Risk assessment with low-pass whole-genome sequencing of cell-free DNA before CD19 CAR T-cell therapy for large B-cell lymphoma.

Patients with relapsed or refractory large B-cell lymphomas (rrLBCL) can achieve long-term remission after CD19 chimeric antigen receptor T-cell therapy (CART19). However, more than half of recipients will experience treatment failure. Thus, approaches are needed to identify high-risk patients who may benefit from alternative or consolidative therapy. We evaluated low-pass whole-genome sequencing (lpWGS) of cell-free DNA (cfDNA) before CART19 as a new approach for risk stratification. We performed lpWGS on pretreatment plasma samples from 122 patients at time of leukapheresis who received standard-of-care CART19 for rrLBCL to define DNA copy number alterations (CNAs). In multivariable selection, high focal CNA score (FCS) denoting genomic instability was the most significant pretreatment variable associated with inferior 3-month complete response rates (28% vs 56%, P = .0029), progression-free survival (PFS; P = .0007; hazard ratio, 2.11), and overall survival (OS; P = .0026; hazard ratio, 2.10). We identified 34 unique focal CNAs in 108 (89%) patients; of these, deletion 10q23.3 leading to loss of FAS death receptor was the most highly associated with poor outcomes, leading to inferior PFS (P < .0001; hazard ratio, 3.49) and OS (P = .0027; hazard ratio, 2.68). By combining FCS with traditional markers of increased tumor bulk (elevated lactate dehydrogenase and >1 extranodal site), we built a simple risk model that could reliably risk stratify patients. Thus, lpWGS of cfDNA is a minimally invasive assay that could rapidly identify high-risk patients and may guide patient selection for and targeted therapies to evaluate in future clinical trials.

First Evidence of Hindered Amine Light Stabilizers As Abundant, Ubiquitous, Emerging Pollutants in Dust and Air Particles: A New Concern for Human Health.

Hindered amine light stabilizers (HALSs) represent a crucial class of polymer additives that are extensively used in plastics and other polymeric materials. However, their environmental presence and related exposure risks have until now remained unexplored. This study addressed this critical knowledge by examining dust and air particles collected in South China, utilizing a comprehensive analytical approach to identify and quantify nine monomeric HALSs. A total of seven of the nine studied HALSs were detected in the samples, with bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate (Tinuvin 770) and methyl 1,2,2,6,6-pentamethyl-4-piperidyl sebacate (HS-508) identified as the most abundant and widespread pollutants. Median total concentrations of HALSs ranged from 417 to 8,830 ng/g in urban dust samples and from 28.6 to 70.9 pg/m3 in urban air particles. Notably, dust concentrations of HALSs significantly exceeded those of traditional well-known light stabilizers such as UV absorbers. Human exposure assessment indicated that in contrast to air inhalation dust ingestion represented a more substantial exposure pathway owing to the relatively low volatility of these newly identified chemicals. Predictive modeling suggests that many of the examined HALSs exhibited characteristics of persistence, high toxicity, or strong potential for long-range transport, underscoring their hazardous nature. This study represents the first comprehensive investigation into the prevalence of HALSs as a class of emerging pollutants widespread in the environment, necessitating heightened attention and further research in the future.

Comprehensive Identification and Ubiquitous Occurrence of Eight Classes of Rubber-Derived Vulcanization Accelerators in Urban Dusts.

Vulcanization accelerators (VAs) serve as crucial additives in synthetic rubber on a global scale. Despite their widespread use, the environmental presence, distribution, and associated exposure risks of VAs remain poorly understood. This study compiled a target list and conducted a screening for eight classes encompassing 42 VAs in diverse urban dust samples from South China. A total of 40 of the 42 target VAs were detectable across all four studied regions, among which 30 were identified for the first time in the environment. Among the eight structure-classified VA classes, xanthates exhibited the highest concentrations (median: 3810-81,300 ng/g), followed by thiazoles, guanidines, sulfenamides, dithiocarbamates, thiurams, thioureas, and others. The median total concentrations of all target VAs (∑VAs) were determined to be 5060 ng/g in road dust, 5730 ng/g in parking lot dust, 29,200 ng/g in vehicle repair plant dust, and 84,300 ng/g in household dust, indicating the widespread presence of numerous rubber-derived VAs in various urban environments. This study marked the first systematic effort to identify a wide range of emerging rubber-derived VAs prevalent in urban environments. The findings call for increased attention to these widely utilized but less well-evaluated chemicals in future research and environmental management efforts.

