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Objectives: Acupuncture has been found to be effective at relieving many inflammatory pain conditions, including rheumatoid arthritis (RA). We aimed to assess the anti-inflammatory potential of manual acupuncture (MA) treatment of RA using adjuvant-induced arthritic (AIA) rats and to explore the underlying mechanisms. Methods: The anti-inflammatory and analgesic actions of MA at ST36 ( Zusanli) in AIA rats were assessed using paw withdrawal latency and swelling, histological examination and cytokine detection by enzyme-linked immunoassay (ELISA). The cell–cell communication (CCC) network was analyzed with a multiplex immunoassay of 24 immune factors expressed in the inflamed joints, and the macrophage and Treg populations and associated cytokines regulated by MA were investigated using reverse-transcription quantitative polymerase chain reaction (RT-qPCR), ELISA and flow cytometry. Results: MA markedly decreased heat hyperalgesia and paw swelling in AIA rats. MA-treated rats also exhibited decreased levels of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β) coupled with increased anti-inflammatory cytokines (IL-10, transforming growth factor (TGF)-β1) in the ankle joints at protein and mRNA levels. CCC network analysis confirmed that macrophages are of critical importance and are potential therapeutic targets in RA. Repeated treatment with MA triggered a macrophage phenotypic switch in the paws, with fewer M1 macrophages. Prominent increases in the Treg cell population and TGF-β1 in the popliteal lymph nodes demonstrated the immunomodulatory effects of MA. Furthermore, a selective TGF-β1-receptor inhibitor, SB431542, attenuated the anti-inflammatory effects of MA and MA-induced suppression of the levels of M1-released cytokines. Conclusion: These findings provide novel evidence that the anti-inflammatory and analgesic effects of MA on RA act through phenotypic modulation involving the inhibition of M1 macrophage polarization and an increase in the Treg cell population, highlighting the potential therapeutic advantages of acupuncture in controlling pain and ameliorating inflammatory conditions.

1. Accurate estimates of wildlife distributions and population persistence are essential for conservation programs. Occupancy models that account for detection probability have been used to characterize the occupancy and habitat selection of imperilled species. However, failure to distinguish between true-presence and pseudo-presence associated with territorial behaviour can result in the overestimation of the occupancy probability of target species in unsuitable habitats, and this can have major implications for the development of conservation strategies.2. For highly territorial wildlife species requiring high-quality habitat for survival, occasional ‘Presence’ in unsuitable areas might be related to dispersal or migration, but this does not reflect actual occupancy and habitat use. ‘True-Presence’ and ‘Pseudo-Presence’ should be distinguished for target species to better reflect their actual occupancy and habitat use.3. To investigate the effect of ‘True-Presence’ and ‘Pseudo-Presence’ on wildlife occupancy estimation, we developed a modified model (Mm) that considers the territorial behaviour of the Amur tiger in northeast China, which distinguished between ‘True-Presence’ and ‘Pseudo-Presence’. We compared two models, Mmand M0(conventional occupancy model), and assessed model performance using goodness-of-fit evaluation, detection and occupancy probability, and favourable variable selection.4. We found that Mm, which has fewer favourable variables, is more powerful than M0for estimating detection and occupancy probability, as well as characterizing the effect of various factors on the habitat use of Amur tigers. Furthermore, Mmsignificantly reduced the overestimation of occupancy probability outside the home range compared with M0, and detection probability estimates did not significantly differ between M0and Mm. Finally, Mmprovided more empirical habitat selection variables for the Amur tiger.5. Our results revealed how ‘True-Presence’ and ‘Pseudo-Presence’ affect the occupancy probability and habitat selection of Amur tigers. Our method improves the accuracy of occupancy models; it can also be used to characterize the habitat selection and distribution of wildlife species and be applied to other territorial species.

Photocatalysis is a promising advanced oxidation technology for treating wastewater; however, the complexity, diversity, and variability of actual wastewater make its application difficult at the c...

