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Abstract Sclerotinia stem rot (SSR), caused by the necrotrophic fungus Sclerotinia sclerotiorum, is one of the most devastating diseases for several major oil-producing crops. Despite its impact, the genetic basis of SSR resistance in plants remains poorly understood. Here, through a genome-wide association study, we identify a key gene, BnaA07. MKK9, that encodes a mitogen-activated protein kinase kinase that confers SSR resistance in oilseed rape. Our functional analyses reveal that BnaA07.MKK9 interacts with BnaC03.MPK3 and BnaC03.MPK6 and phosphorylates them at the TEY activation motif, triggering a signaling cascade that initiates biosynthesis of ethylene, camalexin, and indole glucosinolates, and promotes accumulation of H2O2 and the hypersensitive response, ultimately conferring resistance. Furthermore, variations in the coding sequence of BnaA07.MKK9 alter its kinase activity and improve SSR resistance by ~30% in cultivars carrying the advantageous haplotype. These findings enhance our understanding of SSR resistance and may help engineer novel diversity for future breeding of oilseed rape.

Abstract Objectives This study evaluated the effectiveness, psychological effects, and sleep quality using intramuscular diazepam infusion compared with placebo in patients with herpes zoster (HZ)-related pain. Methods The patients were randomized to either the diazepam or control group. The diazepam group received an intramuscular injection of diazepam for 3 consecutive days, while the control group received an intramuscular injection of 0.9% normal saline. The primary outcome was pain relief on posttreatment day 4, as measured using the Visual Analog Scale (VAS). Moreover, anxiety and depression were evaluated using the Generalized Anxiety Disorder-7 (GAD7) and Patient Health Questionnaire-9 (PHQ9), respectively. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Results In total, 78 patients were enrolled in the trial. The mean differences in VAS scores between the two groups were 0.62 (P = 0.049) on posttreatment day 3 and 0.66 (P = 0.037) on posttreatment day 4. The effective rates of pain management in the diazepam group ranged from 10.26 to 66.67%, which were higher than those in the control group on posttreatment days 3 and 4 (P

Rationale and objectives: To compare the performance of SS, FOCUS SS, MUSE, and FOCUS MUSE DWI for pulmonary lesions to obtain a better technique for pulmonary DWI imaging. Materials and methods: 44 patients with pulmonary lesions were recruited to perform pulmonary DWI using SS, FOCUS SS, MUSE, and FOCUS MUSE sequences. Then, two radiologists with 12 and 10 years of chest MRI experiences assessed the overall image quality while another two radiologists both with 3 years of experiences evaluated the SNR, DR, and ADC of pulmonary lesions. Using interclass correlation coefficient (ICC) and kappa statistics to assess consistency of readers, Friedman test and Dunn-Bonferroni post hoc were used to calculate the difference between sequences. Mann-Whitney test and ROC curve were used to distinguish malignant from benign lesions. Results: All the assessed variables of the four sequences presented good to excellent intra-/inter-observer consistency. Compared with SS, FOCUS SS and MUSE, FOCUS MUSE demonstrated better image quality, including significantly higher 5-point Likert scale score (P 0.05) while MUSE presented with significantly higher SNR over them (P

IntroductionImmunoglobulin G (IgG) is important in mediating humoral immunity and in the maintenance of immune homeostasis in the intestinal mucosa. Oregano essential oil (OEO) is a natural herbal extract that possesses antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory properties. As the effects of OEO on intestinal mucosal immunity in Holstein dairy bulls remained unclear, we investigated the effect of dietary supplementation of OEO on IgG levels and IgG+ cells residing in the intestinal tract in Holstein dairy bulls.MethodsTwelve Holstein bulls in good health of approximately 10 months of age were selected for the experiment and randomly equally divided into two groups. The control (CK) group was fed a basal ration, and in the OEO group, the basal ration was supplemented with OEO (20 g/head/day). After 300 days of feeding, tissue samples of the jejunum, ileum, and colon of the bulls in each group were collected for histopathological analysis, immunohistochemistry, and enzyme-linked immunosorbent assays, respectively.ResultsThe jejunum, ileum, and colon of bulls in the CK group had obvious pathological damage, whereas the structure of each intestinal segment was clear and intact. In the OEO group, pathological damage was significantly reduced. IgG+ plasma cells were diffusely distributed in the lamina propria of the jejunum, ileum, and colon in the CK and OEO groups, with no significant difference between the groups. OEO supplementation significantly reduced the number of IgG+ plasma cells in each intestinal segment, with the highest decrease rate being noted for the ileum (22.87%), followed by the colon (19.45%) and jejunum (8.52%). ELISA test results and immunohistochemical results were mutually verified. The change in IgG content was consistent with the trend of change in the number of IgG+ plasma cells.DiscussionOur findings suggest that OEO supplementation does not alter the diffuse spatial distribution of IgG+ plasma cells in the intestines of Holstein dairy bulls, but lowers immunoglobulin levels to normal levels, significantly reduces intestinal damage, and may enhance mucosal immune defence barrier function by inhibiting inflammatory reactions.

The development of messenger RNA (mRNA) vaccines and therapeutics necessitates the production of high-quality in vitro-transcribed mRNA drug substance with specific critical quality attributes (CQAs), which are closely tied to the uniformity of linear DNA template. The supercoiled plasmid DNA is the precursor to the linear DNA template, and the supercoiled DNA percentage is commonly regarded as a key in-process control (IPC) during the manufacturing of linear DNA template. In this study, we investigate the influence of supercoiled DNA percentage on key mRNA CQAs, including purity, capping efficiency, double-stranded RNA (dsRNA), and distribution of poly(A) tail. Our findings reveal a significant impact of supercoiled DNA percentage on mRNA purity and in vitro transcription yield. Notably, we observe that the impact on mRNA purity can be mitigated through oligo-dT chromatography, alleviating the tight range of DNA supercoiled percentage to some extent. Overall, this study provides valuable insights into IPC strategies for DNA template chemistry, manufacturing, and controls (CMC) and process development for mRNA drug substance.

