SHMT2 Mediates Small-Molecule-Induced Alleviation of Alzheimer Pathology Via the 5'UTR-dependent ADAM10 Translation Initiation.

It is long been suggested that one-carbon metabolism (OCM) is associated with Alzheimer's disease (AD), whereas the potential mechanisms remain poorly understood. Taking advantage of chemical biology, that mitochondrial serine hydroxymethyltransferase (SHMT2) directly regulated the translation of ADAM metallopeptidase domain 10 (ADAM10), a therapeutic target for AD is reported. That the small-molecule kenpaullone (KEN) promoted ADAM10 translation via the 5' untranslated region (5'UTR) and improved cognitive functions in APP/PS1 mice is found. SHMT2, which is identified as a target gene of KEN and the 5'UTR-interacting RNA binding protein (RBP), mediated KEN-induced ADAM10 translation in vitro and in vivo. SHMT2 controls AD signaling pathways through binding to a large number of RNAs and enhances the 5'UTR activity of ADAM10 by direct interaction with GAGGG motif, whereas this motif affected ribosomal scanning of eukaryotic initiation factor 2 (eIF2) in the 5'UTR. Together, KEN exhibits therapeutic potential for AD by linking OCM with RNA processing, in which the metabolic enzyme SHMT2 "moonlighted" as RBP by binding to GAGGG motif and promoting the 5'UTR-dependent ADAM10 translation initiation.

Experimental investigation of seismic response of precast concrete panels with castellated keys support pillar connections under in-plane cyclic loading.

The reliable joint connection between precast members is vital to resisting earthquake loads in precast concrete structures. To further improve the convenience of precast construction, this paper presents a new horizontal joint of precast concrete panels with castellated keys supports pillar connections based on the stable mechanical properties of the wet concrete joint. To examine the seismic response of this connection type, a series of in-plane cyclic loading tests were carried out using six full-size precast specimens and one cast-in-place specimen for comparison. The influences of axial compression ratio, joint width, and joint concrete strength on the seismic indicators of the precast concrete panel were considered in the design of specimens. The test results showed all specimens had the same damage process, and the ultimate failure modes combined compression and bending. The precast specimens exhibited similar seismic performance to the cast-in-place specimen, especially whose joint concrete strength is higher than the precast concrete panel. Based on the load-displacement test curve, a hysteretic curve model that included both the envelope curve and the stiffness degradation law was proposed. The predictions from the model showed good compatibility with the experimental results, and the model can be used as a reference for analyzing the elastic-plastic response of the precast concrete panels with castellated keys supporting pillar connections.

Catalytic ozonation mechanism over M1-N3C1 active sites.

The structure-activity relationship in catalytic ozonation remains unclear, hindering the understanding of activity origins. Here, we report activity trends in catalytic ozonation using a series of single-atom catalysts with well-defined M1-N3C1 (M: manganese, ferrum, cobalt, and nickel) active sites. The M1-N3C1 units induce locally polarized M - C bonds to capture ozone molecules onto M atoms and serve as electron shuttles for catalytic ozonation, exhibiting excellent catalytic activities (at least 527 times higher than commercial manganese dioxide). The combined in situ characterization and theoretical calculations reveal single metal atom-dependent catalytic activity, with surface atomic oxygen reactivity identified as a descriptor for the structure-activity relationship in catalytic ozonation. Additionally, the dissociation barrier of surface peroxide species is proposed as a descriptor for the structure-activity relationship in ozone decomposition. These findings provide guidelines for designing high-performance catalytic ozonation catalysts and enhance the atomic-level mechanistic understanding of the integral control of ozone and methyl mercaptan.

Accurate estimation of fractional vegetation cover for winter wheat by integrated unmanned aerial systems and satellite images.

