Reconstructing a 300-year history of phosphorus cycle in west Chaohu Lake, China.

Anthropogenic activities could significantly increase nutrients loading, especially phosphorus (P), into aquatic systems, leading to eutrophication and disturbance of ecosystems. Detailed investigation of P cycling and its controlling factors in modern lakes could help understand mechanisms behind eutrophication, thus provide suggestions for future environmental management. Here, we investigate evolution history of P and iron (Fe) cycling over the last ~300 years in west Chaohu Lake, a typical eutrophic lake in East China. The combination of 210Pb-137Cs dating and elemental analysis demonstrates drastic escalation of P input and organic carbon burial since 1960s, coincided with the rapid growth of human population near this region. P phase partitioning data indicate that Fe-bound P (PFe) is the predominant P pool of sediments in Chaohu Lake, which also regulates the evolving trend of reactive P (Preac). Moreover, the highest fraction of PFe is consistent with observations via P K-edge X-ray absorption near edge structure (P XANES). In addition, Fe speciation results show a principal contribution of Fe (hydr)oxides (Feox) and negligible presence of pyrite, suggesting a generally oxygenated depositional environment, where P could be preferentially sequestrated in sediments in association with Fe oxide minerals. Relatively high molar organic carbon/organic P (Corg/Porg) but low Corg/Preac ratios also support limited recycling of Preac in west Chaohu Lake. This study reveals that human activities play an important role in leading to the eutrophication of Chaohu Lake. Future environmental management could utilize the coupling of P and Fe oxides to remove P from water column.

Red fermented rice elution fractions inhibits cancer cell proliferation by regulating the FGFR1/PI3K/AKT signaling pathway.

This study aims to elucidate the potential targets and molecular mechanisms underlying the anticancer effects of Red fermented rice extract using molecular simulation techniques. The inhibitory effects of different elution fractions of Red fermented rice extract on A549 and MCF-7 cell proliferation were evaluated through CCK-8 assays. Liquid chromatography-mass spectrometry (LC-MS) was employed to elucidate the structural information of active components, while molecular simulation techniques aided in identifying target proteins based on small molecule structures. Protein immunoblotting was utilized to investigate the mechanisms of action of relevant targets. The study found that the petroleum ether-ethyl acetate and ethyl acetate elution fractions of Red fermented rice extract significantly inhibited A549 and MCF-7 cell proliferation, with stronger effects observed on A549 cells. LC-MS structural analysis identified 25 small molecule structures. Molecular simulations successfully revealed interaction between active elution fractions of Red fermented rice extract and the cancer-related protein FGFR1. Further investigation into the phosphorylation of FGFR1 and its downstream pathway targets PI3K/AKT demonstrated that the active elution fractions exerted their anticancer activity by inhibiting the phosphorylation of FGFR1, PI3K, and AKT proteins. This comprehensive study, integrating CCK-8 assays, LC-MS, molecular simulation techniques, and protein immunoblotting, provides a deep understanding of the anticancer mechanisms of Red fermented rice extract, guiding its further development and clinical application.

Nanodrug Delivery Systems for Myasthenia Gravis: Advances and Perspectives.

Myasthenia gravis (MG) is a rare chronic autoimmune disease caused by the production of autoantibodies against the postsynaptic membrane receptors present at the neuromuscular junction. This condition is characterized by fatigue and muscle weakness, including diplopia, ptosis, and systemic impairment. Emerging evidence suggests that in addition to immune dysregulation, the pathogenesis of MG may involve mitochondrial damage and ferroptosis. Mitochondria are the primary site of energy production, and the reactive oxygen species (ROS) generated due to mitochondrial dysfunction can induce ferroptosis. Nanomedicines have been extensively employed to treat various disorders due to their modifiability and good biocompatibility, but their application in MG management has been rather limited. Nevertheless, nanodrug delivery systems that carry immunomodulatory agents, anti-oxidants, or ferroptosis inhibitors could be effective for the treatment of MG. Therefore, this review focuses on various nanoplatforms aimed at attenuating immune dysregulation, restoring mitochondrial function, and inhibiting ferroptosis that could potentially serve as promising agents for targeted MG therapy.

Metal-organic frame material encapsulated Rhodamine 6G: A highly sensitive fluorescence sensing platform for the detection of picric acid contaminants in water.

