The Impact of Impurity Gases on the Hydrogen Embrittlement Behavior of Pipeline Steel in High-Pressure H2 Environments.

The use of hydrogen-blended natural gas presents an efficacious pathway toward the rapid, large-scale implementation of hydrogen energy, with pipeline transportation being the principal method of conveyance. However, pipeline materials are susceptible to hydrogen embrittlement in high-pressure hydrogen environments. Natural gas contains various impurity gases that can either exacerbate or mitigate sensitivity to hydrogen embrittlement. In this study, we analyzed the mechanisms through which multiple impurity gases could affect the hydrogen embrittlement behavior of pipeline steel. We examined the effects of O2 and CO2 on the hydrogen embrittlement behavior of L360 pipeline steel through a series of fatigue crack growth tests conducted in various environments. We analyzed the fracture surfaces and assessed the fracture mechanisms involved. We discovered that CO2 promoted the hydrogen embrittlement of the material, whereas O2 inhibited it. O2 mitigated the enhancing effect of CO2 when both gases were mixed with hydrogen. As the fatigue crack growth rate increased, the influence of impurity gases on the hydrogen embrittlement of the material diminished.

CCDC28A deficiency causes sperm head defects, reduced sperm motility and male infertility in mice.

Mature spermatozoa with normal morphology and motility are essential for male reproduction. The epididymis has an important role in the proper maturation and function of spermatozoa for fertilization. However, factors related to the processes involved in spermatozoa modifications are still unclear. Here we demonstrated that CCDC28A, a member of the CCDC family proteins, is highly expressed in testes and the CCDC28A deletion leads to male infertility. We found CCDC28A deletion had a mild effect on spermatogenesis. And epididymal sperm collected from Ccdc28a-/- mice showed bent sperm heads, acrosomal defects, reduced motility and decreased in vitro fertilization competence whereas their axoneme, outer dense fibers, and fibrous sheath were all normal. Furthermore, we found that CCDC28A interacted with sperm acrosome membrane-associated protein 1 (SPACA1) and glycogen synthase kinase 3a (GSK3A), and deficiencies in both proteins in mice led to bent heads and abnormal acrosomes, respectively. Altogether, our results reveal the essential role of CCDC28A in regulating sperm morphology and motility and suggesting a potential marker for male infertility.

PATL2 regulates mRNA homeostasis in oocytes by interacting with EIF4E and CPEB1.

The accumulation and storage of maternal mRNA is crucial for oocyte maturation and embryonic development. PATL2 is an oocyte-specific RNA-binding protein, and previous studies have confirmed that PATL2 mutation in humans and knockout mice cause oocyte maturation arrest or embryonic development arrest, respectively. However, the physiological function of PATL2 in the process of oocyte maturation and embryonic development is largely unknown. Here, we report that PATL2 is highly expressed in growing oocytes and couples with EIF4E and CPEB1 to regulate maternal mRNA expression in immature oocytes. The germinal vesicle oocytes from Patl2-/- mice exhibit decreasing maternal mRNA expression and reduced levels of protein synthesis. We further confirmed that PATL2 phosphorylation occurs in the oocyte maturation process and identified the S279 phosphorylation site using phosphoproteomics. We found that the S279D mutation decreased the protein level of PATL2 and led to subfertility in Palt2S279D knock-in mice. Our work reveals the previously unrecognized role of PATL2 in regulating the maternal transcriptome and shows that phosphorylation of PATL2 leads to the regulation of PATL2 protein levels via ubiquitin-mediated proteasomal degradation in oocytes.

Application of the En Bloc Concept Combined with Anatomic Resection in Laparoscopic Hepatectomy.

