Exploring pharmacological active ingredients of traditional Chinese medicine by pharmacotranscriptomic map in ITCM.

With the emergence of high-throughput technologies, computational screening based on gene expression profiles has become one of the most effective methods for drug discovery. More importantly, profile-based approaches remarkably enhance novel drug-disease pair discovery without relying on drug- or disease-specific prior knowledge, which has been widely used in modern medicine. However, profile-based systematic screening of active ingredients of traditional Chinese medicine (TCM) has been scarcely performed due to inadequate pharmacotranscriptomic data. Here, we develop the largest-to-date online TCM active ingredients-based pharmacotranscriptomic platform integrated traditional Chinese medicine (ITCM) for the effective screening of active ingredients. First, we performed unified high-throughput experiments and constructed the largest data repository of 496 representative active ingredients, which was five times larger than the previous one built by our team. The transcriptome-based multi-scale analysis was also performed to elucidate their mechanism. Then, we developed six state-of-art signature search methods to screen active ingredients and determine the optimal signature size for all methods. Moreover, we integrated them into a screening strategy, TCM-Query, to identify the potential active ingredients for the special disease. In addition, we also comprehensively collected the TCM-related resource by literature mining. Finally, we applied ITCM to an active ingredient bavachinin, and two diseases, including prostate cancer and COVID-19, to demonstrate the power of drug discovery. ITCM was aimed to comprehensively explore the active ingredients of TCM and boost studies of pharmacological action and drug discovery. ITCM is available at http://itcm.biotcm.net.

Transcriptome and metabolome analyses reveal molecular insights into waterlogging tolerance in Barley.

Waterlogging stress is one of the major abiotic stresses affecting the productivity and quality of many crops worldwide. However, the mechanisms of waterlogging tolerance are still elusive in barley. In this study, we identify key differentially expressed genes (DEGs) and differential metabolites (DM) that mediate distinct waterlogging tolerance strategies in leaf and root of two barley varieties with contrasting waterlogging tolerance under different waterlogging treatments. Transcriptome profiling revealed that the response of roots was more distinct than that of leaves in both varieties, in which the number of downregulated genes in roots was 7.41-fold higher than that in leaves of waterlogging sensitive variety after 72 h of waterlogging stress. We also found the number of waterlogging stress-induced upregulated DEGs in the waterlogging tolerant variety was higher than that of the waterlogging sensitive variety in both leaves and roots in 1 h and 72 h treatment. This suggested the waterlogging tolerant variety may respond more quickly to waterlogging stress. Meanwhile, phenylpropanoid biosynthesis pathway was identified to play critical roles in waterlogging tolerant variety by improving cell wall biogenesis and peroxidase activity through DEGs such as Peroxidase (PERs) and Cinnamoyl-CoA reductases (CCRs) to improve resistance to waterlogging. Based on metabolomic and transcriptomic analysis, we found the waterlogging tolerant variety can better alleviate the energy deficiency via higher sugar content, reduced lactate accumulation, and improved ethanol fermentation activity compared to the waterlogging sensitive variety. In summary, our results provide waterlogging tolerance strategies in barley to guide the development of elite genetic resources towards waterlogging-tolerant crop varieties.

FL-DTD: an integrated pipeline to predict the drug interacting targets by feedback loop-based network analysis.

Drug target discovery is an essential step to reveal the mechanism of action (MoA) underlying drug therapeutic effects and/or side effects. Most of the approaches are usually labor-intensive while unable to identify the tissue-specific interacting targets, especially the targets with weaker drug binding affinity. In this work, we proposed an integrated pipeline, FL-DTD, to predict the drug interacting targets of novel compounds in a tissue-specific manner. This method was built based on a hypothesis that cells under a status of homeostasis would take responses to drug perturbation by activating feedback loops. Therefore, the drug interacting targets can be predicted by analyzing the network responses after drug perturbation. We evaluated this method using the expression data of estrogen stimulation, gene manipulation and drug perturbation and validated its good performance to identify the annotated drug targets. Using STAT3 as a target protein, we applied this method to drug perturbation data of 500 natural compounds and predicted five compounds with STAT3 interacting activities. Experimental assay validated the STAT3-interacting activities of four compounds. Overall, our evaluation suggests that FL-DTD predicts the drug interacting targets with good accuracy and can be used for drug target discovery.

