pathMap: a path-based mapping tool for long noisy reads with high sensitivity.

With the rapid development of single-molecule sequencing (SMS) technologies, the output read length is continuously increasing. Mapping such reads onto a reference genome is one of the most fundamental tasks in sequence analysis. Mapping sensitivity is becoming a major concern since high sensitivity can detect more aligned regions on the reference and obtain more aligned bases, which are useful for downstream analysis. In this study, we present pathMap, a novel k-mer graph-based mapper that is specifically designed for mapping SMS reads with high sensitivity. By viewing the alignment chain as a path containing as many anchors as possible in the matched k-mer graph, pathMap treats chaining as a path selection problem in the directed graph. pathMap iteratively searches the longest path in the remaining nodes; more candidate chains with high quality can be effectively detected and aligned. Compared to other state-of-the-art mapping methods such as minimap2 and Winnowmap2, experiment results on simulated and real-life datasets demonstrate that pathMap obtains the number of mapped chains at least 11.50% more than its closest competitor and increases the mapping sensitivity by 17.28% and 13.84% of bases over the next-best mapper for Pacific Biosciences and Oxford Nanopore sequencing data, respectively. In addition, pathMap is more robust to sequence errors and more sensitive to species- and strain-specific identification of pathogens using MinION reads.

FTO-mediated m6A mRNA demethylation aggravates renal fibrosis by targeting RUNX1 and further enhancing PI3K/AKT pathway.

Chronic kidney disease (CKD) is a global health burden, with ineffective therapies leading to increasing morbidity and mortality. Renal interstitial fibrosis is a common pathway in advanced CKD, resulting in kidney function and structure deterioration. In this study, we investigate the role of FTO-mediated N6-methyladenosine (m6A) and its downstream targets in the pathogenesis of renal fibrosis. M6A modification, a prevalent mRNA internal modification, has been implicated in various organ fibrosis processes. We use a mouse model of unilateral ureteral obstruction (UUO) as an in vivo model and treated tubular epithelial cells (TECs) with transforming growth factor (TGF)-ß1 as in vitro models. Our findings revealed increased FTO expression in UUO mouse model and TGF-ß1-treated TECs. By modulating FTO expression through FTO heterozygous mutation mice (FTO+/- ) in vivo and small interfering RNA (siRNA) in vitro, we observed attenuation of UUO and TGF-ß1-induced epithelial-mesenchymal transition (EMT), as evidenced by decreased fibronectin and N-cadherin accumulation and increased E-cadherin levels. Silencing FTO significantly improved UUO and TGF-ß1-induced inflammation, apoptosis, and inhibition of autophagy. Further transcriptomic assays identified RUNX1 as a downstream candidate target of FTO. Inhibiting FTO was shown to counteract UUO/TGF-ß1-induced RUNX1 elevation in vivo and in vitro. We demonstrated that FTO signaling contributes to the elevation of RUNX1 by demethylating RUNX1 mRNA and improving its stability. Finally, we revealed that the PI3K/AKT pathway may be activated downstream of the FTO/RUNX1 axis in the pathogenesis of renal fibrosis. In conclusion, identifying small-molecule compounds that target this axis could offer promising therapeutic strategies for treating renal fibrosis.

Activation of STING by the novel liposomal TLC388 enhances the therapeutic response to anti-PD-1 antibodies in combination with radiotherapy.

Current immune checkpoint inhibiters (ICIs) have contrasting clinical results in poorly immunogenic cancers such as microsatellite-stable colorectal cancer (MSS-CRC). Therefore, understanding and developing the combinational therapeutics for ICI-unresponsive cancers is critical. Here, we demonstrated that the novel topoisomerase I inhibitor TLC388 can reshape the tumor immune landscape, corroborating their antitumor effects combined with radiotherapy as well as immunotherapy. We found that TLC388 significantly triggered cytosolic single-stranded DNA (ssDNA) accumulation for STING activation, leading to type I interferons (IFN-Is) production for increased cancer immunogenicity to enhance antitumor immunity. TLC388-treated tumors were infiltrated by a vast number of dendritic cells, immune cells, and costimulatory molecules, contributing to the favorable antitumor immune response within the tumor microenvironment. The infiltration of cytotoxic T and NK cells were more profoundly existed within tumors in combination with radiotherapy and ICIs, leading to superior therapeutic efficacy in poorly immunogenic MSS-CRC. Taken together, these results showed that the novel topoisomerase I inhibitor TLC388 increased cancer immunogenicity by ssDNA/STING-mediated IFN-I production, enhancing antitumor immunity for better therapeutic efficacy in combination with radiotherapy and ICIs for poorly immunogenic cancer.

invMap: a sensitive mapping tool for long noisy reads with inversion structural variants.

