Copper-Catalyzed Multicomponent Coupling Reaction of Primary Aromatic Amines, Rongalite, and Alkynes: Access to N-Aryl Propargylamines.

In this work, a practical copper-catalyzed multicomponent coupling reaction of primary aromatic amines, rongalite, and alkynes for the direct synthesis of N-aryl propargylamines has been developed. This method could overcome the substrate limitation in A3 coupling reactions of primary aromatic amines, formaldehyde, and alkynes. Mechanistic studies revealed that rongalite acts as not only the active C1 unit but also the accelerator to activate the in situ-generated N-arylmethanimines for the coupling reaction with alkynes. This coupling reaction is highly efficient and features a broad substrate scope, as well as utility with scale-up synthesis and converting the corresponding product N-aryl propargylamines into useful heterocyclic skeletons.

The role and mechanisms of microvascular damage in the ischemic myocardium.

Following myocardial ischemic injury, the most effective clinical intervention is timely restoration of blood perfusion to ischemic but viable myocardium to reduce irreversible myocardial necrosis, limit infarct size, and prevent cardiac insufficiency. However, reperfusion itself may exacerbate cell death and myocardial injury, a process commonly referred to as ischemia/reperfusion (I/R) injury, which primarily involves cardiomyocytes and cardiac microvascular endothelial cells (CMECs) and is characterized by myocardial stunning, microvascular damage (MVD), reperfusion arrhythmia, and lethal reperfusion injury. MVD caused by I/R has been a neglected problem compared to myocardial injury. Clinically, the incidence of microvascular angina and/or no-reflow due to ineffective coronary perfusion accounts for 5-50% in patients after acute revascularization. MVD limiting drug diffusion into injured myocardium, is strongly associated with the development of heart failure. CMECs account for > 60% of the cardiac cellular components, and their role in myocardial I/R injury cannot be ignored. There are many studies on microvascular obstruction, but few studies on microvascular leakage, which may be mainly due to the lack of corresponding detection methods. In this review, we summarize the clinical manifestations, related mechanisms of MVD during myocardial I/R, laboratory and clinical examination means, as well as the research progress on potential therapies for MVD in recent years. Better understanding the characteristics and risk factors of MVD in patients after hemodynamic reconstruction is of great significance for managing MVD, preventing heart failure and improving patient prognosis.

Dissipative soliton resonance in a figure-eight multimode fiber laser.

We report, for the first time to the best of our knowledge, a spatiotemporal mode-locked (STML) multimode fiber laser based on nonlinear amplifying loop mirror (NALM), generating dissipative soliton resonance (DSR) pulses. Due to the complex filtering characteristics caused by the inherent multimode interference filtering structure and NALM in the cavity, the STML DSR pulse has wavelength tunable function. What's more, kinds of DSR pulses are also achieved, including multiple DSR pulses, and the period doubling bifurcations of single DSR pulse and multiple DSR pulses. These results contribute to further understand the nonlinear properties of STML lasers and may shed some light on improving the performance of the multimode fiber lasers.

Synthesis of primary propargylic alcohols from terminal alkynes using rongalite as the C1 unit.

Here, an efficient leaving group-activated methylene alcohol strategy for the preparation of primary propargyl alcohols from terminal alkynes by employing the bulk industrial product rongalite as the C1 unit has been described. The reaction avoids the low-temperature reaction conditions and inconvenient lithium reagents required for the classical method of preparing primary propargylic alcohols. Preliminary mechanistic studies showed that the reaction may not proceed via formaldehyde intermediates, but through the direct nucleophilic attack of the terminal alkyne on the carbon atom of rongalite by activation through SO2- as a leaving group.

Risk stratification of clinically relevant delayed gastric emptying after pancreaticoduodenectomy.