As a water pollutant with excellent solubility, 2,4,6-trinitrophenol (also known as picric acid, PA) poses a potential threat to the natural environment and human health, so it is crucial important to detect PA in water. In this study, a novel composite material (MIL-53(Al)@R6G) was successfully synthesized by encapsulating Rhodamine 6G into a metal-organic frame material, which was used for fluorescence detection of picric acid (PA) in water. The composite exhibits bright yellow fluorescence emission with a fluorescence quantum yield of 58.23 %. In the process of PA detection, the composite has excellent selectivity and anti-interference performance, and PA can significantly quench the fluorescence intensity of MIL-53(Al)@R6G. MIL-53(Al)@R6G has the advantages of fast detection time (20 s), wide linear range (1-100 µM) and low detection limit (4.8 nM). In addition, MIL-53(Al)@R6G has demonstrated its potential for the detection of PA in environmental water samples with satisfactory results.

Astragaloside IV protects against autoimmune myasthenia gravis in rats via regulation of mitophagy and apoptosis.

Astragaloside IV (AS­IV) has various pharmacological effects, including antioxidant and immunoregulatory properties, which can improve myasthenia gravis (MG) symptoms. However, the potential mechanism underlying the effects of AS­IV on MG remains to be elucidated. The present study aimed to investigate whether AS­IV has a therapeutic effect on MG and its potential mechanism of action. By subcutaneously immunizing rats with R97­116 peptide, an experimental autoimmune (EA) MG rat model was established. AS­IV (40 or 80 mg/kg/day) treatment was then applied for 28 days after modeling. The results demonstrated that AS­IV significantly ameliorated the weight loss, Lennon score and pathological changes in the gastrocnemius muscle of EAMG rats compared with the model group. Additionally, the levels of acetylcholine receptor antibody (AChR­Ab) were significantly decreased, whereas mitochondrial function [ATPase and cytochrome c (Cyt­C) oxidase activities] and ultrastructure were improved in the AS­IV treated rats. Moreover, the mRNA and protein expression levels of phosphatase and tensin homolog­induced putative kinase 1, Parkin, LC3II and Bcl­2, key signaling molecules for mitophagy and apoptosis, were upregulated, whereas the mRNA and protein expression levels of p62, Cyt­C, Bax, caspase 3 and caspase 9 were downregulated following AS­IV intervention. In conclusion, AS­IV may protect against EAMG in a rat model by modulating mitophagy and apoptosis. These findings indicated the potential mechanism underlying the effects of AS­IV on MG and provided novel insights into treatment strategies for MG.

Zirconium-based metal-organic framework encapsulated dye molecules: An excellent sensing platform for sensitive detection of Cu2+ in aqueous environments.

Residual heavy metal ions in water pose a major hazard to ecology as well as human health, and Cu2+, as the most common heavy metal ion in water bodies, can cause a variety of diseases in human beings with prolonged exposure, therefore, a rational sensing platform is needed for the specific detection of Cu2+. In this work, based on the solvothermal method, we successfully prepared the composite UIO-66@FS by encapsulating the dye fluorescein sodium molecule (FS) with a metal-organic framework material (UIO-66). The composite material has bright fluorescence emission properties with a fluorescence quantum yield of 62.03 %, and the composite material has been used to construct a fluorescence sensing platform for detecting the heavy metal Cu2+ in the aqueous environment. The fluorescence of UIO-66@FS can be greatly quenched by Cu2+, which is visible to the naked eye under UV lamp. The sensing platform is able to withstand environmental interference and has the advantages of high selectivity, excellent sensitivity, fast response, wide linear range (2.5 µM-500 µM), and low detection limit (0.246 µM) in the fluorescence quenching detection of Cu2+. In addition, the sensor has been used to detect Cu2+ in real water samples with satisfactory recoveries. Therefore, this sensing probe can be an excellent candidate for Cu2+ detection and has wonderful potential for real water sample detection.

Dynamic redox and nutrient cycling response to climate forcing in the Mesoproterozoic ocean.

