Electrically Driven Deterministic Plasmon Light Sources Based on Arrays of Molecular Tunnel Junctions.

Surface plasmons excited via inelastic tunnelling have led to plasmon light sources with small footprints and ultrafast response speeds, which are favored by integrated optical circuits. Self-assembled monolayers of organic molecules function as highly tunable tunnel barriers with novel functions. However, limited by the low effective contact between the liquid metal electrode and the self-assembled monolayers, it is quite challenging to obtain molecular plasmon light sources with high density and uniform emission. Here, by combining lithographic patterning with a solvent treatment method, we have demonstrated electrically driven deterministic plasmon emission from arrays of molecular tunnel junctions. The solvent treatment could largely improve the effective contact from 9.6% to 48% and simultaneously allow the liquid metal to fill into lithographically patterned micropore structures toward deterministic plasmon emission with desired patterns. Our findings open up new possibilities for tunnel junction-based plasmon light sources, laying the foundation for electrically driven light-emitting metasurfaces.

Surgical Treatment Strategies for Residual or Recurrent Intracranial Aneurysms Following Endovascular Embolization.

OBJECTIVE: To explore how to effectively manage the residual or recurrent intracranial aneurysms after embolization. METHODS: The authors retrospectively reviewed our experience of endovascular interventional therapy, surgical clipping, and cerebrovascular bypass surgery in the treatment of residual or recurrent aneurysms after embolization at the authors' institution from 2018 to 2022. RESULTS: The Glasgow Outcome Scale of 28 patients after the procedure and at discharge showed that 24 recovered well, 3 had severe disability, and 1 died. During the 24-month follow-up, 26 had a good recovery, 1 suffered from disability, and 1 died. Two cases of aneurysm recurrence were detected, and both were treated through endovascular therapy. Among them, 1 case underwent a repeat endovascular embolization, and 1 case was switched to surgical clipping. No residual aneurysms were observed in the remaining patients who underwent bypass surgery, and their bypass grafts were all patent. CONCLUSION: Based on the clinical status of patients, aneurysmal characteristics, surgical risk, and possibility of rerupture of aneurysms, an individualized strategy was proposed for residual or recurrent aneurysms after embolization. The use of endovascular interventional therapy or surgical clipping can be safely and effectively managed, and cerebrovascular bypass surgery can effectively manage complex aneurysms.

Relationship Between Pericarotid Fat Density and Pathology-Based Carotid Plaque Risk Characteristics.

OBJECTIVES: In this study, the authors aimed to evaluate the relationship between pericarotid fat density (PFD) and pathologic carotid plaque risk characteristics. METHODS: The authors retrospectively evaluated 58 patients (mean age: 66.66 ± 7.26 y, 44 males) who were subjected to both carotid endarterectomy and carotid artery computed tomography angiography (CTA) at the authors' institution. The computed tomography values of the adipose tissue around the most severe stenosis carotid artery were measured, and the removed plaques were sent to the Department of Pathology for American Heart Association (AHA) classification. The Wilcoxon signed-rank test was used to detect the difference in PFD values between the operative and nonoperative sides. According to carotid plaque risk characteristics, the associations between PFD and 4 different risk characteristic subgroups were analyzed. The Student t test and χ2 test were used to compare differences between different risk subgroups. Receiver operating characteristic curve analysis was used to evaluate the predictive efficacy of PFD for carotid plaque risk characteristics. RESULTS: The operative side had higher mean Hounsfield units (HU) values compared with the nonoperative side (P < 0.001). The AHA VI and the intraplaque hemorrhage (IPH) subgroups had higher mean HU values compared with the non-AHA VI and the non-IPH subgroups (P < 0.05). Male patients presented with IPH more than female patients (P = 0.047). The results of receiver operating characteristic curve analysis showed that the mean HU value (operative side; area under the curve: 0.729, Sensitivity (SE): 59.26%, Specificity (SP): 80.65%, P = 0.003) had a certain predictive value for diagnosing high-risk VI plaques. Pericarotid fat density ≥ -68.167 HU is expected to serve as a potential cutoff value to identify AHA VI and non-AHA VI subgroups. CONCLUSION: PFD was significantly associated with vulnerable plaques, high-risk AHA VI plaques, and IPH, which could be an indirect clinical marker for vulnerable plaques.

Research progress on the mechanism of traditional Chinese medicine regulating intestinal microbiota to combat influenza a virus infection.