Chronic low back pain (CLBP), lasting >3 months, is the end result of multiple pathogenic factors. Unfortunately, little is known about CLBP pathogenesis, which limits its advancements in clinical therapy and disease management. This paper summarizes the known pathological axes of CLBP, involving both peripheral and central systems. In particular, this paper details injurious nerve stimulation, inflammation-induced peripheral pathway, and central sensitization. Lumbar components, such as intervertebral disc (IVD), facet joints, muscles, fascia, ligaments, and joint capsules, contain pain receptors called nociceptors. Degeneration of the aforementioned lumbar components activates inflammatory pathways, which can directly damage nerves, lower nociceptor threshold to fire action potentials (AP), and cause pain. Additionally, damaged lumbar IVDs and endplates can also lead to the pathologic invasion of nerve growth and innervation, followed by the compression of herniated IVDs on nerve roots, thereby causing traumatic neuropathic pain. The central mechanism of CLBP involves alteration of the sensory processing of the brain and malfunction of the descending pain modulatory system, which facilitates pain amplification in the center nervous system (CNS). Lastly, abnormalities in the brain biochemical metabolism, activation of glial cells, and subsequent inflammation also play important roles in CLBP development. Taken together, inflammation plays an important role in both peripheral and central sensitization of CLBP. Due to the heterogeneity of CLBP, its pathological mechanism remains complex and difficult to understand. Therefore, it is a worthy field for future research into the subcomponents of CLBP pathogenesis, in order to distinguish the specific form of the disease, identify its origins, and develop corresponding highly effective comprehensive therapy against CLBP.

Background: The antagonistic relationship between adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling play a vital role in cancer development. The anti-cancer effects of berberine have been reported as a main component of the traditional Chinese medicine Rhizoma coptidis, although the roles of these signaling pathways in these effects have not been systematically reviewed. Methods: We searched the PubMed database for studies with keywords including [“berberine”] and [“tumor” or “cancer”] and [“AMPK”] or [“AKT”] published between January 2010 and July 2020, to elucidate the roles of the AMPK and PI3K/AKT pathways and their upstream and downstream targets in the anti-cancer effects of berberine. Results: The anti-cancer effects of berberine include inhibition of cancer cell proliferation, promotion of apoptosis and autophagy in cancer cells, and prevention of metastasis and angiogenesis. The mechanism of these effects involves multiple cell kinases and signaling pathways, including activation of AMPK and forkhead box transcription factor O3a (FOXO3a), accumulation of reactive oxygen species (ROS), and inhibition of the activity of PI3K/AKT, rapamycin (mTOR) and nuclear factor-κB (NF-κB). Most of these mechanisms converge on regulation of the balance of AMPK and PI3K/AKT signaling by berberine. Conclusion: This evidence supports the possibility that berberine is a promising anti-cancer natural product, with pharmaceutical potential in inhibiting cancer growth, metastasis and angiogenesis via multiple pathways, particularly by regulating the balance of AMPK and PI3K/AKT signaling. However, systematic preclinical studies are still required to provide scientific evidence for further clinical studies.

To investigate whether blood-brain barrier (BBB) served a key role in the edema-relief effect of bloodletting puncture at hand twelve Jing-well points (HTWP) in traumatic brain injury (TBI) and the potential molecular signaling pathways. Adult male Sprague-Dawley rats were assigned to the sham-operated (sham), TBI, and bloodletting puncture (bloodletting) groups (n=24 per group) using a randomized number table. The TBI model rats were induced by cortical contusion and then bloodletting puncture were performed at HTWP twice a day for 2 days. The neurological function and cerebral edema were evaluated by modified neurological severity score (mNSS), cerebral water content, magnetic resonance imaging and hematoxylin and eosin staining. Cerebral blood flow was measured by laser speckles. The protein levels of aquaporin 4 (AQP4), matrix metalloproteinases 9 (MMP9) and mitogen-activated protein kinase pathway (MAPK) signaling were detected by immunofluorescence staining and Western blot. Compared with TBI group, bloodletting puncture improved neurological function at 24 and 48 h, alleviated cerebral edema at 48 h, and reduced the permeability of BBB induced by TBI (all P

