Larger hypothalamic subfield volumes in patients with chronic insomnia disorder and relationships to levels of corticotropin-releasing hormone.

The hypothalamus is a well-established core structure in the sleep-wake cycle. While previous studies have not consistently found whole hypothalamus volume changes in chronic insomnia disorder (CID), differences may exist at the smaller substructural level of the hypothalamic nuclei. The study aimed to investigate the differences in total and subfield hypothalamic volumes, between CID patients and healthy controls (HCs) in vivo, through an advanced deep learning-based automated segmentation tool. A total of 150 patients with CID and 155 demographically matched HCs underwent T1-weighted structural magnetic resonance scanning. We utilized FreeSurfer v7.2 for automated segmentation of the hypothalamus and its five nuclei. Additionally, correlation and causal mediation analyses were performed to investigate the association between hypothalamic volume changes, insomnia symptom severity, and hypothalamus-pituitary-adrenal (HPA) axis-related blood biomarkers. CID patients exhibited larger volumes in the right anterior inferior, left anterior superior, and left posterior subunits of the hypothalamus compared to HCs. Moreover, we observed a positive association between blood corticotropin-releasing hormone (CRH) levels and insomnia severity, with anterior inferior hypothalamus (a-iHyp) hypertrophy mediating this relationship. In conclusion, we found significant volume increases in several hypothalamic subfield regions in CID patients, highlighting the central role of the HPA axis in the pathophysiology of insomnia.

Acupuncture for generalized anxiety disorder: a study protocol for a randomized controlled trial

During the COVID-19 outbreak, there was a sharp increase in generalized anxiety disorder (GAD). Acupuncture therapy has the advantages of accurate clinical efficacy, safety and reliability, few adverse reactions, and no dependence, and is gradually becoming one of the emerging therapies for treating GAD. We present a study protocol for a randomized clinical trial with the aim of exploring the mechanism of brain plasticity in patients with GAD and evaluate the effectiveness and reliability of acupuncture treatment. Transcranial magnetic stimulation (TMS) will be used to assess cortical excitability in GAD patients and healthy people. Sixty-six GAD patients meeting the inclusion criteria will be randomly divided into two groups: TA group, (treatment with acupuncture and basic western medicine treatment) and SA group (sham acupuncture and basic western medicine treatment). Twenty healthy people will be recruited as the control group (HC). The parameters that will be evaluated are amplitude of motor evoked potentials (MEPs), cortical resting period (CSP), resting motor threshold (RMT), and Hamilton Anxiety Scale (HAMA) score. Secondary results will include blood analysis of γ-aminobutyric acid (GABA), glutamate (Glu), glutamine (Gln), serotonin (5-HT), and brain-derived nerve growth factor (BDNF). Outcomes will be assessed at baseline and after the intervention (week 8). This study protocol is the first clinical trial designed to detect differences in cerebral cortical excitability between healthy subjects and patients with GAD, and the comparison of clinical efficacy and reliability before and after acupuncture intervention is also one of the main contents of the protocol. We hope to find a suitable non-pharmacological alternative treatment for patients with GAD.

Neuroimaging research progress of acupuncture treatment for patients with functional dyspepsia. / é’ˆåˆºæ²»ç–—åŠŸèƒ½æ€§æ¶ˆåŒ–ä¸è‰¯çš„ç¥žç»å½±åƒå­¦ç ”ç©¶è¿›å±•.

Neuroimaging technology provides objective and visualized research tool to study the mechanisms of acupuncture effects. Building on a systematic review of previous clinical studies on acupuncture treatment for functional dyspepsia using neuroimaging technology, this paper summarizes and synthesizes past researches from 4 aspects： acupoint-specific effects, factors influencing the effects, different physiological responses, and predictive factors for acupuncture efficacy. It suggests that acupuncture treatment for FD involves central integration with disease-targeted (acupuncture treatment can target and regulate abnormal brain functional activity patterns in patients with FD), meridian-specific (stimulation of specific acupuncture points along the stomach meridian can significantly regulate abnormal brain functional activity patterns in FD patients), and dynamic conditional features(the effects of acupuncture treatment for FD are influenced by multiple factors). Lastly, considering the current research status, this paper outlines prospects in terms of research subjects, influencing factors, and result validation, aiming to provide references for future in-depth research.