BACKGROUND: Delayed gastric emptying (DGE) remains one of the major complications after pancreaticoduodenectomy (PD), with discrepant reports of its contributing factors. This study aimed to develop a nomogram to identify potential predictors and predict the probability of DGE after PD. METHODS: This retrospective study enrolled 422 consecutive patients who underwent PD from January 2019 to December 2021 at our institution. The LASSO algorithm and multivariate logistic regression were performed to identify independent risk and protective factors associated with clinically relevant delayed gastric emptying (CR-DGE). A nomogram was established based on the selected variables. Then, the calibration curve, ROC curve, decision curve analysis (DCA), and clinical impact curve (CIC) were applied to evaluate the predictive performance of our model. Finally, an independent cohort of 45 consecutive patients from January 2022 to March 2022 was enrolled to further validate the nomogram. RESULTS: Among 422 patients, CR-DGE occurred in 94 patients (22.2%). A previous history of chronic gastropathy, intraoperative plasma transfusion ≥ 400 ml, end-to-side gastrointestinal anastomosis, intra-abdominal infection, incisional infection, and clinically relevant postoperative pancreatic fistula (CR-POPF) were identified as risk predictors. Minimally invasive pancreaticoduodenectomy (MIPD) was demonstrated to be a protective predictor of CR-DGE. The areas under the curve (AUCs) were 0.768 (95% CI, 0.706-0.830) in the development cohort, 0.766 (95% CI, 0.671-0.861) in the validation cohort, and 0.787 (95% CI, 0.633-0.940) in the independent cohort. Then, we built a simplified scale based on our nomogram for risk stratification. CONCLUSIONS: Our study identified seven predictors and constructed a validated nomogram that effectively predicted CR-DGE for patients who underwent PD.

Genetic Architecture Underlying Nascent Speciation-The Evolution of Eurasian Pigs under Domestication.

Speciation is a process whereby the evolution of reproductive barriers leads to isolated species. Although many studies have addressed large-effect genetic footprints in the advanced stages of speciation, the genetics of reproductive isolation in nascent stage of speciation remains unclear. Here, we show that pig domestication offers an interesting model for studying the early stages of speciation in great details. Pig breeds have not evolved the large X-effect of hybrid incompatibility commonly observed between "good species." Instead, deleterious epistatic interactions among multiple autosomal loci are common. These weak Dobzhansky-Muller incompatibilities confer partial hybrid inviability with sex biases in crosses between European and East Asian domestic pigs. The genomic incompatibility is enriched in pathways for angiogenesis, androgen receptor signaling and immunity, with an observation of many highly differentiated cis-regulatory variants. Our study suggests that partial hybrid inviability caused by pervasive but weak interactions among autosomal loci may be a hallmark of nascent speciation in mammals.

Narrow bandwidth spatiotemporal mode-locked Yb-doped fiber laser.

We report a narrow bandwidth spatiotemporal mode-locked (STML) ytterbium-doped fiber laser, based on a homemade carbon nanotube/polyvinyl alcohol composite film and the multimode interference filtering effect. The wavelength-tunable narrow bandwidth STML operations combined with different pulse states are achieved, including single pulse, multiple pulses, and harmonics. The 3-dB bandwidth at the single-pulse state is 103 pm, while at the harmonic state, it is as narrow as 26 pm. To give an insight into the generation of the narrow bandwidth STML pulses, numerical simulations are performed. Such a laser has a wide range of potential applications in fields of optical communication and optical measurement, as well as provides a favorable platform for studying the evolution dynamics of multimode solitons.

Discovery of a major QTL for root-knot nematode (Meloidogyne incognita) resistance in cultivated sweetpotato (Ipomoea batatas).

