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Abstract Triple‐negative breast cancer (TNBC) has higher mortality than non‐TNBC because of its stronger metastatic capacity. Increasing studies reported that TNBC tumors had more macrophage infiltration than non‐TNBC tumors, which promoted the metastasis of TNBC cells. However, how TNBC cells become more malignant after interacting with macrophages is less reported. In this study, it is observed that when TNBC cells are co‐cultured with macrophages, they display higher viability and stronger metastatic ability than non‐TNBC cells. Mechanistic studies reveal that TNBC cells acquired these abilities via interactions with macrophages in three phases. First, within 12 h of co‐culture with macrophages, some TNBC cells have significantly elevated levels of reactive oxygen species (ROS), which upregulate interleukin 1α (IL1α) expression in ERK1/2‐c‐Jun‐ and NF‐κB‐dependent manners at 24−48 h. Second, the secreted IL1α bound to IL1R1 activates the ERK1/2‐ZEB1‐VIM pathway which increases metastasis. Third, IL1α/IL1R1 facilitates its own synthesis and induces the expression of IL1β and IL8 at 72−96 h through the MKK4‐JNK‐c‐Jun and NF‐κB signaling pathways. Moreover, a higher level of IL1α is positively correlated with more macrophage infiltration and shorter overall survival in breast cancer patients. Thus, reducing ROS elevation or downregulating IL1α expression can serve as new strategies to decrease metastasis of TNBC.

ABSTRACT Pseudomonas aeruginosa (P. aeruginosa) is one of the leading causes of chronic infections, including reinfection, relapse, and persistent infection, especially in cystic fibrosis patients. Relapse P. aeruginosa infections are more harmful because of repeated hospitalization and undertreatment of antimicrobials. However, relapse P. aeruginosa infection in China remains largely unknown. Herein, we performed a 3-year retrospective study from 2019 to 2022 in a tertiary hospital, which included 442 P. aeruginosa isolates from 196 patients. Relapse infection was identified by screening clinical records and whole-genome sequencing (WGS). We found that 31.6% (62/196) of patients had relapsed infections. The relapse incidence of carbapenem-resistant P. aeruginosa infection (51.4%) is significantly higher than that of carbapenem-susceptible P. aeruginosa infection (20.2%, P < 0.0001). These isolates were assigned to 50 distinct sequence types and sporadically distributed in phylogeny, indicating that relapsed infections were not caused by certain lineages. Fast adaptation and evolution of P. aeruginosa isolates were reflected by dynamic changes of antimicrobial resistance, gene loss and acquisition, and single-nucleotide polymorphisms during relapse episodes. Remarkably, a convergent non-synonymous mutation that occurs in a pyochelin-associated virulence gene fptA (T1056C, M252T) could be a considerable target for the diagnosis and treatment of relapse P. aeruginosa infection. These findings suggest that integrated utilization of WGS and medical records provides opportunities for improved diagnostics of relapsed infections. Continued surveillance of the genomic dynamics of relapse P. aeruginosa infection will generate further knowledge for optimizing treatment and prevention in the future. IMPORTANCE Pseudomonas aeruginosa is a predominant pathogen that causes various chronic infections. Relapse infections promote the adaptation and evolution of antimicrobial resistance and virulence of P. aeruginosa, which obscure evolutionary trends and complicate infection management. We observed a high incidence of relapse P. aeruginosa infection in this study. Whole-genome sequencing (WGS) revealed that relapse infections were not caused by certain lineages of P. aeruginosa isolates. Genomic dynamics of relapse P. aeruginosa among early and later stages reflected a plasticity scattered through the entire genome and fast adaptation and genomic evolution in different ways. Remarkably, a convergent evolution was found in a significant virulence gene fptA, which could be a considerable target for diagnosis and treatment. Taken together, our findings highlight the importance of longitudinal surveillance of relapse P. aeruginosa infection in China since cystic fibrosis is rare in Chinese. Integrated utilization of WGS and medical records provides opportunities for improved diagnostics of relapse infections.

Introduction: It has been a decade since the first patient with colon cancer underwent colectomy by hybrid transvaginal natural orifice transluminal endoscopic surgery (hvNOTES). However, the efficacy and safety of this procedure is not well established. Methods: This study is an open-label, multicenter, single-arm, phase 2 trial undertaken at six centers in China. Female patients aged over 18 years and below 80 years old with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with pathologically proven, resectable, cT1-3N0-2M0 disease who have previously untreated colon cancer are eligible for inclusion. The primary endpoint is a composite of major intraoperative and postoperative complications (greater than grade III, the Common Terminology Criteria for Adverse Events [CTCAE], version 5.0). Secondary endpoints include conversion to laparoscopic or open surgery, postoperative concentration of C-Reactive Protein and procalcitonine, complete pathological assessment of complete mesocolic excision specimens, postoperative pain, amount of narcotic pain medication administered, time to first flatus after surgery, number of harvested lymph nodes, R0 resection rate, length of hospital stay, sexual function assessment, quality of recovery, satisfaction with surgical scars, quality of life, postoperative recurrence patterns, relapse-free survival, and overall survival. Ethics and dissemination: The study was approved by the Research Ethics Committee, Renmin Hospital of Wuhan University, China, number: WDRY2022-K053. All patients will receive written information of the trial and provide informed consent before enrollment. The results of this trial will be disseminated in academic conferences and peer-reviewed medical journals.Trial registration number NCT04048421.

Adjuvant chemotherapy based on 5-fluorouracil (5-FU), such as FOLFOX, is suggested as a treatment for gastrointestinal cancer. Yet, intestinal damage continues to be a prevalent side effect for which there are no practical prevention measures. We investigated whether Babao Dan (BBD), a Traditional Chinese Medicine, protects against intestinal damage induced by 5-FU by controlling immune response and gut microbiota. 5-FU was injected intraperitoneally to establish the mice model, then 250 mg/kg BBD was gavaged for five days straight. 5-FU led to marked weight loss, diarrhea, fecal blood, and histopathologic intestinal damage. Administration of BBD reduced these symptoms, inhibited proinflammatory cytokine (IL-6, IL-1β, IFN-γ, TNF-α) secretion, and upregulated the ratio of CD3(+) T cells and the CD4(+)/CD8(+) ratio. According to 16S rRNA sequencing, BBD dramatically repaired the disruption of the gut microbiota caused in a time-dependent way, and increased the Firmicutes/Bacteroidetes (F/B) ratio. Transcriptomic results showed that the mechanism is mainly concentrated on the NF-κB pathway, and we found that BBD reduced the concentration of LPS in the fecal suspension and serum, and inhibited TLR4/MyD88/NF-κB pathway activation. Furthermore, at the genus level on the fifth day, BBD upregulated the abundance of unidentified_Corynebacteriaceae, Aerococcus, Blautia, Jeotgalicoccus, Odoribacter, Roseburia, Rikenella, Intestinimonas, unidentified_Lachnospiraceae, Enterorhabdus, Ruminiclostridium, and downregulated the abundance of Bacteroides, Parabacteroides, Parasutterella, Erysipelatoclostridium, which were highly correlated with intestinal injury or the TLR4/MyD88/NF-κB pathway. In conclusion, we established a network involving 5-FU, BBD, the immune response, gut microbiota, and key pathways to explain the pharmacology of oral BBD in preventing 5-FU-induced intestinal injury.