Background Failure of the proliferation and infiltration of tumor-specific T cells in tumor site has been considered as one of important reasons induce the inefficiencies of immune checkpoint therapies in advanced cancers. Therefore, we aimed to demonstrate how combinatorial sympathetic and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blockade affects the tumor growth of melanoma-bearing mice and potential mechanisms. Methods Tumor growth was measured and the infiltrating immune cell populations were observed with flow cytometry in B16-F10 melanoma-bearing mice treated with combined sympathetic and immune checkpoint blockade, using anti-CTLA-4 antibodies. The expression of adrenergic receptors was investigated in human peripheral blood mononuclear cells and their subpopulations, and the proliferation of T cell subsets was detected when stimulated by norepinephrine and its antagonists. Results B16-F10 tumor growth was associated with infiltrating CD8+ T cells. Combinatorial sympathetic and CTLA-4 blockade inhibited tumor growth and enhanced CD8+ infiltration. Meanwhile, all β1, β2 and β3 adrenergic receptors were found to be expressed in human peripheral blood mononuclear cells, activated T cells, monocytes, and monocyte-induced dendritic cells. β2-adrenergic receptors were expressed in most CD4+ T cells with increased expression in activated CD8+ T cells. Moreover, norepinephrine was able to prevent CD4+ T cell proliferation and β2-adrenergic receptor antagonists could reverse the inhibition of CD4+, but not CD8+ cell proliferation. Conclusions We conclude that the combination of sympathetic and CTLA-4 inhibitors is more effective for inhibiting melanoma progression than a single treatment and might enhance the infiltration of T cells in the tumor site, offering a novel therapeutic approach for immune checkpoint targeting.

Oncogenic KRAS-driven cancers have long been considered as “undruggable” due to limited therapeutic options. While the recent success of KRAS-G12C inhibitors argues against the “undruggability” of KRAS, this treatment only benefits a small proportion of patients with KRAS mutant cancers, leaving an urgent need for modalities to target other KRAS mutants. KRAS-calmodulin (CaM) signaling axis reportedly regulates the oncogenic properties of KRAS through its C-terminal hypervariable region. Phosphorylation of KRAS by activated protein kinase C (PKC) uncouples KRAS-CaM, resulting in growth inhibition effective against the entire spectrum of KRAS hotspot mutations. However, broadly activating PKC could mediate tumor promoting signaling nodes and cause systemic toxicity, undermining its applicability as an anti-KRAS therapy. Here, we found that prostratin induces KRAS phosphorylation, resulting in an elevated level of active CaM in the cytosol of KRAS mutant cells, and consequentially suppresses their malignancies. A whole-genome wide CRISPR/Cas9 knockout screening, further confirmed by biochemical analysis, revealed that prostratin acts through activating PKCα. Functional studies confirmed PKCα as the sole kinase to phosphorylate KRAS and, therefore, a KRAS suppressor. Activation of PKCα induces senescence in KRAS mutant tumor cells through PTPN14, accompanied by a secretory phenotype contributing to the growth inhibition, and parallelly mediates a nuclear translocation of a CaM-dependent transcription activator, CAMTA-1, which can be a biomarker to indicate the activity of PKCα-KRAS-CaM axis. Our findings reveal a previously understudied regulation of KRAS-CaM axis by PKCα, which can be an actionable target for developing anti-KRAS therapeutics.One Sentence SummaryThis study deciphers a PKCα-led tumor suppressive effect specific to the “undruggable” KRAS-mutant tumor cells through the phosphorylation of KRAS and a consequently altered KRAS-CaM signaling axis.

To identify the prominent molecular signaling in acupoints and explore their roles in initiating the analgesia effect of manual acupuncture (MA). A three-step study was conducted, the experiment 1 was a genome-wide analysis of the tissue at acupoint Zusanli (ST 36), including 12 Wistar rats which were divided into control, control+MA1, and control+MA7 groups. In the experiment 2, the paw withdrawal latency (PWL), immunohistochemistry and Western blot analysis of phospho-nuclear factor kappa B (NFκB) p65 (p-p65), phospho-NFκB p50 (p-p50) at ST 36 were performed on rats of saline, saline+MA, and complete Freund’s adjuvant (CFA)+MA groups (n=6). In experiment 3, 24 rats were divided into saline+DMSO, CFA+DMSO, CFA+DMSO+MA, and CFA+BAY 11–7082+MA groups, the PWL and immunofluorescence assay of NFκB p65 at ST 36 was conducted. (1) The gene: inhibitor of NFκB (Nfkbia), interleukin-1β (Il1b), interleukin-6 (Il6), chemokine c-x-c motif ligand 1 (Cxcl1), monocyte chemoattractant protein-1 (MCP-1/Ccl2) expressions in the control+MA7 group were significantly increased (P