Influenza A viruses (IAV) are a prevalent respiratory pathogen that can cause seasonal flu and global pandemics, posing a significant global public health threat. Emerging research suggests that IAV infections may disrupt the balance of gut microbiota, while gut dysbiosis can affect disease progression in IAV patients. Therefore, restoring gut microbiota balance may represent a promising therapeutic target for IAV infections. Traditional Chinese medicine, with its ability to regulate gut microbiota, offers significant potential in preventing and treating IAV. This article provides a comprehensive review of the relationship between IAV and gut microbiota, highlighting the impact of gut microbiota on IAV infections. It also explores the mechanisms and role of traditional Chinese medicine in regulating gut microbiota for the prevention and treatment of IAV, presenting novel research avenues for traditional Chinese medicine-based IAV treatments.

Clinical Effect of Rehabilitation New Fluid Combined with Sanjie Analgesic Capsules in the Treatment of Granulomatous Mastitis and Thyroiditis and Impact on Immune Indexes of Patients.

Objective: To analyze the clinical effect of rehabilitation new fluid combined with Sanjie analgesic capsules in the treatment of granulomatous lobular mastitis (GLM) and thyroiditis and the impact on immune indexes of patients. Methods: For a retrospective study, we selected 150 patients with GLM and 150 patients with thyroiditis admitted to The Fourth Hospital of Shijiazhuang from January 2021 to January 2022. We divided them into three groups based on the treatment methods. Control group 1 (CG1) included patients treated with rehabilitation new fluid alone, while control group 2 (CG2) included patients treated with the Sanjie analgesic capsules alone. The third group, the observation group (OG), included patients treated with rehabilitation new fluid (extract of drying body from Periplaneta americana) at an oral dose of 10 ml combined with Sanjie analgesic capsules. There were 50 patients in each group. The clinical efficacy, symptom improvement, the level changes of free triiodothyronine (FT3), free tetraiodothyronine (FT4), and thyroid stimulating hormone (TSH), and the changes of immune indexes such as CD4+ (cluster of differentiation 4+), CD25+ (cluster of differentiation 25+), CD68+ (cluster of differentiation 68+) and CD138+ (cluster of differentiation 138+) were analyzed. Results: After treatment, the total treatment effectiveness of GLM in the OG was 94%, which was significantly higher than 80% in the CG1 and 78% in the CG2 (P = .037, .021), while the total treatment effectiveness of thyroiditis in the OG was 92%, which was significantly higher than 76% in the CG1 and 74% in the CG2 (P = .029, 0.017). The scores of breast pain, breast overflow, tumor size, local skin changes, and axillary fossa lymphadenectasis of the affected side in the OG of GLM were better than those in CG1 (Pbreast pain < .001, 95%CI: 0.573-1.747; Pbreast overflow = .022, 95%CI: 0.074-0.905; Ptumor size = .008, 95%CI: 0.231-1.489; Plocal skin changes = .001, 95%CI: 0.382-1.498; Paxillary fossa lymphadenectasis of the affected side = .011, 95%CI: 0.096-0.704) and CG2 (Pbreast pain = .001, 95%CI: 0.449-1.711; Pbreast overflow = .049, 95%CI: 0.002-0.798; Ptumor size =0.019, 95%CI: 0.132-1.428; Plocal skin changes < .001, 95%CI: 0.563-1.517; Paxillary fossa lymphadenectasis of the affected side = .001, 95%CI: 0.202-0.678). The levels of FT3 and FT4 in the OG of thyroiditis were higher than CG1 (PFT3 < .001, 95%CI: 0.951-1.590; PFT4 < .001, 95%CI: 1.421-2.618) and CG2 (PFT3 < .001, 95%CI: 0.943-1.643; PFT4 < .001, 95%CI: 1.521-2.758), and the TSH level was lower compared with CG1 (PTSH < .001, 95%CI: 2.409-3.070) and CG2 (PTSH < .001, 95%CI: 2.540-3.230). The immune indexes of GLM were improved, and the levels of CD4+, CD25+, CD68+, and CD138+ in the OG were better than those in the CG1 (PCD4+ < .001, 95%CI: 2.967-4.912; PCD25+ < .001, 95%CI: 3.707-5.212; PCD68+ < .001, 95%CI: 1.445-2.200; PCD138+ < .001, 95%CI: 3.922-5.510) and CG2 (PCD4+ < .001, 95%CI: 3.093-4.995; PCD25+ < .001, 95%CI: 3.527-4.904; PCD68+ < .001, 95%CI: 1.334-2.216; PCD138+ < .001, 95%CI: 3.878-5.352). The immune indexes of thyroiditis were improved, and the levels of CD4+, CD25+, CD68+, and CD138+ in the OG were better than those in the CG1 (PCD4+ < .001, 95%CI: 4.235-6.117; PCD25+ < .001, 95%CI: 3.300-4.810; PCD68+ < .001, 95%CI: 1.173-1.939; PCD138+ < .001, 95%CI: 3.704-4.881) and CG2 (PCD4+ < .001, 95%CI: 3.136-5.422; PCD25+ < .001, 95%CI: 3.182-4.615; PCD68+ < .001, 95%CI: 1.216-2.113; PCD138+ < .001, 95%CI: 4.145-5.527). Conclusion: The clinical effect of rehabilitation new fluid combined with Sanjie analgesic capsule in the treatment of GLM and thyroiditis is remarkable, which enables enhancement of the treatment efficiency, and improves patients' clinical symptoms, functional indexes, and the levels of immune indexes, as a direction for the follow-up treatment in the clinic.

