The expression characteristics and clinical significance of ACP6, a potential target of nitidine chloride, in hepatocellular carcinoma.

BACKGROUND: Acid phosphatase type 6 (ACP6) is a mitochondrial lipid phosphate phosphatase that played a role in regulating lipid metabolism and there is still blank in the clinico-pathological significance and functional roles of ACP6 in human cancers. No investigations have been conducted on ACP6 in hepatocellular carcinoma (HCC) up to date. METHODS: Herein, we appraised the clinico-pathological significance of ACP6 in HCC via organizing expression profiles from globally multi-center microarrays and RNA-seq datasets. The molecular basis of ACP6 in HCC was explored through multidimensional analysis. We also carried out in vitro and in vivo experiment on nude mice to investigate the effect of knocking down ACP6 expression on biological functions of HCC cells, and to evaluate the expression variance of ACP6 in xenograft of HCC tissues before and after the treatment of NC. RESULTS: ACP6 displayed significant overexpression in HCC samples (standard mean difference (SMD) = 0.69, 95% confidence interval (CI) = 0.56-0.83) and up-regulated ACP6 performed well in screening HCC samples from non-cancer liver samples. ACP6 expression was also remarkably correlated with clinical progression and worse overall survival of HCC patients. There were close links between ACP6 expression and immune cells including B cells, CD8 + T cells and naive CD4 + T cells. Co-expressed genes of ACP6 mainly participated in pathways including cytokine-cytokine receptor interaction, glucocorticoid receptor pathway and NABA proteoglycans. The proliferation and migration rate of HCC cells transfected with ACP6 siRNA was significantly suppressed compared with those transfected with negative control siRNA. ACP6 expression was significantly inhibited by nitidine chloride (NC) in xenograft HCC tissues. CONCLUSIONS: ACP6 expression may serve as novel clinical biomarker indicating the clinical development of HCC and ACP6 might be potential target of anti-cancer effect by NC in HCC.

Epidermal growth factor receptor mutation p.A864V in small cell lung cancer and lung squamous cell carcinoma: a case report and review of literature.

Mutations in the epidermal growth factor receptor ( EGFR ) have been identified in 10-20% of nonsmall cell lung cancer (NSCLC), specifically lung adenocarcinomas. However, these mutations have rarely been reported in small cell lung cancer (SCLC) and lung squamous cell carcinoma (LUSC). Treatment for SCLC and LUSC patients has not yet been established. We present a rare case of p.A864V mutation in Exon 21 of EGFR gene in a patient with both SCLC and LUSC, which is the first case of such mutation type in lung cancer in the world. The patient was a 55-year-old female nonsmoker with stage IV SCLC and LUSC, gene sequencing revealed EGFR gene mutation, she refused EGFR tyrosine kinase inhibitors (TKIs) targeted therapy and received conservative treatment, which led to disease progression. In conclusion, clinicians should be aware of the possibility of the rare EGFR mutations. Platinum-based chemotherapy can be treated for SCLC and LUSC patients.

Retrospective analysis of LNM risk factors and the effect of chemotherapy in early colorectal cancer: A Chinese multicenter study.

BACKGROUND: Estimating the risk of lymph node metastasis (LNM) is crucial for determining subsequent treatments following curative resection of early colorectal cancer (ECC). This multicenter study analyzed the risk factors of LNM and the effectiveness of postoperative chemotherapy in patients with ECC. METHODS: We retrospectively analyzed the data of 473 patients with ECC who underwent general surgery in five hospitals between January 2007 and October 2018. The correlations between LNM and sex, age, tumor size, tumor location, endoscopic morphology, pathology, depth of invasion and tumor budding (TB) were directly estimated based on postoperative pathological analysis. We also observed the overall survival (OS) and recurrence in ECC patients with and without LNM after matching according to baseline measures. RESULTS: In total, 473 ECC patients were observed, 288 patients were enrolled, and 17 patients had LNM (5.90%). The univariate analysis revealed that tumor size, pathology, and lymphovascular invasion were associated with LNM in ECC (P = 0.026, 0.000, and 0.000, respectively), and the multivariate logistic regression confirmed that tumor size, pathology, and lymphovascular invasion were risk factors for LNM (P = 0.021, 0.023, and 0.001, respectively). There were no significant differences in OS and recurrence between the ECC patients with and without LNM after matching based on baseline measures (P = 0.158 and 0.346, respectively), and no significant difference was observed between chemotherapy and no chemotherapy in ECC patients without LNM after surgery (P = 0.729 and 0.052). CONCLUSION: Tumor size, pathology, and lymphovascular invasion are risk factors for predicting LNM in ECC patients. Adjuvant chemotherapy could improve OS and recurrence in patients with LNM but not always in ECC patients without LNM.