The North Chinese leopard (Panthera pardus japonensis), the least‐known big cat, disappeared in most historical range for decades, following the development of modern civilization. Unfortunately, we have scarce knowledge about the status of this big cat so far, apart from anecdotal reports. In this study, we investigated density, distribution, and habitat use of the leopard, the apex predator, in a complex forest landscape in the Loess Plateau. We used a camera‐trapping network to obtain population estimates for leopards over 2 years through spatially explicit capture–recapture models. Our results, based on maximum likelihood and Bayesian/MCMC methods, reveal that the largest wild population of the leopard was found widely distributed in remnant forests in central Loess plateau. The population is increasing in our study area, and the density of leopards (1.70 (SE = 0.48) − 2.40 (SE = 0.67)/100 km2) is higher than other areas of China. According to the analysis of 2 seasonal occupancy models, prey species drive partially the leopard habitat use, predicting that the big cat thrives from the recovery of prey community. However, human disturbances, especially oil wells, seem to have negative impacts on the habitat use of leopards. Specifically, it is necessary to have joint efforts by the government and researchers to improve human disturbances management and prey species population density, as well as strengthen the investment in research on the North Chinese leopard, which could all further strengthen protection ability and ensure the long‐term survival of this species., The study revealed a wild population of free‐ranging leopards with the highest density in China so far, which also provided the first comprehensive evidence documenting the status of the North Chinese leopard, the rarest known leopard subspecies. The big cat is living in a human‐dominated landscape and still negatively influenced by human associated activities.

To summarize the research status of the changes in local microenvironment of acupoints caused by acupuncture, provide theoretical guidance for the initiation mechanisms of local acupuncture effect at acupoints. Using acupuncture, acupoint as key words to search China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), PubMed and other databases, the representative articles were selected for review. Acupuncture could excite afferent nerves, activate cells, and promote the release of chemical substances like neuropeptide, hormone, cytokines, etc. in the local site of acupoints. Besides, it may cause mechanical deformation of connective tissues, and change chemical ions as well as ion channels. The microenvironment changes around acupoints are crucial to acupuncture effect; the concept of ‘acupoints network’ can be used to objectively describe the local changes around the acupoints after acupuncture.

Due to its own internal laws of development, Chinese medicine (CM) seems more inclined to empirical medicine in a relatively long historical period. It is considered to be lacking objective and unified clinical practice guidelines (CPGs), and the difficulties in diagnosis and therapeutic effect evaluation comes with it, have restricted its further inheritance, development and international communication. Over the years, our research group has been committed to improving the standardization theory and methodology of CM, also perfecting relative techniques for further application, which are all based on the stratified evidence scoring method. We have already applied this method to 45 issued guidelines, including 5 national guidelines, 3 industrial guidelines, and 37 formulation/revision social organization guidelines. The stratified evidence scoring method has been recognized and used widely. It helps scholars and applicators to study, formulate, publish and popularize the acupuncture therapy clinical practice guidelines better, thus further promotes the development of acupuncture therapy.

Acupuncture is used in the treatment of a variety of inflammatory conditions and diseases. However, the mechanisms of its anti-inflammatory action are complex and have not been systematically investigated. Macrophages are key components of the innate immune system, thus, balancing the M1/M2 macrophage ratio and modulating cytokine levels in the inflammatory environment may be desirable therapeutic goals. Evidence has shown that acupuncture has anti-inflammatory actions that affect multiple body systems, including the immune, locomotory, endocrine, nervous, digestive, and respiratory systems, by downregulating pro-inflammatory M1 and upregulating anti-inflammatory M2 macrophages, as well as by modulating associated cytokine secretion. Macrophage polarization is controlled by the interlocking pathways of extrinsic factors, the local tissue microenvironment, and the neural-endocrine-immune systems. It has been suggested that polarization of T lymphocytes and cytokine secretions resulting in modulation of the autonomic nervous system and the hypothalamic–pituitary–adrenal axis, may be upstream mechanisms of acupuncture-induced macrophage polarization. We further propose that macrophage polarization could be the principal pathway involved in acupuncture immune regulation and provide the scientific basis for the clinical application of acupuncture in inflammatory conditions.