Controls on Mesoproterozoic ocean redox heterogeneity, and links to nutrient cycling and oxygenation feedbacks, remain poorly resolved. Here, we report ocean redox and phosphorus cycling across two high-resolution sections from the ~1.4 Ga Xiamaling Formation, North China Craton. In the lower section, fluctuations in trade wind intensity regulated the spatial extent of a ferruginous oxygen minimum zone, promoting phosphorus drawdown and persistent oligotrophic conditions. In the upper section, high but variable continental chemical weathering rates led to periodic fluctuations between highly and weakly euxinic conditions, promoting phosphorus recycling and persistent eutrophication. Biogeochemical modeling demonstrates how changes in geographical location relative to global atmospheric circulation cells could have driven these temporal changes in regional ocean biogeochemistry. Our approach suggests that much of the ocean redox heterogeneity apparent in the Mesoproterozoic record can be explained by climate forcing at individual locations, rather than specific events or step-changes in global oceanic redox conditions.

Biological diversification linked to environmental stabilization following the Sturtian Snowball glaciation.

The body fossil and biomarker records hint at an increase in biotic complexity between the two Cryogenian Snowball Earth episodes (ca. 661 million to ≤650 million years ago). Oxygen and nutrient availability can promote biotic complexity, but nutrient (particularly phosphorus) and redox dynamics across this interval remain poorly understood. Here, we present high-resolution paleoredox and phosphorus phase association data from multiple globally distributed drill core records through the non-glacial interval. These data are first correlated regionally by litho- and chemostratigraphy, and then calibrated within a series of global chronostratigraphic frameworks. The combined data show that regional differences in postglacial redox stabilization were partly controlled by the intensity of phosphorus recycling from marine sediments. The apparent increase in biotic complexity followed a global transition to more stable and less reducing conditions in shallow to mid-depth marine environments and occurred within a tolerable climatic window during progressive cooling after post-Snowball super-greenhouse conditions.

PINK1/Parkin pathway-mediated mitophagy by AS-IV to explore the molecular mechanism of muscle cell damage.

BACKGROUND: Functional disorders of mitochondria are closely related to muscle diseases. Many studies have also shown that oxidative stress can stimulate the production of a large number of reactive oxygen species (ROS), which have various adverse effects on mitochondria and can damage muscle cells. PURPOSE: In this study, based on our previous research, we focused on the PINK1/Parkin pathway to explore the mechanism by which AS-IV alleviates muscle injury by inhibiting excessive mitophagy. METHODS: L6 myoblasts were treated with AS-IV after stimulation with hydrogen peroxide (H2O2) and carbonyl cyanide m-chlorophenylhydrazone (CCCP). Then, we detected the related indices of oxidative stress and mitophagy by different methods. A PINK1 knockdown cell line was established by lentiviral infection to obtain further evidence that AS-IV reduces mitochondrial damage through PINK1/Parkin. RESULTS: After mitochondrial damage, the expression of malondialdehyde (MDA) and intracellular ROS in L6 myoblasts significantly increased, while the expression of superoxide dismutase (SOD) and ATP decreased. The mRNA and protein expression levels of Tom20 and Tim23 were decreased, while those of VDAC1 were increased. PINK1, Parkin, and LC3 II mRNA and protein expression increased, and P62 mRNA and protein expression decreased·H2O2 combined with CCCP strongly activated the mitophagy pathway and impaired mitochondrial function. However, abnormal expression of these factors could be reversed after treatment with AS-IV, and excessive mitochondrial autophagy could also be reversed, thus restoring the regulatory function of mitochondria. However, AS-IV-adjusted function was resisted after PINK1 knockdown. CONCLUSION: AS-IV is a potential drug for myasthenia gravis (MG), and its treatment mechanism is related to mediating mitophagy and restoring mitochondrial function through the PINK1/Parkin pathway.

Moxibustion attenuates liver metastasis of colorectal cancer by regulating gut microbial dysbiosis.

The liver metastasis is the primary factor attributing to the poor prognosis of colorectal cancer (CRC). Moxibustion has been used clinically against multiple malignancies. In this study, we explored the safety, efficacy, and the potential functional mechanisms of moxibustion in modulating the liver metastasis of CRC by using GFP-HCT116 cells-derived CRC liver metastasis model in Balb/c nude mice. The tumor bearing mice were randomly divided into model control and treatment groups. Moxibustion was applied to the BL18 and ST36 acupoints. CRC liver metastasis was measured by fluorescence imaging. Furthermore, feces from all mice were collected, and 16S rRNA analysis was used to assess their microbial diversity, which was analyzed for its correlation with liver metastasis. Our results indicated that the liver metastasis rate was decreased significantly by moxibustion treatment. Moxibustion treatment also caused statistically significant changes in the gut microbe population, suggesting that moxibustion reshaped the imbalanced gut microbiota in the CRC liver metastasis mice. Therefore, our findings provide new insights into the host-microbe crosstalk during CRC liver metastasis and suggest moxibustion could inhibit CRC liver metastasis by remolding the structure of destructed gut microbiota community. Moxibustion may serve as a complementary and alternative therapy for the treatment of patients with CRC liver metastasis.

