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Tb3+@Zn-CP achieved the transformation from invisible to visible, and from single emission luminescence sensing to ratiometric luminescence sensing of BP through a postsynthetic modification strategy.

Introduction: The mortality rate of hospitalized patients with severe hospital-acquired pneumonia (SHAP) remains high. Empirical broad-spectrum antibiotic coverage and the misuse of high-grade antibiotics could lead to the emergence of multi-drug and even pandrug-resistant bacteria. In addition to metagenomic next-generation sequencing (mNGS), microbiological rapid on-site evaluation(M-ROSE) might be a useful technique to identify the pathogens in the early stage, however the effect of M-ROSE guiding anti-infection treatment on prognostic outcomes of SHAP patients is still unclear. Methods/design: This is a multicenter, single-blind, prospective, randomized controlled trial to evaluate the effect of M-ROSE guiding anti-infection treatment in SHAP patients, which will provide new strategies for the prevention and control of clinical multi-drug resistance bacteria. A total of 166 patients with SHAP, aged 18 years and over, will be recruited from seven centers in Beijing and randomly assigned to the intervention group (M-ROSE combined with mNGS) or the control group (mNGS only) in a 1:1 ratio using the central randomization system. Patients in the intervention group will accept M-ROSE and mNGS analysis, and the control group will accept mNGS analysis. Individualized anti-infective treatment and routine treatment will be selected according to the analysis results. The primary outcome is the 28-day mortality. The safety of the intervention measures will be evaluated during the entire trial period. This trial will be the first randomized controlled trial to evaluate the effect of M-ROSE guiding treatment on mortality in patients with SHAP, and may change the prevalence of multi-drug resistant bacteria. Ethics and dissemination: This trial adheres to the Declaration of Helsinki and guidelines of Good Clinical Practice. Signed informed consent will be obtained from all participants. The trial has been approved by the Chinese PLA General Hospital (Approval Number: 20220322001). Trail registration number: ClinicalTrials.gov, NCT05300776. Registered on 25 March 2022.

Supplementary Methods

Supplementary Table 8. Sequence of primers for real-time PCR. Supplementary Table 9. Sequence of primers for CHIP real-time PCR.

Supplementary Table 5. Proteins in the two distict bands specific to GClnc1 identified by Liquid Chromatography-Mass Spectrometry.

Supplementary Table 4. RNA-seq analysis in BGC823 cells after GClnc1 shRNA and control shRNA transfection.

Supplementary Table 6. A, ChIP-Seq Library Statistics. B, ChIP-Seq Library Peak Calls. C, WDR5 and KAT2A peaks within 2kb of RefSeq gene promoters where read coverage were significant decreased in BGC823 GC cells after transduction of GClnc1 shRNA virus,compared with transduction of control shRNA virus. D, the differentiated expression genes in BGC823 cells after downregulation of GClnc1. E, Intersection of ChIP-Seq and RNA seq data. Supplementary Table 7. The association between GClnc1 with target genes in the coexpression network analysis.

Supplementary Figure 1, related to Figure 1. Clinical relevance of lncRNA candidate BC041951 in gastric cancer. Supplementary Figure 2, related to Figure 2. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) in gastric cancer cells and gastric cancer patients with high and low GClnc1 expression. Supplementary Figure 3, related to Figure 3. GClnc1 is an oncogenic lncRNA in gastric cancer. Supplementary Figure 4, related to Figure 4. GClnc1 interacts with WDR5 and KAT2A epigenetic modification complex. Supplementary Figure 5, related to Figure 5. GClnc1 coordinates the localization of WDR5 and KAT2A genome-wide. Supplementary Figure 6, related to Figure 6. GClnc1 promotes gastric cancer progression via SOD2. Supplementary Figure 7, related to Figure 7. GClnc1 is a molecular link among WDR5/KAT2A and SOD2.