Forest understory vegetation plays an important role in providing food, nutrition and habitat for wildlife. The impact of wildlife foraging on forest understory biomass are often subtle processes that are difficult to capture using traditional field measurements. Field measurements are labor-intensive and impractical to cover and detect understory biomass changes at an extensive range with fine spatial resolution, thereby affecting the accuracy of habitat quality and food availability assessment for wildlife. Terrestrial Laser Scanning (TLS) is considered to have potential to improve the accuracy of understory biomass prediction, allowing for detailed monitoring of biomass changes under the influence of wildlife at fine scale. In this study, we first developed an efficient method to predict forest understory biomass by using variables from TLS with regression models, and second, we compared the prediction accuracy between TLS-based variables and field-measured variables. Third, the optimal models with TLS-based variables were applied to map and quantify the effect of herbivores density on understory biomass in temperate forests in northeastern China. Our results demonstrated that TLS-derived data were more accurate than field measurements in predicting understory biomass, that TLS-derived canopy cover yielded the highest herb layer biomass estimation accuracy (R2 = 0.72, RMSE = 12.73 g/m2), and that TLS-derived vegetation volume obtained the highest accuracy assessment for the shrub layer biomass prediction (R2 = 0.69, RMSE = 43.64 g/m2). There was a significant difference in the understory herb layer biomass in different deer-density plots, but no significant difference in shrub layer biomass. To quantify biomass changes in different plots, consistent monitoring method is needed, TLS data demonstrated the potential to capture and accurately quantify the biomass variation from forest understory. As tool for monitoring understory, TLS can be used as a supplementary to traditional understory monitoring methods to guide forest management policies and wildlife conservation strategies.

Background. Rheumatoid arthritis (RA) is a chronic systemic chronic autoimmune disease characterized by the aggregation of immune cells and secretion of cytokines in the joint synovium, causing hyperblastosis and even bone destruction. Acupuncture has been proven effective in RA treatment. This study aimed to investigate the anti-inflammatory action of acupuncture, specifically, in relation to immune cell interactions and key mediators. Methods. Rats with adjuvant-induced arthritics (AIA) were treated with manual acupuncture (MA) at Zusanli (ST36). Joint edema and paw withdrawal latency were monitored to observe the effects on inflammation. The levels of 24 cytokines, chemokines, and growth factors in ankle joints during the treatment (on days 1, 7, 15, and 21) were detected by multiplex immunoassay. A bioinformatics analysis based on a directed weighted mathematical model was used to construct cell communication network diagrams and identify the key cells through calculation. The monocyte/macrophage polarization in inflamed joints was investigated by detecting M1- and M2-phenotypic populations and their related cytokines. Results. ST36 MA alleviated paw edema and upregulated the nociceptive threshold of AIA rats. Several innate and adaptive immune cytokines were dynamically regulated by MA, and MA-treated rats showed a significant improvement in symptoms compared with AIA rats by day 21. The immune cell-cell communication networks were intensified with the development of RA but were significantly reduced after treatment with MA. MA was found to specifically regulate monocytes/macrophages in inflamed ankle joints ST36 MA also inhibited M1-phenotype macrophages accompanied by decreased levels of IL-1β. Conclusions. ST36 MA showed anti-inflammatory and analgesic effects as well as inhibition of immune cell communication networks in inflamed joints of AIA rats. Inhibiting the polarization of macrophages to the M1-phenotype in inflamed joints may be one of the key mechanisms of MA anti-inflammatory action. This research highlighted a systematic research paradigm for investigating mechanisms of acupuncture action.

Objective. As a first-line treatment for non-small cell lung cancer (NSCLC), the efficacy of chemotherapy is still unsatisfactory. Moxibustion has been shown to improve the side effects of radiotherapy and chemotherapy and regulate immune function. This study aimed to explore the antitumor effects and potential mechanisms of combinatorial cisplatin and moxibustion treatment for NSCLC by targeting the tumor microenvironment. Methods. Lewis lung cancer (LLC)-bearing mice were induced and treated with cisplatin or/and moxibustion at ST36 (Zusanli), and the growth, weight, and area of the tumor were evaluated. The numbers of various T cell subsets and myeloid cells in the tumor were assessed by flow cytometry, and the gene expression of related markers and cytokines was detected with real-time quantitative polymerase chain reaction (RT-qPCR). In addition, the tumor vascular structure was investigated using CD31 and α-smooth muscle actin (α-SMA) immunofluorescence staining. The expression of the vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) was detected by immunohistochemical staining. Results. Both cisplatin and moxibustion inhibited LLC tumor growth and reduced both the tumor area and weight, with the combinatorial therapy showing superior outcomes. Moxibustion upregulated the infiltration of CD4+ T cells and Th1 cells in the tumor, and the combinatorial therapy increased the proportion of CD8+ cytotoxic T cells (CTLs), CD4+T cells, Th1, Th9 cells, and M1 macrophages, as well as the expression of Cd69, Ifng, and Cd86 mRNA. The combinatorial therapy improved vascular normalization by increasing both the microvessel density (MVD) and pericyte coverage (α-SMA area density) and inhibiting the expression of the VEGF. Conclusions. Combinatorial cisplatin and moxibustion treatment inhibited the LLC tumor growth by mechanisms related to the improvement of the tumor immune microenvironment and vascular normalization, providing an effective combinatorial therapy beneficial for patients with NSCLC.

