Parathyroid hormone receptor-1 signaling aggravates hepatic fibrosis through upregulating cAMP response element-binding protein-like 2.

BACKGROUND AND AIMS: Parathyroid hormone receptor-1 (PTH1R) is a class B G protein-coupled receptor central to skeletal development, bone turnover, and calcium homeostasis. However, the role of PTH1R signaling in liver fibrosis is largely unknown. Here, the role of PTH1R signaling in the activation of HSCs and hepatic fibrosis was examined. APPROACH AND RESULTS: PTH1R was highly expressed in activated HSCs and fibrotic liver by using human liver specimens or carbon tetrachloride (CCl 4 )-treated or methionine and choline-deficient diet (MCD)-fed C57/BL6 mice. The mRNA level of hepatic PTH1R was positively correlated to α-smooth muscle actin in patients with liver cirrhosis. Mice with HSCs-specific PTH1R deletion were protected from CCl 4 , MCD, or western diet, plus low-dose CCl 4 -induced liver fibrosis. Conversely, parathyroid hormone (PTH) aggravated liver fibrosis in CCl 4 -treated mice. Mouse primary HSCs and LX2 cell lines were used for in vitro experiments. Molecular analyses by luciferase reporter assays and chromatin immunoprecipitation assays in combination with mRNA sequencing in HSCs revealed that cAMP response element-binding protein-like 2 (Crebl2), a novel regulator in HSCs treated by PTH that interacted with mothers against decapentaplegic homolog 3 (SMAD3) and increased the transcription of TGFß in activating HSCs and collagen deposition. In agreement, HSCs-specific Crebl2 deletion ameliorated PTH-induced liver fibrosis in CCl 4 -treated mice. CONCLUSIONS: In both mouse and human models, we found that PTH1R was highly expressed in activated HSCs and fibrotic liver. PTH1R signaling regulated collagen production in the HSCs through Crebl2/SMAD3/TGFß regulatory circuits. Blockade of PTH1R signaling in HSCs might help mitigate the development of liver fibrosis.

Inhibitory Effect of Fingolimod on Head and Neck Squamous Cell Carcinoma and Its Mechanism: Gene Set Enrichment Analysis.

This study aimed to clarify the therapeutic effect of Fingolimod on head and neck squamous cell carcinoma (HNSC) and initially explore its mechanism through data mining, clinical sample analysis and basic experiments. The normalized Enrichment Score (NES) of Fingolimod in tumor tissues was obtained by SwissTargetPrediction and The Cancer Genome Atlas (TCGA) database. IC50 (50% inhibitory concentration) of Fingolimod for HNSC was verified based on the Genomics of Drug Sensitivity in Cancer (GDSC) database. SCC9 cells were cultured in vitro for the application of Fingolimod. Cell proliferation was determined by the Cell Counting Kit-8 (CCK-8). The expression levels of genes were determined by reverse transcription-polymerase chain reaction (RT-PCR). The molecular regulatory mechanism of Fingolimod acting on HNSC was analyzed with WebGestalt. Cyclin expression was determined by Western blot assay. The key targeted genes for Fingolimod against HNSC were screened with the TCGA database and verified in clinical samples. Gene Set Enrichment Analysis (GSEA) showed the highest NES score in HNSC (NES=1.53, P<0.05). GDSC showed the lowest IC50 in Fingolimod SSC9 cells. IC50 calculated by the cell activity detected by CCK8 was 4.34 µmol/L, and RT-PCR showed significantly suppressed expression of proliferation-related gene Ki-67 after adding Fingolimod (P<0.05). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the targeted genes for Fingolimod were mainly enriched in cell cycle-related pathways. Western blot showed significantly decreased cyclin expression in SSC9 cells after the treatment with Fingolimod (P<0.05). TCGA analysis revealed that PLK1 is a key targeted gene for Fingolimod in the treatment of HNSC. RT-PCR showed the significantly increased activity of SCC9 after over-expressing PLK1, and the increased proliferation and anti-apoptosis abilities (P<0.05), as well as the significantly inhibited expression of Ki-67 and Bcl-2 after adding Fingolimod. Fingolimod can promote the arrest in G0/G1 of SCC9 cells, and PLK1 is a key targeted gene for the treatment of HNSC. Fingolimod can inhibit cell proliferation caused by PLK1 over-expression.