Acupuncture-Neuroimaging Research Trends over Past Two Decades: A Bibliometric Analysis.

OBJECTIVE: To identify topics attracting growing research attention as well as frontier trends of acupuncture-neuroimaging research over the past two decades. METHODS: This paper reviewed data in the published literature on acupuncture neuroimaging from 2000 to 2020, which was retrieved from the Web of Science database. CiteSpace was used to analyze the publication years, countries, institutions, authors, keywords, co-citation of authors, journals, and references. RESULTS: A total of 981 publications were included in the final review. The number of publications has increased in the recent 20 years accompanied by some fluctuations. Notably, the most productive country was China, while Harvard University ranked first among institutions in this field. The most productive author was Tian J with the highest number of articles (50), whereas the most co-cited author was Hui KKS (325). Evidence-Based Complementary and Alternative Medicine (92) was the most prolific journal, while Neuroimage was the most co-cited journal (538). An article written by Hui KKS (2005) exhibited the highest co-citation number (112). The keywords "acupuncture" (475) and "electroacupuncture" (0.10) had the highest frequency and centrality, respectively. Functional magnetic resonance imaging (fMRI) ranked first with the highest citation burst (6.76). CONCLUSION: The most active research topics in the field of acupuncture-neuroimaging over the past two decades included research type, acupoint specificity, neuroimaging methods, brain regions, acupuncture modality, acupoint specificity, diseases and symptoms treated, and research type. Whilst research frontier topics were "nerve regeneration", "functional connectivity", "neural regeneration", "brain network", "fMRI" and "manual acupuncture".

"Swiss Army Knife" black phosphorus-based nanodelivery platform for synergistic antiparkinsonian therapy via remodeling the brain microenvironment.

The combination of excessive reactive oxygen species (ROS) levels, neuroinflammation, and pathogenic protein aggregation disrupt the homeostasis of brain microenvironment, creating conditions conducive to the progression of Parkinson's disease (PD). Restoring homeostasis by remodeling the brain microenvironment could reverse this complex pathological progression. However, treatment strategies that can induce this effect are currently unavailable. Herein, we developed a "Swiss Army Knife" nanodelivery platform consisting of matrine (MT) and polyethylene glycol-modified black phosphorus nanosheets (BP) that enables PD treatment by restoring brain microenvironment homeostasis. Under NIR irradiation, the photothermal effect induced by BP allowed the nanomedicine to cross the blood-brain barrier (BBB) and entered the brain parenchyma. In PD brains, the biological effects of BP and MT resulted in the removal of excess ROS, effective reduction of neuroinflammation, decreased aggregation of pathogenic proteins, and improved neurotransmitter delivery, eventually restoring dopamine levels in the striatum. This study demonstrated the effective capacity of a BP-based nanodelivery platform to enter the brain parenchyma and trigger multiple neuropathological changes in PD brains. The platform serves as a safe and effective anti-PD nanomedicine with immense clinical potential.

[Effect of acupuncture on hypothalamic functional connectivity in patients with premature ova-rian insufficiency based on resting-state functional magnetic resonance imaging].