Genome-wide association studies reveal novel loci for grain size in two-rowed barley (Hordeum vulgare L.).

KEY MESSAGE: SNP-based and InDel-based GWAS on multi-environment data identified genomic regions associated with barley grain size. Barley yield and quality are greatly influenced by grain size. Improving barley grain size in breeding programs requires knowledge of genetic loci and alleles in germplasm resources. In this study, a collection of 334 worldwide two-rowed barley accessions with extensive genetic diversity was evaluated for grain size including grain length (GL), grain width (GW), and thousand-grain weight (TGW) across six independent field trials. Significant differences were observed in genotype and environments for all measured traits. SNP- and InDel-based GWAS were applied to dissect the genetic architecture of grain size with an SLAF-seq strategy. Two approaches using the FarmCPU model revealed 38 significant marker-trait associations (MTAs) with PVE ranging from 0.01% to 20.68%. Among these MTAs, five were on genomic regions where no previously reported QTL for grain size. Superior alleles of TGW-associated SNP233060 and GL-associated InDel11006 exhibited significantly higher levels of phenotype. The significant MTAs could be used in marker-assisted selection breeding.

Interaction of Asn297-Linked Glycan Ligands with the Fc Fragment of the Immunoglobulin Class G1: A Molecular Dynamics Simulation Study.

The allosteric modulation of the homodimeric H10-03-6 protein to glycan ligands L1 and L2, and the STAB19 protein to glycan ligands L3 and L4, respectively, has been studied by molecular dynamics simulations and free energy calculations. The results revealed that the STAB19 protein has a significantly higher affinity for L3 (-11.38 ± 2.32 kcal/mol) than that for L4 (-5.51 ± 1.92 kcal/mol). However, the combination of the H10-03-6 protein with glycan L2 (1.23 ± 6.19 kcal/mol) is energetically unfavorable compared with that of L1 (-13.96 ± 0.35 kcal/mol). Further, the binding of glycan ligands L3 and L4 to STAB19 would result in the significant closure of the two CH2 domains of the STAB19 conformation with the decrease of the centroid distances between the two CH2 domains compared with the H10-03-6/L1/L2 complex. The CH2 domain closure of STAB19 relates directly to the formation of new hydrogen bonds and hydrophobic interactions between the residues Ser239, Val240, Asp265, Glu293, Asn297, Thr299, Ser337, Asp376, Thr393, Pro395, and Pro396 in STAB19 and glycan ligands L3 and L4, which suggests that these key residues would contribute to the specific regulation of STAB19 to L3 and L4. In addition, the distance analysis revealed that the EF loop in the H10-03-6/L1/L2 model presents a high flexibility and partial disorder compared with the stabilized STAB19/L3/L4 complex. These results will be helpful in understanding the specific regulation through the asymmetric structural characteristics in the CH2 and CH3 domains of the H10-03-6 and STAB19 proteins.

Platelet-derived circFAM13B associated with anti-platelet responsiveness of ticagrelor in patients with acute coronary syndrome.

BACKGROUND: Platelet is enriched with Circular RNAs (circRNAs), with circFAM13B rank among the 10 most abundant circRNAs in platelets. The aim of the present study was to evaluate the predictive value of platelet-derived circFAM13B for the antiplatelet responsiveness and efficacy of ticagrelor in patients with acute coronary syndrome (ACS). METHODS: Consecutive ACS patients treated with ticagrelor were enrolled, and the antiplatelet responsiveness of 3 days of ticagrelor maintenance treatment was assessed by measuring the adenosine diphosphate (ADP)-induced platelet inhibition rate (ADP%) using thromboelastography. The expression of circFAM13B in the patients' platelets was analyzed by quantitative real-time polymerase chain reaction. The correlation between circFAM13B expression and ticagrelor antiplatelet responsiveness, as well as the independent contribution of circFAM13B to the composite of adverse ischemic events during a follow-up period of at least 12 months was evaluated. RESULTS: A total of 129 eligible ACS patients treated with ticagrelor were enrolled in the study. A negative correlation was found between the expression of circFAM13B and the ADP% value (r = -0.41, P < 0.001). Patients with ADP% ≥ 76% had a significantly lower level of circFAM13B compared to those with ADP% < 76% (adjusted P = 0.009). Receiver operating characteristic curve analysis demonstrated that combining circFAM13B expression > 1.05 with clinical risk factors could effectively predict the risk of adverse ischemic events (AUC = 0.81, 95% CI: 0.69 to 0.92, P < 0.001). Kaplan-Meier survival analysis showed that patients with circFAM13B > 1.05 had a significantly higher risk of adverse ischemic events compared to those with circFAM13B ≤ 1.05 (P = 0.003). Multivariate logistic hazard analysis identified circFAM13B > 1.05 as an independent risk factor for adverse ischemic events in in ticagrelor-treated ACS patients (adjusted OR: 5.60, 95% CI: 1.69-18.50; P = 0.005). CONCLUSIONS: Platelet-derived circFAM13B could be utilized for predicting the antiplatelet responsiveness and efficacy of ticagrelor in patients with ACS.

