Head and neck squamous cell carcinoma (HNSCC) is the major histological type of head and neck cancer and no curative treatments are currently available. Using advanced sequencing technologies, The Cancer Genome Atlas (TCGA) has produced large‑scale sequencing data, which provide unprecedented opportunities to reveal molecular mechanisms of cancer. The present study analyzed the mRNA and micro (mi)RNA expression data of HNSCC and normal control tissues released by the TCGA database using a bioinformatics approach to explore underlying molecular mechanisms. The mRNA and miRNA expression data were downloaded from the TCGA database and differentially expressed genes (DEGs) and miRNAs (DEMs) between HNSCC and normal head and neck tissues were identified using TwoClassDif. Subsequently, the gene functions and pathways which are significantly altered in HNSCC were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Regulatory networks among DEGs and DEMs were then constructed, and transcription factors (TFs) potentially regulating the DEGs and DEMs were determined and a TF ‑ miRNA ‑ gene network was established. A total of 2,594 significant DEGs (1,087 upregulated and 1,507 downregulated), and 25 DEMs (8 upregulated and 17 downregulated) were identified in HNSCC compared with normal control samples. These DEGs were significantly enriched in GOs and KEGG pathways such as mitosis, cell cycle, Wnt, JAK/STAT and TLR signaling pathway. CPBP, NF‑AT1 and miR‑1 were situated in the central hub of the TF ‑ miRNA ‑ gene network, underlining their central roles in regulatory processes specific for HNSCC. The present study enhanced the current understanding of the molecular mechanisms underlying HNSCC and may offer novel strategies for its prevention, diagnosis and treatment.

A thymoma is a common cancer within the anterior mediastinum; however, the prognostic characteristics have not been established. The aim of this study was to identify the prognostic factors and develop a nomogram for the prognostic prediction of patients with thymoma based on data from the Surveillance, Epidemiology, and End Results (SEER) database.

Tropical rainforests play important roles in carbon sequestration and are hot spots for biodiversity. Tropical forests are being replaced by rubber (Hevea brasiliensis) plantations, causing widespread concern of a crash in biodiversity. Such changes in aboveground vegetation might have stronger impacts on belowground biodiversity. We studied tropical rainforest fragments and derived rubber plantations at a network of sites in Xishuangbanna, China, hypothesizing a major decrease in diversity with conversion to plantations. We used metabarcoding of the 18S rRNA gene and recovered 2313 OTUs, with a total of 449 OTUs shared between the two land-use types. The most abundant phyla detected were Annelida (66.4% reads) followed by arthropods (15.5% reads) and nematodes (8.9% reads). Of these, only annelids were significantly more abundant in rubber plantation. Taken together, α- and β-diversity were significantly higher in forest than rubber plantation. Soil pH and spatial distance explained a significant portion of the variability in phylogenetic community structure for both land-use types. Community assembly was primarily influenced by stochastic processes. Overall it appears that forest replacement by rubber plantation results in an overall loss and extensive replacement of soil micro- and mesofaunal biodiversity, which should be regarded as an additional aspect of the impact of forest conversion.

Previous studies have identified potential risk factors for pulmonary carcinoid tumors and evaluated the effect of various treatments; however, the results were not entirely consistent. We conducted a population-based study to further explore relevant prognostic issues. We extracted cases with pulmonary carcinoid tumors from the Surveillance Epidemiology and End Results database. Cox proportional hazard regression was utilized to identify potential significant risk factors, which helped establish a nomogram for predicting long-term survival. Survival analysis and a competing risk study were conducted to evaluate the value of different surgical approaches. There were 7057 cases included in the study. Univariate and multivariate analyses showed that age, sex, tumor size, stage, histology, surgical type, chemotherapy, and radiation therapy were all significant prognostic factors. A nomogram with good accuracy for predicting 10-year survival was formulated. Furthermore, patients who had undergone surgery had a significantly better survival than those who did not undergo surgery. There was no significant prognostic difference between lobectomy and sublobectomy stratified by tumor stage; however, lobectomy was associated with a significantly better survival in atypical tumors, especially those with regional disease. Our research identified possible risk factors in a large cohort and constructed a nomogram to visually predict 10-year survival of pulmonary carcinoid tumors. We showed that lobectomy and sublobectomy should be considered as the mainstay of treatment, especially lobectomies for atypical tumor.