Improved Skip-Gram Based on Graph Structure Information.

Applying the Skip-gram to graph representation learning has become a widely researched topic in recent years. Prior works usually focus on the migration application of the Skip-gram model, while Skip-gram in graph representation learning, initially applied to word embedding, is left insufficiently explored. To compensate for the shortcoming, we analyze the difference between word embedding and graph embedding and reveal the principle of graph representation learning through a case study to explain the essential idea of graph embedding intuitively. Through the case study and in-depth understanding of graph embeddings, we propose Graph Skip-gram, an extension of the Skip-gram model using graph structure information. Graph Skip-gram can be combined with a variety of algorithms for excellent adaptability. Inspired by word embeddings in natural language processing, we design a novel feature fusion algorithm to fuse node vectors based on node vector similarity. We fully articulate the ideas of our approach on a small network and provide extensive experimental comparisons, including multiple classification tasks and link prediction tasks, demonstrating that our proposed approach is more applicable to graph representation learning.

An Allelic Variant of the Broad-Spectrum Blast Resistance Gene Ptr in Weedy Rice Is Associated with Resistance to the Most Virulent Blast Race IB-33.

Rice resistance (R) genes have been effectively deployed to prevent blast disease caused by the fungal pathogen Magnaporthe oryzae, one of the most serious threats for stable rice production worldwide. Weedy rice competing with cultivated rice may carry novel or lost R genes. The quantitative trait locus qBR12.3b was previously mapped between two single nucleotide polymorphism markers at the 10,633,942-bp and 10,820,033-bp genomic positions in a black-hull-awned (BHA) weed strain using a weed-crop-mapping population under greenhouse conditions. In this study, we found a portion of the known resistance gene Ptr encoding a protein with four armadillo repeats and confers a broad spectrum of blast resistance. We then analyzed the sequences of the Ptr gene from weedy rice, PtrBHA, and identified a unique amino acid glutamine at protein position 874. Minor changes of protein conformation of the PtrBHA gene were predicted through structural analysis of PtrBHA, suggesting that the product of PtrBHA is involved in disease resistance. A gene-specific codominant marker HJ17-13 from PtrBHA was then developed to distinguish alleles in weeds and crops. The PtrBHA gene existed in 207 individuals of the same mapping population, where qBR12.3b was mapped using this gene-specific marker. Disease reactions of 207 individuals and their parents to IB-33 were evaluated. The resistant individuals had PtrBHA whereas the susceptible individuals did not, suggesting that HJ17-13 is reliable to predict qBR12.3b. Taken together, this newly developed marker, and weedy rice genotypes carrying qBR12.3b, are useful for blast improvement using marker assisted selection.

Bypass Surgery Management of Complex Proximal and Distal Posterior Inferior Cerebellar Artery Aneurysms.

