LASP-1 is an actin-binding protein that regulates cytoskeletal dynamics and cell migration. LASP-1 was previously identified in a cDNA library from metastatic breast cancer samples. This protein has since been detected in multiple human cancers, including liver cancer, gastric cancer and pancreatic cancer. S100P is a small calcium-binding protein in the S100 protein family that regulates cellular, physiological and pathological processes in various cancers. However, the clinical significance of LASP-1 and S100P expression in gallbladder cancer (GBC) is not yet clear. In our study, we focused on the clinical significance, biological function and mechanism of LASP-1 in gallbladder cancer and detected LASP-1 and S100P overexpression in GBC tissues. The expression of LASP-1 was significantly correlated with poor prognosis in GBC patients (P < 0.05). Furthermore, down-regulation of LASP-1 expression resulted in the obvious inhibition of proliferation and migration and caused cell cycle arrest by down-regulating S100P via the PI3K/AKT pathway; in mice, tumor volume was significantly decreased. In conclusion, LASP-1 may act as an oncogene to regulate the expression of S100P to influence cellular functions in GBC. LASP-1 could serve as a genetic treatment target in GBC patients.

Epidural fibrosis is a common complication after laminectomy. It is associated with intractable lower back pain and additional complications. To date, no study has evaluated whether the local application of rapamycin (RAPA) can inhibit fibroblast proliferation and reduce epidural scar adhesion after laminectomy. The results of the present study showed that the local application of RAPA reduces epidural fibrosis after laminectomy in rats.

Perfect and low cost of fungal amylolytic and cellulolytic enzymes are prerequisite for the industrialization of plant biomass biorefinergy to biofuels. Genetic engineering of fungal strains based on regulatory network of transcriptional factors (TFs) and their targets is an efficient strategy to achieve the above described aim. Talaromyces pinophilus produces integrative amylolytic and cellulolytic enzymes; however, the regulatory mechanism associated with the expression of amylase and cellulase genes in T. pinophilus remains unclear. In this study, we screened for and identified novel TFs regulating amylase and/or cellulase gene expression in T. pinophilus 1-95 through comparative transcriptomic and genetic analyses.

Raw-starch-digesting glucoamylases (RSDGs) from filamentous fungi have great commercial values in starch processing; however, the regulatory mechanisms associated with their production in filamentous fungi remain unknown. Penicillium oxalicum HP7-1 isolated by our laboratory secretes RSDG with suitable properties but at low production levels. Here, we screened and identified novel regulators of RSDG gene expression in P. oxalicum through transcriptional profiling and genetic analyses.

Recently, several studies suggested that PPARG c.1347C>T polymorphism was correlated with cancer risk. However, past results remained controversial. In this study, we performed a case-control study on the relationship of PPARG c.1347C>T polymorphism with risk of non-small cell lung cancer (NSCLC) and subsequently carried out a meta-analysis to further assess the association between PPARG c.1347C>T and overall cancer. In our case-control study, after adjusting by age, sex, body mass index (BMI), smoking and drinking, a tendency to increased NSCLC risk was noted (CT/TT vs. CC: adjusted OR, 1.21; 95% CI, 0.97-1.51; P = 0.097). In the meta-analysis, we found a significant association between PPARG c.1347C>T polymorphism and overall cancer risk (T vs. C: OR, 1.13; 95% CI, 1.03-1.23; P = 0.006; TT vs. CC: OR, 1.29; 95% CI, 1.07-1.56; P = 0.008, CT/TT vs. CC: OR, 1.11; 95% CI, 1.02-1.21; P = 0.014 and TT vs.