Objective: The prognosis of malignant tumors with peritoneal metastases and cancerous ascites has generally been poor, with limited treatment options. The PRaG regimen, which comprised of hypofractionated radiotherapy, programmed cell death-1 (PD-1) inhibitor, and granulocyte-macrophage colony-stimulating factor (GM-CSF), showed a survival advantage in patients with advanced solid tumors who failed at least the first line of standard systemic treatment. Intraperitoneal infusion of PD-1 inhibitors may be a novel therapeutic strategy for managing malignant ascites. Integrating the PRaG regimen with intraperitoneal perfusion of a PD-1 inhibitor might control malignant ascites and provide further survival benefits in these patients. This proposed study aims to investigate the safety and efficacy of intraperitoneal infusion of serplulimab in combination with the PRaG regimen in patients with simultaneous advanced solid tumors and cancerous ascites who fail at least the first-line treatment. Methods: This proposed study is a prospective, single-arm, open-label, multicenter clinical trial. All eligible patients will receive 2 cycles of intensive treatment, a combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor. The patients who are beneficially treated with intensive treatment will receive consolidation treatment every 2 weeks until ascites disappear, disease progression occurs, intolerable toxicity occurs, or for up to 1 year. Phase I of this study will be conducted using a modified 3 + 3 design. The dose of intraperitoneal infusion of PD-1 inhibitor for phase II will be determined according to dose-limiting toxicity evaluation in the phase I study. Conclusion: This prospective, open-label, multicenter study will potentially lead to intraperitoneal perfusion of a PD-1 inhibitor being a new strategy for malignant ascites patients and provide a meaningful efficacy and safety of the combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor for these patients.

Abstract Background Delaying the development and lowering the progression of myopia in children is the focus of current ophthalmology researches. We aimed to evaluate the role of orthokeratology in controlling myopia of children, to provide insights to the clinical treatment and care of children with myopia. Methods Two investigators searched the The Cochrane Library, Embase, Pubmed, China national knowledge infrastructure, China biomedical literature database, WanFang and Weipu databases for randomized controlled trials(RCTs) on the role of orthokeratology in controlling myopia of children up to November 5, 2022. Two researchers independently searched, screened and extracted the studies according to the inclusion and exclusion standards. RevMan5.3 software was used for statistical analysis. Results A total of 14 RCTs involving 2058 children were included in this meta-analysis. Synthesized outcomes indicated that orthokeratology improved the uncorrected visual acuity(MD = 0.40, 95%CI: 0.05 ~ 0.74), reduced the diopter change(MD=-3.19, 95%CI: -4.42~-1.95), changes of corneal curvature(MD=-3.21, 95%CI: -3.64~-2.79), the length of ocular axis (MD=-0.66, 95%CI: -1.27~-0.06) and amount of ocular axis change(MD=-0.42, 95%CI: -0.64~-0.21) after 1 year of wearing orthokeratology(all P 0.05). Conclusions Orthokeratology delays the progression of myopia in children, the long-term effects of orthokeratology need further investigations in future studies.

The energy landscape of sodium chloride-nitrogen mixtures has been comprehensively explored to examine the ability of the formation of unknown compounds under pressures of up to 100 GPa, using swarm-intelligence structure prediction methodology and first-principles calculations. We identified a thermodynamically stable NaN_{5}ClN_{5} compound containing two cyclo-N_{5} species under pressures exceeding 53 GPa, representing milder conditions in comparison to those requisite for pure solid nitrogen. In NaN_{5}ClN_{5}, the high electron affinity of the cyclo-N_{5} motif allows it to oxidize the chlorine atoms, resulting in the formation of two cyclo-N_{5} anions. Additionally, the weak covalent interactions between Cl and nearby N atoms plays a key role in stabilization of structure. It has been demonstrated that simple NaN_{5} salt was a suitable precursor for the synthesis of NaN_{5}ClN_{5} at high pressure. Ab initio molecular dynamics simulations demonstrated the recoverability of NaN_{5}ClN_{5} as a metastable phase at ambient pressure-temperature conditions. Additionally, NaN_{5}ClN_{5} exhibits a higher energy density of 3.86 kJ/g and a lower mass density of 1.67 g/cm^{3} in comparison to metal pentazolate salts, highlighting its potential as a high energy-density material.

Introduction The PRaG regimen, which consists of hypofractionated radiotherapy combined with a programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitor and granulocyte-macrophage colony stimulating factor (GM-CSF), has been demonstrated to have a survival benefit in patients with advanced solid tumours who have failed at least two lines of treatment. Nonetheless, lymphopenia poses an impediment to the enduring efficacy of PD-1/PD-L1 inhibitor therapy. Adequate lymphocyte reserves are essential for the efficacy of immunotherapy. Coupling the PRaG regimen with immunomodulatory agents that augment the number and functionality of lymphocytes may yield further survival benefits in this cohort of patients.Objective The aim of this study is to investigate the effectiveness and safety of a meticulously thymalfasin-controlled PRaG regimen in patients with advanced and chemotherapy-resistant solid tumours.Methods and analysis The study has a prospective, single-arm, open-label, multicentre design and aims to recruit up to 60 patients with histologically confirmed advanced solid tumours that have relapsed or metastasised. All eligible patients will receive a minimum of two cycles of the PRaG regimen comprising thymalfasin followed by maintenance treatment with a PD-1/PD-L1 inhibitor and thymalfasin for 1 year or until disease progression. Patients will be monitored according to the predetermined protocol for a year or until disease progression after initiation of radiotherapy.Ethics and dissemination The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University, on 25 November 2022 (JD-LK-2022-151-01) and all other participating hospitals. Findings will be disseminated through national and international conferences. We also plan to publish our findings in high-impact peer-reviewed journal.Trial registration number NCT05790447.