Laparoscopic hepatectomy has been reported in many studies, and it is the mainstream method of liver resection. In some particular cases, such as when there are tumors adjacent to the cystic bed, surgeons cannot palpate the surgical margins through the laparoscopic approach, which leads to uncertainty about R0 resection. Conventionally, the gallbladder is resected first, and the hepatic lobes or segments are resected second. However, tumor tissues can be disseminated in the above cases. To address this issue, based on the recognition of the porta hepatis and intrahepatic anatomy, we propose a unique approach to hepatectomy combined with gallbladder resection by en bloc anatomic resection in situ. Firstly, after dissecting the cystic duct, without cutting the gallbladder primarily, the porta hepatis is pre-occluded by the single lumen ureter; secondly, the left hepatic pedicle is made free by the gap of the Laennec membrane and Hilar plate; thirdly, the assistant is asked to drag the fundus of the gallbladder, and the liver parenchyma tissue is resected using a harmonic scalpel along the ischemia line on the liver surface and intraoperative ultrasound. The whole middle hepatic vein (MHV) and its tributaries appear completely; lastly, the left hepatic vein (LHV) is disconnected, and the specimen is taken out from the abdominal cavity. The tumor, gallbladder, and other surrounding tissues are resected en bloc, which meets the tumor-free criterion, and a wide incisal margin and R0 resection are achieved. Therefore, the laparoscopic hepatectomy with the combination of the en bloc concept and anatomic resection is a safe, effective, and radical method with low postoperative recurrence and metastasis.

Classification of Liquid Ingress in GFRP Honeycomb Based on One-Dimension Sequential Model Using THz-TDS.

Honeycomb structure composites are taking an increasing proportion in aircraft manufacturing because of their high strength-to-weight ratio, good fatigue resistance, and low manufacturing cost. However, the hollow structure is very prone to liquid ingress. Here, we report a fast and automatic classification approach for water, alcohol, and oil filled in glass fiber reinforced polymer (GFRP) honeycomb structures through terahertz time-domain spectroscopy (THz-TDS). We propose an improved one-dimensional convolutional neural network (1D-CNN) model, and compared it with long short-term memory (LSTM) and ordinary 1D-CNN models, which are classification networks based on one dimension sequenced signals. The automated liquid classification results show that the LSTM model has the best performance for the time-domain signals, while the improved 1D-CNN model performed best for the frequency-domain signals.

IQUB deficiency causes male infertility by affecting the activity of p-ERK1/2/RSPH3.

STUDY QUESTION: Can new genetic factors responsible for male infertility be identified, especially for those characterized by asthenospermia despite normal sperm morphology? SUMMARY ANSWER: We identified the novel pathogenetic gene IQ motif and ubiquitin-like domain-containing (IQUB) as responsible for male infertility characterized by asthenospermia, involving sperm radial spoke defects. WHAT IS KNOWN ALREADY: To date, only a few genes have been found to be responsible for asthenospermia with normal sperm morphology. Iqub, encoding the IQUB protein, is highly and specifically expressed in murine testes and interacts with the proteins radial spoke head 3 (RSPH3), CEP295 N-terminal like (CEP295NL or DDC8), glutathione S-transferase mu 1 (GSTM1) and outer dense fiber of sperm tails 1 (ODF1) in the yeast two-hybrid system. STUDY DESIGN, SIZE, DURATION: The IQUB variant was identified by whole-exome sequencing in a cohort of 126 male infertility patients with typical asthenospermia recruited between 2015 and 2020. Knockout (KO) and knockin (KI) mouse models, scanning and transmission electron microscopy (TEM), and other functional assays were performed, between 2019 and 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: The IQUB variant was identified by whole-exome sequencing and confirmed by Sanger sequencing. Iqub KO and KI mice were constructed to mimic the phenotype of the affected individual. After recapitulating the phenotype of human male infertility, scanning and TEM were performed to check the ultrastructure of the sperm. Western blot and co-immunoprecipitation were performed to clarify the pathological mechanism of the IQUB variant. MAIN RESULTS AND THE ROLE OF CHANCE: We identified a homozygous nonsense IQUB variant (NM_001282855.2:c.942T> G(p.Tyr314*)) from an infertile male. Iqub KO and KI mice mimicked the infertility phenotype and confirmed IQUB to be the pathogenetic gene. Scanning and TEM showed that sperm of both the mouse models and the affected individual had radial spoke defects. The functional assay suggested that IQUB may recruit calmodulin in lower Ca2+ environments to facilitate the normal assembly of radial spokes by inhibiting the activity of RSPH3/p-ERK1/2 (a nontypical AKAP (A-Kinase Anchoring Protein) forming by RSPH3 and phosphorylation of extracellular signal-regulated kinase 1 and 2 (p-ERK1/2)). LIMITATIONS, REASONS FOR CAUTION: Additional cases are needed to confirm the genetic contribution of IQUB variants to male infertility. In addition, because no IQUB antibody is available for immunofluorescence and the polyclonal antibody we generated was only effective in western blotting, immunostaining for IQUB was not performed in this study. Therefore, this study lacks direct in vivo proof to confirm the effect of the variant on IQUB protein level. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest a causal relation between IQUB variants and male infertility owing to asthenospermia, and partly clarify the pathological mechanism of IQUB variants. This expands our knowledge of the genes involved in human sperm asthenospermia and potentially provides a new genetic marker for male infertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research and Development Program of China (2021YFC2700100), the National Natural Science Foundation of China (32130029, 82171643, 81971450, 82001538, and 81971382) and the Guangdong Science and Technology Department Guangdong-Hong Kong-Macao Joint Innovation Project (2020A0505140003). There are no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Idiopathic tenosynovitis of the wrist with multiple rice bodies: A case report and review of literature.

