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Zanthoxylum bungeanum Maxim. (huajiao) and Zanthoxylum armatum DC. (tengjiao), also known as Sichuan pepper, is a popular spice owing to its unique aroma and taste. Fried pepper oils are liquid condiments with unique flavors extracted from the pericarps of huajiao and tengjiao. To investigate the volatile profiles of the two different fried pepper oils, solid-phase microextraction (SPME) coupled with gas chromatography–mass spectrometry (GC-MS) was employed. The results revealed that D-limonene, linalyl acetate, linalool, myrcene, and ocimene significantly contributed to the overall flavor of huajiao oils. In addition, linalool, D-limonene, sabinene, myrcene, and linalyl acetate were identified as the main odorants in tengjiao oils. Finally, a characteristic chromatogram for the volatile compounds of each oil was established through the Similarity Evaluation System for the Chromatographic Fingerprint of Traditional Chinese Medicine, and the similarity thresholds of huajiao oils and tengjiao oils were 0.984 and 0.998, respectively. Linalool, sabinene, and linalyl acetate were markers for distinguishing between ZAOV samples and ZAOC samples. And germacrene D, linalool, sabinene, linalyl acetate, and β-myrcene were markers for distinguishing ZBOV samples from ZBOC samples.

Medical crowdfunding provides opportunities for individuals who lack financial resources to access the health services that they need. Despite the popularity of medical crowdfunding, the current understanding of the success of medical crowdfunding campaigns is fragmented and inadequate. We aimed to comprehensively investigate which factors lead to the success of medical crowdfunding campaigns. A search was conducted in PubMed, PsycINFO, Web of Science, ACM Digital Library, and ScienceDirect from 2010 to June 2020. Papers directly and indirectly related to the success of medical crowdfunding campaigns were included. Two reviewers independently extracted information on the success of medical crowdfunding campaigns. Our search yielded 441 articles, of which 13 met the inclusion criteria. Medical crowdfunding is increasingly attracting academic attention, and most studies leverage text analysis as their research methods; however, there is a lack of consensus on the definition of medical crowdfunding among researchers. Four categories of factors that affect the success of medical crowdfunding were identified: platforms, raisers, donors, and campaigns. Although some limitations exist in our systematic review, our study captured and mapped literatures of the success of medical crowdfunding campaigns systematically, which can be used as the basis for future research on this topic.

Anthocyanin stability substantially determines the postharvest storage quality of red Huajiao (Zanthoxylum bungeanum Maxim.). Herein, the composition of red Huajiao anthocyanins (RHAs) was characterized, and the copigmentation performance of seven phenolic compounds with RHAs was comparatively evaluated, together with verifying their practical efficacy in maintaining the overall quality of red Huajiao during frozen storage. UPLC-Q-TOF-MS/MS analysis identified ten anthocyanin monomers in RHAs, among which delphinidin-3,5-diglucoside (D3,5G, 28.23%), and delphinidin-3-O-glucoside (D3G, 14.86%) were verified as the predominant monomers. Naringin (NA) exhibited an optimal copigmentation effect, achieving a maximum color enhancement rate of 19.46% at a 1:40 molar ratio and a pH of 3.0 at 20 °C, while thermodynamic tests verified the excellent stability of the naringin–RHA complex. The copigmentation interactions between RHAs and copigments were largely attributed to hydrogen bonds, π–π stacking, and alkyl hydrophobic interactions. Considering practical application cost and flavor compatibility, chlorogenic acid (CGA) was selected as the preferred alternative copigment. Frozen storage tests suggested that soaking pretreatment with 10 mmol/L CGA effectively delayed color fading and maintained the integrity of the oil gland and the good sensory quality and color attributes of red Hujiao, with no adverse impacts on its inherent flavor and numbing components. Collectively, phenolic-mediated intermolecular copigmentation represents an efficient technical means for stabilizing color and maintaining the commercial quality of postharvest red Huajiao during frozen storage.

BackgroundDysfunction of the thalamocortical connectivity network is thought to underlie the pathophysiology of the migraine. This current study aimed to explore the thalamocortical connectivity changes during 4 weeks of continuous transcutaneous vagus nerve stimulation (taVNS) treatment on migraine patients.Methods70 migraine patients were recruited and randomized in an equal ratio to receive real taVNS or sham taVNS treatments for 4 weeks. Resting-state functional MRI was collected before and after treatment. The thalamus was parceled into functional regions of interest (ROIs) on the basis of six priori-defined cortical ROIs covering the entire cortex. Seed-based functional connectivity analysis between each thalamic subregion and the whole brain was further compared across groups after treatment.ResultsOf the 59 patients that finished the study, those in the taVNS group had significantly reduced number of migraine days, pain intensity and migraine attack times after 4 weeks of treatment compared with the sham taVNS. Functional connectivity analysis revealed that taVNS can increase the connectivity between the motor-related thalamus subregion and anterior cingulate cortex/medial prefrontal cortex, and decrease the connectivity between occipital cortex-related thalamus subregion and postcentral gyrus/precuneus.ConclusionOur findings suggest that taVNS can relieve the symptoms of headache as well as modulate the thalamocortical circuits in migraine patients. The results provide insights into the neural mechanism of taVNS and reveal potential therapeutic targets for migraine patients.

