Genomic landscape defines peritoneal metastatic pattern and related target of peritoneal metastasis in colorectal cancer.

The primary objective of this study is to develop a prediction model for peritoneal metastasis (PM) in colorectal cancer by integrating the genomic features of primary colorectal cancer, along with clinicopathological features. Concurrently, we aim to identify potential target implicated in the peritoneal dissemination of colorectal cancer through bioinformatics exploration and experimental validation. By analyzing the genomic landscape of primary colorectal cancer and clinicopathological features from 363 metastatic colorectal cancer patients, we identified 22 differently distributed variables, which were used for subsequent LASSO regression to construct a PM prediction model. The integrated model established by LASSO regression, which incorporated two clinicopathological variables and seven genomic variables, precisely discriminated PM cases (AUC 0.899; 95% CI 0.860-0.937) with good calibration (Hosmer-Lemeshow test p = .147). Model validation yielded AUCs of 0.898 (95% CI 0.896-0.899) and 0.704 (95% CI 0.622-0.787) internally and externally, respectively. Additionally, the peritoneal metastasis-related genomic signature (PGS), which was composed of the seven genes in the integrated model, has prognostic stratification capability for colorectal cancer. The divergent genomic landscape drives the driver genes of PM. Bioinformatic analysis concerning these driver genes indicated SERINC1 may be associated with PM. Subsequent experiments indicate that knocking down of SERINC1 functionally suppresses peritoneal dissemination, emphasizing its importance in CRCPM. In summary, the genomic landscape of primary cancer in colorectal cancer defines peritoneal metastatic pattern and reveals the potential target of SERINC1 for PM in colorectal cancer.

Dissolved organic matter promoted hydroxyl radical formation and phenanthrene attenuation during oxygenation of iron-pillared montmorillonites.

The oxygenation of Fe(II)-bearing minerals for hydroxyl radicals (HO•) formation and contaminant attenuation receives increasing attentions. However, information on dissolved organic matter (DOM) with different types, concentrations, and molecular weights (MWs) in manipulating HO• formation and contaminant attenuation during mineral oxygenation remain unclear. In this study, four iron-pillared montmorillonites (IPMs) and two DOM samples [e.g., humic acids (HA) and fulvic acids (FA)] were prepared to explore the HO• formation and phenanthrene attenuation during the oxygenation of IPMs in the presence or absence of DOMs. Results showed that iron-pillared and high-temperature calcination procedures extended the interlayer domain of IPMs, which provided favorable conditions for a high HO• production from 1293 to 14537 µmol kg-1. The surface-absorbed/low crystalline Fe(Ⅱ) was the predominant Fe(Ⅱ) fractionations for HO• production, and presence of DOMs significantly enhanced the HO• production and phenanthrene attenuation. Moreover, regardless of the types and concentrations, the low MW (LMW, <1 kDa) fraction within DOM pool contributed highest to HO• production and phenanthrene attenuation, followed by the bulk and high MW (HMW-, 1 kDa∼0.45 µm) fractions, and FA exhibited more efficient effects in promoting HO• production and phenanthrene attenuation than HA. The fluorescent spectral analysis further revealed that phenolic-like fluorophores in LMW-fraction were the main substances responsible for the enhanced HO• production and phenanthrene attenuation. The results deepen our understandings toward the behaviors and fate of aquatic HO• and contaminants, and also provide technical guidance for the remediation of contaminated environments.

Impact of Molecular Status on Cytoreductive Surgery for Peritoneal Metastases from Colorectal Cancer.

Colorectal cancer peritoneal metastases (CRC-PM) are present in 5 to 15% of instances of CRC, and the overall survival (OS) of patients with CRC-PM is much lower than that of patients with other isolated metastatic locations. In recent years, the introduction of cytoreductive surgery (CRS) in conjunction with hyperthermic intraperitoneal chemotherapy has resulted in a significant improvement in CRC-PM patients' OS. Despite this, a significant proportion of CRS patients continue to suffer complications of grades III to V or even die during the perioperative period. Early diagnosis, optimization of patient selection criteria, and refining of individualized combination therapy are necessary for these patients. In this review, we evaluate studies examining the relationship between molecular status and CRS in CRC-PM. Our objective is to gain a comprehensive understanding of how the altered molecular status of CRC-PM impacts CRS, which could increase the likelihood of tailored therapy in the future.