BACKGROUND: Multiple rice bodies in the wrist is a rare disorder that requires surgery, and there are still many uncertainties regarding its diagnosis and treatment. CASE SUMMARY: We described a rare case of chronic idiopathic tenosynovitis with rice bodies of the wrist in a 71-year-old man and reviewed similar topics in the literature. A total of 43 articles and 61 cases were included in the literature review. Our case had a usual presentation: it was similar to those in the literature. The affected population was mainly older adults, with an average age of 59.43 (range, 3 to 90) years. The male-to-female ratio was 1.54:1 (37/24).Most of them showed limited swelling and pain, only 23.0% had carpal tunnel symptoms, and the average disease duration was 18.03 (0.5-60) mo. Wrist flexor tendon sheath involvement was the most common (95.1%, 58/61), and only 3 cases had extensor tendon sheath involvement.The main causes were tuberculosis (34.4%, 21/61), non-tuberculous mycobacteria (24.6%, 15/61), idiopathic tenosynovitis (31.1%, 19/61), and others (9.84%, 6/61). There were 10 patients with recurrences; in 6 of them, were due to non-tuberculous mycobacterial infections. CONCLUSION: We reported a case of wrist idiopathic tenosynovitis with rice body formation, and established a clinical management algorithm for wrist tenosynovitis with rice bodies, which can provide some reference for our clinical diagnosis and treatment. The symptoms of rice-body bursitis of the wrist are insidious, nonspecific, and difficult to identify. The aetiology is mainly idiopathic tenosynovitis and mycobacterial (tuberculosis or non-tuberculous) infections; the latter are difficult to treat and require long-duration systemic combination antibiotic therapies. Therefore, before a diagnosis of idiopathic tenosynovitis is made, we must exclude other causes, especially mycobacterial infections.

Responses of dissolved organic matter (DOM) characteristics in eutrophic lake to water diversion from external watershed.

Eutrophication is an important water environment issue facing global lakes. Diversion of water from external watersheds into lakes is considered as effective in ameliorating eutrophication and reducing algal blooms. Nevertheless, the changes in lake water environment caused by external water diversion, especially the influence of water diversion on the characteristics of dissolved organic matters (DOM), are still poorly understood. We therefore used a combination of EEM-PARAFAC, Principal Component Analysis (PCA), and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) to investigate the effects of water diversion from the Niulan River on DOM characteristics in Lake Dianchi. The results showed that the water diversion from the Niulan River significantly improved the water quality of Lake Dianchi, the concentrations of TN, TP, COD and Chla decreased rapidly, and the degree of humification of dissolved organic matter (DOM) increased, which was in sharp contrast with that of pre-implementation. Firstly, the diversion of water from the Niulan River mainly led to changes in the structure of pollution sources. The load of influent rivers and sewage treatment plants rich in lignin and tannins increased, and the input of terrestrial humus increased. Second, the improved water quality reduced algal enrichment and frequency of blooms, and reduced the release of lipid- and protein-riched algal-derived DOM. Finally, the hydraulic retention time of Lake Dianchi caused by water diversion was shortened, the hydrodynamic conditions were significantly improved, and the dissolved oxygen (DO) level gradually recovered, which played a positive role in improving the humification degree of DOM. Our findings provide new insights for exploring the improvement of eutrophic lake eco-environmental quality caused by water diversion projects.