Prenatal diagnosis and treatment for fetal angiotensin converting enzyme deficiency.

OBJECTIVE: To elucidate an etiology in a case with persistent oligohydramnios by prenatal diagnosis and actively treat the case to achieve good prognosis. METHODS: We performed whole exome sequencing (WES) of DNA from the fetus and parents. Serial amnioinfusions were conducted until birth. Pressors were required to maintain normal blood pressure. The infant angiotensin-converting enzyme (ACE) activity, angiotensin II (Ang II, a downstream product of ACE), and compensatory enzymes (CEs) activities were measured. Compensatory enzyme activities in plasma from age-matched healthy controls were also detected. RESULTS: We identified a fetus with a severe ACE mutation prenatally. The infant was born prematurely without pulmonary dysplasia. Hypotension and anuria resolved spontaneously. He had almost no ACE activity, but his Ang II level and CE activity exceeded the upper limit of the normal range and the upper limit of the 95% confidence interval of controls, respectively. His renal function also largely recovered. CONCLUSION: Fetuses with ACE mutations can be diagnosed prenatally through WES. Serial amnioinfusion permits the continuation of pregnancy in fetal ACE deficiency. Compensatory enzymes for defective ACE appeared postnatally. Renal function may be spared by preterm delivery; furthermore, for postnatal vasopressor therapy to begin, improving renal perfusion pressure before nephrogenesis has been completed.

Identification and Validation of Basement Membrane Related LncRNA Signatures as a Novel Prognostic Model for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a significant cancer with limited treatments and a poor prognosis, with the basement membrane (BM) playing a crucial role in its initiation and growth. This study utilized data from The Cancer Genome Atlas and the Gene Expression Omnibus (GEO) databases to identify basement membrane-related genes differentially expressed in HCC. Through gene co-expression analysis, BM-associated long non-coding RNAs (lncRNAs) were discovered. LncRNAs related to HCC survival were selected via univariate analysis, and a prognostic model was constructed using LASSO regression and multivariate analysis. This model effectively classified HCC patients into high and low-risk groups, uncovering significant differences in prognosis, immune response, mutation, and drug sensitivity. Six BM-related lncRNAs (GSEC, MIR4435-2HG, AC092614.1, AC127521.1, LINC02580, and AC008050.1) were validated in normal and HCC cell lines, and the key role of AC092614.1 in regulating proliferation, migration, and invasion of HCC cells in vitro was explored. This research emphasizes the prognostic and therapeutic relevance of BM-related lncRNAs in HCC, highlighting AC092614.1's role in disease progression and as a potential target for targeted therapy.

New Set of Isobaric Labeling Reagents for Quantitative 16Plex Proteomics.

Peptide labeling by isobaric tags is a powerful approach for the relative quantitative analysis of proteomes in multiple groups. There has been a revolution in the innovation of new isobaric reagents; however, great effort is being made to expand simultaneous labeling groups to identify more labeled peptides and reduce reporter ion signal suppression. We redesigned the original chemical structure of the deuterium isobaric amine-reactive tag developed in our laboratory. We optimized the synthetic pathway to create a new set of 16-plex isobaric tags (IBT-16plex). The novel reagent enabled almost complete labeling of peptides within 90 min, with all labeling reporter ions exhibiting comparable MS/MS signals. Compared to a typical 16plex reagent, TMTpro-16plex, the peptides and proteins identified by IBT-16plex in trypsinized HeLa cells were significantly increased by 14.8 and 8.6%, respectively. Moreover, differences in peptide abundance within 10-fold among multiple groups were barely suppressed in IBT-16plex, whereas the dynamic range in TMTpro-16plex-labeled groups was smaller. After quantitative examination of MCF7 cell proteins, IBT-16plex was confirmed as feasible and useful for evaluating protein responses of glucose-starved MCF7 cells to a glucose-rich medium.

