Hypoxia exposure induces lactylation of Axin1 protein to promote glycolysis of esophageal carcinoma cells.

The hypoxic microenvironment in esophageal carcinoma is an important factor promoting the rapid progression of malignant tumor. This study was to investigate the lactylation of Axin1 on glycolysis in esophageal carcinoma cells under hypoxia exposure. Hypoxia treatment increases pan lysine lactylation (pan-kla) levels of both TE1 and EC109 cells. Meanwhile, ECAR, glucose consumption and lactate production were also upregulated in both TE1 and EC109 cells. The expression of embryonic stem cell transcription factors NANOG and SOX2 were enhanced in the hypoxia-treated cells. Axin1 overexpression partly reverses the induction effects of hypoxia treatment in TE1 and EC109 cells. Moreover, lactylation of Axin1 protein at K147 induced by hypoxia treatment promotes ubiquitination modification of Axin1 protein to promote glycolysis and cell stemness of TE1 and EC109 cells. Mutant Axin1 can inhibit ECAR, glucose uptake, lactate secretion, and cell stemness in TE1 and EC109 cells under normal or hypoxia conditions. Meanwhile, mutant Axin1 further enhanced the effects of 2-DG on inhibiting glycolysis and cell stemness. Overexpression of Axin1 also inhibited tumor growth in vivo, and was related to suppressing glycolysis. In conclusion, hypoxia treatment promoted the glycolysis and cell stemness of esophageal carcinoma cells, and increased the lactylation of Axin1 protein. Overexpression of Axin1 functioned as a glycolysis inhibitor, and suppressed the effects of hypoxia exposure in vitro and inhibited tumor growth in vivo. Mechanically, hypoxia induces the lactylation of Axin1 protein and promotes the ubiquitination of Axin1 to degrade the protein, thereby exercising its anti-glycolytic function.

InnTl4-nH+ (n = 0∼4): Tetracoordinate Hydrogen in a Planar Fashion?

The recent report of planar tetracoordinate hydrogen (ptH) in In4H+ is very intriguing in planar hypercoordinate chemistry. Our high-level CCSD(T) calculations revealed that the proposed D4h-symmetric ptH In4H+ is a first-order saddle point with an imaginary frequency in the out-of-plane mode of the hydrogen atom. In fact, at the CCSD(T)/aug-cc-pV5Z/aug-cc-pV5Z-PP level, the C4v isomer, with the H atom located 0.70 Å above the In4 plane, is 0.5 kcal/mol more stable than the D4h isomer. However, given the small perturbation from planarity and essentially barrierless C4v ↔ D4h ↔ C4v transition, the vibrationally averaged structure can still be considered as a planar. Extending our exploration to the InnTl4-nH+ (n = 0-3) systems, we found all these ptH structures, except for In2Tl2H+, to be the putative global minimum. The single σ-delocalized interaction between the central hydrogen atom and InnTl4-n ligand rings proves pivotal in establishing planarity and aromaticity and conferring substantial stability upon these rule-breaking ptH species.

Exploring the Use of "Honorary Transition Metals" To Push the Boundaries of Planar Hypercoordinate Alkaline-Earth Metals.

The quest for planar hypercoordinate atoms (phA) beyond six has predominantly focused on transition metals, with dodecacoordination being the highest reported thus far. Extending this bonding scenario to main-group elements, which typically lack d orbitals despite their larger atomic radius, has posed significant challenges. Intrigued by the potentiality of covalent bonding formation using the d orbitals of the heavier alkaline-earth metals (Ae = Ca, Sr, Ba), the so-called "honorary transition metals", we aim to push the boundaries of planar hypercoordination. By including rings formed by 12-15 atoms of boron-carbon and Ae centers, we propose a design scheme of 180 candidates with a phA. Further systematic screening, structural examination, and stability assessments identified 10 potential clusters with a planar hypercoordinate alkaline-earth metal (phAe) as the lowest-energy form. These unconventional structures embody planar dodeca-, trideca-, tetradeca-, and pentadecacoordinate atoms. Chemical bonding analyses reveal the important role of Ae d orbitals in facilitating covalent interactions between the central Ae atom and the surrounding boron-carbon rings, thereby establishing a new record for coordination numbers in the two-dimensional realm.