KEY MESSAGE: Utilizing a high-density integrated genetic linkage map of hexaploid sweetpotato, we discovered a major dominant QTL for root-knot nematode (RKN) resistance and modeled its effects. This discovery is useful for development of a modern sweetpotato breeding program that utilizes marker-assisted selection and genomic selection approaches for faster genetic gain of RKN resistance. The root-knot nematode [Meloidogyne incognita (Kofoid & White) Chitwood] (RKN) causes significant storage root quality reduction and yields losses in cultivated sweetpotato [Ipomoea batatas (L.) Lam.]. In this study, resistance to RKN was examined in a mapping population consisting of 244 progenies derived from a cross (TB) between 'Tanzania,' a predominant African landrace cultivar with resistance to RKN, and 'Beauregard,' an RKN susceptible major cultivar in the USA. We performed quantitative trait loci (QTL) analysis using a random-effect QTL mapping model on the TB genetic map. An RKN bioassay incorporating potted cuttings of each genotype was conducted in the greenhouse and replicated five times over a period of 10 weeks. For each replication, each genotype was inoculated with ca. 20,000 RKN eggs, and root-knot galls were counted ~62 days after inoculation. Resistance to RKN in the progeny was highly skewed toward the resistant parent, exhibiting medium to high levels of resistance. We identified one major QTL on linkage group 7, dominant in nature, which explained 58.3% of the phenotypic variation in RKN counts. This work represents a significant step forward in our understanding of the genetic architecture of RKN resistance and sets the stage for future utilization of genomics-assisted breeding in sweetpotato breeding programs.

The recombination landscape and multiple QTL mapping in a Solanum tuberosum cv. 'Atlantic'-derived F1 population.

There are many challenges involved with the genetic analyses of autopolyploid species, such as the tetraploid potato, Solanum tuberosum (2n = 4x = 48). The development of new analytical methods has made it valuable to re-analyze an F1 population (n = 156) derived from a cross involving 'Atlantic', a widely grown chipping variety in the USA. A fully integrated genetic map with 4285 single nucleotide polymorphisms, spanning 1630 cM, was constructed with MAPpoly software. We observed that bivalent configurations were the most abundant ones (51.0~72.4% depending on parent and linkage group), though multivalent configurations were also observed (2.2~39.2%). Seven traits were evaluated over four years (2006-8 and 2014) and quantitative trait loci (QTL) mapping was carried out using QTLpoly software. Based on a multiple-QTL model approach, we detected 21 QTL for 15 out of 27 trait-year combination phenotypes. A hotspot on linkage group 5 was identified with co-located QTL for maturity, plant yield, specific gravity, and internal heat necrosis resistance evaluated over different years. Additional QTL for specific gravity and dry matter were detected with maturity-corrected phenotypes. Among the genes around QTL peaks, we found those on chromosome 5 that have been previously implicated in maturity (StCDF1) and tuber formation (POTH1). These analyses have the potential to provide insights into the biology and breeding of tetraploid potato and other autopolyploid species.

Quantitative Trait Locus Mapping for Common Scab Resistance in a Tetraploid Potato Full-Sib Population.

Despite the negative impact of common scab (Streptomyces spp.) on the potato industry, little is known about the genetic architecture of resistance to this bacterial disease in the crop. We evaluated a mapping population (∼150 full sibs) derived from a cross between two tetraploid potatoes ('Atlantic' × B1829-5) in three environments (MN11, PA11, ME12) under natural common scab pressure. Three measures to common scab reaction, namely percentage of scabby tubers and disease area and lesion indices, were found to be highly correlated (>0.76). Because of the large environmental effect, heritability values were zero for all three traits in MN11, but moderate to high in PA11 and ME12 (∼0.44 to 0.79). We identified a single quantitative trait locus (QTL) for lesion index in PA11, ME12, and joint analyses on linkage group 3, explaining ∼22 to 30% of the total variation. The identification of QTL haplotypes and candidate genes contributing to disease resistance can support genomics-assisted breeding approaches in the crop.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Sequencing depth and genotype quality: accuracy and breeding operation considerations for genomic selection applications in autopolyploid crops.