Introduction Tumors are usually refractory to anti-cancer therapeutics under hypoxic conditions. However, the underlying molecular mechanism remains to be elucidated. Objectives Our study intended to identify hypoxia inducible lncRNAs and their biological function in gastric cancer (GC). Methods Differentially expressed lncRNAs were determined by microarray analysis between GC cells exposed to hypoxia (1% O2) and normoxia (21% O2) for 24 h. The expression level of CBSLR was manipulated in several GC cell lines to perform molecular and biological analyses both in vitro and in vivo. Results We identified a hypoxia-induced lncRNA-CBSLR that protected GC cells from ferroptosis, leading to chem-resistance. Mechanically, CBSLR interacted with YTHDF2 to form a CBSLR/YTHDF2/CBS signaling axis that decreased the stability of CBS mRNA by enhancing the binding of YTHDF2 with the m6A-modified coding sequence (CDS) of CBS mRNA. Furthermore, under decreased CBS levels, the methylation of the ACSL4 protein was reduced, leading to protein polyubiquitination and degradation of ACSL4. This, in turn, decreased the pro-ferroptosis phosphatidylethanolamine (PE) (18:0/20:4) and PE (18:0/22:4) content and contributed to ferroptosis resistance. Notably, CBSLR is upregulated, whereas CBS is downregulated in GC tissues compared to matched normal tissues; and GC patients with high CBSLR/low CBS levels have a worse clinical outcome and a poorer response to chemotherapy. Conclusion Our study reveals a novel mechanism in how HIF1α/CBSLR modulates ferroptosis/chemoresistance in GC, illuminating potential therapeutic targets for refractory hypoxic tumors.

Lossy compression causes the degradation of the classification accuracy of remote sensing (RS) images due to the introduced distortion by compression. In this letter, a convolutional sparse coding (CSC)-based method is proposed to quantitatively measure such an effect. In detail, the filters used in CSC are learned by online convolutional dictionary learning (OCDL) to construct the dictionary. Thereafter, the sparse coefficient maps are obtained based on the alternating direction method of multipliers (ADMM) algorithm. In addition, multiple kernel learning (MKL) is used to estimate the corresponding classification accuracy. The experimental results demonstrate that our method performs better in predicting the classification accuracy of RS images compared with the other state-of-the-art algorithms.

Background In sepsis, vitamin D binding protein (VDBP) has been shown to be low-expressed. The current study examined the relationship between serum VDBP level and liver injury in sepsis patients, as well as in a mouse model for sepsis and in cultured liver epithelial cell line exposed to lipopolysaccharide (LPS). Methods The human study included 78 sepsis patients and 50 healthy volunteers. Sepsis patients were categorized into sepsis survivor group (n = 43) and sepsis non-survivor group (n = 35) based on 28-day mortality for data analysis. Adult male C57BL/6 mice were subjected to cecal ligation and puncture (CLP). Serum samples were collected on day 1, 3, 5 and 7 to determine the levels of VDBP, 25-hydroxyvitamin D [25(OH)D3], 1,25-dihydroxyvitamin D [1,25(OH)2D3], interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Potential protective effects of VDBP overexpression against LPS-induced liver damage were examined in cultured THLE2 cells. Results Serum levels of VDBP, 25(OH)D3, and 1,25(OH)2D3 were significantly lower in sepsis patients vs. the healthy control (P P P = 0.0338, or P = 0.0013, respectively). Lower serum VDBP level was associated with higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (r = − 0.2565, P = 0.0234) and Sequential Organ Failure Assessment score (r = − 0.3522, P = 0.0016), but lower serum albumin (ALB, r = 0.4628, P r = 0.263, P = 0.02). In CLP mice, there was a 5-day period of serum VDBP reduction, followed by return towards the baseline on day 7. VDBP was also decreased in LPS-treated THLE2 cells (P Conclusion VDBP may be protective against sepsis-induced liver injury.

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer with high metastatic potential. To date, no directed treatment options have been developed for the treatment of metastatic or advanced TNBC. The oncogene TMEM158, also known as RIS1, is upregulated by Ras-induced cellular senescence. Although TMEM158 has been shown to be involved in tumor progression, little is known about the molecular function and expression of TMEM158 in breast cancer. The present study evaluated the expression and prognostic relevance of TMEM158 in breast cancer patients from several databases. Gene set enrichment analysis (GSEA) showed that TMEM158 was closely associated with epithelial-mesenchymal transition (EMT) and TGF-β pathways. Gain- and loss-of-function assays indicated that overexpressed TMEM158 might participate in EMT by activating the TGF-β pathway, which in turn promotes tumor migration, invasion, and metastasis. These findings suggest that TMEM158 has the potential to become a new therapeutic target for TNBC.

Supplementary Methods. Description of additional methods and procedures used in the study.

supplemental Figure 1-12. Expression levels of 10 lncRNAs by qRT-PCR in 15 GBC tissues and paired non-tumor tissues (Figure 1). Expression levels of 8 mRNAs by qRT-PCR in 15 GBC tissues and paired non-tumor tissues (Figure 2). Molecular characteristics of GCASPC (Figure 3). Nucleotide sequence of the full-length human GCASPC gene (Figure 4). GCASPC has no coding capability (Figure 5). The expression level of GCASPC in gallbladder cancer cells (Figure 6). Manipulation of GCASPC expression level (Figure 7). Anti-proliferative activity of GCASPC (Figure 8). GCASPC acts in trans (Figure 9). The effect of GCASPC on the protein, activity and mRNA levels of PC (Figure 10). GCASPC destabilizes PC protein (Figure 11). GCASPC directly binds to miR-17-3p (Figure 12).

