Exercise training decreases lactylation and prevents myocardial ischemia-reperfusion injury by inhibiting YTHDF2.

Exercise improves cardiac function and metabolism. Although long-term exercise leads to circulating and micro-environmental metabolic changes, the effect of exercise on protein post-translational lactylation modifications as well as its functional relevance is unclear. Here, we report that lactate can regulate cardiomyocyte changes by improving protein lactylation levels and elevating intracellular N6-methyladenosine RNA-binding protein YTHDF2. The intrinsic disorder region of YTHDF2 but not the RNA m6A-binding activity is indispensable for its regulatory function in influencing cardiomyocyte cell size changes and oxygen glucose deprivation/re-oxygenation (OGD/R)-stimulated apoptosis via upregulating Ras GTPase-activating protein-binding protein 1 (G3BP1). Downregulation of YTHDF2 is required for exercise-induced physiological cardiac hypertrophy. Moreover, myocardial YTHDF2 inhibition alleviated ischemia/reperfusion-induced acute injury and pathological remodeling. Our results here link lactate and lactylation modifications with RNA m6A reader YTHDF2 and highlight the physiological importance of this innovative post-transcriptional intrinsic regulation mechanism of cardiomyocyte responses to exercise. Decreasing lactylation or inhibiting YTHDF2/G3BP1 might represent a promising therapeutic strategy for cardiac diseases.

Effects of exogenous N-acyl homoserine lactones (AHLs) on methanogenic activities and microbial community differences during anaerobic digestion.

N-acyl homoserine lactones (AHLs) function as signaling molecules influencing microbial community dynamics. This study investigates the impact of exogenously applied AHLs on methane production during waste-activated sludge (WAS) anaerobic digestion (AD). Nine AHL types, ranging from 10-4 to 10 µg/g VSS, were applied, comparing microbial community composition under optimal AHL concentrations. Firmicutes, Bacteroidetes, Chloroflexi, and Proteobacteria were identified in anaerobic digesters with C4-HSL, C6-HSL, and C8-HSL. Compared to the control, Halobacterota increased by 19.25%, 20.87%, and 9.33% with C7-HSL, C10-HSL, and C12-HSL. Exogenous C7-HSL enhanced the relative abundance of Methanosarcina, Romboutsia, Sedimentibacter, Proteiniclasticum, Christensenellaceae_R-7_group. C10-HSL increased Methanosarcina abundance. C4-HSL, C6-HSL, C8-HSL, C10-HSL, and C12-HSL showed potential to increase unclassified_Firmicutes. Functional Annotation of Prokaryotic Taxa (FAPROTAX) predicted AHLs' impact on related functional genes, providing insights into their role in AD methanogenesis regulation. This study aimed to enhance the understanding of the influence of different types of exogenous AHLs on AD and provide technical support for regulating the methanogenesis efficiency of AD by exogenous AHLs.

Engineered Saccharomyces cerevisiae harbors xylose isomerase and xylose transporter improves co-fermentation of xylose and glucose for ethanol production.

Saccharomyces cerevisiae cannot assimilate xylose, second to glucose derived from lignocellulosic biomass. Here, the engineered S. cerevisiae strains INVSc-XI and INVSc-XI/XT were constructed using xylA and Xltr1p to co-utilize xylose and glucose, achieving economic viability and sustainable production of fuels. The xylose utilization rate of INVSc-XI/XT was 2.3-fold higher than that of INVSc-XI, indicating that overexpressing Xltr1p could further enhance xylose utilization. In mixed sugar media, a small amount of glucose enhanced the consumption of xylose by INVSc-XI/XT. Transcriptome analysis showed that glucose increased the upregulation of acetate of coenzyme A synthetase (ACS), alcohol dehydrogenase (ADH), and transketolase (TKL) gene expression in INVSc-XI/XT, further promoting xylose utilization and ethanol yield. The highest ethanol titer of 2.91 g/L with a yield of 0.29 g/g at 96 h by INVSc-XI/XT was 56.9% and 63.0% of the theoretical ethanol yield from glucose and xylose, respectively. These results showed overexpression of xylA and Xltr1p is a promising strategy for improving xylose and glucose conversion to ethanol. Although the ability of strain INVSc-XI/XT to produce ethanol was not very satisfactory, glucose was discovered to influence xylose utilization in strain INVSc-XI/XT. Altering the glucose concentration is a promising strategy to improve the xylose and glucose co-utilization.