Emerging evidence suggests that the microbiota present in feces plays a role in Parkinson's disease (PD). However, the alterations of the microbiome in the blood of PD patients remain unknown. To test this hypothesis, we conducted this case-control study to explore the microbiota compositions in the blood of Chinese PD patients. Microbiota communities in the blood of 45 patients and their healthy spouses were investigated using high-throughput Illumina HiSeq sequencing targeting the V3-V4 region of 16S ribosomal RNA (rRNA) gene. The relationships between the microbiota in the blood and PD clinical characteristics were analyzed. No difference was detected in the structure and richness between PD patients and healthy controls. The following genera were enriched in the blood of PD patients: Isoptericola, Cloacibacterium, Enhydrobacter and Microbacterium; whereas genus Limnobacter was enriched in the healthy controls after adjusting for age, gender, body mass index (BMI) and constipation. Additionally, the findings regarding these genera were validated in another independent group of 58 PD patients and 57 healthy controls using real-time PCR targeting genus-specific 16S rRNA genes. Furthermore, not only the genera Cloacibacterium and Isoptericola (which were identified as enriched in PD patients) but also the genera Paludibacter and Saccharofermentans were positively associated with disease duration. Some specific genera in the blood were related to mood disorders. We believe this is the first report to provide direct evidence to support the hypothesis that the identified microbiota in the blood are associated with PD. Additionally, some microbiota in the blood are closely associated with the clinical characteristics of PD. Elucidating these differences in blood microbiomes will provide a foundation to improve our understanding of the role of microbiota in the pathogenesis of PD.

Stress-induced hyperglycemia is a fundamental adaptive response that mobilizes energy stores in response to threats. Here, our examination of the contributions of the central catecholaminergic (CA) neuronal system to this adaptive response revealed that CA neurons in the ventrolateral medulla (VLM) control stress-induced hyperglycemia. Ablation of VLM CA neurons abolished the hyperglycemic response to both physical and psychological stress, whereas chemogenetic activation of these neurons was sufficient to induce hyperglycemia. We further found that CA neurons in the rostral VLM, but not those in the caudal VLM, cause hyperglycemia via descending projections to the spinal cord. Monosynaptic tracing experiments showed that VLM CA neurons receive direct inputs from multiple stress-responsive brain areas. Optogenetic studies identified an excitatory PVN-VLM circuit that induces hyperglycemia. This study establishes the central role of VLM CA neurons in stress-induced hyperglycemia and substantially expands our understanding of the central mechanism that controls glucose metabolism.

Intronic microRNAs (in-miRNAs) as a class of miRNA family that regulates gene expression are still poorly understood in plants. In this study, we systematically identified rice in-miRNAs by re-mining eight published small RNA-sequencing datasets of rice. Furthermore, based on the collected expression, annotation, and putative target data, we investigated the structures, potential functions, and expression features of these in-miRNAs and the expression patterns of their host genes. A total of 153 in-miRNAs, which account for over 1/4 of the total rice miRNAs, were identified. In silico expression analysis showed that most of them (∼63%) are tissue or stage-specific. However, a majority of their host genes, especially those containing clustered in-miRNAs, exhibit stable high-level expressions among 513 microarray datasets. Although in-miRNAs show diversity in function and mechanism, the DNA methylation directed by 24 nt in-miRNAs may be the main pathway that controls the expressions of target genes, host genes, and even themselves. These findings may enhance our understanding on special functions of in-miRNAs, especially in mediating DNA methylation that was concluded to affect the stability of expression and structure of host and target genes.

