Genome-wide view and characterization of natural antisense transcripts in Cannabis Sativa L.

Natural Antisense Transcripts (NATs) are a kind of complex regulatory RNAs that play crucial roles in gene expression and regulation. However, the NATs in Cannabis Sativa L., a widely economic and medicinal plant rich in cannabinoids remain unknown. In this study, we comprehensively predicted C. sativa NATs genome-wide using strand-specific RNA sequencing (ssRNA-Seq) data, and validated the expression profiles by strand-specific quantitative reverse transcription PCR (ssRT-qPCR). Consequently, a total of 307 NATs were predicted in C. sativa, including 104 cis- and 203 trans- NATs. Functional enrichment analysis demonstrated the potential involvement of the C. sativa NATs in DNA polymerase activity, RNA-DNA hybrid ribonuclease activity, and nucleic acid binding. Finally, 18 cis- and 376 trans- NAT-ST pairs were predicted to produce 621 cis- and 5,679 trans- small interfering RNA (nat-siRNAs), respectively. These nat-siRNAs were potentially involved in the biosynthesis of cannabinoids and cellulose. All these results will shed light on the regulation of NATs and nat-siRNAs in C. sativa.

Analysis of Correlation between Rab1A Expression and its Prognosis in Cancers: a Meta-Analysis.

BACKGROUND: Rab1A not only regulates eukaryotic secretion, autophagy and intracellular traffic, but also extensively participates in the development of cancer. Thus, we collected data to investigate the clinical value of Rab1A in cancers. METHODS: English web database was searched for appropriate studies. The role of Rab1A in cancer patients was evaluated by combining hazard ratios and odds ratios. RESULTS: There were 15 studies in 14 articles, including 1,791 cancer patients. The results showed that upregulated Rab1A led to poor prognosis in cancer patients (pooled HR = 2.545, 95% CI = 1.924 - 3.367, p < 0.001). Notably, a high level of Rab1A was associated with a poorer prognosis than patients with a low level of Rab1A in digestive system cancer (pooled HR = 2.484, 95% CI = 1.796 - 3.437, p < 0.001). In order to explore the possible carcinogenic mechanism, we further analyzed and confirmed that high expression of Rab1A was associated with worse histologic grade, deeper tumor invasion, higher TNM stage, positive LN metastasis, positive neural invasion, positive vascular invasion, and larger tumor size (p < 0.05). CONCLUSIONS: Rab1A overexpression was associated with poor prognosis and adverse clinicopathological parameters in cancer patients and had the potential to be a target for future cancer therapy.

Management of cognitive frailty: A network meta-analysis of randomized controlled trials.

OBJECTIVES: We aimed to compare the effectiveness of interventions in cognitive function and frailty status and rank these interventions. METHODS: Data Sources-We searched PubMed, Embase, CINAHL, PsycINFO, Web of Science, Cochrane Library, Central Register of Controlled Trials (CENTRAL), CNKI, Wanfang, VIP and Google scholar. Data synthesis-The risk of bias was assessed using the Cochrane risk bias assessment tool. Statistical heterogeneity was assessed using the Chi-square test and quantified by I2 . The results were pooled using the standardized mean difference (SMD). The rank probability for each intervention was calculated using the surface under the cumulative ranking curve (SUCRA). Additionally, the quality of the evidence was evaluated using the GRADE approach. RESULTS: A total of 10 randomized controlled trials (RCTs) involving 1110 patients were included in our analysis. The network map of cognitive function comprised 9 RCTs with 1347 participants, examining eight different interventions. Nutritional support (SUCRA = 99.9%, SMD = 3.02, 95% CI: 2.53, 3.51) may be the most effective intervention to improve cognitive function. The network map of frailty (including 9 RCTs with 1017 participants and 9 interventions) suggested that multicomponent exercises (SUCRA = 96.4%, SMD = -5.10, 95% CI: -5.96, -4.23) tended to have a greater effect. CONCLUSIONS: Community-based multicomponent exercises have shown significant benefits for improving cognitive function and frailty status in older adults, with moderate certainty. For hospitalized older patients with Cognitive frailty (CF), current evidence suggests that nutritional support yields the most improvement. Additionally, aerobic exercise and dual-task training have proven effective in managing CF. Further studies are needed to validate these preliminary findings and exploring more accessible and effective physical and cognitive interventions to prevent CF in aging.