BackgroundBehcet's disease is a vasculitis of unknown origin that can involve multiple organs or tissues. Aneurysm or pseudoaneurysm, also one of the complications of Behcet's disease, is usually accompanied by a poor prognosis. Surgery is usually accompanied by a high risk of complications, such as the recurrence of anastomotic pseudoaneurysms and blockage of the target vessel. Using hybrid surgery, we successfully treated a complex and recurrent abdominal aortic pseudoaneurysm in a patient with BD.MethodsWe report a 32-year-old female diagnosed with Behcet's disease with recurrent thoracoabdominal aortic aneurysm. Adequate immunotherapy was given during the perioperative period. The splanchnic artery branches were reconstructed, and the aneurysm was sequestered with endovascular repair. The patient recovered uneventfully and was discharged from the hospital 8 days after hybrid surgery. At the 60-month follow-up, no aneurysm was observed, the stent had no displacement or internal leakage, and the reconstructed blood vessels were unobstructed.ConclusionHybrid surgery could be a feasible and effective strategy for BD aneurysms. Adequate preoperative and postoperative immunotherapy with arterial anastomosis away from the diseased artery may be the key to success.

Abstract Background Valtrate, a natural compound isolated from the root of Valeriana, exhibits antitumor activity in many cancers through different mechanisms. However, its efficacy for the treatment of glioblastoma (GBM), a tumor type with a poor prognosis, has not yet been rigorously investigated. Methods GBM cell lines were treated with valtrate and CCK-8, colony formation and EdU assays, flow cytometry, and transwell, 3D tumor spheroid invasion and GBM-brain organoid co-culture invasion assays were performed to assess properties of proliferation, viability, apoptosis and invasion/migration. RNA sequencing analysis on valtrate-treated cells was performed to identify putative target genes underlying the antitumor activity of the drug in GBM cells. Western blot analysis, immunofluorescence and immunohistochemistry were performed to evaluate protein levels in valtrate-treated cell lines and in samples obtained from orthotopic xenografts. A specific activator of extracellular signal-regulated kinase (ERK) was used to identify the pathways mediating the effect. Results Valtrate significantly inhibited the proliferation of GBM cells in vitro by inducing mitochondrial apoptosis and suppressed invasion and migration of GBM cells by inhibiting levels of proteins associated with epithelial mesenchymal transition (EMT). RNA sequencing analysis of valtrate-treated GBM cells revealed platelet-derived growth factor receptor A (PDGFRA) as a potential target downregulated by the drug. Analysis of PDGFRA protein and downstream mediators demonstrated that valtrate inhibited PDGFRA/MEK/ERK signaling. Finally, treatment of tumor-bearing nude mice with valtrate led to decreased tumor volume (fivefold difference at day 28) and enhanced survival (day 27 vs day 36, control vs valtrate-treated) relative to controls. Conclusions Taken together, our study demonstrated that the natural product valtrate elicits antitumor activity in GBM cells through targeting PDGFRA and thus provides a candidate therapeutic compound for the treatment of GBM.

Abstract Background Patients with normal preoperative serum albumin still suffer from a significant reduction in serum albumin after major abdominal surgery. The current study aims to explore the predictive value of ∆ALB for AL in patients with normal serum albumin and examine whether there is a gender difference in the prediction of AL. Methods Medical reports of consecutive patients undergoing elective sphincter-preserving rectal surgery between July 2010 and June 2016 were reviewed. Receiver operating characteristic (ROC) analysis was adopted to examine the predictive ability of ∆ALB and determine the cut-off value according to the Youden index. The logistic regression model was performed identify independent risk factors for AL. Results Out of the 499 eligible patients, 40 experienced AL. Results of the ROC analyses showed that ΔALB displayed a significant predictive value for females, and the AUC value was 0.675 (P = 0.024), with a sensitivity of 93%. In male patients, the AUC was 0.575 (P = 0.22), but did not reach a significant level. In the multivariate analysis, ∆ALB ≥ 27.2% and low tumor location prove to be independent risk factors for AL in female patients. Conclusions The current study suggested that there may be a gender difference in the prediction of AL and ∆ ALB can serve as a potential predictive biomarker for AL in females. A cut-off value of the relative decline in serum albumin can help predict AL in female patients as early as postoperative day 2. Although our study needs further external validation, our findings may provide an earlier, easier and cheaper biomarker for the detection of AL.

Deep learning methods have been widely explored in motor imagery (MI)-based brain computer interface (BCI) systems to decode electroencephalography (EEG) signals. However, most studies fail to fully explore temporal dependencies among MI-related patterns generated in different stages during MI tasks, resulting in limited MI-EEG decoding performance. Apart from feature extraction, learning temporal dependencies is equally important to develop a subject-specific MI-based BCI because every subject has their own way of performing MI tasks. In this paper, a novel temporal dependency learning convolutional neural network (CNN) with attention mechanism is proposed to address MI-EEG decoding. The network first learns spatial and spectral information from multi-view EEG data via the spatial convolution block. Then, a series of non-overlapped time windows is employed to segment the output data, and the discriminative feature is further extracted from each time window to capture MI-related patterns generated in different stages. Furthermore, to explore temporal dependencies among discriminative features in different time windows, we design a temporal attention module that assigns different weights to features in various time windows and fuses them into more discriminative features. The experimental results on the BCI Competition IV-2a (BCIC-IV-2a) and OpenBMI datasets show that our proposed network outperforms the state-of-the-art algorithms and achieves the average accuracy of 79.48%, improved by 2.30% on the BCIC-IV-2a dataset. We demonstrate that learning temporal dependencies effectively improves MI-EEG decoding performance. The code is available at https://github.com/Ma-Xinzhi/LightConvNet

Pancreatic β-cell compensation is a major mechanism in delaying T2DM progression. Here, the authors show that circGlis3 levels are affected by QKI and FUS expression, and that increasing circGlis3 lengthens β-cell compensation via enhancing insulin secretion and reducing apoptosis.

Based on the 0.25°×0.25° ERA5 reanalysis data and surface observation data of China Meteorological Administration， a study is conducted to investigate a large-scale sea fog event caused by an extratropical cyclone over the Yellow Sea in May 2020.Results are as follows： （1） The sea fog mainly occurred in the western and northern of the extratropical cyclone with properties of advection cooling fog and frontal fog.（2） The air sea temperature difference is between 0.5 ℃ and 2.5 ℃ during the occurrence of fog in the Yellow Sea and Bohai Sea.The dew point temperature of 2m is slightly higher than the sea surface temperature.（3） The phenomenon of rain turning into fog both in the western and northern of the extratropical cyclone.The temperature profile monitored by Qingdao L-band radar shows "double inversion" at 500 m and 1500 m altitude.（4） The convergence of moist air caused by extratropical cyclone is an important water vapor source for the occurrence and maintenance of this sea fog process.The humidification and evaporative cooling effects of precipitation also make the atmospheric saturation near the sea surface increase rapidly.（5） The sensible and latent heat fluxes in most of the Yellow Sea and Bohai Sea are negative.The turbulent heat flux is mainly represented by the transport from the atmosphere to the ocean.The vertical wind shear caused by extratropical cyclone enhances the atmospheric mechanical turbulence， which makes the atmosphere and the ocean carry out sufficient heat exchange， thus promoting the development of sea fog in the vertical direction.