Long noncoding RNAs (lncRNA) are being implicated in the development of many cancers. Here, we report the discovery of a critical role for the lncRNA GCASPC in determining the progression of gallbladder cancer. Differentially expressed lncRNAs and mRNAs between gallbladder cancer specimens and paired adjacent nontumor tissues from five patients were identified and validated by an expression microarray analysis. Quantitative real-time PCR was used to measure GCASPC levels in tissues from 42 gallbladder cancer patients, and levels of GCASPC were confirmed further in a separate cohort of 89 gallbladder cancer patients. GCASPC was overexpressed or silenced in several gallbladder cancer cell lines where molecular and biological analyses were performed. GCASPC levels were significantly lower in gallbladder cancer than adjacent nontumor tissues and were associated with tumor size, American Joint Committee on Cancer tumor stage, and patient outcomes. GCASPC overexpression suppressed cell proliferation in vitro and in vivo, whereas GCASPC silencing had opposite effects. By RNA pull-down and mass spectrometry, we identified pyruvate carboxylase as an RNA-binding protein that associated with GCASPC. Because GCASPC is a target of miR-17-3p, we confirmed that both miR-17-3p and GCASPC downregulated pyruvate carboxylase level and activity by limiting protein stability. Taken together, our results defined a novel mechanism of lncRNA-regulated cell proliferation in gallbladder cancer, illuminating a new basis for understanding its pathogenicity. Cancer Res; 76(18); 5361–71. ©2016 AACR.

Supplemental Table 1-9. Clinical characteristics of 5 GBC patients used for lncRNA array (Table 1). Clinicopathological characterisitcs of 42 GBC patients (Cohort 1) (Table 2). Clinicopathological characterisitcs of 89 GBC patients (Cohort 2) (Table 3). Correlation between GCASPC expression and GBC clinicopathological characteristics in 42 patients (Cohort 1) (Table 4). Univariate and multivariate analyses of OS in 89 GBC patients by Cox regression analysis (Table 5). Proteins in the three bands specific to GCASPC identified by MALDI-TOF mass spectrometry (Table 6). miRNAs binding sites of GCASPC by MirTarget2 (Table 7). Information on antibodies used for correlation analysis (Table 8). Primer sequence used in this study (Table 9). supplemental Figure 1-12. Expression levels of 10 lncRNAs by qRT-PCR in 15 GBC tissues and paired non-tumor tissues (Figure 1). Expression levels of 8 mRNAs by qRT-PCR in 15 GBC tissues and paired non-tumor tissues (Figure 2). Molecular characteristics of GCASPC (Figure 3). Nucleotide sequence of the full-length human GCASPC gene (Figure 4). GCASPC has no coding capability (Figure 5). The expression level of GCASPC in gallbladder cancer cells (Figure 6). Manipulation of GCASPC expression level (Figure 7). Anti-proliferative activity of GCASPC (Figure 8). GCASPC acts in trans (Figure 9). The effect of GCASPC on the protein, activity and mRNA levels of PC (Figure 10). GCASPC destabilizes PC protein (Figure 11). GCASPC directly binds to miR-17-3p (Figure 12).

Supplementary Table S2. LncRNAs associated with CNVs.

Supplementary Figures S1-S4. Binding of transcription factors to upregulated lncRNAs (S1); P53 mutant R248W transactivated GAPLINC through specifically binding to its promoter (S2); Knockdown of GAPLINC by two different siRNAs respectively inhibited gastric cancer cell proliferation (S3); CD44 could rescue the invasion inhibition effect of GAPLINC knockdown (S4).

Supplementary Methods. Description of additional methods and procedures used in the study.

Supplementary Table S4. Univariable and multivariable Cox regression analysis of survival prediction.

Supplementary Table S1. Deregulated lncRNAs in gastric cancer.

Supplementary Table S3. LncRNAs associated with mutant p53 and Stat1.

Supplementary Table S5. Growth of human gastric cancer xenograft in nude mice injected by GAPLINC stable knockdown clone and control clone.