Digital Pupillometry and Centroid Shift Changes in Dominant and Nondominant Eyes.

PURPOSE: To investigate the differences between dominant and nondominant eyes in a predominantly young patient population by analyzing the angle kappa, pupil size, and center position in dominant and nondominant eyes. METHODS: A total of 126 young college students (252 eyes) with myopia who underwent femtosecond laser-combined LASIK were randomly selected. Ocular dominance was determined using the hole-in-card test. The WaveLight Allegro Topolyzer (WaveLight Laser Technologies AG, Erlangen, Germany) was used to measure the pupil size and center position. The offset between the pupil center and the coaxially sighted corneal light reflex (P-Dist) of the patients was recorded by the x- and y-axis eyeball tracking adjustment program of the WaveLight Eagle Vision EX500 excimer laser system (Wavelight GmbH). The patient's vision (uncorrected distance visual acuity [UDVA], best-corrected visual acuity (BCVA), and refractive power (spherical equivalent, SE) were observed preoperatively, 1 week, 4 weeks, and 12 weeks postoperatively, and a quality of vision (QoV) questionnaire was completed. RESULTS: Ocular dominance occurred predominantly in the right eye [right vs. left: (178) 70.63% vs. (74) 29.37%; p < 0.001]. The P-Dist was 0.202 ± 0.095 mm in the dominant eye and 0.215 ± 0.103 mm in the nondominant eye (p = 0.021). The horizontal pupil shift was - 0.07 ± 0.14 mm in dominant eyes and 0.01 ± 0.13 mm in nondominant eyes (p = 0.001) (the temporal displacement of the dominant eye under mesopic conditions). The SE was negatively correlated with the P-Dist (r = - 0.223, p = 0.012 for the dominant eye and r = - 0.199, p = 0.025 for the nondominant eye). At 12 weeks postoperatively, the safety index (postoperative BDVA/preoperative BDVA) of the dominant and nondominant eyes was 1.20 (1.00, 1.22) and 1.20 (1.00, 1.20), respectively, and the efficacy index (postoperative UDVA/preoperative BDVA) was 1.00 (1.00, 1.20) and 1.00 (1.00, 1.20), respectively; the proportion of residual SE within ± 0.50 D was 98 and 100%, respectively. CONCLUSIONS: This study found that ocular dominance occurred predominantly in the right eye. The pupil size change was larger in the dominant eye. The angle kappa of the dominant eye was smaller than that of the nondominant eye and the pupil center of the dominant eye was slightly shifted to the temporal side under mesopic conditions. The correction of myopia in the dominant and nondominant eyes exhibits good safety, efficacy, and predictability in the short term after surgery, and has good subjective visual quality performance after correction. We suggest adjusting the angle kappa percentage in the dominant eye to be lower than that of the nondominant eye in individualized corneal refractive surgery in order to find the ablation center closest to the visual axis.

LncRNA ITGB2-AS1 promotes cisplatin resistance of non-small cell lung cancer by inhibiting ferroptosis via activating the FOSL2/NAMPT axis.

Cisplatin resistance is a major therapeutic challenge in non-small cell lung cancer (NSCLC). Herein, the regulatory role of long non-coding RNA (lncRNA) ITGB2-AS1 in regulating NSCLC cisplatin resistance was investigated. NSCLC cisplatin resistance cells were constructed using A549 and H1975 cells. Cell viability and proliferation were detected by MTT assay and colony formation assay, respectively. Cell apoptosis and cell cycle were examined by flow cytometry. GSH, MDA, ROS, and Fe2+ levels were measured by the corresponding kits. The expressions of ferroptosis-negative regulation genes (GPX4 and SLC7A11) were determined by qRT-PCR and western blot. Molecular interactions were analyzed by RNA pull-down, RIP, ChIP, and dual-luciferase reporter assays. The effects of ITGB2-AS1 silencing on NSCLC cisplatin resistance in vivo were elevated by the tumor xenograft experiment. ITGB2-AS1 expression was increased in NSCLC patients and cisplatin-resistant NSCLC cells, which was positively correlated with ferroptosis-negative regulation genes. ITGB2-AS1 knockdown suppressed resistant cell proliferation and promoted cell apoptosis and ferroptosis. ITGB2-AS1 increased NAMPT expression by binding to FOSL2, thereby repressing p53 expression. The ITGB2-AS1 knockdown also inhibited NSCLC cisplatin resistance in vivo. ITGB2-AS1 promoted NSCLC cisplatin resistance by inhibiting p53-mediated ferroptosis via activating the FOSL2/NAMPT axis.