Diagnostic value of exosomal noncoding RNA in lung cancer: a meta-analysis.

Background: Lung cancer is one of the most dangerous cancers in the world. Most lung cancer patients are diagnosed in the middle and later stages, which can lead to poor survival rates. The development of lung cancer is often accompanied by abnormal expression of exosomal non-coding RNAs, which means that they have the potential to serve as noninvasive novel molecular markers for lung cancer diagnosis. Methods: For this study, we conducted a comprehensive literature search in PubMed, Web of science, Science direct, Embase, Cochrane, and Medline databases, and by reviewing published literature, The diagnostic capacity of exosomal microRNAs (miRNAs), long-chain non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) for lung cancer was evaluated. Functional enrichment analysis of miRNA target genes was performed. Results: The study included 41 papers, a total of 68 studies. More than 60 miRNAs, 9 lncRNAs and 14 circRNAs were involved. The combined sensitivity and specificity were 0.83(95%CI, 0.80~0.86) and 0.83(95% CI,0.79~0.87); 0.71(95% CI,0.68~0.74) and 0.79(95%CI, 0.75~0.82); 0.79(95%CI,0.67~0.87) and 0.81(95%CI,0.74~0.86), and constructed overall subject operating characteristic curves with the summarized area under the curve values of 0.90, 0.82, and 0.86. Conclusion: Our study shows that exosomes miRNAs, lncRNAs and circRNAs are effective in the diagnosis of lung cancer, providing evidence for studies related to novel lung cancer diagnostic markers. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023457087.

Survival benefits of adjuvant chemotherapy for patients with residual pathologic disease after neoadjuvant chemotherapy and surgery for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Although preoperative neoadjuvant chemotherapy (NACT) or chemoradiation is the current standard of care for esophageal cancer in China, the impact of subsequent adjuvant therapy on patient prognosis remains unknown. This study aims to analyze the effect of adjuvant chemotherapy (ACT) on the survival rates of patients who have achieved a non-pathological complete response (non-pCR) after NACT and subsequent surgery. METHODS: We reviewed the data of 2193 patients with locally advanced thoracic esophageal squamous cell carcinoma (ESCC) who underwent radical surgery between January 2006 and January 2016. Of these patients, 46 received NACT and ACT, while 109 received NACT only. Propensity score matching was used to compare 86 patients, with 43 patients in the NACT + ACT group and 43 patients in the NACT group. Univariate analysis was performed using the Kaplan-Meier method and log-rank test, while Cox regression analysis was used for multivariate analysis. RESULTS: Multivariate analysis revealed that pathological lymph node status (positive vs negative) (P < .001) and treatment modalities (NACT + ACT vs NACT) (P = .005) were independent prognostic factors. There was a significant difference in long-term survival rates between the NACT + ACT and NACT groups, with 5-year survival rates of 55.8% vs 39.5%, respectively (χ2 = 4.270, P = .039). In patients with ypN+ status, the 5-year survival rate was 31.8% for those who received ACT after NACT and surgery, compared to 10.0% for those who did not receive additional ACT (χ2 = 6.101, P = .014). The corresponding percentages in patients with ypN- were 81.0% and 65.2%, respectively (χ2 = 1.993, P = .158). CONCLUSION: Adjuvant chemotherapy should be recommended for locally advanced ESCC patients with residual cancer after NACT and surgery, especially for patients with nodal metastases after NACT.

Clusters and bulky Lewis acid protected complexes with planar hexacoordinate beryllium and magnesium.