Tea Polyphenols Protects Tracheal Epithelial Tight Junctions in Lung during Actinobacillus pleuropneumoniae Infection via Suppressing TLR-4/MAPK/PKC-MLCK Signaling.

Actinobacillus pleuropneumoniae (APP) is the causative pathogen of porcine pleuropneumonia, a highly contagious respiratory disease in the pig industry. The increasingly severe antimicrobial resistance in APP urgently requires novel antibacterial alternatives for the treatment of APP infection. In this study, we investigated the effect of tea polyphenols (TP) against APP. MIC and MBC of TP showed significant inhibitory effects on bacteria growth and caused cellular damage to APP. Furthermore, TP decreased adherent activity of APP to the newborn pig tracheal epithelial cells (NPTr) and the destruction of the tight adherence junction proteins ß-catenin and occludin. Moreover, TP improved the survival rate of APP infected mice but also attenuated the release of the inflammation-related cytokines IL-6, IL-8, and TNF-α. TP inhibited activation of the TLR/MAPK/PKC-MLCK signaling for down-regulated TLR-2, TLR4, p-JNK, p-p38, p-PKC-α, and MLCK in cells triggered by APP. Collectively, our data suggest that TP represents a promising therapeutic agent in the treatment of APP infection.

Investigation of cytotoxic cadmium in aquatic green algae by synchrotron radiation-based Fourier transform infrared spectroscopy: Role of dissolved organic matter.

The heavy metal Cd can cause severe toxicity on aquatic algae, but there are few studies on the cytotoxicity of heavy metal on algae based on synchrotron radiation technology. In this study, synchrotron radiation-based Fourier transform infrared spectromicroscopy (SR-FTIR) was used to characterize in vivo the toxic effects of Cd on Cosmarium sp. cells, emphasizing the influence of dissolved organic matter (DOM) on Cd toxicity. Results showed that, in the absence of DOM, obvious growth inhibition, cell volume reduction, and photosynthesis disruption could be observed with increasing Cd concentrations (0-500 µg/L). Based on the SR-FTIR imaging and functional group quantification, it was shown that the biosynthesis of biomolecules such as proteins, lipids, and carbohydrates was inhibited in algal cells. However, the addition of DOM caused significant heterogeneities in biomacromolecule biosynthesis that an increased biosynthesis of carbohydrates and structural lipids but an inhibited biosynthesis of proteins and storage lipids were observed. Furthermore, the correlation analysis and principal component analysis showed a good correlation between v(C-OH)/Amide II and biochemical parameters, indicating that changes of carbohydrates could be used as the biomarker to indicate the cytotoxicity of heavy metals to algal cells. These findings provide insight into the mechanisms of heavy metal cytotoxicity to aquatic algae and systematic cytotoxicity assessment under various aquatic conditions.

Discovery of Novel 3,11-Bispeptide Ester Arenobufagin Derivatives with Potential in Vivo Antitumor Activity and Reduced Cardiotoxicity.

Arenobufagin, one of the bufadienolides isolated from traditional Chinese medicine Chan'su, exhibits potent antitumor activity. However, serious toxicity and small therapeutic window limits its drug development. In the present study, to our knowledge, novel 3,11-bispeptide ester arenobufagin derivatives have been firstly designed and synthesized on the base of our previous discovery of active 3-monopeptide ester derivative. The in vitro antiproliferative activity evaluation revealed that the moiety at C3 and C11 hydroxy had an important influence on cytotoxic activity and selectivity. Compound ZM350 notably inhibited tumor growth by 58.8 % at a dose 10 mg/kg in an A549 nude mice xenograft model. Therefore, compound ZM350 also presented a concentration-dependent apoptosis induction and low inhibitory effect against both hERG potassium channel and Cav1.2 calcium channel. Our study suggests that novel 3,11-bispeptide ester derivatives will be a potential benefit to further antitumor agent development of arenobufagin.

