Short-chain fatty acids: bridges between diet, gut microbiota, and health.

In recent years, gut microbiota has become a hot topic in the fields of medicine and life sciences. Short-chain fatty acids (SCFAs), the main metabolites of gut microbiota produced by microbial fermentation of dietary fiber, play a vital role in healthy and ill hosts. SCFAs regulate the process of metabolism, immune, and inflammation and have therapeutic effects on gastrointestinal and neurological disorders, as well as antitumor properties. This review summarized the production, distribution, and molecular mechanism of SCFAs, as well as their mechanisms of action in healthy and ill hosts. In addition, we also emphasized the negative effects of SCFAs, aiming to provide the public with a more comprehensive understanding of SCFAs.

Targeting leucine-rich repeat serine/threonine-protein kinase 2 sensitizes pancreatic ductal adenocarcinoma to anti-PD-L1 immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is not sensitive to immune checkpoint blockade therapy, and negative feedback of tumor immune evasion might be partly responsible. We isolated CD8+ T cells and cultured them in vitro. Proteomics analysis was performed to compare changes in Panc02 cell lines cultured with conditioned medium, and leucine-rich repeat kinase 2 (LRRK2) was identified as a differential gene. LRRK2 expression was related to CD8+ T cell spatial distribution in PDAC clinical samples and upregulated by CD8+ T cells via interferon gamma (IFN-γ) simulation in vitro. Knockdown or pharmacological inhibition of LRRK2 activated an anti-pancreatic cancer immune response in mice, which meant that LRRK2 acted as an immunosuppressive gene. Mechanistically, LRRK2 phosphorylated PD-L1 at T210 to inhibit its ubiquitination-mediated proteasomal degradation. LRRK2 inhibition attenuated PD-1/PD-L1 blockade-mediated, T cell-induced upregulation of LRRK2/PD-L1, thus sensitizing the mice to anti-PD-L1 therapy. In addition, adenosylcobalamin, the activated form of vitamin B12, which was found to be a broad-spectrum inhibitor of LRRK2, could inhibit LRRK2 in vivo and sensitize PDAC to immunotherapy as well, which potentially endows LRRK2 inhibition with clinical translational value. Therefore, PD-L1 blockade combined with LRRK2 inhibition could be a novel therapy strategy for PDAC.

Serum lipidomics-based study of electroacupuncture for skin wound repair in rats.

Lipid metabolism plays an important role in the repair of skin wounds. Studies have shown that acupuncture is very effective in skin wound repair. However, there is little knowledge about the mechanism of electroacupuncture. Thirty-six SD rats were divided into three groups: sham-operated group, model group and electroacupuncture group, with six rats in each group. After the intervention, orbital venous blood was collected for lipid metabolomics analysis, wound perfusion was detected and finally the effect of electroacupuncture on skin wound repair was comprehensively evaluated by combining wound healing rate and histology. Lipid metabolomics analysis revealed 11 differential metabolites in the model versus sham-operated group. There were 115 differential metabolites in the model versus electro-acupuncture group. 117 differential metabolites in the electro-acupuncture versus sham-operated group. There were two differential metabolites common to all three groups. Mainly cholesteryl esters and sphingolipids were elevated after electroacupuncture and triglycerides were largely decreased after electroacupuncture. The electroacupuncture group recovered faster than the model group in terms of blood perfusion and wound healing (p < 0.05). Electroacupuncture may promote rat skin wound repair by improving lipid metabolism and improving local perfusion.

KRAS mutations upregulate Runx1 to promote occurrence of head and neck squamous cell carcinoma.

Gene mutations play an important role in head and neck squamous cell carcinoma (HNSCC) by not only promoting the occurrence and progression of HNSCC but also affecting sensitivity to treatment and prognosis. KRAS is one of the most frequently mutated oncogenes, which has been reported to have a mutation rate from 1.7% to 12.7% and may lead to poor prognosis in HNSCC, but its role remains unclear. Here, we found that the KRAS mutation can promote HNSCC generation through synergism with 4-Nitroquinoline-1-Oxide(4NQO). Mechanistically, KRAS mutations can significantly upregulate Runx1 to promote oral epithelial cell proliferation and migration and inhibit apoptosis. Runx1 inhibitor Ro 5-3335 can effectively inhibit KRAS-mutated HNSCC progression both in vitro and in vivo. These findings suggest that the KRAS mutation plays an important role in HNSCC and that Runx1 may be a novel therapeutic target for KRAS-mutated HNSCC.