MOTIVATION: Longer reads produced by PacBio or Oxford Nanopore sequencers could more frequently span the breakpoints of structural variations (SVs) than shorter reads. Therefore, existing long-read mapping methods often generate wrong alignments and variant calls. Compared to deletions and insertions, inversion events are more difficult to be detected since the anchors in inversion regions are nonlinear to those in SV-free regions. To address this issue, this study presents a novel long-read mapping algorithm (named as invMap). RESULTS: For each long noisy read, invMap first locates the aligned region with a specifically designed scoring method for chaining, then checks the remaining anchors in the aligned region to discover potential inversions. We benchmark invMap on simulated datasets across different genomes and sequencing coverages, experimental results demonstrate that invMap is more accurate to locate aligned regions and call SVs for inversions than the competing methods. The real human genome sequencing dataset of NA12878 illustrates that invMap can effectively find more candidate variant calls for inversions than the competing methods. AVAILABILITY AND IMPLEMENTATION: The invMap software is available at https://github.com/zhang134/invMap.git.

Large viewing angle integral imaging 3D display system based on a symmetrical compound lens array.

We propose a large viewing angle integral imaging 3D display system based on a symmetrical compound lens array (SCLA). The display system comprises a high-resolution 2D display panel, an SCLA, and a light shaping diffuser. The high-resolution 2D display panel presents an elemental image array, the SCLA modulates the light rays emitted from the 2D display panel to form 3D images in space, and the light shaping diffuser eliminates the gaps between 3D pixels of the 3D images. We find that the lateral aberration is a crucial factor that affects the resolution of the reconstructed 3D image. The symmetrical structure of the SCLA enables a reduced focal length and the elimination of lateral aberration, improving the viewing angle and the 3D image resolution simultaneously. The experimental results confirm that the proposed display system increases the viewing angle to 68.6°, achieving a comparable resolution of the full field of view while maintaining a simple structure.

The association between systemic inflammatory response index and contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. AIMS: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure. RESULTS: The incidence of CA-AKI was 6.1% (n = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p < 0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group. CONCLUSIONS: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.

Knowledge mapping analysis of safety ergonomics: a bibliometric study.

Although a significant attention, the field of safety ergonomics has not yet been systematically profiled based on recent studies. To fully understand the current research status, basis, hotspots, and development trends in the field, 533 documents from the Web of Science core database were used for knowledge mapping analysis by the bibliometric method. The study found that the USA is the top country in publications, and Tehran University is the institution with the highest number of publications. Ergonomics and Applied Economics are the authoritative safety ergonomics journals. Through co-occurrence and co-citation analysis, current safety ergonomics research is focussed on healthcare, product design, and occupational health and safety. The keyword timeline view indicates that the main research paths are occupational health and safety, and patient safety research. The analysis of burst keywords shows that safety ergonomics research in management, model design, and system design areas are research frontiers in the field.Practitioner summary: This paper presents a knowledge mapping of safety ergonomics research through bibliometric analysis. The research results show the research status, research hotspots, and research frontiers in the field of safety ergonomics, which provides a direction for other scholars to quickly understand the development of this field.

CRISPR/Gal4BD-Cas donor adapting systems based on miniaturized Cas proteins for improved gene editing.

