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The development of protocols for the construction of congested quaternary centers is highly sought-after. Herein, we report a method for the cross-coupling of C(sp 3 ) tertiary Grignard reagents with C(sp 2 ) styrenyl bromides using readily available nickel precatalysts. We identified conditions that afford the products in practical yield for several combinations of electrophiles and nucleophiles, including sensitive α-magnesiated Grignard reagents. Dependent upon the nature of their substituents, regiodivergency was observed when α-vinyl bromides were employed.

The aim of this research was to examine the correlation between the exposure to bisphenol analogues (BPs), such as bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), and the risk of developing systemic lupus erythematosus (SLE). Ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was utilized to measure the levels of BPA, BPF, and BPS in the urine of 168 female participants diagnosed with SLE and 175 female participants who were deemed healthy controls. Logistic regression models were utilized to assess the connections between levels of bisphenol and the risk of SLE. The findings indicated that levels of BPA and BPF in the urine of individuals with SLE were markedly elevated compared to those in the control group. Higher exposure to BPA and BPF exhibited positive dose-response relationships with increased SLE risk. No significant associations were identified between BPS and the risk of SLE. These findings suggest exposure to BPA and BPF may be implicated as novel environmental triggers in the development of autoimmunity such as SLE. The significantly increased levels of these bisphenol analogues detected in SLE patients versus healthy controls, along with the associations between higher exposures and elevated SLE risk, which offers crucial hints for comprehending how endocrine-disrupting substances contribute to the genesis of autoimmune illnesses. Further research using robust longitudinal assessments of bisphenol analogue exposures is warranted to corroborate these epidemiological findings. Overall, this study highlights potential environmental risk factors for SLE while calling for additional investigation into the impact of bisphenol exposures on autoimmunity development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure to pesticides has been proposed to be a positive association in suicide and suicidality. Many studies have explored this topic, but have reported inconsistent findings. We carried out a systematic review and meta-analysis of the now existing evidence on the association between pesticide exposure and the risk of suicide and suicidality. We searched PubMed, EMBASE and Web of Science databases for studies published up to February 1, 2023. For studies that provided detailed data, we applied quantitative meta-analysis to calculate Odds ratio (OR) with 95% Confidence Intervals (CIs) to evaluate the results. Heterogeneity among the included studies was assessed using Cochran's Q test, I 2 statistic and tau-squared (τ 2 ). Publication bias was evaluated by funnel plots, Egger's test, and Begg's test. In addition, subgroup analyses according to pesticides category and geographical area were performed. 2906 studies were initially identified, and 20 studies were eventually included. Fifteen of the studies were on suicide deaths and suicide attempts, and five were on suicidal ideation. Pesticide exposure was positively related to suicide deaths and suicide attempts (pooled OR = 1.31; 95%CI: 1.04-1.64, p < 0.001) and suicidal ideation (pooled OR = 2.43; 95%CI: 1.51-3.91, p = 0.015). In the subgroup analysis, mixed pesticide type (pooled OR = 1.55; 95%CI: 1.39-1.74) increased the risk of suicide deaths and suicide attempts. The results of the analysis by geographic area showed that the risk of suicide deaths and suicide attempts with pesticide exposure was 2.27 (95%CI = 1.36-3.78), and 1.33 (95%CI = 1.14-1.56) in Asia and Europe, respectively. The risk of suicidal ideation caused by pesticide exposure in Asia and America were 2.19 (95%CI = 1.08-4.42) and 2.99 (95%CI = 1.76-5.06). In conclusion, pesticide exposure may increase the risk of suicide and suicidality based on the current evidence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: We assessed whether perioperative circulating tumor DNA (ctDNA) could be a biomarker for early detection of molecular residual disease (MRD) and prediction of postoperative relapse in resected non-small cell lung cancer (NSCLC)., Experimental Design: Based on our prospective, multicenter cohort on dynamic monitoring of ctDNA in lung cancer surgery patients (LUNGCA), we enrolled 950 plasma samples obtained at three perioperative time points (before surgery, 3 days and 1 month after surgery) of 330 stage I-III NSCLC patients (LUNGCA-1), as a part of the LUNGCA cohort. Using a customized 769-gene panel, somatic mutations in tumor tissues and plasma samples were identified with next-generation sequencing and utilized for ctDNA-based MRD analysis., Results: Preoperative ctDNA positivity was associated with lower recurrence-free survival (RFS; HR = 4.2; P < 0.001). The presence of MRD (ctDNA positivity at postoperative 3 days and/or 1 month) was a strong predictor for disease relapse (HR = 11.1; P < 0.001). ctDNA-based MRD had a higher relative contribution to RFS prediction than all clinicopathologic variables such as the TNM stage. Furthermore, MRD-positive patients who received adjuvant therapies had improved RFS over those not receiving adjuvant therapy (HR = 0.3; P = 0.008), whereas MRD-negative patients receiving adjuvant therapies had lower RFS than their counterparts without adjuvant therapy (HR = 3.1; P < 0.001). After adjusting for clinicopathologic variables, whether receiving adjuvant therapies remained an independent factor for RFS in the MRD-positive population (P = 0.002) but not in the MRD-negative population (P = 0.283)., Conclusions: Perioperative ctDNA analysis is effective in early detection of MRD and relapse risk stratification of NSCLC, and hence could benefit NSCLC patient management., (©2021 American Association for Cancer Research.)