Ubiquity of Synthetic Phenolic Antioxidants in Children's Cerebrospinal Fluid from South China: First Evidence for Their Penetration across the Blood-Cerebrospinal Fluid Barrier.

Synthetic phenolic antioxidants (SPAs) and relevant transformation products (TPs) are potentially neurotoxic pollutants to which humans are widely exposed. However, their penetration behavior across the brain barrier and associated exposure to the central nervous system (CNS) remain unknown. This study is the first to investigate a wide range of 30 SPAs and TPs, including emerging SPAs, in matched serum and cerebrospinal fluid (CSF) samples from children in Guangzhou, China. Sixty-two children of either sex aged <14 years with nonbloody CSF and complete clinical information were included. The findings demonstrated the ubiquitous occurrence of many SPAs and TPs, particularly BHT, 2,4-di-tert-butylphenol (DBP), AO 1010, AO 1076, BHT-Q, and BHT-quinol, not only in serum but also in the CSF. Median total concentrations of SPAs and TPs were up to 22.0 and 2.63 ng/mL in serum and 14.5 and 2.11 ng/mL in CSF, respectively. On calculating the penetration efficiencies across the blood-CSF barrier (BCSFB) (RCSF/serum, CCSF/Cserum) for selected SPAs and TPs, their RCSF/serum values (median 0.52-1.41) were highly related to their physicochemical properties, indicating that passive diffusion may be the potential mechanism of BCSFB penetration. In addition, the RCSF/serum values were positively correlated with the barrier permeability index RAlb (AlbuminCSF/Albuminserum), indicating that barrier integrity is an important determinant of BCSFB penetration. Overall, these results will improve our perception of human internal exposure to SPAs and lay a solid foundation for assessing the risk of CNS exposure to various SPAs.

Sphingomonas lacusdianchii sp. nov., an attached bacterium inhibited by metabolites from its symbiotic cyanobacterium.

An alpha-proteobacterial strain JXJ CY 53 T was isolated from the cyanosphere of Microcystis sp. FACHB-905 (MF-905) collected from Lake Dianchi, China. JXJ CY 53 T was observed to be an aerobic, Gram-stain-negative, oval shaped, and mucus-secreting bacterium. It had C18:1ω7c and C16:0 as the major cellular fatty acids, Q-10 as the predominant ubiquinone, and sphingoglycolipid, diphosphatidylglycerol, phosphatidylcholine, and phosphatidylmethylethanolamine as the polar lipids. The G + C content of DNA was 65.85%. The bacterium had 16S rRNA gene sequence identities of 98.9% and 98.7% with Sphingomonas panni DSM 15761 T and Sphingomonas hankookensis KCTC 22579 T, respectively, while less than 97.4% identities with other members of the genus. Further taxonomic analysis indicated that JXJ CY 53 T represented a new member of Sphingomonas, and the species epithet was proposed as Sphingomonas lacusdianchii sp. nov. (type strain JXJ CY 53 T = KCTC 72813 T = CGMCC 1.17657 T). JXJ CY 53 T promoted the growth of MF-905 by providing bio-available phosphorus and nitrogen, plant hormones, vitamins, and carotenoids. It could modulate the relative abundances of nonculturable bacteria associated with MF-905 and influence the interactions of MF-905 and other bacteria isolated from the cyanobacterium, in addition to microcystin production characteristics. Meanwhile, MF-905 could provide JXJ CY 53 T dissolved organic carbon for growth, and control the growth of JXJ CY 53 T by secreting specific chemicals other than microcystins. Overall, these results suggest that the interactions between Microcystis and its attached bacteria are complex and dynamic, and may influence the growth characteristics of the cyanobacterium. This study provided new ideas to understand the interactions between Microcystis and its attached bacteria. KEY POINTS: • A novel bacterium (JXJCY 53 T) was isolated from the cyanosphere of Microcystis sp. FACHB-905 (MF-905) • JXJCY 53 T modulated the growth and microcystin production of MF-905 • MF-905 could control the attached bacteria by specific chemicals other than microcystins (MCs).