Hypoxia-inducible factor prolyl 4-hydroxylases (HIF-PHDs) are important targets against oxidative stress. We hypothesized that inhibition HIF-PHD by adaptaquin reduces hypoxic-ischemic brain injury in a neonatal mouse model. The pups were treated intraperitoneally immediately with adaptaquin after hypoxia-ischemia (HI) and then every 24 h for 3 days. Adaptaquin treatment reduced infarction volume by an average of 26.3% at 72 h after HI compared to vehicle alone, and this reduction was more pronounced in males (34.8%) than in females (11.7%). The protection was also more pronounced in the cortex. The subcortical white matter injury as measured by tissue loss volume was reduced by 24.4% in the adaptaquin treatment group, and this reduction was also more pronounced in males (28.4%) than in females (18.9%). Cell death was decreased in the cortex as indicated by Fluoro-Jade labeling, but not in other brain regions with adaptaquin treatment. Furthermore, in the brain injury area, adaptaquin did not alter the number of cells positive for caspase-3 activation or translocation of apoptosis-inducing factor to the nuclei. Adaptaquin treatment increased glutathione peroxidase 4 mRNA expression in the cortex but had no impact on 3-nitrotyrosine, 8-hydroxy-2 deoxyguanosine, or malondialdehyde production. Hif1α mRNA expression increased after HI, and adaptaquin treatment also stimulated Hif1α mRNA expression, which was also more pronounced in males than in females. However, nuclear translocation of HIF1α protein was decreased after HI, and adaptaquin treatment had no influence on HIF1α expression in the nucleus. These findings demonstrate that adaptaquin treatment is neuroprotective, but the potential mechanisms need further investigation. Read the Editorial Highlight for this article on page 645.

Soil ascomycete fungi produce plant-biomass-degrading enzymes to facilitate nutrient and energy uptake in response to exogenous stress. This is controlled by a complex signal network, but the regulatory mechanisms are poorly understood. An essential Zn2Cys6 transcription factor (TF) PoxCxrA was identified to be required for cellulase and xylanase production in Penicillium oxalicum. The genome-wide regulon and DNA binding sequences of PoxCxrA were further identified through RNA-Sequencing, DNase I footprinting experiments and in vitro electrophoretic mobility shift assays. Moreover, a minimal DNA-binding domain in PoxCxrA was recognised.

The aim of this case-control study was to assess the relationship between the tagging polymorphisms in methylenetetrahydrofolate reductase (MTHFR) gene and the susceptibility to colorectal cancer (CRC) in a Chinese Han population. A custom-by-design 48-Plex SNPscan Kit was used to determine the genotypes of MTHFR rs3753584 T>C, rs9651118 T>C, rs1801133 G>A, rs4846048 A>G and rs4845882 G>A polymorphisms in 387 CRC patients and 1,536 non-cancer controls. The results revealed that MTHFR rs1801133 G>A polymorphism was associated with a decreased risk of overall CRC. While MTHFR rs4845882 G>A polymorphism conferred an increased risk to overall CRC. In a stratified analysis by CRC region, we found MTHFR rs3753584 T>C and rs9651118 T>C polymorphisms were associated with the increased risk of colon cancer. In addition, a significantly increased risk of rectum cancer associated with MTHFR rs3753584 T>C polymorphism was overt. However, MTHFR rs1801133 G>A polymorphism conferred a decreased risk to colon cancer. In conclusion, findings of the present study reveal that the tagging polymorphisms in MTHFR gene (rs3753584 T>C, rs9651118 T>C and rs4845882 G>A) are associated with the increased risk of CRC. However, MTHFR rs1801133 G>A polymorphism confers a decreased risk to CRC. Additional studies with larger sample size are needed to confirm these findings.

Chemical modifications on histones constitute a key mechanism for gene regulation in chromatin context. Recently, histone lysine β-hydroxybutyrylation (Kbhb) was identified as a new form of histone acylation that connects starvation-responsive metabolism to epigenetic regulation. Sirtuins are a family of NAD+-dependent deacetylases. Through systematic profiling studies, we show that human SIRT3 displays class-selective histone de-β-hydroxybutyrylase activities with preference for H3 K4, K9, K18, K23, K27, and H4K16, but not for H4 K5, K8, K12, which distinguishes it from the Zn-dependent HDACs. Structural studies revealed a hydrogen bond-lined hydrophobic pocket favored for the S-form Kbhb recognition and catalysis. β-backbone but not side chain-mediated interactions around Kbhb dominate sequence motif recognition, explaining the broad site-specificity of SIRT3. The observed class-selectivity of SIRT3 is due to an entropically unfavorable barrier associated with the glycine-flanking motif that the histone Kbhb resides in. Collectively, we reveal the molecular basis for class-selective histone de-β-hydroxybutyrylation by SIRT3, shedding lights on the function of sirtuins in Kbhb biology through hierarchical deacylation.