Development of a highly efficient and specific L-theanine synthase.

γ-Glutamylcysteine synthetase (γ-GCS) from Escherichia coli, which catalyzes the formation of L-glutamylcysteine from L-glutamic acid and L-cysteine, was engineered into an L-theanine synthase using L-glutamic acid and ethylamine as substrates. A high-throughput screening method using a 96-well plate was developed to evaluate the L-theanine synthesis reaction. Both site-saturation mutagenesis and random mutagenesis were applied. After three rounds of directed evolution, 13B6, the best-performing mutant enzyme, exhibited 14.6- and 17.0-fold improvements in L-theanine production and catalytic efficiency for ethylamine, respectively, compared with the wild-type enzyme. In addition, the specific activity of 13B6 for the original substrate, L-cysteine, decreased to approximately 14.6% of that of the wild-type enzyme. Thus, the γ-GCS enzyme was successfully switched to a specific L-theanine synthase by directed evolution. Furthermore, an ATP-regeneration system was introduced based on polyphosphate kinases catalyzing the transfer of phosphates from polyphosphate to ADP, thus lowering the level of ATP consumption and the cost of L-theanine synthesis. The final L-theanine production by mutant 13B6 reached 30.4 ± 0.3 g/L in 2 h, with a conversion rate of 87.1%, which has great potential for industrial applications.

Telephone Follow-up Design and Practice for Advanced Cancer Pain Patients.

To describe the design of a telephone follow-up protocol and to evaluate the feasibility of this protocol for advanced cancer pain patients. A series of nine telephone follow-up calls was implemented with 40 advanced cancer pain patients within 3 months after their discharge from the Department of Chemotherapy. Cancer pain information and the pain-related knowledge of the patients were collected by nurses using pain follow-up information sheets and the Patient Pain Questionnaire (PPQ); pain self-efficacy and the quality of life were reported by patients using the Chronic Pain Self-Efficacy Scale (CPSS) Chinese version and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) Chinese version. The average score assessed by advanced cancer pain patients of the need for pain care from nurses was 24.28 (SD = 4.90). Twenty-one and eight patients completed all nine telephone follow-up calls and seven self-reported questionnaires, respectively. The pain intensity of patients at the time of follow-up was mild, but there had been breakthrough pain in the previous week. All patients were satisfied with the nurses' pain follow-up practices. There was a highly positive correlation between the time of follow-up and the patients' pain-related knowledge scores (r = 0.963**, p < 0.01). Patients' pain self-efficacy scores and quality of life scores varied across different dimensions. The baseline pain self-efficacy subscales were associated with all dimensions of quality of life (p < 0.05 or p < 0.01). Telephone follow-up can be an effective method of transitional care. For advanced cancer pain patients, it is still necessary to further explore the cost effectiveness of this method, including the appropriate follow-up duration, endpoints, and outcome measures based on government requirements and policies.

Engineering the effector specificity of regulatory proteins for the in vitro detection of biomarkers and pesticide residues.