Planar hexacoordination (ph) is only rarely reported in the literature. So far, only a few neutral and cationic molecules possessing phE (E = C, Si, B, Al, Ga) in the most stable isomer are predicted theoretically. Present electronic structure calculations report hitherto unknown anionic planar hexcoordinate beryllium and magnesium, phBe/Mg, as the most stable isomer. Global minimum searches show that the lowest energy structure of BeC6M3- (M = Al, Ga) and MgC6M3- (M = Ga, In, Tl) is the D3h symmetric phBe/Mg clusters, where beryllium/magnesium is covalently bonded with six carbon centers and M is located in a bridging position between two carbon centers. These global minimum phBe/Mg clusters are highly kinetically stable against isomerization, facilitating the experimental confirmation by photoelectron spectroscopy. Noteworthy is the fact that the phBe/Mg center is linked with carbon centers through three 7c-2e delocalized σ bonds and three 7c-2e π bonds, making the cluster double aromatic (σ + π) in nature. The bonding between the Be/Mg and outer ring moiety can be best expressed as an electron-sharing σ-bond between the s orbital of Be+/Mg+ and C6M32- followed by three dative interactions involving empty pπ and two in-plane p orbitals of Be/Mg. Furthermore, Lewis basic M centers of the title clusters can be passivated through the complexation with bulky Lewis acid, 9-boratriptycene, lowering the overall reactivity of the cluster, which can eventually open up the possibility of their large-scale syntheses.

B7 Be6 B7 : A Boron-Beryllium Sandwich Complex.

Planar boron clusters have often been regarded as "π-analogous" to aromatic arenes because of their similar delocalized π-bonding. However, unlike arenes such as C5 H5 - and C6 H6 , boron clusters have not previously shown the ability to form sandwich complexes. In this study, we present the first sandwich complex involving beryllium and boron, B7 Be6 B7 . The global minimum of this combination adopts a unique architecture having a D6h geometry, featuring an unprecedented monocyclic Be6 ring sandwiched between two quasi-planar B7 motifs. The thermochemical and kinetic stability of B7 Be6 B7 can be attributed to strong electrostatic and covalent interactions between the fragments. Chemical bonding analysis shows that B7 Be6 B7 can be considered as a [B7 ]3- [Be6 ]6+ [B7 ]3- complex. Moreover, there is a significant electron delocalization within this cluster, supported by the local diatropic contributions of the B7 and Be6 fragments.

Prediction and bioactivity of small-molecule antimicrobial peptides from Protaetia brevitarsis Lewis larvae.

Antimicrobial peptides (AMPs) are widely recognized as promising natural antimicrobial agents. Insects, as the group of animals with the largest population, have great potential as a source of AMPs. Thus, it is worthwhile to investigate potential novel AMPs from Protaetia brevitarsis Lewis larvae, which is a saprophagous pest prevalent in China. In this study, comparing the whole-genome sequence of Protaetia brevitarsis Lewis larvae with the Antimicrobial Peptide Database (APD3) led to the identification of nine peptide templates that were potentially AMPs. Next, based on the peptide templates, 16 truncated sequences were predicted to the AMPs by bioinformatics software and then underwent structural and physicochemical property analysis. Thereafter, candidate small-molecule AMPs were artificially synthesized and their minimal inhibitory concentration (MIC) values were assessed. A candidate peptide, designated FD10, exhibited strong antimicrobial activity against both bacteria and fungi comprising Escherichia coli (MIC: 8 µg/mL), Pseudomonas aeruginosa (MIC: 8 µg/mL), Bacillus thuringiensis (MIC: 8 µg/mL), Staphylococcus aureus (MIC: 16 µg/mL), and Candida albicans (MIC: 16 µg/mL). Additionally, two other candidate peptides, designated FD12 and FD15, exhibited antimicrobial activity against both E. coli (MIC: both 32 µg/mL) and S. aureus (MIC: both 16 µg/mL). Moreover, FD10, FD12, and FD15 killed almost all E. coli and S. aureus cells within 1 h, and the hemolytic effect of FD10 (0.31%) and FD12 (0.40%) was lower than that of ampicillin (0.52%). These findings indicate that FD12, FD15, and especially FD10 are promising AMPs for therapeutic application. This study promoted the development of antibacterial drugs and provided a theoretical basis for promoting the practical application of antimicrobial peptides in the Protaetia brevitarsis Lewis larvae.