Genome-wide analysis and expression pattern of the ZoPP2C gene family in Zingiber officinale Roscoe.

BACKGROUND: Protein phosphatases type 2C (PP2C) are heavily involved in plant growth and development, hormone-related signaling pathways and the response of various biotic and abiotic stresses. However, a comprehensive report identifying the genome-scale of PP2C gene family in ginger is yet to be published. RESULTS: In this study, 97 ZoPP2C genes were identified based on the ginger genome. These genes were classified into 15 branches (A-O) according to the phylogenetic analysis and distributed unevenly on 11 ginger chromosomes. The proteins mainly functioned in the nucleus. Similar motif patterns and exon/intron arrangement structures were identified in the same subfamily of ZoPP2Cs. Collinearity analysis indicated that ZoPP2Cs had 33 pairs of fragment duplicated events uniformly distributed on the corresponding chromosomes. Furthermore, ZoPP2Cs showed greater evolutionary proximity to banana's PP2Cs. The forecast of cis-regulatory elements and transcription factor binding sites demonstrated that ZoPP2Cs participate in ginger growth, development, and responses to hormones and stresses. ZoERFs have plenty of binding sites of ZoPP2Cs, suggesting a potential synergistic contribution between ZoERFs and ZoPP2Cs towards regulating growth/development and adverse conditions. The protein-protein interaction network displayed that five ZoPP2Cs (9/23/26/49/92) proteins have robust interaction relationship and potential function as hub proteins. Furthermore, the RNA-Seq and qRT-PCR analyses have shown that ZoPP2Cs exhibit various expression patterns during ginger maturation and responses to environmental stresses such as chilling, drought, flooding, salt, and Fusarium solani. Notably, exogenous application of melatonin led to notable up-regulation of ZoPP2Cs (17/59/11/72/43) under chilling stress. CONCLUSIONS: Taken together, our investigation provides significant insights of the ginger PP2C gene family and establishes the groundwork for its functional validation and genetic engineering applications.

Versatile CYP98A enzymes catalyse meta-hydroxylation reveals diversity of salvianolic acids biosynthesis.

Salvianolic acids (SA), such as rosmarinic acid (RA), danshensu (DSS), and their derivative salvianolic acid B (SAB), etc. widely existed in Lamiaceae and Boraginaceae families, are of interest due to medicinal properties in the pharmaceutical industries. Hundreds of studies in past decades described that 4-coumaroyl-CoA and 4-hydroxyphenyllactic acid (4-HPL) are common substrates to biosynthesize SA with participation of rosmarinic acid synthase (RAS) and cytochrome P450 98A (CYP98A) subfamily enzymes in different plants. However, in our recent study, several acyl donors and acceptors included DSS as well as their ester-forming products all were determined in SA-rich plants, which indicated that previous recognition to SA biosynthesis is insufficient. Here, we used Salvia miltiorrhiza, a representative important medicinal plant rich in SA, to elucidate the diversity of SA biosynthesis. Various acyl donors as well as acceptors are catalysed by SmRAS to form precursors of RA and two SmCYP98A family members, SmCYP98A14 and SmCYP98A75, are responsible for different positions' meta-hydroxylation of these precursors. SmCYP98A75 preferentially catalyses C-3' hydroxylation, and SmCYP98A14 preferentially catalyses C-3 hydroxylation in RA generation. In addition, relative to C-3' hydroxylation of the acyl acceptor moiety in RA biosynthesis, SmCYP98A75 has been verified as the first enzyme that participates in DSS formation. Furthermore, SmCYP98A enzymes knockout resulted in the decrease and overexpression leaded to dramatic increase of SA accumlation. Our study provides new insights into SA biosynthesis diversity in SA-abundant species and versatility of CYP98A enzymes catalytic preference in meta-hydroxylation reactions. Moreover, CYP98A enzymes are ideal metabolic engineering targets to elevate SA content.