Accurate estimation of fractional vegetation cover (FVC) is essential for crop growth monitoring. Currently, satellite remote sensing monitoring remains one of the most effective methods for the estimation of crop FVC. However, due to the significant difference in scale between the coarse resolution of satellite images and the scale of measurable data on the ground, there are significant uncertainties and errors in estimating crop FVC. Here, we adopt a Strategy of Upscaling-Downscaling operations for unmanned aerial systems (UAS) and satellite data collected during 2 growing seasons of winter wheat, respectively, using backpropagation neural networks (BPNN) as support to fully bridge this scale gap using highly accurate the UAS-derived FVC (FVCUAS) to obtain wheat accurate FVC. Through validation with an independent dataset, the BPNN model predicted FVC with an RMSE of 0.059, which is 11.9% to 25.3% lower than commonly used Long Short-Term Memory (LSTM), Random Forest Regression (RFR), and traditional Normalized Difference Vegetation Index-based method (NDVI-based) models. Moreover, all those models achieved improved estimation accuracy with the Strategy of Upscaling-Downscaling, as compared to only upscaling UAS data. Our results demonstrate that: (1) establishing a nonlinear relationship between FVCUAS and satellite data enables accurate estimation of FVC over larger regions, with the strong support of machine learning capabilities. (2) Employing the Strategy of Upscaling-Downscaling is an effective strategy that can improve the accuracy of FVC estimation, in the collaborative use of UAS and satellite data, especially in the boundary area of the wheat field. This has significant implications for accurate FVC estimation for winter wheat, providing a reference for the estimation of other surface parameters and the collaborative application of multisource data.

The vertically-stratified resistomes in mangrove sediments was driven by the bacterial diversity.

Early evidence has elucidated that the spread of antibiotic (ARGs) and metal resistance genes (MRGs) are mainly attributed to the selection pressure in human-influenced environments. However, whether and how biotic and abiotic factors mediate the distribution of ARGs and MRGs in mangrove sediments under natural sedimentation is largely unclear. Here, we profiled the abundance and diversity of ARGs and MRGs and their relationships with sedimental microbiomes in 0-100 cm mangrove sediments. Our results identified multidrug-resistance and multimetal-resistance as the most abundant ARG and MRG classes, and their abundances generally decreased with the sediment depth. Instead of abiotic factors such as nutrients and antibiotics, the bacterial diversity was significantly negatively correlated with the abundance and diversity of resistomes. Also, the majority of resistance classes (e.g., multidrug and arsenic) were carried by more diverse bacterial hosts in deep layers with low abundances of resistance genes. Together, our results indicated that bacterial diversity was the most important biotic factor driving the vertical profile of ARGs and MRGs in the mangrove sediment. Given that there is a foreseeable increasing human impact on natural environments, this study emphasizes the important role of biodiversity in driving the abundance and diversity of ARGs and MRGs.

Antimony efflux underpins phosphorus cycling and resistance of phosphate-solubilizing bacteria in mining soils.

Microorganisms play crucial roles in phosphorus (P) turnover and P bioavailability increases in heavy metal-contaminated soils. However, microbially driven P-cycling processes and mechanisms of their resistance to heavy metal contaminants remain poorly understood. Here, we examined the possible survival strategies of P-cycling microorganisms in horizontal and vertical soil samples from the world's largest antimony (Sb) mining site, which is located in Xikuangshan, China. We found that total soil Sb and pH were the primary factors affecting bacterial community diversity, structure and P-cycling traits. Bacteria with the gcd gene, encoding an enzyme responsible for gluconic acid production, largely correlated with inorganic phosphate (Pi) solubilization and significantly enhanced soil P bioavailability. Among the 106 nearly complete bacterial metagenome-assembled genomes (MAGs) recovered, 60.4% carried the gcd gene. Pi transportation systems encoded by pit or pstSCAB were widely present in gcd-harboring bacteria, and 43.8% of the gcd-harboring bacteria also carried the acr3 gene encoding an Sb efflux pump. Phylogenetic and potential horizontal gene transfer (HGT) analyses of acr3 indicated that Sb efflux could be a dominant resistance mechanism, and two gcd-harboring MAGs appeared to acquire acr3 through HGT. The results indicated that Sb efflux could enhance P cycling and heavy metal resistance in Pi-solubilizing bacteria in mining soils. This study provides novel strategies for managing and remediating heavy metal-contaminated ecosystems.