Identification of circular RNAs of Cannabis sativa L. potentially involved in the biosynthesis of cannabinoids.

MAIN CONCLUSION: We identified circRNAs in the Cannabis sativa L. genome and examined their association with 28 cannabinoids in three tissues of C. sativa. Nine circRNAs are potentially involved in the biosynthesis of six cannabinoids. Cannabis sativa L. has been widely used in the production of medicine, textiles, and food for over 2500 years. The main bioactive compounds in C. sativa are cannabinoids, which have multiple important pharmacological actions. Circular RNAs (circRNAs) play essential roles in growth and development, stress resistance, and the biosynthesis of secondary metabolites. However, the circRNAs in C. sativa remain unknown. In this study, to explore the role of circRNAs in cannabinoid biosynthesis, we performed RNA-Seq and metabolomics analysis on the leaves, roots, and stems of C. sativa. We identified 741 overlapping circRNAs by three tools, of which 717, 16, and 8 circRNAs were derived from exonic, intronic, and intergenic, respectively. Functional enrichment analysis indicated that the parental genes (PGs) of circRNAs were enriched in many processes related to biological stress responses. We found that most of the circRNAs showed tissue-specific expression and 65 circRNAs were significantly correlated with their PGs (P < 0.05, |r|≥ 0.5). We also determined 28 cannabinoids by High-performance liquid chromatography-ESI-triple quadrupole-linear ion trap mass spectrometry. Ten circRNAs, including ciR0159, ciR0212, ciR0153, ciR0149, ciR0016, ciR0044, ciR0022, ciR0381, ciR0006, and ciR0025 were found to be associated with six cannabinoids by weighted gene co-expression network analysis. Twenty-nine of 53 candidate circRNAs, including 9 cannabinoids related were validated successfully using PCR amplification and Sanger sequencing. Taken together, all these results would help to enhance our acknowledge of the regulation of circRNAs, and lay the foundation for breeding new C. sativa cultivars with high cannabinoids through manipulating circRNAs.

Polymeric structure of the Cannabis sativa L. mitochondrial genome identified with an assembly graph model.

Cannabis sativa L. belongs to the family Cannabaceae in Rosales. It has been widely used as medicines, building materials, and textiles. Elucidating its genome is critical for molecular breeding and synthetic biology study. Many studies have shown that the mitochondrial genomes (mitogenomes) and even chloroplast genomes (plastomes) had complex polymeric structures. Using the Nanopore sequencing platform, we sequenced, assembled, and analyzed its mitogenome and plastome. The resulting unitig graph suggested that the mitogenome had a complex polymeric structure. However, a gap-free, circular sequence was further assembled from the unitig graph. In contrast, a circular sequence representing the plastome was obtained. The mitogenome major conformation was 415,837 bp long, and the plastome was 153,927 bp long. To test if the repeat sequences promote recombination, which corresponds to the branch points in the structure, we tested the sequences around repeats by long-read mapping. Among 208 pairs of predicted repeats, the mapping results supported the presence of cross-over around 25 pairs of repeats. Subsequent PCR amplification confirmed the presence of cross-over around 15 of the 25 repeats. By comparing the mitogenome and plastome sequences, we identified 19 mitochondria plastid DNAs, including seven complete genes (trnW-CCA, trnP-UGG, psbJ, trnN-GUU, trnD-GUC, trnH-GUG, trnM-CAU) and nine gene fragments. Furthermore, the selective pressure analysis results showed that five genes (atp1, ccmB, ccmC, cox1, nad7) had 19 positively selected sites. Lastly, we predicted 28 RNA editing sites. A total of 8 RNA editing sites located in the coding regions were successfully validated by PCR amplification and Sanger sequencing, of which four were synonymous, and four were nonsynonymous. In particular, the RNA editing events appeared to be tissue-specific in C. sativa mitogenome. In summary, we have confirmed the major confirmation of C. sativa mitogenome and characterized its structural features in detail. These results provide critical information for future variety breeding and resource development for C. sativa.