Oregano essential oil (OEO) primarily contains phenolic compounds and can serve as a dietary supplement for fattening bulls. However, the precise molecular mechanism underlying this phenomenon remains largely elusive. Therefore, this study investigated the impact of adding OEO to diet on the integrity of the intestinal barrier, composition of the colonic microbiome, and production of microbial metabolites in fattening bulls. Our goal was to provide insights into the utilization of plant essential oil products in promoting gastrointestinal health and welfare in animals. We employed amplicon sequencing and metabolome sequencing techniques to investigate how dietary supplementation with OEO impacted the intestinal barrier function in bulls. The inclusion of OEO in the diet resulted in several notable effects on the colon of fattening bulls. These effects included an increase in the muscle thickness of the colon, goblet cell number, short-chain fatty acid concentrations, digestive enzyme activity, relative mRNA expression of intestinal barrier-related genes, and relative expression of the anti-inflammatory factor IL-10. Additionally, α-amylase activity and the relative mRNA expression of proinflammatory cytokines decreased. Moreover, dietary OEO supplementation increased the abundance of intestinal Bacteroides, Coprobacillus, Lachnospiraceae_UCG_001, and Faecalitalea. Metabolomic analysis indicated that OEO primarily increased the levels of 5-aminovaleric acid, 3-methoxysalicylic acid, and creatinine. In contrast, the levels of maltose, lactulose, lactose, and D-trehalose decreased. Correlation analysis showed that altered colonic microbes and metabolites affected intestinal barrier function. Taken together, these results demonstrate that OEO facilitates internal intestinal environmental homeostasis by promoting the growth of beneficial bacteria while inhibiting harmful ones.

Topological quantum materials have significant potential for application as anode materials due to their intrinsically high electronic conductivity against perturbation from defects or impurities. In this work, we utilize a combination of a swarm-intelligence structure search method and first-principles calculations to predict the global minimum of a BeN monolayer, suggesting it as a promising nodal-line semimetal anode for Li-ion batteries. BeN anode demonstrates a substantial specific capacity of 3489 mAh/g and a low average open-circuit voltage of 0.15 V, resulting in an ultrahigh energy density of 9681 mWh/g (referenced to the standard hydrogen electrode potential). This energy density represents the highest among all two-dimensional (2D) topological quantum anodes and surpasses that of most currently known 2D anode materials for Li-ion batteries. Furthermore, the formation of a vacancy in the BeN monolayer induces a unique “self-doping” effect that promotes high electronic conductivity. Additionally, the BeN monolayer exhibits a diffusion energy barrier of 0.30 eV for Li-ion migration, a small-scale area expansion of 0.96% during the process of lithiation, and excellent wettability with the contacted electrolytes.

Background: The “obesity paradox” has been elucidated in patients with heart failure (HF). Current guidelines introduce a target diastolic blood pressure (DBP) 70 mmHg in HF patients. Due to reduced coronary perfusion, low DBP has a deleterious impact on cardiovascular outcomes. This present study aimed to assess the relationship between BMI and adjudicated clinical outcomes in HFpEF patients according to the status of DBP. Methods: We analyzed the data in 1749 HFpEF patients from the Americas of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) Trial. The population was stratified by DBP (

Patients with chemo-refractory metastatic colorectal cancer (mCRC) have poor prognoses. The application of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors encouragingly improved the survival of mCRC patients with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR). Unfortunately, it was ineffective for mCRC with microsatellite-stable (MSS)/proficient mismatch repair (pMMR), which accounted for 95% of mCRC. Radiotherapy can promote local control by directly killing tumor cells and inducing positive immune activities, which might help synergistically with immunotherapy. We present the report of an advanced MSS/pMMR mCRC patient who had progressive disease (PD) after first-line chemotherapy, palliative surgery and second-line chemotherapy combined with targeted therapy. Then the patient received the therapy of PD-1 inhibitor combined with radiotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF). According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST1.1), the patient showed a complete response (CR) after triple-combined therapy with progression-free survival (PFS) for more than 2 years so far. The patient had no other significant adverse reactions except for fatigue (Grade 1). The triple-combination therapy provided a promising strategy for metastatic chemo-refractory MSS/pMMR mCRC patients.

The aim of this study was to investigate the effect of oregano essential oil on IgA+, IgG+, and IgM+ cells in the jejunum of castrated Holstein bulls. Twelve castrated Holstein bulls were randomly divided into control (YCK) and oregano essential oil (YEO) groups. Pathological changes in the jejunum were observed by HE staining, and the expression levels of IgA, IgG, and IgM in the jejunum were detected by ELISA. The distributions of IgA+, IgG+, and IgM+ cells in the jejunum were analysed by multiplex immunofluorescence and immunohistochemistry. The results showed that the jejunal villi were detached in the YCK group, which may have been related to inflammation, while the intestinal epithelium was clear and intact in the YEO group. The expressions of IgA, IgG, and IgM were significantly reduced by 40.75%, 30.76%, and 50.87%. The IgA+, IgG+, and IgM+ cells were diffusely distributed in the lamina propria of the jejunum, and were reduced by 17.07%, 6.44%, and 6.15%, respectively. Oregano essential oil did not alter the distribution characteristics of IgA+, IgG+, or IgM+ cells in the jejunum, but it suppressed inflammatory response, decreased immunoglobulin content, and significantly enhanced the formation of an immune barrier in the gastrointestinal mucosa.