Constitutive secretory expression and characterization of nitrilase from Alcaligenes faecalis in Pichia pastoris for production of R-mandelic acid.

Nitrilases can directly hydrolyze nitrile compounds into carboxylic acids and ammonium. To solve the current problems of bioconversions using nitrilases, including the difficult separation of products from the resting cells used as the catalyst and high costs of chemical inducers, a nitrilase from Alcaligenes faecalis was heterologously expressed in Pichia pastoris X33. The stable nitrilase-expressing strain No.39-6-4 was obtained after three rounds of screening based on a combined detection method including dot-blot, SDS-PAGE, and western blot analyses, which confirmed the presence of recombinant nitrilase with a molecular mass of about 50 kDa. The temperature and pH optima of the nitrilase were 45°C and pH 7.5, respectively. Cu2+ , Zn2+ , and Tween 80 strongly inhibited the enzyme activity, but the optical purity of the product R-mandelic acid (R-MA) was stable, with practically 100% enantiomeric excess (ee). The nitrilase-producing P. pastoris strain developed in this study provides a basis for further research on the enzyme.

Influence of the Hollowness and Size Distribution on the Magnetic Properties of Fe3O4 Nanospheres.

In this study, Fe3O4 nanospheres with different levels of hollowness were successfully prepared by the solvent thermal method. The synthesized Fe3O4 nanospheres were characterized by transmission electron microscopy, X-ray diffraction, and vibrating sample magnetometry, and Image-Pro software was used to analyze the hollowness of the Fe3O4 nanospheres for the first time. It was found that excess reactants could lead to the disappearance of the hollow structure of the Fe3O4 nanospheres, and the reason for this phenomenon was discussed as due to entropy increase theory. Furthermore, the influence of the hollowness and size distribution on the magnetic properties of the Fe3O4 nanospheres was evaluated. The magnetic properties of a Fe3O4 nanosphere with a hollowness of 10.48% showed a relatively high saturation magnetization of 103 emu/g and a rather low coercivity (54 Oe). The as-prepared Fe3O4 nanospheres are expected to be useful in a wide range of fields such as drug-delivery and energy applications.

Oscillation of Branching Ratios Between the D(2s)+D(1s) and the D(2p)+D(1s) Channels in Direct Photodissociation of D_{2}.

The direct photodissociation of D_{2} at excitation energies above 14.76 eV occurs via two channels, D(2s)+D(1s) and D(2p)+D(1s). The branching ratios between the two have been measured from the dissociation threshold to 3200 cm^{-1} above it, and it is found that they show cosine oscillations as a function of the fragment wave vector magnitudes. The oscillation is due to an interference effect and can be simulated using the phase difference between the wave functions of the two channels, analogous to Young's double-slit experiment. By fitting the measured branching ratios, we have determined the depths and widths of the effective spherical potential wells related to the two channels, which are in agreement with the effective depths and widths of the ab initio interaction potentials. The results of this Letter illustrate the importance of the relative phase between the fragments in controlling the branching ratios of the photodissociation channels.

Electronic and Tunneling Predissociations in the 2pπC1Πu±(υ = 19) and 3pπD1Πu±(υ = 4, 5) States of D2 Studied by a Combination of XUV Laser and Velocity Map Imaging.

The predissociation mechanism of D2 near the threshold for the production of the D(2s, 2p) fragments has been studied by measuring the fragment yield spectra, fragment velocity map images, and fragment branching ratios D(2s)/(D(2s) + D(2p)) using a combination of XUV laser and velocity map imaging. The predissociation dynamics of the 2pπC1Πu±(υ = 19) and 3pπD1Πu±(υ = 4,5) states were studied. The 2pπC1Πu±(υ = 19) state is a bound state due to a shallow barrier. For the R(0) transition to the 2pπC1Πu+(υ = 19) state, the experimental results suggest that the predissociation occurs via three channels with decreasing importance: l-uncoupling with the 2pσB1Σu+ state, tunneling, and l-uncoupling with the 3pσB'1Σu+ state. For the R(1) transition to the 2pπC1Πu+(υ = 19) state, the first channel plays the dominant role. For the Q(1) transition to the 2pπC1Πu-(υ = 19) state, the predissociation occurs via tunneling as required by symmetry. For the predissociation of the 3pπD1Πu+(υ = 4,5) states, the experimental data confirm the earlier results indicating that the main perturbing state is 3pσB'1Σu+. The Beutler-Fano profiles and the associated spectroscopic parameters for the various predissociations have also been obtained. The measured Fano-parameters q for the P- and R-branches of the 3pπD1Πu+ state are found to have opposite signs, and their relationships are in agreement with a formula derived from the Fano equation. Rotationally resolved Beutler-Fano profiles were measured for the P(2) and P(3) lines.