Mesocarnivores uniquely and profoundly impact ecosystem function, structure, and dynamics. Sympatric species tend to spatially and temporally partition limited resources to facilitate coexistence. We investigated the seasonal spatial and temporal cooccurrences among six mesocarnivores, the leopard cat (Prionailurus bengalensis), red fox (Vulpes vulpes), Asian badger (Meles leucurus), Siberian weasel (Mustela sibirica), masked palm civet (Paguma larvata) and yellow-throated marten (Martes flavigula), as well as a single apex predator (Northern Chinese leopard, Panthera pardus japonensis). We used a camera trapping dataset collected from June 2016 to May 2017 (16,636 camera trapping days, 52 camera locations). The activity patterns varied among seasons and species. Most species were most active during summer. Leopards were most active in winter. Siberian weasels and yellow-throated martens were mainly diurnal, tended to spatially avoid each other, and were temporally segregated from the other mesocarnivores. Leopard cats, Asian badgers, red foxes and masked palm civets were nocturnal and showed high overlap in every season, but their highest peaks of activity were staggered. Mesocarnivores may be affected by the threat of the apex carnivore; they mainly avoided leopards spatially, showing low spatial overlap with leopards in all seasons. Interestingly, we found that the animals may engage in temporal-spatial coordination to facilitate coexistence, as increased temporal overlap in a given season was associated with decreased spatial overlap. Our results provide new insight into the carnivore community of terrestrial mammals in northern China and will facilitate future studies on the mechanisms determining the coexistence of animal species within the trophic cascade. Keywords: Camera trap, Sympatric species, Mesocarnivore coexistence, Activity pattern, Spatial overlap

Spinal cord injury (SCI) is a structural event with devastating consequences worldwide. Due to the limited intrinsic regenerative capacity of the spinal cord in adults, the neural restoration after SCI is difficult. Acupuncture is effective for SCI-induced neurologic deficits, and the potential mechanisms responsible for its effects involve neural protection by the inhibition of inflammation, oxidation, and apoptosis. Moreover, acupuncture promotes neural regeneration and axon sprouting by activating multiple cellular signal transduction pathways, such as the Wnt, Notch, and Rho/Rho kinase (ROCK) pathways. Several studies have demonstrated that the efficacy of combining acupuncture with mesenchymal stem cells (MSCs) transplantation is superior to either procedure alone. The advantage of the combined treatment is dependent on the ability of acupuncture to enhance the survival of MSCs, promote their differentiation into neurons, and facilitate targeted migration of MSCs to the spinal cord. Additionally, the differentiation of MSCs into neurons overcomes the problem of the shortage of endogenous neural stem cells (NSCs) in the acupuncture-treated SCI patients. Therefore, the combination of acupuncture and MSCs transplantation could become a novel and effective strategy for the treatment of SCI. Such a possibility needs to be verified by basic and clinical research.

Neurodegenerative disorders are heterogeneous diseases associated with either acute or progressive neurodegeneration, causing the loss of neurons and axons in the central nervous system (CNS), showing high morbidity and mortality, and there are only a few effective therapies. Here, we summarized that the energy sensor adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK), and its agonist berberine can combat the common underlying pathological events of neurodegeneration, including oxidative stress, neuroinflammation, mitochondrial disorder, glutamate excitotoxicity, apoptosis, autophagy disorder, and disruption of neurovascular units. The abovementioned effects of berberine may primarily depend on activating AMPK and its downstream targets, such as the mammalian target of rapamycin (mTOR), sirtuin1 (SIRT1), nuclear factor erythroid-2 related factor-2 (Nrf2), nuclear factor-κB (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), nicotinamide adenine dinucleotide (NAD+), and p38 mitogen-activated protein kinase (p38 MAPK). It is hoped that this review will provide a strong basis for further scientific exploration and development of berberine's therapeutic potential against neurodegeneration.