Transcriptional regulatory proteins (TRPs)-based whole-cell biosensors are promising owing to their specificity and sensitivity, but their applications are currently limited. Herein, TRPs were adapted for the extracellular detection of a disease biomarker, uric acid, and a typical pesticide residue, carbaryl. A mutant regulatory protein that specifically recognizes carbaryl as its non-natural effector and activates transcription upon carbaryl binding was developed by engineering the regulatory protein TtgR from Pseudomonas putida. The TtgR mutant responsive to carbaryl and a regulatory protein responsive to uric acid were used for in vitro detection, based on their allosteric binding of operator DNA and inducer molecules. Based on the quantitative polymerase chain reactions (qPCRs) output, the minimum detectable concentration was between 1 nM-1 µM and 1-10 nM for uric acid and carbaryl, respectively. Our results demonstrated that engineering the effector specificity of regulatory proteins is a potential technique for generating molecular recognition elements for not only in vivo but also in vitro applications.

The Clinicopathological Significance and Correlative Signaling Pathways of an Autophagy-Related Gene, Ambra1, in Breast Cancer: a Study of 25 Microarray RNA-Seq Datasets and in-House Gene Silencing.

BACKGROUND/AIMS: The activating molecule in Beclin1-regulated autophagy (Ambra1) has been observed to be over-expressed in several cancers, but the clinical contribution of Ambra1 in breast cancer (BC) remains unknown. Hence, in this study, we conducted a comprehensive investigation into the expression, biological role, and underlying functional mechanism of Ambra1 in BC. METHODS: Microarray and RNA-seq datasets providing Ambra1 expression data were obtained from Gene Expression Omnibus (GEO), ArrayExpress, Oncomine, and The Cancer Genome Atlas (TCGA). Both standard mean deviation (SMD) and summary receiver operating characteristic methods were employed to assess Ambra1 expression in BC. We then silenced Ambra1 in MDA-MB-231 cells and performed in vitro experiments to explore the biological effects of Ambra1 on BC cells. Furthermore, differentially expressed genes (DEGs) after Ambra1 knock-down were profiled with a microarray and overlapped with the genes correlated with Ambra1 from Multi Experiment Matrix (MEM) and genes similar to Ambra1 from Gene Expression Profiling Interactive Analysis. These overlapping genes were collected for further bioinformatics analyses to investigate the underlying molecular mechanism of Ambra1 in BC. RESULTS: A total of 25 microarray and RNA-seq datasets involving 2460 breast cancer samples were included. The pooled results demonstrated that Ambra1 was markedly up-regulated in BC tissues (SMD=0.39, 95% CI=0.15-0.63; P=0.002), and the Ambra1 level was also significantly related to the progression of BC, especially metastasis status (P=0.004). In vitro experiments suggested that the proliferation of MDA-MB-231 cells transfected with Ambra1 short hairpin RNA (sh-RNA 2450) showed a decreasing trend at 48 h compared with the control (CK) group. However, apoptosis was similar in cells transfected with Ambra1 sh-RNAs and in the CK cells. Furthermore, we performed a microarray-based comparison of genes after Ambra1 knock-down. The 828 DEGs from microarray analysis were intersected with 4266 Ambra1 co-expressed genes from MEM. Eventually, the overlapped 183 genes were found to be enriched in several well-known cancer-related pathways, including the MAPK signaling pathway, chronic myeloid leukemia pathway, and VEGF signaling pathway. CONCLUSION: These results indicate that the level of Ambra1 up-regulation is clearly related to tumorigenesis and progression of BC, probably via influencing several vital pathways. However, this hypothesis needs to be validated with more in-depth experiments in the future.

LncRNA NEAT1 Promotes Deterioration of Hepatocellular Carcinoma Based on In Vitro Experiments, Data Mining, and RT-qPCR Analysis.

