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Abstract Background High-power short-duration (HPSD) ablation strategy has emerged as a popular approach for treating atrial fibrillation (AF), with shorter ablation time. The utilized Smart Touch Surround Flow (STSF) catheter, with 56 holes around the electrode, lowers electrode-tissue temperature and thrombus risk. Thus, we conducted this prospective, randomized study to investigate if the HPSD strategy with STSF catheter in AF ablation procedures reduces the silent cerebral embolism (SCE) risk compared to the conventional approach with the Smart Touch (ST) catheter. Methods From June 2020 to September 2021, 100 AF patients were randomized 1:1 to the HPSD group using the STSF catheter (power set at 50 W) or the conventional group using the ST catheter (power set at 30 to 35 W). Pulmonary vein isolation was performed in all patients, with additional lesions at operator’s discretion. High-resolution cerebral diffusion-weighted magnetic resonance imaging (hDWI) with slice thickness of 1 mm was performed before and 24–72 h after ablation. The incidence of new periprocedural SCE was defined as the primary outcome. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) test. Results All enrolled AF patients (median age 63, 60% male, 59% paroxysmal AF) underwent successful ablation. Post-procedural hDWI identified 106 lesions in 42 enrolled patients (42%), with 55 lesions in 22 patients (44%) in the HPSD group and 51 lesions in 20 patients (40%) in the conventional group (p = 0.685). No significant differences were observed between two groups regarding the average number of lesions (p = 0.751), maximum lesion diameter (p = 0.405), and total lesion volume per patient (p = 0.669). Persistent AF and CHA2DS2-VASc score were identified as SCE determinants during AF ablation procedure by multivariable regression analysis. No significant differences in MoCA scores were observed between patients with SCE and those without, both immediately post-procedure (p = 0.572) and at the 3-month follow-up (p = 0.743). Conclusions Involving a small sample size of 100 AF patients, this study reveals a similar incidence of SCE in AF ablation procedures, comparing the HPSD strategy using the STSF catheter to the conventional approach with the ST catheter. Trial registration Clinicaltrials.gov: NCT04408716. Graphical Abstract AF = Atrial fibrillation, DWI = Diffusion-weighted magnetic resonance imaging, HPSD = High-power short-duration, ST = Smart Touch, STSF = Smart Touch Surround Flow.

Abstract Background In this retrospective study, we aimed to develop a nomogram to predict recurrence during a 1-year period of spinal manipulation/mobilization (SM/M) in patients with low back pain (LBP) with greater pain intensity, more severe comorbid conditions, or a neuropathic component. Methods A total of 786 consecutive patients with LBP treated with SM/M as primary therapy were divided into training (n = 545) and validation (n = 241) sets. Cox regression analyses were used to assess the relative value of clinical factors and lumbar magnetic resonance imaging features associated with recurrence during the 1-year period. Predictors of recurrence with significant differences were used to construct a nomogram in the training set. We evaluated the performance of the model on the training and validation sets to determine its discriminative ability, calibration, and clinical utility. The prognostic value of the nomogram for predicting recurrence was assessed using Kaplan–Meier analysis and time-dependent receiver operating characteristic analyses. Results A nomogram comprising hospitalization time, previous history of LBP, disease duration, lumbar range of motion, lower extremity tendon reflex, muscle strength, ratio of herniation to uncompressed dural sac area, and Pfirrmann classification was established for recurrence during a 1-year period after SM/M in patients with LBP. Favorable calibration and discrimination were observed in the nomogram training and validation sets (C-index 0.753 and 0.779, respectively). Decision curve analysis confirmed the clinical utility of the nomogram. Over a 1-year period, the nomogram showed satisfactory performance in predicting recurrence in LBP after SM/M. Conclusion We established and validated a novel nomogram that can accurately predict a patient's risk of LBP recurrence following SM/M. This realistic prognostic model may aid doctors and therapists in their decision-making process and strategy optimization for non-surgical treatment of LBP using SM/M.