It has been reported that peroxisome proliferator-activated receptor gamma (PPARG) and peroxisome proliferator-activated receptor gamma co-activator 1 (PPARGC1) family (e.g. PPARGC1A and PPARGC1B) are key agents in the development and pathophysiology of type 2 diabetes mellitus (T2DM). In this study, we designed a case-control study and selected PPARG rs1801282 C>G, PPARG rs3856806 C>T, PPARGC1A rs8192678 C>T, PPARGC1A rs2970847 C>T, PPARGC1A rs3736265 G>A, PPARGC1B rs7732671 G>C and PPARGC1B rs17572019 G>A polymorphisms to assess the relationship between these polymorphisms and T2DM using the SNPscan method. A total of 502 T2DM patients and 784 non-diabetic controls were enrolled. We found that PPARGC1A rs3736265 G>A polymorphism was correlated with a borderline decreased susceptibility of T2DM. In a subgroup analysis by age, sex, alcohol use, smoking status and body mass index, a significantly decreased risk of T2DM in <65 years and female groups was found. Haplotype comparison analysis indicated that CTTCGGG and CTCTGGG haplotypes with the order of PPARG rs1801282 C>G, PPARG rs3856806 C>T, PPARGC1A rs8192678 C>T, PPARGC1A rs2970847 C>T, PPARGC1A rs3736265 G>A, PPARGC1B rs7732671 G>C and PPARGC1B rs17572019 G>A polymorphisms in gene position significantly increased the risk of T2DM. However, CCCCACA haplotype conferred a decreased risk to T2DM. We also found that PPARGC1A rs3736265 A allele decreased the level of fasting plasma glucose (FPG), while increased the level of Triglyceride. In conclusion, Our findings suggest that variants of PPARGC1A rs3736265 G>A polymorphism decrease the level of FPG, improving the expectation of study in individual's prevention strategies to T2DM.

The objective of this case-control study was to extensively explore the relationship of Cytotoxic T-lymphocyte antigen-4 (CTLA-4) tagging polymorphisms with susceptibility to non-small-cell lung cancer (NSCLC). We recruited 521 sporadic NSCLC cases and 1,030 non-cancer controls. The genotypes of CTLA-4 rs16840252 C>T, rs231775 G>A, rs3087243 G>A and rs733618 T>C polymorphisms were evaluated using a custom-by-design 48-Plex SNPscan Kit. Our findings revealed there was no statistically significant difference in CTLA-4 genotypes distribution among NSCLC patients and non-cancer controls. Similar findings were observed in the logistic regression analyses. However, the stratified analyses suggested CTLA-4 rs733618 vatiants were correlated with the development of NSCLC in ≥ 60 years subgroup (TC vs. TT: adjusted OR = 1.45, 95% CI = 1.04-2.02, P = 0.030) and even drinking subgroup (TC vs. TT: adjusted OR = 2.27, 95% CI = 1.11-4.60, P = 0.024 and TC/CC vs. TT: adjusted OR = 2.26, 95% CI = 1.15-4.43, P = 0.018). In conclusion, the present case-control study highlights that the CTLA-4 rs733618 T>C polymorphism was associated with the development of NSCLC in ≥ 60 years and even drinking subgroups. A fine-mapping study with functional assessment is necessary to confirm or refute our findings.

To evaluate the effects of group counseling programs, cognitive behavioral therapy (CBT), and sports intervention on Internet addiction (IA), a systematic search in ten databases was performed to identify eligible studies without language restrictions up to January 2017. A meta-analysis and trial sequential analysis (TSA) was performed, respectively. A total of 58 randomized controlled trials (RCTs), which included 2871 participants, were incorporated into our meta-analysis. The results showed that group counseling programs, CBT, and sports intervention could significantly reduce IA levels (group counseling program: standardized mean difference (SMD), -1.37; 95% confidence interval (CI), -1.89 to -0.85; CBT: SMD, -1.88; 95% CI, -2.53 to -1.23; sports intervention: SMD, -1.70; 95% CI, -2.14 to -1.26). For group counseling programs, this treatment was more effective in four dimensions of IA, including time management, interpersonal and health issues, tolerance, and compulsive Internet use. For CBT, this treatment yielded a positive change in depression, anxiousness, aggressiveness, somatization, social insecurity, phobic anxiety, paranoid ideation, and psychoticism. For sports intervention, the significant effects were also observed in all dimensions of the IA scale. Each of group counseling programs, cognitive behavioral therapy, and sports intervention had a significant effect on IA and psychopathological symptoms. Sports intervention could improve withdrawal symptoms especially.