New cassane-type alkaloids and diterpenoids from the pericarps of Caesalpinia bonduc.

The phytochemical investigation of the pericarps of Caesalpinia bonduc led to the isolation and identification of five new cassane-type alkaloids: caesalminines C - G (1-5) and six new diterpenoids: caesalbonducin K - P (6-11), along with seven known compounds (12-18). Compounds 1-5 were identified as a group of rare alkaloids possessing a tetracyclic cassane-type diterpenoid skeleton with a lactam D-ring instead of a typical furan or lactone moiety. The structures of 1-11 were elucidated on the basis of 1D and 2D NMR including HSQC, HMBC, COSY and NOESY, and other spectroscopic analyses. The cytotoxic activities of the isolated compounds were evaluated in the A431, A549 and U87MG cancer cell lines.

Genus Gelsemium and its Endophytic Fungi - Comprehensive Review of their Traditional Uses, Phytochemistry, Pharmacology, and Toxicology.

BACKGROUND: The use of ethnic medicinal plants has revitalized wide popularity in Africa, Asia, and most of the world because of the energy consumption barriers increase of synthetic drugs. Gelsemium is a traditional genus of plants with famous cultural and medicinal significance in Southeast Asia and North America. Three species are reported from the genus Gelsemium, including Gelsemium elegans (Gardn. & Camp.) Benth., Gelsemium sempervirens (L.) J.St.-Hil., and Gelsemium rankinii Small. Among them, G. elegans is well known for its toxicity and is used as a traditional remedy for skin problems, neuralgia, fractures, and cancer. The first record of the toxic medicine G. elegans is the Chinese herbal medicine classically known as Shen-Nong Ben-Cao Jing. In the legend, the Shennong emperor was poisoned by G. elegans, hence, it is also wellknown as Duan Chang Cao in China. In addition, G. sempervirens tincture is also used in the treatment of inflammation of the spinalcolumn, and diminishes blood to the cerebrospinal centers. INTRODUCTION: This review aims to provide up-to-date information on Gelsemium and its endophytic fungi on their traditional uses, phytochemistry, pharmacology, and toxicology. Mechanism studies regarding the detoxification profile of Gelsemium are also reviewed. METHODS: For this updated review, the literature survey and search were performed on the scientific databases PubMed, ScienceDirect, Wiley, China CNKI, Web of Science, SciFinder, and Google Scholar using the relevant keywords. RESULTS: The plants of the genus Gelsemium are all reported as rich sources of monoterpene indole alkaloids. Previous phytochemical studies published more than 200 alkaloids from Gelsemium and its endophytic fungi, which have attracted considerable attention from pharmaceutists and phytochemists due to their diverse and complex structures. The bioactivities of Gelsemium phytoconstituents studied using various chemical methods are summarized and described herein. Considering the huge influence of Gelsemium regarding its traditional applications, the activities of isolated compounds were focused on the anti-tumor, anti-inflammatory, analgesic and antianxiety, immunostimulatory, and immunosuppressive properties, which provide evidence supporting the ethnopharmacological effectiveness of the genus Gelsemium. Unlike all previous reviews of genus Gelsemium, to the best of our knowledge, the recently reported natural products from its endophytic fungi are first time summarized in this review. CONCLUSION: It is clearly suggested from the literature information that the structures and biological activities of Gelsemium have a wide range of attraction from folk to the community of scholars. However, as a highly toxic genus, the work on the detoxification mechanism and toxicology of Gelsemium is urgently needed before entering clinical research. It is noteworthy that the discussion about the relationship between structural and biological activities are a valuable topic of expectation, while the structural modification for active or toxic components may shed light on toxicological breakthrough. Besides the compounds from the plants of genus Gelsemium, the recently reported natural products from its endophytic fungi may provide a supplement for its ethnomedicinal uses and ethnological validity.