Devosia lacusdianchii sp. nov., an attached bacterium inhibited by metabolites from its symbiotic Microcystis.

A novel alphaproteobacterial strain JXJ CY 41T was isolated from a culture mass of Microcystis, collected from Lake Dianchi, south-west, China. Strain JXJ CY 41T was gram-strain-negative, aerobic, motile, with rod-shaped cells (0.4-1.0 × 1.7-3.5 µm). It was positive for catalase and starch hydrolysis, negative for oxidase and hydrolysis of Tweens (20, 40, and 80). Growth occurred at 10-44 °C, pH 5.0-10.0, and 0-5.0% (w/v) NaCl. Major fatty acids included C16:0 (28.1%), 11-methyl C18:1 ω7c (36.7%) and C18:1 ω7c (20.8%). Q10 was the sole ubiquinone. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, glycolipid, and an unidentified lipid. The DNA G + C content was 63.1%. Its 16S rRNA gene sequence showed high similarities with Devosia oryziradicis G19T (99.5%; not validly published), D. yakushimensis Yak96BT (98.3%) and D. ginsengisoli Gsoil 520T (98.1%), and less than 98.1% similarities with other members of the genus Devosia. The digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values between strain JXJ CY 41T and its 5 closest similar strains were 19.9-24.1% and 75.7-80.5%, respectively. Based on the data above, strain JXJ CY 41T was identified as a novel species of the genus Devosia, for which the epithet Devosia lacusdianchii sp. nov. was proposed. The type strain is JXJ CY 41T (= KCTC 72812T = CGMCC 1.17502T). Strain JXJ CY 41T exhibited different interactions with Microcystis aeruginosa FACHB-905 (Maf) under different conditions, and Maf could control the bacterial cellular density by secreting unknown specific chemical compounds according to its nutritional requirements.

Beyond silence: evolving ultrasound strategies in the battle against cardiovascular thrombotic challenges.

Cardiovascular thrombotic events have long been a perplexing factor in clinical settings, influencing patient prognoses significantly. Ultrasound-mediated acoustic therapy, an innovative thrombolytic treatment method known for its high efficiency, non-invasiveness, safety, and convenience, has demonstrated promising potential for clinical applications and has gradually become a focal point in cardiovascular thrombotic disease research. The current challenge lies in the technical complexities of preparing ultrasound-responsive carriers with thrombus-targeting capabilities and high thrombolytic efficiency. Additionally, optimizing the corresponding acoustic treatment mode is crucial to markedly enhance the thrombolytic effectiveness of ultrasound-mediated acoustic therapy. In light of the current status, this article provides a comprehensive review of the research progress in innovative ultrasound-mediated acoustic therapy for cardiovascular thrombotic diseases. It explores the impact of technical methods, therapeutic mechanisms, and influencing factors on the thrombolytic efficiency and clinical potential of ultrasound-mediated acoustic therapy. The review places particular emphasis on identifying solutions and key considerations in addressing the challenges associated with this cutting-edge therapeutic approach.

Dual-mode nanoprobe strategy integrating ultrasound and near-infrared light for targeted and synergistic arterial thrombolysis.