Diagnostic value of pleural fluid SMRP, CA125, MMP-7, and MMP-9 in malignant pleural effusion.

This study aimed to investigate the clinical value of mesothelin soluble related peptide (SMRP), cancer antigen 125 (CA125), matrix metalloproteinase-7 (MMP-7), and matrix metalloproteinase-9 (MMP-9) in benign and malignant pleural exudative effusion. A total of 105 adult patients with pleural exudative effusion admitted in our hospital from December 2019 to December 2020 were selected. Patients were divided into the benign group (n = 60) and the malignant group (n = 45) according to their condition. The levels of SMRP, CA125, MMP-7, and MMP-9 in the pleural effusion were determined by enzyme linked immunosorbent assay. Receiver operating characteristic curves were used to analyze the individual and combined predictive value of SMRP, MMP-7, MMP-9, and CA125 levels. In the malignant group, the SMRP, CA125, MMP-7, and MMP-9 levels were all significantly higher than those in benign group (P = .01). The detection efficiency of the 4 indicators in the combined diagnosis were higher than that of single index and combination of any 2 indices. There was a moderate positive correlation between SMRP and CA125 and MMP-7 in malignant pleural effusion. The correlation between MMP-7 and MMP-9 was moderately positive. The diagnostic efficacy of SMRP combined with CA125, MMP-7, and MMP-9 in pleural effusion for malignant pleural effusion and BPE are better than single index, which has certain clinical values for the selection of early intervention scheme for BPE patients.

Siglec-15 as a New Perspective Therapy Target in Human Giant Cell Tumor of Bone.

The main features of a giant cell tumor of bone (GCTB) are frequent recurrence and aggressive osteolysis, which leads to a poor prognosis in patients. Although the treatment methods for a GCTB, such as scraping and resection, effectively inhibit the disease, the tendency toward malignant transformation remains. Therefore, it is important to identify new treatment methods for a GCTB. In this study, we first found high Siglec-15 expression in GCTB tissues, which was significantly associated with Campanacci staging and tumor recurrence. In Spearman's analysis, Siglec-15 expression was significantly correlated with Ki-67 levels in tumor tissues. In vitro, the mRNA and protein levels of Siglec-15 were high in GCTB stromal cells (Hs737. T), and Siglec-15 knockdown inhibited the biological characteristics of GCTB stromal cells. The RNA sequencing results enabled a prediction of the downstream genes by using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and MCODE analyses, and the findings showed that CXCL8 was significantly regulated by Siglec-15 and might be a promising downstream target gene of Siglec-15. Therefore, Siglec-15 may be a potential immunotherapy target for a GCTB.

Be4 B12 + : A Covalently Bonded Archimedean Beryllo-Borospherene.

A new class of beryllium-boron clusters, beryllo-borospherene, is described herein theoretically. When beryllium is gradually added to the B12 motif, it undergoes drastic structural modifications. The global minimum of the Be4 B12 + cluster is an Archimedean beryllo-borospherene in a 2 A1 electronic ground state, composed of four boron triangles linked at each corner, resulting in a truncated tetrahedron with four B6 rings capped with four beryllium atoms. Beryllium forms strong bonding with the boron clusters through strong electrostatic and covalent interactions. For instance, the bonding between a beryllium atom and Be3 B12 unit is best described as a Be+ fragment in a 2 P excited state forming a strong and polarized electron-sharing bond with Be3 B12 , followed by several dative interactions by employing its vacant s, p, and very high-lying d orbitals. Counterintuitively, for an s-block element, the p orbitals of beryllium are the most crucial atomic orbitals for bonding rather than s orbitals.