B-rich metal compounds have garnered significant attention due to their diverse polymeric boron structures and versatile properties including high melting temperature, exceptional hardness, and superconductivity. In this paper, we systematically investigate the ternary phase diagram of the Li-Mn-B system at 0–100 GPa, employing a combination of crystal structure prediction methods and first-principles calculations. We identify five pressure-stabilized compounds with stoichiometries of Li_{2}MnB_{2}, LiMnB_{3}, LiMnB_{4}, Li_{2}MnB_{8}, and LiMnB_{10}. These pressure-induced compounds can be recovered to ambient pressure conditions. Notably, the boron atoms in these compounds exhibit diverse polymerization patterns, forming structures such as dimers, zigzag chains, ribbons, kagome lattices, and three-dimensional channel frameworks. The five Li-Mn-B compounds are potential hard materials, with LiMnB_{4} standing out with a remarkable hardness value of 39.47 GPa. LiMnB_{4} and LiMnB_{10} are indirect semiconductors with band gaps of 0.92 and 0.64 eV, respectively. Notably, LiMnB_{10} exhibits a lower effective mass than silicon, superior solar cell efficiency compared with silicon, and a work function comparable with that of silicon. These properties highlight the considerable potential of LiMnB_{10} as a viable material for photovoltaic applications. Li_{2}MnB_{8} is predicted to be a superconductor with a critical temperature of 15 K at 50 GPa. When the pressure is reduced to 0 GPa, Li_{2}MnB_{8} displays antiferromagnetic properties. LiMnB_{3} is a suitable precursor to obtain a B_{20}-caged structure with remarkable superconductivity at ambient pressure, reaching a T_{c} of 31 K. In this paper, we provide comprehensive insights into the ternary phase diagram of the Li-Mn-B system at high pressure, elucidating the formation of various stable compounds with intriguing properties.

ObjectiveThis study aims to highlight the use of robots in surgery and that of tube-assisted minimally invasive surgery for spinal metastases, as well as elaborate on the concept of invasion-controlled surgery (ICS).Summary of backgroundMany patients with spinal metastasis cancer cannot afford serious complications when undergoing traditional open surgery because of their poor physical condition. Robots and minimally invasive technology have been introduced into the field of spine surgery and they have shown significant advantages.MethodsSix patients who underwent robot and working tube-assisted ICS for spinal metastases. Relevant demographic, medical, surgical, and postoperative data were collected from medical records and analyzed.ResultsMean operative time was 3.8 h and the mean length of the surgical incision was 4.9 cm. The mean estimated blood loss was 400 ml. The mean bedtime and hospital length of stay were 3.2 days and 6.5 days, respectively. No obvious complications were reported during treatment. The mean accuracy of screw placement was 98%. The mean time for further system treatment after surgery was 5.8 days. All patients experienced significant pain relief. The mean preoperative visual analog scale (VAS) was 7.83 points. The mean VAS at 1 day, 1 week, and 1 month after surgery were 2.83, 1.83, and 1.17 points, respectively. Frankel grade was improved in five of six patients. One patient preoperatively with Frankel grade D was the same postoperatively.ConclusionThe concept of ICS is suitable for patients with spinal metastases. Robot and working tube-assisted ICS for spinal metastases is one of the safest and most effective treatment methods.

Polymeric nitrogen possessing ambient quench recoverability is considered to be the most powerful and green high-energy density material, which has triggered extensive interest. Herein, we predicted two hitherto unknown nitrogen-rich nitrogen fluorine compounds with stoichiometries N2F and N10F using structure searching method and first-principles calculations. N2F and N10F are thermodynamically stable relative to ε-N and fluorine at 67–110 and 87–110 GPa, respectively. Both N2F and N10F encompass N6 rings, forming one-dimensional N∞ ribbons by edge-sharing and three-dimensional channel-like open framework by edge-sharing and two N atoms-bridging, respectively. Phonon spectra calculations and molecular dynamics simulations demonstrate the ambient-pressure quench recoverability of the two predicted phases. Interestingly, after the removal of F atoms from open channel in N10F, the polymeric nitrogen framework mC10-N is retained at ambient conditions with the energy density of 11.20 kJ/g, rendering it a remarkable high-energy density material.

ObjectiveOur study aims to estimate intra-fraction six-dimensional (6D) tumor motion with rotational correction and the related correlations between motions of different degrees of freedom (DoF), as well as quantify sufficient anisotropic clinical target volume (CTV) to planning target volume (PTV) margins during stereotactic body radiotherapy (SBRT) of liver cancer with fiducial tracking technique.MethodsA cohort of 12 patients who were implanted with 3 or 4 golden markers were included in this study, and 495 orthogonal kilovoltage (kV) pairs of images acquired during the first fraction were used to extract the spacial position of each golden marker. Translational and rotational motions of tumor were calculated based on the marker coordinates by using an iterative closest point (ICP) algorithm. Moreover, the Pearson product-moment correlation coefficients (r) were applied to quantify the correlations between motions with different degrees of freedom (DoFs). The population mean displacement (MP¯), systematic error (Σ) and random error (σ) were obtained to calculate PTV margins based on published recipes.ResultsThe mean translational variability of tumors were 0.56, 1.24 and 3.38 mm in the left-right (LR, X), anterior-posterior (AP, Y), and superior-inferior (SI, Z) directions, respectively. The average rotational angles θX , θY and θZ around the three coordinate axes were 0.88, 1.24 and 1.12, respectively. (|r|>0.4) was obtainted between Y -Z , Y - θZ , Z -θZ and θX - θY . The PTV margins calculated based on 13 published recipes in X, Y, and Z directions were 1.08, 2.26 and 5.42 mm, and the 95% confidence interval (CI) of them were (0.88,1.28), (1.99,2.53) and (4.78,6.05), respectively.ConclusionsThe maximum translational motion was in SI direction, and the largest correlation coefficient of Y-Z was obtained. We recommend margins of 2, 3 and 7 mm in LR, AP and SI directions, respectively.

Patients with metastatic gastric cancer had limited treatments and often had a somber prognosis, especially when patients were unable to tolerate high-intensity cytotoxic treatment due to poor physical condition or organ dysfunction after the failure of standard therapy. Here, we reported a metastatic and proficient mismatch repair (pMMR) gastric adenocarcinoma patient with the Eastern Cooperative Oncology Group (ECOG) performance status score of 2 associated with hypoproteinemia and fatigue, and poor appetite that was unable to tolerate high-intensity therapy after several chemotherapy regimens and anti-angiogenic therapy. After receiving novel triple-combination therapy, which consists of PD-1 inhibitor, Radiotherapy and Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy (PRaG for short), the patient achieved a complete response (CR) with a progression-free survival time of 14 months, and ECOG performance status score improved from 2 to 0. A significant systemic effect was observed in this case and the PRaG triple-combination therapy might provide a novel treatment strategy for metastatic pMMR gastric cancer patients.