Efficient thrombolysis in time is crucial for prognostic improvement of patients with acute arterial thromboembolic disease, while limitations and complications still exist in conventional thrombolytic treatment methods. Herein, our study sought to investigate a novel dual-mode strategy that integrated ultrasound (US) and near-infrared light (NIR) with establishment of hollow mesoporous silica nanoprobe (HMSN) which contains Arginine-glycine-aspartate (RGD) peptide (thrombus targeting), perfluoropentane (PFP) (thrombolysis with phase-change and stable cavitation) and indocyanine green (ICG) (thrombolysis with photothermal conversion). HMSN is used as the carrier, the surface is coupled with targeted RGD to achieve high targeting and permeability of thrombus, PFP and ICG are loaded to achieve the collaborative diagnosis and treatment of thrombus by US and NIR, so as to provide a new strategy for the integration of diagnosis and treatment of arterial thrombus. From the in vitro and in vivo evaluation, RGD/ICG/PFP@HMSN can aggregate and penetrate at the site of thrombus, and finally establish the dual-mode directional development and thrombolytic treatment under the synergistic effect of US and NIR, providing strong technical support for the accurate diagnosis and treatment of arterial thrombosis.

An international relations quantitative evaluation model (IRQEM) based on an integrated method.

International relations (IR) have great uncertainty and instability. Bad IR or conflicts will bring about heavy economic losses and widespread social unrest domestically and internationally. The accurate prediction for bilateral relations can support decision making for timely responses, which will be used to find ways to maintain development in the complex international situation. An international relations quantitative evaluation model (IRQEM) is proposed by integrating a variety of research models and methods like the interpretative structural modeling method (ISM), Bayesian network (BN) model, the Bayesian search (BS), and the expectation-maximization (EM) algorithm, which is novel for IR research. Factors from several different fields are identified as BN nodes. Each node is assigned different state values. The hierarchical structure of these BN nodes is obtained by ISM. The data collection of 192 cases is used to construct the BN model by GeNIe 4.0. The IRQEM can be used to evaluate the influence of emergencies on IR. The critical factors of IR also can be explored through our proposed model. Results show that the prediction of bilateral relations under emergencies can be realized by updating the indicator set when emergencies occur. The capability to anticipate threats of IR changes is advanced by optimizing the reporting information of IR forecasting through a combination of qualitative and quantitative methods, charts, and texts. Relevant analysis results can provide support for national security decision making.

A robust and flexible CRISPR/Cas9-based system for neutrophil-specific gene inactivation in zebrafish.

CRISPR/Cas9-based tissue-specific knockout techniques are essential for probing the functions of genes in embryonic development and disease using zebrafish. However, the lack of capacity to perform gene-specific rescue or live imaging in the tissue-specific knockout background has limited the utility of this approach. Here, we report a robust and flexible gateway system for tissue-specific gene inactivation in neutrophils. Using a transgenic fish line with neutrophil-restricted expression of Cas9 and ubiquitous expression of single guide (sg)RNAs targeting rac2, specific disruption of the rac2 gene in neutrophils is achieved. Transient expression of sgRNAs targeting rac2 or cdk2 in the neutrophil-restricted Cas9 line also results in significantly decreased cell motility. Re-expressing sgRNA-resistant rac2 or cdk2 genes restores neutrophil motility in the corresponding knockout background. Moreover, active Rac and force-bearing F-actins localize to both the cell front and the contracting tail during neutrophil interstitial migration in an oscillating fashion that is disrupted when rac2 is knocked out. Together, our work provides a potent tool that can be used to advance the utility of zebrafish in identifying and characterizing gene functions in a tissue-specific manner.

Genome-wide systematic characterization of the NRT2 gene family and its expression profile in wheat (Triticum aestivum L.) during plant growth and in response to nitrate deficiency.