KEY MESSAGE: Polypoid crop breeders can balance resources between density and sequencing depth, dosage information and fewer highly informative SNPs recommended, non-additive models and QTL advantages on prediction dependent on trait architecture. The autopolyploid nature of potato and sweetpotato ensures a wide range of meiotic configurations and linkage phases leading to complex gene-action and pose problems in genotype data quality and genomic selection analyses. We used a 315-progeny biparental F1 population of hexaploid sweetpotato and a diversity panel of 380 tetraploid potato, genotyped using different platforms to answer the following questions: (i) do polyploid crop breeders need to invest more for additional sequencing depth? (ii) how many markers are required to make selection decisions? (iii) does considering non-additive genetic effects improve predictive ability (PA)? (iv) does considering dosage or quantitative trait loci (QTL) offer significant improvement to PA? Our results show that only a small number of highly informative single nucleotide polymorphisms (SNPs; ≤ 1000) are adequate for prediction in the type of populations we analyzed. We also show that considering dosage information and models considering only additive effects had the best PA for most traits, while the comparative advantage of considering non-additive genetic effects and including known QTL in the predictive model depended on trait architecture. We conclude that genomic selection can help accelerate the rate of genetic gains in potato and sweetpotato. However, application of genomic selection should be considered as part of optimizing the entire breeding program. Additionally, since the predictions in the current study are based on single populations, further studies on the effects of haplotype structure and inheritance on PA should be studied in actual multi-generation breeding populations.

Quantitative trait loci and differential gene expression analyses reveal the genetic basis for negatively associated ß-carotene and starch content in hexaploid sweetpotato [Ipomoea batatas (L.) Lam.].

KEY MESSAGE: ß-Carotene content in sweetpotato is associated with the Orange and phytoene synthase genes; due to physical linkage of phytoene synthase with sucrose synthase, ß-carotene and starch content are negatively correlated. In populations depending on sweetpotato for food security, starch is an important source of calories, while ß-carotene is an important source of provitamin A. The negative association between the two traits contributes to the low nutritional quality of sweetpotato consumed, especially in sub-Saharan Africa. Using a biparental mapping population of 315 F1 progeny generated from a cross between an orange-fleshed and a non-orange-fleshed sweetpotato variety, we identified two major quantitative trait loci (QTL) on linkage group (LG) three (LG3) and twelve (LG12) affecting starch, ß-carotene, and their correlated traits, dry matter and flesh color. Analysis of parental haplotypes indicated that these two regions acted pleiotropically to reduce starch content and increase ß-carotene in genotypes carrying the orange-fleshed parental haplotype at the LG3 locus. Phytoene synthase and sucrose synthase, the rate-limiting and linked genes located within the QTL on LG3 involved in the carotenoid and starch biosynthesis, respectively, were differentially expressed in Beauregard versus Tanzania storage roots. The Orange gene, the molecular switch for chromoplast biogenesis, located within the QTL on LG12 while not differentially expressed was expressed in developing roots of the parental genotypes. We conclude that these two QTL regions act together in a cis and trans manner to inhibit starch biosynthesis in amyloplasts and enhance chromoplast biogenesis, carotenoid biosynthesis, and accumulation in orange-fleshed sweetpotato. Understanding the genetic basis of this negative association between starch and ß-carotene will inform future sweetpotato breeding strategies targeting sweetpotato for food and nutritional security.

Linkage map construction and QTL analysis for internal heat necrosis in autotetraploid potato.

