Excess non-COVID-19-related mortality among inflammatory bowel disease decedents during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare in the United States. AIM: To investigate COVID-19-related and non-COVID-19-related death and characteristics associated with excess death among inflammatory bowel disease (IBD) decedents. METHODS: We performed a register-based study using data from the National Vital Statistics System, which reports death data from over 99% of the United States population, from January 1, 2006 through December 31, 2021. IBD-related deaths among adults 25 years and older were stratified by age, sex, race/ethnicity, place of death, and primary cause of death. Predicted and actual age-standardized mortality rates (ASMRs) per 100000 persons were compared. RESULTS: 49782 IBD-related deaths occurred during the study period. Non-COVID-19-related deaths increased by 13.14% in 2020 and 18.12% in 2021 [2020 ASMR: 1.55 actual vs 1.37 predicted, 95% confidence interval (CI): 1.26-1.49; 2021 ASMR: 1.63 actual vs 1.38 predicted, 95%CI: 1.26-1.49]. In 2020, non-COVID-19-related mortality increased by 17.65% in ulcerative colitis (UC) patients between the ages of 25 and 65 and 36.36% in non-Hispanic black (NHB) Crohn's disease (CD) patients. During the pandemic, deaths at home or on arrival and at medical facilities as well as deaths due to neoplasms also increased. CONCLUSION: IBD patients suffered excess non-COVID-19-related death during the pandemic. Excess death was associated with younger age among UC patients, and with NHB race among CD patients. Increased death at home or on arrival and due to neoplasms suggests that delayed presentation and difficulty accessing healthcare may have led to increased IBD mortality.

Profiling the role of m6A effectors in the regulation of pluripotent reprogramming.

The N6-methyladenosine (m6A) RNA modification plays essential roles in multiple biological processes, including stem cell fate determination. To explore the role of the m6A modification in pluripotent reprogramming, we used RNA-seq to map m6A effectors in human iPSCs, fibroblasts, and H9 ESCs, as well as in mouse ESCs and fibroblasts. By integrating the human and mouse RNA-seq data, we found that 19 m6A effectors were significantly upregulated in reprogramming. Notably, IGF2BPs, particularly IGF2BP1, were among the most upregulated genes in pluripotent cells, while YTHDF3 had high levels of expression in fibroblasts. Using quantitative PCR and Western blot, we validated the pluripotency-associated elevation of IGF2BPs. Knockdown of IGF2BP1 induced the downregulation of stemness genes and exit from pluripotency. Proteome analysis of cells collected at both the beginning and terminal states of the reprogramming process revealed that the IGF2BP1 protein was positively correlated with stemness markers SOX2 and OCT4. The eCLIP-seq target analysis showed that IGF2BP1 interacted with the coding sequence (CDS) and 3'UTR regions of the SOX2 transcripts, in agreement with the location of m6A modifications. This study identifies IGF2BP1 as a vital pluripotency-associated m6A effector, providing new insight into the interplay between m6A epigenetic modifications and pluripotent reprogramming.

Mechanisms underlying therapeutic resistance of tyrosine kinase inhibitors in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a malignant clonal disease involving hematopoietic stem cells that is characterized by myeloid cell proliferation in bone marrow and peripheral blood, and the presence of the Philadelphia (Ph) chromosome with BCR-ABL fusion gene. Treatment of CML has dramatically improved since the advent of tyrosine kinase inhibitors (TKI). However, there are a small subset of CML patients who develop resistance to TKI. Mutations in the ABL kinase domain (KD) are currently recognized as the leading cause of TKI resistance in CML. In this review, we discuss the concept of resistance and summarize recent advances exploring the mechanisms underlying CML resistance. Overcoming TKI resistance appears to be the most successful approach to reduce the burden of leukemia and enhance cures for CML. Advances in new strategies to combat drug resistance may rapidly change the management of TKI-resistant CML and expand the prospects for available therapies.

LncRNAs-circRNAs as Rising Epigenetic Binary Superstars in Regulating Lipid Metabolic Reprogramming of Cancers.