Using the 6-hourly reanalysis data of European Center ERA-Interim with horizontal resolution of 0.25° × 0.25° and hourly typhoon operational data provided by the CMA (China Meteorological Administration), a new high-level environmental field factor is derived, and its application during the recurvature period of No. 14 Typhoon Yagi and No. 18 Typhoon Rumbia in 2018 is compared and analyzed. According to the comparison study, there is always a clear positive abnormal value area of high-level environmental field factor on the northeast of Rumbia during its northward movement, implying an obvious alteration of ∇•u→ and a big negative gradient of ∇u→ on the northeast of Rumbia. With the eastward movement of the westerly trough and the strengthening of the subtropical westerly jet, Rumbia is expected to veer northeast. However, the change of high-level environmental field factor on the northeast of Yagi is not noticeable, and Yagi is far away from the upper-level jet stream, which is not conducive to Yagi's northeast recurvature.

Abstract. Background:. Endovascular abdominal aortic aneurysm repair (EVAR) is the major treatment for abdominal aortic aneurysm (AAA); however, EVAR still carries a considerable risk of acute kidney injury (AKI). The present study aimed to investigate the risk factors for AKI after elective EVAR procedures. Methods:. This was a retrospective observational study. Eligible patients who underwent EVAR from September 2011 to March 2019 in West China Hospital were included. The primary outcome was the occurrence of AKI within two days after EVAR, which was defined by the Kidney Disease Improving Global Outcomes Clinical Practice Guideline. Demographics, comorbidities, medications, laboratory tests, anatomical parameters of AAA, and relative operative details were collected as variables. Univariable and multivariable logistic regression analyses were applied to identify the risk factors among variables, and covariate interactions were further assessed. Results:. A total of 679 eligible patients were included. The incidence of postoperative AKI was 8.2% (56/679) in the whole cohort, and it was associated with a lower 5-year survival rate (63.5% vs. 80.9%; χ2 = 4.10; P = 0.043). The multivariable logistic regression showed that chronic kidney disease (OR, 5.06; 95% CI: 1.43–17.95; P = 0.012), angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) (OR, 2.60; 95% CI: 1.17–5.76; P = 0.019), and short neck (OR, 2.85; 95% CI: 1.08–7.52; P = 0.035) were independent risk factors for postoperative AKI. In the covariate interaction analysis, the effect of ACEIs/ARBs use on postoperative AKI was similar across all subgroups (P > 0.05), thereby suggesting a robust effect of ACEIs/ARBs use in all patients undergoing elective endovascular abdominal aortic aneurysm repair. Conclusions:. Postoperative AKI was associated with lower survival rate, and the use of ACEIs/ARBs was the only adjustable independent risk factor. Clinicians should consider withdrawing ACEIs/ARBs in high-risk patients undergoing elective endovascular abdominal aortic aneurysm repair to prevent postoperative AKI.

Abstract Objective The use of cement or cementless femoral stem prosthesis for hip arthroplasty in elderly patients has been controversial. This study investigated the efficacy and safety of cementless femoral stem in elderly patients (age ≥ 65 years). Methods The short-term efficacy of primary hip arthroplasty with cementless femoral stem in our hospital from January 2014 to June 2021 was retrospectively analyzed. Patients were divided into two groups according to age: young group (

Abstract Background Both disseminated intravascular coagulation and thrombotic microangiopathy are complications of sepsis as Salmonella septicemia, respectively. They are related and have similar clinical characteristics as thrombopenia and organ dysfunctions. They rarely co-occur in some specific cases, which requires a clear distinction. Case presentation A 22-year-old woman had just undergone intracranial surgery and suffered from Salmonella derby septicemia with multiorgan involvement in the hospital. Laboratory workup demonstrated coagulation disorder, hemolytic anemia, thrombocytopenia, and acute kidney injury, leading to the co-occurrence of disseminated intravascular coagulation and secondary thrombotic microangiopathy. She received antibiotics, plasma exchange therapy, dialysis, mechanical ventilation, fluids, and vasopressors and gained full recovery without complications. Conclusion Disseminated intravascular coagulation and secondary thrombotic microangiopathy can co-occur in Salmonella derby septicemia. They should be treated cautiously in diagnosis and differential diagnosis. Thrombotic microangiopathy should not be missed just because of the diagnosis of disseminated intravascular coagulation. Proper and timely identification of thrombotic microangiopathy with a diagnostic algorithm is essential for appropriate treatment and better outcomes.

Gynecologic tract melanoma is a malignant tumor with poor prognosis. Because of the low survival rate and the lack of a standard treatment protocol related to this condition, the investigation of the mechanisms underlying melanoma progression is crucial to achieve advancements in the relevant gynecological surgery and treatment. Mitochondrial transfer between adjacent cells in the tumor microenvironment regulates tumor progression. This study investigated the effects of endothelial mitochondria on the growth of melanoma cells and the activation of specific signal transduction pathways following mitochondrial transplantation. Mitochondria were isolated from endothelial cells (ECs) and transplanted into B16F10 melanoma cells, resulting in the upregulation of proteins associated with tumor growth. Furthermore, enhanced antioxidation and mitochondrial homeostasis mediated by the Sirt1-PGC-1α-Nrf2-HO-1 pathway were observed, along with the inhibition of apoptotic protein caspase-3. Finally, the transplantation of endothelial mitochondria into B16F10 cells promoted tumor growth and increased M2-type macrophages through Nrf2/HO-1-mediated pathways in a xenograft animal model. In summary, the introduction of exogenous mitochondria from ECs into melanoma cells promoted tumor growth, indicating the role of mitochondrial transfer by stromal cells in modulating a tumor’s phenotype. These results provide valuable insights into the role of mitochondrial transfer and provide potential targets for gynecological melanoma treatment.

Abstract Objective Acute respiratory distress syndrome (ARDS) leads to life-threatening acute hypoxemic respiratory failure and requires mechanical ventilation. However, there is a lack of certainty regarding recruitment maneuvers (RMs) and positive end-expiratory pressure (PEEP) levels. Therefore, we performed a network meta-analysis to identify the optimal RM and PEEP levels of patients with ARDS. Methods We searched the PubMed, OVID and Cochrane Central Register of Controlled Trials (Central) databases for randomized controlled trials (RCTs). The primary outcome was death on the 28th day, and the secondary outcomes included in-hospital death, ventilator-free days, and barotrauma. The relative effect sizes were estimated by risk ratios (RRs) for binary variables and standard mean difference (SMD) for continuous variables. The efficacy of the interventions was ranked using surface under the cumulative ranking. Multiple intervention comparisons based on the Bayesian framework were performed to integrate the efficacy of all included strategies. Results Thirteen RCTs comprising 4410 patients were included in the network meta-analysis. In terms of death at 28 days, inconsistencies were found globally and locally in the tests. None of the ventilation strategies was significantly superior to the others on any outcomes. According to the relative rank probabilities, RM + lower PEEP levels showed the highest probability of reducing the risk of in-hospital death and reducing ventilator-free days. Lower PEEP levels showed the highest probability of benefitting barotrauma. The overall quality of the evidence per grade was moderate to low. Conclusions The no ventilation strategy is significantly superior to the other strategies. RM + lower PEEP levels has the highest probability of benefitting survival. The evidence has low overall quality and should be further studied.

