Observation of plaid-like spin splitting in a noncoplanar antiferromagnet.

Spatial, momentum and energy separation of electronic spins in condensed-matter systems guides the development of new devices in which spin-polarized current is generated and manipulated1-3. Recent attention on a set of previously overlooked symmetry operations in magnetic materials4 leads to the emergence of a new type of spin splitting, enabling giant and momentum-dependent spin polarization of energy bands on selected antiferromagnets5-10. Despite the ever-growing theoretical predictions, the direct spectroscopic proof of such spin splitting is still lacking. Here we provide solid spectroscopic and computational evidence for the existence of such materials. In the noncoplanar antiferromagnet manganese ditelluride (MnTe2), the in-plane components of spin are found to be antisymmetric about the high-symmetry planes of the Brillouin zone, comprising a plaid-like spin texture in the antiferromagnetic (AFM) ground state. Such an unconventional spin pattern, further found to diminish at the high-temperature paramagnetic state, originates from the intrinsic AFM order instead of spin-orbit coupling (SOC). Our finding demonstrates a new type of quadratic spin texture induced by time-reversal breaking, placing AFM spintronics on a firm basis and paving the way for studying exotic quantum phenomena in related materials.

Observation of Electronic Nematicity Driven by the Three-Dimensional Charge Density Wave in Kagome Lattice KV3Sb5.

Kagome superconductors AV3Sb5 (A = K, Rb, Cs) provide a fertile playground for studying intriguing phenomena, including nontrivial band topology, superconductivity, giant anomalous Hall effect, and charge density wave (CDW). Recently, a C2 symmetric nematic phase prior to the superconducting state in AV3Sb5 drew enormous attention due to its potential inheritance of the symmetry of the unusual superconductivity. However, direct evidence of the rotation symmetry breaking of the electronic structure in the CDW state from the reciprocal space is still rare, and the underlying mechanism remains ambiguous. The observation shows unconventional unidirectionality, indicative of rotation symmetry breaking from six-fold to two-fold. The interlayer coupling between adjacent planes with π-phase offset in the 2 × 2 × 2 CDW phase leads to the preferred two-fold symmetric electronic structure. These rarely observed unidirectional back-folded bands in KV3Sb5 may provide important insights into its peculiar charge order and superconductivity.

miR-126 regulates the proliferation, migration, invasion, and apoptosis of non-small lung cancer cells via AKT2/HK2 axis.

This study tended to clarify the role of miR-126 in non-small cell lung cancer (NSCLC) cell biological behaviors in vitro, containing cell proliferation, migration, invasion, and apoptosis. miRNA expression microarray related to NSCLC was accessed from gene expression omnibus (GEO) database and subjected to differential analysis using the "limma" package. Real-time quantitative PCR was conducted to assess the expression of miR-126 in NSCLC cell lines. wIn vitro experiments including 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), wound healing assay, Transwell, and flow cytometry assay were used for evaluating the effect of miR-126 on cell proliferation, migration, invasion, and apoptosis. Additionally, target mRNA for miR-126 was predicted and further validated by bioinformatics analysis and dual-luciferase reporter assay, respectively. It suggested that miR-126 was significantly down-regulated in NSCLS based on the expression microarray, and similar expression trend was exhibited in cancer cell lines. In the meantime, overexpression of miR-126 was found to result in inhibition of cell proliferation, migration, and invasion while promotion of cell apoptosis, with reductions in protein expression of AKT2 and phosphorylated HK2 (p-HK2) as well. AKT2, identified to be a direct target of miR-126 in NSCLC as judged by dual-luciferase reporter assay. Additionally, overexpression of AKT2 was observed to have the ability of elevating p-HK2 protein expression and reversing the effect of miR-126 on NSCLC cell proliferation, migration, and invasion. Given the above findings, we can see that miR-126 exerts its role in NSCLC cell proliferation, migration, invasion, and apoptosis with the aid of AKT2/HK2 axis.

[Relations of alcohol consumption and sleep among community-dwelling elderly living in cold region of Russia: a cross-sectional study].