Targeted precise point editing and knock-in can be achieved by homology-directed repair(HDR) based gene editing strategies in mammalian cells. However, the inefficiency of HDR strategies seriously restricts their application in precision medicine and molecular design breeding. In view of the problem that exogenous donor DNA cannot be efficiently recruited autonomously at double-stranded breaks(DSBs) when using HDR strategies for gene editing, the concept of donor adapting system(DAS) was proposed and the CRISPR/Cas9-Gal4BD DAS was developed previously. Due to the large size of SpCas9 protein, its fusion with the Gal4BD adaptor is inconvenient for protein expression, virus vector packaging and in vivo delivery. In this study, two novel CRISPR/Gal4BD-SlugCas9 and CRISPR/Gal4BD-AsCas12a DASs were further developed, using two miniaturized Cas proteins, namely SlugCas9-HF derived from Staphylococcus lugdunensis and AsCas12a derived from Acidaminococcus sp. Firstly, the SSA reporter assay was used to assess the targeting activity of different Cas-Gal4BD fusions, and the results showed that the fusion of Gal4BD with SlugCas9 and AsCas12a N-terminals had minimal distraction on their activities. Secondly, the HDR efficiency reporter assay was conducted for the functional verification of the two DASs and the corresponding donor patterns were optimized simultaneously. The results demonstrated that the fusion of the Gal4BD adaptor binding sequence at the 5'-end of intent dsDNA template (BS-dsDNA) was better for the CRISPR/Gal4BD-AsCas12a DAS, while for the CRISPR/Gal4BD-SlugCas9 DAS, the dsDNA-BS donor pattern was recommended. Finally, CRISPR/Gal4BD-SlugCas9 DAS was used to achieve gene editing efficiency of 24%, 37% and 31% respectively for EMX1, NUDT5 and AAVS1 gene loci in HEK293T cells, which was significantly increased compared with the controls. In conclusion, this study provides a reference for the subsequent optimization of the donor adapting systems, and expands the gene editing technical toolbox for the researches on animal molecular design breeding.

Orthogonal Radical and Cationic Single-Unit Monomer Insertions for Engineering Polymer Architectures.

The single-unit monomer insertion (SUMI), derived from living/controlled polymerization, can be directly functionalized at the end or within the chain of polymers prepared by living/controlled polymerization, offering potential applications in the preparation of polymers with complex architectures. Many scenarios demand the simultaneous incorporation of monomers suitable for different polymerization methods into complex polymers. Therefore, it becomes imperative to utilize SUMI technologies with diverse mechanisms, especially those that are compatible with each other. Here, we reported the orthogonal SUMI technique, seamlessly combining radical and cationic SUMI approaches. Through the careful optimization of monomer and chain transfer agent pairs and adjustments to reaction conditions, we can efficiently execute both radical and cationic SUMI processes in one pot without mutual interference. The utilization of orthogonal SUMI pairs facilitates the integration of radical and cationic reversible addition-fragmentation chain transfer (RAFT) polymerization in various configurations. This flexibility enables the synthesis of diblock, triblock, and star polymers that incorporate both cationically and radically polymerizable monomers. Moreover, we have successfully implemented a mixing mechanism of free radicals and cations in RAFT step-growth polymerization, resulting in the creation of a side-chain sequence-controlled polymer brushes.

Poor pretransplantation minimal residual disease clearance as an independent prognostic risk factor for survival in myelodysplastic syndrome with excess blasts: A multicenter, retrospective cohort study.

BACKGROUND: Minimal residual disease (MRD) is an important prognostic factor for survival in adults with acute leukemia. The role of pretransplantation MRD status in myelodysplastic syndrome with excess blasts (MDS-EB) is unknown. This study retrospectively analyzed the relationship between pretransplantation MRD status and long-term survival. MATERIALS AND METHODS: Patients with MDS-EB who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from March 5, 2005, to November 8, 2020, were included. The relationship between pretransplantation MRD status and long-term survival was analyzed using univariate and multivariate logistic regression models. RESULTS: Of 220 patients with MDS-EB who underwent allo-HSCT, 198 were eligible for inclusion in this multicenter, retrospective cohort study. Complete remission was attained in 121 (61.1%) patients, and 103 patients underwent detection of MRD pretransplantation, with 67 patients being MRD-positive and 36 patients being MRD-negative. The median follow-up time was 16 months, the median age was 41 years (6-65 years), and 58% of the patients were men. The 3-year disease-free survival (DFS) and overall survival (OS) probabilities for all patients were 70.1% and 72.9%, respectively. For patients in complete remission, the 3-year DFS and OS probabilities were 72.2% and 74.8%, respectively. Further analysis found that the 3-year DFS rates of MRD-negative and MRD-positive patients were 85.6% and 66.5% (p = .045), respectively, whereas the 3-year OS rates were 91.3% and 66.4% (p = .035), respectively. Univariate and multivariate analyses showed that poor pretransplantation MRD clearance was an independent prognostic risk factor for DFS and OS. CONCLUSION: Poor pretransplantation MRD clearance is an independent prognostic risk factor for long-term survival after allo-HSCT for patients with MDS-EB. PLAIN LANGUAGE SUMMARY: Poor minimal residual disease clearance pretransplanation is an independent prognostic risk factor for long-term survival after allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome with excess blasts.

Targeting CD73 increases therapeutic response to immunogenic chemotherapy by promoting dendritic cell maturation.