INVSc-XI and INVSc-XI/XT strains were newly constructed to utilize xylose and glucose.XylA, in combination with xylose transporter Xltr1p, enhances xylose consumption.A small amount of glucose enhanced xylose utilization in INVSc-XI/XT strain.The expression of ACS, ADH, and TKL genes is upregulated in the media containing mixed sugars.The highest ethanol yield of 0.29 g/g was produced in a 2-L scale-up fermenter.

How to Avoid Misdiagnosing Spontaneous Cervical Spinal Epidural Hematoma as Ischemic Stroke: 3 Case Reports and Literature Review.

When spontaneous cervical spinal epidural hematoma (SCEH) presents with hemiparesis, it can be misdiagnosed with ischemic stroke (IS), and the treatment of IS such as thrombolysis may deteriorate the symptoms of patients with SCEH, leading to worse sequelae or even death. We reported 3 SCEH patients who were initially suspected as IS in our center between Jun 2020 and April 2022 and analyzed their clinical characteristics together with 48 patients reported in the literature from Jan 1995 to April 2022. Two of the 3 SCEH patients had neck symptoms, while none of them presented cranial nerve symptoms. Cranial computed tomography (CT) scans were negative; however, abnormal signals in the cervical spinal canal were observed during cranial computed tomography angiography (CTA) and subsequent cervical CT confirmed the diagnosis of SCEH. All of them avoid mistreatment with recombinant tissue plasminogen activator (rt-PA). Subsequently, we analyzed the clinical characteristics of a total of 51 patients. Thirteen of them developed symptoms during activity. Neck pain was an important sign of SCEH because 35 patients had neck pain or neck discomfort. Sensory impairment was reported in a small proportion of patients (11/51), which varied a lot in the patients. Some special manifestations highly suggested spinal cord lesions and provided evidence for the early differential diagnosis of SCEH and stroke, but the incidence of which was quite low: ipsilateral Horner syndrome in 2 patients, Brown-Séquard syndrome in 2 cases, and Lhermitte's sign in 1 case. Only a minority (8/51) of the patients were correctly diagnosed at the emergency unit using cervical CT. Six patients were correctly diagnosed when performing CTA. A large portion of the cases (21/51) were first misdiagnosed as IS, but no responsible lesions were found on cranial magnetic resonance imaging (MRI), and subsequent cervical MRI confirmed the diagnosis. Sixteen patients were diagnosed with SCEH after the deterioration of symptoms. A total of 13 patients received rt-PA, and 10 of them had symptoms aggravation after thrombolysis. For patients with acute onset of hemiparesis but without cranial nerve symptoms, especially those accompanied by clinical features such as neck pain, ipsilateral Horner syndrome, Brown-Séquard syndrome, and Lhermitte's sign, SCEH should be highly suspected rather than stroke. Careful differential diagnosis should be performed with a comprehensive medical history and thorough physical examination. Cervical CT scan is a reasonable choice for quick differential diagnosis prior to administering potentially harmful therapy, especially rt-PA.

Circular RNA Translation in Cardiovascular Diseases.

Circular RNAs (circRNAs) are a class of endogenous functional RNA generated by back-splicing. Recently, circRNAs have been found to have certain coding potential. Proteins/peptides translated from circRNAs play essential roles in various diseases. Here, we briefly summarize the basic knowledge and technologies that are usually applied to study circRNA translation. Then, we focus on the research progress of circRNA translation in cardiovascular diseases and discuss the perspective and future direction of translatable circRNA study in cardiovascular diseases.

Predictive value of proteomic markers for advanced rectal cancer with neoadjuvant chemoradiotherapy.