The Correlation between the Inflammatory Effects of Activated Macrophages in Atherosclerosis and Aortic Dissection.

BACKGROUND: To study the correlation between lipid metabolism index, inflammatory factor index, and M1 macrophage content and aortic dissection. METHODS: Patients with only basic atherosclerotic diseases were selected as the control group, and patients with only basic atherosclerotic diseases and aortic dissection were set as the experiment group. Blood of patients was collected. Chemiluminescent immunoassay was applied to determine the concentration of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B1 (ApoB1). Enzyme-linked immunosorbent assay was applied to measure the concentration of tumor necrosis factor-α (TNF-α), Interleukin 1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-10 (IL-10). The content of M1 macrophages in blood was measured with the flow cytometry (FCM) method. The correlation between the inflammatory effects of activated macrophages in atherosclerosis and aortic dissection was analyzed by a simple linear regression analysis. RESULTS: Concentration of TC, TG, LDL-C, and ApoB and the concentration of TNF-α, IL-1ß, and IL-6 in the experiment group were markedly higher compared to those in the control group, whereas the concentration of HDL-C and ApoA1 and IL-10 concentration in the experiment group was markedly lower. The content of M1 macrophage in the control group was significantly lower compared to the experiment group. The proportion of M1 macrophages, concentration of TC, TG, LDL, HDL, ApoA1, and ApoB1, and concentration of TNF-α, IL-1ß, IL-6, and IL-10 were all significantly correlated to the occurrence of aortic dissection. CONCLUSIONS: The proportion of M1 macrophages, concentration of TC, TG, LDL, HDL, ApoA1, and ApoB1, and concentration of TNF-α, IL-1ß, IL-6, and IL-10 are significantly correlated with the occurrence of aortic dissection.

Prognostic value of Siglec-15 expression in patients with solid tumors: A meta-analysis.

Background: Siglec-15 is expressed in a variety of cancers. However, the role of Siglec-15 in the prognosis of cancer patients remains controversial. Therefore, we conducted a meta-analysis to clarify the potential prognostic value of Siglec-15 in solid tumors. Methods: The PubMed, Web of Science, Embase and CNKI databases were comprehensively searched to identify studies assessing the effect of Siglec-15 on the survival of cancer patients. Hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS), progression-free survival (PFS) and disease-specific survival (DSS) from individual studies were evaluated. Results: The data from 13 observational studies consisting of 1376 patients were summarized. Elevated baseline Siglec-15 expression was significantly correlated with poor OS (pooled HR = 1.28, 95% CI: 1.05-1.56; P = 0.013). However, high Siglec-15 expression predicted a significantly better DSS (pooled HR = 0.73 (95% CI: 0.57-0.94; P = 0.015) but not PFS (pooled HR = 1.49, 95% CI: 0.46-4.87; P=0.510). In addition, high Siglec-15 expression was not associated with PD-L1 (OR=0.64, 95% CI: 0.42-0.95; P = 0.028). High Siglec-15 expression was associated with male sex (OR = 1.39, 95% CI: 1.05-1.84; P = 0.022), larger tumor size (OR = 1.896, 95% CI: 1.26-2.9; P = 0.002), and advanced tumor-node-metastasis (TNM) stage (OR = 1.84; 95% CI: 1.19-2.84; P =0.006) in solid tumors. Conclusions: This updated study suggested the expression of Siglec-15 is significantly associated with poor outcomes in human solid tumors, but further studies are needed to determine the prognostic value of Siglec-15 in solid tumors.

Cyclin B1 acts as a tumor microenvironment-related cancer promoter and prognostic biomarker in hepatocellular carcinoma.