Background: Suspected non-Alzheimer disease pathophysiology (SNAP) refers to the subjects who feature negative β-amyloid (Aβ) but positive tau or neurodegeneration biomarkers. It accounts for a quarter of the elderly population and is associated with cognitive decline. However, the underlying pathophysiology is still unclear. Methods: We included 111 non-demented subjects, then classified them into three groups using cerebrospinal fluid (CSF) Aβ 1-42 (A), phosphorylated tau 181 (T), and total tau (N). Specifically, we identified the normal control (NC; subjects with normal biomarkers, A-T-N-), SNAP (subjects with normal amyloid but abnormal tau, A-T+), and predementia Alzheimer's disease (AD; subjects with abnormal amyloid and tau, A+T+). Then, we used the static amplitude of low-frequency fluctuation (sALFF) and dynamic ALFF (dALFF) variance to reflect the intrinsic functional network strength and stability, respectively. Further, we performed a correlation analysis to explore the possible relationship between intrinsic brain activity changes and cognition. Results: SNAP showed decreased sALFF in left superior frontal gyrus (SFG) while increased sALFF in left insula as compared to NC. Regarding the dynamic metric, SNAP showed a similarly decreased dALFF in the left SFG and left paracentral lobule as compared to NC. By contrast, when compared to NC, predementia AD showed decreased sALFF in left inferior parietal gyrus (IPG) and right precuneus, while increased sALFF in the left insula, with more widely distributed decreased dALFF variance across the frontal, parietal and occipital lobe. When directly compared to SNAP, predementia AD showed decreased sALFF in left middle occipital gyrus and IPG, while showing decreased dALFF variance in the left temporal pole. Further correlation analysis showed that increased sALFF in the insula had a negative correlation with the general cognition in the SNAP group. Besides, sALFF and dALFF variance in the right precuneus negatively correlated with attention in the predementia AD group. Conclusion: SNAP and predementia AD show distinct functional impairment patterns. Specifically, SNAP has functional impairments that are confined to the frontal region, which is usually spared in early-stage AD, while predementia AD exhibits widely distributed functional damage involving the frontal, parietal and occipital cortex.

Cerebral malaria (CM) is a life-threatening diffuse encephalopathy caused by Plasmodium falciparum, in which the destruction of the blood-brain barrier (BBB) is the main cause of death. However, increasing evidence has shown that antimalarial drugs, the current treatment for CM, do little to protect against CM-induced BBB damage. Therefore, a means to alleviate BBB dysfunction would be a promising adjuvant therapy for CM. The adhesion molecule CD146 has been reported to be expressed in both endothelial cells and proinflammatory immune cells and mediates neuroinflammation. Here, we demonstrate that CD146 expressed on BBB endothelial cells but not immune cells is a novel therapeutic target in a mouse model of experimental cerebral malaria (eCM). Endothelial CD146 is upregulated during eCM development and facilitates the sequestration of infected red blood cells (RBCs) and/or proinflammatory lymphocytes in CNS blood vessels, thereby promoting the disruption of BBB integrity. Mechanistic studies showed that the interaction of CD146 and Galectin-9 contributes to the aggregation of infected RBCs and lymphocytes. Deletion of endothelial CD146 or treatment with the anti-CD146 antibody AA98 prevents severe signs of eCM, such as limb paralysis, brain vascular leakage, and death. In addition, AA98 combined with the antiparasitic drug artemether improved the cognition and memory of mice with eCM. Taken together, our findings suggest that endothelial CD146 is a novel and promising target in combination with antiparasitic drugs for future CM therapies.