OBJECTIVE: To compare the differences in functional connectivity(FC) between the hypothalamus and whole brain regions in patients with premature ovarian insufficiency (POI) and healthy volunteers based on resting-state functional magnetic resonance imaging (rs-fMRI) and investigate the mechanism of acupuncture on treatment of POI. METHODS: Twelve POI patients were recruited to the acupuncture group and 12 healthy volunteers to the control group. Patients in the acupuncture group received acupuncture at two groups of acupoints alternatively, including Baihui (GV20), Zhongwan (CV12), Shenting (GV24), Shenshu (BL23), Ciliao（BL32） and so on, 30 min once time, 3 times per week for 12 weeks. The state of patients was evaluated by modified Kupperman Index (KI) and self-rating anxiety scale (SAS). Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-mullerian hormone (AMH) were tested by microparticle-based chemiluminescence. B ultrasonography was used to detect the antral follicle count (AFC). Meanwhile, POI patients and healthy volunteers underwent the rs-fMRI examination before and after acupuncture treatment and after enrollment, respectively. With hypothalamus as the region of interest, the differences in FC between the hypothalamus and other brain regions in POI patients and healthy volunteers and the changes of FC between the hypothalamus and whole brain regions in POI patients before and after acupuncture were observed. RESULTS: The SAS and KI scores of pre-treatment POI patients were higher than those in the control group （P<0.01）.In compa-rison with those pre-treatment, FSH, LH, and SAS and KI scores of POI patients decreased after treatment, while AFC increased (P<0.05). Compared with the control group, the FC of the left hypothalamus with left central sulcus, right middle occipital gyrus, and left paracentral lobule increased, but decreased with left globus pallidus of the lenticular nucleus in POI patients. Furthermore, the FC of the right hypothalamus with the left hippocampus, the left para-central lobule, and the right central sulcus increased, while the FC between the right hypothalamus and the right superior frontal gyrus decreased (P<0.05). For the acupuncture group, compared with the conditions before treatment, the FC of the right hypothalamus with the left inferior frontal gyrus, the left insula, and right inferior frontal gyrus was strengthened, but weakened with the left gyrus rectus (P<0.05). CONCLUSION: The abnormal FC between the hypothalamus and whole brain regions may be one of the central pathological factors of POI. Acupuncture can improve the ovarian function and clinical symptoms of patients with POI, which may be related to its effect in regulating the FC between the hypothalamus and multiple brain regions.

Electroacupuncture Attenuates Post-Inflammatory IBS-Associated Visceral and Somatic Hypersensitivity and Correlates With the Regulatory Mechanism of Epac1-Piezo2 Axis.

Electroacupuncture (EA) is considered to have a therapeutic effect in the relief of irritable bowel syndrome (IBS)-associated visceral hypersensitivity via the reduction of the level of 5-hydroxytryptamine (5-HT) and 5-HT3 receptors (5-HT3R). However, whether Epac1/Piezo2, as the upstream of 5-HT, is involved in this process remains unclear. We investigated whether EA at the ST36 and ST37 acupoints alleviated visceral and somatic hypersensitivity in a post-inflammatory IBS (PI-IBS) model mice via the Epac1-Piezo2 axis. In this study, we used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced PI-IBS as a mouse model. Visceral sensitivity was assessed by the abdominal withdrawal reflex test. Somatic sensitivity was evaluated by the hind paw withdrawal threshold. Quantitative real-time PCR, immunofluorescence staining, ELISA, and Western blotting were performed to examine the expressions of Epac1, Piezo2, 5-HT, and 5-HT3R from the mouse distal colon/L5-S2 dorsal root ganglia (DRG). Our results showed that EA improved the increased visceral sensation and peripheral mechanical hyperalgesia in PI-IBS model mice, and the effects of EA were superior to the sham EA. EA significantly decreased the protein and mRNA levels of Epac1 and Piezo2, and reduced 5-HT and 5-HT3R expressions in the distal colon. Knockdown of colonic Piezo2 eliminated the effect of EA on somatic hypersensitivity. Combined knockdown of colonic Epac1 and Piezo2 synergized with EA in relieving visceral hypersensitivity and blocked the effect of EA on somatic hypersensitivity. Additionally, protein levels of Epac1 and Piezo2 were also found to be decreased in the L5-S2 DRGs after EA treatment. Taken together, our study suggested that EA at ST36 and ST37 can alleviate visceral and somatic hypersensitivity in PI-IBS model mice, which is closely related to the regulation of the Epac1-Piezo2 axis.

[Application of Tiaoshen Jianpi acupuncture and moxibustion in hospice care for terminal cancer patients].

To analyze the application feasibility of Tiaoshen Jianpi acupuncture and moxibustion in hospice care for terminal cancer patients. Tiaoshen Jianpi acupuncture and moxibustion adjusts the spirit to regulate emotions and fortifies the spleen to supplement and boost foundation of acquired (postnatal) constitution. And it could relieve adverse reactions after radiotherapy and chemotherapy, alleviate pain and regulate emotions in hospice care for terminal cancer patients, so as to promote the progress of hospice care for terminal cancer patients.

Mitochondrial dynamics and biogenesis indicators may serve as potential biomarkers for diagnosis of myasthenia gravis.