Molecular insights into the responses of barley to yellow mosaic disease through transcriptome analysis.

BACKGROUND: Barley (Hordeum vulgare L.) represents the fourth most essential cereal crop in the world, vulnerable to barley yellow mosaic virus (BaYMV) and/or barley mild mosaic virus (BaMMV), leading to the significant yield reduction. To gain a better understanding of the mechanisms regarding barley crop tolerance to virus infection, we employed a transcriptome sequencing approach and investigated global gene expression among three barley varieties under both infected and control conditions. RESULTS: High-throughput sequencing outputs revealed massive genetic responses, reflected by the barley transcriptome after BaYMV and/or BaMMV infection. Significant enrichments in peptidase complex and protein processing in endoplasmic reticulum were clustered through Gene ontology and KEGG analysis. Many genes were identified as transcription factors, antioxidants, disease resistance genes and plant hormones and differentially expressed between infected and uninfected barley varieties. Importantly, general response genes, variety-specific and infection-specific genes were also discovered. Our results provide useful information for future barley breeding to resist BaYMV and BaMMV. CONCLUSIONS: Our study elucidates transcriptomic adaptations in barley response to BaYMV/BaMMV infection through high-throughput sequencing technique. The analysis outcome from GO and KEGG pathways suggests that BaYMV disease induced regulations in multiple molecular-biology processes and signalling pathways. Moreover, critical DEGs involved in defence and stress tolerance mechanisms were displayed. Further functional investigations focusing on these DEGs contributes to understanding the molecular mechanisms of plant response to BaYMV disease infection, thereby offering precious genetic resources for breeding barley varieties resistant to BaYMV disease.

Angiogenesis modulated by CD93 and its natural ligands IGFBP7 and MMRN2: a new target to facilitate solid tumor therapy by vasculature normalization.

The tumor vasculature was different from the normal vasculature in both function and morphology, which caused hypoxia in the tumor microenvironment (TME). Previous anti-angiogenesis therapy had led to a modest improvement in cancer immunotherapy. However, antiangiogenic therapy only benefitted a few patients and caused many side effects. Therefore, there was still a need to develop a new approach to affect tumor vasculature formation. The CD93 receptor expressed on the surface of vascular endothelial cells (ECs) and its natural ligands, MMRN2 and IGFBP7, were now considered potential targets in the antiangiogenic treatment because recent studies had reported that anti-CD93 could normalize the tumor vasculature without impacting normal blood vessels. Here, we reviewed recent studies on the role of CD93, IGFBP7, and MMRN2 in angiogenesis. We focused on revealing the interaction between IGFBP7-CD93 and MMRN2-CD93 and the signaling cascaded impacted by CD93, IGFBP7, and MMRN2 during the angiogenesis process. We also reviewed retrospective studies on CD93, IGFBP7, and MMRN2 expression and their relationship with clinical factors. In conclusion, CD93 was a promising target for normalizing the tumor vasculature.

HvNCX, a prime candidate gene for the novel qualitative locus qS7.1 associated with salinity tolerance in barley.