The complete eradication of tumor cells is extremely challenging. An alternative strategy is tumor containment, which utilizes the interaction of tumor cells and has achieved promising results. However, effective interaction and controllability are not guaranteed for a given tumor. Here, we proposed a novel strategy comprising an impactive cell population and a control system and realized it in leukemic mouse model. To identify impactive cells, we xenografted six leukemic cell lines together. We found NALM-6 cells strongly impact the infiltration of other leukemic cells. To control NALM-6 cells, we introduced the herpes simplex virus thymidine kinase/ganciclovir suicide system. We found they effectively controlled the infiltration of NALM-6 cells. To evaluate the effectiveness, we used this strategy in mice xenografted with REH cells. The survival time was significantly elongated. In summary, our strategy guaranteed the impact and controllability of effector cells, thereby extending the tumor containment strategy.

From December 2022 to January 2023, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections caused by BA.5 and BF.7 subvariants of B.1.1.529 (Omicron) swept across mainland China. It is crucial to estimate the protective effect of the neutralizing antibodies generated by such mass infections against the next potential SARS-CoV-2 reinfection wave, especially if driven by CH.1.1 or XBB.1.5. Previously, we recruited and continuously followed a cohort of individuals that experienced Omicron BA.1, BA.2, and BA.5 breakthrough infections, as well as a control cohort with no history of SARS-CoV-2 infection. In the previously uninfected cohort, the total symptomatic infection rate surveyed during the outbreak was 91.6%, while the symptomatic reinfection rate was 32.9%, 10.5%, and 2.8% among individuals with prior Omicron BA.1, BA.2 and BA.5 infection, respectively, with median intervals between infections of 335, 225 and 94 days. Pseudovirus neutralization assays were performed in plasma samples collected from previously Omicron BA.1-infected individuals approximately 3 months before the outbreak. Results indicate a robust correlation between the plasma neutralizing antibody titers and the protective effect against symptomatic reinfection. The geometric mean of the 50% neutralizing titers (NT50) against D614G, BA.5, and BF.7 were 2.0, 2.5, and 2.3-fold higher in individuals without symptomatic reinfection than in those with symptomatic reinfection (p< 0.01). Low plasma neutralizing antibody titer (below the geometric mean of NT50) was associated with an enhanced cumulative risk of symptomatic reinfection, with a hazard ratio (HR) of 23.55 (95% CI: 9.23-60.06) against BF.7 subvariant. Importantly, neutralizing antibodies titers post one month after BF.7/BA.5 breakthrough infections against CH.1.1 and XBB.1.5 are similar to that against BF.7 from individuals with prior BA.1 infection while not experiencing a symptomatic BF.7/BA.5 reinfection (plasma collected 3 months before the outbreak), suggesting that the humoral immunity generated by the current BF.7/BA.5 breakthrough infection may provide protection against CH.1.1 and XBB.1.5 symptomatic reinfection wave for 4 months. Of note, the higher hACE2 binding of XBB.1.5 may reduce the protection period since the potential increase of infectivity.

Emerging evidence suggests that cytotoxic therapy may promote drug resistance and metastasis while inhibiting the growth of primary tumors. As yet, however, the underlying mechanisms remain unclear. Here, we aimed to investigate the pro-metastatic effects of adriamycin (ADR) therapy on breast cancer cells and to investigate the mechanisms underlying these effects. Differentially expressed genes between MCF-7 and ADR-resistant MCF-7 breast cancer cells were identified using high-throughput RNA-seq and differential gene expression analyses. In vitro transwell and scratch wound-healing assays, and an in vivo spontaneous metastasis model were used to study the metastatic potential of the breast cancer cells. The relationship between SIRT7 and TEK expression was studied using promoter activity, electrophoretic mobility shift (EMSA), CHIP-qPCR and Co-IP assays. Using transcriptome sequencing, we identified two key genes (SIRT7 and TEK) that might contribute to the pro-metastatic effect of ADR on breast cancer cells. SIRT7 acted as a negative regulator for TEK by inducing deacetylation of H3K18 at the TEK promoter. Through transcription factor prediction and double fluorescence experiments, we found that EST-1 could bind to the TEK promoter. Knockdown of EST-1 removed the transcriptional inhibition of TEK that was mediated by up-regulation of SIRT7. Co-IP showed that SIRT7 interacts directly with EST-1 in breast cancer cells, indicating that SIRT7 may induce H3K18 deacetylation at the TEK promoter region by directly binding to EST-1. In vitro and in vivo results showed that overexpression of SIRT7 or inhibition of TIE2 significantly reduced ADR-dependent breast cancer cell invasion/metastasis. Our findings suggest that ADR therapy may accelerate breast cancer metastasis in a SIRT7/TEK(TIE2) dependent manner.