Vibration analysis of a high-pressure multistage centrifugal pump.

High-pressure multistage centrifugal pumps have been widely used in modern industry and required low vibration and noise. In this study, modal analysis of the rotor system of a seven-stage centrifugal pump was carried out numerically by introducing fluid force to ensure that the centrifugal pump would not resonate. A vibration test bench was established to investigate the characteristics with flow rates of 0.8Qd, 1.0Qd, and 1.2Qd, and the vibration data of ten measuring points were collected. The period of the vibration at the bearing was found to be around 20 ms and the period was related to the shaft frequency (SF) and the blade passing frequency (BPF). The vibration of the pump casing was mainly determined by the SF, two times the SF, and two times the BPF. Mechanical motion is the main factor causing pump vibration, and fluid unstable motion is also an important cause.

Whole-exome sequencing identified a homozygous novel RAG1 mutation in a child with omenn syndrome.

INTRODUCTION AND OBJECTIVES: Omenn syndrome (OS) is a very rare type of severe combined immunodeficiencies manifested with erythroderma, eosinophilia, hepatosplenomegaly, lymph-adenopathy, and elevated level of serum IgE. OS is inherited with an autosomal recessive mode of inheritance. Germline mutations in the human RAG1 gene cause OS. MATERIALS AND METHODS: In this study, we investigated a 2-month-old boy with cough, mild anaemia, pneumonia, immunodeficiency, repeated infection, feeding difficulties, hepatomegaly, growth retardation, and heart failure. Parents of the proband were phenotypically normal. RESULTS: Karyotype analysis and chromosomal microarray analysis found no chromosomal structural abnormalities (46, XY) and no pathogenic copy number variations (CNVs) in the proband. Whole-exome sequencing identified a novel homozygous single nucleotide deletion (c.2662delC) in exon 2 of the RAG1 gene in the proband. Sanger sequencing confirmed that both the proband parents were carrying this variant in a heterozygous state. This variant was not identified in two elder sisters and one elder brother of the proband and in the 100 ethnically matched normal healthy individuals. This novel homozygous deletion (c.2662delC) leads to the frameshift, which finally results in the formation of the truncated protein (p.Leu888Phefs*3) V(D)J recombination-activating protein 1 with 890 amino acids compared with the wildtype V(D)J recombination-activating protein 1 of 1043 amino acids. Hence, it is a loss-of-function variant. CONCLUSIONS: Our present study expands the mutational spectrum of the RAG1 gene associated with OS. We also strongly suggested the importance of whole-exome sequencing for the genetic screening of patients with OS.

Phylogenomic analysis and development of molecular markers for the determination of twelve plum cultivars (Prunus, Rosaceae).

BACKGROUND: Plums are one of the most important economic crops of the Rosaceae family and are produced all over the world. China has many local varieties, but the genomic information is limited for genetic studies. Here, we first sequenced, assembled, and analyzed the plastomes of twelve plum cultivars and developed molecular markers to distinguish them. RESULTS: The twelve plastomes of plum cultivars have a circular structure of 157,863-157,952 bp containing a large single-copy region (LSC) of 86,109-86,287 bp, a small copy region (SSC) of 18,927-19,031 bp, and two inverted repeats (IR) of 26,353-26,387 bp each. The plastomes of plum cultivars encode 131 genes, including 86 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. We detected 50, 54, 54, 53, 53, 50, 54, 54, 54, 49, 50, 54 SSRs in the twelve analyzed varieties, respectively. For repeat sequences, we identified 553 tandem repeats, 204 direct repeats, and 270 palindromic repeats. We also analyzed the expansion/contraction of IR regions. The genes rpl22, rps19, rpl2, ycf1, ndhF, and the trnH span on or near the boundary of IR and single-copy regions. Phylogenetic analysis showed that the twelve cultivars were clustered with the P. salicina and P. domestica. We developed eight markers LZ01 to LZ08 based on whole plastomes and nuclear genes and validated them successfully with six repetitions. CONCLUSIONS: The results obtained here could fill in the blanks of the plastomes of these twelve plum cultivars and provide a wider perspective based on the basis of the plastomes of Prunus to the molecular identification and phylogenetic construction accurately. The analysis from this study provides an important and valuable resource for studying the genetic basis for agronomic and adaptive differentiation of the Prunus species.