Clinical-functional brain connectivity signature predicts longitudinal symptom improvement after acupuncture treatment in patients with functional dyspepsia.

Whilst acupuncture has been shown to be an effective treatment for functional dyspepsia (FD), its efficacy varies significantly among patients. Knowing beforehand how each patient responds to acupuncture treatment will facilitate the ability to produce personalized prescriptions, therefore, improving acupuncture efficacy. The objective of this study was to construct the prediction model, based on the clinical-neuroimaging signature, to forecast the individual symptom improvement of FD patients following a 4-week acupuncture treatment and to identify the critical predictive features that could potentially serve as biomarkers for predicting the efficacy of acupuncture for FD. Clinical-functional brain connectivity signatures were extracted from samples in the training-test set (100 FD patients) and independent validation set (60 FD patients). Based on these signatures and support vector machine algorithms, prediction models were developed in the training test set, followed by model performance evaluation and predictive features extraction. Subsequently, the external robustness of the extracted predictive features in predicting acupuncture efficacy was evaluated by the independent validation set. The developed prediction models possessed an accuracy of 88% in predicting acupuncture responders, as well as an R2 of 0.453 in forecasting symptom relief. Factors that contributed significantly to stronger responsiveness of patients to acupuncture therapy included higher resting-state functional connectivity associated with the orbitofrontal gyrus, caudate, hippocampus, and anterior insula, as well as higher baseline scores of the Symptom Index of Dyspepsia and shorter durations of the condition. Furthermore, the robustness of these features in predicting the efficacy of acupuncture for FD was verified through various machine learning algorithms and independent samples and remained stable in univariate and multivariate analyses. These findings suggest that it is both feasible and reliable to predict the efficacy of acupuncture for FD based on the pre-treatment clinical-neuroimaging signature. The established prediction framework will promote the identification of suitable candidates for acupuncture treatment, thereby improving the efficacy and reducing the cost of acupuncture for FD.

Jujuboside B suppresses angiogenesis and tumor growth via blocking VEGFR2 signaling pathway.

Jujuboside B (JuB), one of the main active triterpenoid saponins from the traditional Chinese medicine Ziziphus jujuba, possesses a wide range of pharmacological activities. However, it is unknown whether JuB can inhibit tumor angiogenesis, a crucial step in solid tumor growth. In this study, we found that JuB significantly inhibited the proliferation, migration, and tube formation of human umbilical vein endothelial cells in a dose-dependent manner. JuB also suppressed angiogenesis in chick embryo chorioallantoic membranes and Matrigel plugs. Moreover, through angiogenesis inhibition, JuB delayed the growth of human HCT-15 colorectal cancer xenograft in mice. Western blot assay demonstrated that JuB inhibited the phosphorylation of VEGFR2 and its key downstream protein kinases, such as Akt, FAK, Src, and PLCγ1. In conclusion, the antiangiogenic potency and molecular mechanism of JuB are revealed for the first time, indicating that this triterpene saponin may be further explored as a potential drug candidate or lead compound for antiangiogenic cancer therapy.

Structural Elucidation and Cytotoxic Activity of New Monoterpenoid Indoles from Gelsemium elegans.

Two new monoterpenoid indole alkaloids, gelselegandines F (1) and G (2), were isolated from the aerial parts of Gelsemium elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. The ECD calculations were conducted at the B3LYP/6-311G(d,p) level and NMR calculations were carried out using the Gauge-Including Atomic Orbitals (GIAO) method. Structurally, the two new compounds possessed rare, cage-like, monoterpenoid indole skeletons. All isolated compounds and the total alkaloids extract were tested for cytotoxicity against four different tumor cell lines. The total alkaloids extract of G. elegans exhibited significant antitumor activity with IC50 values ranging from 32.63 to 82.24 ug/mL. In order to discover anticancer leads from the active extraction, both new indole compounds (1-2) were then screened for cytotoxicity. Interestingly, compound 2 showed moderate cytotoxicity against K562 leukemia cells with an IC50 value of 57.02 uM.