BACKGROUND: For the complex posterior inferior cerebellar artery (PICA) aneurysms, standard microsurgical or endovascular technical options were not feasible. To determine the efficacy and outcomes of bypass surgery for complex PICA aneurysms, the authors herein review our recent surgical experience for complex PICA aneurysms. METHODS: The authors retrospectively reviewed our experience of extracranial-intracranial bypass and intracranial-intracranial bypass surgery in treatment of proximal and distal complex PICA aneurysms at our institution from 2016 to 2020. RESULTS: Twelve patients harboring 12 complex PICA aneurysms received bypass surgery at our institution. Seven (58.3%) patients with proximal PICA aneurysms underwent extracranial-intracranial bypass. Five (41.7%) patients with distal PICA aneurysms accepted intracranial-intracranial bypass. The postoperative symptom improvement: Of the 6 patients with preoperative hypoperfusion or ischemic of the cerebellar hemisphere, the symptom resolved in 5 patients, improved in 1 patient, of 5 patients with preoperative mass effect, the symptom resolved in 5 patients. During the follow-up period, ten patients had a modified Rankin scale (mRS) score of 0 to 1, and 1 patient had an mRS score of 2. One patient had an mRS score of 3. The long-term graft patency rate was 91.7%. All patients had no recurrence of intracranial aneurysm. CONCLUSIONS: Base on the complexity of anatomy structure and the vascular architecture, an individualized strategy was proposed for each patient. The use of different types of bypass procedures (occipital artery-PICA end-to-end bypass, PICA-PICA end-to-end anastomosis, and/or occipital artery graft) can safely and effectively manage these complex PICA aneurysms.

Kinetics of Magnetic Skyrmion Crystal Formation from the Conical Phase.

The particle-like magnetic skyrmion or skyrmion lattice (SkX) formation has promoted strong application and fundamental science interests. Despite extensive research, the kinetic of the SkX development is much less understood because of the ultrafast spin rotation and high sensitivity to external perturbations. Here, using in situ Lorentz transmission electron microscopy, we successfully measured the dynamics of SkX formation from the conical phase with precise control of both the temperature and the magnetic field. We discovered that the Avrami equation can accurately describe the transition process with an initial Avrami constant around 1, suggesting that the rate-limiting step for the quasiparticle lattice formation is one-dimensional heterogeneous nucleation of individual skyrmions. A modified Arrhenius rate law is established, with an energy barrier that has a square-root dependence on temperature and a quadratic dependence on the magnetic field. This study paves the way toward precise and predictable manipulation of topological spin structures.

Platelet-rich plasma inhibits Adriamycin-induced inflammation via blocking the NF-κB pathway in articular chondrocytes.

BACKGROUND: Previous studies showed that doxorubicin could lead to osteoarthritis (OA) by inducing chondrocyte inflammation and apoptosis. Besides, it is reported that platelet-rich plasma (PRP) could suppress the activation of inflammatory NF-κB signaling. Here, we aimed to determine whether PRP was able to exert a protective effect against doxorubicin-induced chondrocyte damages. METHODS: To determine whether PRP protects chondrocytes against destabilization of the medial meniscus (DMM)-induced osteoarthritis, mice were treated with PRP and doxorubicin, and the cartilage destruction was observed through Safranin O-fast green staining and osteoarthritis scoring. ELISA assay was used to check the release of TNF-α and ILs. In vitro, we treated chondrocytes with doxorubicin and PRP; CCK-8 was used to measure cell viability. Western blot, real-time PCR, and ELISA were applied to check apoptosis-related signaling and inflammation-associated factors. RESULTS: The results from the mouse model suggested that PRP attenuated doxorubicin-induced cartilage destruction in vivo. Doxorubicin promoted chondrocyte apoptosis while PRP ameliorated this damage. PRP inhibited doxorubicin-induced dysregulation of cell matrix-related factors, including SOX9, Col2A1, Col10A1, and Aggrecan, reduced protein levels of doxorubicin-induced inflammatory markers, COX-2, and iNOS, and blocked doxorubicin-induced phosphorylation of IκB and NF-κB in articular chondrocytes. CONCLUSIONS: PRP improved doxorubicin-induced damage on chondrocytes. This research might provide a new theoretical basis for the clinical treatment of osteoarthritis caused by doxorubicin.

A CeCoOx Core/Nb2 O5 @TiO2 Double-Shell Nanocage Catalyst Demonstrates High Activity and Water Resistance for Catalytic Combustion of o-Dichlorobenzene.