Prognostic and clinicopathological significance of CD155 expression in cancer patients: a meta-analysis.

BACKGROUND: It has been previously reported that CD155 is often over-expressed in a variety of cancer types. In fact, it is known to be involved in cancer development, and its role in cancer has been widely established. However, clinical and mechanistic studies involving CD155 yielded conflicting results. Thus, the present study aimed to evaluate overall prognostic value of CD155 in cancer patients, using a comprehensive analysis. METHODS: Online databases were searched, data was collected, and clinical value of CD155 was evaluated by combining hazard ratios (HRs) or odds ratios (ORs). RESULTS: The present study involved meta-analysis of 26 previous studies that involved 4325 cancer patients. These studies were obtained from 25 research articles. The results of the study revealed that increased CD155 expression was significantly associated with reduced OS in patients with cancer as compared to low CD155 expression (pooled HR = 1.772, 95% CI = 1.441-2.178, P < 0.001). Furthermore, subgroup analysis demonstrated that the level of CD155 expression was significantly associated with OS in patients with digestive system cancer (pooled HR = 1.570, 95% CI = 1.120-2.201, P = 0.009), hepatobiliary pancreatic cancer (pooled HR = 1.677, 95% CI = 1.037-2.712, P = 0.035), digestive tract cancer (pooled HR = 1.512, 95% CI = 1.016-2.250, P = 0.042), breast cancer (pooled HR = 2.137, 95% CI = 1.448-3.154, P < 0.001), lung cancer (pooled HR = 1.706, 95% CI = 1.193-2.440, P = 0.003), head and neck cancer (pooled HR = 1.470, 95% CI = 1.160-1.862, P = 0.001). Additionally, a significant correlation was observed between enhanced CD155 expression and advanced tumor stage (pooled OR = 1.697, 95% CI = 1.217-2.366, P = 0.002), LN metastasis (pooled OR = 1.953, 95% CI = 1.253-3.046, P = 0.003), and distant metastasis (pooled OR = 2.253, 95% CI = 1.235-4.110, P = 0.008). CONCLUSION: Altogether, the results of the present study revealed that CD155 acted as an independent marker of prognosis in cancer patients, and it could provide a new and strong direction for cancer treatment.

SOX2 contributes to invasion and poor prognosis of gastric cancer: A meta-analysis.

BACKGROUND: The sex-determining region Y-box 2 (SOX2) has been identified to be involved in tumor progression and prognosis in patients with gastric cancer (GC). However, its action is paradoxical. Thus, we conducted the first meta-analysis based on eligible studies to evaluate the clinical utility of SOX2 in GC only. METHODS: A thorough electronic search was performed to collect eligible studies. The hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were generated from included studies to assess the strength of the association between SOX2 and prognosis and clinicopathological characteristics in GC. RESULTS: A total of 10 studies comprising 1321 patients with GC were identified for the meta-analysis. The pooled results revealed that high SOX2 expression was significantly associated with poor overall survival compared to low SOX2 expression (pooled HR = 1.485; 95% CI: 1.022-2.160; 𝑃 = .04). The statistical significance between SOX2 expression and overall survival was also established in univariate analysis (pooled HR = 1.606; 95% CI: 1.134-2.274; 𝑃 < .01), as well as recruitment time exceeding 2010 (pooled HR = 1.873; 95% CI: 1.041-3.371; 𝑃 = .04), follow-up time more than 5 years (pooled HR = 1.642; 95% CI: 1.066-2.527; 𝑃 = .02), and cutoff value of more than 5% of cells stained (pooled HR = 1.730; 95% CI: 1.162-2.577; 𝑃 < .01). Moreover, we verified that positive SOX2 expression was correlated with advanced tumor invasion depth (pooled OR = 0.494; 95% CI: 0.362-0.675; 𝑃 < .01) and positive vascular invasion (pooled OR = 1.515; 95% CI: 1.078-2.130; 𝑃 = .02). CONCLUSION: SOX2 could not only be an independent prognostic marker in GC but might also be a novel target for cancer therapy.

Identification of two potential immune-related biomarkers of Graves' disease based on integrated bioinformatics analyses.

