The relationship between parental support for exercise and depression: The mediating effects of physical exercise and physical self-esteem.

The mental health challenges among Chinese college students have become a pressing social concern. This study examined the relationship between parental support for exercise and depression among freshmen and also explored the mediating role of physical exercise and physical self-esteem. Utilizing the Parental Exercise Support Scale, Depression Self-Rating Scale, Physical Activity Rating Scale, and Physical Self-Esteem Scale, a questionnaire survey was conducted. Convenient samples from two universities were recruited by university teachers, which included 766 university freshmen. Correlation and linear regression analyses were employed to assess the overall associations while bootstrapping method was used to test mediation effects. Results indicated significant correlations between parental support for exercise and physical exercise, physical self-esteem, and depression. Physical exercise and physical self-esteem were found to mediate the relationship between parental support for exercise and depression, both individually and sequentially. These findings highlight the potential association between parental support for exercise and the mental health of college freshmen and also offer a mechanism to understand this association.

Malignant transformation rate of oral leukoplakia in the past 20 years: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis aimed to assess the rate of malignant transformation (MT) of oral leukoplakia (OL) and to study potential risk factors for the MT of OL into oral squamous cell carcinoma (OSCC). METHOD: We performed a bibliographic search on nine electronic databases, including PubMed, MEDLINE, and Wanfang Data, for data on the MT rate of OL. Possible risk factors were calculated using Comprehensive Meta-Analysis and Open Meta [Analyst] software. RESULTS: The pooled proportion of OL MT for the total population described in the 26 selected studies was 7.20% (95% confidence interval: 5.40-9.10%). Nonhomogeneous type lesions, higher grades of dysplasia, the location of the lesion (tongue and multifocal), and female sex had significant effects on the MT of OL. CONCLUSION: OL tended to develop into OSCC (7.2%), and those with significant MT risk factors should be subjected to regular follow-up and observation. However, we require large-scale prospective studies to validate these results, together with unified clinicopathological diagnostic criteria, standardized risk factor recording/assessment methods, and long-term follow-up guidelines.

Special transcriptome landscape and molecular prognostic signature of non-smoking head and neck cancer patients.

As a well-known behavioral risk factor for human health, smoking is involved in carcinogenesis, tumor progression, and therapeutic interventions of head and neck squamous cell carcinoma (HNSCC). The stratification of disease subtypes according to tobacco use is expressively needed for HNSCC precision therapy. High-throughput transcriptome profiling by RNA sequencing (RNA-seq) from The Cancer Genome Atlas (TCGA) was collected and collated for differential expression analysis and pathway enrichment analysis to characterize the molecular landscape for non-smoking HNSCC patients. Molecular prognostic signatures specific to non-smoking HNSCC patients were identified by the least absolute shrinkage and selection operator (LASSO) analysis and were then verified via internal and external validation cohorts. While proceeding to immune cell infiltration and after drug sensitivity analysis was further carried out, a proprietary nomogram was finally developed for their respective clinical applications. In what it relates to the non-smoking cohort, the enrichment analysis pointed to human papillomavirus (HPV) infection and PI3K-Akt signaling pathway, with the prognostic signature consisting of another ten prognostic genes (COL22A1, ADIPOQ, RAG1, GREM1, APBA2, SPINK9, SPP1, ARMC4, C6, and F2RL2). These signatures showed to be independent factors, and the related nomograms were, thus, constructed for their further and respective clinical applications. While the molecular landscapes and proprietary prognostic signature were characterized based on non-smoking HNSCC patients, a clinical nomogram was constructed to provide better HNSCC patient classification and guide treatment for non-smoking HNSCC patients. Nonetheless, there are still significant challenges in the recognition, diagnosis, treatment, and understanding of the potentially efficient mechanisms of HNSCC with no tobacco use.

Identification of immunogenic cell death-associated subtypes and characterization of the tumor microenvironment in endometrial cancer.