Abstract. Background:. For patients with severe neck angulation (SNA), hemodynamic and clinical outcomes following endovascular aneurysm repair (EVAR) are still unclear. This study aimed to explore the influence of SNA on hemodynamic and clinical outcomes following EVAR. Methods:. This study included a hemodynamic analysis and a retrospective cohort study from West China Hospital of Sichuan University between January 2011 and December 2020. The Cox regression model, inverse probability of treatment weighting (IPTW) analysis, sensitivity analysis, and subgroup analysis were applied. Primary outcome was type IA endoleak (T1AEL). Results:. In this hemodynamic analysis, nine non-severe neck angulation (nSNA) and 16 SNA idealized models were constructed. We found a significant difference in drag force between SNA and nSNA models (7.016 ± 2.579 N vs. 4.283 ± 1.460 N, P = 0.008), and proximal neck angles were significantly associated with the magnitude of drag force (F = 0.082 × α–0.006 × β + 2.818, α: 95% confidence interval [CI] 0.070–0.094; P = 0.001; β: 95% CI −0.019 to 0.007; P = 0.319). In our cohort study, 514 nSNA patients (71.5 ± 8.5 years; 459 males) and 208 SNA patients (72.5 ± 7.8 years; 135 males) were included, with a median follow-up duration of 34 months (16–63 months). All baseline characteristics were well balanced after IPTW matching. We found that SNA was associated with a significant risk of adverse limb event (hazard ratio [HR] 2.18, 95% CI 1.09–3.12), yet was not associated with T1AEL, overall survival, or reintervention. In patients without proximal or distal additional procedures (DAP), subgroup analyses suggested a significant risk of T1AEL (Proximal: HR 5.25, 95% CI 1.51–18.23; Distal: HR 5.07, 95% CI 1.60–16.07) and adverse limb event (Proximal: HR 2.27, 95% CI 1.01–5.07; Distal: HR 2.91, 95% CI 1.30–6.54) in SNA patients. However, no noticeable difference was observed in patients with proximal or DAP. Conclusions:. SNA has a critical influence on hemodynamic and clinical outcomes following EVAR. Appropriate additional procedures may be of great benefit to SNA patients.

Abstract The solar X-ray and Extreme Ultraviolet Imager (X-EUVI), developed by the Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences (CIOMP), is the first space-based solar X-ray and Extreme ultraviolet (EUV) imager of China loaded on the Fengyun-3E (FY-3E) satellite supported by the China Meteorological Administration (CMA) for solar observation. Since started work on July 11, 2021, X-EUVI has obtained many solar images. The instrument employs an innovative dual-band design to monitor a much larger temperature range on the Sun, which covers 0.6–8.0 nm in the X-ray region with six channels and 19.5 nm in the EUV region. X-EUVI has a field of view of 42′, an angular resolution of 2.5″ per pixel in the EUV band and an angular resolution of 4.1″ per pixel in the X-ray band. The instrument also includes an X-ray and EUV irradiance sensor (X-EUVS) with the same bands as its imaging optics, which measures the solar irradiance and regularly calibrates the solar images. The radiometric calibration of X-EUVS on the ground has been completed, with a calibration accuracy of 12%. X-EUVI is loaded on the FY-3E satellite and rotates relative to the Sun at a uniform rate. Flat-field calibration is conducted by utilizing successive rotation solar images. The agreement between preliminarily processed X-EUVI images and SDO/AIA and Hinode/XRT images indicates that X-EUVI and the data processing algorithm operate properly and that the data from X-EUVI can be applied to the space weather forecast system of CMA and scientific investigations on solar activity.

Abstract Camellia chekiangoleosa is a popular variety of Oil-camellia that has high oil production and ornamental value. Microsatellite (SSR) markers are the preferred tool for the molecular marker-assisted breeding of C. chekiangoleosa. By focusing on the problems of the low development efficiency of polymorphic SSR markers and the lack of available functional markers in Oil-camellia, we identified 97,510 SSR loci based on the full-length transcriptome sequence of C. chekiangoleosa. An analysis of SSR characteristics showed that mononucleotide (51.29%) and dinucleotide (34.36%) SSRs were the main repeat types. The main SSR distribution areas based on proportion covered were ordered as follows: 5'UTR > 3'UTR > CDS. By comparing our data with those in databases such as GO and KEGG, we obtained functional annotations of unigene sequences containing SSR sites. The data showed that the amplification efficiency of the SSR primers was 51.72%, and the development efficiency of polymorphic SSR primers was 26.72%. Experiments verified that dinucleotide and pentanucleotide SSRs located in UTR regions could produce more polymorphic markers. An investigation into the genetic diversity of several C. chekiangoleosa populations also suggested that the developed SSR markers had higher levels of polymorphism. This study will provide a reference and high-quality markers for the large-scale development of functional SSR markers and genetic research in Oil-camellia.

With the increase in electric vehicle sales, the construction of charging and switching stations has caused unnecessary waste of land resources and load on the power grid, so it is necessary to consider the “centralized charging and unified distribution” model. Based on this, this paper proposes a shared charging and switching station model under the “centralized charging and unified distribution” model, in which centralized charging stations are built in suburban areas, and switching stations are built in urban areas. This model allows horizontal transfer between switching stations and establishes corresponding site selection decision guidelines. Considering that the existing charging and switching infrastructure can be converted into shared charging and switching station facilities, the MCDM (Multi-Criteria Decision Making) method is used to select sites for shared charging and switching stations. The SECA method is used to determine the weight of each secondary criterion, and the TRUST method is used to rank the alternatives. The results show that the traffic flow and the impact on the residents’ lives are important influencing factors for the location of the shared charging station, and the results show that the optimal solution is A4. Sensitivity analysis is performed by calculating the weight of each criterion or subjective assignment by different MCDM methods. The results prove that the improved method can obtain more objective optimal solutions and analyze when The results prove that the improved method can obtain more objective optimal solutions and analyze the change in solution ranking when decision-makers value different indicators.

Abstract Prodigiosin (PG), a member of a family of natural red pigments produced by a variety of bacteria, was first discovered in Serratia marcescens. PG has been reported to have an apoptosis-inducing effect in many cancers, such as lymphoma, colon cancer and nasopharyngeal carcinoma. For this study, we used three glioblastoma (GBM) cell lines (LN229, U251 and A172) to explore the effect of prodigiosin on GBM cells. A CCK8 assay was used to evaluate cell viability. We determinedthe cell cycle distribution by flow cytometry and measured proliferation by an EdU incorporation assay. The expression of different molecules was investigated by western blotting and RT-PCR. We further confirmed our results by plasmid transfection and lentiviral transduction. The LN229 xenograft model was used to study the effect of prodigiosin in vivo. We confirmed that prodigiosin played an anticancer role in several GBM cell lines through the KIAA1524/PP2A/Akt signalling pathway. Prodigiosin inhibited the protein expression of KIAA1524 by suppressing its transcription, which led to activation of PP2A. Afterward, PP2A inhibited the phosphorylation of Akt, thereby inducing increased expression of p53/p21. Furthermore, it was verified that prodigiosin inhibited the KIAA1524/PP2A/Akt axis in vivo in the LN229 xenograft model. These data improve the understanding of the anticancer effects of prodigiosin and further highlight the potential of prodigiosin for the development of anti-glioma drugs.

The nonlinear deformation and vibrations of beams are frequently encountered as a typical example of structural analysis as well as a mathematical problem. There have been many methods and techniques for the approximate and exact solutions of nonlinear differential equations arising from the nonlinear phenomena of elastic beam structures. One method is particularly more powerful and flexible is proposed recently as the extended Rayleigh-Ritz method (ERRM) by adding the temporal variable as another dimension of deformation formulation but eliminated through the integration over a period of vibrations. Such a procedure leads to a simple, elegant, and powerful method for the approximate solutions of nonlinear vibration and deformation problems in dynamics and structural analysis. By utilizing the usual displacement function of beams, the nonlinear vibration frequencies of Euler-Bernoulli and Timoshenko beams are obtained with the same accuracy as from other approximate solutions.