BACKGROUND: Preoperative neoadjuvant chemoradiation (nCRT) has been the standard treatment for locally advanced rectal cancer. Serum biomarkers to stratify patients with respect to prognosis and response to nCRT are needed due to the diverse response to the therapy. METHODS: Thirteen paired pre- and post-nCRT sera from rectal cancer patients were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ) method. Twenty-five proteins were selected for validation by parallel reaction monitoring (PRM) in ninety-one patients. RESULTS: Totally, 310 proteins were identified and quantified in sera samples. Reactome pathway analysis showed that the immune activation-related pathways were enriched in response to nCRT. Twenty-five proteins were selected for further validation. PRM result showed that the level of PZP was higher in pathological complete response (pCR) patients than non-pCR patients. The Random Forest algorithm identified a prediction model composed of 10 protein markers, which allowed discrimination between pCR patients and non-pCR patients (area under the curve (AUC) = 0.886 on testing set). Higher HEP2 and GELS or lower S10A8 in baseline sera were associated with better prognosis. Higher APOA1 in post nCRT sera was associated with better disease-free survival (DFS). CONCLUSIONS: We identified and confirmed a 10-protein panel for nCRT response prediction and four potential biomarkers HEP2, GELS, S10A8 and APOA1 for prognosis of rectal cancer based on iTRAQ-based comparative proteomics screening and PRM-based targeted proteomic validation.

Chemical element concentrations in cord whole blood and the risk of preterm birth for pregnant women in Guangdong, China.

Maternal exposure to chemical elements, including essential and non-essential elements, have been found to be associated with preterm births (PTB). However, few studies have measured element concentrations in cord whole blood, which reflects activity at the maternal-fetal interface and may be biologically associated with PTBs. In this study, we determined concentrations of 21 elements in cord whole blood and explored the associations between element concentrations and PTB in a nested case-control study within a birth cohort in Guangdong, China. Finally, 515 preterm infants and 595 full-term infants were included. We performed single-element and multi-element logistic regressions to evaluate linear relationships between element concentrations and PTB. According to the results of single-element models, most essential elements (including K, Ca, Si, Zn, Se, Sr and Fe) were negatively associated with PTB, while Cu, V, Co and Sn were positively associated with PTB. Of the non-essential elements, Sb, Tl, and U were positively associated with PTB, while Pb was negatively associated with PTB. The multi-element model results for most elements were similar, except that the association between Mg and PTB was shown to be significantly positive, and the association for Cu became much larger. A possible explanation is that the effects of Mg and Cu may be influenced by other elements. We performed restricted cubic spline (RCS) regressions and found significantly non-linear exposure-response relationships for Mg, Se, Sr, K and Sb, indicating that the effects of these elements on PTB are not simply detrimental or beneficial. We also examined the joint effect using a Bayesian kernel machine regression (BKMR) model and found the risk of PTB decreased significantly with element mixture concentration when lnC was larger than the median. Bivariate interaction analysis suggested antagonistic effects of Sb on Zn and Sr, which may be attributed to Sb negating the antioxidant capacity of Zn and Sr. This study provides additional evidence for the effect of element exposures on PTB, and will have implications for the prevention of excessive exposures or inappropriate element supplementation during pregnancy.

A comparative study of the in vitro antitumor effect of mannose-doxorubicin conjugates with different linkers.

In this work, five Man-DOX conjugates with different linkers were developed for targeted DOX delivery. The five Man-DOX conjugates with different linkers were characterized by 1 H NMR, HRMS, HPLC, UV-vis, and fluorescence spectroscopy. Man-Suc-DOX, Man-TDG-DOX, and Man-DG-DOX can self-assemble into near-spherical nanoparticles with hydrodynamic diameters of 150-200 nm and negative zeta potentials in deionized water, whereas Man-SS-DOX and Man-SeSe-DOX are hardly dispersed in deionized water. The self-assembly behaviors of Man-Suc-DOX, Man-TDG-DOX, and Man-DG-DOX were studied by dissipative particle dynamics simulation and the results show that Man-Suc-DOX, Man-TDG-DOX, and Man-DG-DOX all self-assemble into spherical particles with Man and linkers on the surfaces and DOX in the interiors. The in vitro drug release study shows that Man-Suc-DOX, Man-TDG-DOX, and Man-DG-DOX exhibit limited drug release, while Man-SS-DOX and Man-SeSe-DOX exhibit glutathione-responsive drug release. The cellular uptake study shows that Man-DG-DOX exhibits the highest cellular uptake amount on HepG2 cells. Finally, Man-DG-DOX exhibits the best in vitro antitumor effect against HepG2 cells among the five Man-DOX conjugates with different linkers. Although the in vitro antitumor activity of Man-DG-DOX is still lower than free DOX, Man-DG-DOX shows significant selectivity toward HepG2 cells. Man-DG-DOX might achieve selective DOX delivery for mannose receptor overexpressed tumors.