Patients with metastatic cancer refractory to standard systemic therapies have a poor prognosis and few therapeutic options. Radiotherapy can shape the tumor microenvironment (TME) by inducing immunogenic cell death and promoting tumor recognition by natural killer cells and T lymphocytes. Granulocyte macrophage-colony stimulating factor (GM-CSF) was known to promote dendric cell maturation and function, and might also induce the macrophage polarization with anti-tumor capabilities. A phase II trial (ChiCTR1900026175) was conducted to assess the clinical efficacy and safety of radiotherapy, PD-1 inhibitor and GM-CSF (PRaG regimen). This trial was registered at http://www.chictr.org.cn/index.aspx. A PRaG cycle consisted of 3 fractions of 5 or 8 Gy delivered for one metastatic lesion from day 1, followed by 200 μg subcutaneous injection of GM-CSF once daily for 2 weeks, and intravenous infusion of PD-1 inhibitor once within one week after completion of radiotherapy. The PRaG regimen was repeated every 21 days for at least two cycles. Once the PRaG therapy was completed, the patient continued PD-1 inhibitor monotherapy until confirmed disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). A total of 54 patients were enrolled with a median follow-up time of 16.4 months. The ORR was 16.7%, and the disease control rate was 46.3% in intent-to-treat patients. Median progression-free survival was 4.0 months (95% confidence interval [CI], 3.3 to 4.8), and median overall survival was 10.5 months (95% CI, 8.7 to 12.2). Grade 3 treatment-related adverse events occurred in five patients (10.0%) and grade 4 in one patient (2.0%). Therefore, the PRaG regimen was well tolerated with acceptable toxicity and may represent a promising salvage treatment for patients with chemotherapy-refractory solid tumors. It is likely that PRaG acts via heating upthe TME with radiotherapy and GM-CSF, which was further boosted by PD-1 inhibitors.

Abstract Objective We aimed to compare the dosimetric characteristics of 6‐MV flattening filter mode (FF) and flattening filter‐free mode (FFF) volumetric‐modulated arc therapy (VMAT) plans in preoperative radiotherapy for rectal cancer using an Edge linear accelerator. Methods Two‐arc FF‐VMAT and FFF‐VMAT plans were generated for 15 patients with rectal cancer using the Philips Pinnacle treatment planning system (version 9.10). The homogeneity index, conformity index, planning target volume covered by 105% isodose lines, organ‐at‐risk dosimetry characteristics, and monitor units (MUs) were compared between the plans. The results were analyzed using paired t‐tests. Results The conformity index of the FF‐VMAT plan and FFF‐VMAT plan were (0.93 ± 0.01) and (0.92 ± 0.02), and the homogeneity index of the two groups were (0.07 ± 0.03) and (0.08 ± 0.01), the differences were not statistically significant (both P > 0.05). The volume covered by 105% isodose lines of the FFF‐VMAT plan was significantly higher than that of the FF‐VMAT plan. The FFF‐VMAT plan required a higher monitor unit (t = 11.49, P = 0.002) and shorter beam‐on time (t = 5.78, P = 0.001) compared with the FF‐VMAT plan. There were no significant differences in the absolute volume receiving 30 Gy and 40 Gy of the bladder between the plans. The absolute volume receiving 30 Gy and absolute volume receiving 40 Gy of the intestine and colon in the FFF‐VMAT plan increased by 5.5% and 2.1% compared with those in the FF‐VMAT plans that increased by 7.2% and 2.2%, respectively (both P > 0.05). The absolute volume receiving 20 Gy of the left and right femoral head in the FFF‐VMAT plan decreased by 3.7% and 4.9% compared with those in the FF‐VMAT plans (P > 0.05). Conclusion Both FF‐VMAT and FFF‐VMAT plans met the clinical requirements.

Abstract Background Collecting (Bellini) duct carcinoma (CDC) is a highly malignant and rare kidney tumor. We report our 12-year experience with CDC and the results of a retrospective analysis of patients and tumor characteristics, clinical manifestations, and imaging features by computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT. Methods Retrospective examination of tumors between January 2007 and December 2019 identified 13 cases of CDC from three medical centers in northern China. All 13 patients underwent CT scan, among which eight underwent dynamic enhanced CT scan, two underwent PET/CT scan, and one underwent magnetic resonance cholangiopancreatography (MRCP) examination. The lesions were divided into nephritis type and mass type according to the morphology of the tumors. Results The study group included ten men and three women with an average age of 64.23 ± 10.74 years. The clinical manifestations were gross hematuria, flank pain, and waist discomfort. The mean tumor size was 8.48 ± 2.48 cm. Of the 13 cases, six (46.2%) were cortical-medullary involved type and seven (53.8%) were cortex–medullary–pelvis involved type. Eleven (84.6%) cases were nephritis type and two (15.4%) were mass type. The lesions appeared solid or complex solid and cystic on CT and MRI. The parenchymal area of the tumors showed isodensity or slightly higher density on unenhanced CT scan in the 13 cases. PET/CT in two cases showed increased radioactivity intake. Evidence of intra-abdominal metastatic disease was present on CT in nine (69.2%) cases. Conclusions The imaging characteristics of CDC differ from those of other renal cell carcinomas. In renal tumors located in the junction zone of the renal cortex and medulla that show unclear borders, slight enhancement, and metastases in the early stage, a diagnosis of CDC needs to be considered. PET/CT provides crucial information for the diagnosis of CDC, as well as for designing treatment strategies including surgery.