Wood smoke particulate matter (WSPM2.5) induces pyroptosis through both Caspase-1/IL-1ß/IL-18 and ATP/P2Y-dependent mechanisms in human bronchial epithelial cells.

Emerging evidences have linked the air pollution particulate matters, especially the fine particulate matter PM2.5, to the disease development of chronic obstructive pulmonary disease (COPD). Our previous studies reported that biofuel PM2.5 can induce devastated damage of human bronchial epithelial cells, this study aims to further investigate the underlying molecular mechanisms how biofuel PM2.5 induces bronchial epithelial cell death and dysfunction. In this study, biofuel PM2.5 extracted from wood smoke (WSPM2.5) was used according to our previous publication. A 16-HBE cell line was used as the cell model. Results showed that: Firstly, WSPM2.5 induced significant pyroptosis in 16-HBE cells, reflected by the typical changes including elevated release of lactate dehydrogenase release (LDH) and activated activity and expression of Caspase-1/IL-1ß/IL-18 signaling pathway. Then, specific inhibitors for both Caspases (Z-VAD-FMK) and Caspase-1 (VX-765), as well as specific siRNA knockdown of IL-1ß all effectively attenuated the WSPM2.5-induced upregulation of downstream inflammatory cytokines and chemokines (IL-6, IL-8, CXCL-1, CXCL-2, etc), respectively. Notably, WSPM2.5 caused a novel increase of intracellular-to-extracellular ATP secretion, which could also contribute to the WSPM2.5-induced pyroptosis and inflammation by activating the Caspase-1/IL-1ß/IL-18 signaling pathway through possible autocrine and/or paracrine mechanisms. Antagonism of ATP (Apyrase) or specific siRNA knockdown against ATP receptors (P2Y2 and P2Y7) both significantly inhibited the WSPM2.5-induced pyroptosis and inflammation. These results add up to the current knowledge and bring up novel insights that WSPM2.5 could induce significant pyroptosis and inflammation of human bronchial epithelial cells, through both a classic NLRP3/Caspase-1/IL-1ß-dependent and a novel ATP/P2Y-dependent mechanisms.

Research of control method for pneumatic control of pneumatic microchips.

A novel composite control method for actuated chamber air pressure of pneumatic microfluidic chip via a three-way electromagnetic microvalve is presented in this paper. The purpose of the control methods is to improve air pressure controlling precision for pneumatic control. By using the Bang-Bang (on-off) controller for pneumatic control, the step-response time, air pressure steady-state accuracy, and air pressure fluctuations are performed with different maximum thresholds and minimum thresholds. Moreover, by using the k (proportional ) plus PWM (Pulse-Width Modulation) control method for pneumatic control, the step-response time, air pressure steady-state accuracy, and air pressure fluctuations are performed with different carrier frequencies and carrier amplitudes. Both advantages and disadvantages of the two control methods are compared and analyzed based on the experimental data. According to the variable volume of the actuated chamber and the response characteristics of the three-way electromagnetic microvalve, the composite control method of the Bang-Bang plus k plus PWM is developed to control the actuated chamber air pressure. The experimental results show that when the absolute air pressure of the actuated chamber is set to 150kPa, the rising time is 69.3ms, which is about 8.0ms shorter than that of the k+PWM control method alone. The steady-state error is reduced from 0.90kPa to 0.65kPa, and the air pressure steady-state fluctuation is reduced from 1.60kPa to 0.90kPa, compared with the Bang-Bang control method alone.

[A new measurement method of offset in total hip arthroplasty].