Variability in the psychological impact of four waves of COVID-19: a time-series study of 60 000 text-based counseling sessions.

BACKGROUND: Continuous exposure to stressors can lead to vulnerability and, in some cases, resilience. This study examined the variation in its psychological impact across the first four waves of COVID-19 in Hong Kong. METHODS: Transcripts from Open Up, an online text-based counseling service, between January 2019 and January 2021 were analyzed (N = 60 775). We identified COVID-19 mentioned sessions using keywords and further categorized them into those that also mentioned symptoms of common mental disorders (CMDs) and those that did not. Autoregressive integrated moving average models were used to analyze the associations between the severity of the outbreak and the mention of COVID-19 and CMDs. RESULTS: Results revealed that the pandemic led to increased psychological distress. Compared to prior to its advent, more people sought help in the initial months of the outbreak. Furthermore, associations were found between the severity of the outbreak and the number of help-seeker mentioning the pandemic, as well as between the outbreak severity and the number of help-seekers disclosing psychological distress. However, these relationships were not uniform across the four waves of outbreaks; a dissociation between outbreak severity and help-seekers' concern was found in the fourth wave. CONCLUSION: As the pandemic waxes and wanes, people may become habituated to its psychological toll. This may be interpreted as a form of resilience. Instead of worsening with time, the psychological impact of COVID-19 may reduce with repeated exposure.

Renal-hepatic-pancreatic dysplasia-1 with a novel NPHP3 genotype: a case report and review of the literature.

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 1 (RHPD1) is a rare sporadic and autosomal recessive disorder with unknown incidence. RHPD1 is caused by biallelic pathogenic variants in NPHP3, which encode nephrocystin, an important component of the ciliary protein complex. CASE PRESENTATION: In this case report, we describe a male newborn who was confirmed by ultrasound to have renal enlargement with multiple cysts, pancreatic enlargement with cysts, and increased liver echogenicity, leading to the clinical diagnosis of RHPD. In addition, a compound heterozygous pathogenic variant, namely, NPHP3 c.1761G > A (p. W587*) and the c.69delC (p. Gly24Ala24*11) variant, was detected by WES. The patient was clinically and genetically diagnosed with RHPD1. At 34 h of life, the infant died of respiratory insufficiency. CONCLUSION: This is the first published case of RHPD1 in China. This study broadens the known range of RHPD1 due to NPHP3 pathogenic variants.

Encapsulation of lipases by nucleotide/metal ion coordination polymers: enzymatic properties and their applications in glycerolysis and esterification studies.

BACKGROUND: In the present study, lipases of TLL (lipase from Thermomyces lanuginosus), AOL (lipase from Aspergillus oryzae), RML (lipase from Rhizomucor miehei), BCL (lipase from Burkholderia cepacia), CALA (Candida antarctica lipase A) and LU (Lecitase® Ultra) were encapsulated into nucleotide-hybrid metal coordination polymers (CPs). Enzyme concentration was optimized for encapsulation and the enzymatic properties of the obtained lipases were investigated. In addition, their performance in glycerolysis and esterification was evaluated, and glycerolysis conditions (water content, temperature and time) were optimized. RESULTS: Hydrolysis activity over 10 000 U g-1 and activity recovery over 90% were observed from AOL@GMP/Tb, TLL@GMP/Tb and RML@GMP/Tb. GMP/Tb encapsulation (of AOL, TLL, RML and LU) improved their thermostability when incubated in air. The encapsulated lipases exhibited moderate [triacylglycerols (TAG) conversion 30-50%] and considerable glycerolysis activity (TAG conversion over 60%). TAG conversions from 69.37% to 82.35% and diacylglycerols (DAG) contents from 58.62% to 64.88% were obtained from CALA@GMP/metal samples (except for CALA@GMP/Cu). Interestingly, none of the encapsulated lipases initiated the esterification reaction. AOL@GMP/Tb, TLL@GMP/Tb, RML@GMP/Tb and CALA@GMP/Tb showed good reusability in glycerolysis, with 88.80%, 94.67%, 89.85% and 78.16% of their initial glycerolysis activity, respectively, remaining after five cycles of reuse. The relationships between temperature and TAG conversion were LnV0  = 6.5364-3.7943/T and LnV0  = 13.8820-6.4684/T for AOL@GMP/Tb and CALA@GMP/Tb, respectively; in addition, their activation energies were 31.55 and 53.78 kJ mol-1 , respectively. CONCLUSION: Most of the present encapsulated lipases exhibited moderate and considerable glycerolysis activity. In addition, AOL@GMP/Tb, TLL@GMP/Tb, RML@GMP/Tb and CALA@GMP/Tb exhibited good reusability in glycerolysis reactions and potential in practical applications. © 2022 Society of Chemical Industry.