A series of catalysts with different core-shell structures has been successfully prepared by a hydrothermal method. They consisted of CeCoOx @TiO2 (single shell), CeCoOx @Nb2 O5 (single shell) and CeCoOx @Nb2 O5 @TiO2 (double shell) core-shell nanocages and CeCoOx nanocages, in which CeCoOx was the core and TiO2 and Nb2 O5 were shells. The influence of the core-shell structure on the catalytic performance of o-dichlorobenzene was investigated by activity, water-resistance, and thermal stability tests as well as catalyst characterization. The temperatures corresponding to 90 % conversion of o-dichlorobenzene (T90 ) of CeCoOx , CeCoOx @TiO2 , CeCoOx @Nb2 O5 , and CeCoOx @Nb2 O5 @TiO2 catalysts were 415, 383, 362 and 367 °C, respectively. CeCoOx @Nb2 O5 exhibited excellent catalytic activity, mainly owing to the special core-shell structure, large specific surface area, abundant activity of Co3+ , Ce3+ , Nb5+ , strong reducibility, and more active oxygen vacancies. It can be seen that the Nb2 O5 coating can greatly improve the catalytic activity of the catalyst. In addition, due to the protective effect of the TiO2 shell on CeCoOx , CeCoOx @Nb2 O5 @TiO2 catalysts exhibited outstanding thermal and hydrothermal stability for 20 hours. The T90 of CeCoOx @Nb2 O5 @TiO2 was slightly lower than that of CeCoOx @Nb2 O5 , but it had higher stability and hydrothermal stability. Furthermore, possible reaction pathways involving the Mars-van-Krevelen (MvK) and Langmuir-Hinshelwood (L-H) models were deduced based on studies of the temperature-programmed desorption of O2 (O2 -TPD), X-ray photoelectron spectroscopy (XPS), and in situ diffuse reflectance FTIR spectroscopy (DRIFTS) characterization.

Maternal regulation of SATB2 in osteo-progeniters impairs skeletal development in offspring.

Nutritional status during intrauterine and/or early postnatal life has substantial influence on adult offspring health. Along these lines, there is a growing body of evidence illustrating that high fat diet (HFD)-induced maternal obesity can regulate fetal bone development. Thus, we investigated the effects of maternal obesity on both fetal skeletal development and mechanisms linking maternal obesity to osteoblast differentiation in offspring. Embryonic osteogenic calvarial cells (EOCCs) were isolated from fetuses at gestational day 18.5 (E18.5) of HFD-induced obese rat dams. We observed impaired differentiation of EOCCs to mature osteoblasts from HFD obese dams. ChIP-seq-based genome-wide localization of the repressive histone mark H3K27me3 (mediated via the polycomb histone methyltransferase, enhancer of zeste homologue 2 [Ezh2]) showed that this phenotype was associated with increased enrichment of H3K27me3 on the gene of SATB2, a critical transcription factor required for osteoblast differentiation. Knockdown of Ezh2 in EOCCs and ST2 cells increased SATB2 expression; while Ezh2 overexpression in EOCCs and ST2 cells decreased SATB2 expression. These data were consistent with experimental results showing strong association between H3K27me3, Ezh2, and SATB2 in cells from rats and humans. We have further presented that SATB2 mRNA and protein expression were increased in bones, and increased trabecular bone mass from pre-osteoblast specific Ezh2 deletion (Ezh2flox/flox Osx-Cre+ cko) mice compared with those from control Cre+ mice. These findings indicate that maternal HFD-induced obesity may be associated with decreasing fetal pre-osteoblastic cell differentiation, under epigenetic control of SATB2 expression via Ezh2-dependent mechanisms.

Apatinib exhibits cytotoxicity toward leukemia cells by targeting VEGFR2-mediated prosurvival signaling and angiogenesis.

OBJECTIVE: Vascular permeability contributes to disease progression and drug resistance in hematological malignancies, including AML. Thus, targeting angiogenic signaling is a promising treatment strategy, especially for relapsed and resistant AML. The aim of this study was to evaluate the efficacy of apatinib, a novel receptor tyrosine kinase inhibitor that selectively targets VEGFR2. METHODS: Several AML cell lines were exposed to various concentrations of apatinib, and then CCK8 and Annexin V/PI assays were performed to determine IC50 values and apoptosis, respectively. The effect of apatinib against primary AML cells from 57 adult patients and 11 normal controls was also analyzed utilizing an apoptosis assay. Next, we tested the underlying mechanism of apatinib in AML using western blotting and mass cytometry (CyTOF). Finally, the activity of apatinib against tumor growth and angiogenesis was further evaluated in vivo in xenograft models. RESULTS: We found apatinib significantly inhibited growth and promoted apoptosis in AML cell lines in vitro. Similarly, apatinib showed cytotoxicity against primary AML cells but didn't affect normal BMMCs. Its effect was highly correlated with several clinical features, such as NPM1 mutation, extramedullary infiltration, relapsed/refractory disease, and M2 and M5 FAB subtypes. In addition, apatinib suppressed AML growth and attenuated angiogenesis in xenograft models. Mechanistically, apatinib-induced cytotoxicity was closely associated with inhibition of the VEGFR2-mediated Src/STAT3 and AKT/mTOR pathways and induction of mitochondria-mediated apoptosis. CONCLUSION: Apatinib exerts antileukemia effects by targeting VEGFR2-induced prosurvival signaling and angiogenesis, thus providing a rationale for the application of apatinib in AML.