As one of novel hallmarks of cancer, lipid metabolic reprogramming has recently been becoming fascinating and widely studied. Lipid metabolic reprogramming in cancer is shown to support carcinogenesis, progression, distal metastasis, and chemotherapy resistance by generating ATP, biosynthesizing macromolecules, and maintaining appropriate redox status. Notably, increasing evidence confirms that lipid metabolic reprogramming is under the control of dysregulated non-coding RNAs in cancer, especially lncRNAs and circRNAs. This review highlights the present research findings on the aberrantly expressed lncRNAs and circRNAs involved in the lipid metabolic reprogramming of cancer. Emphasis is placed on their regulatory targets in lipid metabolic reprogramming and associated mechanisms, including the clinical relevance in cancer through lipid metabolism modulation. Such insights will be pivotal in identifying new theranostic targets and treatment strategies for cancer patients afflicted with lipid metabolic reprogramming.

Virulence Characterization of Puccinia striiformis f. sp. tritici in China Using the Chinese and Yr Single-Gene Differentials.

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most important diseases of wheat. Identifying Pst races is essential for developing resistant cultivars and managing the disease. In this study, 608 isolates collected from China in 2021 were tested with the Chinese set of 19 wheat variety differentials and the set of 18 Yr single-gene differentials. Of the 119 races detected with the Chinese set of differentials, 94 were new. A higher number (149) of races were identified using the Yr single-gene differentials. The frequencies of virulence factors to 17 of the 19 Chinese differential varieties and to 10 of the 18 Yr single-gene differentials were high (>60%). None of the isolates were virulent to the differentials Zhong 4 (Yr genes unknown) and Triticum spelta Album (Yr5) in the Chinese set and the Yr5 and Yr15 lines in the single-gene set of differentials, indicating that these genes or varieties are effective against the Pst population detected in 2021. Using Nei's genetic distance, the 16 provincial Pst populations were clustered into six groups based on the Chinese set and eight groups based on the Yr single-gene set of differentials. In addition, we found that the same races identified using the Chinese differentials could be further differentiated into different races using the Yr single-gene differentials, suggesting a higher differential capability than the Chinese set of differentials. The results provide a scientific basis for monitoring Pst populations and guiding resistance breeding in China.

Understanding the One Belt One Road Initiative (BRI) influence on exportations of Chinese smartphones: The moderating role of the GDP per capita.

The One Belt One Road Initiative (BRI) has been the subject of multitudinous studies from various angles. Most previous studies have focused on BRI's economic, geopolitical, or commercial implications for China. However, the few studies that focused on BRI's influence on the exportations or importations of Chinese products via the Chinese Cross-border Electronic Commerce Market (CCBECM) have been carried out based only on authors' opinions rather than on empirical evidence. Therefore, the actual effect of BRI on the exportations of Chinese product brands via CCBECM in BRI countries still needs to be discovered. Utilizing B2C exportation data of Chinese smartphones and a Difference-in Difference Model (DIDM), we have first examined the actual and direct impact of BRI policy on Chinese smartphone brands exportations via the Chinese Cross-border Electronic Commerce Market (CCBECM) from 2012 to 2019 in BRI countries. Secondly, we assessed the moderating role of GDP per capita (GDP) and Internet Access Rate (IAR) between BRI policy and exportations of Chinese smartphone brands. The results showed that the impact of BRI remains insignificant on the exportations of Chinese smartphones via CCBECM in BRI countries. However, it could be significant if BRI includes more developed and economically strong countries. The study also highlighted a negative moderating role of GDP per capita between BRI policy and exportations, showing that the higher the BRI effect is, the less GDP per capita will influence Chinese smartphone exportations in BRI countries.

Profiling mitochondria-polyribosome lncRNAs associated with pluripotency.

Pluripotent stem cells (PSCs) provide unlimited resources for regenerative medicine because of their potential for self-renewal and differentiation into many different cell types. The pluripotency of these PSCs is dynamically regulated at multiple cellular organelle levels. To delineate the factors that coordinate this inter-organelle crosstalk, we profiled those long non-coding RNAs (lncRNAs) that may participate in the regulation of multiple cellular organelles in PSCs. We have developed a unique strand-specific RNA-seq dataset of lncRNAs that may interact with mitochondria (mtlncRNAs) and polyribosomes (prlncRNAs). Among the lncRNAs differentially expressed between induced pluripotent stem cells (iPSCs), fibroblasts, and positive control H9 human embryonic stem cells, we identified 11 prlncRNAs related to stem cell reprogramming and exit from pluripotency. In conjunction with the total RNA-seq data, this dataset provides a valuable resource to examine the role of lncRNAs in pluripotency, particularly for studies investigating the inter-organelle crosstalk network involved in germ cell development and human reproduction.