Objective: To investigate the changes in the cortical thickness of the region of interest (ROI) and plasma Aβ40, Aβ42, and phosphorylated Tau (P-Tau) concentrations in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) as the disease progressed with surface-based morphometry (SBM), to analyze the correlation between ROI cortical thickness and measured plasma indexes and neuropsychological scales, and to explore the clinical value of ROI cortical thickness combined with plasma Aβ40, Aβ42, and P-Tau in the early recognition and diagnosis of AD., Methods: This study enrolled 33 patients with AD, 48 patients with aMCI, and 33 healthy controls (normal control, NC). Concentration changes in plasma Aβ42, Aβ40, and P-Tau collected in each group were analyzed. Meanwhile, the whole brain T1 structure images (T1WI-3D-MPRAGE) of each group of patients were collected, and T1 image in AD-aMCI, AD-NC, and aMCI-NC group were analyzed and processed by SBM technology to obtain brain regions with statistical differences as clusters, and the cortical thickness of each cluster was extracted. Multivariate ordered logistic regression analysis was used to screen out the measured plasma indexes and the indexes with independent risk factors in the cortical thickness of each cluster. Three comparative receiver operating characteristic (ROC) curves of AD-aMCI, AD-NC, and aMCI-NC groups were plotted, respectively, to explore the diagnostic value of multi-factor combined prediction for cognitive impairment. The relationship between cortical thickness and plasma indexes, and between cortical thickness and Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores were clarified by Pearson correlation analysis., Results: Plasma Aβ40, Aβ42, and P-Tau proteins in the NC, aMCI, and AD groups increased with the progression of AD ( P < 0.01); cortical thickness reductions in the AD-aMCI groups and AD-NC groups mainly involved the bilateral superior temporal gyrus, transverse temporal gyrus, superior marginal gyrus, insula, right entorhinal cortex, right fusiform gyrus, and cingulate gyrus. However, there were no statistical significances in cortical thickness reductions in the aMCI and NC groups. The cortical thickness of the ROI was negatively correlated with plasma Aβ40, Aβ42, and P-Tau concentrations ( P < 0.05), and the cortical thickness of the ROI was positively correlated with MMSE and MoCA scores. Independent risk factors such as Aβ40, Aβ42, P-Tau, and AD-NC cluster 1R (right superior temporal gyrus, temporal pole, entorhinal cortex, transverse temporal gyrus, fusiform gyrus, superior marginal gyrus, middle temporal gyrus, and inferior temporal gyrus) were combined to plot ROC curves. The diagnostic efficiency of plasma indexes was higher than that of cortical thickness indexes, the diagnostic efficiency of ROC curves after the combination of cortical thickness and plasma indexes was higher than that of cortical thickness or plasma indexes alone., Conclusion: Plasma Aβ40, Aβ42, and P-Tau may be potential biomarkers for early prediction of AD. As the disease progressed, AD patients developed cortical atrophy characterized by atrophy of the medial temporal lobe. The combined prediction of these region and plasma Aβ40, Aβ42, and P-Tau had a higher diagnostic value than single-factor prediction for cognitive decline., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Qu, Ma, Xia, Cai, Han, Zhang, Gu and Ma.)