Abstract Postharvest pathogens can affect a wide range of fresh fruit and vegetables, including grapes, resulting in significant profit loss. Isoquinoline alkaloids of Mahonia fortunei, a Chinese herbal medicine, have been used to treat infectious microbes, which might be effective against postharvest pathogens. The phytochemical and bioactive investigation of this plant led to the isolation of 18 alkaloids, of which 9 compounds inhibited the growth of Botrytis cinerea and 4 compounds against Penicillium italicum. The antifungal alkaloids could change the mycelium morphology, the total lipid content, and leak the cell contents of B. cinerea. Furthermore, the two most potent antifungal alkaloids, berberine (13) completely inhibited effect on gray mold of table grape at 512 mg L−1, while jatrorrhizine (18) exhibited an inhibition rate > 90% on grape rot at the same concentration, with lower cytotoxicity and residue than chlorothalonil, which suggested that ingredients of M. fortunei might be a low-toxicity, low-residue, eco-friendly botanical fungicide against postharvest pathogens. Graphical Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that generally affects the joints. In the face of inflammation-induced cartilage and bone damage, RA treatment remains insufficient. While research evidence indicates that acupuncture can exert anti-inflammatory and analgesic effects, improve the joint function of RA patients, and delay the disease, data on whether it can promote RA repair are lacking. Findings from the present work demonstrated that both the antigen-induced arthritis (AIA) and collagen-induced arthritis (CIA) models can simulate joint swelling of RA. The AIA model was more stable than the CIA model, with a higher incidence of successful arthritis modeling. Moreover, the AIA mice model could simulate the signal molecules and related pathological processes of the autoimmune response in RA, as well as major pathways related to RA and antigen immune response mechanisms. Manual acupuncture (MA) at Zusanli (ST36) significantly improved paw redness and swelling, pain, and inflammatory cell infiltration in the joints in AIA mice. The therapeutic effect of MA on AIA is achieved primarily through the regulation of steroid hormone biosynthesis, cell metabolism, and tissue repair processes. MA at ST36 can increase the gene contents of tissue repair growth factors, including PEG3, GADD45A, GDF5, FGF5, SOX2, and ATP6V1C2 in the inflammatory side joints of AIA mice, as well as the gene expression of the anti-inflammatory cytokine IL-10. In conclusion, acupuncture may alleviate RA in the joints via modulating the tissue healing process.

Extracellular vesicles are tiny lipid bilayer-enclosed membrane particles, including apoptotic bodies, micro vesicles, and exosomes. Organisms of all life forms can secrete extracellular vesicles into their surrounding environment, which serve as important communication tools between cells and between cells and the environment, and participate in a variety of physiological processes. According to new evidence, plant extracellular vesicles play an important role in the regulation of transboundary molecules with interacting organisms. In addition to carrying signaling molecules (nucleic acids, proteins, metabolic wastes, etc.) to mediate cellular communication, plant cells External vesicles themselves can also function as functional molecules in the cellular microenvironment across cell boundaries. This review introduces the source and extraction of plant extracellular vesicles, and attempts to clarify its anti-tumor mechanism by summarizing the current research on plant extracellular vesicles for disease treatment. We speculate that the continued development of plant extracellular vesicle-based therapeutic and drug delivery platforms will benefit their clinical applications.

Abstract Background More than 2500 species belong to the Meloidae family (Coleoptera: Tenebrionoidea), members of which produce the potent defensive blistering agent cantharidin and are commonly known as blister beetles or Spanishflies. Cantharidin has recently been used for cancer therapy. Hycleus cichorii and Hycleus phaleratus have been used in traditional Chinese medicine for more than 2000 years due to their ability to biosynthesize cantharidin. To understand the role of the chemosensory system in beetle evolution, we comparatively analysed the chemosensory receptor families of both blister beetle species and compared them with those of other beetles. Results We identified 89 odorant receptors (ORs), 86 gustatory receptors (GRs), and 45 ionotropic receptors (IRs) in H. phaleratus and 149 ORs, 102 GRs and 50 IRs in H. cichorii. Nine groups of beetle ORs were recovered, and a similar pattern of ORs in Coleoptera emerged. Two evident expanded clades in Hycleus (Groups 5A and 3) were reconstructed in the phylogenetic tree. Four of eight genes with evidence of positive selection were clustered in the expanded clades of Group 5A. Three, eight and three orthologous pairs of CO2, sugar and fructose receptors, respectively, were identified in both blister beetles. Two evident expanded clades of putative bitter GRs in Hycleus were also found, and the GR in one clade had notably low divergence. Interestingly, IR41a was specifically expanded in blister beetles compared to other insects identified to date, and IR75 was also clearly expanded in both blister beetles based on our phylogenetic tree analysis. Moreover, evidence of positive selection was detected for eight ORs, three GRs and two IRs, half of which were from five duplicate clades. Conclusions We first annotated the chemosensory receptor families in a pair of sister beetle genomes (Meloidae: Hycleus), which facilitated evolutionary analysis of chemosensory receptors between sibling species in the Coleoptera group. Our analysis suggests that changes in chemosensory receptors have a possible role in chemical-based species evolution in blister beetles. Future studies should include more species to verify this correlation, which will help us understand the evolution of blister beetles.