BACKGROUND/AIMS: Accumulated evidence indicates that lncRNA NEAT1 has important roles in various malignant tumors. In this study, we conducted a comprehensive analysis to explore the exact role of NEAT1 in hepatocellular carcinoma (HCC). METHODS: The effects of NEAT1 on cell proliferation, apoptosis, migration, and invasion were measured by in vitro experiments. The expression level and clinical value of NEAT1 in HCC was evaluated based on data from The Cancer Genome Atlas (TCGA), Oncomine, and in-house real-time quantitative (RT-qPCR). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) network analyses were conducted to investigate the potential molecular mechanisms of NEAT1. RESULTS: NEAT1 siRNA not only inhibited proliferation, migration, and invasion of HCC cells but also induced HCC cell apoptosis. A total of four records from TCGA, Oncomine, and RT-qPCR analysis were combined to assess the expression level of NEAT1 in HCC. The pooled standard mean deviation (SMD) indicated that NEAT1 was up-regulated in HCC (SMD = 0.54; 95% CI, 0.36-0.73; P < 0.0001). The area under the curve value of the summary receiver operating characteristic curve was 0.71. NEAT1 expression was also related to race (P = 0.025) and distant metastasis (P = 0.002). Additionally, the results of GO, KEGG pathway, and PPI network analyses suggest that NEAT1 may promote the progression of HCC by interacting with several tumor-related genes (SP1, MDM4, CREBBP, TRAF5, CASP8, TRAF1, KAT2A, and HIST4H4). CONCLUSIONS: NEAT1 contributes to the deterioration of HCC and provides a potential biomarker for the diagnosis and therapy of HCC.

The LncRNA NEAT1 Accelerates Lung Adenocarcinoma Deterioration and Binds to Mir-193a-3p as a Competitive Endogenous RNA.

BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) contribute to the development of multiple malignant tumors. Here, we focused on the biological function and underlying molecular mechanism of an lncRNA, nuclear-enriched abundant transcript 1 (NEAT1), in lung adenocarcinoma (LUAD). METHODS: In vitro experiments were conducted to determine the biological effects of NEAT1 in LUAD cells. A luciferase activity reporter assay was performed to corroborate the interaction between NEAT1 and miR-193a-3p. Data from Gene Expression Omnibus (GEO), Oncomine, The Cancer Genome Atlas (TCGA), and our in-house reverse transcription quantitative PCR (RT-qPCR) were combined to examine the expression of NEAT1 and miR-193a-3p in LUAD. To further explore the regulatory mechanism of NEAT1, we searched for putative target genes of miR-193a-3p from 12 online prediction databases and determined genes positively correlated with NEAT1 as candidate targets. Furthermore, we analyzed the expression of these selected genes using data from TCGA. RESULTS: In vitro experiments showed that knockdown of NEAT1 in LUAD cells markedly restrained cell proliferation, invasion, and migration and stimulated cell apoptosis. The dual-luciferase reporter assay demonstrated that miR-193a-3p directly targeted NEAT1 at its 3'-UTR. We then detected NEAT1 and miR-193a-3p in LUAD cells and normal lung epithelial cells and discovered high expression of NEAT1 and low expression of miR-193a-3p in LUAD cell lines. Simultaneously, the pooled results from the GEO, Oncomine, TCGA, and in-house RT-qPCR showed that the NEAT1 expression increased while the miR-193a-3p expression decreased in LUAD tissues versus normal lung tissues. Furthermore, the USF1 gene was not only upregulated in LUAD, but also positively correlated with NEAT1, suggesting that NEAT1 may function as a ceRNA to sponge miR-193a-3p and abrogate the inhibitory effect of miR-193a-3p on USF1. CONCLUSIONS: Our findings indicate that NEAT1 plays important roles in the occurrence and progression of LUAD. It may exert its role by acting as a ceRNA to regulate miR-193a-3p.

A circRNA-miRNA-mRNA network identification for exploring underlying pathogenesis and therapy strategy of hepatocellular carcinoma.