Metabolomics and proteomics analyses revealed mechanistic insights on the antimicrobial activity of epigallocatechin gallate against Streptococcus suis.

Streptococcus suis (S. suis) is a highly virulent zoonotic pathogen and causes severe economic losses to the swine industry worldwide. Public health security is also threatened by the rapidly growing antimicrobial resistance in S. suis. Therefore, there is an urgent need to develop new and safe antibacterial alternatives against S. suis. The green tea polyphenol epigallocatechin gallate (EGCG) with a number of potential health benefits is known for its antibacterial effect; however, the mechanism of its bactericidal action remains unclear. In the present, EGCG at minimal inhibitory concentration (MIC) showed significant inhibitory effects on S. suis growth, hemolytic activity, and biofilm formation, and caused damage to S. suis cells in vitro. EGCG also reduced S. suis pathogenicity in Galleria mellonella larvae in vivo. Metabolomics and proteomics analyses were performed to investigate the underlying mechanism of antibacterial activity of EGCG at MIC. Many differentially expressed proteins involved in DNA replication, synthesis of cell wall, and cell membrane, and virulence were down-regulated after the treatment of S. suis with EGCG. EGCG not only significantly reduced the hemolytic activity of S. suis but also down-regulated the expression of suilysin (Sly). The top three shared KEGG pathways between metabolomics and proteomics analysis were ABC transporters, glycolysis/gluconeogenesis, and aminoacyl-tRNA biosynthesis. Taken together, these data suggest that EGCG could be a potential phytochemical compound for treating S. suis infection.

Application of a fluorine strategy in the lead optimization of betulinic acid to the discovery of potent CD73 inhibitors.

The ecto-5'-nucleotidase (CD73) is an important enzyme in the adenosine pathway and catalyzes the extracellular hydrolysis of adenosine monophosphate (AMP) yielding adenosine which is involved in the inflammation and immunosuppression. Inhibitors of CD73 have potential as novel immunotherapy agents for the treatment of cancer and infection. In this study, we discovered a series of fluorinated betulinic acid derivatives as potent CD73 inhibitors by a fluorine scanning strategy. Among these, three compounds ZM522, ZM553 and ZM557 exhibited inhibitory activity with IC50 values of 0.56 uM, 0.74 uM and 0.47 uM, respectively. In addition, these compounds showed a 7-fold, 5-fold and 8-fold increase in activity compared to the positive control drug α, ß-methylene adenosine diphosphate (APCP) against the human CD73 enzyme. Two of these (ZM522 and ZM553) also exhibited effective interferon gamma (INF-γ) elevation and indicated the regulation of rescued T cell activation. Therefore, our study provides both a lead optimization strategy and potential compounds for further development of small molecule CD73 inhibitors.

Serial Circulating Tumor DNA in Monitoring the Effect of Neoadjuvant and Adjuvant Immunotherapy in Patients With Colon Cancer: Case Series and Review of the Literature.

Although programmed death 1 blockade has significantly improved the survival of advanced colorectal cancer patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H), clinical data in neoadjuvant and adjuvant setting are limited. The role of circulating tumor DNA (ctDNA) in precision oncology is promising, but its clinical significance in immunotherapy needs to be validated. We report a case series of 3 colon patients who received neoadjuvant and adjuvant immunotherapy and serial ctDNA analysis. This report summarizes clinical and molecular details for 3 patients with locally advanced or recurrent dMMR/MSI-H/polymerase epsilon ( POLE ) mutation-positive tumors treated with neoadjuvant/adjuvant immunotherapy. One stage IV recurrent colon cancer patient diagnosed with Lynch syndrome received adjuvant sintilimab monotherapy and had a progression-free survival (PFS) over 16 months, one stage Ⅲc colon cancer patient with MSI-H/high tumor mutation burden received neoadjuvant toripalimab monotherapy, was assessed as clinical complete response before surgery, continued with adjuvant sintilimab monotherapy and had a PFS over 17 months, one stage Ⅱ colon cancer patient with POLE P286R also received adjuvant sintilimab monotherapy and had a PFS over 17 months. All patients had detectable ctDNA after radical surgery and clearance of ctDNA during adjuvant immunotherapy. All 3 patients are free of tumor disease at the time of this report. Further studies are warranted to evaluate the long-term efficacy of neoadjuvant and adjuvant programmed death 1 blockade in locally advanced and metastasis in dMMR/MSI-H/ POLE mutated colorectal cancer and the role of ctDNA monitoring.