Discovery of novel indole derivatives that inhibit NEDDylation and MAPK pathways against gastric cancer MGC803 cells.

A series of novel indole derivatives were synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (MGC803, EC-109 and PC-3). Among these analogues, 2-(5-methoxy-1H-indol-1-yl)-N-(4-methoxybenzyl)-N-(3,4,5-trimethoxyphenyl)acetamide (V7) showed the best inhibitory activity against MGC803 cells with an IC50 value of 1.59 µM. Cellular mechanisms elucidated that V7 inhibited colony formation, induced apoptosis and arrested cell cycle at G2/M phase. Importantly, indole analogue V7 inhibited NEDDylation pathway and MAPK pathway against MGC803 cells.

Discovery of 1,2,4-triazine-based derivatives as novel neddylation inhibitors and anticancer activity studies against gastric cancer MGC-803 cells.

Neddylation modification is often over-expressed in a variety of human tumor cells. Therefore, targeting neddylation pathway may represent a potential approach to the treatment of human tumors. Herein, we describe the discovery of a hit scaffold from our in-house library and further structure-based optimizations. In this work, compound V11 could block the neddylation and inhibit the activity of NAE (with an EC50 value of 3.56 µM), and a dose-dependent reduction of the Ubc12-NEDD8 conjugations was also observed. Molecular docking results suggest compound V11 could bind tightly to NAE via hydrogen bonds and hydrophobic interactions. Compound V11 showed the best antiproliferative ability with an IC50 value of 8.22 µM against gastric cancer MGC-803 cells. Further anticancer activity studies suggested that compound V11 inhibited MGC-803 cell growth, caused a cell cycle arrestment at G2/M phase and induced apoptosis via extrinsic and intrinsic apoptosis pathways. All the findings suggest that 1,2,4-triazine scaffold might provide a novel scaffold for the further development of neddylation inhibitors and compound V11 might be a potential neddylation inhibitor with anticancer activity.

The binding of an anti-PD-1 antibody to FcγRΙ has a profound impact on its biological functions.

Antibodies targeting PD-1 have been demonstrated durable anti-cancer activity in certain cancer types. However, the anti-PD-1 antibodies are less or not efficacious in many situations, which might be attributed to co-expression of multiple inhibitory receptors or presence of immunosuppressive cells in the tumor microenvironment. Most of the anti-PD-1 antibodies used in clinical studies are of IgG4 isotype with the S228P mutation (IgG4S228P). The functional impact by the interaction of anti-PD-1 IgG4S228P antibody with Fc gamma receptors (FcγRs) is poorly understood. To assess the effects, we generated a pair of anti-PD-1 antibodies: BGB-A317/IgG4S228P and BGB-A317/IgG4-variant (abbreviated as BGB-A317), with the same variable regions but two different IgG4 Fc-hinge sequences. There was no significant difference between these two antibodies in binding to PD-1. However, BGB-A317/IgG4S228P binds to human FcγRI with high affinity and mediates crosslinking between PD-1 and FcγRI. In contrast, BGB-A317 does neither. Further cell-based assays showed that such crosslinking could reverse the function of an anti-PD-1 antibody from blocking to activating. More importantly, the crosslinking induces FcγRI+ macrophages to phagocytose PD-1+ T cells. In a mouse model transplanted with allogeneic human cancer cells and PBMCs, BGB-A317 showed significant tumor growth inhibition, whereas BGB-A317/IgG4S228P had no such inhibition. Immunohistochemistry study revealed an inverse correlation between FcγRI+ murine macrophage infiltration and the density of CD8+PD-1+ human T cells within tumors in the BGB-A317/IgG4S228P-treated group. These evidences suggested that FcγRI+ binding and crosslinking had negative impact on the anti-PD-1 antibody-mediated anti-cancer activity.