Small extracellular vesicles (sEVs) carry molecular information from their source cells and are desired biomarkers for cancer diagnosis. We establish a machine learning-assisted dual-marker detection method to analyze the expression of epidermal growth factor receptor (EGFR) and C-X-C chemokine receptor 4 (CXCR4) in serum sEVs for the diagnosis and prognosis prediction of non-small cell lung cancer (NSCLC). We find that the serum sEV EGFR and CXCR4 are significantly higher in advanced stage NSCLC (A/NSCLC) patients compared to early stage NSCLC (E/NSCLC) patients and the healthy donors (HDs). A receiver operating characteristic curve (ROC) analysis demonstrates that the combination of EGFR and CXCR4 in serum sEVs as an efficient diagnostic index and malignant degree indicator for NSCLC. Machine learning further shows a diagnostic accuracy of 97.4% for the training cohort and 91.7% for the validation cohort based on the combinational marker. Moreover, this machine leaning-assisted serum sEV analysis successfully predicts the possibility of tumor relapse in three NSCLC patients by comparing their serum sEVs before and three days after surgery. This study provides an intelligent serum sEV-based assay for the diagnosis and prognosis prediction of NSCLC, and will benefit the precision management of NSCLC.

Chinese yew ( Taxus wallichiana var. mairei ) is ranked as a rare and endangered plant of first-grade protection of China. It has been widely cultivated in 17 provinces of China over the past few decades. However, little is known about the dispersion, rewilding, and ecological influence of Chinese yew's offspring during cultivation. Here, we report a noteworthy case of this species, via ex situ conservation, which has successfully spread into different secondary forests, thus forming a stable regenerating population in eastern China. The establishment of this yew population, which has > 900 individuals and 7 ha area, can be ascribed to two key ecological factors: (1) secondary forest near the parent yews that provided suitable microhabitats in which progeny yews could germinate and grow, and (2) seed-foraging and transportation by native birds. Thus, this case may offer a pathway for conserving endangered Chinese Taxus species, which can attract frugivorous birds to disperse their seeds. In addition, it is necessary to monitor the growth performance of progeny population in the field., Competing Interests: The authors declare there are no competing interests., (©2021 Li et al.)

Multiple stressors associated with global change are influencing the phytoplankton taxonomic composition and biomass in plateau lakes, such as higher levels of ultraviolet radiation (UVR, 280-400 nm) and the risk of eutrophication. Although the restrictive effects of high UVR on phytoplankton are generally recognized, the effects will be impacted by the UVR levels of seasonal changes and the nutrient status. In this study, in situ phytoplankton productivity was measured seasonally under full solar radiation and only visible light (photosynthetically active radiation, PAR) conditions in the plateau oligotrophic Lake Fuxian, Southwest China. To determine the single effects of UVR and nutrient enrichment and their combined impact on phytoplankton communities, a mesocosm experiment (1 month) was conducted outdoors during late summer (rainy season). The interactive experiment was designed with two radiation treatments (UVR + PAR and PAR) and four nutrient treatments (raw water, nitrogen addition, phosphorus addition, nitrogen and phosphorus addition). Our results suggested that the response of phytoplankton to UVR depended largely on nutrient availability, which was embodied in the no significant responses of phytoplankton productivity and total biomass to UVR in the oligotrophic raw water from Lake Fuxian, but the positive responses of total biomass to UVR in the nutrient enrichment treatment. Furthermore, the response of phytoplankton to UVR was also taxa dependent. Chlorophytes and dinoflagellates showed positive response to UVR, whereas chrysophytes were quite sensitive to UVR; diatoms had no significant response to UVR under all nutrient conditions, while the response of cyanobacteria to UVR was highly dependent on nutrient status. This study highlights that the increase in nutrient concentrations in oligotrophic lake not only directly promotes the growth of phytoplankton but also combines with low UVR during summer to benefit the growth of eutrophic taxa based on the non-negative effect of UVR on total phytoplankton biomass and the positive effect on eutrophic taxa.

The epidermal growth factor receptor (EGFR) plays an important role in the proliferation of various cancers, and the expression level of EGFR in tumor tissues can provide a basis for the diagnosis and prognosis. Improving the detection technology of EGFR to achieve high sensitivity and faster speed will benefit the diagnosis of many types of tumors. Trace biological samples can be sensitively measured with terahertz (THz) metamaterial devices. Here, a bow-tie array THz metamaterial biosensor is presented and modified with gold nanoparticles (GNPs) and EGFR antibodies for specific EGFR detection. The effect of the size of the GNP on the sensitivity enhancement was also analyzed. Enhanced sensing for EGFR was achieved with the assistance of GNPs and EGFR antibodies. Importantly, the metamaterial functionalized by GNPs and antibodies with a bigger GNP diameter achieves a greater resonance frequency shift. The proposed metamaterial biosensor can also realize tiny-volume EGFR solution detection. Our proposed technique can therefore sense EGFR sensitively with high speed, and can potentially be applied to achieve quick and accurate detection of EGFR related tumors., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

We demonstrated a method of fabricating three-dimensional (3D) metal structures in hydrogels with good conductivity by using femtosecond laser ablation and electroplating. The hydrogel containing A g + was first ablated by a femtosecond laser to form microchannels with an entrance achieving surface and then sandwiched between the anode and cathode to operate electroplating. Silver structures were formed along the microchannel from the microchannel entrance close to the cathode due to reduction of A g + . The average resistivity of metal structures is measured to be about 4×10 -7 Ω m . A tetrahedron metallic microstructure embedded in hydrogel by this method was demonstrated to show its ability of 3D micromachining.