Investigation of the effect of fly ash content on the bonding performance of CFRP-concrete interface in sulfate environment.

The present study focuses on the investigation of the interfacial bond behavior of carbon fiber-reinforced polymer (CFRP)-concrete under dry-wet sulfate cycles by double-sided shear testing. Besides, the effects of fly ash content on the interfacial failure characteristics, interfacial debonding bearing capacity, CFRP strain distribution, and interfacial shear stress peak were analyzed. The interfacial debonding capacity, maximum CFRP strain, and peak value of interfacial shear stress of the CFRP-concrete interface decreased with increasing erosion time under the sulfate dry-wet cycle's action, according to the sulfate dry-wet cycle test results. The sulfate resistance of the CFRP-concrete interface increased after the addition of fly ash. However, the final decrease amplitude of interfacial debonding capacity, CFRP maximum strain, and maximum interfacial shear stress all reduced as the fly ash content increased. The effective bond length of the interface gradually increased with increasing erosion time; however, the change in fly ash content had little effect on the effective bond length, and the final effective bond length of the samples with different fly ash content was the same. Moreover, the CFRP-concrete interfacial bearing capacity model under the sulfate dry-wet cycle was established by introducing sulfate's comprehensive influence coefficient and considering fly ash content's influence. In conclusion, the comparative analysis of the prediction model and test results revealed that the prediction model could well reflect the degradation law of interfacial debonding bearing capacity with sulfate attack time.

Integrative Bioinformatics Analysis Reveals CHEK1 and UBE2C as Luminal A Breast Cancer Subtype Biomarkers.

In light of the limited number of targetable oncogenic drivers in breast cancer (BRCA), it is important to identify effective and druggable gene targets for the treatment of this devastating disease. Herein, the GSE102484 dataset containing expression profiling data from 683 BRCA patients was re-analyzed using weighted gene co-expression network analysis (WGCNA). The yellow module with the highest correlation to BRCA progression was screened out, followed by functional enrichment analysis and establishment of a protein-protein interaction (PPI) network. After further validation through survival analysis and expression evaluation, CHEK1 and UBE2C were finally identified as hub genes related to the progression of BRCA, especially the luminal A breast cancer subtype. Notably, both hub genes were found to be dysregulated in multiple types of immune cells and closely correlated with tumor infiltration, as revealed by Tumor Immune Estimation Resource (TIMER) along with other bioinformatic tools. Construction of transcription factors (TF)-hub gene network further confirmed the existence of 11 TFs which could regulate both hub genes simultaneously. Our present study may facilitate the invention of targeted therapeutic drugs and provide novel insights into the understanding of the mechanism beneath the progression of BRCA.

Quercetin Inhibits KBM7R Cell Proliferation through Wnt/ß-Catenin Signaling.

Background: Tyrosine kinase inhibitors could treat chronic myelogenous leukemia (CML) effectively, but they have no effect on patients with T315I mutation. It is necessary to find drugs to overcome the resistance. Quercetin (Qu) is a kind of bioflavonoid with an antitumor effect. In this study, we observed the effect of Qu on proliferation and Wnt/ß-catenin pathway in KBM7R cells, an imatinib-resistant cell with T315I mutation. Methods: The IC50 of Qu was detected by trypan blue staining. The KBM7R cell apoptosis and cycle were detected through the method of flow cytometry (FCM). The expression of the related mRNA and protein was evaluated by means of an RT-PCR assay and western blot in KBM7 (sensitive to IM) and KBM7R cells. Results: These results showed that in the KBM7R cell, the proliferation inhibition effect was increased after 48 h administration with different Qu concentrations. The IC50 to Qu was 241.7 µmol/L. The different doses of Qu (50, 100, and 200 µmol/L) would raise apoptosis and depress the cell cycle at the G1 phase. Dealing with a median Qu concentration (100 µmol/L) for 48 h, the mRNA and the protein level of caspase-3, caspase-8, and caspase-9 along with p21 and p27 raised compared with the control. The median concentration of Qu could inhibit both the mRNA and protein levels of GSK-3ß, ß-catenin, and Lef-1 in the Wnt/ß-catenin signal pathway and also the downstream targets PPAR-δ and cyclin D1 in both KBM7 and KBM7R cells. Conclusions: Our findings suggest that Qu could inhibit proliferation, induce apoptosis, and arrest the cell cycle on IM-resistant KBM7R cells with T315I mutation. And this effect could be related with the inhibition of the Wnt/ß-catenin signal pathway and downstream targets.