The CD39-CD73-adenosinergic pathway converts adenosine triphosphate (ATP) to adenosine for inhibiting anti-tumor immune responses. Therefore, targeting CD73 to reinvigorate anti-tumor immunity is considered the novel cancer immunotherapy to eradicate tumor cells. To fully understand the critical role of CD39/CD73 in colon adenocarcinoma (COAD), this study aims to comprehensive investigate the prognostic significance of CD39 and CD73 in stage I-IV COAD. Our data demonstrated that CD73 staining strongly marked malignant epithelial cells and CD39 was highly expressed in stromal cells. Attractively, tumor CD73 expression was significantly associated with tumor stage and the risk of distant metastasis, which suggested CD73 was as an independent factor for colon adenocarcinoma patients in univariate COX analysis [HR = 1.465, 95%CI = 1.084-1.978, p = 0.013]; however, high stromal CD39 in COAD patients was more likely to have favorable survival outcome [HR = 1.458, p = 1.103-1.927, p = 0.008]. Notably, high CD73 expression in COAD patients showed poor response to adjuvant chemotherapy and high risk of distant metastasis. High CD73 expression was inversely associated with less infiltration of CD45+ and CD8+ immune cells. However, administration with anti-CD73 antibodies significantly increased the response to oxaliplatin (OXP). Blockade of CD73 signaling synergistically enhanced OXP-induced ATP release, which is a marker of immunogenic cell death (ICD), promotes dendritic cell maturation and immune cell infiltration. Moreover, the risk of colorectal cancer lung metastasis was also decreased. Taken together, the present study revealed tumor CD73 expression inhibited the recruitment of immune cells and correlated with a poor prognosis in COAD patients, especially patients received adjuvant chemotherapy. Targeting CD73 to markedly increased the therapeutic response to chemotherapy and inhibited lung metastasis. Therefore, tumor CD73 may be an independent prognostic factor as well as the potential of therapeutic target for immunotherapy to benefit colon adenocarcinoma patients.

Comprehensive in silico analysis of glycosylphosphatidylinositol- anchored protein (GPI-AP) related genes expression profiles in human normal and cancer tissues.

In human cells, there are more than 146 glycosylphosphatidylinositol-anchored proteins (GPI-APs), including receptors, ligands, adhesion molecules and enzymes. The proteins are associated with membrane microdomains called lipid rafts through GPI, and plays a variety of important biological functions. At present, plenty of studies have been carried out on the biosynthesis of GPI-APs. The biosynthesis of GPI-APs requires at least 20 steps, and more than 40 GPI biosynthetic genes have been identified. However, it remains unclear how expression of GPI-AP related genes is regulated in normal and cancer tissues. In this study, we utilized gene expression data from both the TCGA database and GTEx portal to analysis the gene expression involved in GPI-AP biosynthesis and encoding GPI-APs in normal and cancer tissues. In order to perform a comprehensive analysis, we employed the GlycoMaple, a tool that is specifically designed to analyze glycosylation pathways. The results showed that compared with normal tissues, the expression of genes involved in GPI-AP biosynthesis in cancer tissues such as early glioma, glioblastoma multiforme, pancreatic cancer, testicular germ cell carcinoma, skin primary cutaneous melanoma and skin metastatic cutaneous melanoma, was changed significantly. Particularly, the expression of PIGY in these six cancers was increased. In addition, the expression of CD14, a GPI-AP gene, was increased in these six cancers. The expression of GAS1, GPC2 and GPC4 was increased only in early glioma and glioblastoma multiforme indicating that some GPI-APs such as GAS1 can be used as biomarkers of glioma. This study provides new insights into the expression of GPI-AP related genes in normal and cancer tissues, and lays a solid foundation for the development of GPI-APs as biomarkers.

Improving the Identification of Lysine-Acetylated Peptides Using a Molecularly Imprinted Monolith Prepared by a Deep Eutectic Solvent Monomer.