Silicon carbide (SiC) has good chemical resistance, excellent mechanical properties, thermal conductivity, especially in extreme conditions of application, and has proved to be a very promising electromagnetic absorption material. However, single silicon carbide cannot meet the increasing demand for high performance of absorbing materials. It has become an important research direction to combine it with other absorbing materials to improve its absorbing performance. In this study, a composite absorber material was prepared by 50 wt.% micron-sized beta-silicon carbide (β-sic) powder, mixed with a 0.2 wt.% multiwalled carbon nanotubes (MWCNTs) and 50 wt.% polyurethane (PU) substrate. The mixture was stirred and deaerated to form a slurry, and sprayed onto synthetic fabric. The results showed that the composite material was flexible, with a thickness of less than 2 mm and favorable adhesion. The results obtained by reflection graph of the radar waves, indicated that the return loss within the X-band range (8–12 GHz) was less than −40 dB, indicating favorable radar wave absorption. Therefore, composite materials could thus be used successfully as radar wave absorbers, and was suitable for stealth materials in “asymmetric warfare”.

Radix Asteris (RA), also known as ‘Zi Wan’, is the dried root and rhizome of Aster tataricus L. f., which has been used to treat cough and asthma in many countries such as China, Japan, Korea and Vietnam. This article summarizes the available information on RA in ancient Chinese medicine books and modern research literature: its botanical properties, traditional uses, chemical composition, pharmacological activity, toxicity and quality control. Studies have shown that RA extracts contain terpenes, triterpenoid saponins, organic acids, peptides and flavonoids, and have various pharmacological activities such as anti-inflammatory, anti-tumor, anti-oxidation, and anti-depression. RA is considered to be a promising medicinal plant based on its traditional use, chemical constituents and pharmacological activities. However, there are few studies on its toxicity and the consistency of its components, which indicates the need for further in-depth studies on the toxicity and quality control of RA and its extracts.

Abstract Background Cervical cancer (CC) is one of the most common cancers among females worldwide. Spindle and kinetochore-associated complex subunit 3 (SKA3), located on chromosome 13q, was identified as a novel gene involved in promoting malignant transformation in cancers. However, the function and underlying mechanisms of SKA3 in CC remain unknown. Using the Oncomine database, we found that expression of SKA3 mRNA is higher in CC tissues than in normal tissues and is linked with poor prognosis. Methods In our study, immunohistochemistry showed increased expression of SKA3 in CC tissues. The effect of SKA3 on cell proliferation and migration was evaluated by CCK8, clone formation, Transwell and wound-healing assays in HeLa and SiHa cells with stable SKA3 overexpression and knockdown. In addition, we established a xenograft tumor model in vivo. Results SKA3 overexpression promoted cell proliferation and migration and accelerated tumor growth. We further identified that SKA3 is involved in regulating cell cycle progression and the PI3K/Akt signaling pathway via RNA-sequencing (RNA-Seq) and gene set enrichment analyses. Western blotting results revealed that SKA3 overexpression increased levels of p-Akt, cyclin E2, CDK2, cyclin D1, CDK4, E2F1 and p-Rb in HeLa cells. Additionally, the use of an Akt inhibitor (GSK690693) significantly reversed the cell proliferation capacity induced by SKA3 overexpression in HeLa cells. Conclusions We suggest that SKA3 overexpression contributes to CC cell growth and migration by promoting cell cycle progression and activating the PI3K–Akt signaling pathway, which may provide potential novel therapeutic targets for CC treatment.