Comprehensive Analysis of Microsatellite-Related Transcriptomic Signature and Identify Its Clinical Value in Colon Cancer.

Background: Microsatellite has been proved to be an important prognostic factor and a treatment reference in colon cancer. The transcriptome profile and tumor microenvironment of different microsatellite statuses are different. Metastatic colon cancer patients with microsatellite instability-high (MSI-H) are sensitive to immune checkpoint inhibitors (ICIs), but not fluorouracil. Efforts have been devoted to identify the predictive factors of immunotherapy. Methods: We analyzed the transcriptome profile of different microsatellite statuses in colon cancer by using single-cell and bulk transcriptome data from publicly available databases. The immune cells in the tumor microenvironment were analyzed by the ESTIMATION algorithm. The microsatellite-related gene signature (MSRS) was constructed by the least absolute shrinkage and selection operator (LASSO) Cox regression based on the differentially expressed genes (DEGs) and its prognostic value and predictive value of response to immunotherapy were assessed. The prognostic value of the MSRS was also validated in another cohort. Results: The MSI-H cancers cells were clustered differentially in the dimension reduction plot. Most of the immune cells have a higher proportion in the tumor immune microenvironment, except for CD56 bright natural killer cells. A total of 238 DEGs were identified. Based on the 238 DEGs, a neural network was constructed with a Kappa coefficient of 0.706 in the testing cohort. The MSRS is a favorable prognostic factor of overall survival, which was also validated in another cohort (GSE39582). Besides, MSRS is correlated with tumor mutation burden in MSI-H colon cancer. However, the MSRS is a barely satisfactory factor in predicting immunotherapy with the area under the curve (AUC) of 0.624. Conclusion: We developed the MSRS, which is a robust prognostic factor of overall survival in spite of a barely satisfactory immunotherapy predictor. Further studies may need to improve the predictive ability.

Development and Validation of a Novel Prognostic Nomogram Combined With Desmoplastic Reaction for Synchronous Colorectal Peritoneal Metastasis.

Purpose: The prognostic value of desmoplastic reaction (DR) has not been investigated in colorectal cancer (CRC) patients with synchronous peritoneal metastasis (SPM). The present study aimed to identify whether DR can predict overall survival (OS) and develop a novel prognostic nomogram. Methods: CRC patients with SPM were enrolled from a single center between July 2007 and July 2019. DR patterns in primary tumors were classified as mature, intermediate, or immature according to the existence and absence of keloid-like collagen or myxoid stroma. Cox regression analysis was used to identify independent factors associated with OS and a nomogram was developed subsequently. Results: One hundred ninety-eight and 99 patients were randomly allocated into the training and validation groups. The median OS in the training group was 36, 25, and 12 months in mature, intermediate, and immature DR categories, respectively. Age, T stage, extraperitoneal metastasis, differentiation, cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and DR categorization were independent variables for OS, based on which the nomogram was developed. The C-index of the nomogram in the training and validation groups was 0.773 (95% CI 0.734-0.812) and 0.767 (95% CI 0.708-0.826). The calibration plots showed satisfactory agreement between the actual outcome and nomogram-predicted OS probabilities in the training and validation cohorts. Conclusions: DR classification in the primary tumor is a potential prognostic index for CRC patients with SPM. The novel prognostic nomogram combined with DR classification has good discrimination and accuracy in predicting the OS for CRC patients with SPM.

Green tea polyphenols inhibit growth, pathogenicity and metabolomics profiles of Streptococcus suis.

Streptococcus suis (SS) is an important pathogen in pigs and can also cause severe infection in humans. Currently, more and more drug resistance is reported, resulting in the search for new drugs being needed urgently. Green tea polyphenols (GTP) was reported to inhibit many bacteria. However, SS response to GTP has not been studied before. In this report, the effect of GTP on growth, cell integrity, pathogenicity and metabolic pathway of SS was examined. The GTP inhibited growth, led to cellular damage, and attenuated pathogenicity of SS. Finally, GTP affected many important metabolic pathways of SS, such as ABC transporters, pyrimidine metabolism, protein digestion and absorption. The results provide new insight into the prevention and control of SS infection.