To overcome the identification challenge of low-abundance lysine acetylation (Kac), a novel approach based on a molecularly imprinted polymer (MIP) was developed to improve the extraction capacity of Kac peptides in real samples. Green deep eutectic solvents (DESs) were introduced and used as one of the synergistic functional monomers with zinc acrylate (ZnA). Glycine-glycine-alanine-lysine(ac)-arginine (GGAKacR) was chosen as a template and N,N'-methylenbisacrylamide (MBAA) was used as a cross-linker. The obtained GGAKacR-MIP had excellent selectivity for the template with an imprinting factor (IF) of up to 21.4. The histone digest addition experiment demonstrated that GGAKacR-MIP could successfully extract GGAKacR from a complex sample. Finally, the application to the extraction of Kac peptides from mouse liver protein digestion was studied in detail. The number of Kac peptides and Kac proteins identified was 130 and 110, which were 3.71-fold and 3.93-fold higher than those of the untreated sample. In addition, the number of peptides and proteins identified after treatment increased from 5535 and 1092 to 17 149 and 4037 (3.10-fold and 3.70-fold, respectively). The results showed that the obtained MIP may provide an effective technical tool for the identification of Kac-modification and peptide fractionation, as well as a potential approach for simultaneously identifying post-translational-modified proteomic and proteomic information.

Deletion of p38γ attenuates ethanol consumption- and acetaminophen-induced liver injury in mice through promoting Dlg1.

Acetaminophen (APAP) is one of the major causes of drug-induced acute liver injury, and ethanol may aggravate APAP-induced liver injury. The problem of ethanol- and APAP-induced liver injury becomes increasingly prominent, but the mechanism of ethanol- and APAP-induced liver injury remains ambiguous. p38γ is one of the four isoforms of P38 mitogen activated protein kinases, that contributes to inflammation in different diseases. In this study we investigated the role of p38γ in ethanol- and APAP-induced liver injury. Liver injury was induced in male C57BL/6 J mice by giving liquid diet containing 5% ethanol (v/v) for 10 days, followed by gavage of ethanol (25% (v/v), 6 g/kg) once or injecting APAP (200 mg/kg, ip), or combined the both treatments. We showed that ethanol significantly aggravated APAP-induced liver injury in C57BL/6 J mice. Moreover, the expression level of p38γ was up-regulated in the liver of ethanol-, APAP- and ethanol+APAP-treated mice. Knockdown of p38γ markedly attenuated liver injury, inflammation, and steatosis in ethanol+APAP-treated mice. Liver sections of p38γ-knockdown mice displayed lower levels of Oil Red O stained dots and small leaky shapes. AML-12 cells were exposed to APAP (5 mM), ethanol (100 mM) or combined treatments. We showed that P38γ was markedly increased in ethanol+APAP-treated AML-12 cells, whereas knockdown of p38γ significantly inhibited inflammation, lipid accumulation and oxidative stress in ethanol+APAP-treated AML-12 cells. Furthermore, we revealed that p38γ could combine with Dlg1, a member of membrane-associated guanylate kinase family. Deletion of p38γ up-regulated the expression level of Dlg1 in ethanol+APAP-treated AML-12 cells. In summary, our results suggest that p38γ functions as an important regulator in ethanol- and APAP-induced liver injury through modulation of Dlg1.

Copper-Catalyzed Difluoroalkylation Reaction.

This review describes recent advances in copper-catalyzed difluoroalkylation reactions. The RCF2 radical is generally proposed in the mechanism of these reactions. At present, various types of copper-catalyzed difluoroalkylation reactions have been realized. According to their characteristics, we classify these difluoroalkylation reactions into three types.

Deep learning modeling of public's sentiments towards temporal evolution of COVID-19 transmission.

Public sentiments towards global pandemics are important for public health assessment and disease control. This study develops a modularized deep learning framework to quantify public sentiments towards COVID-19, followed by leveraging the predicted sentiments to model and forecast the daily growth rate of confirmed COVID-19 cases globally, via a proposed G parameter. In the proposed framework, public sentiments are first modeled via a valence dimensional indicator, instead of discrete schemas, and are classified into 4 primary emotional categories: (a) neutral; (b) negative; (c) positive; (d) ambivalent, by using multiple word embedding models and classifiers for text sentiments analyses and classification. The trained model is subsequently applied to analyze large volumes (millions in quantity) of daily Tweets pertaining to COVID-19, ranging from 22 Jan 2020 to 10 May 2020. The results demonstrate that the global community gradually evokes both positive and negative sentiments towards COVID-19 over time compared to the dominant neural emotion at its inception. The predicted time-series sentiments are then leveraged to train a deep neural network (DNN) to model and forecast the G parameter by achieving the lowest possible mean absolute percentage error (MAPE) score of around 17.0% during the model's testing step with the optimal model configuration.

A CRISPR/Cas9-Gal4BD donor adapting system for enhancing homology-directed repair.