Systematic analysis of nuclear localization of Autographa californica multiple nucleopolyhedrovirus proteins.

Baculoviruses are large DNA viruses that replicate within the nucleus of infected host cells. Therefore, many viral proteins must gain access to the nucleus for efficient viral genome replication, gene transcription and virion assembly. To date, the global protein localization pattern of baculoviral proteins is unknown. In this study, we systematically analysed the nuclear localization of 154 ORFs encoded by the prototypic baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), either during transient expression or with super-infection of the virus. By transient expression of vectors containing egfp-fused ORFs, we found that in the absence of virus infection, 25 viral proteins were localized in the nucleus. Most of these, which we called 'auto-nuclear localization' proteins, are related to virus replication, transcription or virion structure, and 20 of them contain predicted classical nuclear localization signal. Upon virus infection, 11 proteins, which originally localized in the cytoplasm or both cytoplasm and nucleus in the transfection assays, were completely translocated into the nucleus, suggesting that their nuclear import is facilitated by other viral or host proteins. Further co-transfection experiments identified that four of the 11 proteins, including P143, P33, AC73 and AC114, were imported into the nucleus with the assistance of the auto-nuclear localization proteins LEF-3 (for P143), TLP (for P33) and VP80 (for both AC73 and AC114). This study presents the first global nuclear localization profile of AcMNPV proteins and provides useful information for further elucidation of the mechanisms of baculovirus nuclear entry and gene functions.

A comparison of mycophenolate mofetil and calcineurin inhibitor as maintenance immunosuppression for kidney transplant recipients: A meta-analysis of randomized controlled trials

Background/aim: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the comparison and its timing between mycophenolate mofetil (MMF) and calcineurin inhibitor (CNI) as maintenance immunosuppression for kidney transplant recipients. Materials and methods: The RCTs of MMF versus CNI as maintenance immunosuppression for kidney transplant recipients were searched from PubMed, Embase, Cochrane Central Register of Controlled Trials (CCRCT), and ClinicalTrials.gov. After screening relevant RCTs, two authors independently assessed the quality of included studies and performed a meta-analysis using RevMan5.3. Relative risk (RR) was used to report dichotomous data, while mean difference (MD) with 95% confidence interval (CI) was used to report continuous outcomes. The analysis was conducted using the random-effect model due to the expected heterogeneity among different studies. Four subgroups were allocated to compare MMF with CNI as maintenance immunosuppression: (1) after 3 months of CNI-based therapy, (2) after 6 months of CNI-based therapy, (3) after 12 months of CNI-based therapy, and (4) in recipients with allograft dysfunction. Results: Twelve RCTs with 950 renal transplant recipients were included. This meta-analysis presented the following results upon comparison between MMF and CNI as maintenance immunosuppression for kidney transplant recipients: (1) MMF significantly improved the glomerular filtration rate (GFR) not only in the comparison performed after 3, 6, or 12 months of CNI-based therapy but also in the comparison of recipients with allograft dysfunction, (2) MMF may increase the risk of acute rejection in the comparison performed after 3 months of CNI-based therapy, but no increase was noted in the comparison performed after 6 or 12 months of CNI- based therapy. Conclusion: Our present meta-analysis suggested that MMF followed at least 6 months of CNI-based therapy is an effective maintenance immunosuppressive regimen for kidney transplant recipients to improve renal function but not increase rejection.