Long Noncoding RNA HCG11 Acts as a Tumor Suppressor in Gastric Cancer by Regulating miR-942-5p/BRMS1 Axis.

The functions of long noncoding RNAs (lncRNAs) have been widely investigated in human cancers, including gastric cancer (GC). The purpose of this study was to elucidate the role of lncRNA HCG11 in GC. In this study, mRNA and protein expressions were detected by quantitative real-time polymerase chain reaction assays (RT-qPCR) and Western blot analysis. The proliferation ability of GC cells was examined by (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyl Tetrazolium Bromide) MTT assays. The invasion and migration abilities of GC cells were evaluated by Transwell assays. The binding sites between miR-942-5p and HCG11/BRMS1 were confirmed by dual-luciferase reporter assays. Results showed that LncRNA HCG11 was downregulated in GC cells. Functionally, overexpression of HCG11 inhibited GC cell proliferation, migration, and invasion. In addition, lncRNA HCG11 was found to act as a molecular sponge of miR-942-5p. Furthermore, miR-942-5p promoted GC progression by suppressing lncRNA HCG11 expression. Besides that, BRMS1 was confirmed as a direct target of miR-942-5p. More importantly, breast cancer metastasis suppressor 1 (BRMS1) inhibited GC progression by upregulating lncRNA HCG11 and downregulating miR-942-5p. In conclusion, LncRNA HCG11 inhibited cell proliferation, migration, and invasion in GC by sponging miR-942-5p and upregulating BRMS1.

Temporary impairment of renal function in patients with rectal cancer treated with diverting ileostomy.

BACKGROUND: Fluid and electrolyte disturbance, which impairs renal function, has been reported in patients with temporary ileostomy. However, the dynamic changes in serum electrolytes and renal function in rectal cancer patients with ileostomy have not been well described. In the present study, we aimed to evaluate alterations in serum electrolytes and renal function in rectal cancer patients undergoing ileostomy creation and closure. METHODS: The levels of serum potassium, serum sodium, serum blood urea nitrogen, serum creatinine and estimated glomerular filtration rate (eGFR) were analyzed in 320 patients with rectal cancer including 156 patients with an ileostomy (the ileostomy group) and 164 patients without an ileostomy (the control group). RESULTS: After index surgery, the levels of serum potassium and serum creatinine in the ileostomy group were significantly higher than those in the control group (P<0.05). In contrast, the levels of serum sodium and the eGFR showed decreases in the ileostomy group compared to the control group after index surgery (P<0.05). At 3 months after ileostomy creation, the ileostomy group had a significantly increased rate of eGFR <60 mL/min/1.73 m2 compared to the control group (5.8% vs. 1.2%, P=0.032). In line with the results of univariate analysis, multivariable analysis identified ileostomy and diabetes as independent risk factors for a decreased eGFR (P=0.005 and P=0.022, respectively). Furthermore, a significantly rebound of eGFR was observed in patients after ileostomy closure (P=0.013). CONCLUSIONS: Ileostomy can cause temporary electrolyte disturbance and renal function impairment in patients with rectal cancer. Diabetes is an independent risk factor for renal function damage in patients with rectal cancer who receive a temporary ileostomy.

Longitudinal dynamics of gut bacteriome, mycobiome and virome after fecal microbiota transplantation in graft-versus-host disease.

Fecal microbiota transplant (FMT) has emerged as a potential treatment for severe colitis associated with graft-versus-host disease (GvHD) following hematopoietic stem cell transplant. Bacterial engraftment from FMT donor to recipient has been reported, however the fate of fungi and viruses after FMT remains unclear. Here we report longitudinal dynamics of the gut bacteriome, mycobiome and virome in a teenager with GvHD after receiving four doses of FMT at weekly interval. After serial FMTs, the gut bacteriome, mycobiome and virome of the patient differ from compositions before FMT with variable temporal dynamics. Diversity of the gut bacterial community increases after each FMT. Gut fungal community initially shows expansion of several species followed by a decrease in diversity after multiple FMTs. In contrast, gut virome community varies substantially over time with a stable rise in diversity. The bacterium, Corynebacterium jeikeium, and Torque teno viruses, decrease after FMTs in parallel with an increase in the relative abundance of Caudovirales bacteriophages. Collectively, FMT may simultaneously impact on the various components of the gut microbiome with distinct effects.