KEY MESSAGE: A major QTL (qS7.1) for salinity damage score and Na+ exclusion was identified on chromosome 7H from a barley population derived from a cross between a cultivated variety and a wild accession. qS7.1 was fine-mapped to a 2.46 Mb physical interval and HvNCX encoding a sodium/calcium exchanger is most likely the candidate gene. Soil salinity is one of the major abiotic stresses affecting crop yield. Developing salinity-tolerant varieties is critical for minimizing economic penalties caused by salinity and providing solutions for global food security. Many genes/QTL for salt tolerance have been reported in barley, but only a few of them have been cloned. In this study, a total of 163 doubled haploid lines from a cross between a cultivated barley variety Franklin and a wild barley accession TAM407227 were used to map QTL for salinity tolerance. Four significant QTL were identified for salinity damage scores. One (qS2.1) was located on 2H, determining 7.5% of the phenotypic variation. Two (qS5.1 and qS5.2) were located on 5H, determining 5.3-11.7% of the phenotypic variation. The most significant QTL was found on 7H, explaining 27.8% of the phenotypic variation. Two QTL for Na+ content in leaves under salinity stress were detected on chromosomes 1H (qNa1.1) and 7H(qNa7.1). qS7.1 was fine-mapped to a 2.46 Mb physical interval using F4 recombinant inbred lines. This region contains 23 high-confidence genes, with HvNCX which encodes a sodium/calcium exchanger being most likely the candidate gene. HvNCX was highly induced by salinity stress and showed a greater expression level in the sensitive parent. Multiple nucleotide substitutions and deletions/insertions in the promoter sequence of HvNCX were found between the two parents. cDNA sequencing of the HvNCX revealed that the difference between the two parents is conferred by a single Ala77/Pro77 amino acid substitution, which is located on the transmembrane domain. These findings open new prospects for improving salinity tolerance in barley by targeting a previously unexplored trait.

Nonlinear Modeling of Contact Stress Distribution in Thin Plate Substrates Subjected to Aspect Ratio.

The foundation substrate's basal contact stresses are typically thought to have a linear distribution, although the actual form is nonlinear. Basal contact stress in thin plates is experimentally measured using a thin film pressure distribution system. This study examines the nonlinear distribution law of basal contact stresses in thin plates with various aspect ratios under concentrated loading, and it establishes a model for the distribution of contact stresses in thin plates using an exponential function that accounts for aspect ratio coefficients. The outcomes demonstrate that the thin plate's aspect ratio significantly affects how the substrate contact stress is distributed during concentrated loading. The contact stresses in the thin plate's base exhibit significant nonlinearity when the aspect ratio of the test thin plate is greater than 6~8. The aspect ratio coefficient-added exponential function model can better optimize the strength and stiffness calculations of the base substrate and more accurately describe the actual distribution of contact stresses in the base of the thin plate compared to linear and parabolic functions. The correctness of the exponential function model is confirmed by the film pressure distribution measurement system that directly measures the contact stress at the base of the thin plate, providing a more accurate nonlinear load input for the calculation of the internal force of the base thin plate.

Citric Acid and Poly-glutamic Acid Promote the Phytoextraction of Cadmium and Lead in Solanum nigrum L. Grown in Compound Cd-Pb Contaminated Soils.

Phytoextraction is an efficient strategy for remediating heavy metal-contaminated soil. Chelators can improve the bioavailability of heavy metals and increase phytoextraction efficiency. However, traditional chelators have gradually been replaced due to secondary pollution. In this study, a typical organic acid (citric acid, CA) and a novel biodegradable chelator (poly-glutamic acid, PGA), were investigated using pot experiments to compare the phytoextraction efficiency of Solanum nigrum L. (a Cd (hyper)accumulator) for cadmium (Cd) and lead (Pb) in contaminated soil. The results showed CA and PGA significantly improved plant growth, and total Cd and Pb amounts of S. nigrum, both CA and PGA significantly increased the shoot Cd and Pb concentrations. However, only PGA significantly increased the root Pb concentration. CA and PGA application promoted the bioavailability of Cd and Pb in rhizosphere soils and their translocations from roots to shoots in S. nigrum. Both CA and PGA increased the phytoextraction efficiency of Cd and Pb in S. nigrum plants, and the PGA for Cd and Pb phytoextraction was more effective than CA. Our findings demonstrate that the biodegradable chelator PGA has great potential for enhancing phytoextraction from compound Cd-Pb contaminated soils, suggesting that biodegradable chelator-assisted phytoextraction with (hyper)accumulator is strongly recommended in severely contaminated sites.

Risk Factors for Death Among the First 80 543 Coronavirus Disease 2019 (COVID-19) Cases in China: Relationships Between Age, Underlying Disease, Case Severity, and Region.

