Urinary malate dehydrogenase 2 is a new biomarker for early detection of non-small-cell lung cancer.

Reliable and noninvasive biomarkers for the early diagnosis of non-small-cell lung cancer (NSCLC) are an unmet need. This study aimed to screen and validate potential urinary biomarkers for the early diagnosis of NSCLC. Using protein mass spectrometry, urinary MDH2 was found to be abundant both in patients with lung cancer and lung cancer model mice compared with controls. Urine samples obtained as retrospective and prospective cohorts including 1091 NSCLC patients and 736 healthy controls were measured using ELISA. Patients with stage I NSCLC had higher urinary MDH2 compared with healthy controls. The area under the receiver-operating characteristic curve (AUC) for the urinary MDH2 was 0.7679 and 0.7234 in retrospective and prospective cohorts to distinguish stage I cases from controls. Urinary MDH2 levels correlated with gender and smoking history. MDH2 expression levels were elevated in lung cancer tissues. MDH2 knockdown using shRNA inhibited the proliferation of lung cancer cells. Our study demonstrated that urinary MDH2 concentration was higher in early-stage NSCLC patients compared with that in controls and that MDH2 could serve as a potential biomarker for early detection of NSCLC.

Evidence of recombinant strains of porcine epidemic diarrhea virus, United States, 2013.

To investigate the evolutionary process by which porcine epidemic diarrhea virus (PEDV) in the United States hypothetically descended from strains in China, we analyzed PEDV-positive samples collected in China during January 2012-July 2013. Recombination in 2 strain sublineages was likely associated with identification of PEDV in the United States in 2013.

Effective model and electron correlations in trilayer nickelate superconductor La4Ni3O10.

Recently, signatures of superconductivity with critical temperature from 20 to 30 K have been reported in pressured trilayer nickelate La4Ni3O10through a pressure-induced structure transition. Here we explore the evolution of electronic structures and electronic correlations in different phases of La4Ni3O10under corresponding pressure regions, by using density functional theory (DFT) combined with dynamical mean-field theory (DMFT). Similar to bilayer superconductor La3Ni2O7, the electronic bands in superconducting La4Ni3O10are dominated by Ni-3dx2-y2and 3dz2orbits near the Fermi level, in contrast, the inner Ni-O plane in La4Ni3O10generates a doublet hole-pocket Fermi surfaces around the Brillouin-zone corner, meanwhile one branch of the Ni-3dz2bands is pushed very close above the Fermi level, which can induce an electron pocket through small electron doping. The DFT+DMFT simulations suggest that the electronic correlations only give minor modification to the Fermi surfaces, meanwhile the Ni-3dz2and 3dx2-y2states on outer Ni-O layers have considerable greater mass enhancements than on the inner layer. The sensitiveness of electronic structure under doping and unique layer dependence of correlation suggest a distinct superconducting mechanism with respect to bilayer La3Ni2O7. Based on the DFT and DFT+DMFT simulations, we eventually derive a trilayer effective tight-binding model, which can produce rather precise electronic bands and Fermi surfaces, hence can serve as an appropriate model to further study the superconducting mechanism and paring symmetry in trilayer La4Ni3O10.

[Analysis of Mechanism and Start-up Thresholds of Seasonal Algal Blooms in a Northern Eutrophic Stratified Reservoir].

Seasonal algal blooms produce a high risk for water supply safety. To explore the mechanism of seasonal algal blooms in northern eutrophic stratified reservoirs, the combination of taxonomic and functional classifications, local weighted regression (LOWESS), and Boundary line analysis (BLA) were employed to obtain the succession features and environmental thresholds of seasonal (e.g., spring and summer) algal blooms, based on the long-term and high-frequency monitoring from 2017 to 2020 in Lijiahe Reservoir. The results showed that:① the succession and response mechanisms of algal blooms were different in spring and summer. In detail, Chlorophyta, Bacillariophyta, and Dinoflagellates (e.g., low-temperature, small, high surface-to-volume genera) dominated in spring, whereas Chlorophyta, Bacillariophyta, and Cyanobacteria (e.g., high-temperature, large or colonial, low surface-to-volume genera) dominated in summer. The differences in physiological and morphological characteristics of algae were the internal cause triggering seasonal algal blooms. ② The main drivers of algal blooms were different in spring and summer. Spring blooms were controlled by water temperature (WT), mixing depth (i.e., Zmix), and light availability (i.e., Zeu/Zmix), whereas summer blooms were jointly influenced by WT, Zmix, Zeu/Zmix, and total phosphorus (TP). The differences in the changes of the major drivers were external causes triggering seasonal algal blooms. ③ The water environment thresholds starting seasonal algal blooms were different in spring and summer. The thresholds of WT, Zmix, and Zeu/Zmix in spring were>9.4℃, <10.9 m, and>0.24, respectively, whereas the thresholds of WT, Zmix, Zeu/Zmix, and TP in summer were>16.0℃, <11.6 m, >0.16, and>0.011 mg·L-1, respectively. Based on the research on the mechanism of seasonal algal blooms and related thresholds, this work will provide a reference for the control of subsequent algal blooms.