Immunogenic cell death (ICD) is one of the mechanisms regulating cell death, which activates adaptive immunity in immunocompetent hosts and is associated with tumor progression, prognosis and therapeutic response. Endometrial cancer (EC) is one of the most common malignancies of the female genital tract, and the potential role of immunogenic cell death-related genes (IRGs) in the tumor microenvironment (TME) remains unclear. We describe the variation of IRGs and assess the expression patterns in EC samples from The Cancer Genome Atlas and Gene Expression Omnibus cohorts. Based on the expression of 34 IRGs, we identified two different ICD-related clusters and subsequently differentially expressed genes between the two ICD-related clusters were used for the identification of two ICD gene clusters. We identified the clusters and found that alterations in the multilayer IRG were associated with patient prognosis and TME cell infiltration characteristics. On this basis, ICD score risk scores were calculated, and ICD signatures were constructed and validated for their predictive power in EC patients. To help clinicians better apply the ICD signature, an accurate nomogram was constructed. The low ICD risk group was characterized by high microsatellite instability, high tumor mutational load, high IPS score and stronger immune activation. Our comprehensive analysis of IRGs in EC patients suggested a potential role in the tumor immune interstitial microenvironment, clinicopathological features and prognosis. These findings may improve our understanding of the role of ICDs, and provide a new basis for assessing prognosis and developing more effective immunotherapeutic strategies in EC.

Sensomics analysis of the effect of the withering method on the aroma components of Keemun black tea.

Withering is a key process that affects the aroma of Keemun black tea (KBT). In this study, the aroma composition of KBT through natural withering, sun withering, and warm-air withering was analysed using gas chromatography-mass spectrometry. The results revealed significant differences in the three samples. Gas chromatography-olfactometry and aroma extract dilution analysis were performed with screening through a relative odour activity value (rOAV) > 1. In total, 11 aroma-active compounds (geraniol, (Z)-4-heptenal, 1-octen-3-ol, (E)-ß-ionone, 3-methylbutanal, linalool, ß-damascenone, (E, E)-2,4-decadienal, methional, (E, E)-2,4-nonadienal, and (E)-2-nonenal) were found to be responsible for the differences in aroma caused by different withering methods. Linalool (rOAV, 161) and geraniol (rOAV, 785) were responsible for the higher flowery and fruity aromas when sun withering was applied, whereas methional (rOAV, 124) contributed to the intense roasty aroma when warm-air withering was employed. Moreover, our results were verified by quantitative descriptive analysis and addition experiments.

Construction of a ferroptosis scoring system and identification of LINC01572 as a novel ferroptosis suppressor in lung adenocarcinoma.

Background: Ferroptosis is a novel process of programmed cell death driven by excessive lipid peroxidation that is associated with the development of lung adenocarcinoma. N6-methyladenosine (m6a) modification of multiple genes is involved in regulating the ferroptosis process, while the predictive value of N6-methyladenosine- and ferroptosis-associated lncRNA (FMRlncRNA) in the prognosis of patients remains with LUAD remains unknown. Methods: Unsupervised cluster algorithm was applied to generate subcluster in LUAD according to ferroptosis-associated lncRNA. Stepwise Cox analysis and LASSO algorithm were applied to develop a prognostic model. Cellular location was detected by single-cell analysis. Also, we conducted Gene set enrichment analysis (GSEA) enrichment, immune microenvironment and drug sensitivity analysis. In addition, the expression and function of the LINC01572 were investigated by several in vitro experiments including qRT-PCR, cell viability assays and ferroptosis assays. Results: A novel ferroptosis-associated lncRNAs-based molecular subtype containing two subclusters were determined in LUAD. Then, we successfully created a risk model according to five ferroptosis-associated lncRNAs (LINC00472, MBNL1-AS1, LINC01572, ZFPM2-AS1, and TMPO-AS1). Our nominated model had good stability and predictive function. The expression patterns of five ferroptosis-associated lncRNAs were confirmed by polymerase chain reaction (PCR) in LUAD cell lines. Knockdown of LINC01572 significantly inhibited cell viability and induced ferroptosis in LUAD cell lines. Conclusion: Our data provided a risk score system based on ferroptosis-associated lncRNAs with prognostic value in LUAD. Moreover, LINC01572 may serve as a novel ferroptosis suppressor in LUAD.