KEY MESSAGE: A tetraploid potato population was mapped for internal heat necrosis (IHN) using the Infinium ® 8303 potato SNP array, and QTL for IHN were identified on chromosomes 1, 5, 9 and 12 that explained 28.21% of the variation for incidence and 25.3% of the variation for severity. This research represents a significant step forward in our understanding of IHN, and sets the stage for future research focused on testing the utility of these markers in additional breeding populations. Internal heat necrosis (IHN) is a significant non-pathogenic disorder of potato tubers and previous studies have identified AFLP markers linked to IHN susceptibility in the tetraploid, B2721 potato mapping population. B2721 consists of an IHN susceptible×resistant cross: Atlantic×B1829-5. We developed a next-generation SNP-based linkage map of this cross using the Infinium® 8303 SNP array and conducted additional QTL analyses of IHN susceptibility in the B2721 population. Using SNP dosage sensitive markers, linkage maps for both parents were simultaneously analyzed. The linkage map contained 3427 SNPs and totaled 1397.68 cM. QTL were detected for IHN on chromosomes 1, 5, 9, and 12 using LOD permutation thresholds and colocation of high LOD scores across multiple years. Genetic effects were modeled for each putative QTL. Markers associated with a QTL were regressed in models of effects for IHN incidence and severity for all years. In the full model, the SNP markers were shown to have significant effects for IHN (p < 0.0001), and explained 28.21% of the variation for incidence and 25.3% of the variation for severity. We were able to utilize SNP dosage information to identify and model the effects of putative QTL, and identify SNP loci associated with IHN resistance that need to be confirmed. This research represents a significant step forward in our understanding of IHN, and sets the stage for future research focused on testing the utility of these markers in additional breeding populations.

Quantitative trait loci influencing forking defects in an outbred pedigree of loblolly pine.

BACKGROUND: The use of wood as an industrial raw material has led to development of plantation forestry, in which trees are planted, managed, and harvested as crops. The productivity of such plantations often exceeds that of less-intensively-managed forests, and land managers have the option of choosing specific planting stock to produce specific types of wood for industrial use. Stem forking, or division of the stem into two or more stems of roughly equal size, is a character trait important in determining the quality of the stem for production of solid wood products. This trait typically has very low individual-tree heritability, but can be more accurately assessed in clonally-replicated plantings where each genotype is represented by several individual trees. We report results from a quantitative trait mapping experiment in a clonally-replicated full-sibling family of loblolly pine (Pinus taeda L.). RESULTS: Quantitative trait loci influencing forking defects were identified in an outbred full-sibling family of loblolly pine, using single-nucleotide polymorphism markers. Genetic markers in this family segregated either in 1:2:1 (F2 intercross-like segregation) or 1:1 ratio (backcross-like segregation). An integrated linkage map combining markers with different segregation ratios was assembled for this full-sib family, and a total of 409 SNP markers were mapped on 12 linkage groups, covering 1622 cM. Two and three trait loci were identified for forking and ramicorn branch traits, respectively, using the interval mapping method. Three trait loci were detected for both traits using multiple-trait analysis. CONCLUSIONS: The detection of three loci for forking and ramicorn branching in a multiple-trait analysis could mean that there are genes with pleiotropic effects on both traits, or that separate genes affecting different traits are clustered together. The detection of genetic loci associated with variation in stem quality traits in this study supports the hypothesis that marker-assisted selection can be used to decrease the rate of stem defects in breeding populations of loblolly pine.

[Research on Quantitative Method for the Determination of Carbon Isotopic Composition of CO2 with Micro-Laser Raman Spectroscopy].

In this study, a series of 12CO2/N2 and 13CO2/N2 binary mixtures with various molar fraction ratios were synthesized. It was found that the Raman peak area ratios were proportional to molar fraction ratios. The linearity of the working curves was very good. Moreover, the slopes of working curves were regarded as Raman quantification factor (F12CO2 and F13CO2). The natural fluids only containing 12CO2 and N2 composition in the gas phase have been applied to estimate their molar fraction ratios when F12CO2 is 1.163 49. As F13CO2 and F12CO2 are equal to 1.610 86 and 1.163 49, their ratio (F13CO2/F12CO2) is 1.384 5. Based on the study of principles and feasibility of the method of laser Raman spectroscopy, the molar fraction ratio C12/C13 would be calculated using the product of A12CO2/A13CO2 (the ratio of Raman peak area) and F13CO2/F12CO2. In addition, man-made inclusions with known molar fraction ratios (C12/C13) were presented to testify the validity and precision of the method. The possibility of quantifying carbon isotopic composition of CO2 with Micro-Laser Raman Spectroscopy is demonstrated.