Objective: To report a new offset parameter for total hip arthroplasty (THA)-greater trochanter offset (GTO), and analyze the effectiveness and feasibility of this parameter based on clinical data. Methods: The 47 patients who met the selection criteria and admitted between January 2016 and May 2020 were selected as the research object. The global offset (GO) was used as the offset parameter in preoperative design. Firstly, the test-retest reliability and inter-rater reliability of GTO were analyzed based on pelvic X-ray films. The GTO reconstruction was defined as the difference between the operative side and the healthy side within ±5 mm, and 47 patients were divided into the reconstruction group and the non-reconstruction group. General data (age, gender, type and side of fracture, the interval between injury and operation), visual analogue scale (VAS) score, Harris score, gait score, and leg length discrepancy (LLD) were recorded and compared between two groups. Then, the GTO was used as the offset parameter in preoperative design of 21 patients (GTO group) admitted between June 2020 and December 2020. The pre- and post-operative clinical data were compared between GTO group and GO group to explore the feasibility of GTO for THA. Results: Statistical analysis showed that GTO had good test-retest reliability (P<0.001) and inter-rater reliability (P<0.001). There was no significant difference in gender, age, type and side of fracture, the interval between injury and operation, preoperative VAS score, and LLD at 1 year after operation between the GTO reconstruction group and the non-reconstruction group, as well as between the GO and GTO groups (P>0.05). The Harris score and gait score at 1 year after operation, and difference of VAS score between pre- and post- operation in the reconstruction group and GTO group were significantly better than those in the non-reconstruction group and GO group, respectively (P<0.05). There were 23 cases (48.9%) in the GO group and 19 cases (90.5%) in the GTO group with GTO reconstruction, and the difference was significant (χ2=10.606, P=0.001). There were 25 cases (53.2%) in the GO group and 13 cases (61.9%) in the GTO group with GO reconstruction, and the difference was not significant (χ2=0.447, P=0.504). There were 34 cases (72.3%) in the GO group and 19 cases (90.5%) in the GTO group with LLD reconstruction, and the difference was not significant (χ2=2.777, P=0.096). Conclusion: GTO has reliable test-retest reliability and inter-rater reliability. GTO as a parameter of preoperative offset reconstruction plan of THA can obtain good reconstruction of offset and limb length, and obtain a good effectiveness.

Platelet-lymphocyte ratio is a prognostic marker in small cell lung cancer-A systemic review and meta-analysis.

Aim: The aim of this study was to evaluate the relationship between platelet-lymphocyte ratio (PLR) and prognosis in small cell lung cancer (SCLC) patients. Method: A comprehensive search was carried out to collect related studies. Two independent investigators extracted the data of hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) or progression-free survival (PFS). A random-effect model was applied to analyze the effect of different PLR levels on OS and PFS in SCLC patients. Moreover, subgroup analysis was conducted to seek out the source of heterogeneity. Results: A total of 26 articles containing 5,592 SCLC patients were included for this meta-analysis. SCLC patients with a high PLR level had a shorter OS compared with patients with a low PLR level, in both univariate (HR = 1.56, 95% CI 1.28-1.90, p < 0.0001) and multivariate (HR = 1.31, 95% CI 1.08-1.59, p = 0.007) models. SCLC patients with a high PLR level had a shorter PFS compared with patients with a low PLR level, in the univariate model (HR = 1.71, 95% CI 1.35-2.16, p < 0.0001), but not in the multivariate model (HR = 1.17, 95% CI 0.95-1.45, p = 0.14). Subgroup analysis showed that a high level of PLR shortened OS in some subgroups, including the Asian subgroup, the younger subgroup, the mixed-stage subgroup, the chemotherapy-dominant subgroup, the high-cutoff-point subgroup, and the retrospective subgroup. PLR level did not affect OS in other subgroups. Conclusion: PLR was a good predictor for prognosis of SCLC patients, especially in patients received chemotherapy dominant treatments and predicting OS. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022383069.

A new ionic liquid bridged periodic mesoporous organosilicas stationary phase for per aqueous liquid chromatography and its application in the detection of biogenic amines.