Dendritic cells (DCs) play a key role in initiating and regulating the immune responses to pathogens, self-antigens, and cancers. Human blood DCs comprise a family of different subsets: plasmacytoid DCs (pDCs) and CD16+, CD1c/BDCA1+, and BDCA3+ (CD141+) myeloid DCs and possess different phenotypes and functional characteristics. Lung cancer is the most common cancer, with the highest morbidity and mortality in the world. However, which DC subset plays a leading role in the lung cancer immune responses is unclear. We reanalyzed C-type lectin domain family 9 member A (CLEC9A) and CD141 (THBD) gene expression profiles from the Cancer Genome Atlas (TCGA) database and performed the Kaplan-Meier survival analysis of overall survival for several cancers according to their expression levels. Next, we investigated the capacities of five human blood DC subsets to stimulate T cell proliferation and capture, process and (cross-) present tumor antigen. Human BDCA3+ (CD141+) DCs have a superior capacity to stimulate allogeneic CD4+T cells proliferation and induce superior Th1 response compared with other DC subsets. Interestingly, toll-like receptor (TLR) agonists have little effect on DCs to induce the proliferation of naïve CD4+ T cells, but contribute to their differentiation. Importantly, BDCA3+ (CD141+) DCs possess the most potent ability to cross-present human tumor antigen after their uptake of necrotic lung cancer cells despite their lower antigen uptake. These findings suggest that human BDCA3+ (CD141+) DCs are critical mediators of cytotoxic T lymphocyte responses against EGFR-positive lung cancer. Therefore, our findings may provide theoretical basis for the development of DC-based antitumor vaccines.

Agarwood is generally used to make incense sticks in China and Southeast Asia. It emits smoke with a pleasant odor when burned. There are few reports on the chemical components of smoke generated by burning or heating agarwood. The agarwoods were produced by the whole-tree agarwood-inducing technique (AWIT), agarwood induced by axe wounds (AAW), burning-chisel-drilling agarwood (BCDA), wood of Aquilaria sinensis trees (AS), respectively. Herein, we used GC-MS to analyze the chemical constituents of incense smoke generated from AWIT, AAW, BCDA, AS, and the extracts of sticks from agarwood produced by the whole-tree agarwood-inducing technique (EAWIT), and 484 compounds were identified. A total of 61 chemical constituents were shared among AWIT, AAW, and BCDA. The experimental data showed that aromatic compounds were the main chemical constituents in agarwood smoke and that some chromone derivatives could be cracked into low-molecular-weight aromatic compounds (LACs) at high temperature. Furthermore, agarwood incense smoke showed anti-inflammatory activities by inhibiting lipopolysaccharide- (LPS-) induced TNF-α and IL-1α release in RAW264.7 cells.

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.

Schwann cells play an important role in the peripheral nervous system, especially in nerve repair following injury, so artificial nerve regeneration requires an effective technique for obtaining purified Schwann cells. In vivo and in vitro pre-degeneration of peripheral nerves have been shown to obtain high-purity Schwann cells. We believed that in vitro pre-degeneration was simple and controllable, and available for the clinic. Thus, we co-cultured the crushed sciatic nerves with bone marrow-derived cells in vitro. Results demonstrated that, 3 hours after injury, a large number of mononuclear cells moved to the crushed nerves and a large number of bone marrow-derived cells infiltrated the nerve segments. These changes promoted the degradation of the nerve segments, and the dedifferentiation and proliferation of Schwann cells. Neural cell adhesion molecule and glial fibrillary acidic protein expression were detected in the crushed nerves. Schwann cell yield was 9.08 ± 2.01 × 10 4 /mg. The purity of primary cultured Schwann cells was 88.4 ± 5.79%. These indicate a successful new method for obtaining Schwann cells of high purity and yield from adult crushed sciatic nerve using bone marrow-derived cells.

Abstract Crizotinib is a multi-targeted tyrosine kinase inhibitor (TKI) with activity against mesenchymal-epithelial transition factor (MET) and anaplastic lymphoma kinase (ALK). However, the concomitant oncogenic drivers may affect the sensitivity of crizotinib. Herein, we present a 69-year-old never-smoker Chinese male with advanced lung adenocarcinoma harboring concomitant spectrin beta non-erythrocytic 1 (SPTBN1)-ALK fusion, c-Met overexpression, and human epidermal growth factor receptor-2 (HER-2) amplification with inherent resistance to crizotinib, chemotherapy, and radiotherapy. Although the patient received timely and comprehensive treatment, the overall survival was only 8 months. Therefore, c-Met overexpression, HER-2 gene amplification, and SPTBN1-ALK gene fusion can coexist in lung adenocarcinoma and may become a potential biomarker of cancer refractory to crizotinib, chemotherapy, and radiotherapy as well as of a relatively poor prognosis. In addition, the novel SPTBN1-ALK fusion gene may become a potential target for anti-tumor therapy.