BACKGROUND: Wheat (Triticum aestivum L.) is a major cereal crop that is grown worldwide, and it is highly dependent on sufficient N supply. The molecular mechanisms associated with nitrate uptake and assimilation are still poorly understood in wheat. In plants, NRT2 family proteins play a crucial role in NO3- acquisition and translocation under nitrate limited conditions. However, the biological functions of these genes in wheat are still unclear, especially their roles in NO3- uptake and assimilation. RESULTS: In this study, a comprehensive analysis of wheat TaNRT2 genes was conducted using bioinformatics and molecular biology methods, and 49 TaNRT2 genes were identified. A phylogenetic analysis clustered the TaNRT2 genes into three clades. The genes that clustered on the same phylogenetic branch had similar gene structures and nitrate assimilation functions. The identified genes were further mapped onto the 13 wheat chromosomes, and the results showed that a large duplication event had occurred on chromosome 6. To explore the TaNRT2 gene expression profiles in wheat, we performed transcriptome sequencing after low nitrate treatment for three days. Transcriptome analysis revealed the expression levels of all TaNRT2 genes in shoots and roots, and based on the expression profiles, three highly expressed genes (TaNRT2-6A.2, TaNRT2-6A.6, and TaNRT2-6B.4) were selected for qPCR analysis in two different wheat cultivars ('Mianmai367' and 'Nanmai660') under nitrate-limited and normal conditions. All three genes were upregulated under nitrate-limited conditions and highly expressed in the high nitrogen use efficiency (NUE) wheat 'Mianmai367' under low nitrate conditions. CONCLUSION: We systematically identified 49 NRT2 genes in wheat and analysed the transcript levels of all TaNRT2s under nitrate deficient conditions and over the whole growth period. The results suggest that these genes play important roles in nitrate absorption, distribution, and accumulation. This study provides valuable information and key candidate genes for further studies on the function of TaNRT2s in wheat.

A national risk analysis model (NRAM) for the assessment of COVID-19 epidemic.

COVID-19 has caused a critical health concern and severe economic crisis worldwide. With multiple variants, the epidemic has triggered waves of mass transmission for nearly 3 years. In order to coordinate epidemic control and economic development, it is important to support decision-making on precautions or prevention measures based on the risk analysis for different countries. This study proposes a national risk analysis model (NRAM) combining Bayesian network (BN) with other methods. The model is built and applied through three steps. (1) The key factors affecting the epidemic spreading are identified to form the nodes of BN. Then, each node can be assigned state values after data collection and analysis. (2) The model (NRAM) will be built through the determination of the structure and parameters of the network based on some integrated methods. (3) The model will be applied to scenario deduction and sensitivity analysis to support decision-making in the context of COVID-19. Through the comparison with other models, NRAM shows better performance in the assessment of spreading risk at different countries. Moreover, the model reveals that the higher education level and stricter government measures can achieve better epidemic prevention and control effects. This study provides a new insight into the prevention and control of COVID-19 at the national level.

Simple and Versatile Nitrooxylation: Noncyclic Hypervalent Iodine Nitrooxylating Reagent.

Organic nitrates are broadly applied as pharmaceuticals (acting as efficient nitric oxide donor), energetic materials, building blocks in organic synthesis, etc. However, practical and direct methods to access organic nitrates efficiently are still rare, mainly due to the lack of powerful nitrooxylating reagents. Herein, we report bench-stable and highly reactive noncyclic hypervalent iodine nitrooxylating reagents, oxybis(aryl-λ3 -iodanediyl) dinitrates (OAIDNs, 2), which are prepared just by using aryliodine diacetate and HNO3 . The reagents are used to achieve a mild and operationally simple protocol to access diverse organic nitrates. By employing of 2, zinc-catalyzed regioselective nitrooxylation of cyclopropyl silyl ethers is realized efficiently to access the corresponding ß-nitrooxy ketones with high functional-group tolerance. Moreover, a series of direct and catalyst-free nitrooxylations of enolizable C-H bonds are carried out smoothly to afford the desired organic nitrates within minutes by just mixing the substrates with 2 in dichloromethane.

Mitofusin 2 regulates neutrophil adhesive migration and the actin cytoskeleton.