The electronic structures and open-shell diradical character of organic diradicaloids endow them with potentially useful optical, electronic and magnetic properties. Here, an open-shell nitrogen-centered diradicaloid is reported and shown to readily react with Lewis and Brønsted acids to form acid-base adducts, allowing for tuning of ground-state electronic structure, diradical character and spin density distribution.

Abstract Background Small peptides encoded by long non-coding RNAs (lncRNAs) have attracted attention for their various functions. Recent studies indicate that these small peptides participate in immune responses and antigen presentation. However, the significance of RNA modifications remains unclear. Methods Thirteen non-m6A-related neoantigen-coding lncRNAs were selected for analysis from the TransLnc database. Next, a neoantigen activation score (NAS) model was established based on the characteristics of the lncRNAs. Machine learning was employed to expand the model to two additional RNA-seq and two single-cell sequencing datasets for further validation. The DLpTCR algorithm was used to predict T cell receptor (TCR)-peptide binding probability. Results The non-m6A-related NAS model predicted patients’ overall survival outcomes more precisely than the m6A-related NAS model. Furthermore, the non-m6A-related NAS was positively correlated with tumor cells’ evolutionary level, immune infiltration, and antigen presentation. However, high NAS gliomas also showed more PD-L1 expression and high mutation frequencies of T-cell positive regulators. Interestingly, results of intercellular communication analysis suggest that T cell-high neoplastic cell interaction is weaker in both of the NAS groups which might arise from decreased IFNGR1 expression. Moreover, we identified unique TCR-peptide pairs present in all glioma samples based on peptides encoded by the 13 selected lncRNAs. And increased levels of neoantigen-active TCR patterns were found in high NAS gliomas. Conclusions Our work suggests that non-m6A-related neoantigen-coding lncRNAs play an essential role in glioma progression and that screened TCR clonotypes might provide potential avenues for chimeric antigen receptor T cell (CAR-T) therapy for gliomas.

This paper presents a numerical investigation into the high strength steel (HSS) welded Isection overall buckling performance with respect to the major axis under combined axial compression and bending. The validation of FE models compared with the existing test data to verify the appropriateness of the element division and boundary condition was firstly conducted. In line with the FE arrangement verified, separate 890 numerical models, covering a broader range of eight steel grades (460 MPa, 500 MPa, 550 MPa, 620 MPa, 690 MPa, 800 MPa, 890 MPa and 960 MPa), different overall slenderness and various eccentricities were designated. Subsequently, the comparison of the resistance prediction codified design rules in EN1993-1-1, ANSI/AISC 360-10 and GB50017-2017 was preferentially operated, by the instrumentality of the normalized axial compression-bending moment curves. The results graphically revealed that, the provision given in ANSI/AISC 360-10 concerned in the present work was the most loose, whereas, the corresponding content set out in EN1993-1-1 and GB50017-2017 was relatively on the safe side. Taking account of the FE results, the conservative shortcomings of the considered rules in EN1993-1-1 and GB50017-2017 were further highlighted. Especially, the disparity of EN1993-1-1 and numerical results was higher to 27%, from the perspective of a definition given in the present work. In contrast, the provision in ANSI/AISC 360-10 yielded a relatively accurate prediction, on average. Based on the numerical program, an alternative formula for the HSS welded I-section beam-columns with a general expression form was sought, which intimately reflected the effect of overall slenderness.

BackgroundAppalachia is a region with significant cancer disparities in incidence and mortality compared to Kentucky and the United States. However, the contribution of these cancer health disparities to subsequent primary cancers (SPCs) among survivors of adult-onset cancers is limited. This study aimed to quantify the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types, residence and sex.MethodsThis retrospective cohort study from the Kentucky Cancer Registry included 148,509 individuals aged 20-84 years diagnosed with FPCs from 2000-2014 (followed until December 31, 2019) and survived at least 5 years. Expected numbers of SPC were derived from incidence rates in the Kentucky population; standardized incidence ratio (SIR) compared with those expected in the general Kentucky population.ResultsAmong 148,509 survivors (50.2% women, 27.9% Appalachian), 17,970 SPC cases occurred during 829,530 person-years of follow-up (mean, 5.6 years). Among men, the overall risk of developing any SPCs was statistically significantly higher for 20 of the 30 FPC types, as compared with risks in the general population. Among women, the overall risk of developing any SPCs was statistically significantly higher for 20 of the 31 FPC types, as compared to the general population. The highest overall SIR were estimated among oral cancer survivors (SIR, 2.14 [95% CI, 1.97-2.33] among men, and among laryngeal cancer survivors (SIR, 3.62 [95% CI, 2.93-4.42], among women. Appalachian survivors had significantly increased risk of overall SPC and different site specific SPC when compared to non-Appalachian survivors. The highest overall SIR were estimated among laryngeal cancer survivors for both Appalachian and non-Appalachian residents (SIR, 2.50: 95%CI, 2.10-2.95; SIR, 2.02: 95% CI, 1.77-2.03, respectively).ConclusionAmong adult-onset cancer survivors in Kentucky, several FPC types were significantly associated with greater risk of developing an SPC, compared with the general population. Risk for Appalachian survivors was even higher when compared to non-Appalachian residents, but was not explained by higher risk of smoking related cancers. Cancers associated with smoking comprised substantial proportions of overall SPC incidence among all survivors and highlight the importance of ongoing surveillance and efforts to prevent new cancers among survivors.

ABSTRACT Colistin has been considered a last-line option for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Heterogeneous resistance to colistin leads to unexplained clinical colistin treatment failure for CRKP. Our study aimed to investigate the extent of colistin heteroresistance among CRKP strains in China. A total of 455 colistin-susceptible strains, collected from six tertiary care hospitals in China, were characterized. The overall rate of colistin heteroresistance was 6.2%, as determined by the population analysis profiles (PAPs). Genomic analysis revealed that 60.7% of the colistin-heteroresistant isolates belonged to the epidemic sequence type 11 (ST11) clone. Single-nucleotide polymorphisms (SNPs) suggested that 6 ST5216 strains shared the same origin. Each of the subpopulations had a ≥8-fold decrease in colistin MIC in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), which indicated that heteroresistance could be suppressed by an efflux pump inhibitor. In addition, our results suggested that the PhoPQ pathway plays an important role in the mechanisms of heteroresistance. IMPORTANCE The problem of CRKP has raised alarms concerning global health. Our study enriches the epidemiological study of colistin heteroresistance among CRKP strains in China, where the prevalence of this phenomenon was previously unknown. Importantly, colistin-heteroresistant strains may cause the failure of clinical treatment with colistin, even if the clinical laboratory reports that the strains are sensitive. The commonly used broth microdilution method is unable to detect this special phenomenon. Additionally, our results indicate that efflux pumps play a major role in colistin heteroresistance, and inhibitors can effectively reverse it. Our study is the first to provide a detailed analysis of the prevalence of colistin heteroresistance in China, as well as an analysis of the genetic mechanisms of this phenomenon.