TRPP2 ion channels: The roles in various subcellular locations.

TRPP2 (PC2, PKD2 or Polycytin-2), encoded by PKD2 gene, belongs to the nonselective cation channel TRP family. Recently, the three-dimensional structure of TRPP2 was constructed. TRPP2 mainly functions in three subcellular compartments: endoplasmic reticulum, plasma membrane and primary cilia. TRPP2 can act as a calcium-activated intracellular calcium release channel on the endoplasmic reticulum. TRPP2 also interacts with other Ca2+ release channels to regulate calcium release, like IP3R and RyR2. TRPP2 acts as an ion channel regulated by epidermal growth factor through activation of downstream factors in the plasma membrane. TRPP2 binding to TRPC1 in the plasma membrane or endoplasmic reticulum is associated with mechanosensitivity. In cilium, TRPP2 was found to combine with PKD1 and TRPV4 to form a complex related to mechanosensitivity. Because TRPP2 is involved in regulating intracellular ion concentration, TRPP2 mutations often lead to autosomal dominant polycystic kidney disease, which may also be associated with cardiovascular disease. In this paper, we review the molecular structure of TRPP2, the subcellular localization of TRPP2, the related functions and mechanisms of TRPP2 at different sites, and the diseases related to TRPP2.

Plasma CXCL14 as a Candidate Biomarker for the Diagnosis of Lung Cancer.

Background: Effective biomarkers for early diagnosis of lung cancer are needed. Previous studies have indicated positive associations between abnormal circulating cytokines and the etiology of lung cancer. Methods: Blood samples were obtained from 286 patients with pretreatment lung cancer and 80 healthy volunteers. Circulating cytokine levels were detected with a Luminex assay and enzyme-linked immunosorbent assay (ELISA). Urine samples were obtained from 284 patients and 122 healthy volunteers. CXC chemokine ligand 14 (CXCL14) expression in tumors and nontumor regions of lung tissues from 133 lung cancer cases was detected by immunohistochemical (IHC) staining and immunofluorescence (IF) staining of formalin fixed paraffin-embedded (FFPE) tissues. Results: Compared with healthy volunteers, a 65.7-fold increase was observed in the level of CXCL14 in the plasma of lung cancer patients, and a 1.7-fold increase was observed in the level of CXCL14 in the urine of lung cancer patients, achieving a 0.9464 AUC (area under the curve) value and a 0.6476 AUC value for differentiating between lung cancer patients and healthy volunteers, respectively. Stromal CXCL14 expression was significantly associated with advanced pathologic stage (P<0.001), pathologic N stage (P<0.001), and recurrence and metastasis (P=0.014). Moreover, multivariate analysis suggested stromal CXCL14 expression as an independent predictor of DFS and OS. Conclusions: Our study demonstrates that CXCL14 might serve as a potential diagnostic and prognostic biomarker in patients with lung cancer. Impact: CXCL14 might serve as a potential diagnostic and prognostic biomarker in patients with lung cancer.

LncRNA H19 downregulation confers erlotinib resistance through upregulation of PKM2 and phosphorylation of AKT in EGFR-mutant lung cancers.

First-generation EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib have significant activity in NSCLC patients with activating EGFR mutations. However, EGFR-TKI resistance inevitably occurs after approximately 12 months of treatment. Acquired mechanisms of resistance, other than secondary mutations in EGFR (T790 M) which account for 50-60%, are less well understood. Here, we identified lncRNA H19 as a significantly downregulated lncRNA in vitro models and clinical specimens with acquired EGFR-TKI resistance, H19 knockdown or overexpression conferred resistance or sensitivity, respectively, both in vitro and in vivo models. H19 downregulation contributed to erlotinib resistance through interaction and upregulation of PKM2, which enhanced the phosphorylation of AKT. AKT inhibitors restored the sensitivity of erlotinib-resistant cells to erlotinib. In EGFR-mutant patients treated with EGFR-TKIs, low H19 levels were associated with a shorter progression-free survival (PFS) (P = 0.021). These findings revealed a novel mechanism of low-level H19 in the regulation of erlotinib resistance in EGFR-mutant lung cancers. Combination of AKT inhibitors and EGFR-TKIs could be a rational therapeutic approach for some subgroups of EGFR-mutant lung cancer patients.

Enhanced electronic coupling in a molecular pair of dimolybdenum units bridged by a tetrathioterephthalate dianion.

