Construction of an alternative NADPH regeneration pathway improves ethanol production in Saccharomyces cerevisiae with xylose metabolic pathway.

Full conversion of glucose and xylose from lignocellulosic hydrolysates is required for obtaining a high ethanol yield. However, glucose and xylose share flux in the pentose phosphate pathway (PPP) and glycolysis pathway (EMP), with glucose having a competitive advantage in the shared metabolic pathways. In this work, we knocked down ZWF1 to preclude glucose from entering the PPP. This reduced the [NADPH] level and disturbed growth on both glucose or xylose, confirming that the oxidative PPP, which begins with Zwf1p and ultimately leads to CO2 production, is the primary source of NADPH in both glucose and xylose. Upon glucose depletion, gluconeogenesis is necessary to generate glucose-6-phosphate, the substrate of Zwf1p. We re-established the NADPH regeneration pathway by replacing the endogenous NAD+-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene TDH3 with heterogenous NADP + -GAPDH genes GDH, gapB, and GDP1. Among the resulting strains, the strain BZP1 (zwf1Δ, tdh3::GDP1) exhibited a similar xylose consumption rate before glucose depletion, but a 1.6-fold increased xylose consumption rate following glucose depletion compared to the original strain BSGX001, and the ethanol yield for total consumed sugars of BZP1 was 13.5% higher than BSGX001. This suggested that using the EMP instead of PPP to generate NADPH reduces the wasteful metabolic cycle and excess CO2 release from oxidative PPP. Furthermore, we used a copper-repressing promoter to modulate the expression of ZWF1 and optimize the timing of turning off the ZWF1, therefore, to determine the competitive equilibrium between glucose-xylose co-metabolism. This strategy allowed fast growth in the early stage of fermentation and low waste in the following stages of fermentation.

Sex-specific association of exposure to a mixture of phenols, parabens, and phthalates with thyroid hormone and antibody levels in US adolescents and adults.

Individuals are exposed to multiple phenols, parabens, and phthalates simultaneously since they are important endocrine-disrupting compounds (EDCs) and share common exposure pathways. It is necessary to assess the effects of the co-exposure of these EDCs on thyroid hormones (THs). In this study, data included 704 adolescents and 2911 adults from the 2007-2012 National Health and Nutrition Examination Survey (NHANES). Serum THs measured total triiodothyronine (T3), total thyroxine (T4), free forms of T3 (FT3) and T4 (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb). And 16 EDCs (3 phenols, 2 parabens, and 11 phthalates) were measured from urine. The relationship between single EDCs and single THs was analyzed using generalized linear regression. And results showed that several EDCs were positively associated with serum T3 and FT3 levels in boys but negatively associated with serum T4 and FT4 levels in girls. And in adults, five EDCs were negatively associated with T3, T4, or FT4. The effects of co-exposure to 16 EDCs on THs were calculated using Bayesian kernel machine regression and quantile-based g-computational modeling, confirmed that co-exposure was related to the increase of T3 in adolescents and the decrease of T4 in both adolescents and adults. Besides, nonlinear and linear relationships were identified between co-exposure and the risk of positive TPOAb and TgAb in girls and adult females, respectively. In conclusion, phenols, parabens, and phthalates as a mixture might interfere the concentrations of THs and thyroid autoantibodies, and the interfering effect varies significantly by sex as well as by age. Further prospective research is warranted to investigate the causal effects and underlying mechanisms of co-exposure on thyroid dysfunction.

The regulatory roles of socio-economic status, social and intellectual activity in the relationship between alcohol consumption and cognitive decline trajectory in middle-aged and elderly Chinese: A prospective cohort study.