Predissociation dynamics in the 3pπD(1)Πu (±)υ=3 and 4pσB(″) (1)Σu (+)υ=1 states of H2 revealed by product branching ratios and fragment angular distributions.

The predissociation dynamics of H2+XUV→H2 (*)→H(1s)+H(2s,2p) has been studied by measuring the fragment branching ratios between the H(2s) and H(2p) states and the fragment angular distributions using the XUV (extreme ultraviolet) laser pump and UV(ultraviolet) laser probe method. The fragment angular distributions for the predissociation of the 3pπD(1)Πu (+)υ=3 state show parallel transitions, demonstrating that the main components of the dissociating state have (1)Σu (+) symmetry. The measured fragment branching ratios, H(2s)/(H(2s) + H(2p)), for the transitions R(0), R(1), and P(2) in 3pπD(1)Πu (+)υ=3←X(1)Σg (+)υ(″)=0 are in good agreement with one of the previous theoretical predictions. The predissociations of the 3pπD(1)Πu (-)(υ=3) state arising from the Q(1), Q(2), and Q(3) lines have also been observed. The angular distributions and the state distributions of the excited fragments (all found from the H(2p) state) illustrate that the dissociating states for the Q lines have the expected Πu (-) symmetry. The predissociation dynamics of the transition 4pσB(″1)Σu (+)υ=1←X(1)Σg (+)υ(″)=0 was also studied. Their fragment angular distributions show the expected parallel transitions, and most of the fragments are in the H(2s) states. The Beutler-Fano profiles and the associated spectroscopic parameters for the predissociations have also been obtained by measuring the fragment yield of H(2s, 2p) as a function of excitation photon energies.

Zerumbone protects INS-1 rat pancreatic beta cells from high glucose-induced apoptosis through generation of reactive oxygen species.

The aim of this study is to explore the effect of zerumbone, a natural sesquiterpene isolated from Zingiber zerumbet Smith, on high glucose-induced cytotoxicity in pancreatic ß cells. INS-1 rat pancreatic ß cells were treated with 33 mM glucose with or without different concentrations of zerumbone and cell viability and apoptosis were assessed. The involvement of reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) signaling in the action of zerumbone was examined. Notably, zerumbone significantly (P < 0.05) prevented the reduction of cell viability induced by high glucose. Such protection was in a concentration-dependent fashion up to 60 µM of zerumbone. Annexin-V/propidium iodide staining analysis showed that zerumbone impaired the apoptotic response of high glucose-treated INS-1 cells, which was coupled with a significant decline in cleaved caspase-3 and caspase-9. Pretreatment with the ROS inhibitor N-acetylcysteine abrogated the phosphorylation of p38 and JNK induced by high glucose. Zerumbone significantly (P < 0.05) decreased the generation of ROS and the phosphorylation of p38 and JNK MAPKs in high glucose-treated INS-1 cells. Pharmacological activation of p38 and JNK with anisomycin reversed the anti-apoptotic effect of zerumbone. Additionally, simultaneous inhibition of p38 and JNK significantly (P < 0.05) reduced the apoptotic response in high glucose-treated INS-1 cells. In conclusion, zerumbone confers protection against high glucose-induced apoptosis of INS-1 pancreatic ß cells, largely through interfering with ROS production and p38 and JNK activation. Zerumbone may have potential therapeutic effects against hyperglycemia-induced ß cell damage in diabetes.

Photodissociation dynamics of superexcited O2: dissociation channels O(5S) vs. O(³S).