AIM: Alcohol consumption is high in the colder regions of Russia, and it is related to poor sleep quality, mental and physical health problems. Little known on the actual situation, and no appropriate amount of drinking has been shown as a health guidance. The purpose of this study is to examine the relationship between alcohol consumption (in pure alcohol) and sleep among older people living in the Russian Siberian region, and the factors related to alcohol consumption. METHODS: A self-reported questionnaire survey was administered to 422 elderly over the age of 60 living in Novosibirsk, the central city of Siberia. Question items were basic attributes, health status, drinking habits, Short Form-8 Health Survey, Geriatric Depression Scale, and Pittsburgh Sleep Quality Index. For drinking elderly, daily amount of alcohol converted in pure alcohol was calculated, and logistic regression analysis among the two groups was compared based on the median value (32 g). RESULTS: The valid responses from the survey was 416 (98.9%). Of these, 293 with drinking habits were subjected to logistic regression analysis using pure alcohol (≥32 g/day) as the dependent variable. Significant relationships were found with gender (OR=0.586; 95%CI: 0.345-0.995), years of education (OR=1.538; 95%CI: 1.239-1.910), insomnia (OR=2.442; 95%CI: 1.185-5.032), alcohol intake, due to better sleep (OR=4.120; 95%CI: 1.044-16.258), effects of drinking, arousal during the night (OR=2.586; 95%CI: 1.317-5.077), effects of drinking, from family (OR=26.938; 95%CI: 3.368-215.431). CONCLUSIONS: Among the elderly people in colder regions of Russia, high alcohol consumption reduces sleep quality, suggesting the need for appropriate standards for pure alcohol and health education.

Metformin Alleviates the Bone Loss Induced by Ketogenic Diet: An In Vivo Study in Mice.

Metformin (Met), an anti-diabetes drug, has also shown therapeutic effects for ovariectomy-induced (OVX) osteoporosis. However, similar effects against bone loss induced by a ketogenic diet (KD) have not been tested. This study was aimed to evaluate the microarchitectures and biomechanics of KD-induced osteoporosis with and without administration of Met, and compare the effect of Met on bone loss induced by KD with OVX. Forty female C57BL/6J mice were randomly divided into Sham, OVX, OVX + Met (100 mg/kg/day), KD (3:1 ratio of fat to carbohydrate and protein), and KD + Met (100 mg/kg/day) groups. After 12 weeks, the bone mass and biomechanics were measured in distal cancellous bone and in mid-shaft cortical bone of the femur. The activities of serum alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP), together with immunohistochemistry staining of osteocalcin (OCN) and TRAP, were evaluated. Both OVX and KD induced significant bone loss and compromised biomechanical properties in the cancellous bone, but no effect was found in cortical bone. The administration of Met increased the cancellous bone volume fraction (BV/TV) from 3.78 to 5.23% following the OVX and from 4.04 to 6.33% following the KD, it also enhanced the compressive stiffness from 47 to 160 N/mm following the OVX and from 35 to 340 N/mm with the KD. Met effectively increased serum ALP in the KD group while decreased serum TRAP in the OVX group, but up-regulated expression of OCN and down-regulated expression of TRAP in both OVX and KD groups. The present study demonstrated that Met effectively attenuated the cancellous bone loss induced by KD and maintained the biomechanical properties of long bones, providing evidence for Met as a treatment of by KD-induced osteoporosis in teenage skeleton.

Ketogenic diet compromises vertebral microstructure and biomechanical characteristics in mice.

Ketogenic diet (KD) compromised the microstructure of cancellous bone and the mechanical property in the appendicular bone of mice, while the effects of KD on the axial bone have not been reported. This study aimed to compare the changes in the microstructure and mechanical properties of the forth lumbar (L4) vertebra in KD and ovariectomized (OVX) mice. Forty eight-week-old female C57BL/6J mice were assigned into four groups: SD (standard diet) + Sham, SD + OVX, KD + Sham, and KD + OVX groups. L4 vertebra was scanned by micro-CT to examine the microstructure of cancellous bone, after which simulative compression tests were performed using finite element (FE) analysis. Vertebral compressive test and histological staining of the L4 and L5 vertebrae were performed to observe the biomechanical and histomorphologic changes. The KD + Sham and SD + OVX exhibited a remarkable declination in the parameters of cancellous bone compared with the SD + Sham group, while KD + OVX demonstrated the most serious bone loss in the four groups. The stiffness was significantly higher in the SD + Sham group than the other three groups, but no difference was found between the remaining groups. The trabecular parameters were significantly correlated with the stiffness. Meanwhile, the OVX + Sham and KD + OVX groups showed a significant decrease in the failure load of compressive test, while there was no difference between the KD + Sham and SD + Sham groups. These findings suggest that KD may compromise the vertebral microstructure and compressive stiffness to a similar level as OVX did, indicating adverse effects of KD on the axial bone of the mice.