In order to solve the problems of using a large proportion of acetonitrile on the hydrophilic interaction liquid chromatography (HILIC) columns that was not environmentally friendly, and the poor acid and base resistance of traditional bonded silica columns, we reported a novel stationary phase of Au nanoparticles (Au NPs) covalently bonded to ionic liquid (ILs) bridged periodic mesoporous organosilicas (PMO) hydrophilic microspheres (PMO-ILs-Au NPs) for per aqueous liquid chromatography (PALC). The PMO hydrophilic microspheres were prepared by condensation of 1,3-bis(trimethoxysilylpropyl)imidazoliumchloride and 1, 2-Bis (triethoxysilyl) ethane and then modified with Au NPs the surface. The obtained materials were characterized by elemental analysis, FT-IR spectra, scanning electron microscope and transmission electron microscopy. The retention behavior was evaluated by investigating the effect of various chromatographic factors on the retention of different types of solutes. The retention mechanism of the stationary phases in PALC was a mixed type of anion-exchange and hydrophobic interaction. Compared with C18-SiO2 column, the acid and base resistance of the stationary phase were greatly improved. Compared with the HILIC column and C18 column, some hydrophilic compounds such as six organic acids and eight biogenic amines were baseline separated with the enhanced resolution of the PMO-ILs-Au NPs column under the PALC mode. The efficiency of the new column was significantly higher than that of the HILIC column. Furthermore, the analysis of PALC-triple quadrupole mass spectrometry was developed for simultaneous detection of eight biogenic amines. This method could improve detection efficiency, save reagent and reduce environmental pollution. PALC as a green chromatography analytical method was suitable for the replacement of HILIC.

IL-17-Mediated Inflammation Promotes Cigarette Smoke-Induced Genomic Instability.

(1) Background: Chronic inflammation has been regarded as a risk factor for the onset and progression of human cancer, but the critical molecular mechanisms underlying this pathological process have yet to be elucidated. (2) Methods: In this study, we investigated whether interleukin (IL)-17-mediated inflammation was involved in cigarette smoke-induced genomic instability. (3) Results: Higher levels of both IL-17 and the DNA damage response (DDR) were found in the lung tissues of smokers than in those of non-smokers. Similarly, elevated levels of IL-17 and the DDR were observed in mice after cigarette smoke exposure, and a positive correlation was observed between IL-17 expression and the DDR. In line with these observations, the DDR in the mouse lung was diminished in IL-17 KO when exposed to cigarette smoke. Besides this, the treatment of human bronchial epithelium cells with IL-17 led to increased levels of the DDR and chromosome breakage. (4) Conclusions: These results suggest that cigarette smoke induces genomic instability at least partially through IL-17-mediated inflammation, implying that IL-17 could play an important role in the development of lung cancer.

Nitric oxide in occurrence, progress and therapy of lung Cancer: a systemic review and meta-analysis.

BACKGROUND: Nitric oxide (NO) plays an important role in lung cancer. However, the results of previous studies about NO in the occurrence, progress and therapy were not consistent. Therefore, we conducted a meta-analysis to evaluate the relationship between NO and lung cancer. METHOD: We carried out comprehensive search in the databases, and collected related studies. The data of fraction of exhaled nitric oxide (FeNO) or blood NO in different populations (lung cancer patients and control subjects) and different time points (before therapy and after therapy) were extracted by two investigators. A random effect model was applied to analyze the differences of FeNO and blood NO in different populations and different time points. To further compare NO level of each subgroup with different pathological types and different stages, a network meta-analysis (NMA) was performed. RESULTS: Fifty studies including 2551 cases and 1691 controls were adopted in this meta-analysis. The FeNO (SMD 3.01, 95% CI 1.89-4.13, p < 0.00001) and blood NO (SMD 1.34, 95% CI 0.84-1.85, p < 0.00001) level in lung cancer patients was much higher than that in control subjects. NMA model indicated blood NO level in each cancer type except SCLC was higher than that in control patients. There was no significant difference of blood NO level among four kinds of lung cancer patients. Blood NO level in LCC patients (SUCRA = 83.5%) was the highest. Blood NO level in advanced stage but not early stage was higher than that in control subjects. Patients in advanced stage (SUCRA = 95.5%) had the highest blood NO level. No significant difference of FeNO (SMD -0.04, 95% CI -0.46-0.38, p > 0.05) and blood NO level (SMD -0.36, 95% CI -1.08-0.36, p > 0.05) was observed between pretreatment and posttreatment in all patients. However, FeNO level elevated (SMD 0.28, 95% CI 0.04-0.51, p = 0.02) and blood NO level decreased in NSCLC patients (SMD -0.95, 95% CI -1.89-0.00, p = 0.05) after therapy. CONCLUSION: FeNO and blood NO level would contribute to diagnosis of lung cancer and evaluation of therapy effect, especially for NSCLC patients.