Orbital teratoma in the foetus: a rare case without proptosis.

BACKGROUND: Congenital orbital teratoma is relatively rare, and few reports of prenatal ultrasound findings in such cases have been published. CASE PRESENTATION: A rare case of congenital orbital teratoma at 24 + 2 weeks of gestation was previously diagnosed as microphthalmia, noting how orbital teratoma without proptosis is different from microphthalmia, retinoblastoma and intracranial teratoma. Ultrasound examination, analysis of gross specimens, and histopathological evaluation confirmed the diagnosis of orbital teratoma. CONCLUSION: Prenatal ultrasound examination is useful for diagnosis and differential diagnosis of congenital orbital teratoma.

Neuropilin1 silencing impairs the proliferation and migration of cells in pancreatic cancer.

BACKGROUND: Neuropilin1 (NRP1) participates in cancer cell proliferation, migration, and metastasis as a multifunctional co-receptor by interacting with multiple signal pathways, but few studies have addressed the precise function of NRP1 in pancreatic cancer (PACA) cells. We aimed to study whether NRP1 gene silencing involved in the proliferation and migration of PACA cells in vitro. METHODS: A lentiviral vector expressing NRP1 shRNA was constructed and transfected into human PACA cells (CFPAC-1 and PANC-1). The expression of NRP1 protein and mRNA was detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) assay, respectively. CCK-8 assay, wound healing assay, and transwell assay were conducted to examine the effect of NRP1 silencing on cells proliferation and migration capability. RESULTS: Results of qRT-PCR and Western blot showed successfully established, stably transfected shRNA-NRP1 cells in PACA cells. The proliferation capacity of PACA cells in NRP1 shRNA group was lower significantly than that in the negative control (NC) group (P < .05). The invasion and migration capability of PACA cells in NRP1 shRNA group was lower significantly than that in the NC group (P < .01). CONCLUSIONS: NRP1-shRNA lentiviral interference vectors can effectively decrease NRP1 gene expression in PACA cells, thereby inhibiting cells proliferation and migration, which provides a basis for finding a valuable therapeutic target for PACA therapy.

Multiplex one-step real-time PCR assay for rapid simultaneous detection of velogenic and mesogenic Newcastle disease virus and H5-subtype avian influenza virus.

H5 avian influenza virus (AIV) and velogenic Newcastle disease virus (v-NDV) are pathogens listed in the OIE Terrestrial Animal Health Code and are considered key pathogens to be eliminated in poultry production. Molecular techniques for rapid detection of H5 AIV and v-NDV are required to investigate their transmission characteristics and to guide prevention. Traditional virus isolation, using embryonated chicken eggs, is time-consuming and cannot be used as a rapid diagnostic technology. In this study, a multiplex real-time RT-PCR (RRT-PCR) detection method for six H5 AIV clades, three v-NDV subtypes, and one mesogenic NDV subtype was successfully established. The detection limit of our multiplex NDV and H5 AIV RRT-PCR was five copies per reaction for each pathogen, with good linearity and efficiency (y = -3.194x + 38.427 for H5 AIV and y = -3.32x + 38.042 for NDV). Multiplex PCR showed good intra- and inter-assay reproducibility, with coefficient of variance (CV) less than 1%. Furthermore, using the RRT-PCR method, H5 AIV and NDV detection rates in clinical samples were higher overall than those obtained using the traditional virus isolation method. Therefore, our method provides a promising technique for surveillance of various H5 AIV clades and multiple velogenic and mesogenic NDV subtypes in live-poultry markets.

MiR-375 inhibits the hepatocyte growth factor-elicited migration of mesenchymal stem cells by downregulating Akt signaling.