Neutrophils rely on glycolysis for energy production. How mitochondria regulate neutrophil function is not fully understood. Here, we report that mitochondrial outer membrane protein Mitofusin 2 (MFN2) regulates neutrophil homeostasis and chemotaxis in vivoMfn2-deficient neutrophils are released from the hematopoietic tissue, trapped in the vasculature in zebrafish embryos, and not capable of chemotaxis. Consistent with this, human neutrophil-like cells that are deficient for MFN2 fail to arrest on activated endothelium under sheer stress or perform chemotaxis on 2D surfaces. Deletion of MFN2 results in a significant reduction of neutrophil infiltration to the inflamed peritoneal cavity in mice. Mechanistically, MFN2-deficient neutrophil-like cells display disrupted mitochondria-ER interaction, heightened intracellular Ca2+ levels and elevated Rac activation after chemokine stimulation. Restoring a mitochondria-ER tether rescues the abnormal Ca2+ levels, Rac hyperactivation and chemotaxis defect resulting from MFN2 depletion. Finally, inhibition of Rac activation restores chemotaxis in MFN2-deficient neutrophils. Taken together, we have identified that MFN2 regulates neutrophil migration via maintaining the mitochondria-ER interaction to suppress Rac activation, and uncovered a previously unrecognized role of MFN2 in regulating cell migration and the actin cytoskeleton.This article has an associated First Person interview with the first authors of the paper.

Subtype-specific and co-occurring genetic alterations in B-cell non-Hodgkin lymphoma.

B-cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL, such as diffuse large B-cell lymphoma, have been comprehensively interrogated at the genomic level, but rarer subtypes, such as mantle cell lymphoma, remain less extensively characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 685 B-NHL tumors at high depth, including diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, and Burkitt lymphoma. We identified conserved hallmarks of B-NHL that were deregulated in the majority of tumors from each subtype, including frequent genetic deregulation of the ubiquitin proteasome system. In addition, we identified subtype-specific patterns of genetic alterations, including clusters of co-occurring mutations and DNA copy number alterations. The cumulative burden of mutations within a single cluster were more discriminatory of B-NHL subtypes than individual mutations, implicating likely patterns of genetic cooperation that contribute to disease etiology. We therefore provide the first cross-sectional analysis of mutations and DNA copy number alterations across major B-NHL subtypes and a framework of co-occurring genetic alterations that deregulate genetic hallmarks and likely cooperate in lymphomagenesis.

Study on the expression of TOP2A in hepatocellular carcinoma and its relationship with patient prognosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate. However, the molecular mechanism of HCC formation remains to be explored and studied. OBJECTIVE: To investigate the expression of TOP2A in hepatocellular carcinoma (HCC) and its prognosis. METHODS: The data set of hepatocellular carcinoma was downloaded from GEO database for differential gene analysis, and hub gene was identified by Cytoscape. GEPIA was used to verify the expression of HUB gene and evaluate its prognostic value. Then TOP2A was selected as the research object of this paper by combining literature and clinical sample results. Firstly, TIMER database was used to study TOP2A, and the differential expression of TOP2A gene between normal tissues and cancer tissues was analyzed, as well as the correlation between TOP2A gene expression and immune infiltration of HCC cells. Then, the expression of top2a-related antibodies was analyzed using the Human Protein Atlas database, and the differential expression of TOP2A was verified by immunohistochemistry. Then, SRTING database and Cytoscape were used to establish PPI network for TOP2A and protein-protein interaction analysis was performed. The Oncomine database and cBioPortal were used to express and identify TOP2A mutation-related analyses. The expression differences of TOP2A gene were identified by LinkedOmics, and the GO and KEGG pathways were analyzed in combination with related genes. Finally, Kaplan-Meier survival analysis was performed to analyze the clinical and prognosis of HCC patients. RESULTS: TOP2A may be a new biomarker and therapeutic target for hepatocellular carcinoma.

Reduced electron transport chain complex I protein abundance and function in Mfn2-deficient myogenic progenitors lead to oxidative stress and mitochondria swelling.