Osteosarcomas (OS) are highly metastatic and usually lead to poor outcomes. Epithelial-mesenchymal transition (EMT) is reported to be a critical event in metastasis. SIRT2 exerts dual functions in many different tumors. However, the underlying molecular mechanisms of SIRT2 in osteosarcoma cell metastasis and the question of whether SIRT2 regulates EMT have not been fully explored. In this study, we confirmed that SIRT2 was highly-expressed in human osteosarcoma MG63 and Saos-2 cell lines. The viability, migration and invasion of osteosarcoma cells were inhibited by knockdown of SIRT2 and were enhanced by overexpression of SIRT2. Moreover, SIRT2 positively regulated EMT and upregulated the protein levels of the mesenchymal markers N-cadherin and Vimentin and the levels of MMP2 and MMP9. A xenograft mouse model showed that SIRT2 knockdown in osteosarcoma cells led to reduced tumor growth, decreased expression of mesenchymal markers and impaired lung and liver metastasis in vivo. Furthermore, we showed that SIRT2 interacted with and upregulated the protein level of the EMT-associated transcription factor Snail. SIRT2 inhibited Snail degradation via its deacetylase activity. Knockdown of Snail abrogated the promoting effects of SIRT2 on migration and invasion of osteosarcoma cells. In conclusion, SIRT2 plays a crucial role in osteosarcoma metastasis by inhibiting Snail degradation and may serve as a novel therapeutic target to manage osteosarcoma.

Electrooxidation has emerged as an increasingly viable platform in molecular syntheses that can avoid stoichiometric chemical redox agents. Despite major progress in electrochemical C−H activations, these arene functionalizations generally require directing groups to enable the C−H activation. The installation and removal of these directing groups call for additional synthesis steps, which jeopardizes the inherent efficacy of the electrochemical C−H activation approach, leading to undesired waste with reduced step and atom economy. In sharp contrast, herein we present palladium-electrochemical C−H olefinations of simple arenes devoid of exogenous directing groups. The robust electrocatalysis protocol proved amenable to a wide range of both electron-rich and electron-deficient arenes under exceedingly mild reaction conditions, avoiding chemical oxidants. This study points to an interesting approach of two electrochemical transformations for the success of outstanding levels of position-selectivities in direct olefinations of electron-rich anisoles. A physical organic parameter-based machine learning model was developed to predict position-selectivity in electrochemical C−H olefinations. Furthermore, late-stage functionalizations set the stage for the direct C−H olefinations of structurally complex pharmaceutically relevant compounds, thereby avoiding protection and directing group manipulations. Electrochemistry has emerged as an increasingly viable tool in molecular synthesis. Here the authors realize electrocatalyzed C−H activations, with the aid of data science and artificial intelligence, towards selective alkenylations for late-stage drug diversifications.

Introduction Preoperative evaluation of inferior vena cava (IVC) wall invasion is very important to improve outcomes of patients with renal cell carcinoma (RCC), and may allow surgical urologists to treat the IVC more effectively. The objective of this study was to evaluate preoperative 18 F-FDG PET/CT in patients with RCC and IVC tumor thrombus (IVCTT) for the diagnosis of IVC wall invasion. Methods This retrospective case-control study evaluated 68 patients with RCC with level I-IV tumor thrombus. According to the histopathologic examination result, the patients were divided into IVC wall invasion group and non-invasion group. The 18 F-FDG PET/CT features between two groups were analyzed. Furthermore, a logistic regression model was used to determine if there was an association between PET/CT features and IVC wall invasion. Results Sixty-eight patients were evaluated, and 55.9% (38/68) had IVC wall invasion. Compared with non-invasion group, invasion group had higher SUVmax of RCC, higher SURmax (tumor to tumor thrombus ratio, Tu/Th), higher IVCTT coronal diameter, and longer IVCTT craniocaudal extent (all p  < 0.05). Multivariate analysis showed that SURmax (Tu/Th) (OR 8.760 [95%CI, 1.019–75.310]; p  = 0.048) and the maximum coronal diameter of IVCTT (OR 1.143 [95%CI, 1.029–1.269]; p  = 0.028) were predictors of IVC wall invasion. A model combining SURmax (Tu/Th) and the maximum coronal diameter of IVCTT achieved an AUC of 0.855 (95%CI, 0.757–0.954). The specificity and sensitivity for assessing IVC wall invasion was 92.1% and 76.7%, respectively. Conclusions Increases in SURmax (Tu/Th) and the maximum coronal diameter of IVCTT are associated with a higher probability of IVC wall invasion. Preoperative 18 F-FDG PET/CT imaging may be used to assess IVC wall invasion.