BACKGROUND: Graves' disease (GD) is an autoimmune disease, the incidence of which is increasing yearly. GD requires long-life therapy. Therefore, the potential immune-related biomarkers of GD need to be studied. METHOD: In our study, differentially expressed genes (DEGs) were derived from the online Gene Expression Omnibus (GEO) microarray expression dataset GSE71956. Protein‒protein interaction (PPI) network analyses were used to identify hub genes, which were validated by qPCR. GSEA was used to screen potential pathways and related immune cells. Next, CIBERSORT analysis was used to further explore the immune subtype distribution pattern among hub genes. ROC curves were used to analyze the specificity and sensitivity of hub genes. RESULT: 44 DEGs were screened from the GEO dataset. Two hub genes, EEF1A1 and EIF4B, were obtained from the PPI network and validated by qPCR (p < 0.05). GSEA was conducted to identify potential pathways and immune cells related to these the two hub genes. Immune cell subtype analysis revealed that hub genes had extensive associations with many different types of immune cells, particularly resting memory CD4+ T cells. AUCs of ROC analysis were 0.687 and 0.733 for EEF1A1 and EIF4B, respectively. CONCLUSION: Our study revealed two hub genes, EEF1A1 and EIF4B, that are associated with resting memory CD4+ T cells and potential immune-related molecular biomarkers and therapeutic targets of GD.

Hydrodynamic cavitation as an efficient water treatment method for various sewage:- A review.

With the development of industry and the rapid growth of population, the current water treatment technologies face many challenges. Hydrodynamic cavitation as a green and efficient means of water treatment has attracted much attention. During the hydrodynamic cavitation, enormous energy could be released into the surrounding liquid which causes thermal effects (local hotspots with 4600 K), mechanical effects (pressures of 1500 bar) and chemical effects (hydroxyl radicals). These conditions can degrade bacteria and organic substance in sewage. Moreover, the combination of hydrodynamic cavitation and other water treatment methods can produce a coupling effect. In this review, we summarize the methods of hydrodynamic cavitation and the performance of water treatment for different types of sewage. The application of hydrodynamic cavitation reactors with different structures in water treatment are also evaluated and discussed. The design and optimization of high-performance hydrodynamic cavitation reactor are the most crucial issues for the application of hydrodynamic cavitation in water treatment. Finally, recommendations are provided for the future progress of hydrodynamic cavitation for water treatment.

Cavitation characteristics analysis of a novel rotor-radial groove hydrodynamic cavitation reactor.

Hydrodynamic cavitation was widely used in sterilization, emulsion preparation and other industrial fields. Cavitation intensity is the key performance index of hydrodynamic cavitation reactor. In this study, a novel rotor-radial groove (RRG) hydrodynamic cavitation reactor was proposed with good cavitation intensity and energy utilization. The cavitation performances of RRG hydrodynamic cavitation reactor was analyzed by utilizing computational fluid dynamics method. The cavitation intensity and the cavitation energy efficiency were used as evaluation indicators for RRG hydrodynamic cavitation reactor with different internal structures. The amount of generated cavitation for various shapes of the CGU, interaction distances and rotor speed were analyzed. The evolution cycle of cavitation morphology is periodicity (0.46 ms) in the CGU of RRG hydrodynamic cavitation reactor. The main cavitation regions of CGU were the outflow and inflow separation zones. The cavitation performance of rectangular-shaped CGU was better than the cylindrical-shaped CGU. In addition, the cavitation performance could be improved more effectively by increasing the rotor speed and decreasing the interaction distance. The research results could provide theoretical support for the research of cavitation mechanism of cavitation equipment.

Synthesis and pharmacological validation of fluorescent diarylsulfonylurea analogues as NLRP3 inhibitors and imaging probes.

The NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) is a key cytosolic pattern recognition receptor that senses diverse pathogen- and host-originated threat signals. Aberrant activation of NLRP3 inflammasomes is closely associated with the pathogenesis of various complex inflammatory diseases. Nevertheless, the detailed regulation mechanism of NLRP3 inflammasome and its pathogenic roles in the inflammation progression remain to be fully elucidated. Fluorescent imaging with small molecule probe can provide valuable visualization information on the expression, occupancy and bio-distribution of target protein. Herein, we reported a series of diarylsulfonylurea NLRP3 fluorescent inhibitors bearing an amino benzodiazole fluorophore. Compared to the previously reported NLRP3 fluorescent probes, these inhibitors are more structurally concise and membrane permeable due to no additionally appended fluorophore via a linker. Among this series, compound 13a exhibited the most potent cellular NLRP3 inhibitory effect with an IC50 value of 49 nM, and significantly suppressed LPS/Nigericin-induced secretion of active caspase-1 and mature IL-1ß in a dose-dependent manner to block the activation of NLRP3 inflammasome. Meanwhile, this new probe exhibited promising fluorescent properties for specifically detecting and imaging the LPS-induced or constitutively expressed NLRP3 proteins in RAW264.7 cells. Collectively, probe 13a is a potent NLRP3 fluorescent inhibitor with cellular NLRP3 imaging ability, which is useful for NLRP3 inhibitor screening and related mechanism study.

Development of a 5-Gene Signature to Evaluate Lung Adenocarcinoma Prognosis Based on the Features of Cancer Stem Cells.

Cancer stem cells (CSCs) can induce recurrence and chemotherapy resistance of lung adenocarcinoma (LUAD). Reliable markers identified based on CSC characteristic of LUAD may improve patients' chemotherapy response and prognosis. OCLR was used to calculate mRNA expression-based stemness index (mRNAsi) of LUAD patients' data in TCGA. Association analysis of mRNAsi was performed with clinical features, somatic mutation, and tumor immunity. A prognostic prediction model was established with LASSO Cox regression. Kaplan-Meier Plotter (KM-plotter) and time-dependent ROC were applied to assess signature performance. For LUAD, univariate and multivariate Cox analysis was performed to identify independent prognostic factors. LUAD tissues showed a noticeably higher mRNAsi in than nontumor tissues, and it showed significant differences in T, N, M, AJCC stages, and smoking history. The most frequently mutated gene was TP53, with a higher mRNAsi relating to more frequent mutation of TP53. The mRNAsi was significantly negatively correlated with immune score, stromal score, and ESTIMATE score in LUAD. The blue module was associated with mRNAsi. The 5-gene signature was confirmed as an independent indicator of LUAD prognosis that could promote personalized treatment of LUAD and accurately predict overall survival (OS) of LUAD patients.

Bilirubin oxidation end product B prevents CoCl2-induced primary cortical neuron apoptosis by promoting cell survival Akt/mTOR/p70S6K signaling pathway.

Bilirubin oxidation end products (BOXes) are associated with the late-developing neurological deficits after subarachnoid hemorrhage (SAH) possibly by direct constricting the cerebral arteries, but their specific impacts on neurons especially in the state of hypoxia, a prominent feature during the late stage of SAH, remain unclear. Here, we explored the effects of BOXes on the primary cortical neurons subjected to CoCl2-induced hypoxia by evaluating the morphological and apoptotic changes of neurons. The present study showed that Z-BOX B but not Z-BOX A greatly alleviated CoCl2-induced neuronal cell deterioration and apoptosis. Immunocytochemical staining assay showed Z-BOX B significantly increased neurite length, the numbers of both secondary and tertiary branches, and the protein level of Synaptophysin. Caspase 3/7 apoptosis assay and DAPI staining showed that Z-BOX B markedly reduced primary cortical neurons apoptosis. The expression of cleaved Caspase-3 was suppressed by Z-BOX B treatment, while the expression of Bcl-xL was upregulated. To further discover the mechanism of the neuroprotective effect observed in Z-BOX B, we found Z-BOX B increased the expression of p-mTOR, p-Akt, and p-p70S6K. In general, our results implicated Z-BOX B may prevent CoCl2-induced primary cortical neurons apoptosis by activating sAkt/mTOR/p70S6K signaling pathway. Hence, the present data may provide new insights into the pathophysiological mechanism of delayed neurological dysfunction after SAH and novel targets for treating SAH.

Risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children: a Meta analysis. / å„¿ç«¥è€ç¢³é’éœ‰çƒ¯ç±»è‚ æ†èŒå®šæ¤æˆ–æ„ŸæŸ“å±é™©å› ç´ çš„Meta分析.