First Report of Root Rot Caused by the Fusarium oxysporum Species Complex on Codonopsis pilosula in China.

Codonopsis pilosula Franch., also known as Dangshen, is an important medicinal plant in China. It is widely cultivated for a major income of local farmers in Dingxi, Gansu Province. Its dried roots have the effects of supplementing vital energy, nourishing spleen and lung, enhancing organic immunity, helping depressurization, and improving microcirculation, etc., for humans. In June to October, 2018-2020, root rot disease was observed on C. pilosula with incidences up to 20% in the Dingxi region. We collected ten diseased and healthy plants from Dingxi (35°06'N, 104°29'E, 2206 m a.s.l.) in October 2019. The rotting root tissues were sterilized with 70% ethanol for 30 s and 3% NaOCl for 5 min and placed on potato dextrose agar (PDA) plates incubated at 25℃to isolate the pathogen (Shang et al. 2014). From the similar fungal cultures isolated after 7 days on PGA, isolate B17 was purified for morphological and molecular characterization. Its colony appeared light purple and produced long aerial hyphae. Slightly curved macroconidia (12.3 to 31.7 × 3.1 to 5.1 µm, n=40) and oval-ellipsoid and cylindrical microconidia (6.1 to 9.9 × 2.8 to 4.5 µm, n=30) were observed. The internal transcribed spacer region (ITS) and the translation elongation factor-1 alpha (TEF-1α) gene were amplified using primers ITS1/ITS4 and EF-1/EF-2 (Uwaremwe et al. 2020), respectively. The 489 bp (ITS) and 631 bp (TEF-1α) sequences were deposited in GenBank (Accession No. MN744360 and MN786974, respectively). The ITS sequence had 100% homology to isolate JJF2 (No. MN626452, ITS) (Ma et al. 2020), and the TEF-1α sequence had 100% homology to isolate Fo353 (No. KM065860) (Koyyappurath et al. 2016) of Fusarium oxysporum Schlecht. emend. Snyder & Hansen, which caused root rot of Panax ginseng and Vanilla planifolia, respectively. A phylogenetic tree was generated using the unweighted pair-group method with arithmetic average in the MycoBank database (O'Donnell et al. 2015), which clustered isolate B17 in the F. oxysporum species complex. Twenty 1-year-old plants of C. pilosula were inoculated with were inoculated by dipping the washed roots in a conidial suspension (2 ×106 conidia/ml added with 0.2% Tween 20) for 20 min before transplanted into pots (16 × 16 × 23 cm) with four plants per pot filled with sterilized peat and soil mixture (2:1 v/v) and grown in a greenhouse at 26oC with >70% humidity and 16 h light. Sterilized water added with 0.2% Tween 20 was used as a control. One week after inoculation, the leaves of pathogen-inoculated plants became yellow, and wilting occurred at the leaf tips 18 days later. Some of the inoculated plants died 45 days after inoculation, and the low part of roots had dark brown to black lesions and became rotting. The control plants did not show symptoms. The pathogenicity test was repeated three times with the same fungus isolated from the infected root tissue. To the best of our knowledge, this is the first report that F. oxysporum causes root rot on C. pilosula in China. F. oxysporum is a serious threat to C. pilosula cultivation, and the finding of this pathogen provides a clear target for root rot control.

Mechanisms of Skyrmion and Skyrmion Crystal Formation from the Conical Phase.