Qualitative and quantitative method for quality control of Itea ilicifolia based on antioxidant Q-markers.

Itea ilicifolia Oliv is a folk medicine with antioxidant potential. In this study, the fingerprints of 14 batches of I. ilicifolia were established by HPLC with 17 common peaks. The similarities evaluated by Similarity Evaluation System for Chromatographic Fingerprint of Chinese Materia (version 2012) were >0.89. Ten compounds were identified with definite structures by comparing the retention time and characteristic UV spectral pattern with those of reference substances. The antioxidant capacities of 14 batches of I. ilicifolia were evaluated based on O2 ·- , DPPH and ABTS·+ radical scavenging assays in combination with ferric reducing antioxidant power assay. Via multivariate statistical analyses of gray relation analysis, bivariate correlation analysis and partial least squares regression analysis, a study on the spectrum-effect relationship was then performed to screen eight peaks as the antioxidant Q-markers of I. ilicifolia. The contents of representative antioxidant Q-markers (isoorientin, orientin, vitexin, isovitexin and iteafuranal A) in samples were accurately determined to be 0.054-0.118%, 0.034-0.080%, 0.018-0.055%, 0.031-0.091% and 0.033-0.140%, respectively. The qualitative and quantitative analytical method based on Q-markers helps to control the antioxidant quality of I. ilicifolia, which will lay the foundation to promote the rational utilization of I. ilicifolia in curing diseases related to oxidative stress.

Balancing acid and redox sites of phosphorylated CeO2 catalysts for NOx reduction: The promoting and inhibiting mechanism of phosphorus.

The role of phosphorus in metal oxide catalysts is still controversial. The precise tuning of the acidic and redox properties of metal oxide catalysts for the selective catalytic reduction in NOx using NH3 is also a great challenge. Herein, CeO2 catalysts with different degrees of phosphorylation were used to study the balance between the acidity and redox property by promoting and inhibiting effects of phosphorus. CeO2 catalysts phosphorylated with lower phosphorus content (5 wt%) exhibited superior NOx reduction performance with above 90% NOx conversion during 240-420 °C due to the balanced acidity and reducibility derived from the highest content of Brønsted acid sites on PO43- to adsorb NH3 and surface adsorbed oxygen species. Plenty of PO3- over CeO2 catalysts phosphorylated with the higher phosphorus content (≥ 10 wt%) significantly disrupted the balance between the acidity and the redox property due to the reduced acid/redox sites, which resulted in the less active NOx species. The mechanism of different structural phosphorus species (PO43- and PO3-) in promoting or inhibiting the NOx reduction over CeO2 catalysts was revealed. This work provides a novel method for qualitative and quantitative study of the relationship between acidity/redox property and activity of catalysts for NOx reduction.

Biological Activities and Secondary Metabolites from Sophora tonkinensis and Its Endophytic Fungi.

The roots of Sophora tonkinensis Gagnep., a traditional Chinese medicine, is known as Shan Dou Gen in the Miao ethnopharmacy. A large number of previous studies have suggested the usage of S. tonkinensis in the folk treatment of lung, stomach, and throat diseases, and the roots of S. tonkinensis have been produced as Chinese patent medicines to treat related diseases. Existing phytochemical works reported more than 300 compounds from different parts and the endophytic fungi of S. tonkinensis. Some of the isolated extracts and monomer compounds from S. tonkinensis have been proved to exhibit diverse biological activities, including anti-tumor, anti-inflammatory, antibacterial, antiviral, and so on. The research progress on the phytochemistry and pharmacological activities of S. tonkinensis have been systematically summarized, which may be useful for its further research.

Effect of Acupuncture on Blood Pressure and Metabolic Profile Among Patients With Essential Hypertension: Protocol of a Randomized Clinical Trial.