Expression level of Fibulin-2 gene in breast cancer cells was evaluated to explore the impact of Fibulin-2 gene on the proliferation, migration and invasion of breast cancer cells. MDA-MB-231, BT483, MCF-7 and SK-BR-3 breast cancer cells were cultured in vitro. Then, expression of Fibulin-2 in cells was upregulated and downregulated using ribonucleic acid interference (RNAi) and lentiviral transfection techniques, respectively. Thereafter, expression levels of Fibulin-2 messenger RNA (mRNA) and protein were measured via quantitative real-time reverse transcription-polymerase chain reaction and western blotting, respectively. Cell Counting Kit-8 assay was applied to detect the proliferation ability, and wound healing assay was performed to determine the effect of transfection on the metastatic capacity of cells. The influence of transfection on the invasive ability of breast cancer cells was detected through Transwell chamber assay. MDA-MB-231 and MCF-7 cells did not express Fibulin-2, while BT483 and SK-BR-3 cells expressed Fibulin-2. Expression of Fibulin-2 mRNA and protein in SK-BR-3 Fibulin-2 siRNA group was significantly lower than that in SK-BR-3 NC siRNA group 48 h after transfection (P<0.01), while the expression of Fibulin-2 mRNA and protein in MDA-MB-231 Fibulin-2 lentiviral transfection (LAP) group was significantly higher than that in MDA-MB-231 NC LAP group. Compared with the MDA-MB-231 NC LAP group, the cell proliferation, migration and invasion ability of MDA-MB-231 Fibulin-2 LAP group were weakened. The tumor volume and weight of the MDA-MB-231 Fibulin-2 LAP group were significantly lower than those of the MDA-MB-231 NC LAP group. Low expression of Fibulin-2 is able to promote proliferation, migration and invasion of breast cancer cells, and can reduce the rate of tumor growth in nude mice. Therefore, Fibulin-2 may be a potential therapeutic target and an indicator of prognosis for breast cancer.

The automated harvesting of strawberry brings benefits such as reduced labor costs, sustainability, increased productivity, less waste, and improved use of natural resources. The accurate detection of strawberries in a greenhouse can be used to assist in the effective recognition and location of strawberries for the process of strawberry collection. Furthermore, being able to detect and characterize strawberries based on field images is an essential component in the breeding pipeline for the selection of high-yield varieties. The existing manual examination method is error-prone and time-consuming, which makes mechanized harvesting difficult. In this work, we propose a robust architecture, named "improved Faster-RCNN," to detect strawberries in ground-level RGB images captured by a self-developed "Large Scene Camera System." The purpose of this research is to develop a fully automatic detection and plumpness grading system for living plants in field conditions which does not require any prior information about targets. The experimental results show that the proposed method obtained an average fruit extraction accuracy of more than 86%, which is higher than that obtained using three other methods. This demonstrates that image processing combined with the introduced novel deep learning architecture is highly feasible for counting the number of, and identifying the quality of, strawberries from ground-level images. Additionally, this work shows that deep learning techniques can serve as invaluable tools in larger field investigation frameworks, specifically for applications involving plant phenotyping.

A fundamental question of physiology is how gut-brain signaling stimulates appetite. While many studies have emphasized the importance of vagal afferents to the brain in inducing satiation, little is known about whether and how the vagal-mediated gut-brain pathway senses orexigenic signals and stimulates feeding. Here, we identified a previously uncharacterized population of fasting-activated catecholaminergic neurons in the nucleus of the solitary tract (NTS). After characterizing the anatomical complexity among NTS catecholaminergic neurons, we surprisingly found that activation of NTS epinephrine (ENTS) neurons co-expressing neuropeptide Y (NPY) stimulated feeding, whereas activation of NTS norepinephrine (NENTS) neurons suppressed feeding. Monosynaptic tracing/activation experiments then showed that these NTS neurons receive direct vagal afferents from nodose neurons. Moreover, activation of the vagal→NPY/ENTS neural circuit stimulated feeding. Our study reveals an orexigenic role of the vagal→NTS pathway in controlling feeding, thereby providing important insights about how gut-brain signaling regulates feeding behavior.