PCycDB: a comprehensive and accurate database for fast analysis of phosphorus cycling genes.

BACKGROUND: Phosphorus (P) is one of the most essential macronutrients on the planet, and microorganisms (including bacteria and archaea) play a key role in P cycling in all living things and ecosystems. However, our comprehensive understanding of key P cycling genes (PCGs) and microorganisms (PCMs) as well as their ecological functions remains elusive even with the rapid advancement of metagenome sequencing technologies. One of major challenges is a lack of a comprehensive and accurately annotated P cycling functional gene database. RESULTS: In this study, we constructed a well-curated P cycling database (PCycDB) covering 139 gene families and 10 P metabolic processes, including several previously ignored PCGs such as pafA encoding phosphate-insensitive phosphatase, ptxABCD (phosphite-related genes), and novel aepXVWPS genes for 2-aminoethylphosphonate transporters. We achieved an annotation accuracy, positive predictive value (PPV), sensitivity, specificity, and negative predictive value (NPV) of 99.8%, 96.1%, 99.9%, 99.8%, and 99.9%, respectively, for simulated gene datasets. Compared to other orthology databases, PCycDB is more accurate, more comprehensive, and faster to profile the PCGs. We used PCycDB to analyze P cycling microbial communities from representative natural and engineered environments and showed that PCycDB could apply to different environments. CONCLUSIONS: We demonstrate that PCycDB is a powerful tool for advancing our understanding of microbially driven P cycling in the environment with high coverage, high accuracy, and rapid analysis of metagenome sequencing data. The PCycDB is available at https://github.com/ZengJiaxiong/Phosphorus-cycling-database . Video Abstract.

iTRAQ-derived quantitative proteomics uncovers the neuroprotective property of bexarotene in a mice model of cerebral ischemia-reperfusion injury.

Bexarotene, a FDA-approved drug for cutaneous lymphoma, has been shown to exert brain protective effects. In previous study, we demonstrated that Bexarotene protects against cerebral ischemic stroke by suppressing the JNK/Caspase-3 signaling pathway. However, the molecular mechanisms by which Bexarotene-mediated neuroprotective are not fully understood. Based on the isobaric tags for relative and absolute quantification (iTRAQ)-derived proteomics and bioinformatics analysis, 4,454 differentially expressed proteins (DEPs) were identified in upstream of the JNK signaling pathway. Among them, 149 DEPs showed aberrant expression in the vehicle-versus Bexarotene-treated mice. DEPs were primarily enriched in the metabolism, calcium, and MAPK signaling pathways. The largest DEP increase was seen with heat shock protein HSP 70, whereas the largest DEP decrease was seen with JNK scaffold protein JIP3, both of which are involved in the MAPK network. Furthermore, we illustrated the Bexarotene obviously abolished oxygen and glucose deprivation/reperfusion (OGD/R)- induced LDH leakage, cells apoptosis, and the protein expression level of the JIP3,p-ASK1, p-JNK, and Cleaved Caspase3. Together, these results suggest a potential neuroprotective role of Bexarotene via inhibition of the JIP3/ASK1/JNK/Caspase 3 signaling pathway.