Essential hypertension is a polygenic cardiovascular disease that is associated with maladaptive metabolic changes. Acupuncture as a non-pharmacologic intervention is used to lower blood pressure and improve metabolic dysfunction. However, such effects have not been clinically characterized. We will conduct a randomized clinical trial to evaluate the antihypertensive effect of acupuncture among patients with essential hypertension and determine the associated metabolic improvements. This study is a phase II, two-arm, randomized, sham-controlled trial (Trial registration: ChiCTR2100043737), in which biospecimens will be collected for metabolic profiling. A total of 64 patients with a clinical diagnosis of essential hypertension will be randomly assigned to either the acupuncture or the sham acupuncture group in a 1:1 ratio. All participants will receive 10 treatments over 4 weeks, with three sessions per week for the first 2 weeks and two sessions per week for the remaining weeks. The primary outcome is the change of the systolic and diastolic blood pressure measured by the 24-h ambulatory blood pressure monitoring from baseline to 4 weeks. Secondary outcomes include the circadian rhythm of blood pressure, sleep quality measured by the Insomnia Severity Index, cognitive function measured by the Montreal Cognitive Assessment, and others. Fasting blood serum and urine samples will be collected at baseline and 4 weeks for targeted and untargeted metabolomics analysis. We will use the mixed-effects model and other related bioinformatics approaches to analyze the clinical and metabolome data. This metabolomic-based trial will provide important clinical data regarding the efficacy of acupuncture for essential hypertension to better inform evidence-based care delivery for hypertension patients. Moreover, the findings will offer important insights into the mechanism of action of acupuncture for hypertension by revealing its effect on metabolism. The results of this study will be used to inform the design of a statistically powered, multicenter, randomized trial. We will publish the study findings in peer-reviewed journals. The ethical approval of this study has been reviewed and approved by the Sichuan Regional Ethics Review Committee on Traditional Chinese Medicine (ID: 2021KL-006). The outcomes of the trial will be disseminated through peer-reviewed publications.

Effects of expressive art therapy on health status of patients with chronic obstructive pulmonary disease: a community-based cluster randomized controlled trial.

BACKGROUND AND OBJECTIVE: This study was performed to investigate the effect of expressive art therapy (EAT) on the health status of patients with chronic obstructive pulmonary disease (COPD). METHODS: This community-based cluster randomized controlled trial involved patients with COPD from 16 communities in China. Participants received either EAT plus usual care (UC) or UC only. General practitioners were trained in EAT before the intervention. The primary outcomes were depression and anxiety symptoms, measured with the Hospital Anxiety and Depression Scale (HADS) and expressed as the HADS score for depression or anxiety (HADS-D or HADS-A, respectively). The secondary outcomes were the quality of life and dyspnoea, measured with the COPD assessment test (CAT). Dyspnoea was assessed using the modified Medical Research Council (mMRC) dyspnoea scale. Lung function was expressed as the forced expiratory volume in 1 s as a percentage of the predicted value [FEV1 (% pred)]. Outcome data were collected from all participants at baseline, 2 and 6 months. RESULTS: In total, 360 participants with COPD and comorbid depression were included in the analysis with the control group of 181 receiving UC only and the intervention group of 179 receiving EAT plus UC. The EAT group showed significantly greater improvement in the HADS-D and HADS-A scores than the UC group at 2 months (p < 0.0001 and p < 0.001, respectively) and 6 months (p < 0.001 for both). The CAT and mMRC scores were significantly lower in the EAT group than in the UC group at 2 and 6 months (p < 0.001 for all). The FEV1 (% pred) was significantly higher in the EAT group than in the UC group at 6 months (p < 0.01). CONCLUSION: General practitioners can deliver EAT interventions. EAT can effectively reduce anxiety and depression symptoms and dyspnoea, improve quality of life and improve the pulmonary function of patients with COPD.

Therapeutic effects and central mechanism of acupuncture and moxibustion for treating functional dyspepsia: study protocol for an fMRI-based randomized controlled trial.