Due to challenges in diagnosing myasthenia gravis (MG), identifying novel diagnostic biomarkers for this disease is essential. Mitochondria are key organelles that regulate multiple physiological functions, such as energy production, cell proliferation and cell death. In the present study, Mfn1/2, Opa1, Drp1, Fis1, AMPK, PGC-1α, NRF-1 and TFAM were compared between patients with MG and healthy subjects to identify potential diagnostic biomarkers for MG. Blood samples were collected from 50 patients with MG and 50 healthy subjects. The participants' demographic information and routine blood test results were recorded. Mitochondrial dynamics were evaluated and levels of Mfn1/2, Opa1, Drp1, Fis1, AMPK, PGC-1α, NRF-1 and TFAM were determined in peripheral blood mononuclear cells using western blotting and reverse transcription-quantitative PCR, respectively. Receiver operating characteristic curve analysis was used to evaluate the diagnostic accuracy of these indicators. The areas under the curve values of Mfn1/2, Opa1, Drp1, Fis1,AMPK, PGC-1α, NRF-1 and TFAM were 0.5408-0.8696. Compared with control subjects, mRNA expression levels of Mfn1/2, Opa1, AMPK, PGC-1α, NRF-1 and TFAM were lower, while those of Drp1 and Fis1 were higher in patients with MG. The protein expression levels of all these molecules were lower in patients with MG than in control subjects. These results suggested that mitochondrial dynamics and biogenesis indicators may be diagnostic biomarkers for MG.

Networks Are Associated With Acupuncture Treatment in Patients With Diarrhea-Predominant Irritable Bowel Syndrome: A Resting-State Imaging Study.

Background: Irritable Bowel Syndrome (IBS), as a functional gastrointestinal disorder, is characterized by abdominal pain and distension. Recent studies have shown that acupuncture treatment improves symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D) by altering networks in certain brain regions. However, few studies have used resting-state functional magnetic resonance imaging (fMRI) to compare altered resting-state inter-network functional connectivity in IBS-D patients before and after acupuncture treatment. Objective: To analyze altered resting-state inter-network functional connectivity in IBS-D patients before and after acupuncture treatment. Methods: A total of 74 patients with IBS-D and 31 healthy controls (HCs) were recruited for this study. fMRI examination was performed in patients with IBS-D before and after acupuncture treatment, but only at baseline in HCs. Data on the left frontoparietal network (LFPN), default mode network (DMN), salience network (SN), ventral attention network (VAN), auditory network (AN), visual network (VN), sensorimotor network (SMN), dorsal attention network (DAN), and right frontoparietal network (RFPN) were subjected to independent component analysis (ICA). The functional connectivity values of inter-network were explored. Results: Acupuncture decreased irritable bowel syndrome symptom severity score (IBS-SSS) and Hamilton Anxiety Scale (HAMA). It also ameliorated symptoms related to IBS-D. Notably, functional connectivity between AN and VAN, SMN and DMN, RFPN and VAN in IBS-D patients after acupuncture treatment was different from that in HCs. Furthermore, there were differences in functional connectivity between DMN and DAN, DAN and LFPN, DMN and VAN before and after acupuncture treatment. The inter-network changes in DMN-VAN were positively correlated with changes in HAMA, life influence degree, and IBS-SSS in IBS-D. Conclusion: Altered inter-network functional connectivity is involved in several important hubs in large-scale networks. These networks are altered by acupuncture stimulation in patients with IBS-D.

A Bibliometric Analysis of Research Trends of Acupuncture Therapy in the Treatment of Migraine from 2000 to 2020.