Purpose: Lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths worldwide. Although tumor cell-T cell interactions are known to play a fundamental role in promoting tumor progression, these interactions have not been explored in LUAD. Methods: The 10x genomics single-cell RNA sequencing (scRNA-seq) and gene expression data of LUAD patients were obtained from ArrayExpress, TCGA, and GEO databases. scRNA-seq data were analyzed and infiltrating tumor cells, epithelial cells, and T cells were identified in the tumor microenvironment. Differentially expressed ligand-receptor pairs were identified in tumor cells/normal epithelial cells and tumor T cells/non-tumor T cells based on corresponding scRNA-seq and gene expression data, respectively. These important interactions inside/across cancer cells and T cells in LUAD were systematically analyzed. Furthermore, a valid prognostic machine-learning model based on ligand-receptor interactions was built to predict the prognosis of LUAD patients. Flow cytometry and qRT-PCR were performed to validate the significantly differently expressed ligand-receptor pairs. Results: Overall, 39,692 cells in scRNA-seq data were included in our study after quality filtering. A total of 65 ligand-receptor pairs (17 upregulated and 48 downregulated), including LAMB1-ITGB1, CD70-CD27, and HLA-B-LILRB2, and 96 ligand-receptor pairs (41 upregulated and 55 downregulated), including CCL5-CCR5, SELPLG-ITGB2, and CXCL13-CXCR5, were identified in LUAD cancer cells and T cells, respectively. To explore the crosstalk between cancer cells and T cells, 114 ligand-receptor pairs, including 11 ligand-receptor pair genes that could significantly affect survival outcomes, were identified in our research. A machine-learning model was established to accurately predict the prognosis of LUAD patients and ITGB4, CXCR5, and MET were found to play an important role in prognosis in our model. Flow cytometry and qRT-PCR analyses indicated the reliability of our study. Conclusion: Our study revealed functionally significant interactions within and between cancer cells and T cells. We believe these observations will improve our understanding of potential mechanisms of tumor microenvironment contributions to cancer progression and help identify potential targets for immunotherapy in the future.

Background: The association between NOD2/CARD15 (nucleotide binding oligomerisation domain containing 2) gene polymorphisms and susceptibility to sarcoidosis have been extensively investigated in recent years. However, the results from previous studies remain controversial. To assess the association of NOD2/CARD15 polymorphisms and sarcoidosis susceptibility, we performed a meta-analysis. Methods: PubMed, Embase, CNKI and Wanfang databases were examined for all relevant studies up until 8th October 2016. In all, 968 cases and 1549 controls in eight case-control studies were included which mainly consisted of Caucasian participants. The relevant data were extracted and the odds ratio (OR) with 95% confidence intervals (95% CI) calculated to assess the strength of any associations. Statistical analyses were calculated using STATA12.0 software and Revman5.3 software. The associations between NOD2/CARD15 SNP rs2066844, rs2066845, rs2066847, rs1861759 polymorphisms and the risk of sarcoidosis were evaluated in allelic, dominant, recessive and additive models. Results: The pooled data showed that the NOD2/CARD15 rs2066845 polymorphism was associated with sarcoidosis susceptibility in allelic model (C vs. G, OR=1.86, 95% CI: 1.14-3.04, P=0.01), dominant model (GC + CC vs. GG, OR=1.84, 95% CI: 1.11-3.05, P=0.02) and additive model (GC vs. GG, OR=1.79, 95% CI: 1.08-2.97, P=0.02). However, the results suggested that the rs2066844, rs2066847 and rs1861759 polymorphisms might not be associated with a risk of sarcoidosis. Conclusions: This meta-analysis indicated that the 'C' allele of SNP rs2066845 may be a risk factor for sarcoidosis, especially in Caucasians, whilst rs2066844, rs2066847 and rs1861759 may not be associated with a risk of developing sarcoidosis. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 115-122).

Targeting CD40 with agonist antibodies is a promising approach to cancer immunotherapy. CD40 acts as a master regulator of immunity by mobilizing multiple arms of the immune system to initiate highly effective CD8 + T-cell-mediated responses against foreign pathogens and tumors. The clinical development of CD40 agonist antibodies requires careful optimization of the antibody to maximize therapeutic efficacy while minimizing adverse effects. Both epitope specificity and isotype are critical for CD40 agonist antibody mechanism of action and potency. We developed a novel antibody, APX005M, which binds with high affinity to the CD40 ligand-binding site on CD40 and is optimized for selective interaction with Fcγ receptors to enhance agonistic potency while limiting less desirable Fc-effector functions like antibody-dependent cellular cytotoxicity of CD40-expressing immune cells. APX005M is a highly potent inducer of innate and adaptive immune effector responses and represents a promising CD40 agonist antibody for induction of an effective anti-tumor immune response with a favorable safety profile.