Two covalently bonded dimolybdenum units have been assembled with a tetrathioterephthalate dianion (tttp(2-)), yielding the first full S-donor dimetal molecular dyad [Mo(2)(DAniF)(3)](S(2)CC(6)H(4)CS(2))[Mo(2)(DAniF)(3)] (DAniF = N,N'-di-p-anisylformamidinate). This linear molecule has a Mo(2)...Mo(2) separation of 12 A as determined by X-ray crystallographic analysis. Large potential separations (DeltaE(1/2)) for the successive oxidations of the two dimetal centers and greatly red-shifted metal-to-ligand charge-transfer absorption have been observed as compared to the terephthalate and dithioterephthalate analogues. In addition, further electrochemical oxidations result in a pair of quasi-reversible two-electron redox waves separated by ca. 250 mV.

Expression of Ihh signaling pathway in condylar cartilage after bite-raising in adult rats.

Temporomandibular joint osteoarthritis (TMJOA) is a complex inflammatory condition with multiple factors and degenerative processes co-occurring. However, its pathogenesis remains uncertain. The purpose of the study was to observe the expression of Indian hedgehog (Ihh) signal related molecules in TMJOA induced by bite-raising and to study the effect and mechanism of Ihh signaling. Our research indicated that Ihh signaling pathway can be activated in condylar cartilage induced by bite-raising. The histological analysis showed TMJOA-like structural changes of condylar cartilage in experiment groups. Ihh, Smoothened (Smo), and Gli zinc finger transcription factors-1 (Gli-1) were activated in the experimental groups, and the expression levels increased significantly over time, whereas the sham control groups showed no fluctuation. Additionally, the expression levels of matrix metalloproteinase-13 (MMP-13) and cysteinyl aspartate specific proteinase-3 (Caspase-3) in the experiment groups increased in a time-dependent manner compared with the matched sham control groups. In conclusion, our results indicated that the Ihh signaling pathway may activate the occurrence of TMJOA by mediating the hypertrophy of chondrocytes, which may be an important regulatory mechanism and potential therapeutic target in the repair of condylar cartilage.

Effect of soft tissue thickness on the morphology of lip in orthodontic treatment / Efecto del grosor del tejido blando en la morfología del labio en el tratamiento de ortodoncia

The aim of this study was to evaluate the effect of soft tissue thickness of upper lip on lip retraction in orthodonticaltreated females and identify the ratio of maxillary incisor retraction to upper lip retraction. Pre- and post-treatment lateral cephalograms of 100 adults were examined to measure the lip thickness in upper lip and establish the classification standard. All subjects were treated with 4 first premolar extractions followed by upper central incisors retraction. Pre- and post-treatment lateral cephalograms of 19 patients were reviewed to determine the changes of the upper lip and incisor positions through landmarks displacement. An independent-samples t test and one-way analysis of variance were performed. The correlations between maxillary incisor retraction and upper lip retraction were explored by the Pearson correlation method. P-values<0.05 were considered statistically significant. The lip thickness of adult male patients was greater than that of adult female patients. The average ratio of maxillary incisor retraction to upper lip repositioning was 1.6:1,1.9:1 and 2.2:1 in the thin lips group, normal lips group and thick lips group, respectively. Gender differences exist in the thickness of upper lip. Horizontal changes of the maxillary incisor showed a significant correlation to horizontal changes of the upper lip (P<0.001).There were negative correlations between the thickness of upper lip and the ratio between change in maxillary incisor protrusion and change in upper lip protrusion.

El objetivo de este estudio fue evaluar el efecto del grosor de los tejidos blandos del labio superior, sobre la retracción del labio en mujeres tratadas con ortodoncia e identificar la proporción de retracción del diente incisivo maxilar con respecto a la retracción del labio superior. Se examinaron cefalogramas laterales, previos y posteriores al tratamiento de 100 adultos, para medir el grosor del labio superior y establecer un estándar de clasificación. Todos los sujetos fueron tratados con 4 extracciones de los primeros premolares seguidas de retracción de los incisivos centrales superiores. Se revisaron los cefalogramas laterales, previos y posteriores al tratamiento de 19 pacientes, para determinar los cambios del labio superior y las posiciones de los incisivos a través del desplazamiento de los puntos de referencia. Se realizó una prueba t de muestras independientes y un análisis de varianza de una vía. Las correlaciones entre la retracción del incisivo maxilar y la retracción del labio superior se exploraron mediante el método de correlación de Pearson. Los valores de p<0,05 fueron considerados estadísticamente significativos. El grosor de los labios de los pacientes adultos masculinos fue mayor que el de las pacientes adultas. La relación promedio de la retracción del incisivo maxilar al reposicionamiento del labio superior fue de 1,6:1,1; 9:1 y 2,2:1 en el grupo de labios delgados, grupo de labios normales y grupo de labios gruesos, respectivamente. Existen diferencias de sexo en el grosor del labio superior. Los cambios horizontales del incisivo maxilar mostraron una correlación significativa con los cambios horizontales del labio superior (P<0,001). Hubo correlaciones negativas entre el grosor del labio superior y la relación entre el cambio en la protuberancia del incisivo maxilar y el cambio en la protrusión del labio superior.