Abstract Background In China, more than 20 million patients with chronic hepatitis B need antiviral treatment. Side effects of antiviral treatment such as renal complications can be problematic, particularly in an aging population. Methods The data were retrospectively extracted from the hospital medical charts of five centers in eastern China from January 1 to December 31, 2018. Results A total of 8309 patients with CHB was enrolled in this study. The median age of the patients was 46 years. The prevalence of diabetes mellitus, hypertension, and hepatic cirrhosis was respectively 3.49%, 4.42%, and 23.72%. The prevalence of these comorbidities increased with age (P

BackgroundThe diabetes mellitus prevalence is rapidly increasing in most parts of the world and has become a vital health problem. Probiotic and herbal foods are valuable in the treatment of diabetes.Methods and performanceIn this study, Bacillus licheniformis (BL) and Astragalus membranaceus extract (AE) were given with food to InR[E19]/TM2 Drosophila melanogaster, and the blood glucose, antioxidation activity and intestinal microbiota were investigated. The obtained results showed that BA (BL and AE combination) supplementation markedly decreased the blood glucose concentration compared with the standard diet control group, accompanied by significantly increased enzymatic activities of catalase (CAT), decreased MDA levels and prolonged lifespan of InR[E19]/TM2 D. melanogaster. The treatments with BL, AE and BA also ameliorated intestinal microbiota equilibrium by increasing the population of Lactobacillus and significantly decreasing the abundance of Wolbachia. In addition, clearly different evolutionary clusters were found among the control, BL, AE and BA-supplemented diets, and the beneficial microbiota, Lactobacillaceae and Acetobacter, were found to be significantly increased in male flies that were fed BA. These results indicated that dietary supplementation with AE combined with BL not only decreased blood glucose but also extended the lifespan, with CAT increasing, MDA decreasing, and intestinal microbiota improving in InR[E19]/TM2 D. melanogaster.ConclusionThe obtained results showed that dietary supplementation with BL and AE, under the synergistic effect of BL and AE, not only prolonged the lifespan of InR[E19]/TM2 D. melanogaster, increased body weight, and improved the body's antiaging enzyme activity but also effectively improved the types and quantities of beneficial bacteria in the intestinal flora of InR[E19]/TM2 D. melanogaster to improve the characteristics of diabetes symptoms. This study provides scientific evidence for a safe and effective dietary therapeutic method for diabetes mellitus.

Calcium and oxygen are abundant elements in the Earth’s mantle, largely present as calcium oxide. Here the authors show, by experiments and computations, that calcium ozonide (CaO3) is stabilized at the high pressures and temperatures characteristic of the lower mantle, with implications for the deep Earth’s chemistry.

Helium is generally considered too inert to be present in giant ice planet mantles. The authors, by first-principles calculations and crystal structure searches, find stable ammonia–helium compounds at the conditions of Uranus and Neptune’s upper mantles, with possible implications in the planet composition models.

A novel β-cyclodextrin pendant polymer (ε-PL-CD), composed of poly(ε-lysine) (ε-PL) main chain and glycine-β-cyclodextrin (Gly-CD) side chains, was prepared by a simple two-step procedure. The ε-PL-CD was investigated as a drug carrier of hydrophobic drug scutellarin (SCU). The characterization and complexation mode of the SCU:ε-PL-CD were researched in both solution and solid state by means of photoluminescence spectroscopy, 1H and 2D NMR, X-Ray powder diffraction (XRPD), thermal gravimetric analysis, Particle size and Zeta potential. The solubility test indicated that the solubilizing ability of SCU:ε-PL-CD was significantly improved compared with SCU:β-CD and free SCU. Besides, in vitro cell experiment, it was found that SCU:ε-PL-CD has a strong inhibitory effect on the growth and invasion of tumor cells. The present study provides useful information for ε-PL-CD as a drug carrier material.

We, the Editors and Publisher of the journal Artificial Cells, Nanomedicine, and Biotechnology, have retracted the following article:Meiling Xu, Shuangyan Zhang, Hong Zhao, Chi Ma & Yujun Pan (2019) Association between nucleotide-binding oligomerization domain protein 2 (NOD2) gene polymorphisms and Parkinson’s disease (PD) susceptibility. Artificial Cells, Nanomedicine, and Biotechnology, 47:1, 2134–2138, DOI: https://doi.org/10.1080/21691401.2019.1617730It has come to our attention that the full authorship list and affiliations for this manuscript were changed after the article was submitted. In addition, the location of the study site and the ethics committee were also changed. We have contacted the authors for an explanation, but we have not received a response within the requested timeframe. As determining authorship and the location of where the research was conducted, is core to the integrity of published work, we are therefore retracting the article. The authors listed in this publication have been sent notification.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

This paper aims to investigate the physical and 3D printing properties of arrowroot starch (AS), a natural biopolymer with many potential health benefits. Scanning electron microscopy images showed that AS granules had mixed spherical and elongated geometries, with average sizes of 10.5 ± 2.5 μm. The molecular weight of AS measured by gel permeation chromatography (GPC) was 3.24 × 107 g/mol, and the amylose/amylopectin ratio of AS was approximately 4:11. AS has an A-type crystal structure, with a gelatinization temperature of 71.8 ± 0.2 °C. The overlap concentration (C*) of AS in aqueous solutions was 0.42% (w/v). Temperature-dependent dynamic rheological analyses of 10% to 30% (w/v) AS fluids showed that the storage modulus (G’) reached the maximum values around the gelatinization temperatures, while the yield stress (τy) and flow stress (τf) values all increased with the increase in AS concentration. The printing accuracy of AS gels was found to be associated with the interplay between the G’ values and the restorability after extrusion, determined by the three-interval thixotropy tests (3ITT). The optimum 3D printing condition occurred at 20% (w/v) AS, the nozzle diameter of 0.60 mm, the printing speed of 100 mm/s and the extrusion speed of 100 mm/s. Our research provides a promising biopolymer to be used in the design of novel personalized functional foods.

Visual saliency (VS) is an important mechanism for defining which areas of an image will attract more attention of the HVS. Thus, VS can be employed to weight the just noticeable difference (JND) with different attention levels. Some VS-based JND profiles have been proposed in the DCT domain, which used the bottom-up features, such as luminance and texture only. Recently, the research about saliency detection has shown that a better saliency model considering both bottom-up features and top-down features will lead to a significant improvement for the overall saliency detection performance. In this paper, we propose a novel two-layer VS-induced JND profile, which is composed of the bottom-up features and the top-down feature extracted from DCT blocks in the transformed domain. In this model, the luminance and texture features are adapted to calculate the bottom-up features maps, while the top-down feature of focus is used to guide the generation of final salient regions since the camerapersons are used to facilitate the attention regions in focus. The proposed two-layer saliency-induced JND model is further applied to modulate the quantization step in the watermarking framework, which can make full use of its individual merits to achieve a better tradeoff between fidelity and robustness. The experimental results show that the proposed scheme has superior performance than the previous watermarking schemes.