We herein report a general, practical, and highly efficient method for asymmetric synthesis of a wide range of chiral vicinal diamines via reductive coupling of imines templated by chiral diboron. The protocol features high enantioselectivity and stereospecificity, mild reaction conditions, simple operating procedures, use of readily available starting materials, and a broad substrate scope. The method signifies the generality of diboron-enabled [3,3]-sigmatropic rearrangement.

Complete and highly accurate reference genomes and gene annotations are indispensable for basic biological research and trait improvement of woody tree species. In this study, we integrated single-molecule sequencing and high-throughput chromosome conformation capture techniques to produce a high-quality and long-range contiguity chromosome-scale genome assembly of the soft-seeded pomegranate cultivar 'Tunisia'. The genome covers 320.31 Mb (scaffold N50 = 39.96 Mb; contig N50 = 4.49 Mb) and includes 33 594 protein-coding genes. We also resequenced 26 pomegranate varieties that varied regarding seed hardness. Comparative genomic analyses revealed many genetic differences between soft- and hard-seeded pomegranate varieties. A set of selective loci containing SUC8-like, SUC6, FoxO and MAPK were identified by the selective sweep analysis between hard- and soft-seeded populations. An exceptionally large selective region (26.2 Mb) was identified on chromosome 1. Our assembled pomegranate genome is more complete than other currently available genome assemblies. Our results indicate that genomic variations and selective genes may have contributed to the genetic divergence between soft- and hard-seeded pomegranate varieties., (© 2019 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Porous photocatalysts have attracted significant attention for their large specific surface area, numerous surface catalytic active sites, and high photocatalytic activity. In this study, porous SrTiO₃/TiO₂ composites were successfully fabricated through a hydrothermal approach utilizing porous TiO₂ as a substrate. The as-synthesized SrTiO₃/TiO₂ composites were then characterized by X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy, Brunauer-Emmett-Teller (BET), and ultraviolet-visible spectroscopy (UV-Vis) analysis. The results of SEM and BET indicate that such composites have a porous structure and large surface area. Compared to unadulterated TiO₂, SrTiO₃ /TiO₂ composites exhibit higher photocatalytic performance for the photodegradation of rhodamine B under UV-Vis irradiation. Additionally, it was found that when the content of SrTiO₃ reaches 20%, it achieves the maximum photodegradation efficiency of 98.6% under UV-Vis irradiation over 60 min. These results demonstrate that SrTiO₃/TiO₂ composites are a promising material in terms of environmental cleanliness.

To assess the seasonal and spatial variations and long-term trends in water optical properties in Lake Fuxian, investigations based on field work in four seasons and a long-term analysis of data from 1980 to 2014 were conducted. The results show that there was no significant variation in the euphotic depth (Z eu ) across the four seasons, and no significant correlations between Z eu and potential influencing factors in seasons other than summer, suggesting that the water itself may be a major factor regulating the Z eu in general. Nevertheless, significant differences in Z eu between the north region (NR) and the south region (SR) were observed in all seasonal tests except spring. This finding relates to a higher abundance of chromophoric dissolved organic matter (CDOM) in the NR due to runoff, especially in the rainy seasons (summer and autumn). CDOM and its terrigenous component had an important impact on Z eu in summer, with the highest precipitation, and impacts from suspended solids and non-algal particles were also found in the NR in summer. The Secchi disk depth in the lake decreased clearly over the years, with significantly negative correlations with the increasing permanganate index and air temperature, implying that organic contaminants (CDOM and/or phytoplankton) are important regulators of water transparency. We estimate that the combined effects of climate warming and changes in land use and land cover are also indirect regulating factors. These findings should be considered in the protection of Lake Fuxian, owing to the importance of light penetration in aquatic ecosystems., (Copyright © 2018. Published by Elsevier B.V.)