Metal-promoted intermolecular electron transfer in tetrathiafulvalene-thiacalix[4]arene conjugates and tetrachlorobenzoquinone.

In this work, two series of tetrathiafulvalene (TTF) and thiacalix[4]arene (TCA) conjugates (TTF-TCA) were designed by CuAAC click reactions. The results obtained from NMR and (1)H NMR NOE indicated that their conformations of thiacalix[4]arene framework may prefer to 1,3-alternate. The cyclic voltammograms of four TTF-TCA compounds containing electroactive TTF units were provided. Meanwhile, their intermolecular electron-transfer (ET) behaviors with tetrachlorobenzoquinone (Q) mediated by different metal ions, Sc(3+), Pb(2+), Ag(+), Cd(2+), and Zn(2+), in CH3CN-CH2Cl2 (V/V = 1:1) solution were studied and analyzed via UV-vis spectroscopy. It was determined that intermolecular ET between each TTF-TCA and Q ensemble was not observed without introduction of the metal ions mentioned above. The added specified metal ions most likely induced the intermolecular ET between TTF-TCA and Q ensemble, and the effects of Sc(3+) functions were the most imperative. The intermolecular ET also proved to be reliant on the structure of TTF-TCA, where TTF-TCA 7a and 7b were more effective than TTF-TCA 6a and 6b. The difference may be credited to TTF-TCA 7a or 7b possessing two independent TTF pendants and providing a more synergic coordination among the TTF radical cation and Q radical anion with a metal ion.

Mapping epistatic quantitative trait loci.

BACKGROUND: How to map quantitative trait loci (QTL) with epistasis efficiently and reliably has been a persistent problem for QTL mapping analysis. There are a number of difficulties for studying epistatic QTL. Linkage can impose a significant challenge for finding epistatic QTL reliably. If multiple QTL are in linkage and have interactions, searching for QTL can become a very delicate issue. A commonly used strategy that performs a two-dimensional genome scan to search for a pair of QTL with epistasis can suffer from low statistical power and also may lead to false identification due to complex linkage disequilibrium and interaction patterns. RESULTS: To tackle the problem of complex interaction of multiple QTL with linkage, we developed a three-stage search strategy. In the first stage, main effect QTL are searched and mapped. In the second stage, epistatic QTL that interact significantly with other identified QTL are searched. In the third stage, new epistatic QTL are searched in pairs. This strategy is based on the consideration that most genetic variance is due to the main effects of QTL. Thus by first mapping those main-effect QTL, the statistical power for the second and third stages of analysis for mapping epistatic QTL can be maximized. The search for main effect QTL is robust and does not bias the search for epistatic QTL due to a genetic property associated with the orthogonal genetic model that the additive and additive by additive variances are independent despite of linkage. The model search criterion is empirically and dynamically evaluated by using a score-statistic based resampling procedure. We demonstrate through simulations that the method has good power and low false positive in the identification of QTL and epistasis. CONCLUSION: This method provides an effective and powerful solution to map multiple QTL with complex epistatic pattern. The method has been implemented in the user-friendly computer software Windows QTL Cartographer. This will greatly facilitate the application of the method for QTL mapping data analysis.

IFIT1 modulates the proliferation, migration and invasion of pancreatic cancer cells via Wnt/ß-catenin signaling.

OBJECTIVES: Previously, Interferon-induced Protein with Tetratricopeptide Repeats 1 (IFIT1) has been shown to promote cancer development. Here, we aimed to explore the role of IFIT1 in the development and progression of pancreatic cancer, including the underlying mechanisms. METHODS: We explored IFIT1 expression in pancreatic cancer samples using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cell Counting Kit-8 (CCK8), colony formation, scratch wound-healing and Transwell assays were performed to assess the proliferation, migration and invasion abilities of pancreatic cancer cells. Gene Set Enrichment Analysis (GSEA) and Western blotting were performed to assess the regulatory effect of IFIT1 on the Wnt/ß-catenin pathway. RESULTS: We found that upregulation of IFIT1 expression is common in pancreatic cancer and is negatively associated with overall patient survival. Knockdown of IFIT1 expression led to decreased proliferation, migration and invasion of pancreatic cancer cells. We also found that IFIT1 could regulate Wnt/ß-catenin signaling, and that a Wnt/ß-catenin agonist could reverse this effect. In addition, we found that IFIT1 can promote epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. CONCLUSIONS: Our data indicate that IFIT1 increases pancreatic cancer cell proliferation, migration and invasion by activating the Wnt/ß-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer.