The photodissociation dynamics of O2, O2 + hυ → O((3)P) + O(2p(3)((4)S)3s, (3)S/(5)S), has been studied by combining the XUV laser pump / UV laser probe and velocity map imaging methods in the photon energy range 14.64-15.20 eV. The fragment yield spectra of O((3)S) and O((5)S) and their velocity map images have been recorded using the state-selective (1+1) REMPI method to detect the fragments. The fragment yield spectra show resolved fine structure that arises from the predissociated Rydberg states I, I' and I″ ((3)Π(Ω = 0,1,2)). The branching ratios between the two decay channels have been measured by one-photon ionization of the fragments O((3)S) and O((5)S) simultaneously. It is surprising to find that the dissociation cross sections for the production of O((5)S) are larger than, or comparable to, those of O((3)S) for the I and I' states, while the cross sections for the production of O((5)S) are smaller than those of O((3)S) for the I″ state. All fragments O((5)S) arise from perpendicular transitions, which provides direct experimental evidence about the symmetry assignments of the states I, I' and I″ excited in this energy region. Although most of the fragments O((3)S) arise from perpendicular transitions, some of them are from parallel transitions. Based on the calculated ab initio potential energy curves, we propose that the neutral dissociation into O((3)P) + O((3)S) occurs mainly via the interaction of the Rydberg states I, I', and I″ with the vibrational continuum of the diabatic 8(3)Π(u) state (1π(u)⁻¹(a4Π(u))3sσ(g), ³Π(u)), while the neutral dissociation into O((3)P) + O((5)S) occurs mainly via the interaction of Rydberg states I, I', and I″ with the diabatic 7(3)Π(u) (1π(g)⁻¹(X²Π(g))3pσ(u), ³Π(u)).

Development of a finite element full spine model with active muscles for quantitatively analyzing sarcopenia effects on lumbar load.

BACKGROUND AND OBJECTIVE: The musculoskeletal imbalance caused by disease is one of the most critical factors leading to spinal injuries, like sarcopenia. However, the effects of musculoskeletal imbalances on the spine are difficult to quantitatively investigate. Thus, a complete finite element spinal model was established to analyze the effects of musculoskeletal imbalance, especially concerning sarcopenia. METHODS: A finite element spinal model with active muscles surrounding the vertebrae was established and validated from anatomic verification to the whole spine model in dynamic loading at multiple levels. It was then coupled with the previously developed neuromuscular model to quantitatively analyze the effects of erector spinae (ES) and multifidus (MF) sarcopenia on spinal tissues. The severity of the sarcopenia was classified into three levels by changing the physiological cross-sectional area (PCSA) of ES and MF, which were mild (60% PCSA of ES and MF), moderate (48% PCSA of ES and MF), and severe (36% PCSA of ES and MF). RESULTS: The stress and strain levels of most lumbar tissues in the sarcopenia models were more significant than those of the normal model during spinal extension movement. The sarcopenia caused load concentration in several specific regions. The stress level of the L4-L5 intervertebral disc and L1 vertebra significantly increased with the severity of sarcopenia and showed relatively larger values than other segments. From the normal model to a severe sarcopenia model, the stress value of the L4-L5 intervertebral disc and L1 vertebra increased by 128% and 113%, respectively. The strain level of L5-S1 also inclined significantly with the severity of sarcopenia, and the relatively larger capsule strain values occurred at lower back segments from L3 to S1. CONCLUSIONS: In summary, the validated spinal coupling model can be used for spinal injury risk analysis caused by musculoskeletal imbalance. The results suggested that sarcopenia can primarily lead to high injury risk of the L4-L5 intervertebral disc, L1 vertebrae, and L3-S1 joint capsule regarding significant stress or strain variance.

A neuromuscular human body model for lumbar injury risk analysis in a vibration loading environment.