Tea polyphenols inhibit the growth and virulence of ETEC K88.

Diarrhea caused by Enterotoxigenic Escherichia coli (ETEC) causes high levels of morbidity and mortality in neonatal piglets. Owing to the abuse of antibiotics and emergence of drug resistance, antibiotics are no longer considered only beneficial, but also potentially harmful drugs. Supplements that can inhibit the growth of bacteria are expected to replace antibiotics. Tea polyphenols have numerous important biological functions, including antibacterial, antiviral, antioxidative, anti-inflammatory, and antihypertensive effects. We investigated the role of tea polyphenols in ETEC K88 infection using a mouse model. Pretreating with tea polyphenols attenuated the symptoms induced by ETEC K88. Furthermore, in a cell adherence assay, tea polyphenols inhibited ETEC K88 adherence to IPEC-J2 cells. When cells were infected with ETEC K88, mRNA and protein levels of claudin-1 were significantly decreased compared with those of control cells. However, when cells were pretreated with tea polyphenols, claudin-1 mRNA and protein levels were higher than those in cells without pretreatment upon cell infection with ETEC K88. TLR2 mRNA levels were also higher following cell infection with ETEC K88 when cells were pretreated with tea polyphenols. These data revealed that tea polyphenols could increase the barrier integrity of IPEC-J2 cells by upregulating expression of claudin-1 through activation of TLR2. Tea polyphenols had beneficial effects on epithelial barrier function. Therefore, tea polyphenols could be used as a novel strategy to control and treat pig infections caused by ETEC K88.

Elucidation of Proteus mirabilis as a Key Bacterium in Crohn's Disease Inflammation.

BACKGROUND & AIMS: Proteus spp, Gram-negative facultative anaerobic bacilli, have recently been associated with Crohn's disease (CD) recurrence after intestinal resection. We investigated the genomic and functional role of Proteus as a gut pathogen in CD. METHODS: Proteus spp abundance was assessed by ure gene-specific polymerase chain in 54 pairs of fecal samples and 101 intestinal biopsies from patients with CD and healthy controls. The adherence, invasion, and intracellular presence of 2 distinct isolates of Proteus mirabilis in epithelial cells were evaluated using immunofluorescence and electron microscopy. Intracellular gene expression profiles and regulated pathways were analyzed by RNA sequencing and KEGG pathway analysis. Biologic functions of 2 isolates of P mirabilis were determined by in vitro cell culture, and in vivo using conventional mice and germ-free mice. RESULTS: Proteus spp were significantly more prevalent and abundant in fecal samples and colonic tissue of patients with CD than controls. A greater abundance of the genus Fusobacterium and a lesser abundance of the genus Faecalibacterium were seen in patients with CD with a high Proteus spp abundance. All 24 Proteus monoclones isolated from patients with CD belonged to members of P mirabilis lineages and 2 isolates, recovered from stool or mucosa, were used in further studies. Mice gavaged with either P mirabilis strain had more severe colonic inflammation. Co-culture of the isolates with epithelial cell lines showed bacterial adherence, invasion, increased production of pro-inflammatory cytokines IL-18 and IL-1α, and cell necrosis. Both isolates induced key pro-inflammatory pathways, including NOD-like receptor signaling, Jak-STAT signaling, and MAPK signaling, and induced pro-inflammatory genes and activated inflammation-related pathways in gnotobiotic mice. CONCLUSIONS: P mirabilis in the gut is associated with CD and can induce inflammation in cells and animal models of colitis. P mirabilis can act as a pathobiont and play a crucial role in the pathogenesis of CD.

Surface proteins mhp390 (P68) contributes to cilium adherence and mediates inflammation and apoptosis in Mycoplasma hyopneumoniae.