Real-World COPD Management Over 3 Years at the Community Health Service Center of Shanghai During the COVID-19 Pandemic in China.

Objective: To evaluate the real-world situation for the management of chronic obstructive pulmonary disease (COPD) and poorly controlled disease risk factors in the Chinese community. Methods: This retrospective multicentre study analysed data from COPDMICand MICHC in Shanghai Songjiang District, Shanghai, China. The differences in COPD Assessment Test (CAT), the modified Medical Research Council (mMRC) dyspnea scale, and the number of emergency cases, emergency visits, inpatient cases, and hospitalisations from January 2018 to December 2020 were analysed. The impact of coronavirus disease 2019 (COVID-19) on COPD management was also assessed. Results: For 2020 versus 2018, analysis of 468 COPD cases from COPDMIC matched with MICHC data showed significantly more patients with improved mMRC grades, significantly fewer emergency cases and emergency visits, and significantly fewer hospitalisation cases and hospitalisations. Differences in the number of emergency visits and hospitalisations per capita were statistically significant. Compared to GOLD 3-4, GOLD 1-2 patients showed significant improvements in CAT score, mMRC grade, the number of emergency visits and hospitalisations per capita. Treatment adherence from 2018 to 2020 was 25%, 29.1%, and 6.8%, and the proportion of medication regimens consistent with guidelines was 43.44%, 50.98%, and 71.87%, respectively. Higher treatment adherence resulted in significantly improved CAT scores and mMRC grades and fewer emergency department visits and hospitalisations per capita. Conclusion: Combined with remote management tools, patients with COPD achieved continuous improvement in symptoms and exacerbations over 3 years. In the context of COVID-19 prevention/control measures, improvements were significant for patients with GOLD 1-2 COPD but limited with GOLD 3-4. Pharmacologic treatment significantly improved clinical symptoms and reduced emergency visits and hospitalisations. Severe airflow limitation and poor adherence to pharmacologic treatment were important risk factors for lack of disease remission.

Prognostic value and immune infiltration of ARMC10 in pancreatic adenocarcinoma via integrated bioinformatics analyses.

Background: Armadillo repeat-containing 10 (ARMC10) is involved in the progression of multiple types of tumors. Pancreatic adenocarcinoma (PAAD) is a lethal disease with poor survival and prognosis. Methods: We acquired the data of ARMC10 in PAAD patients from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) datasets and compared the expression level with normal pancreatic tissues. We evaluated the relevance between ARMC10 expression and clinicopathological factors, immune infiltration degree and prognosis in PAAD. Results: High expression of ARMC10 was relevant to T stage, M stage, pathologic stage, histologic grade, residual tumor, primary therapy outcome (P < 0.05) and related to lower Overall-Survival (OS), Disease-Specific Survival (DSS), and Progression-Free Interval (PFI). Gene set enrichment analysis showed that ARMC10 was related to methylation in neural precursor cells (NPC), G alpha (i) signaling events, APC targets, energy metabolism, potassium channels and IL10 synthesis. The expression level of ARMC10 was positively related to the abundance of T helper cells and negatively to that of plasmacytoid dendritic cells (pDCs). Knocking down of ARMC10 could lead to lower proliferation, invasion, migration ability and colony formation rate of PAAD cells in vitro. Conclusions: Our research firstly discovered ARMC10 as a novel prognostic biomarker for PAAD patients and played a crucial role in immune regulation in PAAD.