ß-Caryophyllene suppresses ferroptosis induced by cerebral ischemia reperfusion via activation of the NRF2/HO-1 signaling pathway in MCAO/R rats.

BACKGROUND: Ischemic stroke is a complex brain disease regulated by several cell death processes, including apoptosis, autophagy, and ferroptosis. ß-Caryophyllene (BCP), a natural bicyclic sesquiterpene abundantly found in essential oils, has been demonstrated to have potential pharmacological benefits in many diseases, including ischemic stroke. PURPOSE: This research was to determine the existence of ferroptosis in the pathogenesis of acute ischemic stroke and investigate whether BCP can inhibit ferroptosis to improve cerebral ischemia injury by activating the NRF2/HO-1 signaling pathway in rats. METHODS: First, we verified ferroptosis by assessing proferroptotic changes after middle cerebral artery occlusion reperfusion (MCAO/R), along with protein and lipid peroxidation levels. Then male rats were divided randomly into Sham, MCAO/R, ML385 (NRF2-specific inhibitor) and BCP groups. The effects of BCP on cerebral injury were detected by the modified neurological severity score, TTC staining, and hematoxylin-eosin staining. We conducted western blotting analyzes of proteins, including those involved in ferroptosis and related signaling pathways. To demonstrate the neuroprotective effect of BCP in vitro, primary astrocytes were pretreated with different concentrations of BCP (10, 20, and 40 µM) for 24 h before oxygen-glucose deprivation/re-oxygenation (ODG/R). RESULTS: We concluded that ferroptosis was engaged in the process of I/R-induced neurological damage, implying that this novel type of cell death might provide new therapeutic options for the clinical treatment of ischemic stroke. In vivo study proved that BCP improved neurological scores, infarct volume, and pathological features after MCAO/R. We demonstrated that BCP evidently enhanced NRF2 nuclear translocation, activated the NRF2/HO-1 pathway, which protected against ferroptosis. In vitro investigation revealed the same results. BCP decreased OGD/R-induced ROS generation and iron accumulation. Furthermore, the neuroprotective effects of BCP were reversed by the NRF2 inhibitor ML385. CONCLUSION: Our results indicated the critical role of ferroptosis in cerebral I/R injury. For the first time, we showed that the significant neuroprotective effects of BCP in attenuating ischemic stroke injury are correlated with ferroptosis regulation, and its mechanism is associated with activation of the NRF2/HO-1 axis.

Interactions and Stability of Gut Microbiota in Zebrafish Increase with Host Development.

Understanding interactions within the gut microbiome and its stability are of critical importance for deciphering ecological issues within the gut ecosystem. Recent studies indicate that long-term instability of gut microbiota is associated with human diseases, and recovery of stability is helpful in the return to health. However, much less is known about such topics in fish, which encompass nearly half of all vertebrate diversity. Here, we examined the assembly and succession of gut microbiota in more than 550 zebrafish, and evaluated the variations of microbial interactions and stability across fish development from larva to adult using molecular ecological network analysis. We found that microbial interactions and stability in the fish gut ecosystem generally increased with host development. This could be attributed to the development of the zebrafish immune system, the increasing amount of space available for microbial colonization within the gut, and the greater stability of nutrients available for the colonized microbiota in adult zebrafish. Moreover, the potential keystone taxa, even those with relatively low abundances, played important roles in affecting the microbial interactions and stability. These findings indicate that regulating rare keystone taxa in adult fish may have great potential in gut microbial management to maintain gut ecosystem stability, which could also provide references for managing gut microbiota in humans and other animals. IMPORTANCE Understanding gut microbial stability and the underlying mechanisms is an important but largely ignored ecological issue in vertebrate fish. Here, using a zebrafish model and network analysis of the gut microbiota we found that microbial interactions and stability in the gut ecosystem increase with fish development. This finding has important implications for microbial management to maintain gut homeostasis and provide better gut ecosystem services for the host. First, future studies should always consider using fish of different age groups to gain a full understanding of gut microbial networks. Second, management of the keystone taxa, even those that are only present at a low abundance, during the adult stage may be a viable pathway to maintain gut ecosystem stability. This study greatly expands our current knowledge regarding gut ecosystem stability in terms of ecological networks affected by fish development, and also highlights potential directions for gut microbial management in humans and other animals.

