Discrete Element Simulation of the Relationship between Composition, ITZ Property, and Tensile Behavior of Eco-Friendly UHPC Matrix

To combat global warming, the development of eco-friendly ultra-high performance concrete (UHPC) has become one of the current research hotspots. Understanding the relationship between composition and performance of eco-friendly UHPC from a meso-mechanical point will be of great significance in proposing a more scientific and effective mix design theory. In this paper, the 3D discrete element model (DEM) of an eco-friendly UHPC matrix was constructed. The mechanism of the effect of the interface transition zone (ITZ) properties on the tensile behavior of an eco-friendly UHPC matrix was studied. The relationship between composition, ITZ property, and tensile behavior of eco-friendly UHPC matrix was analyzed. The results show that ITZ strength influences the tensile strength and cracking behavior of eco-friendly UHPC matrix. The effect of ITZ on the tensile properties of eco-friendly UHPC matrix is more significant than that of normal concrete. The tensile strength of UHPC will be increased by 48% when the ITZ property is changed from normal condition to perfect. Improving the reactivity of the binder system of UHPC will improve the performance of ITZ. The cement content in UHPC was reduced from 80% to 35%, and the σITZ/σPaste was reduced from 0.7 to 0.32. Both nanomaterials and chemical activators can promote the hydration reaction of the binder material, which in turn leads to better ITZ strength and tensile properties for an eco-friendly UHPC matrix

Host Selection, Oviposition and Feeding by a Phytopathogen Vector, Diaphorina citri (Hemiptera: Liviidae), Modulated by Plant Exposure to Formic Acid

Citrus volatiles and their breakdown products, such as formic and acetic acids, guide host finding by Asian citrus psyllids (Diaphorina citri). Formic acid elicits psyllid antennal responses and stimulates probing. This study investigated how exposure to vapor phase formic acid induced changes in plant volatile emissions, expression of plant defense genes, and modified psyllid host finding and feeding behaviors on susceptible and resistant citrus cultivars. Chemical analyses of headspace volatiles and behavioral assays were performed before and after exposure of D. citri susceptible and resistant plants to vapor phase formic acid. RT-qPCR elucidated changes in plant defense-associated gene expression following exposure. Electrical Penetration Graph (EPG) measured D. citri feeding behavior on citrus with and without exposure to formic acid. Volatilized formic acid caused a 200–500% increase in release of citrus volatiles 1–3 h after exposure, increased attraction of D. citri to Poncirus trifoliata (resistant) and increased oviposition compared with controls. RT-qPCR showed significant increases in expression of WRKY22, GST1, RAR1, and EDS1 genes following exposure that also reduced phloem, but not xylem, ingestion by adult D. citri. Formic acid exposure caused increased citrus volatile release that modified host finding and feeding behaviors of an important phytopathogen vector

Case Report: ALK rearranged locally advanced lung adenocarcinoma showing inconsistent radiographic findings and pathological responses during neoadjuvant alectinib therapy

Alectinib has been approved as first-line treatment for anaplastic lymphoma kinase (ALK)-positive non-small cell lung carcinoma. Oncologists are also exploring the possibility of applying alectinib in the perioperative period. Here, we present a patient with locally advanced lung adenocarcinoma associated with EML4-ALK fusion mutation, who received neoadjuvant chemotherapy and alectinib treatment, and then underwent thoracoscopic left lower lung lobectomy. The patient initially received eight chemotherapy cycles and achieved partial remission. After eight cycles of chemotherapy, the lymph nodes in the hilar region again enlarged. The patient was then switched to 4 months of alectinib therapy, but no significant lesion changes were detected on imaging during this period. This raised the question of whether the patient developed alectinib resistance. The pathological findings of the postoperative lung lobe specimens indicated extensive necrosis in the tumor area with no residual tumor cells and massive chronic inflammatory cell infiltration around the tumor area, confirming inconsistency between the imaging findings and pathological results. Multi-point tumor specimen sampling was postoperatively performed. Tumor immune-related gene expression was detected in the sample with the help of the PanCancer IO360™ panel based on the nCounter platform. This is a rare case of a patient who was treated with neoadjuvant alectinib and had paradoxical radiographic findings and pathological responses. The possibility that intratumoral immune heterogeneity was responsible for this phenomenon has been discussed. Based on the findings, it is argued that the pathological response should be an important basis for assessing the effectiveness of neoadjuvant alectinib therapy

Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Flg22-triggered immunity correlates with canker resistance and Huanglongbing tolerance; the role of FLS2 in the improvement of citrus bacterial disease resistance

The bacterial agents of citrus canker (Xanthomonas citri ssp. citri, Xcc) and Huanglongbing (HLB) (Candidatus Liberibacter asiaticus, CLas) have caused tremendous economic losses to the citrus industry. Pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) is important to plant immunity. In this study, comparison of the defense response of citrus canker resistant and susceptible genotypes to the Xcc-derived PAMP, flg22 (Xflg22), and of HLB tolerant and sensitive genotypes to the CLas-derived flg22 (Lflg22), was performed by analyzing the expression of several citrus defense-associated genes. The Xflg22 treatment significantly induced the expression of EDS1, NDR1, PBS1, RAR1, SGT1, PAL1, NPR2 and NPR3 in the resistant ‘Nagami’ kumquat but not in the highly susceptible 'Duncan' grapefruit. Similarly, Lflg22 triggered gene transcriptional reprogramming in the HLB tolerant ‘Sun Chu Sha’ mandarin but not in the HLB sensitive ‘Duncan’ grapefruit. Moreover, Xflg22 induced a stronger oxidative burst and inhibited Xcc growth only in the canker resistant genotypes, and a flagellin-deficient Xcc strain (XccΔfliC) showed greater growth increase in the apoplast relative to wild-type Xcc in ‘Nagami’ kumquat than in ‘Duncan’ grapefruit. These results indicate that flg22 initiates PTI in canker resistant and HLB tolerant genotypes, but not in susceptible/sensitive ones, and that a robust induction of PTI is an important component of citrus resistance to bacterial diseases. In citrus, two flg22 receptor candidate genes (CiFLS2-1 and CiFLS2-2) were identified using the citrus genomic databases. The two FLS2s were sequenced from 7 citrus species and interestingly, only one FLS2 ( kqFLS2-1) was identified from ‘Nagami’ kumquat. For the protein function analysis of citrus FLS2s, we selected kqFLS2-1 (the only FLS2 in canker highly resistant ‘Nagami’ kumquat), mdFLS2-2 (highly Xflg22-inducible FLS2 in resistant ‘Sun Chu Sha’ mandarin) and gfFLS2-2 (highly Xflg22-inducible FLS2 in susceptible ‘Duncan’ grapefruit), and expressed them using an Agrobacterium-mediated transient expression system in ‘Duncan’ grapefruit. It was found that leaves expressing kqFLS2-1 and mdFLS2-2 conferred higher responsiveness to Xflg22 treatment than the ones expressing gfFLS2-2. This result suggests that kqFLS2-1 and mdFLS2-2 have potential for engineering enhanced PTI in susceptible citrus genotypes for the control of citrus canker and other bacterial diseases

Generation of Tunable Microwave Frequency Comb Utilizing a Semiconductor Laser Subject to Optical Injection from an SFP Module Modulated by an Arbitrary Periodic Signal

In this paper, a microwave frequency comb (MFC) is generated from a semiconductor laser subject to optical injection from a commercial small form-factor pluggable (SFP) optical module which is modulated by an arbitrary periodic signal. A sinusoidal signal or square wave signal is employed as the arbitrary periodic signal instead of the electric pulse signal adopted in the former references. When the frequency of the modulated signal is 1 GHz, the MFC with a maximal bandwidth of 15 GHz can be obtained. In addition, taking a sinusoidal signal as an example, the influence of the injection optical power to the slave laser and the modulation frequency of the optical module on the generation of the MFC is analyzed in detail. Finally, the results of MFC generated with a square wave signal injection are presented. The experimental results of this paper provide an important reference for the practical applications of MFC