Acupuncture is a centuried and unfading treatment of traditional Chinese medicine, which has been proved to exert curative effects on various disorders. Numerous works have been put in to uncover the effective mechanisms of acupuncture. And the interdependent interaction between acupuncture and acupoint microenvironment is a crucial topic. As a benign minimally invasive stimulation, the insertion and manipulation of needle at acupoint could cause deformation of local connective tissue and secretion of various molecules, such as high mobility group box 1 and ATP. The molecules are secreted into extracellular space and bind to the corresponding receptors thus active NF-κB, MAPK, ERK pathways on mast cells, fibroblasts, keratinocytes, and monocytes/macrophages, among others. This is supposed to trigger following transcription and translation of immune factors and neural active substance, as well as promote the free ion movement (such as Ca2+ influx) and the expansion of blood vessels to recruit more immune cells to acupoint. Finally, acupuncture could enhance network connectivity of local microenvironment at acupoints. The earlier mentioned substances further act on a variety of receptors in local nerve endings, transmitting electrical and biochemical signals to the CNS, and giving full play to the acupuncture action. In conclusion, we portrayed a neuro-immune microenvironment network of acupoints that medicates the acupuncture action, and would lay a foundation for the systematic study of the complex network relationship of acupoints in the future.

Background: Traumatic brain injury (TBI) can cause disorders of consciousness (DOC) by impairing the neuronal circuits of the ascending reticular activating system (ARAS) structures, including the hypothalamus, which are responsible for the maintenance of the wakefulness and awareness. However, the effectiveness of drugs targeting ARAS activation is still inadequate, and novel therapeutic modalities are urgently needed. Methods: The goal of this work is to describe the neural loops of wakefulness, and explain how these elements participate in DOC, with emphasis on the identification of potential new therapeutic options for DOC induced by TBI. Results: Hypothalamus has been identified as a sleep/wake center, and its anterior and posterior regions have diverse roles in the regulation of the sleep/wake function. In particular, the posterior hypothalamus (PH) possesses several types of neurons, including the orexin neurons in the lateral hypothalamus (LH) with widespread projections to other wakefulness-related regions of the brain. Orexins have been known to affect feeding and appetite, and recently their profound effect on sleep disorders and DOC has been identified. Orexin antagonists are used for the treatment of insomnia, and orexin agonists can be used for narcolepsy. Additionally, several studies demonstrated that the agonists of orexin might be effective in the treatment of DOC, providing novel therapeutic opportunities in this field. Conclusion: The hypothalamic-centered orexin has been adopted as the point of entry into the system of consciousness control, and modulators of orexin signaling opened several therapeutic opportunities for the treatment of DOC.

This work studies the attitude control of reentry vehicle with control input constraints, unknown external disturbances, and modeling inaccuracies. Firstly, a manifold direct adaptive fuzzy control is designed to guarantee the robustness and fast convergence property. Then, the direct adaptive fuzzy control is combined with integral sliding mode control to achieve the higher accuracy. Furthermore, to solve the problem of control input constraints, we design an auxiliary sliding mode manifold variable that can converge to zero in finite time. Finally, numerical simulations are presented to verify the robustness and effectiveness of the proposed attitude control system.

As a complex microecological system, the gut microbiota plays crucial roles in many aspects, including immunology, physiology and development. The specific function and mechanism of the gut microbiota in birds are distinct due to their body structure, physiological attributes and life history. Data on the gut microbiota of the common kestrel, a second-class protected animal species in China, are currently scarce. With high-throughput sequencing technology, we characterized the bacterial community of the gut from nine fecal samples from a wounded common kestrel by sequencing the V3-V4 region of the 16S ribosomal RNA gene. Our results showed that Proteobacteria (41.078%), Firmicutes (40.923%) and Actinobacteria (11.191%) were the most predominant phyla. Lactobacillus (20.563%) was the most dominant genus, followed by Escherichia-Shigella (17.588%) and Acinetobacter (5.956%). Our results would offer fundamental data and direction for the wildlife rescue.