Two-Dimensional High-Entropy Metal Phosphorus Trichalcogenides for Enhanced Hydrogen Evolution Reaction.

Developing earth-abundant and highly effective electrocatalysts for hydrogen evolution reaction (HER) is a prerequisite for the upcoming hydrogen energy society. Two-dimensional (2D) high-entropy metal phosphorus trichalcogenides (MPCh3) have the advantages of both near-continuous adsorption energies of high-entropy alloys (HEAs) and large specific surface area of 2D materials, which are excellent catalytic platforms. As a typical 2D high-entropy catalyst, Co0.6(VMnNiZn)0.4PS3 nanosheets with high-concentration active sites are successfully demonstrated to show enhanced HER performance: an overpotential of 65.9 mV at a current density of 10 mA cm-2 and a Tafel slope of 65.5 mV dec-1. Decent spectroscopy characterizations are combined with density function theory analyses to show the scenario for the enhancement mechanism by a high-entropy strategy. The optimized S sites on the edge and P sites on the basal plane provide more active sites for hydrogen adsorption, and the introduced Mn sites boost water dissociation during the Volmer step. Two-dimensional high-entropy MPCh3 provides an avenue for the combination of HEAs and 2D materials to enhance the HER performance, which also provides an alternative materials platform to explore and design superior catalysts for various electrochemical systems.

Efficacy and safety of laparoscopic common bile duct exploration via choledochotomy with primary closure for the management of acute cholangitis caused by common bile duct stones.

BACKGROUND: T-tube drainage after laparoscopic common bile duct exploration (LCBDE) has been demonstrated to be safe and effective for patients with acute cholangitis caused by common bile duct stones (CBDSs). The outcomes after LCBDE with primary closure in patients with CBDS-related acute cholangitis are unknown. The present study aimed to evaluate the efficacy and safety of LCBDE with primary closure for the management of acute cholangitis caused by CBDSs. METHODS: Between June 2015 and June 2020, 368 consecutive patients with choledocholithiasis combined with cholecystolithiasis, who underwent laparoscopic cholecystectomy (LC) + LCBDE in our department, were retrospectively reviewed. A total of 193 patients with CBDS-related acute cholangitis underwent LC + LCBDE with primary closure of the CBD (PC group) and 62 patients underwent LC + LCBDE followed by T-tube placement (T-tube group). A total of 113 patients who did not have cholangitis were excluded. The clinical data were compared and analyzed. RESULTS: There was no mortality in either group. No significant differences were noted in morbidity, bile leakage rate, retained CBD stones, or readmission rate within 30 days between the two groups. Compared with the T-tube group, the PC group avoided T-tube-related complications and had a shorter operative time (121.12 min vs. 143.37 min) and length of postoperative hospital stay (6.59 days vs. 8.81 days). Moreover, the hospital expenses in the PC group were significantly lower than those in the T-tube group ($4844.47 vs. $5717.22). No biliary stricture occurred during a median follow-up of 18 months in any patient. No significant difference between the two groups was observed in the rate of stone recurrence. CONCLUSIONS: LCBDE with primary closure is a safe and effective treatment for cholangitis caused by CBDSs. LCBDE with primary closure is not inferior to T-tube drainage for the management of CBDS-related acute cholangitis in suitable patients.

Extracellular proteins of Desulfovibrio vulgaris as adsorbents and redox shuttles promote biomineralization of antimony.