The migration of mesenchymal stem cells (MSCs) is critical for their use in cell-based therapies. Accumulating evidence suggests that microRNAs are important regulators of MSC migration. Here, we report that the expression of miR-375 was downregulated in MSCs treated with hepatocyte growth factor (HGF), which strongly stimulates the migration of these cells. Overexpression of miR-375 decreased the transfilter migration and the migration velocity of MSCs triggered by HGF. In our efforts to determine the mechanism by which miR-375 affects MSC migration, we found that miR-375 significantly inhibited the activation of Akt by downregulating its phosphorylation at T308 and S473, but had no effect on the activity of mitogen-activated protein kinases. Further, we showed that 3'phosphoinositide-dependent protein kinase-1 (PDK1), an upstream kinase necessary for full activation of Akt, was negatively regulated by miR-375 at the protein level. Moreover, miR-375 suppressed the phosphorylation of focal adhesion kinase (FAK) and paxillin, two important regulators of focal adhesion (FA) assembly and turnover, and decreased the number of FAs at cell periphery. Taken together, our results demonstrate that miR-375 inhibits HGF-elicited migration of MSCs through downregulating the expression of PDK1 and suppressing the activation of Akt, as well as influencing the tyrosine phosphorylation of FAK and paxillin and FA periphery distribution.

Efficacy and safety of everolimus plus low-dose calcineurin inhibitor vs. mycophenolate mofetil plus standard-dose calcineurin inhibitor in renal transplant recipients: A systematic review and meta-analysis
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BACKGROUND: To seek an optimized immunotherapy which can preserve renal function while maintaining low acute rejection rates, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of everolimus (EVR) plus low-dose calcineurin inhibitor (CNI) vs. mycophenolate mofetil (MMF) plus standard-dose CNI regimen after kidney transplantation (KT). MATERIALS AND METHODS: We searched for RCTs comparing the outcomes of EVR plus low-dose CNI and MMF plus standard-dose CNI regimen after KT and identified eligible RCTs according to strict inclusion and exclusion criteria. Two authors independently assessed the quality of included studies and performed a meta-analysis using RevMan5.3. RESULTS: Eleven RCTs with 850 renal transplant recipients were included. This meta-analysis showed that EVR plus low-dose CNI regimen was associated with comparable renal function (standardized mean difference (SMD) 0.16, 95% CI (-0.03, 0.35), p = 0.09) and a similar rate of acute rejection (risk ratio (RR) 1.16, 95% CI (0.96, 1.42), p = 0.13), graft loss (RR 0.89, 95% CI (0.63, 1.24), p = 0.49) and mortality (RR 1.19, 95% CI (0.69, 2.08), p = 0.53) compared to MMF plus standard-dose CNI regimen. In addition, EVR plus low-dose CNI regimen could reduce the rate of cytomegalovirus and infection, whereas a lower rate of other adverse events were noted in MMF plus standard-dose CNI regimen. CONCLUSION: EVR plus low-dose CNI regimen was similar in efficacy and safety to MMF plus standard-dose CNI regimen after KT. However, this should be confirmed by further studies.
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MiR-9-5p promotes MSC migration by activating ß-catenin signaling pathway.

Mesenchymal stem cells (MSCs) have the potential to treat various tissue damages, but the very limited number of cells that migrate to the damaged region strongly restricts their therapeutic applications. Full understanding of mechanisms regulating MSC migration will help to improve their migration ability and therapeutic effects. Increasing evidence shows that microRNAs play important roles in the regulation of MSC migration. In the present study, we reported that miR-9-5p was upregulated in hepatocyte growth factor -treated MSCs and in MSCs with high migration ability. Overexpression of miR-9-5p promoted MSC migration, whereas inhibition of endogenous miR-9-5p decreased MSC migration. To elucidate the underlying mechanism, we screened the target genes of miR-9-5p and report for the first time that CK1α and GSK3ß, two inhibitors of ß-catenin signaling pathway, were direct targets of miR-9-5p in MSCs and that overexpression of miR-9-5p upregulated ß-catenin signaling pathway. In line with these data, inhibition of ß-catenin signaling pathway by FH535 decreased the miR-9-5p-promoted migration of MSCs, while activation of ß-catenin signaling pathway by LiCl rescued the impaired migration of MSCs triggered by miR-9-5p inhibitor. Furthermore, the formation and distribution of focal adhesions as well as the reorganization of F-actin were affected by the expression of miR-9-5p. Collectively, these results demonstrate that miR-9-5p promotes MSC migration by upregulating ß-catenin signaling pathway, shedding light on the optimization of MSCs for cell replacement therapy through manipulating the expression level of miR-9-5p.