BACKGROUND: Circular RNAs (circRNAs) have received increasing attention in human tumor research. However, there are still a large number of unknown circRNAs that need to be deciphered. The aim of this study is to unearth novel circRNAs as well as their action mechanisms in hepatocellular carcinoma (HCC). METHODS: A combinative strategy of big data mining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and computational biology was employed to dig HCC-related circRNAs and to explore their potential action mechanisms. A connectivity map (CMap) analysis was conducted to identify potential therapeutic agents for HCC. RESULTS: Six differently expressed circRNAs were obtained from three Gene Expression Omnibus microarray datasets (GSE78520, GSE94508 and GSE97332) using the RobustRankAggreg method. Following the RT-qPCR corroboration, three circRNAs (hsa_circRNA_102166, hsa_circRNA_100291 and hsa_circRNA_104515) were selected for further analysis. miRNA response elements of the three circRNAs were predicted. Five circRNA-miRNA interactions including two circRNAs (hsa_circRNA_104515 and hsa_circRNA_100291) and five miRNAs (hsa-miR-1303, hsa-miR-142-5p, hsa-miR-877-5p, hsa-miR-583 and hsa-miR-1276) were identified. Then, 1424 target genes of the above five miRNAs and 3278 differently expressed genes (DEGs) on HCC were collected. By intersecting the miRNA target genes and the DEGs, we acquired 172 overlapped genes. A protein-protein interaction network based on the 172 genes was established, with seven hubgenes (JUN, MYCN, AR, ESR1, FOXO1, IGF1 and CD34) determined from the network. The Gene Oncology, Kyoto Encyclopedia of Genes and Genomes and Reactome enrichment analyses revealed that the seven hubgenes were linked with some cancer-related biological functions and pathways. Additionally, three bioactive chemicals (decitabine, BW-B70C and gefitinib) based on the seven hubgenes were identified as therapeutic options for HCC by the CMap analysis. CONCLUSIONS: Our study provides a novel insight into the pathogenesis and therapy of HCC from the circRNA-miRNA-mRNA network view.

Improving key enzyme activity in phenylpropanoid pathway with a designed biosensor.

Overexpressing key enzymes of biosynthetic pathways for overproduction of value-added products usually imposes metabolic burdens on cells, which can be circumvented by improving the key enzyme activities. p-Coumarate: CoA ligase (4CL) is a critical enzyme in the phenylpropanoid pathway that synthesizes various natural products. To screen for 4CL with improved activity, a biosensor of resveratrol whose biosynthetic pathway involves 4CL was designed by engineering the TtgR regulatory protein. The biosensor exhibited good specificity and robustness, allowing rapid and sensitive selection of resveratrol hyper-producers. A 4CL variant with improved activity was selected from a 4CL mutagenesis library constructed in the resveratrol biosynthetic pathway in Escherichia coli. This mutant led to increased production of not only resveratrol but also the flavonoid naringenin, when introduced in their corresponding biosynthetic pathways. These findings demonstrate the feasibility of improving key enzyme activities in important biosynthetic pathways with the aid of designed biosensors of pathway products.

Clinical Value of miR-101-3p and Biological Analysis of its Prospective Targets in Breast Cancer: A Study Based on The Cancer Genome Atlas (TCGA) and Bioinformatics.

BACKGROUND MiR-101-3p can promote apoptosis and inhibit proliferation, invasion, and metastasis in breast cancer (BC) cells. However, its mechanisms in BC are not fully understood. Therefore, a comprehensive analysis of the target genes, pathways, and networks of miR-101-3p in BC is necessary. MATERIAL AND METHODS The miR-101 profiles for 781 patients with BC from The Cancer Genome Atlas (TCGA) were analyzed. Gene expression profiling of GSE31397 with miR-101-3p transfected MCF-7 cells and scramble control cells was downloaded from Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) were identified. The potential genes targeted by miR-101-3p were also predicted. Gene Ontology (GO) and pathway and network analyses were constructed for the DEGs and predicted genes. RESULTS In the TCGA data, a low level of miR-101-2 expression might represent a diagnostic (AUC: 0.63) marker, and the miR-101-1 was a prognostic (HR=1.79) marker. MiR-101-1 was linked to the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), and miR-101-2 was associated with the tumor (T), lymph node (N), and metastasis (M) stages of BC. Moreover, 427 genes were selected from the 921 DEGs in GEO and the 7924 potential target genes from the prediction databases. These genes were related to transcription, metabolism, biosynthesis, and proliferation. The results were also significantly enriched in the VEGF, mTOR, focal adhesion, Wnt, and chemokine signaling pathways. CONCLUSIONS MiR-101-1 and miR-101-2 may be prospective biomarkers for the prognosis and diagnosis of BC, respectively, and are associated with diverse clinical parameters. The target genes of miR-101-3p regulate the development and progression of BC. These results provide insight into the pathogenic mechanism and potential therapies for BC.