Exposure to biomass smoke induces pulmonary Th17 cell differentiation by activating TLR2 on dendritic cells in a COPD rat model.

Almost three billion people in developing countries are exposed to biomass smoke (BS), which predisposes them to developing chronic obstructive pulmonary disease (COPD). COPD is associated with abnormal innate and adaptive immune responses in the lungs and systemic circulation, but the mechanisms underlying BS-COPD development are uncertain. We investigated the role of dendritic cells (DCs) and interleukin (IL)-17A in BS-COPD. We investigated T helper cell responses in the BS-exposed COPD rat model by flow cytometry, quantitative PCR, and enzyme-linked immunosorbent assays. We conducted ex vivo experiments to determine which antigen-presenting cells induce Th17 cell responses. We evaluated the in vitro effects of BS-related particulate matter (BRPM) (2.5 µm) on the function of bone marrow-derived dendritic cells (BMDCs). We found that BS exposure enhanced Th17 responses in the lungs of the COPD-modelled rats, and the stimulated DCs (but not the macrophages) were sufficient to induce naïve CD4 + T cells to produce IL-17A in ex vivo experiments. BRPM significantly enhanced the maturation and activation of DCs through Toll-like receptor 2 (TLR2), but not TLR4, and induced Th17 responses. Therefore, BS activated lung DCs through TLR2, which led to Th17 responses and emphysema in the rats. This process is possibly therapeutically targetable.

Senescence associated long non-coding RNA 1 regulates cigarette smoke-induced senescence of type II alveolar epithelial cells through sirtuin-1 signaling.

OBJECTIVE: The primary aim of our study was to explore the mechanisms through which long non-coding RNA (lncRNA)-mediated sirtuin-1 (SIRT1) signaling regulates type II alveolar epithelial cell (AECII) senescence induced by a cigarette smoke-media suspension (CSM). METHODS: Pharmacological SIRT1 activation was induced using SRT2104 and senescence-associated lncRNA 1 (SAL-RNA1) was overexpressed. The expression of SIRT1, FOXO3a, p53, p21, MMP-9, and TIMP-1 in different groups was detected by qRT-PCR and Western blotting; the activity of SA-ß gal was detected by staining; the binding of SIRT1 to FOXO3a and p53 gene transcription promoters was detected by Chip. RESULTS: We found that CSM increased AECII senescence, while SAL-RNA1 overexpression and SIRT1 activation significantly decreased levels of AECII senescence induced by CSM. Using chromatin immunoprecipitation, we found that SIRT1 bound differentially to transcriptional complexes on the FOXO3a and p53 promoters. CONCLUSION: Our results suggested that lncRNA-SAL1-mediated SIRT1 signaling reduces senescence of AECIIs induced by CSM. These findings suggest a new therapeutic target to limit the irreversible apoptosis of lung epithelial cells in COPD patients.

Metabolomics strategy for revealing the components in fermented barley extracts with Lactobacillus plantarum dy-1.

Fermentation has been considered as effective tools to promote the functional properties of cereals. In this paper, barley flour was fermented with Lactobacillus plantarum dy-1 (L. plantarum dy-1) and the main components in the fermented barley aqueous extracts were identified using by ultra-high performance liquid chromatography tandem with high resolution mass spectrometry (UPLC-HRMS), and investigated by metabolomics strategy involved on chemometrics. The barley extracts were prepared at the fermentation time of 0, 4, 8, 12, 16, 20, 24, 28 h, respectively and a total of 124 compounds were detected in the samples. Principal component analysis (PCA) was performed and the results indicated that the fermentation process became to slow down from 16 h until terminated. During fermentation, saccharides, amino acids, nucleosides, and some organic acids decreased, while lipids and bioactive molecules in barley were released and metabolites were accumulated by L. plantarum dy-1. Meanwhile, partial least squares discrimination analysis (PLS-DA) was performed for revealing the characteristic components in fermented barley aqueous extracts, including some functional molecules such as indole-3-lactic acid, phenyllactic acid, homovanillic acid and cafestol, etc., which provided the roles of them and the basis for further investigation on the functional bioactivities and application.