Osteogenic inducer sustained-release system promotes the adhesion, proliferation, and differentiation of osteoblasts on titanium surface.

OBJECTIVE: Biomaterial can be locally applied to promote the osseointegration of dental implants. This study aimed to fabricate an osteogenic inducer (OI) sustained-release system and to evaluate its effects on the adhesion, proliferation, and differentiation of osteoblasts on titanium surfaces. METHODS: First of all, different contents of OI solution were added to the poly (lactic-co-glycolic acid) (PLGA) gel individually to investigate the best physical properties and drug-release rate. Moreover, osteoblasts were isolated from the calvaria of two-month-old New Zealand rabbits through sequential enzymatic digestion. Osteoblasts were seeded onto the surface of Ti disks (control group), Ti coated with PLGA gel (PLGA group), and Ti coated with the OI sustained-release system (PLGA+OI group). Cell adhesion was observed by scanning electron microscopy. Cell proliferation was analyzed by cell counting kit-8. Cell differentiation was tested by alizarin red staining, alkaline phosphatase (ALP) activity and osteogenic-related gene expression. RESULTS: The OI sustained-release system contained 15% OI solution had appropriate physical properties and drug-release rate. The osteoblasts in the PLGA+OI group were in a typical spindle shape with a considerable number indicating the promotion of adhesion and proliferation. The expression of early and late stage osteoblast differentiation genes in the PLGA+OI group were significantly higher than that of the control group and PLGA group at each time point. The PLGA group showed accelerated adhesion and differentiation but reduced proliferation compared with the control. CONCLUSION: The OI sustained-release system promotes the adhesion, proliferation, and differentiation of osteoblasts on titanium surfaces. This system is a cost-effective osteoconductive biomaterial that might be promising for use in dental implantation.

Ameliorating the Metabolic Burden of the Co-expression of Secreted Fungal Cellulases in a High Lipid-Accumulating Yarrowia lipolytica Strain by Medium C/N Ratio and a Chemical Chaperone.

Yarrowia lipolytica, known to accumulate lipids intracellularly, lacks the cellulolytic enzymes needed to break down solid biomass directly. This study aimed to evaluate the potential metabolic burden of expressing core cellulolytic enzymes in an engineered high lipid-accumulating strain of Y. lipolytica. Three fungal cellulases, Talaromyces emersonii-Trichoderma reesei chimeric cellobiohydrolase I (chimeric-CBH I), T. reesei cellobiohydrolase II (CBH II), and T. reesei endoglucanase II (EG II) were expressed using three constitutive strong promoters as a single integrative expression block in a recently engineered lipid hyper-accumulating strain of Y. lipolytica (HA1). In yeast extract-peptone-dextrose (YPD) medium, the resulting cellulase co-expressing transformant YL165-1 had the chimeric-CBH I, CBH II, and EG II secretion titers being 26, 17, and 132 mg L-1, respectively. Cellulase co-expression in YL165-1 in culture media with a moderate C/N ratio of ∼4.5 unexpectedly resulted in a nearly two-fold reduction in cellular lipid accumulation compared to the parental control strain, a sign of cellular metabolic drain. Such metabolic drain was ameliorated when grown in media with a high C/N ratio of 59 having a higher glucose utilization rate that led to approximately twofold more cell mass and threefold more lipid production per liter culture compared to parental control strain, suggesting cross-talk between cellulase and lipid production, both of which involve the endoplasmic reticulum (ER). Most importantly, we found that the chemical chaperone, trimethylamine N-oxide dihydride increased glucose utilization, cell mass and total lipid titer in the transformants, suggesting further amelioration of the metabolic drain. This is the first study examining lipid production in cellulase-expressing Y. lipolytica strains under various C/N ratio media and with a chemical chaperone highlighting the metabolic complexity for developing robust, cellulolytic and lipogenic yeast strains.