Long Noncoding RNA MALAT-1 Can Predict Poor Prognosis: A Meta-Analysis.

BACKGROUND: MALAT-1 is a highly conserved nuclear long non-coding RNA (lncRNA). The overexpression of MALAT-1 has been reported in several types of cancers. This meta-analysis was conducted to further investigate its potential role as a prognostic indicator in various cancers. MATERIAL/METHODS: The meta-analysis was performed by use of systematic search terms in 13 databases for qualified papers on prognosis in cancer from inception to June 30, 2015. The combined hazard ratios (HRs) with 95% confidence interval (95% CI) were computed to demonstrate the effect of MALAT-1 on prognosis of cancers. RESULTS: A total of 590 papers were initially identified, and 17 studies were finally included in this paper. Meta-analysis was accomplished with a total of 1626 patients. Combined HRs and 95% CI were calculated by fixed-effects or random-effects models. The quality assessment of included studies was performed by the Newcastle-Ottawa scale (NOS). High expression of MALAT-1 was found to be an indicator of poor prognosis in overall survival (OS) (HR=1.84, 95% CI: 1.27-2.67) and disease-free survival (DFS) (HR=2.37, 95% CI: 1.55-3.62). In subgroups, the associations between MALAT-1 and survival were also apparent, for instance, in country subgroup: China (HR=1.85, 95% CI: 1.14-2.99). CONCLUSIONS: The overexpression of MALAT-1 may be a potential prognostic indicator for various human cancers.

Decoy Receptor 3 (DcR3) as a Biomarker of Tumor Deterioration in Female Reproductive Cancers: A Meta-Analysis.

BACKGROUND DcR3 (decoy receptor 3) has been proposed be involved in development and prognosis of female reproductive cancers, including cervical cancer, ovarian cancer, and breast cancer. The purpose of this meta-analysis was to explore the evidence for the correlation between DcR3 and the clinicopathological characteristics, as well as the overall survival time, in female reproductive cancers. MATERIAL AND METHODS Relevant studies were searched for in PubMed, Wiley Online Library, Web of Science, Science Direct, Cochrane Central Register of Controlled Trials, Google Scholar, EMBASE, Ovid, LILACS, Chinese CNKI, Chong Qing VIP, Wan Fang, and China Biology Medicine disc up to 30 September 2015. Data on the relationship between DcR3 expression and TNM stage, differentiation, lymph node metastasis, age, and overall survival time were extracted. Pooled odds ratios (ORs) and 95% CIs (confidence intervals) were estimated by forest plot. RESULTS Twelve studies with 1127 patients met the inclusion criteria for this meta-analysis. Overexpression of DcR3 was significantly related to the risk of female reproductive cancers (OR=10.69, 95% CI: 6.33-18.05), TNM stage (OR=5.51, 95% CI: 2.83-10.71), differentiation (OR=4.16, 95% CI: 2.28-7.60), lymph node metastasis (OR=5.89, 95% CI: 3.16-10.9), age (OR=0.85, 95% CI: 0.51-1.44), and overall survival time (OR=1.84, 95% CI: 0.58-5.83). Subgroup analyses showed that overexpression of DcR3 in cervical, ovarian, and breast cancer all had similar relationships with these clinicopathological parameters. CONCLUSIONS Our meta-analysis suggests that overexpression of DcR3 may play vital roles in the tumorigenesis and deterioration of female reproductive cancers. However, the relationship between DcR3 expression and prognosis needs further investigation.