The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here we use high-throughput yeast display screening1,2 to determine the profiles of RBD escaping mutations for 247 human anti-RBD neutralizing antibodies and show that the neutralizing antibodies can be classified by unsupervised clustering into six epitope groups (A-F)-a grouping that is highly concordant with knowledge-based structural classifications3-5. Various single mutations of Omicron can impair neutralizing antibodies of different epitope groups. Specifically, neutralizing antibodies in groups A-D, the epitopes of which overlap with the ACE2-binding motif, are largely escaped by K417N, G446S, E484A and Q493R. Antibodies in group E (for example, S309)6 and group F (for example, CR3022)7, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but a subset of neutralizing antibodies are still escaped by G339D, N440K and S371L. Furthermore, Omicron pseudovirus neutralization showed that neutralizing antibodies that sustained single mutations could also be escaped, owing to multiple synergetic mutations on their epitopes. In total, over 85% of the tested neutralizing antibodies were escaped by Omicron. With regard to neutralizing-antibody-based drugs, the neutralization potency of LY-CoV016, LY-CoV555, REGN10933, REGN10987, AZD1061, AZD8895 and BRII-196 was greatly undermined by Omicron, whereas VIR-7831 and DXP-604 still functioned at a reduced efficacy. Together, our data suggest that infection with Omicron would result in considerable humoral immune evasion, and that neutralizing antibodies targeting the sarbecovirus conserved region will remain most effective. Our results inform the development of antibody-based drugs and vaccines against Omicron and future variants.

Colorectal cancer (CRC) has become the second deadliest cancer in the world and severely threatens human health. An increasing number of studies have focused on the role of the RNA helicase DEAD-box (DDX) family in CRC. However, the mechanism of DDX10 in CRC has not been elucidated.

Coronavirus disease 2019 (COVID-19), the result of infection by the SARS-CoV-2 virus, has caused a global pandemic. To respond to this outbreak rapidly and properly, clinical pharmacists in Shanghai Children's Hospital carried out innovative measures based on previous artificial intelligence experiences, such as using service robots for contactless drug delivery between Fever Clinic and Pharmacy Storage, providing telemedicine counseling on specific platforms and offering multimedia health education. With good control of the pandemic in Shanghai, these contactless services have been retained and expanded at the patients' request. The aim of this article is to share our strategies and efforts with peers who are fighting against COVID-19 in other countries and regions.

Low-temperature plasma, an engineered technology to generate various reactive species, is actively studied in cancer treatment in recent years, yet mainly by using a traditional 2D cell culture system. In this study, we explored the effect of the plasma-activated medium (PAM) on lung cancer cells in vitro and in vivo by using a 3D cell culture model. The results showed that PAM markedly inhibited 3D spheroid formation and downregulated stemness-related gene expression. We found that reactive oxygen species (ROS) penetrated throughout the whole spheroids and induced cell death surrounding and in the core of the tumor spheroid. Besides, PAM treatment suppressed migration and invasion of lung cancer cells and downregulated epithelial-mesenchymal transition- (EMT-) related gene expression. In the mouse xenograft model, the tumor volume was significantly smaller in the PAM-treated group compared with the control group. By using transcriptome sequencing, we found that PI3K/Akt and MAPK pathways were involved in the inhibition effects of PAM on lung cancer cells. Therefore, our results indicated that PAM exhibits potential anticancer effects on lung cancer and provides insight into further exploration of PAM-induced cell death and translational preclinical use.

Acquired and intrinsic radioresistance remains a major challenge during the treatment of patients with colorectal cancer (CRC). Aberrant cholesterol metabolism precipitates the development of multiple cancers. Here, we report that exogenous or endogenous cholesterol enhances the radioresistance of CRC cells. The addition of cholesterol protects CRC cells against irradiation both in vitro and in vivo. Sterol response element-binding protein 1/fatty acid synthase (SREBP1/FASN) signaling is rapidly increased in response to radiation stimuli, resulting in cholesterol accumulation, cell proliferation and inhibition of apoptosis. Blocking the SREBP1/FASN pathway impedes cholesterol synthesis and accelerates radiation-induced CRC cell death. Our findings provide novel insights into the role of the SREBP1/FASN/cholesterol axis in radiotherapy and suggest that it may be a potential target for CRC treatment. Clinically, our results suggest that CRC patients undergoing radiotherapy may benefit from a lowered cholesterol intake.

Our study aimed to validate pathologic findings of ground-glass nodules (GGOs) of different consolidation tumor ratios (CTRs), and to explore whether GGOs could be stratified according to CTR with an increment of 0.25 based on its prognostic role.

To establish a microsatellite instability (MSI) predictive model in pan-cancer and compare the multi-omics characterization of MSI-related molecular features.