Abstract Background The majority of ruptured intracranial aneurysms are combined with subarachnoid hemorrhage, but patients with only intracerebral hematoma without any subarachnoid hemorrhage are extremely rare. Case presentation The patient was hospitalized due to sudden dizziness combined with slurred speech. The patient showed considerable decreased physical activity without any nuchal rigidity. Head CT showed hematoma in the left temporal lobe, and the shape of hematoma was extremely irregular. MRI indicated the absence of any vascular malformations. The patient was diagnosed with middle cerebral artery bifurcation aneurysm in the left by head CTA. Intracranial aneurysm clip and removal of hematoma in the left temporal lobe were performed under general anesthesia. The patient did not show any significant neurological dysfunction after the surgery and was followed up for 4 months after discharge with GOS score of 5 points. Conclusions Intracranial hematoma with irregular morphology around the lateral fissure of the brain should be considered critical in order to avoid misdiagnosis and any possibility of missed diagnosis of vascular lesions, so as to ensure an exact therapeutic strategy with good prognosis for the patients.

Purpose: We aim to evaluate the robustness of multi-field IMRT and VMAT plans to target motion for left-sided BC radiotherapy. Methods: The 7-field hybrid IMRT (7F-H-IMRT) and 2-arc VMAT (2A-VMAT) plans were generated for ten left-sided BC patients. Shifts of 3 mm, 5 mm, and 10 mm in six directions were introduced and the perturbed dose distributions were recalculated. The dose differences (∆D) of the original plan and perturbed plan corresponded to the plan robustness for the structure. Results: Higher ∆D98%, ∆D95%, and ∆Dmean of CTV were observed in 2A-VMAT plans, which induced higher tumor control probability reductions. A higher ∆Dmean of CTV Boost was found in 7F-H-IMRT plans despite lower ∆D98% and ∆D95%. Shifts in the S-I direction exerted the largest effect on CTV and CTV Boost. Regarding OARs, shifts in R, P, and I directions contributed to increasing the received dose. The 2A-VMAT plans performed better dose sparing, but had a higher robustness in a high-dose volume of the left lung and heart. The 2A-VMAT plans decreased the max dose of LAD but exhibited lower robustness. Conclusion: The 2A-VMAT plans showed higher sensitivity to position deviation. Shifts in the S-I direction exerted the largest effect for CTV and CTV Boost.

Abstract Background Allopolyploids require rapid genetic and epigenetic modifications to reconcile two or more sets of divergent genomes. To better understand the fate of duplicate genes following genomic mergers and doubling during allopolyploid formation, in this study, we explored the global gene expression patterns in resynthesized allotetraploid Brassica napus (AACC) and its diploid parents B. rapa (AA) and B. oleracea (CC) using RNA sequencing of leaf transcriptomes. Results We found that allopolyploid B. napus formation was accompanied by extensive changes (approximately one-third of the expressed genes) in the parental gene expression patterns (‘transcriptome shock’). Interestingly, the majority (85%) of differentially expressed genes (DEGs) were downregulated in the allotetraploid. Moreover, the homoeolog expression bias (relative contribution of homoeologs to the transcriptome) and expression level dominance (total expression level of both homoeologs) were thoroughly investigated by monitoring the expression of 23,766 B. oleracea-B. rapa orthologous gene pairs. Approximately 36.5% of the expressed gene pairs displayed expression bias with a slight preference toward the A-genome. In addition, 39.6, 4.9 and 9.0% of the expressed gene pairs exhibited expression level dominance (ELD), additivity expression and transgressive expression, respectively. The genome-wide ELD was also biased toward the A-genome in the resynthesized B. napus. To explain the ELD phenomenon, we compared the individual homoeolog expression levels relative to those of the diploid parents and found that ELD in the direction of the higher-expression parent can be explained by the downregulation of homoeologs from the dominant parent or upregulation of homoeologs from the nondominant parent; however, ELD in the direction of the lower-expression parent can be explained only by the downregulation of the nondominant parent or both homoeologs. Furthermore, Gene Ontology (GO) enrichment analysis suggested that the alteration in the gene expression patterns could be a prominent cause of the phenotypic variation between the newly formed B. napus and its parental species. Conclusions Collectively, our data provide insight into the rapid repatterning of gene expression at the beginning of Brassica allopolyploidization and enhance our knowledge of allopolyploidization processes.

Abstract Background Meningeal carcinomatosis (MC) is characterized by diffuse infiltration of tumor cells in meninges. There is no tumor mass in the brain and parenchyma of the spinal cord. MC is divided into primary and metastatic types. MC cases were previously diagnosed postoperatively or at autopsy. Recent advances in spinal abbreviation cytology and imaging have led to increase in number of reported cases. In this study, we discuss the manifestations of MC patients based on magnetic resonance imaging (MRI) findings, as well as the correlation between the manifestations and pathology. Case presentation MC was confirmed in all three cases by lumbar puncture and gadopentetate dimeglumine-enhanced magnetic resonance imaging. Due to different primary diseases, the patients had specific imaging manifestations. Conclusion Enhanced MRI examination is extremely sensitive for detecting abnormalities in meninges, which plays a very important role in the diagnosis of MC. Since meninges of some MC patients cannot be enhanced, the enhanced MRI examination cannot be replaced by conventional cerebrospinal abbreviation examination. Attribute to the diversity of MR contrast agents, which could provide higher lesion conspicuity and enhances lesion detection, there may be some more choices to improve the detection rate of MC patients and prolong their survival lifetime.