and purpose: We investigated the effectiveness of cupping therapy with three different pressures in patients with chronic fatigue syndrome (CFS).The participants were randomly assigned to three groups, as follows: cupping pressure of -0.02 mpa (n = 38), -0.03 mpa (n = 38), or -0.05 mpa (n = 36). Each group received cupping treatment that consisted of 10 sessions over 5 weeks (2 sessions per week). The primary outcomes were Fatigue Scale (FS-14) score and Fatigue Assessment Instrument (FAI) score after 5 and 10 sessions. The secondary outcomes were the Self-Rating Anxiety Scale (SAS) score, the Self-Rating Depression Scale (SDS) score, and the Pittsburgh Sleep Quality Index (PSQI) score.There were 91 participants who completed the trial. After five sessions of treatment, the primary outcome of FS-14 score decreased by 3.20 (2.19, 4.21) in the -0.02 mpa group, by 2.39 (1.51, 3.27) in the -0.03 mpa group, and by 3.40 (2.28, 4.52) in the -0.05 mpa group (P = 0.667). After 10 sessions of treatment, the outcome of FS-14 score decreased by 5.00 (3.79, 6.21) in the -0.02 mpa group, by 4.06 (3.07, 5.05) in the -0.03 mpa group, and by 4.77 (3.52, 5.94) in the -0.05 mpa group (P = 0.929). And, the results were statistically different between 5 sessions and 10 sessions of treatment (P 0.01). However, there were no statistical differences in FAI, SAS, SDS, and PSQI scores between the three groups after 5 sessions and 10 sessions of treatment.In conclusion, cupping therapy has significantly relieved fatigue symptoms and improved emotion and sleep condition of CFS patients, and 10 sessions of treatment had superior results compared with 5 sessions in each group. Moreover, in 5 sessions of treatment, cupping with high pressure showed better improvement in fatigue syndromes and sleep condition according to effective rates.Chinese clinical trial registry (ChiCTR1800017590); Ethical approval number: ChiECRCT-20180085.

With cancer deaths increasing, the initiation, pathophysiology and curative management of cancer is receiving increasing attention. Traditional therapies such as surgery and chemoradiotherapy are often accompanied by suppression of host immunity, which increase the risk of metastasis. Astragalus membranceus (AM) is commonly utilized as one herbal medicine of traditional Chinese medicines (TCMs) with a variety of biological activities. Studies have shown that the active ingredients of AM and AM-based TCMs, combined with chemotherapy, can enhance anti-tumor efficacy in cancer patients, in addition to reduce complications and avoid side effects induced by chemotherapy. By using various cancer models and cell lines, AM has been found to be capable of shrinking or stabilizing tumors by direct anti-proliferation or pro-apoptosis effect on tumor cells. Further, AM ameliorates immunosuppression by activating M1 macrophages and T cells tumor-kill function in tumor microenvironment (TME). AM is also found to improve systemic immunity which may help promoting efficacy of chemotherapy and preventing metastasis. Thereby this review contributes to an understanding of AM as an adjunctive therapy in the whole course of cancer treatment, at the same time providing useful information for development of more effective anti-tumor medication. The combination of AM and immune checkpoint therapies has a promising therapeutic prospect, and the observation of direct efficacy and mechanisms on tumor growth and metastasis of AM combined with chemotherapies or other therapies require more in vivo validations and further clinical investigation as well.

Pain and inflammatory diseases are important clinical indications of acupuncture, which have been widely accepted in the international community. Previous studies have been focusing on rapid analgesia of acupuncture through the regulation of nervous system, but few studies on the inflammation regulatory mechanisms in which acupuncture inhibits the peripheral sensitization-induced pain. Based on studies concerning acupoint mechanisms of acupuncture actions and related researches on acupuncture regulating neuroendocrine and immune systems, we put forward the scientific hypothesis that acupuncture regulates neuroendocrine-immune (NEI) network and key response media therein, so as to achieve anti-inflammatory and analgesic effects in target organs. We have established a platform for acupuncture at ST36 to alleviate inflammatory pain in adjuvant induced arthritic rats. Based on the complex network analysis of multi-dimensional data from multi-time point and multi-site detection of NEI common signaling molecules, we have clarified the regulatory effects of acupuncture on NEI network and corresponding downstream immune network. Results indicated that monocytes/macrophages are the key targeting cells of acupuncture regulation, and acupuncture may display the anti-inflammatory and analgesic effects by regulating polarization of T cells in lymph nodes and polarization of M1/M2 macrophages in inflamed joints/paws. In addition, we have spotted a key molecule for acupuncture analgesia, CXCL1, as well as clarified the novel central analgesic mechanism of acupuncture mediated by CXCL1/CXCR2 desensitization. Thereby, we have provided novel evidence of the anti-inflammatory and analgesic actions of acupuncture through regulating NEI network and several key substances, highlighting a systemic research paradigm for investigating mechanisms of acupuncture actions.