Mitochondrial remodeling through fusion and fission is crucial for progenitor cell differentiation but its role in myogenesis is poorly understood. Here, we characterized the function of mitofusin 2 (Mfn2), a mitochondrial outer membrane protein critical for mitochondrial fusion, in muscle progenitor cells (myoblasts). Mfn2 expression is upregulated during myoblast differentiation in vitro and muscle regeneration in vivo. Targeted deletion of Mfn2 gene in myoblasts (Mfn2MKO ) increases oxygen-consumption rates (OCR) associated with the maximal respiration and spare respiratory capacity, and increased levels of reactive oxygen species (ROS). Skeletal muscles of Mfn2MKO mice exhibit robust mitochondrial swelling with normal mitochondrial DNA content. Additionally, mitochondria isolated from Mfn2MKO muscles have reduced OCR at basal state and for complex I respiration, associated with decreased levels of complex I proteins NDUFB8 (NADH ubiquinone oxidoreductase subunit B8) and NDUFS3 (NADH ubiquinone oxidoreductase subunit S3). However, Mfn2MKO has no obvious effects on myoblast differentiation, muscle development and function, and muscle regeneration. These results demonstrate a novel role of Mfn2 in regulating mitochondrial complex I protein abundance and respiratory functions in myogenic progenitors and myofibers.

Acid-Free Copper-Catalyzed Electrophilic Nitration of Electron-Rich Arenes with Guanidine Nitrate.

A practical copper-catalyzed nitration of electron-rich arenes with trimethylsilyl chloride and guanidine nitrate is reported. A variety of nitrated products were generated in moderate to excellent yields (32-99%) at ambient temperature under acid-free, open-flask, and operationally simple conditions.

Phenotypical microRNA screen reveals a noncanonical role of CDK2 in regulating neutrophil migration.

Neutrophil migration is essential for inflammatory responses to kill pathogens; however, excessive neutrophilic inflammation also leads to tissue injury and adverse effects. To discover novel therapeutic targets that modulate neutrophil migration, we performed a neutrophil-specific microRNA (miRNA) overexpression screen in zebrafish and identified 8 miRNAs as potent suppressors of neutrophil migration. Among those, miR-199 decreases neutrophil chemotaxis in zebrafish and human neutrophil-like cells. Intriguingly, in terminally differentiated neutrophils, miR-199 alters the cell cycle-related pathways and directly suppresses cyclin-dependent kinase 2 (Cdk2), whose known activity is restricted to cell cycle progression and cell differentiation. Inhibiting Cdk2, but not DNA replication, disrupts cell polarity and chemotaxis of zebrafish neutrophils without inducing cell death. Human neutrophil-like cells deficient in CDK2 fail to polarize and display altered signaling downstream of the formyl peptide receptor. Chemotaxis of primary human neutrophils is also reduced upon CDK2 inhibition. Furthermore, miR-199 overexpression or CDK2 inhibition significantly improves the outcome of lethal systemic inflammation challenges in zebrafish. Our results therefore reveal previously unknown functions of miR-199 and CDK2 in regulating neutrophil migration and provide directions in alleviating systemic inflammation.

Comparative Study of Government Response Measures and Epidemic Trends for COVID-19 Global Pandemic.

The ongoing novel coronavirus (COVID-19) epidemic has evolved into a full range of challenges that the world is facing. Health and economic threats caused governments to take preventive measures against the spread of the disease. This study aims to provide a correlation analysis of the response measures adopted by countries and epidemic trends since the COVID-19 outbreak. This analysis picks 13 countries for quantitative assessment. We select a trusted model to fit the epidemic trend curves in segments and catch the characteristics based on which we explore the key factors of COVID-19 spread. This review generates a score table of government response measures according to the Likert scale. We use the Delphi method to obtain expert judgments about the government response in the Likert scale. Furthermore, we find a significant negative correlation between the epidemic trend characteristics and the government response measure scores given by experts through correlation analysis. More stringent government response measures correlate with fewer infections and fewer waves in the infection curves. Stringent government response measures curb the spread of COVID-19, limit the number of total infectious cases, and reduce the time to peak of total cases. The clusters of the results categorize the countries into two specific groups. This study will improve our understanding of the prevention of COVID-19 spread and government response.