BACKGROUND: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders, with a high prevalence and significant influence on the quality of life (QoL). Either acupuncture or moxibustion is effective for dyspepsia, which is confirmed by both ancient documents and modern research. However, the therapeutic advantage and underlying mechanism between acupuncture and moxibustion for FD remain unclear. METHODS: This randomized controlled fMRI trial aims to (i) evaluate the therapeutic advantages of acupuncture and moxibustion treatment for FD, (ii) investigate the similarities and differences in cerebral activity elicited by acupuncture and moxibustion, and (iii) analyze the possible correlations between brain responses and clinical variables thus to explore the potential central mechanism of acupuncture and moxibustion for treating FD. Ninety-two FD patients will be randomly assigned to either the acupuncture group or the moxibustion group in a 1:1 ratio. Twenty sessions of acupuncture or moxibustion treatment over 4 weeks will be performed on each patient. The short form Leeds Dyspepsia Questionnaire, the Nepean Dyspepsia Index, etc., are used to evaluate the therapeutic effects. The heart rate variability will be analyzed to investigate the autonomic nerve function. Thirty-six FD patients in each group will be randomly selected for the fMRI scan to detect cerebral activity changes. DISCUSSION: We expect the results will deepen our knowledge on the clinical value and underlying mechanism of acupuncture and moxibustion and provide a reference for a better selection of interventions for treating FD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100049496. Registered on 2 August 2021.

LM-Jelly: Liquid Metal Enabled Biomimetic Robotic Jellyfish.

Jellyfish have attracted worldwide attention owing to their fantastic moving styles, which also inspired development in soft robotics to meet the demands of underwater surveillance. In this study, a soft robotic jellyfish integrated liquid metal coil, and magnetic field is proposed for the first time to mimic the soft rowing propulsion of oblate jellyfish. The soft robotic jellyfish is actuated by the entirely soft electromagnetic actuators that enabled the gentle motion. Through conceptual experiments and computational fluid dynamics simulations, we systematically interpreted the mechanism of this robotic jellyfish and various factors to dominate its movement behaviors, which involve vortex formation and ascending modalities. Besides, underwater monitoring and bio-friendliness of robotic jellyfish were also demonstrated to illustrate its potential application scenarios and gentle motion characteristics. This study will help to broaden the vistas for liquid metal enabled bionic robotics in a wide range of underwater applications.

A multifunctional carbon dot-based nanoplatform for bioimaging and quaternary ammonium salt/photothermal synergistic antibacterial therapy.

The emergence of drug resistance and superbugs poses a devastating threat to public health and can even lead to death. Thus, it is significant to develop a novel antibacterial agent to combat bacterial infections. Herein, we developed quaternary ammonium salt (QAS) modified near-infrared carbon dots (RCDs-C35), which possesses synergistic antibacterial performance under 808 nm irradiation. This nanocomposite exhibits excellent photothermal performance and the photothermal conversion efficiency (PCE) could reach 35%. Generally speaking, the bacterial membrane sensitivity to hyperthermia would be enhanced after QAS caused the initial damage, and thus it can more easily cause bacterial inactivation after irradiation. In vitro and in vivo experiments indicated that the RCDs-C35 exhibit excellent biocompatibility, predominant synergistic antibacterial performance, and the capability of promoting wound healing. The antibacterial ratio against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) could reach 99.5% and 99.8%, respectively, after 808 nm irradiation. Additionally, the cellular imaging indicated that the RCDs-C35 could be used as a fluorescent probe in bioimaging. Therefore, RCDs-C35 with synergistic antibacterial performance and inherent luminescence possess great potential for application in the biomedical field.

Shikonin Attenuates Cochlear Spiral Ganglion Neuron Degeneration by Activating Nrf2-ARE Signaling Pathway.