IntroductionMethods and tools evaluating treatment effect have been primarily developed for binary type of treatment. Yet, treatment is rarely binary outside the experimental setting, varies by dosage, frequency and time. Treatment is routinely adjusted, initiated or stopped when being administered over a period of time.MethodsBoth Gaussian Process (GP) regression and Bayesian additive regression tree (BART) have been used successfully for handling complex setting involving time-varying treatments that is either adaptive or non-adaptive. Here, we introduce an application programming interface (API) that implements both BART and GP for estimating averaged treatment effect (ATE) and conditional averaged treatment (CATE) for the two-stage time-varying treatment strategies.ResultsWe provide two real applications for evaluating comparative effectiveness of time-varying treatment strategies. The first example evaluates an early aggressive treatment strategies for caring children with newly diagnosed Juvenile Idiopathic Arthritis (JIA). The second evaluates the persistent per-protocol treatment effectiveness in a large randomized pragmatic trial. The examples demonstrate the use of the API calling from R and Python, for handling both non-adaptive or adaptive treatments, with presences of partially observed or missing data issues. Summary tables and interactive figures of the results are downloadable.

ObjectiveThe aims of the present study were to explore the risk factors for type 2 endoleaks (T2ELs) after endovascular aneurysm repair (EVAR) and the association between T2ELs and the iliolumbar artery.Materials and methodsA single-center, retrospective case–control study in West China Hospital was conducted among patients with infrarenal abdominal aortic aneurysm (AAA) who underwent EVAR between June 2010 and June 2019. The associations of patient characteristics, anatomical factors, internal iliac artery embolization, and ILA with the primary outcome were analyzed. The secondary objective was to analyze survival and reintervention between the T2EL group and the non-T2EL group. Kaplan–Meier survival, propensity matching analysis and multivariate logistic regression analysis were used.ResultsA total of 603 patients were included. The median follow-up was 51 months (range 5.0–106.0). There was a significant difference in the diameter of the lumbar artery (LA), middle sacral artery (MSA) and inferior mesentery artery (IMA), proportion of thrombus and LA numbers. The univariate analysis showed that T2ELs were more likely to develop more thrombus in aneurysm cavity (OR = 0.294, p = 0.012), larger MSA (OR = 1.284, p = 0.04), LA (OR = 1.520, p = 0.015), IMA (OR = 1.056, p

Carbapenem-resistant (CR) Klebsiella oxytoca complex can be associated with high mortality, emerging as a new threat to the public health. K. oxytoca complex is phylogenetically close to K. pneumoniae, one of most common species associated with multidrug resistance in Enterobacterale. The latest research showed that K. oxytoca is a complex of six species. Currently, the epidemiological and genomic characteristics of CR K. oxytoca complex in China are still unclear. Here, we conducted a multi-center study on 25 CR K. oxytoca complex collected from five representative regions in China. These isolates were, respectively, recovered from respiratory tract (12 cases, 48.0%), abdominal cavity (5 cases, 20.0%), blood (4 cases, 16.0%), urine tract (3 cases, 12.0%) and skin or soft tissue (1 cases, 4.0%). Among them, 32.0% (8/25) of patients infected with K. oxytoca complex had a poor prognosis. In this study, three K. oxytoca complex species were detected, namely K. michiganensis, K. oxytoca and K. pasteurii, among which K. michiganensis was the most common. Three carbapenemase genes were identified, including blaNDM-1 (10, 38.5%), blaKPC-2 (9, 34.6%) and blaIMP (6 blaIMP-4 and 1 blaIMP-8; 7, 26.9%). Subsequent multilocus sequence typing identified various sequence types (STs), among which ST43, ST92 and ST145 were relatively common. Different from the clonal dissemination of high-risk carbapenem-resistant K. pneumoniae strains, our research revealed a polyclonal dissemination characteristic of CR K. oxytoca complex in China. S1-nuclease PFGE and Southern blot experiment showed that carbapenemase genes were encoded in plasmids of different sizes. Two blaNDM-harboring plasmids were subsequently sequenced, and were characterized to be IncX3 and IncC incompatibility groups, respectively. This is the first multi-center study of CR K. oxytoca complex in China, which improved our understanding of the prevalence and antimicrobial resistance characteristics of CR K. oxytoca complex in China.

ObjectiveDuring the past decade, the concept of complete mesocolic excision (CME) has been developed in an attempt to minimize recurrence for right-sided colon cancer. This study aims to compare outcomes of robotic versus laparoscopic right hemicolectomy with CME for right-sided colon cancer.MethodsWe performed a retrospective multicenter propensity score matching study. From July 2016 to July 2021, 382 consecutive patients from different Chinese surgical departments were available for inclusion out of an initial cohort of 412, who underwent robotic or laparoscopic right hemicolectomy with CME. Data of all patients were retrospectively collected and reviewed. Of these, 149 cases were performed by a robotic approach, while the other 233 cases were done by laparoscopy. Propensity score matching was applied at a ratio of 1:1 to compare perioperative, pathologic, and oncologic outcomes between the robotic and the laparoscopic groups (n = 142).ResultsBefore propensity score matching, there were no statistical differences regarding the sex, history of abdominal surgery, body mass index (BMI), American Joint Committee on Cancer (AJCC) staging system, tumor location, and center between groups (p > 0.05), while a significant difference was observed regarding age (p = 0.029). After matching, two comparable groups of 142 cases were obtained with equivalent patient characteristics (p > 0.05). Blood loss, time to oral intake, return of bowel function, length of stay, and complications were not different between groups (p > 0.05). The robotic group showed a significantly lower conversion rate (0% vs. 4.2%, p = 0.03), but a longer operative time (200.9 min vs. 182.3 min, p < 0.001) and a higher total hospital cost (85,016 RMB vs. 58,266 RMB, p < 0.001) compared with the laparoscopic group. The number of harvested lymph nodes was comparable (20.4 vs. 20.5, p = 0.861). Incidence of complications, mortality, and pathologic outcomes were similar between groups (p > 0.05). The 2-year disease-free survival rates were 84.9% and 87.1% (p = 0.679), and the overall survival rates between groups were 83.8% and 80.7% (p = 0.943).ConclusionDespite the limitations of a retrospective analysis, the outcomes of robotic right hemicolectomy with CME were comparable to the laparoscopic procedures with fewer conversions to open surgery. More clinical advantages of the robotic surgery system need to be further confirmed by well-conducted randomized clinical trials with large cohorts of patients.

Photonic lantern is a key device in space division multiplexing (SDM) system. The key challenge of a photonic lantern is mode scalability, which requires the taper length to increase nonlinearly as the mode number scales up. The traditional photonic lantern fabrication method requires stacking the input fibers into the hollow, low-index outer cladding before tapering. It implicitly sets geometric constraints on the input fibers’ core positioning. We propose a photonic lantern design with drilling preform and reduced cladding fibers to lift these constraints and make photonic lanterns more adiabatic. By analyzing the effects of loosening the constraints on the adiabatic requirement of a three-mode photonic lantern, we find further progress could be made to alleviate this adiabatic requirement. The optimal structure for our design is proposed and demonstrated through the beam propagation method (BPM). Our findings could help further improve the mode scalability of photonic lanterns.

Meloidogyne spp. are important parasitic nematodes affecting a variety of plants worldwide. We investigated the nematicidal properties of specific compounds found in bio-fumigant plants, particularly linalool, nonanal, methylene chloride, and 2-Decanal. Laboratory findings revealed that methylene chloride and 2-Decenal effectively reduced populations of second-stage juveniles (J2s). Additionally, the research explored the effects of tomato (Solanum lycopersicum L.) on M. incognita J2s, observing that tomato leaves significantly increased J2 mortality for all time measurements and different temperatures, while the opposite results were observed for root-stems. In the study, leaf treatment resulted in a maximum mortality response (MRmax) and half-maximal effective concentration (EC50) of approximately 100% and 4.0 µg/mg, respectively, at a temperature of 35 °C by week 8. In contrast, the root-stems treatment showed an MRmax of 13.5% and an EC50 of 3.0 ± 1.7 µg/mg. GC-MS analysis identified key compounds in tomato leaves and root-stems, such as α-pinene, d-limonene, and linalool. The results suggest that tomato leaves have potential as effective bio-fumigants for controlling root-knot nematodes.