Real-space topological magnetic structures such as skyrmions and merons are promising candidates for information storage and transport. However, the microscopic mechanisms that control their formation and evolution are still unclear. Here, using in situ Lorentz transmission electron microscopy, we demonstrate that skyrmion crystals (SkXs) can nucleate, grow, and evolve from the conical phase in the same ways that real nanocrystals form from vapors or solutions. More intriguingly, individual skyrmions can also "reproduce" by division in a mitosis-like process that allows them to annihilate SkX lattice imperfections, which is not available to crystals made of mass-conserving particles. Combined string method and micromagnetic calculations show that competition between repulsive and attractive interactions between skyrmions governs particle-like SkX growth, but nonconservative SkX growth appears to be defect mediated. Our results provide insights toward manipulating magnetic topological states by applying established crystal growth theory, adapted to account for the new process of skyrmion mitosis.

Hippuric acid and 3-(3-hydroxyphenyl) propionic acid inhibit murine osteoclastogenesis through RANKL-RANK independent pathway.

Nutritional factors influence bone development. Previous studies demonstrated that bone mass significantly increased with suppressed bone resorption in early life of rats fed with AIN-93G semi-purified diets supplemented with 10% whole blueberry (BB) powder for 2 weeks. However, the effects of increased phenolic acids in animal serum due to this diet on bone and bone resorption were unclear. This in vitro and in ex vivo study examined the effects of phenolic hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA) on osteoclastic cell differentiation and bone resorption. We cultured murine osteoclast (macrophage) cell line, RAW 264.7 cells, and hematopoietic osteoclast progenitor cells (isolated from 4-week-old C57BL6/J mice) with 50 ng/ml of receptor activator of nuclear factor κ-Β ligand (RANKL). Morphologic studies showed decreased osteoclast number with treatment of 2.5% mouse serum from BB diet-fed animals compared with those treated with serum from standard casein diet-fed mice in both RAW 264.7 cell and primary cell cultures. HA and 3-3-PPA, but not 3-4-PPA, had dose-dependent suppressive effects on osteoclastogenesis and osteoclast resorptive activity in Corning osteo-assay plates. Signaling pathway analysis showed that after pretreatment with HA or 3-3-PPA, RANKL-stimulated increase of osteoclastogenic markers, such as nuclear factor of activated T-cells, cytoplasmic 1 and matrix metallopeptidase 9 gene/protein expression were blunted. Inhibitory effects of HA and 3-3-PPA on osteoclastogenesis utilized RANKL/RANK independent mediators. The study revealed that HA and 3-3-PPA significantly inhibited osteoclastogenesis and bone osteoclastic resorptive activity.

Low-dose triptolide enhances antitumor effect of JQ1 on acute myeloid leukemia through inhibiting RNA polymerase II in vitro and in vivo.

The bromodomain and extra-terminal (BET) domain inhibitor JQ1 exerts potent anticancer activity in various cancer cells. However, the resistance to BET inhibitors in leukemia stem cells limits its implication in acute myeloid leukemia (AML). High concentration of triptolide (TPL) presents anticancer activities but with adverse effects. Here, we investigated whether the combination of low-dose TPL with JQ1 could help to circumvent the dilemma of drug resistance and side effect in treating AML. AML cell lines, primary cells from 10 AML patients with different status, as well as AML mice model were subjected to different treatments and apoptotic related protein expression were evaluated. Data showed that low-dose TPL combined with JQ1 effectively killed AML cell lines and primary cells from AML patients without exerting significantly greater lethal activity against normal cells. Mechanism study revealed that low-dose TPL combined with JQ1 triggered reactive oxygen species production and induced mitochondrial-mediated apoptosis in AML cells, in which the inhibition of RNA polymerase II to downregulate c-Myc was mainly responsible for the enhanced activity of TPL in combination with JQ1. In vivo study presented that cotreatment with low-dose TPL and JQ1 significantly reduced tumor burden of the NOD/SCID mice engrafted with MOLM-13 cells. In conclusion, low-dose TPL enhanced the antitumor effect of JQ1 on AML without increasing the side effects, supporting a potential option for AML treatment.

Impairment of Vα24-Jα18+Vß11+ natural killer T cells in adult acute lymphoblastic leukemia patients.