In China, Fusarium head blight is caused mainly by the Fusarium graminearum species complex (FGSC), which produces trichothecene toxins. The FGSC is divided into three chemotypes: 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), and nivalenol (NIV). In order to predict the geographical changes in the distribution of these chemotype populations in major winter wheat-producing areas in China, the biological characteristics of twenty randomly selected isolates from each of the three chemotypes were studied. No significant difference was exhibited in the growth rate of 3-ADON, 15-ADON, and NIV isolates at 15°C. At 20°C and 25°C, the growth rate of 15-ADON isolates was the highest. At 30°C, the growth rate of NIV and 3-ADON isolates was significantly higher than that of 15-ADON isolates. The 15-ADON isolates produced the highest quantities of perithecia and two to three days earlier than the other two populations at each temperature, and released more ascospores at 18°C. The aggressiveness test on wheat seedlings and ears indicated there was no significant difference between the 3-ADON and 15-ADON isolates. However, the aggressiveness of NIV isolates was significantly lower than that of the 3-ADON and 15-ADON isolates. The DON content in grains from heads inoculated with the 3-ADON isolates was higher than the content of 15-ADON and NIV isolates. The results showed that 15-ADON population had the advantage in perithecia formation and ascospore release, and the 3-ADON population produced more DON in wheat grains. We suggested that distribution of these three chemotype populations may be related to these biological characteristics.

Segregation analysis of the mixed genetic model of major gene plus polygene was used to identify the major genes for cotton yield-related traits using six generations P1, P2, F1, B1, B2, and F2 generated from the cross of Baimian 1 × TM-1. In addition to boll size and seed index, the major genes for the other five traits were detected: one each for seed yield, lint percentage, boll number, lint index; and two for lint yield. Quantitative trait locus/loci (QTL) mapping was performed in the F2 and F2:3 populations of above cross through molecular marker technology, and a total of 50 QTL (26 suggestive and 24 significant) for yield-related traits were detected. Four common QTL were discovered: qLP-3b(F2)/qLP-3(F2:3) and qLP-19b (F2)/qLP-19(F2:3) for lint percentage, qBN-17(F2)/qBN-17(F2:3) for boll number, and qBS-26b(F2)/qBS-26(F2:3) for boll size. Especially, qLP-3b(F2)/qLP-3(F2:3), not only had LOD scores

Five new cucurbitane-typetriterpenoid glycosides, named Xuedanoside F−J (1−5), were obtained from the rhizomes of Hemsleya penxianensis (Xue dan), which belongs to the family of Cucurbitaceae. These new compounds were elucidated byspectroscopic analysis, including 1D, 2D NMR, and HR-ESI-MS spectra. Additionally, all the isolates were evaluated for cytotoxicity against three human cancer cell lines (Hela, MCF-7, and A-549) with the IC50 ranging from 2.25 to 49.44 µM in vitro with treatment 48 h and showed low cytotoxicity in human normal liver L-02 cells (IC50 > 50 µM). Compound 5 showed the most significant cytotoxic activity with the IC50 value of 2.25, 4.72, and 5.33 µM in 48 h, respectively.

Five new naphthalene derivatives, named Eleutherols A–C (1–3) and Eleuthinones B–C (4,5), together with three known compounds were isolated from the bulbs of Eleutherine americana. Their structures were elucidated on the basis of spectroscopic analysis including HR-ESI-MS, 1D and 2D NMR techniques. These compounds exhibited a potent effect against the injury of human umbilical vein endothelial cell (HUVECs) induced by high concentrations of glucose in vitro.

Four new 2-(2-phenylethyl)chromone derivatives (1–4) were isolated from the EtOH extract of Chinese agarwood produced via the whole-tree agarwood-inducing technique, coming from Aquilaria sinensis (Lour.) Spreng. (Thymelaeaceae). Their structures were elucidated by extensive spectroscopic methods, such as UV, IR, MS, 1D as well as 2D NMR. All of the isolates were then assessed for their anti-inflammatory activities on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7. Compound 1 exhibited significant inhibitory activity with an IC50 value of 4.6 μM.