received LPB projections. Anatomical tracing, chemogenetic, optogenetic, and local pharmacological approaches were used to investigate the participation of the LPB-l/vlPAG pathway in itch and pain sensation in mice. First, morphological evidence for projections from vesicular glutamate transporter-2-containing neurons in the LPB to l/vlPAG involved in itch transmission has been provided. Furthermore, chemogenetic and optogenetic activation of the LPB-l/vlPAG pathway resulted in both antipruritic effect and analgesic effect, whereas pharmacogenetic inhibition strengthened nociceptive perception without affecting spontaneous scratching behavior. Finally, in vivo pharmacology was combined with optogenetics which revealed that AMPA receptor-expressing neurons in l/vlPAG might play a more essential role in pathway modulation. These findings provide a novel insight about the connections between 2 prominent transmit nuclei, LPB and l/vlPAG, in both pruriceptive and nociceptive sensations and deepen the understanding of l/vlPAG modulatory roles in itch sensation by chosen LPB as source of ascending efferent projections.

Effects of whole body vibration exercise on lumbar-abdominal muscles activation for patients with chronic low back pain.

BACKGROUND: Whole body vibration (WBV) training as an intervention method can cure chronic low back pain (CLBP). Different WBV parameters exert different effects on lumbar-abdominal muscle performance. Currently, there is a lack of study researched the influence of WBV training on patients with CLBP by lumbar-abdominal muscle activity. Therefore, this study aimed to investigate how WBV and exercise and their interactions influence lumbar-abdominal muscle activity in patients with CLBP. METHODS: a group of ambulatory patients with chronic low back pain. Muscle activities of the multifidus (MF), erector spinae (ES), abdominal oblique externus muscle (AOE) and the rectus abdominis muscle (RA) were measured by surface electromyography, whereas participants performed 4 different exercises (single bridge, plank, side stay and V crunch) during three whole body vibration conditions and a no-vibration condition in a single experimental session. RESULTS: Compared with the same exercises without whole body vibration, muscle activity increased when whole body vibration was added to the exercises. MF; the WBV frequency (P = 0.002,) and exercise (P < 0.001) presented significant effects on the root mean square of MF, whereas exercise * frequency (P = 0.044) also resulted in significant interaction effects. ES: the significant differences were detected at WBV frequency (P < 0.001), exercise (P < 0.001), the interaction effect of exercise and frequency (P = 0.225) was no significant. RA: the significant difference was detected at WBV frequency (P = 0.018), the effect of exercise (P = 0.590) and the exercise * frequency interaction (P = 0.572) were no significant. AOE: the significant difference was detected at WBV frequency (P < 0.001), the effect of exercise (P = 0.152) and the exercise * frequency interaction (P = 0.380) were no significant. CONCLUSION: Adding whole body vibration to exercise could increase muscle activation of lumbar-abdominal muscle in patients with CLBP. The optimum frequency for lumbar-abdominal muscles is 15 Hz. The best exercises include plank for multifidus and erector spinae, V crunch for rectus abdominis and single bridge for abdominal oblique externus. CLINICAL REGISTRATION: Trial registration: ChiCTR-TRC-13003708 . Registered 19 October 2013. THE CODE OF ETHICAL APPROVAL: 2014008.

A Neural Circuit from Thalamic Paraventricular Nucleus to Central Amygdala for the Facilitation of Neuropathic Pain.