Folic acid-conjugated temozolomide (TMZ)-loaded chitosan nanoparticles (CS-TMZ-FLA-NP) were developed to target lung cancer in the anticipation that folic acid would increase the affinity of nanoparticles for cancer cells. CS-TMZ-FLA-NP showed the highest anti-proliferative effect on the lung cancer cells in comparison to free TMZ and CS-TMZ-NP (nanoparticles without folic acid). A cellular uptake assay was performed on two different cell lines, L132 and A549. Cellular uptake efficiencies of CS-TMZ-NP and CS-TMZ-FLA-NP were found to be concentration-dependent in both cell lines. CS-TMZ-FLA-NP produced a 2.5 fold greater accumulation of TMZ than CS-TMZ-NP in both cell lines. CS-TMZ-FLA-NP maintained a significantly higher deposition of TMZ in lung tissue (approximately 7.5 μg/g of lung tissue) when compared to free TMZ and CS-TMZ-NP. Mice treated with CS-TMZ-FLA-NP had a 100% survival rate with significant suppression of tumor growth. Histopathological and immunohistochemical studies also demonstrated that CS-TMZ-FLA-NP had superior anticancer activity compared to the other two treatments. Our results indicate that CS-TMZ-FLA-NP can effectively facilitate targeting to human lung cancer cell lines in vitro and to lung tumors in vivo in a sustained manner and so improve the therapeutic efficacy of TMZ., Competing Interests: CONFLICTS OF INTEREST The authors do not report any conflicts of interest with respect to this research.

Rechargeable lithium-iodine batteries with abundant raw materials and low cost are promising electrochemical energy storage systems. Herein, we demonstrate that anchoring iodine to N-doped hollow carbon fold-hemisphere (N-FHS) is highly efficient to overcome slow kinetics and low stability of iodine cathode in lithium-iodine batteries. For the first time, significant effects of carbon framework architecture on the lithium storage performance of iodine cathode are studied in detail. Notably, the fold-hemisphere (N-FHS) is more effective than the similar architectures, such as hollow sphere (N-S) or hemisphere (N-HS), in modifying slow ion transport capability and fast structure deterioration. The superior property of iodine@N-FHS is associated with its highly porous structure and strong interconnection to iodine. The iodine deterioration mechanism in lithium-iodine battery is analyzed, and the deterioration processes of iodine in different carbon frameworks during cycling are investigated. This work opens a new avenue to solve the key problems in lithium-iodine batteries, allowing it an important candidate for energy storage.

Mutations in epidermal growth factor receptor (EGFR) play critical roles in the pathogenesis of non-small cell lung cancer (NSCLC), and they are highly associated with sensitivity to tyrosine kinase inhibitors (TKIs). While the pathogenic and pharmacological characteristics of common mutations in EGFR have been thoroughly investigated, those of uncommon mutations remain to be elucidated. Traditional approaches to study common mutations by randomized controlled trials are not feasible for uncommon mutations owing to their rarity. Therefore, by systematically reviewing laboratory and clinical studies of the G719X mutation, one of the uncommon mutations, we concluded that the G719X mutation was intermediately sensitive to TKIs, with an average response rate of 35.1% (47/134). Moreover, accordingly, we proposed a comprehensive model to investigate uncommon mutations in EGFR. The model involves both basic and clinical components, composed of structural analyses, functional alterations, cell viabilities and animal models with various types of clinical studies. In this review, we systematically reviewed studies of the G719X mutation and put forward a research model that could be generalized to explore uncommon mutations in diseases associated with gene mutations.

The rapeseed branch angle is an important morphological trait because an adequate branch angle enables more efficient light capture under high planting densities. Here, we report that the average angle of the five top branches provides a reliable representation of the average angle of all branches. Statistical analyses revealed a significantly positive correlation between the branch angle and multiple plant-type and yield-related traits. The 60 K Brassica Infinium(®) single nucleotide polymorphism (SNP) array was utilized to genotype an association panel with 520 diverse accessions. A genome-wide association study was performed to determine the genetic architecture of branch angle, and 56 loci were identified as being significantly associated with the branch angle trait via three models, including a robust, novel, nonparametric Anderson-Darling (A-D) test. Moreover, these loci explained 51.1% of the phenotypic variation when a simple additive model was applied. Within the linkage disequilibrium (LD) decay ranges of 53 loci, we observed plausible candidates orthologous to documented Arabidopsis genes, such as LAZY1, SGR2, SGR4, SGR8, SGR9, PIN3, PIN7, CRK5, TIR1, and APD7. These results provide insight into the genetic basis of the branch angle trait in rapeseed and might facilitate marker-based breeding for improvements in plant architecture.