We attempted to investigate the relationship between hsa-let-7c and ANP32E, as well as their influence on the cells phenotype of lung adenocarcinoma. Expression of hsa-let-7c and prognostic values were assessed by bioinformatics analysis based on TCGA database. Quantitative real-time PCR and western blot was employed to measure relative expression of hsa-let-7c or ANP32E. The targeting relationship between let-7c and ANP32E was predicted by biological software and validated by dual luciferase reporter assay. With gene transfection technology, cell proliferation, invasion and migration were appraised by cell counting Kit-8, clone formation and Transwell assays. The results showed that hsa-let-7c was downregulated in lung adenocarcinoma. Downregulation of hsa-let-7c notably led to a poor survival. ANP32E was forecasted and confirmed as a directly target of hsa-let-7c, and was upregulated in lung adenocarcinoma. Furthermore, upregulation of ANP32E had a significant correlation with unsatisfactory survival. Meanwhile, the levels of ANP32E were negatively regulated by hsa-let-7c. Upregulation of hsa-let-7c remarkably suppressed the Calu-3 cell proliferation, invasion and migration, while ANP32E overexpression plasmids rescued the downtrend. Inversely, hsa-let-7c silencing in NCI-H209 cells presented the opposite outcomes. Collectively, hsa-let-7c shows an anti-tumor effect in lung adenocarcinoma by targeting ANP32E and is expected to be a potential therapeutic target for lung adenocarcinoma.

Immune therapy has shown good results in small-cell lung cancer (SCLC), but the impact of immune microenvironment of the disease is unclear. In this work, we detected expression of programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and other immune biomarkers of cancer. We also analyzed the correlations between these markers and survival in SCLC.

Multi-institutional brain imaging studies have emerged to resolve conflicting results among individual studies. However, adjusting multiple variables at the technical and cohort levels is challenging. Therefore, it is important to explore approaches that provide meaningful results from relatively small samples at institutional levels. We studied 87 first episode psychosis (FEP) patients and 62 healthy subjects by combining supervised integrated factor analysis (SIFA) with a novel pipeline for automated structure-based analysis, an efficient and comprehensive method for dimensional data reduction that our group recently established. We integrated multiple MRI features (volume, DTI indices, resting state fMRI-rsfMRI) in the whole brain of each participant in an unbiased manner. The automated structure-based analysis showed widespread DTI abnormalities in FEP and rs-fMRI differences between FEP and healthy subjects mostly centered in thalamus. The combination of multiple modalities with SIFA was more efficient than the use of single modalities to stratify a subgroup of FEP (individuals with schizophrenia or schizoaffective disorder) that had more robust deficits from the overall FEP group. The information from multiple MRI modalities and analytical methods highlighted the thalamus as significantly abnormal in FEP. This study serves as a proof-of-concept for the potential of this methodology to reveal disease underpins and to stratify populations into more homogeneous sub-groups.

Previous research has found that there are high rates of mental health problems among caregivers in rural China and that caregiver mental health may be a significant predictor of developmental delays among infants and toddlers in these rural areas. In this paper, we use data from a survey of 986 caregiver-child pairs in rural China to examine the risk factors of caregiver mental health and measure the association between caregiver mental health and child development outcomes. To conduct the empirical analysis, we assess caregiver mental health using the Depression Anxiety Stress Scales-21 (DASS-21) questionnaire and measure child developmental outcomes using the Bayley Scales of Infant and Toddler Developmental Third Edition (Bayley-III). The results show that 32% of caregivers have depressive symptoms, 42% have anxiety symptoms, and 30% have symptoms of stress. The data also demonstrate that caregiver identity and age as well as different measures of socioeconomic status (SES) (characterized by caregiver education, father's education, and household wealth) are all significantly linked to symptoms of caregiver mental health problems. The analysis shows that caregiver depression, anxiety, and/or stress are significantly associated with lower early childhood development (ECD) outcomes in all areas measured (cognition, language, social-emotion, and motor skills). The heterogeneous analysis demonstrates that there are differences in the effects of caregiver mental health problems on ECD among households are from families that are endowed with different levels of SES. On the basis of the findings the study concludes that policymakers should pay more attention to caregiver mental health problems in order to improve child developmental outcomes in rural China. The study cannot, however, draw casual conclusions and cannot rule out the possibility of recall bias when measuring caregiver mental health, which may limit the external validity of the findings.