Ketogenic diet delays spinal fusion and decreases bone mass in posterolateral lumbar spinal fusion: an in vivo rat model.

BACKGROUND: Ketogenic diet (KD), a low-carbohydrate-and-high-fat diet, causes a metabolic state of ketogenesis and has been used to treat drug-resistance epilepsy. Our recent studies showed KD neuroprotective after spinal cord injury and causing bone loss. Effects of KD on spinal fusion were still unknown. This study was aimed to evaluate effects of KD on spinal fusion in rats. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into KD and standard diet (SD) groups. The KD group was fed with food of 1:4 carbohydrates to fat. All rats were subjected to L4/5 posterolateral lumbar spinal fusion. The blood ketone, and serum calcium, phosphorus, and insulin-like growth factor-1 (IGF-1) were measured, as well as the fusion rates, bone mass (BV), and bone mineral contents (BMC) of fusion sites were estimated at 4 and 8 weeks. RESULTS: There was no significant difference in serum calcium or phosphorus levels between groups at 4 or 8 weeks. However, there was a significant increase of blood ketone (1.02 mmol/L vs 0.38 mmol/L at 4 weeks; 0.83 mmol/L vs 0.32 mmol/L, at 8 weeks) and decrease of serum IGF-1 (339.4 ng/mL vs 630.6 ng/mL at 4 weeks; 418.8 ng/mL vs 628.6 ng/mL, at 8 weeks) in the KD group compared with the SD group. The spinal fusion occurred less in the KD group (1/16 vs 6/16 at 4 weeks; 7/16 vs 10/16, at 8 weeks), particularly at 4 weeks after surgery. The BV and BMC were lower in the KD group than that in the SD group at 4 weeks, but not different between groups at 8 weeks. CONCLUSIONS: This study demonstrated that KD delayed spinal fusion and decreased bone mass in posterolateral lumbar spinal fusion in rats.

Ketogenic Diet Compromises Both Cancellous and Cortical Bone Mass in Mice.

To clarify osteoporotic effects of ketogenic diet (KD) on cancellous and cortical bone compared with ovariectomy (OVX) in mice. Forty female C57BL/6J 8-week-old mice were randomly divided into SD+Sham, SD+OVX, KD+Sham, and KD+OVX groups, and fed for 12 weeks. The distal femur of trabecular bone and the middle femur of cortical bone were evaluated with Micro-CT scanning. The maximum bending force and stiffness of the tibia were calculated using a three-point bending test. Osteoblast and osteoclast expression of femur were identified using tartrate-resistant acid phosphatase (TRAP), collagen type I (CoLI), and osteocalcin (OCN) staining. A 2-factor analysis of variance was used to evaluate effects of KD and OVX on radiological, biomechanical, and histological parameters. KD resulted in not only remarkable cancellous bone decline comparable to OVX, but also unique cortical bone reduction. The maximum bending force and stiffness decreased in the KD+Sham and KD+OVX groups but did not change in the SD+OVX group. The KD+OVX led to significantly higher expression in TRAP and noticeably lower expression in CoLI when compared with other groups. Both KD+Sham and SD+OVX prominently increased expression in TRAP, but decreased expression in CoLI. There was no significant difference in OCN among the four groups. The present results suggest that KD compromises both the cancellous and cortical bone architecture of long bones while OVX only in cancellous bone architecture. A combination of KD and OVX may lead to more bone loss.

Identification of lung adenocarcinoma subtypes based on mitochondrial energy metabolism-related genes.