Longitudinal PET imaging demonstrates biphasic CAR T cell responses in survivors.

Clinical monitoring of adoptive T cell transfer (ACT) utilizes serial blood analyses to discern T cell activity. While useful, these data are 1-dimensional and lack spatiotemporal information related to treatment efficacy or toxicity. We utilized a human genetic reporter, somatostatin receptor 2 (SSTR2), and PET, to quantitatively and longitudinally visualize whole-body T cell distribution and antitumor dynamics using a clinically approved radiotracer. Initial evaluations determined that SSTR2-expressing T cells were detectable at low densities with high sensitivity and specificity. SSTR2-based PET was applied to ACT of chimeric antigen receptor (CAR) T cells targeting intercellular adhesion molecule-1, which is overexpressed in anaplastic thyroid tumors. Timely CAR T cell infusions resulted in survival of tumor-bearing mice, while later infusions led to uniform death. Real-time PET imaging revealed biphasic T cell expansion and contraction at tumor sites among survivors, with peak tumor burden preceding peak T cell burden by several days. In contrast, nonsurvivors displayed unrelenting increases in tumor and T cell burden, indicating that tumor growth was outpacing T cell killing. Thus, longitudinal PET imaging of SSTR2-positive ACT dynamics enables prognostic, spatiotemporal monitoring with unprecedented clarity and detail to facilitate comprehensive therapy evaluation with potential for clinical translation.

novel modifications on C-terminal domain of RNA polymerase II can fine-tune the phosphatase activity of Ssu72.

The C-terminal domain of RNA polymerase II (CTD) modulates the process of transcription through sequential phosphorylation/dephosphorylation of its heptide repeats, through which it recruits various transcription regulators. Ssu72 is the first characterized cis-specific CTD phosphatase that dephosphorylates Ser5 with a requirement for the adjacent Pro6 in a cis conformation. The recent discovery of Thr4 phosphorylation in the CTD calls into question whether such a modification can interfere with Ssu72 binding via the elimination of a conserved intramolecular hydrogen bond in the CTD that is potentially essential for recognition. To test if Thr4 phosphorylation will abolish Ser5 dephosphorylation by Ssu72, we determined the kinetic and structural properties of Drosophila Ssu72-symplekin in complex with the CTD peptide with consecutive phosphorylated Thr4 and Ser5. Our mass spectrometric and kinetic data established that Ssu72 does not dephosphorylate Thr4, but the existence of phosphoryl-Thr4 next to Ser5 reduces the activity of Ssu72 toward the CTD peptide by 4-fold. To our surprise, even though the intramolecular hydrogen bond is eliminated due to the phosphorylation of Thr4, the CTD adopts an almost identical conformation to be recognized by Ssu72 with Ser5 phosphorylated alone or both Thr4/Ser5 phosphorylated. Our results indicate that Thr4 phosphorylation will not abolish the essential Ssu72 activity, which is needed for cell survival. Instead, the phosphatase activity of Ssu72 is fine-tuned by Thr4 phosphorylation and eventually may lead to changes in transcription. Overall, we report the first case of structural and kinetic effects of phosphorylated Thr4 on CTD modifying enzymes. Our results support a model in which a combinatorial cascade of CTD modification can modulate transcription.

Structural and kinetic analysis of prolyl-isomerization/phosphorylation cross-talk in the CTD code.