Erratum: Genome-wide target interactome profiling reveals a novel EEF1A1 epigenetic pathway for oncogenic lncRNA MALAT1 in breast cancer.

[This corrects the article on p. 714 in vol. 9, PMID: 31105998.].

High-throughput RNA sequencing reveals differences between the transcriptomes of the five spore forms of Puccinia striiformis f. sp. tritici, the wheat stripe rust pathogen.

The devastating wheat stripe (yellow) rust pathogen, Puccinia striiformis f. sp. tritici (Pst), is a macrocyclic and heteroecious fungus. Pst produces urediniospores and teliospores on its primary host, wheat, and pycniospores and aeciospores are produced on its alternate hosts, barberry (Berberis spp.) or mahonia (Mahonia spp.). Basidiospores are developed from teliospores and infect alternate hosts. These five spore forms play distinct roles in Pst infection, disease development, and fungal survival, etc. However, the specific genes and mechanisms underlying these functional differences are largely unknown. In this study, we performed, for the first time in rust fungi, the deep RNA sequencing to examine the transcriptomic shift among all five Pst spore forms. Among a total of 29,591 identified transcripts, 951 were specifically expressed in basidiospores, whereas 920, 761, 266, and 110 were specific for teliospores, pycniospores, aeciospores, and urediniospores, respectively. Additionally, transcriptomes of sexual spores, namely pycniospores and basidiospores, showed significant differences from those of asexual spores (urediniospores, teliospores, and aeciospores), and transcriptomes of urediniospores and aeciospores were more similar to each other than to the three other spore forms. Especially, the basidiospores and pycniospores which infected the berberis shows wide differences in the cell wall degrading-enzymes and mating and pheromone response genes. Besides, we also found that there are 6234 differential expressed genes between the urediniospores and pycniospores, while only have 3 genes have alternative splicing enents, suggesting that differential genes expression may make more contribution than AS. This comprehensive transcriptome profiling can substantially improve our understanding of the developmental biology of the wheat stripe rust fungus.

Short-term antithrombotic strategies after left atrial appendage occlusion: a systematic review and network meta-analysis.

Background: Percutaneous left atrial appendage occlusion (LAAO) has emerged as a stroke prevention strategy in patients with nonvalvular atrial fibrillation (NVAF), and these patients were required to receive antithrombotic therapy post-procedure. However, the optimal antithrombotic strategy after LAAO remains controversial. This study explored the safety and efficacy of different antithrombotic strategies after LAAO through a network comparison method. Methods: We systematically searched the MEDLINE, Embase, and Cochrane Library databases for studies that reported the interested efficacy and safety outcomes (stroke, device-related thrombus (DRT), and major bleeding) of different antithrombotic strategies [DAPT (dual antiplatelet therapy), DOACs (direct oral anticoagulants), and VKA (vitamin k antagonist)] in patients who had experienced LAAO. Pairwise comparisons and network meta-analysis were performed for the interested outcomes. Risk ratios (RRs) with their confidence intervals (CIs) were calculated using a random-effects model. The rank of the different strategies was calculated using the surface under the cumulative ranking curve (SUCRA). Results: Finally, 10 observational studies involving 1,674 patients were included. There was no significant difference in stroke, DRT, and major bleeding among the different antithrombotic strategies (DAPT, DOACs, and VKA). Furthermore, DAPT ranked the worst in terms of stroke (SUCRA: 19.8%), DRT (SUCRA: 3.6%), and major bleeding (SUCRA: 6.6%). VKA appeared to be superior to DOACs in terms of stroke (SUCRA: 74.9% vs. 55.3%) and DRT (SUCRA: 82.3% vs. 64.1%) while being slightly inferior to DOACs in terms of major bleeding (SUCRA: 71.0% vs. 72.4%). Conclusion: No significant difference was found among patients receiving DAPT, DOACs, and VKA in terms of stroke, DRT, and major bleeding events after LAAO. The SUCRA indicated that DAPT was ranked the worst among all antithrombotic strategies due to the higher risk of stroke, DRT, and major bleeding events, while VKAs were ranked the preferred antithrombotic strategy. However, DOACs are worthy of consideration due to their advantage of convenience.