BACKGROUND: Identifying subtypes of lung adenocarcinoma (LUAD) patients based on mitochondrial energy metabolism and immunotherapy sensitivity is essential for precision cancer treatment. METHODS: LUAD subtypes were identified using unsupervised consensus clustering, and results were subjected to immune and tumor mutation analyses. DEGs between subtypes were identified by differential analysis. Functional enrichment and PPI network analyses were conducted. Patients were classified into high and low expression groups based on the expression of the top 10 hub genes, and survival analysis was performed. Drugs sensitive to feature genes were screened based on the correlation between hub gene expression and drug IC50 value. qRT-PCR and western blot were used for gene expression detection, and CCK-8 and flow cytometry were for cell viability and apoptosis analysis. RESULTS: Cluster-1 had significantly higher overall survival and a higher degree of immunoinfiltration and immunophenotypic score, but a lower TIDE score, DEPTH score, and TMB. Enrichment analysis showed that pathways and functions of DEGs between two clusters were mainly related to the interaction of receptor ligands with intracellular proteases. High expression of hub genes corresponded to lower patient survival rates. The predicted drugs with high sensitivity to feature genes were CDK1: Ribavirin (0.476), CCNB2: Hydroxyurea (0.474), Chelerythrine (0.470), and KIF11: Ribavirin (0.471). KIF11 and CCNB2 were highly expressed in LUAD cells and promoted cell viability and inhibited cell apoptosis. CONCLUSION: This study identified two subtypes of LUAD, with cluster-1 being more suitable for immunotherapy. These results provided a reference for the development of precision immunotherapy for LUAD patients.

Nonlinear optical signatures of topological Dirac fermion.

Dirac fermion in topological materials exhibits intriguing nonlinear optical responses. However, their direct correlation with the linearly dispersed band remains elusive experimentally. Here, we take topological semimetal ZrSiS as a paradigm, unveiling three unique nonlinear optical signatures of Dirac fermion. These signatures include strong quadrupolar response, quantum interference effect, and exponential divergent four-wave mixing (FWM), all of which are described by the prominent third-order nonlinear optical susceptibility. Resonantly enhanced by linear bands, quadrupolar second harmonic generation in centrosymmetric bulk overwhelms the electric-dipole contribution at the surface with inherent inversion symmetry breaking. Furthermore, owing to the interference between multiple resonant transition pathways within linear bands, difference-frequency FWM is several orders of magnitude stronger than sum-frequency FWM and third harmonic generation. The difference-frequency FWM further displays an inverse-square divergence toward degenerate excitation, whose scaling law perfectly matches with the long-sought behavior of Dirac fermion. These signatures lay the solid foundation toward the practical applications of topological materials in nonlinear optoelectronics and photonics.

Autologous Costal Osteochondral Transplantation for Cystic Osteochondral Lesions of the Talus: Feasible and Effective.

OBJECTIVE: Osteochondral lesions of the talus (OLT) is a common and clinically challenging disease. The optimal management is still under debate. The purpose of this prospective study was to investigate the feasibility and clinical outcomes of autologous costal osteochondral transplantation (ACOT) for the treatment of cystic OLT. METHODS: From November 2021 to April 2023, five patients underwent autologous costal osteochondral transplantation (ACOT) for cystic OLT. The demographic data was described, including age, gender, lesion size and location. We prospectively evaluated their functional and imaging outcomes of the five patients for 12 months postoperatively, including numeric rating score (NRS) for pain when walking, Tegner score, American Orthopedic Foot & Ankle Society (AOFAS) score and Foot and Ankle Ability Measure (FAAM) score, and imaging results. A paired t-test was used for preoperative and postoperative comparison of the paired-design dataset. RESULTS: The average age was 36.6 ± 11.1 years. The average diameter of chondral lesions was 14.95 ± 2.71 mm, the average diameter of subchondral cysts was 10.66 ± 1.84 mm, and their average depth was 10.40 ± 1.86 mm. At 12 months postoperatively, the clinical function indexes improved significantly, including NRS (from 5.2 ± 2.3 to 0), Tegner score (from 3.2 ± 0.4 to 5.8 ± 0.4), AOFAS score (from 72.8 ± 10.0 to 98.2 ± 4.0), and FAAM score (FAAM/ADL from 61.2 ± 24.7 to 99.3 ± 1.6; FAAM/Sports from 32.5 ± 13.73 to 96.3 ± 8.4). Their magnetic resonance observation of cartilage repair tissue (MOCART) scores reached 78.0 ± 7.6 points. ICRS scores of three patients were nearly normal (10 or 11 points). The biopsy of the surviving grafts showed plenty of hyaline cartilage matrix and scattered chondrocytes histologically. No major severe complications were reported during the 12 months follow-up. CONCLUSION: ACOT could significantly relieve the symptoms of patients with OLT and improve their clinical function at short-term follow-up. ACOT might be a feasible and useful method for repairing OLT with subchondral cysts.

MiR-129-2-3p Inhibits Esophageal Carcinoma Cell Proliferation, Migration, and Invasion via Targeting DNMT3B.