OBJECTIVES: The present study aimed to develop a gene signature based on the ESTIMATE algorithm in hepatocellular carcinoma (HCC) and explore possible cancer promoters. METHODS: The ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cells (TICs) in a cohort of HCC patients. The differentially expressed genes (DEGs) were screened by Cox proportional hazards regression analysis and protein-protein interaction (PPI) network construction. Cyclin B1 (CCNB1) function was verified using experiments. RESULTS: The stromal and immune scores were associated with clinicopathological factors and recurrence-free survival (RFS) in HCC patients. In total, 546 DEGs were up-regulated in low score groups, 127 of which were associated with RFS. CCNB1 was regarded as the most predictive factor closely related to prognosis of HCC and could be a cancer promoter. Gene Set Enrichment Analysis (GSEA) and CIBERSORT analyses indicated that CCNB1 levels influenced HCC tumor microenvironment (TME) immune activity. CONCLUSIONS: The ESTIMATE signature can be used as a prognosis tool in HCC. CCNB1 is a tumor promoter and contributes to TME status conversion.

The Combination Analysis Between Bacillus thuringiensis Sip1Ab Protein and Brush Border Membrane Vesicles in Midgut of Colaphellus bowringi Baly.

The secretory insecticidal protein Sip1Ab and crystal protein Cry8Ca from Bacillus thuringiensis (Bt) are widely recognized for their coleopteran insecticidal activities. It is worthwhile to investigate the insecticidal mechanisms of these two proteins against Colaphellus bowringi Baly, which is a serious pest of cruciferous vegetables in China and other Asian countries. To that end, the genes encoding the Sip1Ab and Cry8Ca proteins were amplified from the strain QZL38 genome, then expressed in Escherichia coli, after which bioassays were conducted in C. bowringi larvae. After feeding these two proteins, the histopathological changes in the midguts of C. bowringi larvae were observed using transmission electron microscopy (TEM), and the Brush Border Membrane Vesicle (BBMV) was extracted for competition binding assays. TEM showed that ingestion of Sip1Ab caused a significant reduction in growth of the larvae, disruption of midgut microvilli, and expansion of intercellular spaces. Competition binding assays demonstrated that Sip1Ab bound to C. bowringi BBMV with a high binding affinity. However, a mixture of the two proteins in equal proportions showed no significant difference in insecticidal activity from that of Sip1Ab. These results could provide a molecular basis for the application of Sip1Ab in coleopteran insect control and contribute to the study of the Sip1Ab insecticidal mechanism as well.

Aberrant promoter 2 methylation­mediated downregulation of protein tyrosine phosphatase, non­receptor type 6, is associated with progression of esophageal squamous cell carcinoma.

The human protein tyrosine phosphatase, non­receptor type 6 (PTPN6) gene is located on chromosome 12p13 and encodes an Mr 68,000 non­receptor type protein­tyrosine phosphatase. The PTPN6 gene has been considered as a candidate tumor suppressor in hematological and solid malignancies, and promoter methylation may be an epigenetic modification silencing its expression. However, the detailed role of PTPN6 and its promoter methylation status in the pathogenesis of esophageal squamous cell carcinoma (ESCC) has not been fully elucidated. The aim of the present study was to investigate PTPN6 expression in ESCC tissues and esophageal cancer cell lines, detect the effect of CpG hypermethylation on the activity of PTPN6, and additionally elucidate the role and prognostic significance of PTPN6 in ESCC tumorigenesis and progression. The expression of PTPN6 was identified to be significantly downregulated in esophageal cancer cell lines and ESCC tissues. Marked upregulation of PTPN6 was detected in 5­aza­2'­deoxycytidine­treated esophageal cancer cells, and frequent hypermethylation of the CpG sites within the P2 promoter (P2) was detected in ESCC tissues and esophageal cancer cell lines. The expression and methylation status of PTPN6 was associated with tumor node metastasis stage, pathological differentiation and lymph node metastasis in patients with ESCC. Aberrant hypermethylation of the P2 exhibited marked tumor specificity and was identified to be associated with the expression level of PTPN6. Downregulation and hypermethylation of PTPN6 were identified to be associated with poor ESCC patient survival. Furthermore, upregulation of PTPN6 inhibited the proliferation and invasion of esophageal cancer cells in vitro. The results of the present study suggest that PTPN6 may serve as a tumor suppressor in ESCC, and it may serve as a potential target for antitumor therapy.