BACKGROUND AND OBJECTIVE: Long-term intensive exposure to whole-body vibration substantially increases the risk of low back pain and degenerative diseases in special occupational groups, like motor vehicle drivers, military vehicle occupants, aircraft pilots, etc. This study aims to establish and validate a neuromuscular human body model focusing on improvement of the detailed description of anatomic structures and neural reflex control, for lumbar injury analysis in vibration loading environments. METHODS: A whole-body musculoskeletal in Opensim codes was first improved by including a detailed anatomic description of spinal ligaments, non-linear intervertebral disc, and lumbar facet joints, and coupling a proprioceptive feedback closed-loop control strategy with GTOs and muscle spindles modeling in Python codes. Then, the established neuromuscular model was multi-levelly validated from sub-segments to the whole model, from regular movements to dynamic responses to vibration loadings. Finally, the neuromuscular model was combined with a dynamic model of an armored vehicle to analyze occupant lumbar injury risk in vibration loadings due to different road conditions and traveling velocities. RESULT: Based on a series of biomechanical indexes, including lumbar joint rotation angles, the lumbar intervertebral pressures, the displacement of the lumbar segments, and the lumbar muscle activities, the validation results show that the present neuromuscular model is available and feasible in predicting lumbar biomechanical responses in normal daily movement and vibration loading environments. Furthermore, the combined analysis with the armored vehicle model predicted similar lumbar injury risk to the experimental or epidemiologic studies. The preliminary analysis results also showed that road types and travelling velocities have substantial combined effects on lumbar muscle activities, and indicated that intervertebral joint pressure and muscle activity indexes can need to be jointly considered for lumbar injury risk evaluation. CONCLUSION: In conclusion, the established neuromuscular model is an effective tool to evaluate vibration loading effects on injury risk of the human body and assist vehicle design vibration comfort by directly concerning the human body injury itself.

Identification of Hub Genes Associated With Non-alcoholic Steatohepatitis Using Integrated Bioinformatics Analysis.

Background and aims: As a major cause of liver disease worldwide, non-alcoholic fatty liver disease (NAFLD) comprises non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Due to the high prevalence and poor prognosis of NASH, it is critical to understand its mechanisms. However, the etiology and mechanisms remain largely unknown. In addition, the gold standard for the diagnosis of NASH is liver biopsy, which is an invasive procedure. Therefore, there is a pressing need to develop noninvasive tests for NASH diagnosis. The goal of the study is to discover key genes involved in NASH development and investigate their value as noninvasive biomarkers. Methods: The Gene Expression Omnibus (GEO) database was used to obtain two datasets encompassing NASH patients and healthy controls. We used weighted gene co-expression network analysis (WGCNA) and differential expression analysis in order to investigate the association between gene sets and clinical features, as well as to discover co-expression modules. A protein-protein interaction (PPI) network was created to extract hub genes. The results were validated using another publicly available dataset and mice treated with a high-fat diet (HFD) and carbon tetrachloride (CCl4). Results: A total of 24 differentially co-expressed genes were selected by WGCNA and differential expression analysis. KEGG analysis indicated most of them were enriched in the focal adhesion pathway. GO analysis showed these genes were mainly enriched in circadian rhythm, aging, angiogenesis and response to drug (biological process), endoplasmic reticulum lumen (cellular component), and protein binding (molecular function). As a result, eight genes (JUN, SERPINE1, GINS2, TYMS, HMMR, IGFBP2, BIRC3, TNFRSF12A) were identified as hub genes. Finally, three genes were found significantly changed in both the validation dataset and the mouse model. Conclusion: Our research discovered genes that have the potential to mediate the process of NASH and might be useful diagnostic biomarkers for the disorder.

The Role of Al4C3 Morphology in Tensile Properties of Carbon Fiber Reinforced 2024 Aluminum Alloy during Thermal Exposure.

The aluminum alloy drill pipe suffers long-term high-temperature conditions during ultra-deep well drilling. In this paper, the samples were prepared by vacuum hot pressing, followed by hot extrusion and T6 heat treatment. The mechanical properties of short carbon fiber reinforced 2024 aluminum alloy composites (SCFs/2024 Al) and the microstructure evolution at the interface region thermal exposure at 160 °C for 500 h are discussed. The experimental results showed that the effect of short carbon fiber on 2024 aluminum alloy remained steady throughout the whole process of the heat exposure experiment. The distribution and volume of interface products (Al4C3) changed with the prolonging of heat exposure time, and connected after coarsening. The evolution of the morphology of Al4C3 relieved the stress of the interface between carbon fiber and aluminum alloy matrix and enhanced the mechanical properties of the composite.

Hollow silica-coated porous carbon with embedded iron oxide particles for effective methylene blue degradation.

A novel catalyst, consisting of hollow silica-coated porous carbon with embedded iron oxide particles (FeO x @C/SiO2), was synthesized by the extended Stöber method. Iron ions were incorporated in a resorcinol-formaldehyde resin in the presence of citric acid to form a template, which was then coated with a silica layer. The iron oxide-embedded porous carbon and hollow silica were simultaneously formed during calcination under N2 atmosphere. Through this process, silica endowed the iron oxide with low crystallinity and small size, resulting in a higher catalytic activity in the heterogeneous Fenton system for the decolorization of a methylene blue (MB) solution within 25 min. Moreover, the sample maintained 78.71% of its catalytic activity after three cycles.