Biomineralization is the key process governing the biogeochemical cycling of multivalent metals in the environment. Although some sulfate-reducing bacteria (SRB) are recently recognized to respire metal ions, the role of their extracellular proteins in the immobilization and redox transformation of antimony (Sb) remains elusive. Here, a model strain Desulfovibrio vulgaris Hildenborough (DvH) was used to study microbial extracellular proteins of functions and possible mechanisms in Sb(V) biomineralization. We found that the functional groups (N-H, CO, O-CO, NH2-R and RCOH/RCNH2) of extracellular proteins could adsorb and fix Sb(V) through electrostatic attraction and chelation. DvH could rapidly reduce Sb(V) adsorbed on the cell surface and form amorphous nanometer-sized stibnite and/or antimony trioxide, respectively with sulfur and oxygen. Proteomic analysis indicated that some extracellular proteins involved in electron transfer increased significantly (p < 0.05) at 1.8 mM Sb(V). The upregulated flavoproteins could serve as a redox shuttle to transfer electrons from c-type cytochrome networks to reduce Sb(V). Also, the upregulated extracellular proteins involved in sulfur reduction, amino acid transport and protein synthesis processes, and the downregulated flagellar proteins would contribute to a better adaption under 1.8 mM Sb(V). This study advances our understanding of how microbial extracellular proteins promote Sb biomineralization in DvH.

Weighted Gene Co-Expression Network Analysis and Treatment Strategies of Tumor Recurrence-Associated Hub Genes in Lung Adenocarcinoma.

Despite the recent progress of lung adenocarcinoma (LUAD) therapy, tumor recurrence remained to be a challenging factor that impedes the effectiveness of treatment. The objective of the present study was to predict the hub genes affecting LUAD recurrence via weighted gene co-expression network analysis (WGCNA). Microarray samples from LUAD dataset of GSE32863 were analyzed, and the modules with the highest correlation to tumor recurrence were selected. Functional enrichment analysis was conducted, followed by establishment of a protein-protein interaction (PPI) network. Subsequently, hub genes were identified by overall survival analyses and further validated by evaluation of expression in both myeloid populations and tissue samples of LUAD. Gene set enrichment analysis (GSEA) was then carried out, and construction of transcription factors (TF)-hub gene and drug-hub gene interaction network was also achieved. A total of eight hub genes (ACTR3, ARPC5, RAB13, HNRNPK, PA2G4, WDR12, SRSF1, and NOP58) were finally identified to be closely correlated with LUAD recurrence. In addition, TFs that regulate hub genes have been predicted, including MYC, PML, and YY1. Finally, drugs including arsenic trioxide, cisplatin, Jinfukang, and sunitinib were mined for the treatment of the eight hub genes. In conclusion, our study may facilitate the invention of targeted therapeutic drugs and shed light on the understanding of the mechanism for LUAD recurrence.

Genome-Wide Assessment Characteristics of Genes Overlapping Copy Number Variation Regions in Duroc Purebred Population.

Copy number variations (CNVs) are important structural variations that can cause significant phenotypic diversity. Reliable CNVs mapping can be achieved by identification of CNVs from different genetic backgrounds. Investigations on the characteristics of overlapping between CNV regions (CNVRs) and protein-coding genes (CNV genes) or miRNAs (CNV-miRNAs) can reveal the potential mechanisms of their regulation. In this study, we used 50 K SNP arrays to detect CNVs in Duroc purebred pig. A total number of 211 CNVRs were detected with a total length of 118.48 Mb, accounting for 5.23% of the autosomal genome sequence. Of these CNVRs, 32 were gains, 175 losses, and four contained both types (loss and gain within the same region). The CNVRs we detected were non-randomly distributed in the swine genome and were significantly enriched in the segmental duplication and gene density region. Additionally, these CNVRs were overlapping with 1,096 protein-coding genes (CNV-genes), and 39 miRNAs (CNV-miRNAs), respectively. The CNV-genes were enriched in terms of dosage-sensitive gene list. The expression of the CNV genes was significantly higher than that of the non-CNV genes in the adult Duroc prostate. Of all detected CNV genes, 22.99% genes were tissue-specific (TSI > 0.9). Strong negative selection had been underway in the CNV-genes as the ones that were located entirely within the loss CNVRs appeared to be evolving rapidly as determined by the median dN plus dS values. Non-CNV genes tended to be miRNA target than CNV-genes. Furthermore, CNV-miRNAs tended to target more genes compared to non-CNV-miRNAs, and a combination of two CNV-miRNAs preferentially synergistically regulated the same target genes. We also focused our efforts on examining CNV genes and CNV-miRNAs functions, which were also involved in the lipid metabolism, including DGAT1, DGAT2, MOGAT2, miR143, miR335, and miRLET7. Further molecular experiments and independent large studies are needed to confirm our findings.