Type I natural killer T (NKT) cells are attractive candidates for cancer immunotherapy. In this study, we examined the characteristics of type I NKT cells in patients with adult B-cell acute lymphoblastic leukemia (ALL). We first identified type I NKT cells as Vα24-Jα18 and Vß11 double-positive CD3+ lymphocytes. Using this method, we found that the adult B-cell ALL patients presented significantly lower level of type I NKT cells than the age- and sex-matching control subjects. The expression of IL-21 by type I NKT cells was then examined using intracellular flow cytometry, which showed that with α-GalCer stimulation, the adult B-cell ALL patients presented significantly lower level of IL-21+ type I NKT cells than control subjects. By both flow cytometry and ELISA, we found that the vast majority of IL-21-expressing type I NKT cells expressed IL-21R, which was also reduced in adult B-cell ALL patients. Using an in vitro co-culture system, we demonstrated that IL-21R+, but not IL-21R-, type I NKT cells could promote the IFN-γ, granzyme B, and perforin expression by CD8 T cells in an IL-21-dependent fashion. This type I NKT cell-mediated stimulatory effect was reduced in adult B-cell ALL patients than in control subjects. In addition, we observed a positive correlation between the frequency of IL-21R+ type I NKT cells and the frequencies of IFN-γ-, granzyme B-, and perforin-expressing circulating CD8 T cells in adult B-cell ALL patients directly ex vivo. Overall, this study identified an IL-21-related impairment in type I NKT cells from adult B-cell ALL patients.

Carbon Monoxide Inhibits the Expression of Proteins Associated with Intestinal Mucosal Pyroptosis in a Rat Model of Sepsis Induced by Cecal Ligation and Puncture.

BACKGROUND Carbon monoxide (CO) has anti-inflammatory effects and protects the intestinal mucosal barrier in sepsis. Pyroptosis, or cell death associated with sepsis, is mediated by caspase-1 activation. This study aimed to investigate the role of CO on the expression of proteins associated with intestinal mucosal pyroptosis in a rat model of sepsis induced by cecal ligation and puncture (CLP). MATERIAL AND METHODS The rat model of sepsis was developed using CLP. Male Sprague-Dawley rats (n=120) were divided into six study groups: the sham group (n=20); the CLP group (n=20); the hemin group (treated with ferric chloride and heme) (n=20); the zinc protoporphyrin IX (ZnPPIX) group (n=20); the CO-releasing molecule 2 (CORM-2) group (n=20); and the inactive CORM-2 (iCORM-2) group (n=20). Hemin and CORM-2 were CO donors, and ZnPPIX was a CO inhibitor. In the six groups, the seven-day survival curves, the fluorescein isothiocyanate (FITC)-labeled dextran 4000 Da (FD-4) permeability assay, levels of intestinal pyroptosis proteins caspase-1, caspase-11, and gasdermin D (GSDMD) were measured by confocal fluorescence microscopy. Proinflammatory cytokines interleukin (IL)-18, IL-1ß, and high mobility group box protein 1 (HMGB1) were measured by Western blot and enzyme-linked immunosorbent assay (ELISA). RESULTS CO reduced the mortality rate in rats with sepsis and reduced intestinal mucosal permeability and mucosal damage. CO also reduced the expression levels of IL-18, IL-1ß, and HMGB1, and reduced pyroptosis by preventing the cleavage of caspase-1 and caspase-11. CONCLUSIONS In a rat model of sepsis induced by CLP, CO had a protective role by inhibiting intestinal mucosal pyroptosis.

CS2164 exerts an antitumor effect against human Non-Hodgkin's lymphomas in vitro and in vivo.

Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of lymphoproliferative disorders. Mounting studies have suggested an involvement of angiogenesis signaling in NHLs progression and resistance to treatment. In this study, we investigated the cytotoxicity of CS2164, a novel receptor tyrosine kinase inhibitor selectively targeting VEGFR-2 and Aurora B in NHL cells. By in vitro culture system and in vivo xenograft model, we found that CS2164 significantly inhibited cell growth and abolished clonogenicity in NHL cells in a dose- and time-dependent manner. Meanwhile, CS2164 significantly induced NHL cells apoptosis and cell cycle arrest in G0/G1 phase. Moreover, CS2164 suppressed NHL cells growth and progression in an in vivo xenograft model. Mechanistically, CS2164-induced cytotoxicity was closely associated with inhibition of VEGFR2 and Aurora B as well as their downstream signaling cascades, including P38, ERK and H3 pathways. In conclusion, CS2164 exerts its cytotoxic effect via inhibition of proliferation and induction of apoptosis by modulating VEGFR2 and Aurora B signaling pathway, supporting a potential role for CS2164 in the treatment of NHLs.