Background A growing body of evidence suggests that transcutaneous auricular vagus nerve stimulation (taVNS) may relieve symptoms of migraineurs. Frequency is one of the key stimulation parameters. The aim of this study is to investigate the modulation effect of taVNS frequency on the descending pain modulation system (DPMS) in patients with migraine. Methods Twenty-four episodic migraineurs without aura (21 females) were recruited for the single-blind, crossover, functional magnetic resonance imaging (fMRI) study. Each participant attended two separate fMRI scan sessions, one for 1 Hz and another for 20 Hz taVNS, in a random order. Seed-based functional connectivity analysis was applied using the ventrolateral periaqueductal gray (PAG) as the region of interest. Results Compared with the pre-taVNS resting state, continuous 1 Hz taVNS (during) produced a significant increase in functional connectivity between the PAG and the bilateral middle cingulate cortex (MCC), right precuneus, left middle frontal gyrus (MFG), and left cuneus. Compared with 20 Hz taVNS, 1 Hz taVNS produced greater PAG connectivity increases with the MCC, right precuneus/posterior cingulate cortex, left insula, and anterior cingulate cortex (ACC). A significant negative correlation was observed between the number of migraine attacks in the previous 4 weeks and the PAG-MCC functional connectivity in the pre-taVNS resting-state before 1 Hz taVNS. Conclusions Our findings suggest that taVNS with different frequencies may produce different modulation effects on the descending pain modulation system, demonstrating the important role of stimulation frequency in taVNS treatment.

To investigate the spatio-temporal distribution characteristics and changing trends of syphilis in Nantong city. Joinpoint regression model, spatial autocorrelation and SaTScan spatio-temporal scanning were used to analyze the trend of syphilis reported incidence and spatio-temporal distribution characteristics in Nantong City. From 2013 to 2022, the reported incidence of syphilis in Nantong City increased at an average annual rate of 6.60%, of which the increase rate of latent syphilis was 13.45%. The high-high clustering areas were mainly distributed in 15 streets of Chongchuan District and all streets of Nantong Development Zone. SaTScan spatio-temporal scanning detected a total of two clustering areas, all from 2021 to 2022. The first cluster includes 24 streets with a radius of 16.27 km, and the second cluster includes 18 streets within a radius of 34.90 km. The reported incidence of syphilis in Nantong City showed an increasing trend, mainly manifested as an increase in latent syphilis, and the reported incidence of syphilis in various towns (streets) showed obvious spatial clustering, and attention should be paid to key areas and targeted interventions should be formulated.

Migraine is a common primary headache disorder. Transcutaneous auricular vagus nerve stimulation (taVNS) has been verified to be effective in patients with migraine without aura (MWoA). However, there are large interindividual differences in patients’ responses to taVNS. This study aimed to explore whether pretreatment fractional amplitude of low frequency fluctuation (fALFF) features could predict clinical outcomes in MWoA patients after 4-week taVNS. Sixty MWoA patients and sixty well-matched healthy controls (HCs) were recruited, and migraineurs received 4-week taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected, and the significant differences of fALFF were detected between MWoA patients and HCs using two-sample t -test. A mask of these significant regions was generated and used for subsequent analysis. The abnormal fALFF in the mask was used to predict taVNS efficacy for MWoA using a support vector regression (SVR) model combining with feature select of weight based on the LIBSVM toolbox. We found that (1) compared with HCs, MWoA patients exhibited increased fALFF in the left thalamus, left inferior parietal gyrus (IPG), bilateral precentral gyrus (PreCG), right postcentral gyrus (PoCG), and bilateral supplementary motor areas (SMAs), but decreased in the bilateral precuneus and left superior frontal gyrus (SFG)/medial prefrontal cortex (mPFC); (2) after 4-week taVNS treatment, the fALFF values significantly decreased in these brain regions based on the pretreatment comparison. Importantly, the decreased fALFF in the bilateral precuneus was positively associated with the reduction in the attack times ( r = 0.357, p = 0.005, Bonferroni correction, 0.05/5), whereas the reduced fALFF in the right PoCG was negatively associated with reduced visual analog scale (VAS) scores ( r = −0.267, p = 0.039, uncorrected); (3) the SVR model exhibited a good performance for prediction ( r = 0.411, p < 0.001),which suggests that these extracted fALFF features could be used as reliable biomarkers to predict the treatment response of taVNS for MWoA patients. This study demonstrated that the baseline fALFF features have good potential for predicting individualized treatment response of taVNS in MWoA patients, and those weight brain areas are mainly involved in the thalamocortical (TC) circuits, default mode network (DMN), and descending pain modulation system (DPMS). This will contribute to well understanding the mechanism of taVNS in treating MWoA patients and may help to screen ideal patients who respond well to taVNS treatment.