An LSPR-based "push-pull" synergetic effect for the enhanced photocatalytic performance of a gold nanorod@cuprous oxide-gold nanoparticle ternary composite.

As promising photocatalysts, nano-sized Cu2O particles suffer from severe charge recombination and insufficient light absorption, resulting in their unsatisfactory photocatalytic performance. Herein, we have designed a core-shell structured Au nanorod@octahedron Cu2O with preferentially edge-loaded Au nanoparticles (Au(R)@Cu2O-Au(P)) for an efficient photocatalytic degradation reaction. A "push-pull" synergetic effect of Au(R) and Au(P) was found to improve the transfer and separation of charge carriers from the bulk to the surface of Cu2O. Furthermore, the light beyond Cu2O particles' absorption range can penetrate the shell (Cu2O) and for being utilized by the Au(R) core via its localized surface plasmon resonance effect (LSPR) to inject hot electrons into the conduction band of Cu2O for photocatalytic reactions. Moreover, the investigation of the size effect of Au(R)@Cu2O-Au(P) reveals that both the short charge transfer distance and the more efficient charge transfer have contributed to its enhanced photocatalytic activity.

Effects of simvastatin on iNOS and caspase­3 levels and oxidative stress following smoke inhalation injury.

The overexpression of inducible nitric oxide synthase (iNOS) induces cell apoptosis through various signal transduction pathways and aggravates lung injury. Caspase­3 is an important protein in the apoptotic pathway and its activation can exacerbate apoptosis. Simvastatin, a hydroxymethyl glutaryl­A reductase inhibitor, protects against smoke inhalation injury by inhibiting the synthesis and release of inflammatory factors and decreasing cell apoptosis. Following the establishment of an animal model of smoke inhalation injury, lung tissue and serum were collected at different time points and the protein and mRNA expression of iNOS and caspase­3 in lung tissue by immunochemistry, western blot and reverse transcription­quantitative polymerase chain reaction, the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in lung tissue and serum were analyzed using thiobarbituric acid method and the WST­1 method. The results were statistically analyzed. The lung tissues of the rats in the saline group and the low­, middle­ and high­dose groups exhibited clear edema and hemorrhage, and had significantly higher pathological scores at the various time points compared with the rats in the control group (P<0.05). Furthermore, lung tissue and serum samples obtained from these four groups had significantly higher mRNA and protein expression levels of iNOS and caspase­3 (P<0.05), significantly lower SOD activity and higher MDA content (P<0.05). Compared with the saline group, the low­, middle­ and high­dose groups had significantly lower pathological scores (P<0.05), significantly lower mRNA and protein expression levels of iNOS, caspase­3 and MDA content in lung tissues (P<0.05) and significantly higher SOD activity in lung tissues and serum. The middle­ and high­dose groups had significantly lower pathological scores (P<0.05), significantly decreased iNOS and caspase­3 mRNA and protein expression in lung tissues, significantly higher SOD activity in lung tissues and serum and a significantly lower MDA content (P<0.05) compared with the low­dose group. With the exception of SOD activity in lung tissues at 24 and 72 h and MDA content in serum at 48 h, no significant differences were observed between the middle­ and high­dose groups. The present study demonstrated that there was an association between the therapeutic effect and dosage of simvastatin within a definitive range. In rats with smoke inhalation injury, simvastatin inhibited iNOS and caspase­3 expression in lung tissues and mitigated oxidative stress, thereby exerting a protective effect. In addition, the effect and dose were associated within a definitive range.

[Corrigendum] Effects of simvastatin on iNOS and caspase­3 levels and oxidative stress following smoke inhalation injury.