PURPOSE: The study aims to explore the regulatory mechanism of miR-129-2-3p underlying esophageal carcinoma (EC) cell progression and generate new ideas for targeted treatment of EC. METHODS: Mature miRNA expression data and total RNA sequencing data of EC in the TCGAESCA dataset were utilized to explore differentially expressed miRNAs (DEmiRNAs). StarBase database was then utilized to predict targets of miRNA. MiR-129-2-3p and DNMT3B expression in EC cell lines was assayed through qRT-PCR and Western blot. CCK-8, scratch healing, and transwell assays were conducted to assess the impact of miR-129-2-3p on EC cell phenotypes. In addition, a dual-luciferase assay was completed to identify the binding relationship between DNMT3B and miR-129-2-3p. RESULTS: MiR-129-2-3p was noticeably less expressed in EC cell lines, while DNMT3B was highly expressed. MiR-129-2-3p could bind to DNMT3B. Furthermore, in vitro functional experiments uncovered that overexpressed miR-129-2-3p repressed EC cell progression while further overexpressing DNMT3B would restore the above inhibitory effect. CONCLUSION: MiR-129-2-3p is a cancer repressor in EC cells, and it could target DNMT3B, thus hampering the progression of EC cells.

Electronic structure and layer-dependent magnetic order of a new high-mobility layered antiferromagnet KMnBi.

Room-temperature two-dimensional antiferromagnetic (AFM) materials are highly desirable for various device applications. In this letter, we report the low-energy electronic structure of KMnBi measured by angle-resolved photoemission spectroscopy, which confirms an AFM ground state with the valence band maximum located at -100 meV below the Fermi level and small hole effective masses associated with the sharp band dispersion. Using complementary Raman, atomic force microscope and electric transport measurement, we systematically study the evolution of electric transport characteristics of micro-mechanically exfoliated KMnBi with varied flake thicknesses, which all consistently reveal the existence of a probable AFM ground state down to the quintuple-layer regime. The AFM phase transition temperature ranges from 220 K to 275 K, depending on the thickness. Our results suggest that with proper device encapsulation, multilayer KMnBi is indeed a promising 2D AFM platform for testing various theoretical proposals for device applications.

Flat bands, non-trivial band topology and rotation symmetry breaking in layered kagome-lattice RbTi3Bi5.

A representative class of kagome materials, AV3Sb5 (A = K, Rb, Cs), hosts several unconventional phases such as superconductivity, [Formula: see text] non-trivial topological states, and electronic nematic states. These can often coexist with intertwined charge-density wave states. Recently, the discovery of the isostructural titanium-based single-crystals, ATi3Bi5 (A = K, Rb, Cs), which exhibit similar multiple exotic states but without the concomitant charge-density wave, has opened an opportunity to disentangle these complex states in kagome lattices. Here, we combine high-resolution angle-resolved photoemission spectroscopy and first-principles calculations to investigate the low-lying electronic structure of RbTi3Bi5. We demonstrate the coexistence of flat bands and several non-trivial states, including type-II Dirac nodal lines and [Formula: see text] non-trivial topological surface states. Our findings also provide evidence for rotational symmetry breaking in RbTi3Bi5, suggesting a directionality to the electronic structure and the possible emergence of pure electronic nematicity in this family of kagome compounds.

Kagome surface states and weak electronic correlation in vanadium-kagome metals.

RV6Sn6(R= Y and lanthanides) with two-dimensional vanadium-kagome surface states is an ideal platform to investigate kagome physics and manipulate the kagome features to realize novel phenomena. Utilizing the micron-scale spatially resolved angle-resolved photoemission spectroscopy and first-principles calculations, we report a systematical study of the electronic structures ofRV6Sn6(R= Gd, Tb, and Lu) on the two cleaved surfaces, i.e. the V- andRSn1-terminated (001) surfaces. The calculated bands without any renormalization match well with the main ARPES dispersive features, indicating the weak electronic correlation in this system. We observe 'W'-like kagome surface states around the Brillouin zone corners showingR-element-dependent intensities, which is probably due to various coupling strengths between V andRSn1layers. Our finding suggests an avenue for tuning electronic states by interlayer coupling based on two-dimensional kagome lattices.

EZH2 affects malignant progression and DNA damage repair of lung adenocarcinoma cells by regulating RAI2 expression.