The C-terminal domain (CTD) of eukaryotic RNA polymerase II is an essential regulator for RNA polymerase II-mediated transcription. It is composed of multiple repeats of a consensus sequence Tyr(1)Ser(2)Pro(3)Thr(4)Ser(5)Pro(6)Ser(7). CTD regulation of transcription is mediated by both phosphorylation of the serines and prolyl isomerization of the two prolines. Interestingly, the phosphorylation sites are typically close to prolines, and thus the conformation of the adjacent proline could impact the specificity of the corresponding kinases and phosphatases. Experimental evidence of cross-talk between these two regulatory mechanisms has been elusive. Pin1 is a highly conserved phosphorylation-specific peptidyl-prolyl isomerase (PPIase) that recognizes the phospho-Ser/Thr (pSer/Thr)-Pro motif with CTD as one of its primary substrates in vivo. In the present study, we provide structural snapshots and kinetic evidence that support the concept of cross-talk between prolyl isomerization and phosphorylation. We determined the structures of Pin1 bound with two substrate isosteres that mimic peptides containing pSer/Thr-Pro motifs in cis or trans conformations. The results unequivocally demonstrate the utility of both cis- and trans-locked alkene isosteres as close geometric mimics of peptides bound to a protein target. Building on this result, we identified a specific case in which Pin1 differentially affects the rate of dephosphorylation catalyzed by two phosphatases (Scp1 and Ssu72) that target the same serine residue in the CTD heptad repeat but have different preferences for the isomerization state of the adjacent proline residue. These data exemplify for the first time how modulation of proline isomerization can kinetically impact signal transduction in transcription regulation.

Tracking dynamics of plant biomass composting by changes in substrate structure, microbial community, and enzyme activity.

BACKGROUND: Understanding the dynamics of the microbial communities that, along with their secreted enzymes, are involved in the natural process of biomass composting may hold the key to breaking the major bottleneck in biomass-to-biofuels conversion technology, which is the still-costly deconstruction of polymeric biomass carbohydrates to fermentable sugars.However, the complexity of both the structure of plant biomass and its counterpart microbial degradation communities makes it difficult to investigate the composting process. RESULTS: In this study, a composter was set up with a mix of yellow poplar (Liriodendron tulipifera) wood-chips and mown lawn grass clippings (85:15 in dry-weight) and used as a model system. The microbial rDNA abundance data obtained from analyzing weekly-withdrawn composted samples suggested population-shifts from bacteria-dominated to fungus-dominated communities. Further analyses by an array of optical microscopic, transcriptional and enzyme-activity techniques yielded correlated results, suggesting that such population shifts occurred along with early removal of hemicellulose followed by attack on the consequently uncovered cellulose as the composting progressed. CONCLUSION: The observed shifts in dominance by representative microbial groups, along with the observed different patterns in the gene expression and enzymatic activities between cellulases, hemicellulases, and ligninases during the composting process, provide new perspectives for biomass-derived biotechnology such as consolidated bioprocessing (CBP) and solid-state fermentation for the production of cellulolytic enzymes and biofuels.

Structure of CBM4 from Clostridium thermocellum cellulase K.

Here, a 2.0 Å resolution X-ray structure of Clostridium thermocellum cellulase K family 4 carbohydrate-binding module (CelK CBM4) is reported. The resulting structure was refined to an R factor of 0.212 and an R(free) of 0.274. Structural analysis shows that this new structure is very similar to the previously solved structure of C. thermocellum CbhA CBM4. Most importantly, these data support the previously proposed notion of an extended binding pocket using a novel tryptophan-containing loop that may be highly conserved in clostridial CBM4 proteins.

In situ imaging of single carbohydrate-binding modules on cellulose microfibrils.

The low efficiency of enzymes used in the bioprocessing of biomass for biofuels is one of the primary bottlenecks that must be overcome to make lignocellulosic biofuels cost-competitive. One of the rate-limiting factors is the accessibility of the cellulase enzymes to insoluble cellulolytic substrates, facilitated by surface absorption of the carbohydrate-binding modules (CBMs), a component of most cellulase systems. Despite their importance, reports of direct observation of CBM function and activity using microscopic methods are still uncommon. Here, we examine the site-specific binding of individual CBMs to crystalline cellulose in an aqueous environment, using the single molecule fluorescence method known as Defocused Orientation and Position Imaging (DOPI). Systematic orientations were observed that are consistent with the CBMs binding to the two opposite hydrophobic faces of the cellulose microfibril, with a well-defined orientation relative to the fiber axis. The approach provides in situ physical evidence indicating the CBMs bind with a well-defined orientation on those planes, thus supporting a binding mechanism driven by chemical and structural recognition of the cellulose surface.