Abstract Ornamental crabapple is an important woody ornamental plant in the Northern Hemisphere. Its flowers, fruits, leaves and tree habit are all important ornamental characters. As there has been no research on the selection of superior parents and phenotypic variation, new varieties of ornamental crabapple are mainly selected from open-pollination progeny. In order to explore the transmission rule of ornamental traits between parents and offspring of crabapple, and to provide a basis for the selection of hybrid parents for directional breeding, 14 pairs of SSR markers were used in this study for paternity analysis of 384 offspring from 4 female parents crossed with 91 candidate male parents. And 273 offspring (71.1%) were matched with only the father at a 95% strict confidence level. We reconstructed 7 full-sib families (number of progeny ≥ 10) on the basis of the paternity analysis results. Genetic analysis of characters in the full-sib families revealed that green leaves and white flowers were dominant traits. All the hybrid offspring from the white flower (♀) × non-white flower (♂) cross produced white flowers, while 7.04% produced non-white flowers when both parents had white flowers. The results showed that white flowers might be a dominant qualitative trait in crabapple, while the depth of red was a quantitative trait. The genetic characteristics of green and non-green leaves and the depth of red of the peel were similar to flower color. Compared with the upright and spreading traits, the weeping trait was recessive. Some progeny showed an earlier blooming period, indicating the possibility of breeding for blooming period. Our findings are important for parent screening and improving the breeding efficiency of new varieties in ornamental crabapple hybridization.

Abstract Background Continuous glucose monitoring systems have been widely used but discrepancies among various brands of devices are rarely discussed. This study aimed to explore differences in glycemic metrics between FreeStyle Libre (FSL) and iPro2 among adults with type 1 diabetes mellitus (T1DM). Methods Participants with T1DM and glycosylated hemoglobin of 7%–10% were included and wore FSL and iPro2 for 2 weeks simultaneously. Datasets collected on the insertion and detachment day, and those with insufficient quantity (

Abstract In a real normed linear space, when the quasirelative interior is not empty, a class of order relation is introduced with Minkowski difference. Two classes of nonlinear functions are introduced, and their properties are discussed. A class of approximately efficient solutions and approximate weakly efficient solutions are introduced for set optimization. With nonlinear functions, optimality conditions are established for approximate solutions. Some examples are given to illustrate our main results.

Abstract Combining well‐drilling hammers with polycrystalline diamond compact bits to break rock under cutting load and impact load is an effective way to improve drilling efficiency. Although impact load can enhance the cutting efficiency of the cutter, excessive impact can also cause the cutter to be subjected to additional vibrations, which can decrease its working life. Knowledge of laws governing the changes in the cutting force of the cutter under impact load is essential for the design and selection of well‐drilling hammers. Based on rock scratch tests and finite element rock cutting model, a discrete element modeling (DEM) rock cutting model was established to analyze the rock breaking and cutting force. Then, the material parameters of rock samples were determined, and the simulation parameters were corrected. Finally, a DEM rock cutting model under an impact load was established. The results showed that when there was an obvious difference between the average cutting force and mean peak cutting force, which corresponded to the rock‐breaking transition from ductile to brittle, with introduction of the impact load leading to an earlier transition. The cutting force variance was proportional to the impact amplitude, and the increase in the cutting force variance became more obvious when the static load exceeded the critical transition weight. When the ratio of the impact amplitude to the static load was greater than 50%, the mean and variance of the cutting force increased rapidly. Under the same impact amplitude, the impact frequency had little effect on the average cutting force, but a higher frequency could significantly reduce the variance of the cutting force under a high static load (i.e., it could alleviate the fluctuation of the cutting force). These results provide a reference for the selection of well‐drilling hammers and optimization of the impact load.

Abstract Background Bloodstream infection (BSI) caused by carbapenem resistant Klebsiella pneumoniae (CRKP), especially in elderly patients, results in higher morbidity and mortality. The purpose of this study was to assess risk factors associated with CRKP BSI and short-term mortality among elderly patients in China. Methods In this retrospective cohort study, we enrolled 252 inpatients aged ≥ 65 years with BSI caused by KP from January 2011 to December 2020 in China. Data regarding demographic, microbiological characteristics, and clinical outcome were collected. Result Among the 252 BSI patients, there were 29 patients (11.5%) caused by CRKP and 223 patients (88.5%) by carbapenem-susceptible KP (CSKP). The overall 28-day mortality rate of elderly patients with a KP BSI episode was 10.7% (27/252), of which CRKP BSI patients (14 / 29, 48.3%) were significantly higher than CSKP patients (13 / 223, 5.83%) (P

BackgroundMendelian randomization (MR) was used to evaluate the bidirectional causal relationship between inflammatory bowel disease (IBD) and interleukins (ILs), chemokines.MethodsGenetic instruments and summary data of five ILs and six chemokines were obtained from a genome-wide association study database, and instrumental variables related to IBD were obtained from the FinnGen Consortium. Inverse variance weighting (IVW) was used as the main MR analysis method, and several other MR methods including MR-Egger and weighted median were used to confirm the reliability of the results. Sensitivity analyses such as heterogeneity and pleiotropy were also performed.ResultsThe IVW method provided evidence to support that genetically predicted IL-16, IL-18, and CXCL10 significantly positively correlated with IBD, while IL-12p70 and CCL23 significantly negatively correlated with IBD. IL-16 and IL-18 had a suggestive association with an increased risk of ulcerative colitis (UC), and CXCL10 had a suggestive association with an increased risk of Crohn’s disease (CD). However, there was no evidence to support that IBD and two main subtypes (UC and CD) are associated with changes in the levels of ILs and chemokines. The results of the sensitivity analyses were robust and no evidence of heterogeneity and horizontal pleiotropy was observed.ConclusionsThe present study showed that some ILs and chemokines affect IBD, but IBD and its main subtypes (UC and CD) have no effect on the level changes of ILs and chemokines.

IntroductionThe continuous application of cow manure in soil for many years leads to the accumulation of heavy metals, pathogenic microorganisms, and antibiotic resistance genes. Therefore, in recent years, cow manure has often been mixed with botanical oil meal as organic fertilizer applied to farmland to improve soil and crop quality. However, the effects of various botanical oil meal and cow manure mixed organic fertilizers on soil microbial composition, community structure, and function, tobacco yield, and quality remain unclear.MethodsTherefore, we prepared organic manure via solid fermentation by mixing cow manure with different oil meals (soybean meal, rape meal, peanut bran, sesame meal). Then, we studied its effects on soil microbial community structure and function, physicochemical properties, enzyme activities, tobacco yield and quality; then we analyzed the correlations between these factors.Results and discussionCompared with cow manure alone, the four kinds of mixed botanical oil meal and cow manure improved the yield and quality of flue-cured tobacco to different degrees. Peanut bran, which significantly improved the soil available phosphorus, available potassium, and NO3–-N, was the best addition. Compared with cow manure alone, soil fungal diversity was significantly decreased when rape meal or peanut bran was combined with cow manure, while soil bacterial and fungal abundance was significantly increased when rape meal was added compared with soybean meal or peanut bran. The addition of different botanical oil meals significantly enriched the subgroup_7 and Spingomonas bacteria and Chaetomium and Penicillium fungi in the soil. The relative abundances of functional genes of xenobiotics biodegradation and metabolism, soil endophytic fungi, and wood saprotroph functional groups increased. In addition, alkaline phosphatase had the greatest effect on soil microorganisms, while NO3–-N had the least effect on soil microorganisms. In conclusion, the mixed application of cow manure and botanical oil meal increased the available phosphorus and potassium contents in soil; enriched beneficial microorganisms; promoted the metabolic function of soil microorganisms; increased the yield and quality of tobacco; and improved the soil microecology.