SIRT3 deacetylated and increased citrate synthase activity in PD model.

SIRT3 have been found to be neuroprotective in many neurological diseases, but its detail mechanism is only partially understood. In this study, MPP+ was used to treat SH-SY5Y cells as the cellular model of PD to test the role of SIRT3 and the mechanism may be involved in. We focused on the changes and relationship between SIRT3 and the key mitochondrial enzymes citrate synthase (CS) and isocitrate dehydrogenase 2 (IDH2). We found MPP+ decreased SIRT3 expression. And our results showed that the enzymatic activities of CS and IDH2 were significantly reduced in MPP+ treatment cells, while protein acetylation of CS and IDH2 increased. However overexpressed-SIRT3 partially reversed at least, the decline of CS activity and the increase of CS protein acetylation. IDH2 did not showed the same changes. The study suggested that SIRT3 deacetylated and activated CS activity. Hence, we conclude that SIRT3 exhibits neuroprotection via deacetylating and increasing mitochondrial enzyme activities.

The epigenetic regulation of HIF-1α by SIRT1 in MPP(+) treated SH-SY5Y cells.

Both silent information regulator 1 (SIRT1) and hypoxia inducible factor 1 (HIF-1) have been found to play important roles in the pathophysiology of Parkinson's disease (PD). However, their mechanisms and their relationship still require further study. In the present study, we focused on the change and relationship of SIRT1 and HIF-1α in PD. PD cell models were established by using methyl-4-phenylpyridinium (MPP(+)), which induced inhibition of cell proliferation, cell cycle arrest and apoptosis. We found that the expression of HIF-1α and its target genes VEGFA and LDHA increased and that SIRT1 expression was inhibited in MPP(+) treated cells. With further analysis, we found that the acetylation of H3K14 combined with the HIF-1α promoter was dramatically increased in cells treated with MPP(+), which resulted in the transcriptional activation of HIF-1α. Moreover, the acetylation of H3K14 and the expression of HIF-1α increased when SIRT1 was knocked down, suggesting that SIRT1 was involved in the epigenetic regulation of HIF-1α. At last, phenformin, another mitochondrial complex1 inhibitor, was used to testify that the increased HIF-1a was not due to off target effects of MPP(+). Therefore, our results support a link between PD and SIRT1/HIF-1α signaling, which may serve as a clue for understanding PD.

Reclassification of Desulfobacterium anilini as Desulfatiglans anilini comb. nov. within Desulfatiglans gen. nov., and description of a 4-chlorophenol-degrading sulfate-reducing bacterium, Desulfatiglans parachlorophenolica sp. nov.

A strictly anaerobic, mesophilic, sulfate-reducing bacterial strain (DS(T)), isolated from river sediment contaminated with volatile organic compounds, was characterized phenotypically and phylogenetically. Cells were Gram-reaction-negative, non-motile short rods. For growth, optimum NaCl concentration was 0.9 g l(-1), optimum temperature was 30 °C and optimum pH was 7.2. Strain DS(T) utilized phenol, benzoate, 4-hydroxybenzoate, 4-methylphenol, 4-chlorophenol, acetate, butyrate and pyruvate as electron donors for sulfate reduction. Electron donors were completely oxidized. Strain DS(T) did not utilize sulfite, thiosulfate or nitrate as electron acceptors. The genomic DNA G+C content of strain DS(T) was 58.9 mol%. Major cellular fatty acids were iso-C14 : 0, anteiso-C15 : 0 and C18 : 1ω7c. Phylogenetic analyses based on the 16S rRNA gene indicated its closest relatives were strains of Desulfobacterium anilini (about 98-99 % sequence similarity) but the DNA-DNA hybridization value with Desulfobacterium anilini Ani1(T) was around 40 %. Although strain DS(T) and its relatives shared most phenotypic and chemotaxonomic characteristics, the utilization of 4-chlorophenol, the range of electron acceptors and the optimum growth conditions differed. Strain DS(T) is closely related to strains of Desulfobacterium anilini, but constitutes a different species within the genus. Based on phylogeny, phenotypic characteristics and chemotaxonomic characteristics, strain DS(T) and Desulfobacterium anilini were clearly different from strains of other species of the genus Desulfobacterium. We thus propose the reclassification of Desulfobacterium anilini within a new genus, Desulfatiglans gen. nov., as Desulfatiglans anilini comb. nov. We also propose Desulfatiglans parachlorophenolica sp. nov. to accommodate strain DS(T). The type strain is DS(T) ( = JCM 19179(T) = DSM 27197(T)).