The molecular mechanisms that regulate the proliferation and differentiation of inner ear spiral ganglion cells (SGCs) remain largely unknown. Shikonin (a naphthoquinone pigment isolated from the traditional Chinese herbal medicine comfrey root) has anti-oxidation, anti-apoptosis and promoting proliferation and differentiation effects on neural progenitor cells. To study the protective effect of shikonin on auditory nerve damage, we isolated spiral ganglion neuron cells (SGNs) and spiral ganglion Schwann cells (SGSs) that provide nutrients in vitro and pretreated them with shikonin. We found that shikonin can reduce ouabain, a drug that can selectively destroy SGNs and induce auditory nerve damage, caused SGNs proliferation decreased, neurite outgrowth inhibition, cells apoptosis and mitochondrial depolarization. In addition, we found that shikonin can increase the expression of Nrf2 and its downstream molecules HO-1 and NQO1, thereby enhancing the antioxidant capacity of SGNs and SGSs, promoting cells proliferation, and inhibiting cells apoptosis by activating the Nrf2/antioxidant response elements (ARE) signal pathway. However, knockdown of Nrf2 rescued the protective effect of shikonin on SGNs and SGSs damage. In addition, we injected shikonin pretreatment into mouse that ouabain-induced hearing loss and found that shikonin pretreatment has a defensive effect on auditory nerve damage. In summary, the results of this study indicate that shikonin could attenuate the level of oxidative stress in SGNs and SGSs through the Nrf2-ARE signaling pathway activated, induce the proliferation and differentiation of SGNs, and thereby improve the neurological hearing damage in mice. Therefore, shikonin may be a candidate therapeutic drug for endogenous antioxidants that can be used to treat neurological deafness.

Abnormal Level of Manganese, Iron, Iodine, and Selenium in the Hair of Children Living in Kashin-Beck Disease Endemic Areas.

Biological geochemistry is a main suggested cause of Kashin-Beck disease (KBD), due to the absence or excess of elements in the environment. Initially, Se deficiency is regarded as the most key role in the etiology of KBD, and selenium supplementation effectively helps to prevent and control KBD. However, several elements are reported to be relevant to KBD or selenium in succession, which indicated selenium deficiency is not the original etiology of KBD. The study comprehensively analyzed the characteristics of the bio-element profile of KBD and further re-examined the unique role of selenium in etiology. The study measured 14 elements, including sodium, potassium, calcium, phosphorus, magnesium, copper, iron, zinc, selenium, iodine, manganese, lead, arsenic, and mercury, which were detected from hair samples collected from 150 boys. Research participants were separated based on whether they had received any preventative treatment (with and without selenium supplementation). From endemic areas, 30 KBD and 30 healthy children without any preventative treatment were selected alongside 30 KBD and 30 healthy children with selenium supplementation. The participants from endemic areas were then compared to 30 healthy children living in non-endemic areas. Compared to the non-endemic group, the levels of iron and manganese were all significantly higher in the endemic groups and were further elevated in KBD participants (p < 0.05). In contrast, selenium and iodine levels in endemic areas were much lower than those of the control group (p < 0.05). The proportions of selenium excess (p < 0.05) and iodine deficiency (p < 0.05) in endemic groups were significantly lower than participants from non-endemic areas. Meanwhile, excess levels of iron (p < 0.05) and manganese (p < 0.05) were higher in the endemic groups. Moreover, the proportions of Zn/Fe and Se/Mn were found to be significantly lower in endemic area participants than those in the control group (p < 0.05). Three pairs of elements had a correlation coefficient value of more than 0.6: 0.7423 for manganese and calcium, 0.6446 for potassium and sodium, and 0.6272 for manganese and iron. The ratios of Se/Mn and Zn/Fe were associated with a correlation coefficient value of 0.8055. Magnesium, sodium, copper, and iodine levels were meticulously examined using binary regression analysis. This was also used to determine the ratios of Ca/Mg, Ca/P, Zn/Fe, Se/Mn, and Se/I. Thus, the study largely revealed the vital role of manganese, iron, and iodine (in conjunction with selenium) in KBD etiology and pathogenesis. High manganese and iron levels with low selenium and iodine levels were identified as characteristic features of the bio-element profile of KBD. The different element ratios reflect the interaction between several elements. The most significant of these were the proportions of Se/Mn and Zn/Fe, which may be significant in the occurrence and development of KBD.