Transmembrane protein (TMEM) is a family of protein that spans cytoplasmic membranes and allows cell–cell and cell–environment communication. Dysregulation of TMEMs has been observed in multiple cancers. However, little is known about TMEM116 in cancer development. In this study, we demonstrate that TMEM116 is highly expressed in non-small-cell lung cancer (NSCLC) tissues and cell lines. Inactivation of TMEM116 reduced cell proliferation, migration and invasiveness of human cancer cells and suppressed A549 induced tumor metastasis in mouse lungs. In addition, TMEM116 deficiency inhibited PDK1-AKT-FOXO3A signaling pathway, resulting in accumulation of TAp63, while activation of PDK1 largely reversed the TMEM116 deficiency induced defects in cancer cell motility, migration and invasive. Together, these results demonstrate that TMEM116 is a critical integrator of oncogenic signaling in cancer metastasis.

SINOPEC has made significant progress in natural gas exploration in terrigenous tight sandstone in the Western Sichuan Depression, making it one of the predominant exploration areas in the Sichuan Basin. Although the Chengdu large gas field was located in the main reservoirs of Upper Jurassic tight sandstone, few geochemical proofs were presented to support the explanation of the gas source, and regional differences in natural gas have been poorly investigated. The Jurassic tight gas in the Chengdu large gas field has a dryness coefficient (C1/C1-5) of 0.939–0.982, and the δ13C1, δ13C2, and δD1 values range from −33.7‰ to −30.7‰, −25.4‰ to −22.3‰, and −162‰ to −153‰, respectively, with positive carbon and hydrogen isotopic series of gaseous alkanes. The carbon and hydrogen isotopic compositions of the Jurassic tight gas indicate that it is typically coal-derived gas. The measured vitrinite reflectance (RO) values of source rocks of Member 5 of the Xujiahe Formation, which are demonstrated as the main source of Jurassic tight gas, are consistent with the calculated RO values according to the two-stage fractionation model of coal-derived gas. Effective source rocks are rare in the Lower Jurassic Baitianba Formation of the study area, which is considered to have only a minor contribution to the Jurassic gas reservoirs. The geochemical characteristics of Jurassic natural gas from various gas fields in the Western Sichuan Depression vary depending on the effect of different gas sources and accumulation processes.

In this paper, the problem of the trajectory design for a group of energy-constrained drones operating in dynamic wireless network environments is studied. In the considered model, a team of drone base stations (DBSs) is dispatched to cooperatively serve clusters of ground users that have dynamic and unpredictable uplink access demands. In this scenario, the DBSs must cooperatively navigate in the considered area to maximize coverage of the dynamic requests of the ground users. This trajectory design problem is posed as an optimization framework whose goal is to find optimal trajectories that maximize the fraction of users served by all DBSs. To find an optimal solution for this non-convex optimization problem under unpredictable environments, a value decomposition based reinforcement learning (VD-RL) solution coupled with a meta-training mechanism is proposed. This algorithm allows the DBSs to dynamically learn their trajectories while generalizing their learning to unseen environments. Analytical results show that, the proposed VD-RL algorithm is guaranteed to converge to a locally optimal solution of the non-convex optimization problem. Simulation results show that, even without meta-training, the proposed VD-RL algorithm can achieve a 53.2% improvement of the service coverage and a 30.6% improvement in terms of the convergence speed, compared to baseline multi-agent algorithms. Meanwhile, the use of the meta-training mechanism improves the convergence speed of the VD-RL algorithm by up to 53.8% when the DBSs must deal with a previously unseen task.

Background We investigate the pain relief and safety of microwave ablation (MWA) combined with percutaneous vertebroplasty (PVP) in the treatment of metastatic vertebral tumors. Methods This prospective pilot study enrolled patients with metastatic vertebral tumors treated between January 2018 and October 2019. The participants were randomized to the PVP and MWA + PVP groups. Clinical parameters, pain visual analog scale (VAS), analgesic use scores (AUS), and quality-of-life score (QLS) were compared between groups. Results Sixty-seven participants were enrolled (PVP: n = 35; MWA + PVP: n = 32). There were no differences in bone cement injection volume, extravasation, and X-ray exposure time between the two groups (p > 0.05), but treatment costs were higher for the MWA + PVP group (26,418 ± 194 vs. 15,606 ± 148 yuan; p 0.05); at 6 and 12 months after the operation, the improvement from baseline was significant in the two groups (p Conclusion MWA combined with PVP might be a safe and effective palliative treatment for pain from metastatic vertebral tumors.