Microvascular decompression can effectively reduce arterial blood pressure in patients with Trigeminal Neuralgia.

BACKGROUND: Microvascular decompression (MVD) has been used in the treatment of Trigeminal Neuralgia (TN) and arterial hypertension (HTN). Results of several reports have supported its clinical effectiveness, however, little attention has been paid on arterial blood pressure changes caused by MVD in patients with TN. METHODS: In this single-center retrospective study, a cohort of 80 patients with TN who underwent MVD between 2021 and 2022 had been reviewed. Clinical data such as age, gender, pain duration, operation time, side and range of pain, HTN history, treatment history, VAS score, mean arterial pressure (MAP), and nausea or vomiting after operation were collected and analyzed via Linear regression to select possible related factors. Then, multiple linear regression of the possible predictors was used to identify the variables that significantly predicted MAP reduction. RESULTS: The VAS scores of TN patients after MVD surgery was significantly lower than that before operation, irrespective of the gender, side and range of pain, HTN history, RF history, and PONV (Wilcoxon test, P < 0.001). MVD can significantly decreased the blood pressure of TN patients, without interference from other factors. (MAP reduction ratio=14.46% ± 12.32%) (paired t-test, P < 0.001). The univariate and Multiple linear regression analysis showed that the preoperative MAP was significantly related to MAP reduction ratio (P < 0.001). CONCLUSIONS: In patients with TN, MVD can significantly decrease arterial blood pressure. Blood pressure reductions were more prominent when cases with higher preoperative MAP.

Precise in-field molecular diagnostics of crop diseases by smartphone-based mutation-resolved pathogenic RNA analysis.

Molecular diagnostics for crop diseases can guide the precise application of pesticides, thereby reducing pesticide usage while improving crop yield, but tools are lacking. Here, we report an in-field molecular diagnostic tool that uses a cheap colorimetric paper and a smartphone, allowing multiplexed, low-cost, rapid detection of crop pathogens. Rapid nucleic acid amplification-free detection of pathogenic RNA is achieved by combining toehold-mediated strand displacement with a metal ion-mediated urease catalysis reaction. We demonstrate multiplexed detection of six wheat pathogenic fungi and an early detection of wheat stripe rust. When coupled with a microneedle for rapid nucleic acid extraction and a smartphone app for results analysis, the sample-to-result test can be completed in ~10 min in the field. Importantly, by detecting fungal RNA and mutations, the approach allows to distinguish viable and dead pathogens and to sensitively identify mutation-carrying fungicide-resistant isolates, providing fundamental information for precision crop disease management.

Therapeutic potential of engineering the mitochondrial genome.

Mitochondrial diseases are a group of clinical disorders caused by mutations in the genes encoded by either the nuclear or the mitochondrial genome involved in mitochondrial oxidative phosphorylation. Disorders become evident when mitochondrial dysfunction reaches a cell-specific threshold. Similarly, the severity of disorders is related to the degree of gene mutation. Clinical treatments for mitochondrial diseases mainly rely on symptomatic management. Theoretically, replacing or repairing dysfunctional mitochondria to acquire and preserve normal physiological functions should be effective. Significant advances have been made in gene therapies, including mitochondrial replacement therapy, mitochondrial genome manipulation, nuclease programming, mitochondrial DNA editing, and mitochondrial RNA interference. In this paper, we review the recent progress in these technologies by focusing on advancements that overcome limitations.

Chromatin-RNA in situ Reverse Transcription Sequencing (CRIST-seq) Approach to Profile the Non-coding RNA Interaction Network.