As one of the thalamic midline nuclei, the thalamic paraventricular nucleus (PVT) is considered to be an important signal integration site for many descending and ascending pathways that modulate a variety of behaviors, including feeding, emotions, and drug-seeking. A recent study has demonstrated that the PVT is implicated in the acute visceral pain response, but it is unclear whether the PVT plays a critical role in the central processing of chronic pain. Here, we report that the neurons in the posterior portion of the PVT (pPVT) and their downstream pathway are involved in descending nociceptive facilitation regarding the development of neuropathic pain conditions in male rats. Lesions or inhibition of pPVT neurons alleviated mechanical allodynia induced by spared nerve injury (SNI). The excitability of pPVT-central amygdala (CeA) projection neurons was significantly increased in SNI rats. Importantly, selective optogenetic activation of the pPVT-CeA pathway induced obvious mechanical hypersensitivity in naive rats. In addition, we used rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques to define a novel neuronal circuit in which glutamatergic neurons in the vlPAG were the target of the pPVT-CeA descending facilitation pathway. Our data suggest that this pPVTGlu+-CeA-vlPAGGlu+ circuit mediates central mechanisms of descending pain facilitation underlying persistent pain conditions.SIGNIFICANCE STATEMENT Studies have shown that the interactions between the posterior portion of the thalamic paraventricular nucleus (pPVT) and central amygdala (CeA) play a critical role in pain-related emotional regulation. However, most reports have associated this circuit with fear and anxiety behaviors. Here, an integrative approach of behavioral tests, electrophysiology, and immunohistochemistry was used to advance the novel concept that the pPVT-CeA pathway activation facilitates neuropathic pain processing. Using rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques, we found that glutamatergic neurons in the vlPAG were the target of the pPVT-CeA pathway. Thus, this study indicates the involvement of a pPVTGlu+-CeA-vlPAGGlu+ pathway in a descending facilitatory mechanism underlying neuropathic pain.

dmPFC-vlPAG projection neurons contribute to pain threshold maintenance and antianxiety behaviors.

The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the function of specific cell types remain largely unclear. Here, we show that lesions in the dmPFC induced an algesic and anxious state. Using multiple tracing methods including a rabies-based transsynaptic tracing method, we outlined an excitatory descending neural pathway from the dmPFC to the ventrolateral periaqueductal gray (vlPAG). Specific activation of the dmPFC/vlPAG neural pathway by optogenetic manipulation produced analgesic and antianxiety effects in a mouse model of chronic pain. Inhibitory neurons in the dmPFC were specifically activated using a chemogenetic approach, which logically produced an algesic and anxious state under both normal and chronic pain conditions. Antagonists of the GABAA receptor (GABAAR) or mGluR1 were applied to the dmPFC, which produced analgesic and antianxiety effects. In summary, the results of our study suggest that the dmPFC/vlPAG neural pathway might participate in the maintenance of pain thresholds and antianxiety behaviors under normal conditions, while silencing or suppressing the dmPFC/vlPAG pathway might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors.

Autophagy-related gene expression classification defines three molecular subtypes with distinct clinical and microenvironment cell infiltration characteristics in colon cancer.

BACKGROUND: Multiple molecular subtypes with distinct clinical outcomes in colon cancer have been identified in recent years. Nonetheless, the autophagy-related molecular subtypes as well as its mediated tumor microenvironment (TME) cell infiltration characteristics have not been fully understood. METHODS: Based on the seven colon cancer cohorts with 1580 samples, we performed a comprehensive genomic analysis to explore the molecular subtypes mediated by autophagy-related genes. The single-sample gene-set enrichment analysis (ssGSEA) was used to quantify the relative abundance of each cell infiltration in the TME. Unsupervised methods were used to perform autophagy subtype clustering. Least absolute shrinkage and selection operator regression (LASSO) was used to construct autophagy characterization score (APCS) signature. RESULTS: We determined three distinct autophagy-related molecular subtypes in colon cancer. The three autophagy subtypes presented significant survival differences. Microenvironment analyses revealed the heterogeneous TME immune cell infiltration characterization between three subtypes. Cluster 1 autophagy subtype was characterized by abundant innate and adaptive immune cell infiltration. This subtype exhibited an enhanced stromal activity including activated pathways of epithelial-mesenchymal transition, TGF-ß and angiogenesis, and an increased infiltration of fibroblasts and endothelial cells. The expression of immune checkpoint molecules was also significantly up-regulated, which may mediate immune escape in Cluster 1 subtype. Cluster 2 subtype was characterized by relatively lower TME immune cell infiltration and enhanced DNA damage repair pathways. Cluster 3 subtype was characterized by the suppression of immunity. Patients with high APCS, with poorer survival, presented a significantly positive correlation with TME stromal activity. Low APCS, relevant to activated damage repair pathways, showed enhanced responses to anti-PD-1/PD-L1 immunotherapy. Two immunotherapy cohorts confirmed patients with low APCS exhibited prominently enhanced clinical response and treatment advantages. CONCLUSIONS: This study may help understand the molecular characterization of autophagy-related subtypes. We demonstrated the autophagy genes in colon cancer could drive the heterogeneity of TME immune cell infiltration. Our study represented a step toward personalized immunotherapy in colon cancer.