OBJECTIVES: To systematically assess the risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children. METHODS: PubMed, Web of Science, China National Knowledge Infrastructure Database, Wanfang Data, China Biology Medicine disc were searched to obtain the articles on risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children published up to May 31, 2021. RevMan 5.3 software was used to perform the Meta analysis. RESULTS: A total of 13 articles were included, with 1 501 samples in total. The Meta analysis showed that indwelling gastric tube (OR=4.91), tracheal intubation (OR=5.03), central venous catheterization (OR=3.75), indwelling urinary catheterization (OR=4.11), mechanical ventilation (OR=3.09), history of hospitalization in the intensive care unit (OR=2.39), history of surgical operation (OR=3.22), previous use of third-generation cephalosporins (OR=2.62), previous use of carbapenem antibiotics (OR=3.82), previous use of glycopeptide antibiotics (OR=3.48), previous use of ß-lactamase inhibitors (OR=2.87), previous use of antifungal drugs (OR=2.48), previous use of aminoglycoside antibiotics (OR=2.54), and Apgar score ≤7 at 1 minute after birth (OR=2.10) were risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children (P<0.05). CONCLUSIONS: Invasive operations, history of hospitalization in the intensive care unit, previous use of antibiotics such as carbapenem antibiotics, and Apgar score ≤7 at 1 minute after birth are risk factors for the colonization or infection of carbapenem-resistant Enterobacteriaceae in children.

Association of the levels of heavy metals and trace elements during pregnancy with congenital heart defects in offspring: a prospective cohort study. / å­•æœŸé‡é‡‘å±žå ƒç´ å’Œå¾®é‡å ƒç´ æ°´å¹³ä¸Žå­ä»£å ˆå¤©æ€§å¿ƒè„ç— ç›¸å ³æ€§çš„å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To study the association of the levels of heavy metals and trace elements during pregnancy with congenital heart defects (CHD) in offspring, and to establish a model for predicting the probability of CHD based on the levels of heavy metals and trace elements during pregnancy. METHODS: Based on the prospective birth cohort study in Gansu Provincial Maternal and Child Health Hospital in 2010-2012, a nested case-control study was conducted for the follow-up observation of 14 359 pregnant women. Among the pregnant women, 97 pregnant women whose offspring were diagnosed with CHD during follow-up were enrolled as the CHD group, and 194 pregnant women whose offspring had no CHD were selected as the control group. Inductively coupled plasma mass spectrometry was used to measure the levels of heavy metals and trace elements in maternal blood samples and fetal umbilical cord blood samples. A multivariate logistic regression analysis was used to evaluate the association between heavy metal and trace elements and CHD in offspring. A nomogram model for predicting the probability of CHD in offspring was established based on the levels of heavy metals and trace elements during pregnancy. RESULTS: Compared with the control group, the CHD group had significantly higher levels of aluminum (Al), natrium (Na), calcium (Ca), titanium (Ti), selenium (Se), strontium (Sr), stannum (Sn), stibium (Sb), barium (Ba), and thorium (Th) in maternal blood samples (P<0.05), as well as significantly higher levels of Al, zinc (Zn), magnesium (Mg), kalium (K), Ca, Ti, chromium (Cr), copper (Cu), arsenic (As), Se, Sr, argentum (Ag), cadmium (Cd), Sn, and plumbum (Pb) in umbilical cord blood (P<0.05). The multivariate logistic regression analysis showed that the increase in the Sb level in maternal blood was associated with the increase in the risk of CHD in offspring [adjusted odds ratio (aOR)=4.81, 95% confidence interval (CI): 1.65-14.07, P=0.004], while in umbilical cord blood, the high levels of Al (aOR=4.22, 95%CI: 1.35-13.16, P=0.013), Mg (aOR=8.00, 95%CI: 1.52-42.08, P=0.014), and Pb (aOR=3.82, 95%CI: 0.96-15.23, P=0.049) were significantly associated with the risk of CHD in offspring. The levels of Al, Th, and Sb in maternal blood and levels of Al, Mg, and Pb in umbilical cord blood were included in the predictive model for CHD in offspring based on the levels of heavy metals and trace elements during pregnancy, and the calibration curve of the nomogram predictive model was close to the ideal curve. CONCLUSIONS: Increases in the levels of Al, Th, Sb, Mg, and Pb during pregnancy may indicate the increase in the risk of CHD in offspring, and the nomogram predictive model based on these indices can be used to predict the probability of CHD in offspring.