Development of a novel uric-acid-responsive regulatory system in Escherichia coli.

A novel uric-acid-responsive regulatory system was developed in Escherichia coli by adapting the HucR-related regulatory elements from Deinococcus radiodurans into E. coli. The induction performance of this system was compared to the performance of both the pBAD and pET systems. Our novel regulatory system was induced in a dose-dependent manner in the presence of uric acid and exhibited low basal expression in its absence. The system was characterized by a wide dynamic range of induction, being compatible with various E. coli strains and not requiring genomic modifications of the bacterial host. E. coli DH5α and DH10B were the most suitable host strains for optimal performance of this system. In conclusion, we developed a regulatory system with potential for applications in both recombinant protein expression and metabolic optimization.

Modifiable risk factors for thyroid cancer: lifestyle and residence environment.

In recent years, there has been a rapid increase in the prevalence of benign and malignant tumours of the thyroid gland worldwide, positioning it as one of the most prevalent neoplasms within the endocrine system. While the pathogenesis of thyroid tumours is still unclear, an increasing number of studies have found that certain lifestyle and residence environments are associated with their occurrence and development. This article endeavours to elucidate the correlation between lifestyle, residential environment, and the increased prevalence of thyroid cancer in recent years. It specifies the frequency of the lifestyle and outlines the scope of the residential environment. It also endeavours to summarise the main mechanistic pathways of various modifiable risk factors that cause thyroid cancer. Factors that prevent thyroid cancer include smoking and alcohol consumption, quality and regular sleep, consumption of cruciferous vegetables and dairy products, and consistent long-term exercise. Conversely, individuals with specific genetic mutations have an elevated risk of thyroid cancer from prolonged and frequent use of mobile phones. In addition, individuals who work in high-pressure jobs, work night shifts, and live near volcanoes or in environments associated with pesticides have an elevated risk of developing thyroid cancer. The impact of living near a nuclear power plant on thyroid cancer remains inconclusive. Raising awareness of modifiable risk factors for thyroid cancer will help to accurately prevent and control thyroid cancer. It will provide a scientific basis for future research on lifestyles and living environments suitable for people at high risk of thyroid cancer.

Engineering and application of LacI mutants with stringent expressions.

Optimal transcriptional regulatory circuits are expected to exhibit stringent control, maintaining silence in the absence of inducers while exhibiting a broad induction dynamic range upon the addition of effectors. In the Plac /LacI pair, the promoter of the lac operon in Escherichia coli is characterized by its leakiness, attributed to the moderate affinity of LacI for its operator target. In response to this limitation, the LacI regulatory protein underwent engineering to enhance its regulatory properties. The M7 mutant, carrying I79T and N246S mutations, resulted in the lac promoter displaying approximately 95% less leaky expression and a broader induction dynamic range compared to the wild-type LacI. An in-depth analysis of each mutation revealed distinct regulatory profiles. In contrast to the wild-type LacI, the M7 mutant exhibited a tighter binding to the operator sequence, as evidenced by surface plasmon resonance studies. Leveraging the capabilities of the M7 mutant, a high-value sugar biosensor was constructed. This biosensor facilitated the selection of mutant galactosidases with approximately a seven-fold improvement in specific activity for transgalactosylation. Consequently, this advancement enabled enhanced biosynthesis of galacto-oligosaccharides (GOS).

The impact of preoperative calcitonin screening on the prognosis of patients with medullary thyroid cancer: a retrospective multicenter cohort study.