ABCA4 gene associated retinal dystrophies (ABCA4-RD) are a group of inherited eye diseases caused by ABCA4 gene mutations, including Stargardt disease, cone-rod dystrophy and retinitis pigmentosa. With the development of next-generation sequencing (NGS), numerous clinical and genetic studies on ABCA4-RD have been performed, and the genotype and phenotype spectra have been elucidated. However, most of the studies focused on the Caucasian population and limited studies of large Chinese ABCA4-RD cohorts were reported. In this study, we summarized the phenotypic and genotypic characteristics of 129 Chinese patients with ABCA4-RD. We found a mutation spectrum of Chinese patients which is considerably different from that of the Caucasian population and identified 35 novel ABCA4 mutations. We also reported some rare and special cases, such as, pedigrees with patients in two generations, patients diagnosed with cone-rod dystrophy or retinitis pigmentosa, patients with subretinal fibrosis and patients with preserved foveal structure. At the same time, we focused on the correlation between the genotypes and phenotypes. By the comprehensive analysis of multiple clinical examinations and the application of multiple regression analysis, we proved that patients with two "null" variants had a younger onset age and reached legal blindness earlier than patients with two "none-null" variants. Patients with one or more "none-null" variants tended to have better visual acuity and presented with milder fundus autofluorescence changes and more preserved rod functions on the full-field electroretinography than patients with two "null" variants. Furthermore, most patients with the p.(Phe2188Ser) variant shared a mild phenotype with a low fundus autofluorescence signal limited to the fovea and with normal full-field electroretinography responses. Our findings expand the variant spectrum of the ABCA4 gene and enhance the knowledge of Chinese patients with ABCA4-RD.

Bacterial biofilms are believed to be principal virulence factors for many localized chronic infectious diseases. Escherichia coli is one of the most common microbial pathogens and frequently causes biofilm-associated opportunistic infections, such as diarrhea, endometritis and mastitis. Cinnamomum camphora essential oil (CCEO) has shown potential in treating intractable chronic endometritis in dairy cows. There is little scientific evidence regarding the effect of CCEO on bacterial biofilms. The objective of this study was to investigate the effect of CCEO on E. coli biofilm formation and how CCEO affects E. coli in suspension and in a biofilm. CCEO killed all clinical E. coli strains in either planktonic or biofilm state isolated from dairy cows with clinical endometritis. The minimum inhibitory concentration (MIC) for 90% of the organisms was 4.297 μL/mL, the minimum bactericidal concentration for 90% of the organisms was 6.378 μL/mL, the minimum biofilm inhibitory concentration for 90% of the organisms was 6.850 μL/mL, and the minimum biofilm eradication concentration (MBEC) for 90% of the organisms was 8.467 μL/mL. The MBECs were generally two times higher than the MICs. Flow cytometry analysis confirmed that significant bacterial killing occurred during the first 1 h after exposure to subinhibitory concentrations of CCEO. In addition, CCEO exerted a significant inhibitory effect on E. coli biofilm formation, and bacterial killing occurred during the first 30 min of exposure to subinhibitory biofilm concentrations of CCEO. The biofilm yield of E. coli was significantly reduced after CCEO treatment, along with an increased dead/live microbial ratio in biofilms compared with that in the non-treated control, as confirmed by scanning electron microscopy images and confocal laser scanning microscopy images. These data revealed that CCEO efficiently kills E. coli during planktonic growth and biofilm formation.

Rupture of intracranial aneurysm (IA) is the leading cause of subarachnoid hemorrhage. However, there are few pharmacological therapies available for the prevention of IA rupture. Therefore, exploring the molecular mechanisms which underlie IA rupture and identifying the potential molecular targets for preventing the rupture of IA is of vital importance.

Jiangzhi Decoction (JZD), a traditional herb mixture, has shown significant clinical efficacy against nonalcoholic fatty liver disease (NAFLD). However, its multicomponent and multitarget characteristics bring difficulty in deciphering its pharmacological mechanisms. Our study is aimed at identifying the core molecular mechanisms of JZD against NAFLD.

Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.