BACKGROUND: Lung adenocarcinoma (LUAD) is featured in high morbidity and mortality. Aberrant activation of the histone methyltransferase EZH2 has close association with cancer progression. This research aimed to deeply dive into the role and possible molecular mechanisms of EZH2 and its downstream genes in malignant progression and DNA damage repair of LUAD cells. METHODS: Expression of EZH2 in LUAD cells was analyzed by qRT-PCR, and the effects of EZH2 on proliferation, and apoptosis of LUAD cells were examined by CCK-8, colony formation and flow cytometry assays. The downstream targets of EZH2 were predicted by bioinformatics analysis. Then, the targeting relationship between EZH2 and RAI2 was examined by CHIP and luciferase reporter assays. Rescue assay were used to further validate the effect of EZH2/RAI2 on the malignant progression of LUAD cells. The expression levels of EZH2, RAI2 and p53 were examined by Western blot. RESULTS: Upregulation of EZH2 was identified in LUAD tissues and cells. RAI2 was a downstream target gene of EZH2, and the two were negatively correlated. Silencing EZH2 suppressed proliferation of LUAD cells, promoted expression of p53, cell cycle arrest and apoptosis. While silencing RAI2 could reverse the above-mentioned effects caused by EZH2 silencing. CONCLUSION: These results demonstrated that EZH2 promoted malignant progression and DNA damage repair of LUAD cells by targeting and negatively regulating RAI2.

Identification of a dysregulated ceRNA network modulated by copy number variation-driven lncRNAs in lung squamous cell carcinoma.

Lung cancer is primarily responsive for cancer death, and its progression is aggressively affected by copy number variation (CNV). Through bioinformatics approach, a ceRNA network of CNV-driven lncRNAs in lung squamous cell carcinoma (LUSC) patients was constructed. Data on normal and LUSC tumor tissue from The Cancer Genome Atlas (TCGA)-LUSC dataset were subjected to differential analysis, and differentially expressed lncRNAs (DElncRNAs), DEmiRNAs, and DEmRNAs were obtained. Based on TCGA-LUSC, CNVs of normal and tumor tissue samples were then compared using a Chi-square test, and lncRNAs were intersected based on their CNVs and expression alternation. In combination with the Kruskal-Wallis test, CNV-driven lncRNAs were acquired. Afterwards, miRNAs and mRNAs that interacted with CNV-driven lncRNAs were obtained based on databases (LncBase, starBase, miRDB, mirDIP and TargetScan), DElncRNAs, DEmiRNAs and DEmRNAs, and correlation analysis. The acquired lncRNAs, miRNAs and mRNAs were subjected to Cytoscape software to construct a CNV-driven ceRNA network, which involved 5 lncRNAs (MIR143HG, LINC00702, MIR22HG, RP11-180 N14.1, RP11-473 M20.9), 6 miRNAs (miR-3200-3p, miR-1301-3p, miR-93-3p, miR-96-5p, miR-96-5p, miR-130b-5p, miR-205-5p) and 80 mRNAs. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses indicated that downstream mRNAs were mainly correlated with blood vessel development and T cell-mediated immunity. In summary, we devoted to analyzing CNV-related lncRNAs, mRNAs, and miRNAs in LUSC, thus clarifying 5 lncRNAs that may influence the malignant progression of LUSC. The ceRNA network regulated by these lncRNAs may be the novel pathogenesis of LUSC.

Extra Spindle Pole Bodies-Like 1 Serves as a Prognostic Biomarker and Promotes Lung Adenocarcinoma Metastasis.

Extra spindle pole bodies-like 1 (ESPL1), a cysteine endopeptidase, plays a vital role in chromosome inheritance. However, the association of ESPL1 with prognosis and immune infiltration in lung adenocarcinoma (LUAD) has not yet been explored. Here, we analyzed the expression level, prognostic values, diagnostic value, and immune infiltration level in LUAD using various databases. Immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) assays were used to detect the expression of ESPL1 in LUAD tissues and cell lines. In this study, we found that ESPL1 was upregulated in LUAD and a higher expression of ESPL1 was correlated with unfavorable prognosis in LUAD. Meanwhile, Cox hazard regression analysis results suggested that ESPL1 may be an independent prognostic factor for LUAD. Moreover, we demonstrated that ESPL1 expression was significantly correlated with immune infiltration of Th2 and dendritic cells in LUAD. We also confirmed that DNA copy number amplification and DNA hypo-methylation were positively correlated with ESPL1 expression in LUAD. Additionally, DNA copy number amplification was significantly associated with adverse clinical outcomes in LUAD. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) confirmed that ESPL1 was mainly involved in the DNA replication and glycolysis signaling pathway. Finally, we revealed that ESPL1 was highly expressed in LUAD tissues and cell lines. Knockdown of ESPL1 significantly inhibited cell migration and the invasion abilities of LUAD. Our study comprehensively confirmed that ESPL1 expression may serve as a novel prognostic biomarker for both the clinical outcome and immune cell infiltration in LUAD.