Non-coding RNAs (ncRNAs) are defined as RNAs that do not encode proteins, but many ncRNAs do have the ability to regulate gene expression. These ncRNAs play a critical role in the epigenetic regulation of various physiological and pathological processes through diverse biochemical mechanisms. However, the existing screening methods to identify regulatory ncRNAs only focus on whole-cell expression levels and do not capture every ncRNA that targets certain genes. We describe a new method, chromatin-RNA in situ reverse transcription sequencing (CRIST-seq), that can identify all the ncRNAs that are associated with the regulation of any given gene. In this article, we targeted the ncRNAs that are associated with pluripotent gene Sox2, allowing us to catalog the ncRNA regulation network of pluripotency maintenance. This methodology is universally applicable for the study of epigenetic regulation of any genes by making simple changes on the CRISPR-dCas9 gRNAs. Key features This method provides a new technique for screening ncRNAs and establishing chromatin interaction networks. The target gene for this method can be any gene of interest and any site in the entire genome. This method can be further extended to detect RNAs, DNAs, and proteins that interact with target genes. Graphical overview.

Perception of the purchase budget (BGT) and purchase intention in smartphone selling industry: A cross-country analysis.

The study explores the direct and mediated impacts of customers' perception of purchase budget (BGT) on purchase intention (PIT) through perceived quality (PPQ), perceived price (PPR), and perceived benefit (PB) in a cross-country setting to understand BGT's role in predicting customer purchase intention in smartphone selling through international online shopping platforms. An online survey was conducted in Kenya, France, and the United States to gather data from 429 consumers who had recently purchased one or more smartphones through international online shopping platforms. SmartPLS-4 was used to test the hypotheses. Results for the entire sample showed a significantly positive mediating role of PPR and PPQ between BGT and PIT. However, the mediating roles of PPQ and PB were not significant in the samples from Kenya, France, and the United States. The results also showed that PPR plays a significant and positive mediating role between BGT and PIT in samples from Kenya, France, the United States, and overall. However, the direct relationships between BGT and PPQ, PPR, and PB are shown to be negatively significant.

Overexpression of TWF1 promotes lung adenocarcinoma progression and is associated with poor prognosis in cancer patients through the MMP1 signaling pathway.

Background: It has been reported that twinfilin actin binding protein 1 (TWF1) is associated with the progression of breast and pancreatic cancers. However, the roles and mechanisms of TWF1 in lung adenocarcinoma (LUAD) have not been reported. Methods: The expression levels of TWF1 in LUAD and normal tissues were analyzed using The Cancer Genome Atlas (TCGA) database, and validation was carried out with 12 clinical samples. The relationship between TWF1 expression and LUAD patients' clinical indices and immunity was investigated. Cell Counting Kit-8 (CCK-8) and migration and invasion assays were employed to explore the effects of downregulated TWF1 on LUAD cell proliferation and metastasis. Results: TWF1 was upregulated in LUAD tissues, and upregulated TWF1 was correlated with the tumor (T) stage, node (N) stage, clinical classification, overall survival (OS), and progression-free interval (PFI) of LUAD patients. Moreover, the Cox regression analysis showed that TWF1 overexpression was an independent risk factor for the poor prognosis of LUAD patients. TWF1 expression was associated with tumor immune infiltration (such as dendritic cells resting, eosinophils, macrophages M0, and others), drug sensitivity (such as A-770041, Bleomycin, and BEZ235), tumor mutation burden (TMB), and sensitivity to immunotherapy. In the cell model, TWF1 expression interference significantly prohibited LUAD cell proliferation, migration, and invasion, which might be relevant to aberrant MMP1 protein downregulation. Conclusions: TWF1 overexpression was correlated with poor prognoses and immune status of LUAD patients. Inhibited TWF1 expression delayed the growth and migration of cancer cells by downregulating MMP protein, implying that TWF1 is a promising biomarker for the prognoses of LUAD patients.

Sensitivity of Puccinia triticina f. sp. tritici from China to Triadimefon and Resistance Risk Assessment.