After the publication of the above paper, the authors have noticed that the affiliations were presented incorrectly; essentially, Drs Rong­qiang Yang, Peng­fei Guo, Qing­nan Meng, Ya Gao, Imran Khan, Xiao­bo Wang and Zheng­jun Cui are based at the Department of Burn and Repair Reconstruction Surgery, The First Affiliated Hospital of Zhengzhou University, whereas Drs Zhao Ma and Cheng Chang are located at The School of Basic Medical Science of Zhengzhou University. Therefore, the affiliations for this paper should have appeared as follows: Rong­Qiang Yang1, Peng­Fei Guo1, Zhao Ma2, Cheng Chang2, Qing­Nan Meng1, Ya Gao1, Imran Khan1, Xiao­Bo Wang1 and Zheng­Jun Cui1. 1Department of Burn and Repair Reconstruction Surgery, The First Affiliated Hospital of Zhengzhou University; 2The School of Basic Medical Science of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China. The authors regret that these errors with the author affiliations were not noticed prior to the publication of their paper, and apologize for any inconvenience caused. [the original article was published in Molecular Medicine Reports 22: 3405-3417, 2020; DOI: 10.3892/mmr.2020.11413].

MicroRNA Let-7f-1-3p attenuates smoke-induced apoptosis in bronchial and alveolar epithelial cells in vitro by targeting FOXO1.

Bronchial and alveolar epithelial cell apoptosis is a vital step in smoke-induced lung injury. We investigated whether and how microRNA (miRNA) Let-7f-1-3p would regulate smoke-induced apoptosis in bronchial and alveolar epithelial cells. Human small airway epithelial cells (HSAEC) and human pulmonary alveolar epithelial cells (HPAEpiC) were cultured using an air-liquid interface cell culture system. These cells were treated with Let-7f-1-3p agomir or antagomir for 24 h before smoke exposure or sham operation, after which the cells were rinsed and cultured for 24 h before cell viability, apoptosis, cytolysis, Caspase-9/8/3 activity assays, quantitative real-time polymerase chain reaction and Western blot. Bioinformatic and luciferase reporter assays were performed to predict or verify the target gene of Let-7f-1-3p. We found that smoke exposure significantly reduced Let-7f-1-3p expression level in HSAEC and HPAEpiC. Let-7f-1-3p agomir significantly attenuated cell apoptosis, cytolysis and Caspase-3, -8 and -9 activation while rescuing cell viability of smoke-exposed HSAEC and HPAEpiC. Let-7f-1-3p agomir downregulated tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), Fas ligand (FasL) and B-cell lymphoma-2 (Bcl2)-like protein 11 (Bim) protein level in HSAEC and HPAEpiC. Forkhead box-O1 (FOXO1) was verified as a putative regulatory target of Let-7f-1-3p. Smoke exposure increased FOXO1 mRNA and protein level in HSAEC and HPAEpiC, which was attenuated by Let-7f-1-3p agomir treatment. FOXO1 inhibition by small-molecule drug partially attenuated the increase in smoke-exposed HSAEC and HPAEpiC apoptosis, cytolysis and the decrease in cell viability caused by Let-7f-1-3p antagomir treatment. We concluded Let-7f-1-3p attenuated smoke-induced apoptosis in HSAEC and HPAEpiC by targeting FOXO1.

miR-506 contributes to malignancy of cutaneous squamous cell carcinoma via targeting of P65 and LAMC1.

Previous research has shown that microRNA 506 (miR-506) functions as an essential modulator in the development of many biological reactions, including multiple cancers. However, its involvement in cutaneous squamous cell carcinoma (CSCC) has been rarely reported. In the present work, we investigated the molecular mechanism and function of miR-506 in the regulation of CSCC cell viability and metastasis (migration and invasion). We observed that miR-506 expression was upregulated in both CSCC tissues and cell lines, and that decreased miR-506 expression led to repressed tumorigenesis in CSCC cells. Furthermore, flow cytometry revealed that the depletion of miR-506 resulted in decreased proliferation and increased apoptotic levels in CSCC cells. Meanwhile, it was found that miR-506 decreased CSCC cell migration and invasion in vitro. The dual-luciferase reporter assay also revealed that miR-506 targets the 3'-UTRs of p65 and Laminin C1 (LAMC1) for silencing. Silencing of p65 expression counteracted the pro-apoptotic influence of miR-506 depletion in CSCC cells, while inhibition of LAMC1 expression restored the migration and invasion properties of the CSCC cells. Therefore, the results provide evidence for the need to probe the biological and molecular mechanisms behind the development and progression of CSCC and may lead to novel treatment CSCC strategies.