MiR-196b Promotes the Invasion and Migration of Lung Adenocarcinoma Cells by Targeting AQP4.

OBJECTIVE: We aimed to investigate the mechanism of the regulatory axis of miR-196b/AQP4 underlying the invasion and migration of lung adenocarcinoma (LUAD) cells. METHODS: LUAD miRNA and mRNA expression profiles were downloaded from TCGA database and then differential analysis was used to identify the target miRNA. Target gene for the miRNA was obtained via prediction using 3 bioinformatics databases and intersection with the differentially expressed mRNAs searched from TCGA-LUAD. Then, qRT-PCR and western blot were used to validate the expression of miR-196b and AQP4. Dual-luciferase reporter assay was performed to confirm the targeting relationship between miR-196b and AQP4. Transwell assay was used to investigate the migration and invasion of LUAD cells. RESULTS: MiR-196b was screened out by differential and survival analyses, and the downstream target gene AQP4 was identified. In LUAD, miR-196b was highly expressed while AQP4 was poorly expressed. Besides, overexpression of miR-196b promoted cell invasion and migration, while overexpression of AQP4 had negative effects. Moreover, the results of the dual-luciferase reporter assay suggested that AQP4 was a direct target of miR-196b. In addition, we also found that overexpressing AQP4 could suppress the promotive effect of miR-196b on cancer cell invasion and migration. CONCLUSION: MiR-196b promotes the invasion and migration of LUAD cells by down-regulating AQP4, which helps us find new molecular targeted therapies for LUAD.

Unilateral cervical spinal cord injury induces bone loss and metabolic changes in non-human primates (Macaca fascicularis).

BACKGROUND/OBJECTIVE: The deleterious effects of chronic spinal cord injury (SCI) on the skeleton in rats, especially the lower extremities, has been proved previously. However, the long-term skeletal changes after SCI in non-human primates (NHP) have been scarcely studied. This study aimed to evaluate the bone loss in limbs and vertebrae and the bone metabolic changes in NHP after unilateral cervical spinal cord contusion injury. METHODS: Twelve Macaca fascicularis were randomly divided into the SCI (n=8) and the Sham (n=4) groups. The SCI models were established using hemi-contusion cervical spinal cord injury on fifth cervical vertebra (C5), and were further evaluated by histological staining and neurophysiological monitoring. Changes of bone microstructures, bone biomechanics, and bone metabolism markers were assessed by micro-CT, micro-FEA and serological kit. RESULTS: The NHP hemi-contusion cervical SCI model led to consistent unilateral limb dysfunction and potential plasticity in the face of loss of spinal cord. Furthermore, the cancellous bone mass of ipsilateral humerus and radius decreased significantly compared to the contralateral side. The bone volume fraction of humerus and radius were 17.2% and 20.1% on the ipsilateral while 29.0% and 30.1% on the contralateral respectively. Similarly, the thickness of the cortical bone in the ipsilateral forelimbs was significantly decreased, as well as the bone strength of the ipsilateral forelimbs. These changes were accompanied by diminished concentration of osteocalcin and total procollagen type 1 N-terminal propeptide (t-P1NP) as well as increased level of ß-C-terminal cross-linking telopeptide of type 1collagen (ß-CTX) in serological testing. CONCLUSIONS: The present study demonstrated that hemi-SCI induced loss of bone mass and compromised biomechanical performance in ipsilateral forelimbs, which could be indicated by both muscle atrophy and serological changes of bone metabolism, and associated with a consistent loss of large-diameter cells of sensory neurons in the dorsal root ganglia. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our study, for the first time, demonstrated the bone loss in limbs and vertebrae as well as the bone metabolic changes in non-human primates after unilateral spinal cord injury (SCI). This may help to elucidate the role of muscle atrophy, serological changes and loss of sensory neurons in the mechanisms of SCI-induced osteoporosis, which would be definitely better compared with rodent models.