The fast-rising CRISPR-derived gene editing technologies has been widely used in the fields of life science and biomedicine, as well as plant and animal breeding. However, the efficiency of homology-directed repair (HDR), an important strategy for gene knock-in and base editing, remains to be improved. In this study, we came up with the term Donor Adapting System (DAS) to summarize those CRISPR/Cas9 systems modified with adaptor for driving aptamer-fused donor DNA. A set of CRISPR/Cas9-Gal4BD DAS was designed in our study. In this system, Gal4 DNA binding domain (Gal4BD) is used as adaptor to fuse with Cas9 protein, and Gal4 binding sequence (Gal4BS) is used as aptamer to bind to the double-stranded DNA (dsDNA) donor, in order to improve the HDR efficiency. Preliminary results from the HEK293T-HDR.GFP reporter cell line show that the HDR editing efficiency could be improved up to 2-4 times when donor homologous arms under certain length (100-60 bp). Further optimization results showed that the choice of fusion port and fusion linker would affect the expression and activity of Cas9, while the Cas9-Gal4BD fusion with a GGS5 linker was the prior choice. In addition, the HDR efficiency was likely dependent on the aptamer-dsDNA donor design, and single Gal4BD binding sequence (BS) addition to the 5'-end of intent dsDNA template was suggested. Finally, we achieved enhanced HDR editing on the endogenous AAVS1 and EMX1 sites by using the CRISPR/Gal4BD-Cas9 DAS, which we believe can be applied to facilitate animal molecular design breeding in the future.

[Characterization of Endocrine Glands Involved in Erdheim-Chester Disease].

Objective To investigate the clinical and imaging characteristics of endocrine glands involved in Erdheim-Chester disease (ECD).Methods A retrospective analysis was performed on 48 ECD cases pathologically diagnosed from January 2014 to October 2020 in Peking Union Medical College Hospital,including 22 cases of endocrine gland involvement.The clinical,imaging,and pathological characteristics were summarized. Results Pituitary was involved in 17 cases (17/48,35.4%),adrenal gland in 8 cases (8/48,16.7%),and both pituitary and adrenal gland in 3 cases (3/48,6.25%).The most common symptom in patients with pituitary involvement was central diabetes insipidus (13/17,76.5%),and the T1-weighted imaging showed posterior pituitary hypersignal disappearance,pituitary stalk thickening,and abnormally enhanced pituitary nodules.The most common symptom in patients with adrenal gland involvement was adrenal function reduction (3/8,37.5%),and the CT scanning showed diffuse thickening of adrenal glands.BRAF V600E mutation was positive in 13 (13/22,59.1%) cases with ECD involving endocrine glands.Conclusion Pituitary and adrenal glands are the most common sites of ECD involving endocrine glands.A definite diagnosis can be achieved by combining clinical,imaging,and pathological characteristics for timely treatment.

Leaf photosynthetic and anatomical insights into mechanisms of acclimation in rice in response to long-term fluctuating light.

Long-term fluctuating light (FL) conditions are very common in natural environments. The physiological and biochemical mechanisms for acclimation to FL differ between species. However, most of the current conclusions regarding acclimation to FL were made based on studies in algae or Arabidopsis thaliana. It is still unclear how rice (Oryza sativa L.) integrate multiple physiological changes to acclimate to long-term FL. In this study, we found that rice growth was repressed under long-term FL. By systematically measuring phenotypes and physiological parameters, we revealed that: (a) under short-term FL, photosystem I (PSI) was inhibited, while after 1-7 days of long-term FL, both PSI and PSII were inhibited. Higher acceptor-side limitation in electron transport and higher overall nonphotochemical quenching (NPQ) explained the lower efficiencies of PSI and PSII, respectively. (b) An increase in pH differences across the thylakoid membrane and a decrease in thylakoid proton conductivity revealed a reduction of ATP synthase activity. (c) Using electron microscopy, we showed a decrease in membrane stacking and stomatal opening after 7 days of FL treatment. Taken together, our results show that electron flow, ATP synthase activity and NPQ regulation are the major processes determining the growth performance of rice under long-term FL conditions.

A nickel-catalyzed silylation reaction of alkyl aryl sulfoxides with silylzinc reagents.

Ni(PEt3)Cl2-catalyzed silylation of alkyl aryl sulfoxides with silylzinc reagents was carried out. This protocol allows alkyl aryl sulfoxides to convert to arylsilicon compounds under mild reaction conditions, tolerates a range of functional groups and is suitable for a wide scope of substrates.