The corrosion behavior of a medium-Mn steel in a simulated marine splash zone was studied by a dry–wet cyclic corrosion experiment and electrochemical experiment. The corrosion products were characterized by corrosion rate calculation, composition detection, morphology observation, element distribution detection, valence analysis, polarization curve, and electrochemical impedance test. The results show that the corrosion products of the sample mainly include γ-FeOOH, FexOy, MnxOy, and a small amount of (Fe,Mn)xOy, and the valence state of iron compounds and manganese compounds in different corrosion stages changed obviously. In the initial corrosion products, Mn is enriched significantly and facilitates the electrochemical reaction of corrosion process. The content of Ni in the inner rust layer is high. The semi-quantitative analysis of the corrosion product elements shows that the atomic concentrations of Cr and Mo increase significantly in later corrosion products, indicating that the dense isolation layer formed by alloy element compounds in the corroded layer is the main factor to improve the protection ability of the rust layer at the end corrosion stage of the sample. With the corrosion durations, the corrosion current density of the sample with the corrosion product film first increases and then decreases, and the corrosion potential first moves negative and then shifts in a positive direction subsequently, indicating that the protective effect of the corrosion product film is gradually significant.

The corrosion behavior of a high manganese steel in simulated marine splash zone environment was studied by dry-wet cyclic corrosion experiment and electrochemical experiment. Corrosion kinetics, composition, surface morphology, cross-section morphology, element distribution, valence state, polarization curve and electrochemical impedance spectroscopy were analyzed with the aim of characterizing the characteristics of corrosion product films. The results show that in chloride-containing environment, in the initial corrosion products, Mn oxides with porous structure lead to higher corrosion rate. As corrosion extends, the formation of alloy element oxides in corrosion products changes the corrosion properties of rust layers at different stages. Mo oxides form a stable passivation film, which reduces the influence of chloride ion on corrosion. Ni oxides in the inner rust layer facilitate the transformation of goethite, and Cr oxides in the outer rust layer increase the densification of the rust layer. The stability and compactness of Fe _3 O _4 , α -FeOOH and FeCr _2 O _4 in the later corrosion products inhibit the corrosion action of manganese iron oxides and slow down the corrosion rate. With the corrosion durations, the corrosion current density of the sample with the corrosion product film first increases and then decreases, and the corrosion potential first moves negative and then shifts in a positive direction subsequently, indicating that the protective effect of the corrosion product film is gradually significant.

The sacred lotus (Nelumbo nucifera Gaertn.) can produce heat autonomously and maintain a relatively stable floral chamber temperature for several days when blooming. Floral thermogenesis is critical for flower organ development and reproductive success. However, the regulatory role of microRNA (miRNA) underlying floral thermogenesis in N. nucifera remains unclear. To comprehensively understand the miRNA regulatory mechanism of thermogenesis, we performed small RNA sequencing and transcriptome sequencing on receptacles from five different developmental stages. In the present study, a total of 172 known miRNAs belonging to 39 miRNA families and 126 novel miRNAs were identified. Twenty-nine thermogenesis-related miRNAs and 3024 thermogenesis-related mRNAs were screened based on their expression patterns. Of those, seventeen differentially expressed miRNAs (DEMs) and 1765 differentially expressed genes (DEGs) had higher expression during thermogenic stages. The upregulated genes in the thermogenic stages were mainly associated with mitochondrial function, oxidoreductase activity, and the energy metabolism process. Further analysis showed that miR156_2, miR395a_5, miR481d, and miR319p may play an important role in heat-producing activity by regulating cellular respiration-related genes. This study provides comprehensive miRNA and mRNA expression profile of receptacle during thermogenesis in N. nucifera, which advances our understanding on the regulation of floral thermogenesis mediated by miRNA.

Accurate prediction of solar irradiance is beneficial in reducing energy waste associated with photovoltaic power plants, preventing system damage caused by the severe fluctuation of solar irradiance, and stationarizing the power output integration between different power grids. Considering the randomness and multiple dimension of weather data, a hybrid deep learning model that combines a gated recurrent unit (GRU) neural network and an attention mechanism is proposed forecasting the solar irradiance changes in four different seasons. In the first step, the Inception neural network and ResNet are designed to extract features from the original dataset. Secondly, the extracted features are inputted into the recurrent neural network (RNN) network for model training. Experimental results show that the proposed hybrid deep learning model accurately predicts solar irradiance changes in a short-term manner. In addition, the forecasting performance of the model is better than traditional deep learning models (such as long short term memory and GRU).

Pyropia yezoensis can survive the severe water loss that occurs during low tide, making it an ideal species to investigate the acclimation mechanism of intertidal seaweed to special extreme environments. In this study, we determined the effects of high salinity on photosynthesis using increasing salinity around algal tissues. Both electron transport rates, ETR (I) and ETR (II), showed continuous decreases as the salinity increased. However, the difference between these factors remained relatively stable, similar to the control. Inhibitor experiments illustrated that there were at least three different cyclic electron transport pathways. Under conditions of severe salinity, NAD(P)H could be exploited as an endogenous electron donor to reduce the plastoquinone pool in Py. yezoensis. Based on these findings, we next examined how these different cyclic electron transport (CETs) pathways were coordinated by cloning the gene (HM370553) for ferredoxin-NADP+ oxidoreductase (FNR). A phylogenetic tree was constructed, and the evolutionary relationships among different FNRs were evaluated. The results indicated that the Py. yezoensis FNR showed a closer relationship with cyanobacterial FNR. The results of both real-time polymerase chain reaction and western blotting showed that the enzyme was upregulated under 90–120‰ salinity. Due to the structure-function correlations in organism, Py. yezoensis FNR was proposed to be involved in NAD(P)H-dependent Fd+ reduction under severe salinity conditions. Thus, through the connection between different donors bridged by FNR, electrons were channeled toward distinct routes according to the different metabolic demands. This was expected to make the electron transfer in the chloroplasts become more flexible and to contribute greatly to acclimation of Py. yezoensis to the extreme variable environments in the intertidal zone.