Mycoplasma hyopneumoniae is the causative agent of porcine enzootic pneumonia (EP) and responsible for major economic losses in global swine industry. After colonization of the respiratory epithelium, M. hyopneumoniae elicits a general mucociliary clearance loss, prolonged inflammatory response, host immunosuppression and secondary infections. Until now, the pathogenesis of M. hyopneumoniae is not completely elucidated. This present study explores the pathogenicity of mhp390 (P68, a membrane-associated lipoprotein) by elucidating its multiple functions. Microtitrer plate adherence assay demonstrated that mhp390 is a new cilia adhesin that plays an important role in binding to swine tracheal cilia. Notably, mhp390 could induce significant apoptosis of lymphocytes and monocytes from peripheral blood mononuclear cells (PBMCs), as well as primary alveolar macrophages (PAMs), which might weaken the host immune response. In addition, mhp390 contributes to the production of proinflammatory cytokines, at least partially, via the release of IL-1ß and TNF-α. To the best of our knowledge, this is the first report of the multiple functions of M. hyopneumoniae mhp390, which may supplement known virulence genes and further develop our understanding of the pathogenicity of M. hyopneumoniae.

Lightweight, Highly Permeable, Biocompatible, and Antiadhesive Composite Meshes for Intraperitoneal Repairs.

Ventral hernia is a public health issue and millions of meshes are used to repair abdominal wall defects every year. Polypropylene-based composite meshes represent an important class of materials for intraperitoneal repair, but the meshes generally give rise to infection, seroma, migration, and adhesion, leading to severe consequence or even reoperation. Here, a facile and versatile one-way fabrication of lightweight, highly permeable, and biocompatible composite meshes with superior antiadhesion properties is proposed by modifying polypropylene meshes with well-defined polydopamine nanocoating. The resulting composite meshes are found to significantly enhance the biocompatibility and antiadhesion effect in rat model. The scalable production and excellent biomedical properties of composite meshes make them a promising candidate for future-generation ventral hernia repair materials.

The mutation of hepatitis B virus and the prognosis of hepatocellular carcinoma after surgery: a pilot study.

BACKGROUND: Although hepatitis B virus (HBV) is still one of the most common etiological factors for hepatocellular carcinoma (HCC), the association between the HBV mutations and the clinical characteristics and prognosis of HBV-related HCC patients (HBV-HCC) after surgical resection remains largely unknown. MATERIALS AND METHODS: A cohort of 131 consecutive patients who received hepatectomy for HBV-HCC were retrospectively enrolled. The HBV genotype and 14 genomic mutations, which have been reported to relate to HCC in liver samples, were sequenced. The associations between the genomic mutations and clinical characteristics and outcomes were analyzed. RESULTS: Both A1762T/G1764A mutation and Pre S deletion related to worse overall survival (OS, p=0.040 and p<0.001, respectively) and disease-free survival (DFS, p=0.040 and p<0.001, respectively), G1899A mutation related to worse OS (p=0.030), A1762T/G1764A mutation correlated with tumor size (r=0.204, p=0.019), G1899A mutation correlated with vascular invasion (r=0.332, p<0.001), and Pre S deletion correlated with alpha-fetoprotein (AFP; r=0.254, p=0.003) positively. Multivariate analysis with Cox proportional hazards model revealed that both A1762T/G1764A mutation and Pre S deletion were independent prognostic factors for OS (hazard ratio [HR]=3.701, 95% CI=1.390-9.855, p=0.009, and HR=4.816, 95% CI=2.311-10.032, p<0.001, respectively) and DFS (HR=3.245, 95% CI=1.400-7.521, p=0.006, and HR=2.437, 95% CI=1.311-4.530, p<0.001, respectively), and patients with dual mutations were found to have the worst OS and DFS (p<0.001 and p<0.001, respectively). Patients with A1762T/G1764A mutation or Pre S deletion were more likely to have early recurrence (p=0.042 and p=0.019, respectively). CONCLUSION: HBV DNA genomic mutations in A1762T/G1764A and Pre S deletion were associated with worse prognoses and early recurrence for HBV-HCC patients after surgery.