BACKGROUND: Knowledge of COVID-19 epidemiology remains incomplete and crucial questions persist. We aimed to examine risk factors for COVID-19 death. METHODS: A total of 80 543 COVID-19 cases reported in China, nationwide, through 8 April 2020 were included. Risk factors for death were investigated by Cox proportional hazards regression and stratified analyses. RESULTS: Overall national case-fatality ratio (CFR) was 5.64%. Risk factors for death were older age (≥80: adjusted hazard ratio, 12.58; 95% confidence interval, 6.78-23.33), presence of underlying disease (1.33; 1.19-1.49), worse case severity (severe: 3.86; 3.15-4.73; critical: 11.34; 9.22-13.95), and near-epicenter region (Hubei: 2.64; 2.11-3.30; Wuhan: 6.35; 5.04-8.00). CFR increased from 0.35% (30-39 years) to 18.21% (≥70 years) without underlying disease. Regardless of age, CFR increased from 2.50% for no underlying disease to 7.72% for 1, 13.99% for 2, and 21.99% for ≥3 underlying diseases. CFR increased with worse case severity from 2.80% (mild) to 12.51% (severe) and 48.60% (critical), regardless of region. Compared with other regions, CFR was much higher in Wuhan regardless of case severity (mild: 3.83% vs 0.14% in Hubei and 0.03% elsewhere; moderate: 4.60% vs 0.21% and 0.06%; severe: 15.92% vs 5.84% and 1.86%; and critical: 58.57% vs 49.80% and 18.39%). CONCLUSIONS: Older patients regardless of underlying disease and patients with underlying disease regardless of age were at elevated risk of death. Higher death rates near the outbreak epicenter and during the surge of cases reflect the deleterious effects of allowing health systems to become overwhelmed.

Highly Dispersed Ru-Co Nanoparticles Interfaced With Nitrogen-Doped Carbon Polyhedron for High Efficiency Reversible Li-O2 Battery.

The lithium-oxygen (Li-O2 ) battery with high energy density of 3860 Wh kg-1 represents one of the most promising new secondary batteries for future electric vehicles and mobile electronic devices. However, slow oxygen reduction/oxygen evolution (ORR/OER) reaction efficiency and unstable cycling performance restrain the practical applications of the Li-O2 battery. Herein, Ru-modified nitrogen-doped porous carbon-encapsulated Co nanoparticles (Ru/Co@CoNx -C) are synthesized through reduction of Ru on metal-organic framework (MOFs) pyrolyzed derivatives strategies. Porous carbon polyhedra provide channels for reactive species and stable structure ensures the cyclic stability of the catalyst; abundant Co-Nx sites and high specific surface area (353 m2 g-1 ) provide more catalytically active sites and deposition sites for reaction products. Theoretical calculations further verify that Ru/Co@CoNx -C can regulate the growth of Li2 O2 to improve reversibility of Li-O2 batteries. Li-O2 batteries with Ru/Co@CoNx -C as cathode catalyst achieve small voltage gaps of 1.08 V, exhibit excellent cycle stability (205 cycles), and deliver high discharge specific capacity (17050 mAh g-1 ). Furthermore, pouch-type Li-O2 batteries that maintain stable electrochemical performance output even under conditions of bending deformation and corner cutting are successfully assembled. This study demonstrates Ru/Co@CoNx -C catalyst's great application potential in Li-O2 batteries.

Engineering of rice varieties with enhanced resistances to both blast and bacterial blight diseases via CRISPR/Cas9.

Rice blast and bacterial blight represent two of major diseases having devastating impact on the yield of rice in most rice-growing countries. Developments of resistant cultivars are the most economic and effective strategy to control these diseases. Here, we used CRISPR/Cas9-mediated gene editing to rapidly install mutations in three known broad-spectrum blast-resistant genes, Bsr-d1, Pi21 and ERF922, in an indica thermosensitive genic male sterile (TGMS) rice line Longke638S (LK638S). We obtained transgene-free homozygous single or triple mutants in T1 generations. While all single and triple mutants showed increased resistance to rice blast compared with wild type, the erf922 mutants displayed the strongest blast resistance similar with triple mutants. Surprisingly, we found that Pi21 or ERF922 single mutants conferred enhanced resistance to most of tested bacterial blight. Both resistances in mutants were attribute to the up-regulation of SA- and JA-pathway associated genes. Moreover, phenotypic analysis of these single mutants in paddy fields revealed that there were no trade-offs between resistances and main agricultural traits. Together, our study provides a rapid and effective way to generate rice varieties with resistance to both rice blast and bacterial blight.