The Protease Locus of Francisella tularensis LVS Is Required for Stress Tolerance and Infection in the Mammalian Host.

Francisella tularensis is the causative agent of tularemia and a category A potential agent of bioterrorism, but the pathogenic mechanisms of F. tularensis are largely unknown. Our previous transposon mutagenesis screen identified 95 lung infectivity-associated F. tularensis genes, including those encoding the Lon and ClpP proteases. The present study validates the importance of Lon and ClpP in intramacrophage growth and infection of the mammalian host by using unmarked deletion mutants of the F. tularensis live vaccine strain (LVS). Further experiments revealed that lon and clpP are also required for F. tularensis tolerance to stressful conditions. A quantitative proteomic comparison between heat-stressed LVS and the isogenic Lon-deficient mutant identified 29 putative Lon substrate proteins. The follow-up protein degradation experiments identified five substrates of the F. tularensis Lon protease (FTL578, FTL663, FTL1217, FTL1228, and FTL1957). FTL578 (ornithine cyclodeaminase), FTL663 (heat shock protein), and FTL1228 (iron-sulfur activator complex subunit SufD) have been previously described as virulence-associated factors in F. tularensis Identification of these Lon substrates has thus provided important clues for further understanding of the F. tularensis stress response and pathogenesis. The high-throughput approach developed in this study can be used for systematic identification of the Lon substrates in other prokaryotic and eukaryotic organisms.

MiR-221 and miR-26b Regulate Chemotactic Migration of MSCs Toward HGF Through Activation of Akt and FAK.

The chemotactic migration of mesenchymal stem cells (MSCs) is fundamental for their use in cell-based therapies, but little is known about the molecular mechanisms that regulate their directed migration. MicroRNAs (miRNAs) participate in the regulation of a large variety of cellular processes. However, their roles in regulating the responses of MSCs to hepatocyte growth factor (HGF) remain elusive. Here, we found that microRNA-221 (miR-221) and microRNA-26b (miR-26b) were upregulated in MSCs subjected to HGF. Overexpression of miR-221 or miR-26b enhanced MSC migration through activation of PI3K/Akt signaling. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) was identified as a potential target of miR-221 and miR-26b; overexpression of miR-221 or miR-26b decreased PTEN expression at both mRNA and protein levels. Overexpression of miR-221 or miR-26b in MSCs increased the phosphorylation of focal adhesion kinase (FAK), a downstream effector of PTEN, which regulates cell migration through assembly and distribution of focal adhesions (FAs), and more dot-like FAs were localized at the periphery of these cells. Altering miR-221 or miR-26b expression influenced the directed migration of MSCs toward HGF. Inhibition of miR-221 or miR-26b suppressed the phosphorylation of Akt and FAK and upregulated PTEN expression, which was partly restored by HGF treatment. Collectively, these results demonstrate that miR-221 and miR-26b participate in regulating the chemotactic response of MSCs toward HGF.

Wear behavior of human enamel against lithium disilicate glass ceramic and type III gold.