BACKGROUND: Migraine is the second-leading cause of disability worldwide. It is often characterized by attacks of severe, mostly unilateral, pulsating headache associated with symptoms such as photophobia, phonophobia, nausea, vomiting, and cutaneous allodynia. Acupuncture therapy has been used worldwide for the treatment of migraine. However, no visual bibliometric analysis has been conducted on the effects of acupuncture on migraine over the past 20 years. Therefore, this study aimed to explore the current status and trends on the use of acupuncture in the treatment of migraine from 2000 to 2020. PURPOSE: The objective of this study is to identify the current status and emerging trends of the global use of acupuncture on migraine from 2000 to 2020 using CiteSpace and VOSviewer. METHODS: Web of Science databases were searched for publications related to acupuncture therapy for treating migraine between 2000 and 2020. CiteSpace and VOSviewer were used to analyze the number of publications per year, countries, institutions, authors, journals, references, and keywords. RESULTS: A total of 572 publications were included in the final analysis. The total number of publications has continued to increase with some fluctuations over the past 20 years. The most productive country and institution in this field were the USA, and Chengdu University of Traditional Chinese Medicine, respectively. The most active and cited authors were Liang FR and Linde K, respectively. Cephalalgia was the most productive, cited, and co-cited journal. The Linde K (2005) had the highest co-citation, citation number and centrality. The keywords "migraine" ranked first in frequency. The common type of migraine (tension-type headache), research method (randomized controlled trial, multicenter, double-blind), acupuncture's role (prophylactic, quality of life, pain), and evaluation (meta-analysis, systematic review) were the hotspots and frontier trends of acupuncture therapy on migraine between 2000 and 2020. CONCLUSION: The present study examined the research-related trend in acupuncture therapy on migraine using bibliometric methods and identified the statement and research frontiers over the past two decades. This may help researchers to identify potential hotspots and new directions for future research in this field.

The mitochondrial biogenesis signaling pathway is a potential therapeutic target for myasthenia gravis via energy metabolism (Review).

Myasthenia gravis (MG) is an autoantibody-mediated autoimmune disease that is characterized by muscle weakness and fatigue. Traditional treatments for MG target the neuromuscular junction (NMJ) or the immune system. However, the efficacy of such treatments is limited, and novel therapeutic options for MG are urgently required. In the current review, a new therapeutic strategy is proposed based on the mitochondrial biogenesis and energy metabolism pathway, as stimulating mitochondrial biogenesis and the energy metabolism might alleviate myasthenia gravis. A number of cellular sensors of the energy metabolism were investigated, including AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1). AMPK and SIRT1 are sensors that regulate cellular energy homeostasis and maintain energy metabolism by balancing anabolism and catabolism. Peroxisome proliferator-activated receptor γ coactivator 1α and its downstream transcription factors nuclear respiratory factors 1, nuclear respiratory factors 2, and transcription factor A are key sensors of mitochondrial biogenesis, which can restore mitochondrial DNA and produce new mitochondria. These processes help to control muscle contraction and relieve the symptoms of MG, including muscle weakness caused by dysfunctional NMJ transmission. Therefore, the present review provides evidence for the therapeutic potential of targeting mitochondrial biogenesis for the treatment of MG.

Qiangji Jianli Decoction Alleviates Hydrogen Peroxide-Induced Mitochondrial Dysfunction via Regulating Mitochondrial Dynamics and Biogenesis in L6 Myoblasts.

Oxidative stress can cause the excessive generation of reactive oxygen species (ROS) and has various adverse effects on muscular mitochondria. Qiangji Jianli decoction (QJJLD) is an effective traditional Chinese medicine (TCM) that is widely applied to improve muscle weakness, and it has active constituents that prevent mitochondrial dysfunction. To investigate the protective mechanism of QJJLD against hydrogen peroxide- (H2O2-) mediated mitochondrial dysfunction in L6 myoblasts. Cell viability was determined with MTT assay. Mitochondrial ultrastructure was detected by transmission electron microscope (TEM). ROS and mitochondrial membrane potential (MMP) were analyzed by fluorescence microscope and flow cytometry. The superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity, and malondialdehyde (MDA) level were determined by WST-1, TBA, and DTNB methods, respectively. The mRNA and protein levels were measured by quantitative real-time PCR (qRT-PCR) and Western blot. The cell viability was decreased, and the cellular ROS level was increased when L6 myoblasts were exposed to H2O2. After treatment with QJJLD-containing serum, the SOD and GSH-Px activities were increased. MDA level was decreased concurrently. ROS level was decreased while respiratory chain complex activity and ATP content were increased in L6 myoblasts. MMP loss was attenuated. Mitochondrial ultrastructure was also improved. Simultaneously, the protein expressions of p-AMPK, PGC-1α, NRF1, and TFAM were upregulated. The mRNA and protein expressions of Mfn1/2 and Opa1 were also upregulated while Drp1 and Fis1 were downregulated. These results suggest that QJJLD may alleviate mitochondrial dysfunction through the regulation of mitochondrial dynamics and biogenesis, the inhibition of ROS generation, and the promotion of mitochondrial energy metabolism.