Effect of zero-valent iron (ZVI) and biogas slurry reflux on methane production by anaerobic digestion of waste activated sludge.

This study aimed to improve anaerobic digestion (AD) efficiency through the addition of zero-valent iron (ZVI) and biogas slurry. This paper demonstrated that methane production was most effectively promoted at a biogas slurry reflux ratio of 60%. The introduction of ZVI into anaerobic systems does not enhance its bioavailability. However, both biogas slurry reflux and the combination of ZVI with biogas slurry reflux increase the relative abundance of microorganisms involved in the direct interspecific electron transfer (DIET) process. Among them, the dominant microorganisms Methanosaeta, Methanobacterium, Methanobrevibacter, and Methanolinea accounted for over 60% of the total methanogenic archaea. The Tax4Fun function prediction results indicate that biogas slurry reflux and the combination of ZVI with biogas slurry reflux can increase the content of key enzymes in the acetotrophic and hydrotrophic methanogenesis pathways, thereby strengthening these pathways. The corrosion of ZVI promotes hydrogen production, and the biogas slurry reflux provided additional alkaline and anaerobic microorganisms for the anaerobic system. Their synergistic effect promoted the growth of hydrotrophic methanogens and improved the activities of various enzymes in the hydrolysis and acidification phases, enhanced the system's buffer capacity, and prevented secondary environmental pollution. PRACTITIONER POINTS: Optimal methane production was achieved at a biogas slurry reflux ratio of 60%. Biogas slurry reflux in anaerobic digestion substantially reduced discharge. ZVI addition in combination with biogas slurry reflux facilitates the DIET process.

The evolution, pathogenicity and transmissibility of quadruple reassortant H1N2 swine influenza virus in China: A potential threat to public health.

Swine are regarded as "intermediate hosts" or "mixing vessels" of influenza viruses, capable of generating strains with pandemic potential. From 2020 to 2021, we conducted surveillance on swine H1N2 influenza (swH1N2) viruses in swine farms located in Guangdong, Yunnan, and Guizhou provinces in southern China, as well as Henan and Shandong provinces in northern China. We systematically analyzed the evolution and pathogenicity of swH1N2 isolates, and characterized their replication and transmission abilities. The isolated viruses are quadruple reassortant H1N2 viruses containing genes from pdm/09 H1N1 (PB2, PB1, PA and NP genes), triple-reassortant swine (NS gene), Eurasian Avian-like (HA and M genes), and recent human H3N2 (NA gene) lineages. The NA, PB2, and NP of SW/188/20 and SW/198/20 show high gene similarities to A/Guangdong/Yue Fang277/2017 (H3N2). The HA gene of swH1N2 exhibits a high evolutionary rate. The five swH1N2 isolates replicate efficiently in human, canine, and swine cells, as well as in the turbinate, trachea, and lungs of mice. A/swine/Shandong/198/2020 strain efficiently replicates in the respiratory tract of pigs and effectively transmitted among them. Collectively, these current swH1N2 viruses possess zoonotic potential, highlighting the need for strengthened surveillance of swH1N2 viruses.

A chromosome-level genome assembly of the pig-nosed turtle (Carettochelys insculpta).