STATEMENT OF PROBLEM: The wear behavior of human enamel that opposes different prosthetic materials is still not clear. PURPOSE: The purpose of this in vitro study was to investigate and compare the friction and wear behavior of human tooth enamel that opposes 2 indirect restorative materials: lithium disilicate glass ceramic and Type III gold. MATERIAL AND METHODS: Friction-wear tests on human enamel (n=5) that opposes lithium disilicate glass ceramic (n=5) and Type III gold (n=5) were conducted in a ball-on-flat configuration with a reciprocating wear testing apparatus. The wear pairs were subjected to a normal load of 9.8 N, a reciprocating amplitude of approximately 200 µm, and a reciprocating frequency of approximately 1.6 Hz for up to 1100 cycles per test under distilled water lubrication. The frictional force of each cycle was recorded, and the corresponding friction coefficient for different wear pairs was calculated. After wear testing, the wear scars on the enamel specimens were examined under a scanning electron microscope. RESULTS: Type III gold had a significantly lower steady-state friction coefficient (P=.009) and caused less wear damage on enamel than lithium disilicate glass ceramic. Enamel that opposed lithium disilicate glass ceramic exhibited cracks, plow furrows, and surface loss, which indicated abrasive wear as the prominent wear mechanism. In comparison, the enamel wear scar that opposed Type III gold had small patches of gold smear adhered to the surface, which indicated a predominantly adhesive wear mechanism. CONCLUSIONS: A lower friction coefficient and better wear resistance were observed when human enamel was opposed by Type III gold than by lithium disilicate glass ceramic in vitro.

Image characteristics and main types of abnormal branching of fetal pulmonary artery in prenatal echocardiography - a retrospective study.

OBJECTIVES: To explore the image characteristics and main types of abnormal branching of fetal pulmonary artery in prenatal echocardiography. MATERIAL AND METHODS: A retrospective analysis of 41 cases diagnosed with abnormal branching of fetal pulmonary artery by prenatal echocardiography was made. The image characteristics of the abnormalities, their combination with intra- or extra-cardiac malformations and chromosomal anomalies were analyzed. RESULTS: The results of prenatal echocardiography showed that, among the 41 cases, 1) 4 cases were with anomalous origin of single pulmonary artery, 8 cases with pulmonary artery agenesis, 9 cases with pulmonary artery sling; 20 cases with crossed pulmonary arteries. 2) 11 cases were complicated with intracardiac malformations and 10 with extracardiac malformations. 3) Only 7 case underwent chromosomal examination and 1 tested abnormal. 4) Pregnancy outcomes: 25 fetuses were born and their abnormalities confirmed by echocardiography (MRI or surgery) to be consistent with prenatal ultrasound diagnosis; 16 cases had their pregnancy terminated due to their combination with other severe malformations, which were confirmed by pathological anatomy after induced abortion. CONCLUSIONS: Prenatal echocardiography can provide detailed images for the diagnosis of abnormal branching of fetal pulmonary artery, which can be complicated by intra- and extracardiac malformations and chromosomal anomalies and should be alerted.

ALYREF-JunD-SLC7A5 axis promotes pancreatic ductal adenocarcinoma progression through epitranscriptome-metabolism reprogramming and immune evasion.

Pancreatic ductal adenocarcinoma (PDAC) is a kind of tumor lacking nutrients due to its poor vascularity and desmoplasia. Recent studies have shown that cancer cells might achieve growth advantage through epitranscriptome reprogramming. However, the role of m5C in PDAC was not fully understood. We found that Aly/REF export factor (ALYREF), a reader of m5C modification, was overexpressed in PDAC, and associated with bad prognosis. In addition, the ALYREF expression was negatively related to CD8+ T cells infiltration in clinical samples. ALYREF knockdown decreased tumor growth in vivo partly dependent of immunity. ALYREF silencing decreased SLC7A5 expression and subsequently inactivated mTORC1 pathway, resulting in decreased tumor proliferation. Mechanically, ALYREF specifically recognized m5C sites in JunD mRNA, maintained the stabilization of JunD mRNA and subsequently upregulated transcription of SLC7A5. Since SLC7A5 was a key transporter of large neutral amino acids (LNAAs), overexpression of SLC7A5 on tumor cells depleted amino acid in microenvironment and restricted CD8+ T cells function. Moreover, ALYREF-JunD-SLC7A5 axis was overexpressed and negatively related with survival through TMA assays. In conclusion, this research revealed the relationship between m5C modification, amino acid transportation and immune microenvironment. ALYREF might be a novel target for PDAC metabolic vulnerability and immune surveillance.