Hemicelluloses are effective renewable biopolymers that can be used in many different industrial processes and preparations. In plants, the content of hemicellulose might change with different developmental stages and/or tissues. Thus, in here chemical and structural differences in hemicellulose isolated from the apical, middle and basal segments of sugarcane stem were characterized using chemical techniques. Further, difference in expression levels of genes related to synthesis of hemicelluloses from these three segments were studied by RNA-seq and qRT-PCR etc. The sugarcane hemicellulose backbone was xylose residues connected via β-1,4 glycosidic linkages which was further substituted with arabinose, acetyl and glucuronic acid side chains. Hemicellulose content was higher in the middle and basal segments with less backbone substitutions compared to apical segments. In terms of gene expression, hemicellulose synthesis and modification genes were intensely expressed in middle and basal segments. Taken together, our research describes differences in hemicellulose content and substitutions in sugarcane during xylogenesis, which will increase our knowledge for finding more refined use of sugarcane bagasse.

Statistical data on the burden and relevant risk factors of lung cancer are valuable for policy-making. This study aimed to compare the mortality of lung cancer attributable to smoking stratified by sex and age among adults in China and the United States (US).

The relationship between kidney function and hearing loss has long been recognized, but evidence of this association mostly comes from small observational studies or other populations. The aim of this study is to explore the association between reduced kidney function and hearing loss in a large population-based study among the middle-aged and elderly Chinese.

Adding alkaline into an anaerobic waste activated sludge (WAS) fermentation with thermophilic bacteria pretreatment could efficiently improve short-chain fatty acids (SCFAs) accumulation to 3550 ± 120 mg COD/L. The acidification rate in combined test was 21.2%, while that was 15.6% and 10.7% in sole thermophilic bacteria pretreatment and control tests respectively. Four distinct groups of microbes could be identified with noticeable shifts using the combined pretreatments, and tremendous effects were analyzed on organic content especially of the soluble proteins and SCFAs concentrations. Particularly, alkaline addition would significantly change the functional microbial structures, including the decrease of Caloramator with the function of thermophilic proteolytic and the increase of Acidobacteria TM7 and Petrimonas sp. The results above suggested that alkaline addition could decrease the hydrolytic substances consume by thermotolerance bacteria and final improve SCFAs accumulation in fermentation process.

The aim of the present study was to prevent cross-infection in the operating room during emergency procedures for patients with confirmed or suspected 2019 novel coronavirus (2019-nCoV) by following anesthesia management protocols, and to document clinical- and anesthesia-related characteristics of these patients.

Limited information on transcription factor (TF)-mediated regulation exists for most filamentous fungi, specifically for regulation of the production of plant-biomass-degrading enzymes (PBDEs). The filamentous fungus, Talaromyces pinophilus, can secrete integrative cellulolytic and amylolytic enzymes, suggesting a promising application in biotechnology. In the present study, the regulatory roles of a Zn2Cys6 protein, TP05746, were investigated in T. pinophilus through the use of biochemical, microbiological and omics techniques. Deletion of the gene TP05746 in T. pinophilus led to a 149.6% increase in soluble-starch-degrading enzyme (SSDE) production at day one of soluble starch induction but an approximately 30% decrease at days 2 to 4 compared with the parental strain ΔTpKu70. In contrast, the T. pinophilus mutant ΔTP05746 exhibited a 136.8-240.0% increase in raw-starch-degrading enzyme (RSDE) production, as well as a 90.3 to 519.1% increase in cellulase and xylanase production following induction by culturing on wheat bran plus Avicel, relative to that exhibited by ΔTpKu70. Additionally, the mutant ΔTP05746 exhibited accelerated mycelial growth at the early stage of cultivation and decreased conidiation. Transcriptomic profiling and real-time quantitative reverse transcription-PCR (RT-qPCR) analyses revealed that TP05746 dynamically regulated the expression of genes encoding major PBDEs and their regulatory genes, as well as fungal development-regulated genes. Furthermore, in vitro binding experiments confirmed that TP05746 bound to the promoter regions of the genes described above. These results will contribute to our understanding of the regulatory mechanism of PBDE genes and provide a promising target for genetic engineering for improved PBDE production in filamentous fungi.