An algorithm for fragment-aware virtual network reconfiguration.

In view of the fact that the current online virtual network embedding algorithms do not consider the fragment resources generated in the embedding process deeply enough, resulting in the problem that the acceptance ratio and the revenue to cost ratio are both low, a mathematical model for virtual network reconfiguration is constructed and a heuristic algorithm for fragment-aware virtual network reconfiguration (FA-VNR) is proposed. The FA-VNR algorithm selects the set of virtual nodes to be migrated according to the fragment degrees of the physical nodes, and selects the best virtual node migration scheme according to the reduction of the fragment degrees of the physical nodes as well as the reduction of the embedding cost of the embedded virtual networks. Extensive simulation results show that the proposed FA-VNR algorithm not only can obviously improve the acceptance ratio and the revenue to cost ratio of the current online virtual network embedding algorithm, but also has better optimization effect than the existing virtual network reconfiguration algorithm.

B7-H4 overexpression contributes to poor prognosis and drug-resistance in triple-negative breast cancer.

BACKGROUND: The expression of the immunoregulatory protein B7-H4 has been reported in many types of cancer, including breast cancer. However, its role in triple-negative breast cancer (TNBC), especially its correlation with patients' prognosis and chemoresistance remains unclear. METHODS: The expression of B7-H4 in TNBC tissues and cell lines were measured with Real-Time PCR and western blotting. 65 cases of TNBC tissue samples and adjacent non-tumor tissue samples were analyzed by immunochemistry to demonstrate the correlation between the B7-H4 expression and clinicopathological characteristics. In vitro studies assessed mAb MIH43 alone and in combination with transfecting B7-H4 siRNA on the growth of chemosensitive and chemoresistant TNBC cell lines by CCK-8 and apoptotic enzyme-linked immunosorbent assay (ELISA). RESULTS: B7-H4 expression was detected positive in 59 of 65 (90.8%) different stage TNBC patients, especially in the samples of recurrence TNBC patients after receiving neoadjuvant chemotherapy treatment. Survival curves showed that patients with B7-H4 overexpression had significantly shorter survival and recurrence time than those with low B7-H4 expression (p < 0.005). Univariate and multivariate COX regression analysis demonstrated that B7-H4 was an independent predictor for advanced tumor stage. The monoclonal antibody of B7-H4 has the potential anti-proliferative effects on inhibiting the chemoresistant TNBC cell lines and increasing the sensitivity of TNBC cell lines to doxorubicin, paclitaxel or carboplatin. RNAi-mediated silencing of B7-H4 in TNBC cells enhanced drug-induced apoptosis via inhibiting PTEN/PI3K/AKT pathway, whereas reexpression of B7-H4 in B7-H4 knockdown and low B7-H4 expressing cells increased the phosphorylation of PI3K and AKT along with restoration of PETN expression. CONCLUSIONS: Our data show that B7-H4 is a biomarker indicative of a poor prognosis in TNBC patients and at least partially downregulated in chemoresistance via PTEN/PI3K/AKT pathway. Targeting B7-H4 might provide an attractive therapeutic approach specifically for TNBC patients.

Isolation and characterization of an avian-origin H3N8 canine influenza virus from a dog in eastern China.

Previous studies have shown that dogs are susceptible to influenza A viruses, and the close contact between dogs and humans poses a threat to public health. In 2015, a novel H3N8 influenza virus was isolated from a dog in eastern China. This strain was characterized by whole-genome sequencing with subsequent phylogenetic analysis and genetic comparison and found to be most closely related to avian influenza viruses co-circulating in China. It was able to replicate in mice without prior adaptation. The continued circulation of this novel H3N8 influenza virus in dogs could endanger other mammalian species.