The pig-nosed turtle (Carettochelys insculpta) represents the only extant species within the Carettochelyidae family, is a unique Trionychia member fully adapted to aquatic life and currently facing endangerment. To enhance our understanding of this species and contribute to its conservation efforts, we employed high-fidelity (HiFi) and Hi-C sequencing technology to generate its genome assembly at the chromosome level. The assembly result spans 2.18 Gb, with a contig N50 of 126 Mb, encompassing 34 chromosomes that account for 99.6% of the genome. The assembly has a BUSCO score above 95% with different databases and strong collinearity with Yangtze giant softshell turtles (Rafetus swinhoei), indicating its completeness and continuity. A total of 19,175 genes and 46.86% repetitive sequences were annotated. The availability of this chromosome-scale genome represents a valuable resource for the pig-nosed turtle, providing insights into its aquatic adaptation and serving as a foundation for future turtle research.

Protecting the non-operative lobe/s of the operative lung can reduce the pneumonia incidence after thoracoscopic lobectomy: a randomised controlled trial.

Lung isolation usually refers to the isolation of the operative from the non-operative lung without isolating the non-operative lobe(s) of the operative lung. We aimed to evaluate whether protecting the non-operative lobe of the operative lung using a double-bronchial blocker (DBB) with continuous positive airway pressure (CPAP) could reduce the incidence of postoperative pneumonia. Eighty patients were randomly divided into two groups (n = 40 each): the DBB with CPAP (Group DBB) and routine bronchial blocker (Group BB) groups. In Group DBB, a 7-Fr BB was placed in the middle bronchus of the right lung for right lung surgery and in the inferior lobar bronchus of the left lung for left lung surgery. Further, a 9-Fr BB was placed in the main bronchus of the operative lung. In Group BB, routine BB placement was performed on the main bronchus on the surgical side. The primary endpoint was the postoperative pneumonia incidence. Compared with Group BB, Group DBB had a significantly lower postoperative pneumonia incidence in the operative (27.5% vs 5%, P = 0.013) and non-operative lung (40% vs 15%) on postoperative day 1. Compared with routine BB use for thoracoscopic lobectomy, using the DBB technique to isolate the operative lobe from the non-operative lobe(s) of the operative lung and providing CPAP to the non-operative lobe(s) through a BB can reduce the incidence of postoperative pneumonia in the operative and non-operative lungs.

A porcine model of familial adenomatous polyposis.

We created gene-targeted pigs with mutations in the adenomatous polyposis coli (APC) gene (APC) that are orthologous to those responsible for human familial adenomatous polyposis (FAP). One-year-old pigs with the APC(1311) mutation (orthologous to human APC(1309)) have aberrant crypt foci and low- and high-grade dysplastic adenomas in the large intestine, similar to the precancerous lesions that develop in patients with FAP. Dysplastic adenomas accumulate ß-catenin and lose heterozygosity of APC. This large-animal, genetic model of FAP will be useful in the development of diagnostics and therapeutics for colorectal cancer. DNA sequence data: NCBI accession number GU951771.

FAP promotes metastasis and chemoresistance via regulating YAP1 and macrophages in mucinous colorectal adenocarcinoma.

Mucinous colorectal adenocarcinoma (MC) is less likely to respond to chemotherapy and is associated with poorer prognosis compared with non-MC (NMC). Fibroblast activation protein (FAP) was found and validated to be upregulated in MC patients and was negatively correlated with prognosis and therapeutic outcomes in colorectal cancer (CRC) patients who were treated with adjuvant chemotherapy. Overexpression of FAP promoted CRC cell growth, invasion and metastasis, and enhanced chemoresistance. Myosin phosphatase Rho-interacting protein (MPRIP) was identified as a direct interacting protein of FAP. FAP may influence the efficiency of chemotherapy and prognosis by promoting the crucial functions of CRC and inducing tumor-associated macrophages (TAMs) recruitment and M2 polarization through regulating theRas Homolog Family Member/Hippo/Yes-associated protein (Rho/Hippo/YAP) signaling pathway. Knockdown of FAP could reverse tumorigenicity and chemoresistance in CRC cells. Thus, FAP may serve as a marker for prognosis and therapeutic outcome, as well as a potential therapeutic target to overcome chemoresistance in MC patients.