Rifampin plays a crucial role in the treatment of staphylococcal implant-associated infection, as it is the only antibiotic capable of eradicating Staphylococcus aureus biofilms. However, the emergence of rifampin resistance strongly limits its use. Combinatorial therapy of antibiotics and bacteriophages may represent a strategy to overcome the resistance. Here, we evaluated the activity of staphylococcal bacteriophage Sb-1 in combination with different antibiotics against the biofilms of 10 rifampin-resistant S. aureus clinical strains, including MRSA and MSSA. S. aureus biofilms formed on porous glass beads were exposed to antibiotics alone or combined with Sb-1 simultaneously or staggered (first Sb-1 for 24 h followed by antibiotic). Recovered bacteria were detected by measuring growth-related heat production at 37°C (isothermal microcalorimetry) and the biofilm eradication was assessed by sonication of beads and plating of the resulting sonication fluid. Minimum biofilm eradication concentration (MBEC) was defined as the lowest concentration of antibiotic required to kill all adherent bacteria, resulting in absence of growth after plating the sonication fluid. Tested antibiotics presented high MBEC values when administered alone (64 to > 1,024 μg/ml). The simultaneous or staggered combination of Sb-1 with daptomycin showed the highest activity against all MRSA biofilms, whereas the exposure to Sb-1 with vancomycin showed no improved anti-biofilm activity. Staggered administration of Sb-1 and flucloxacillin, cefazolin, or fosfomycin improved the antibiofilm activity in four out of six MSSA, whereas simultaneous exposure exhibited similar or lesser synergy. In conclusion, the combinatorial effect of Sb-1 and antibiotics enabled to eradicate rifampin-resistant S. aureus biofilms in vitro.

The spontaneous self-assembly of multicellular ensembles into living materials with synergistic structure and function remains a considerable challenge in biotechnology and synthetic biology. Here, we exploit the aqueous two-phase separation of dextran-in-PEG emulsion micro-droplets for the capture, spatial organization and immobilization of algal cells or algal/bacterial cell communities to produce discrete multicellular spheroids capable of both aerobic (oxygen producing) and hypoxic (hydrogen producing) photosynthesis in daylight under air. We show that localized oxygen depletion results in hydrogen production from the core of the algal microscale reactor, and demonstrate that enhanced levels of hydrogen evolution can be achieved synergistically by spontaneously enclosing the photosynthetic cells within a shell of bacterial cells undergoing aerobic respiration. Our results highlight a promising droplet-based environmentally benign approach to dispersible photosynthetic microbial micro-reactors comprising segregated cellular micro-niches with dual functionality, and provide a step towards photobiological hydrogen production under aerobic conditions.

Yes associated protein 1 (YAP1), which is a standout amongst the most essential effectors of the Hippo pathway, assumes a vital part in a few kinds of cancer. However, whether YAP1 is an oncogene in CRC (colorectal cancer) remains controversial, and the association between the subcellular localization of YAP1 and clinical implications in CRC remains unknown.

Osteosarcoma (OS) is a malignant carcinoma often occurring in adolescents. The critical function of long non-coding RNAs (lncRNAs) in cancer arouses increasing attention. Nevertheless, the specific function of FOXD3 Antisense RNA 1 (FOXD3-AS1) in OS has not been understood yet. In this research, FOXD3-AS1 showed strengthened level in OS specimens and cell lines, and its deficiency restrained cell migration, invasion and epithelial-to-mesenchymal transition (EMT) in OS. Then, we confirmed the interaction of FOXD3-AS1 with microRNA-296-5p (miR-296-5p) and that miR-296-5p overexpression blocked OS cell migration, invasion and EMT. Besides, miR-296-5p targeted zinc finger CCHC-type containing 3 (ZCCHC3), and FOXD3-AS1 released ZCCHC3 via sequestering miR-296-5p. Moreover, rescue assays delineated that ZCCHC3 upregulation neutralized the inhibitory effect of FOXD3-AS1 depletion on in vitro behaviors and in vivo tumorigenesis in OS. In addition, E74 like ETS transcription factor 1 (ELF1) stimulated FOXD3-AS1 transcription, and ELF1 silence-suppressed malignant phenotypes of OS cells were offset by FOXD3-AS1 upregulation. Overall, present work elucidated that ELF1-activated FOXD3-AS1 aggravated cell migration, invasion and EMT in OS via absorbing miR-296-5p to augment ZCCHC3 expression, which might provide potential guidance for researchers to find effective targets for OS treatment.

Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are closely associated with human diseases, and it is useful for the diagnosis and treatment of diseases to get the relationships between lncRNAs and diseases. Due to the high costs and time complexity of traditional bio-experiments, in recent years, more and more computational methods have been proposed by researchers to infer potential lncRNA-disease associations. However, there exist all kinds of limitations in these state-of-the-art prediction methods as well.

Mild hypothermia is a well-established technique for alleviating neurological injuries in clinical surgery. RNA-binding protein motif 3 (RBM3) has been identified as a crucial factor in mediating hypothermic neuroprotection, providing its induction as a promising strategy for mimicking therapeutic hypothermia. However, little is known about molecular control of RBM3 and signaling pathways affected by hypothermia. In the present study, human SH-SY5Y neuroblastoma cells were used as a neural cell model. Screening of signaling pathways showed that cold exposure led to inactivation of ERK and AMPK pathways, and activation of FAK and PLCγ pathways, with activities of p38, JNK and AKT pathways moderately changed. Next, various small molecule inhibitors specific to these signaling pathways were applied. Interestingly, only FAK-specific inhibitor exhibited a significant inhibitory effect on hypothermia-induced RBM3 gene transcription and protein expression. Likewise, FAK silencing using siRNA technique significantly abrogated the induction of RBM3 by hypothermia. Moreover, FAK inhibition accounted for an inactivation of Src, a known kinase downstream of FAK. Next, either the silencing of Src by siRNA or its inactivation by a chemical inhibitor, strongly blocked the induction of RBM3 by cooling. Notably, in HEK293 and PC12 cells, FAK/Src activation was also shown to be indispensable for hypothermia-stimulated RBM3 expression. Lastly, the CCK8 and Western blot assays showed that both FAK/Src inacitivation and their knockdown substantially abrogate the neuroprotective effects of mild hypothermia against rotenone in SH-SY5Y cells. These data suggest that FAK/Src signaling axis regulates the transcription of Rbm3 gene and mediates neuroprotective effects of mild hypothermia.

The expansion of the white adipose tissue (WAT) in obesity goes along with increased mechanical, metabolic and inflammatory stress. How adipocytes resist this stress is still poorly understood. Both in human and mouse adipocytes, the transcriptional co-activators YAP/TAZ and YAP/TAZ target genes become activated during obesity. When fed a high-fat diet (HFD), mice lacking YAP/TAZ in white adipocytes develop severe lipodystrophy with adipocyte cell death. The pro-apoptotic factor BIM, which is downregulated in adipocytes of obese mice and humans, is strongly upregulated in YAP/TAZ-deficient adipocytes under HFD, and suppression of BIM expression reduces adipocyte apoptosis. In differentiated adipocytes, TNFα and IL-1β promote YAP/TAZ nuclear translocation via activation of RhoA-mediated actomyosin contractility and increase YAP/TAZ-mediated transcriptional regulation by activation of c-Jun N-terminal kinase (JNK) and AP-1. Our data indicate that the YAP/TAZ signaling pathway may be a target to control adipocyte cell death and compensatory adipogenesis during obesity.