Genome-Wide Phylogenetic Analysis, Expression Pattern, and Transcriptional Regulatory Network of the Pig C/EBP Gene Family.

The CCAAT/enhancer binding protein (C/EBP) transcription factors (TFs) regulate many important biological processes, such as energy metabolism, inflammation, cell proliferation etc. A genome-wide gene identification revealed the presence of a total of 99 C/EBP genes in pig and 19 eukaryote genomes. Phylogenetic analysis showed that all C/EBP TFs were classified into 6 subgroups named C/EBPα, C/EBPß, C/EBPδ, C/EBPε, C/EBPγ, and C/EBPζ. Gene expression analysis showed that the C/EBPα, C/EBPß, C/EBPδ, C/EBPγ, and C/EBPζ genes were expressed ubiquitously with inconsistent expression patterns in various pig tissues. Moreover, a pig C/EBP regulatory network was constructed, including C/EBP genes, TFs and miRNAs. A total of 27 feed-forward loop (FFL) motifs were detected in the pig C/EBP regulatory network. Based on the RNA-seq data, gene expression patterns related to FFL sub-network were analyzed in 27 adult pig tissues. Certain FFL motifs may be tissue specific. Functional enrichment analysis indicated that C/EBP and its target genes are involved in many important biological pathways. These results provide valuable information that clarifies the evolutionary relationships of the C/EBP family and contributes to the understanding of the biological function of C/EBP genes.

Synergetic Molecular Oxygen Activation and Catalytic Oxidation of Formaldehyde over Defective MIL-88B(Fe) Nanorods at Room Temperature.

Defective MIL-88B(Fe) nanorods are exploited as exemplary iron-bearing metal-organic framework (MOF) catalyst for molecular oxygen (O2) activation at ambient temperature, triggering effective catalytic oxidation of formaldehyde (HCHO), one of the major indoor air pollutants. Defective MIL-88B(Fe) nanorods, growing along the [001] direction, expose abundant coordinatively unsaturated Fe-sites (Fe-CUSs) along extended hexagonal channels with a diameter of ca. 5 Å, larger enough for the diffusion of O2 (3.46 Å) and HCHO (2.7 Å). The Lewis acid-base interaction between Fe-CUSs and accessible HCHO accelerates the FeIII/FeII cycle, catalyzing Fenton-like O2 activation to produce reactive oxidative species (ROSs), including superoxide radicals (•O2-), hydroxyl radicals (•OH), and singlet oxygen (1O2). Consequently, adsorbed HCHO can be oxidized into CO2 with a considerable mineralization efficiency (over 80%) and exceptional recyclability (4 runs, 48 h). Dioxymethylene (CH2OO), formate (HCOO-) species, and formyl radicals (•CHO) are recorded as the main reaction intermediates during HCHO oxidation. HCHO, H2O, and O2 are captured and activated by abundant FeIII/FeII-CUSs as acid/base and redox sites, triggering synergetic ROS generation and HCHO oxidation, involving cooperative acid-base and redox catalysis processes. This study will bring new insights into exploiting novel MOF catalysts for efficient O2 activation and reliable indoor air purification at ambient temperature.