Wheat leaf rust, caused by Puccinia triticina f. sp. tritici (Pt), is distributed widely in wheat-producing areas and results in serious yield losses worldwide. In China, leaf rust has been largely controlled with a demethylation inhibitor (DMI) fungicide, triadimefon. Although high levels of fungicide resistance in pathogens have been reported, no field failure of wheat leaf rust to DMI fungicides has been reported in China. A resistance risk assessment of triadimefon to Pt was investigated in the present study. The sensitivity of 197 Pt isolates across the country to triadimefon was determined, and the density distribution of EC50 values (concentration at which mycelial growth is inhibited by 50%) showed a continuous multimodal curve because of the extensive use of this fungicide in wheat production, with a mean value of 0.46 µg/ml. The majority of the tested Pt isolates were sensitive to triadimefon, whereas 10.2% developed varying degrees of resistance. Characterization of parasitic fitness revealed that the triadimefon-resistant isolates exhibited strong adaptive traits in urediniospore germination rate, latent period, sporulation intensity, and lesion expansion rate. No correlation was observed between triadimefon and tebuconazole and hexaconazole, which have the similar mode of action, or pyraclostrobin and flubeneteram, which have different modes of action. Overexpression of the target gene Cyp51 led to the triadimefon resistance of Pt. The risk of resistance to triadimefon in Pt may be low to moderate. This study provided important data for fungicide resistance risk management against wheat leaf rust.

What matters for international consumers' choice preferences for smartphones: Evidence from a cross-border ecommerce platform.

Despite the growing impact of smartphone use on countries' economies, the literature has rarely investigated the link between economic context and smartphone purchase trends. Based on 20,556 smartphones sold from a Cross-Border E-Commerce (CBEC) platform, the study reveals that relationships between GDP per capita and Smartphone Choice Preferences (SCP) as well as Purchase Quantities (PUR) are direct and partially mediated by Price (PRI), Read-Only Memory (ROM), and Random-Access Memory (RAM). That means that the economic context highlighted by the GDP plays a substantial role in smartphone choices and purchases. The study suggests that e-sellers and smartphone brands should adapt their marketing and manufacturing strategies to the countries' economic contexts to leverage the fearless competition in the smartphone industry.

[Prevalence Survey of Functional Dyspepsia and Irritable Bowel Syndrome in Chinese College Students Based on Rome â £ Diagnostic Criteria].

Objective: To investigate the prevalence and risk factors of functional dyspepsia (FD) and irritable bowel syndrome (IBS) among college students in China. Methods: An online questionnaire survey of college students aged 17-35 from across China was conducted. The online questionnaire survey was supplemented by an offline survey. A total of 2025 valid samples were included for statistical analysis. χ 2 test and logistic regression were performed for statistical analysis. Results: The prevalence of FD among college students who met the Rome Ⅳ diagnostic criteria was 5.5% (112/2025), with most of them, or 66.1% (74/112), suffering from postprandial discomfort syndrome (PDS). Smoking (odds ratio [ OR]=2.334, 95% confidence interval [ CI]: 1.187-4.589, P=0.014), depression ( OR=2.447, 95% CI: 1.421-4.214, P=0.001), and insomnia ( OR=1.947, 95% CI: 1.291-2.937, P=0.001) were positively correlated with the prevalence of FD. The prevalence of IBS was 1.9% (38/2025), with IBS-diarrhea dominant (IBS-D) being the most important subtype that accounted for 44.7%. Anxiety ( OR=3.63, 95% CI: 1.34-9.88, P=0.012) and insomnia ( OR=2.35, 95% CI: 1.18-4.68, P=0.015) were positively correlated with the prevalence of IBS. Conclusion: Based on Rome Ⅳ criteria, IBS and FD are not uncommon among Chinese university students. Psychological disorders and some related lifestyle factors may be related to the development of the disease. In the future, more series of studies based on different diagnostic criteria, different regions, and multiple factors should be conducted in China.

Therapeutic restoration of female reproductive and endocrine dysfunction using stem cells.

Millions of women worldwide suffer from infertility associated with gynecologic disorders such as premature ovarian insufficiency, polycystic ovary syndrome, Asherman syndrome, endometriosis, preeclampsia, and fallopian tube obstruction. These disorders can lead to infertility and thereby affect the quality of life of the infertile couple because of their psychological impact and significant costs. In recent years, stem cell therapy has emerged as a therapeutic approach to repair or replace damaged tissues or organs. This review describes the recent development as well as the underlying mechanisms of stem cell therapy for a variety of female reproductive diseases, offering us new therapeutic options for the treatment of female reproductive and endocrine dysfunction.