PURPOSE: There is still controversy in different guidelines regarding the necessity of routine preoperative calcitonin (Ctn) testing in medullary thyroid cancer (MTC). The level of preoperative Ctn may influence the extent of surgery. METHODS: This retrospective multicenter cohort study involved 149 MTC patients from 6 centers between 2013 to 2023. Clinical characteristics, surgical procedure and clinical outcomes were compared between Ctn-screened and Non-screened group. Kaplan-Meier method was used to estimate recurrence-free survival (RFS) and overall survival (OS). RESULTS: In total, 127 MTC patients with preoperative Ctn screening and 22 MTC patients without screening were analyzed. MTC patients with preoperative Ctn screening underwent more radical surgical procedures including total thyroidectomy and lymph node dissection, compared to those without screening (84.3% vs. 68.2% and 91.3% vs. 72.7%, respectively). The rate of recurrence and death were lower in the Ctn-screened group (16.1% vs. 36.4%, 0.8% vs. 18.2%, respectively). The survival curve showed a significantly better overall survival in Ctn-screened group than Non-screened group (HR:17.932, 95% CI 1.888-170.294, p-value = 0.001), while no significant difference was observed of RFS between two groups (HR:1.6, 95% CI 0.645-3.966, p-value = 0.307). CONCLUSION: Preoperative Ctn screening can prompt surgeons choosing more radical initial surgical treatment for MTC patients, potentially leading to better long-term outcomes. Further evaluation of the cost-effectiveness of routine Ctn screening in thyroid nodule patients is warranted.

Advances in the application of computational pathology in diagnosis, immunomicroenvironment recognition, and immunotherapy evaluation of breast cancer: a narrative review.

BACKGROUND: Breast cancer (BC) is a prevalent and highly lethal malignancy affecting women worldwide. Immunotherapy has emerged as a promising therapeutic strategy for BC, offering potential improvements in patient survival. Neoadjuvant therapy (NAT) has also gained significant clinical traction. With the advancement of computer technology, Artificial Intelligence (AI) has been increasingly applied in pathology research, expanding and redefining the scope of the field. This narrative review aims to provide a comprehensive overview of the current literature on the application of computational pathology in BC, specifically focusing on diagnosis, immune microenvironment recognition, and the evaluation of immunotherapy and NAT response. METHODS: A thorough examination of relevant literature was conducted, focusing on studies investigating the role of computational pathology in BC diagnosis, immune microenvironment recognition, and immunotherapy and NAT assessment. RESULTS: The application of computational pathology has shown significant potential in BC management. AI-based techniques enable improved diagnosis and classification of BC subtypes, enhance the identification and characterization of the immune microenvironment, and facilitate the evaluation of immunotherapy and NAT response. However, challenges related to data quality, standardization, and algorithm development still need to be addressed. CONCLUSION: The integration of computational pathology and AI has transformative implications for BC patient care. By leveraging AI-based technologies, clinicians can make more informed decisions in diagnosis, treatment planning, and therapeutic response assessment. Future research should focus on refining AI algorithms, addressing technical challenges, and conducting large-scale clinical validation studies to facilitate the translation of computational pathology into routine clinical practice for BC patients.

Highly expressed carbohydrate sulfotransferase 11 correlates with unfavorable prognosis and immune evasion of hepatocellular carcinoma.

Despite great advance has been made in multi-modality treatments for HCC patients, the effectiveness is far from satisfactory with worse survival outcome, which may be partly explainable by the anti-tumor deficiency of the immune system. It is necessary to clarify the molecular mechanism of HCC immunodeficiency. Here, we demonstrated that carbohydrate sulfotransferase 11 (CHST11) was upregulated in HCC and related to advanced TNM stage. HCC patients with TP53 mutation showed higher CHST11 expression. Survival analysis revealed that CHST11 was an independent prognostic biomarker in HCC. Cellular functional experiments indicated that knockdown of CHST11 in HCC inhibited cell proliferation and metastasis. Gene functional enrichment analyses indicated that CHST11 modulated pathways related to tumor growth, metastasis and immune regulation. Continuative immune-related analyses revealed that CHST11 expression facilitated Tregs infiltration in HCC and promoted the expression of checkpoints PD-L1/PD-1, resulting in the immunosuppression of HCC. Targeting CHST11 may inhibit Tregs infiltration and enhance the antineoplastic effect of immune checkpoint inhibitors, which provides a novel insight into the combination immunotherapy with Treg-modulating agents and PD-L1/PD-1 inhibitors.