Cardiovascular involvement is an uncommon but severe complication of Epstein–Barr virus (EBV) infection caused by direct damage and immune injury. Recently, it has drawn increasing attention due to its dismal prognosis. It can manifest in various ways, including coronary artery dilation (CAD), coronary artery aneurysm (CAA), myocarditis, arrhythmias, and heart failure, among others. If not treated promptly, cardiovascular damage can progress over time and even lead to death, which poses a challenge to clinicians. Early diagnosis and treatment can improve the prognosis and reduce mortality. However, there is a lack of reliable large-scale data and evidence-based guidance for the management of cardiovascular damage. Consequently, in this review, we attempt to synthesize the present knowledge of cardiovascular damage associated with EBV and to provide an overview of the pathogenesis, classification, treatment, and prognosis, which may enhance the recognition of cardiovascular complications related to EBV and may be valuable to their clinical management.

The auxin/indole-3-acetic acid (Aux/IAA) gene family serves as a principal group of genes responsible for modulating plant growth and development through the auxin signaling pathway. Despite the significance of this gene family, the identification and characterization of members within the well-known Chinese medicinal herb Salvia miltiorrhiza (S. miltiorrhiza) have not been thoroughly investigated. In this study, we employed bioinformatics methods to identify 23 Aux/IAA genes within the genome of S. miltiorrhiza. These genes were classified into typical IAA and atypical IAA based on their domain structure. Our analysis of the promoter regions revealed that the expression of these genes is regulated not only by auxins, but also by other hormones and environmental factors. Furthermore, we found that the expression patterns of these genes varied across various tissues of S. miltiorrhiza. While our initial hypothesis suggested that the primary function of these genes was the interaction between SmIAA and ARF, gene co-expression network analysis revealed that they are also influenced by various other transcription factors, such as WRKY and ERF. The findings establish a sturdy basis for future investigations into the function of the Aux/IAA gene family and exhibit promising prospects for enhancing the genetics of this medicinal flora and its associated species.

Tor onion services provide anonymous service to clients using the Tor browser without disclosing the real address of the server. But an adversary could use a circuit fingerprinting attack to classify circuit types and discovers the network address of the onion service. Recently, Tor has used padding defenses to inject dummy cells to protect against circuit fingerprinting attacks. But we found that circuits still expose much information to the adversary. In this paper, we present a novel circuit fingerprinting attack, which divides the circuit into the circuit generated by the client and the circuit generated by the onion service. To get a more effective attack, we tried three state-of-the-art classification models called SVM, Random Forest and XGBoost, respectively. As the best performance, we attain 99.99% precision and 99.99% recall when using Random Forest and XGBoost classification models, respectively. And we also tried to classify circuit types using our features and the classification model mentioned above, which was first proposed by Kwon. The best performance was achieved with 99.99% precision and 99.99% recall when using the random forest classifier in circuit type classification. The experimental results show that we achieved highly accurate circuit fingerprinting attacks even when application-layer traffic is identical and some type of circuits using the defenses provided by Tor.

Introduction Postoperative renal function decline is a major concern for thoracic endovascular aortic repair (TEVAR) and endovascular abdominal aortic repair (EVAR). Diluting contrast medium in the power injector may be helpful in reducing the risk of contrast-induced nephropathy, but it can also blur fluoroscopic vision during surgery. The quality of the current evidence is very low; thus, this study is designed to investigate the effect of contrast dilution in the power injector on renal function changes in patients after endovascular aortic repair.Method and analysis The study is a prospective, single-blind, parallel, non-inferiority, randomised controlled trial with two independent cohorts: Cohort TEVAR and EVAR. Individuals will enter the appropriate cohort based on clinical interviews if they meet the eligibility criteria. Participants in Cohort TEVAR and EVAR will be randomly allocated to the intervention group (diluting contrast medium to 50% in the power injector) and control group (pure contrast medium in the power injector) separately in a 1:1 ratio. The primary study points consist of the proportion of patients who develop acute kidney injury within 48 hours after TEAVR or EVAR (first stage) and freedom of major adverse kidney events at 12 months after TEAVR or EVAR (second stage). The safety endpoint is freedom of all types of endoleaks at 30 days after TEVAR or EVAR. Follow-up will be conducted at 30 days and 12 months after intervention.Ethics and dissemination The trial was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University (approval number: 20201290). The results of the study will be disseminated through publications in peer-reviewed journals and presentations at academic conferences.Trial registration number Chinese Clinical Trial Registry (ChiCTR2100042555).

Objective: This study investigated the effects of a vitrification/warming procedure on the mRNA transcriptome of human ovarian tissues.Design: Human ovarian tissues were collected and processed through vitrification (T-group) and then subjected to RNA sequencing (RNA-seq) analysis, HE, TdT-mediated dUTP nick-end labeling (TUNEL), and real-time quantitative PCR, and the results were compared to those of the fresh group (CK).Results: A total of 12 patients, aged 15–36 years old, with a mean anti-Müllerian hormone level of 4.57 ± 3.31 ng/mL were enrolled in this study. According to the HE and TUNEL results, vitrification effectively preserved human ovarian tissue. A total of 452 significantly dysregulated genes (|log2FoldChange| > 1 and p < 0.05) were identified between the CK and T groups. Among these, 329 were upregulated and 123 were downregulated. A total of 372 genes were highly enriched for 43 pathways (p < 0.05), which were mainly related to systemic lupus erythematous, cytokine–cytokine receptor interaction, the TNF signaling pathway, and the MAPK signaling pathway. IL10, AQP7, CCL2, FSTL3, and IRF7 were significantly upregulated (p < 0.01), while IL1RN, FCGBP, VEGFA, ACTA2, and ASPN were significantly downregulated in the T-group (p < 0.05) compared to the CK group, which agreed with the results of the RNA-seq analysis.Conclusion: These results showed (for the first time to the authors’ knowledge) that vitrification can induce changes in mRNA expression in human ovarian tissues. Further molecular studies on human ovarian tissues are required to determine whether altered gene expression could result in any downstream consequences.

A Gaussian process (GP) covariance function is proposed as a matching tool for causal inference within a full Bayesian framework under relatively weaker causal assumptions. We demonstrate that matching can be accomplished by utilizing GP prior covariance function to define matching distance. The matching properties of GPMatch is presented analytically under the setting of categorical covariates. Under the conditions of either (1) GP mean function is correctly specified; or (2) the GP covariance function is correctly specified, we suggest GPMatch possesses doubly robust properties asymptotically. Simulation studies were carried out without assuming any a priori knowledge of the functional forms of neither the outcome nor the treatment assignment. The results demonstrate that GPMatch enjoys well-calibrated frequentist properties and outperforms many widely used methods including Bayesian Additive Regression Trees. The case study compares the effectiveness of early aggressive use of biological medication in treating children with newly diagnosed Juvenile Idiopathic Arthritis, using data extracted from electronic medical records. Discussions and future directions are presented.