Certain animals exhibit a special dorsoventral pattern with a lighter ventral side compared to the dorsal one and this phenomenon was preserved in the long-term evolution process. Birds also retain this trait. Recently, Inaba et al. (2019) found that ASIP (agouti signal protein) regulated interconversion between different melanocyte types leads to dorsal stripe pattern, which may partly explain the birds' dorsoventral plumage color difference. In this study, we used the embryo samples of LBM (light brown mottling) ducks (Anas platyrhynchos) with white ventral and dark dorsal body parts to investigate the mechanism of dorsoventral color variation. Firstly, melanin deposition process of duck embryos was investigated. The result indicated that E13 and E16 were the active stages of melanin synthesis. Moreover, the melanin deposition on the dorsum of LBM ducks was higher than that on the ventral side throughout. Then, RNA-seq was conducted for the dorsal and ventral skin tissues from E7 (early), E13 (middle) and E19 (late) of LBM ducks. Expression pattern analysis showed that the mRNA expression of most melanin synthesis related genes were at the highest level at E13, which was consistent with the section analysis. A correlation was found between melanogenesis pathway and dorsoventral color difference by co-expression analysis. In the DEG (differentially expressed gene) analysis, we added the dorsal skin transcriptome of embryonic white and black duck of same subspecies (Anas platyrhynchos domestica) for horizontal comparison. The results showed that 8 melanogenesis related genes (TYR, TYRP1, MLANA, RAB38, OCA2, TSPAN10, MC1R, and MSLN) were the common DEGs (Differential expressed genes) in the comparisons of body parts and breeds suggesting that the underlying molecular regulatory mechanism of dorsoventral plumage color difference may be similar to that of albino and melanic duck, which were caused by the different expression of multiple genes in melanin synthesis pathway. In addition, the molecular regulation of melanin synthesis pathway in the dorsal and ventral side of LBM ducks was analyzed. In this pathway, ASIP, MC1R, TYR, and TYRP1 have differential mRNA expression. ASIP, as an upstream gene in this pathway, was likely to play a decisive role in determining the dorsoventral plumage pattern.

Despite the extensive development of antibacterial biomaterials, there are few reports on the effects of materials on the antibacterial ability of the immune system, and in particular of neutrophils. In this study, we observe differences between the in vivo and in vitro anti-infective efficacies of silver nanoparticles (AgNPs). The present study was designed to further explore the mechanism for this inconsistency using ex vivo models and in vitro experiments.

The detection of mutations in telomerase reverse transcriptase promoter (pTERT) is important since preoperative diagnosis of pTERT status helps with evaluating prognosis and determining the surgical strategy. Here, we aimed to establish a radiomics-based machine-learning algorithm and evaluated its performance with regard to the prediction of mutations in pTERT in patients with World Health Organization (WHO) grade II gliomas. In total, 164 patients with WHO grade II gliomas were enrolled in this retrospective study. We extracted a total of 1,293 radiomics features from multi-parametric magnetic resonance imaging scans. Elastic net (used for feature selection) and support vector machine with linear kernel were applied in nested 10-fold cross-validation loops. The predictive model was evaluated by receiver operating characteristic and precision-recall analyses. We performed an unpaired t-test to compare the posterior predictive probabilities among patients with differing pTERT statuses. We selected 12 valuable radiomics features using nested 10-fold cross-validation loops. The area under the curve (AUC) was 0.8446 (95% confidence interval [CI], 0.7735-0.9065) with an optimal summed value of sensitivity of 0.9355 (95% CI, 0.8802-0.9788) and specificity of 0.6197 (95% CI, 0.5071-0.7371). The overall accuracy was 0.7988 (95% CI, 0.7378-0.8598). The F1-score was 0.8406 (95% CI, 0.7684-0.902) with an optimal precision of 0.7632 (95% CI, 0.6818-0.8364) and recall of 0.9355 (95% CI, 0.8802-0.9788). Posterior probabilities of pTERT mutations were significantly different between patients with wild-type and mutant TERT promoters. Our findings suggest that a radiomics analysis with a machine-learning algorithm can be useful for predicting pTERT status in patients with WHO grade II glioma and may aid in glioma management.

Biotic and abiotic cues can trigger priming in plants, which enables plants to respond to subsequent challenge with stronger and/or faster responses. It is well known that herbivory activates defense-related responses in systemic leaves. However, little is known about whether insect feeding activates priming in systemic leaves. To determine whether and how herbivory induces priming in maize systemic leaves, a combination of insect bioassays, phytohormone and defense metabolite quantification, and genetic and transcriptome analyses were performed. Actual and simulated Mythimna separata herbivory in maize local leaves primed the systemic leaves for enhanced accumulation of jasmonic acid and benzoxazinoids and increased resistance to M. separata. Activation of priming in maize systemic leaves depends on both the duration of simulated herbivory and perception of M. separata oral secretions in the local leaves, and genetic analysis indicated that jasmonic acid and benzoxazinoids mediate the primed defenses in systemic leaves. Consistently, in response to simulated herbivory, the primed systemic leaves exhibited a large number of genes that were uniquely regulated or showed further up- or down-regulation compared with the non-primed systemic leaves. This study provides new insight into the regulation and ecological function of priming in maize.