Percentage of Newly Proposed High-Grade Patterns Is Associated with Prognosis of Pathological T1-2N0M0 Lung Adenocarcinoma.

OBJECTIVE: To evaluate the prognostic value of the percentage of high-grade patterns (micropapillary, solid, and complex glands) in early-stage lung adenocarcinoma (LUAD). METHODS: A total of 1049 patients undergoing radical surgery with pathological T1-2N0M0 LUAD were screened retrospectively, and 191 patients were involved in the final analysis. Disease-free survival (DFS) was evaluated using the Kaplan-Meier curve and Cox regression analysis. The optimal cut-off value was determined using maximally selected rank statistics. RESULTS: The entire cohort was divided into quartile groups based on the percentage of high-grade patterns: Group 1 (≤ 30%), Group 2 (31-55%), Group 3 (56-85%), and Group 4 (≥ 86%). There were significant differences in smoking history (P = 0.041), EGFR mutations (P < 0.001), and ALK rearrangement (P = 0.010) between the four groups, but no significant differences in other clinicopathological features. Kaplan-Meier analysis showed that a higher percentage of high-grade patterns predicted worse DFS (P = 0.001), and multivariate analysis indicated that the percentage of high-grade patterns was an independent predictor (Group 2 vs. Group 1, HR = 2.136, P = 0.228; Group 3 vs. Group 1, HR = 3.355, P = 0.035; Group 4 vs. Group 1, HR = 5.147, P = 0.003, respectively). A cut-off value of 20% (P = 0.048) and 50% (P <0.001) for high-grade patterns were tested, and both revealed a significant difference in distinguishing DFS between subgroups. CONCLUSIONS: The percentage of high-grade patterns is associated with the prognosis of early-stage invasive LUAD. A higher percentage indicates a worse prognosis.

Integratable photodetectors based on photopolymerized conductive polymer via femtosecond laser direct writing.

Conductive polymers have attracted a great deal of attention due to their remarkable electrical conductivity. However, the low solubility and inability to meet the limit for the flexible patterning fabrication ability of conductive polymers hinders their applications in miniaturized and integrated electronic devices. Here, femtosecond laser direct writing (FsLDW) is employed to achieve the in situ fabrication of polypyrrole (PPy) with flexibility. Notably, high-precision flexible patterning with a minimum feature size of 5.2 µm and spatial control over the polymerization of PPy is achieved. Moreover, PPy microwires are constructed into a photodetector that exhibits a responsivity of 644 A/W at 0.1-V bias under ultraviolet (UV) irradiation. Ultimately, an image sensor is fabricated by integrating multiple photodetectors, demonstrating the application potential of FsLDW technology for developing miniaturized and integrated electronic devices based on conductive polymers.

Substituent Engineering-Enabled Structural Rigidification and Performance Improvement for C2/CO2 Separation in Three Isoreticular Coordination Frameworks.

Construction of porous solid materials applied to the adsorptive removal of CO2 from C2 hydrocarbons is highly demanded thanks to the important role C2 hydrocarbons play in the chemical industry but quite challenging owing to the similar physical parameters between C2 hydrocarbons and CO2. In particular, the development of synthetic strategies to simultaneously enhance the uptake capacity and adsorption selectivity is very difficult due to the trade-off effect frequently existing between both of them. In this work, a combination of the dicopper paddlewheel unit and 4-pyridylisophthalate derivatives bearing different substituents afforded an isoreticular family of coordination framework compounds as a platform. Their adsorption properties toward C2 hydrocarbons and CO2 were systematically investigated, and subsequent IAST and density functional theory calculations combined with column breakthrough experiments verified their promising potential for C2/CO2 separations. Furthermore, the substituent engineering endowed the resulting compounds with simultaneous enhancement of uptake capacity and adsorption selectivity and thus better C2/CO2 separation performance compared to their parent compound. The substituent introduction not only mitigated the framework distortion via fixing the ligand conformation for establishment of better permanent porosity required for gas adsorption but also polarized the framework surface for host-guest interaction improvement, thus resulting in enhanced separation performance.