OBJECTIVES: To determine the relationship between alcohol consumption and cognitive decline, and to further explore the potential regulatory role of education, socio-economic status (SES), and social or intellectual activity in this relationship. METHODS: 6197 participants aged 45-75 years with four repeated measures data from 2011 to 2018 were included. A mixed-effect model was used to explore the relationship between alcohol consumption and the rate of change in cognitive decline, a latent class growth mixed model (LCGMM) was applied to determine the potential trajectory of cognitive decline, and finally, the mediating and moderating analyses were used to determine the regulatory effect of all four variables on the relationship between alcohol consumption and potential trajectory. RESULTS: Compared to never-drinkers, moderate alcohol consumption was a protective factor for overall cognitive function (ß = 0.13, 95% CI: 0.04-0.20, p < 0.001), but there was no statistical correlation with the decline rate of cognitive function. And this protective effect was no longer significant after additional adjustments for education, SES, social and intellectual activity. The LCGMM model divided participants into two trajectories, a high-level-to-decline group including 79.75% of participants (quadratic: ß [SE]: -0.90 [0.07], p < 0.001), and a low-level-to-decline group including 20.25% participants (linear: ß [SE]: -3.05 [0.49], p < 0.001). With the latter as the reference, SES played a reverse regulation role in the harmful effect of heavy drinking on cognitive trajectories (odd ratio [OR] = 0.46, 95% CI: 0.23-0.93, p < 0.05). Social and intellectual activities played a negative mediating role in the harmful effect of alcohol consumption on cognitive trajectories (light: OR = 0.96, p < 0.001; moderate: OR = 0.96, p < 0.001; heavy: OR = 0.97, p < 0.01). CONCLUSIONS: Alcohol itself has no protective effect on the decline of longitudinal cognitive trajectory. But the regulatory effect of SES, social and intellectual activities slows down the harm of alcohol consumption on the decline of cognitive function. CLINICAL TRIAL REGISTRATION: The data used in this study are from publicly available databases. They are retrospective cohort studies without any intervention. Therefore, no clinical trial registration has been conducted.

Comparing the efficacy of thyroglobulin and thyroglobulin/ thyroid-stimulating hormone ratio models in predicting a successful response to radioactive iodine therapy.

BACKGROUND: The thyroglobulin (Tg)/ thyroid-stimulating hormone (TSH) ratio has manifested to be a reliable marker for predicting prognosis in patients with differentiated thyroid carcinoma (DTC). The objective of this study was to compare the efficacy of Tg and Tg/TSH ratio models in predicting a successful response to radioactive iodine therapy. METHODS: One thousand six hundred forty-two DTC patients receiving 131I radiotherapy were finally enrolled in this retrospective study. The patients were divided into a training set (n = 973) and a validation set (n = 669) by the patient consultation time (July 2019). A receiver-operating characteristic curve was constructed for Tg and the Tg/TSH ratio to establish their cutoffs. Then, the variables were screened by univariate logistic regression and incorporated into logistic prediction models by stepwise regression, where Tg/TSH was excluded from model 1 and Tg was excluded from model 2. RESULTS: In 1642 enrolled DTC patients, the first 131I radiotherapy had an excellent response in 855 patients. The cut-offs for Tg level and Tg/TSH ratio were 3.40 ng/ mL [area under the curve (AUC): 0.789] and 36.03 ng/mIU (AUC: 0.788), respectively. In addition, the AUC of the model including Tg was higher than that of the model including Tg/TSH in both the training set (0.837 vs 0.833) and the testing set (0.854 vs 0.836). CONCLUSIONS: Both Tg and Tg/TSH ratios could be considered predictors of the effects of the first 131I ablative therapy. However, the prediction model including Tg performed better than the model including Tg/TSH.

Europium-based metal-organic framework with acid-base buffer structure as electrochemiluminescence luminophore for hyperstatic trenbolone trace monitoring under wide pH range.

The wide and even whole pH range electrochemiluminescence (ECL) is attractive for steroid estrogens detection under harsh conditions (such as strong acid and alkali). Herein, we presented an efficient europium-based metal-organic framework (Eu-MOF) as ECL luminophore, which has been synthesized via the specific 2, 4-bis(3, 5-dicarboxyphenylamino)-6-oltriazine (H4BDPO) ligand with acid-base buffering effect. The functional groups with weak acid and base endowed the H4BDPO with eight ionogenic group states, thereout different total charges of H4BDPO were derived, thus high and steady ECL signals of Eu-MOF were acquired under different environments with pH = 1.0-14.0. Most notably, combined with the means of UV-vis, fluorescence spectra, cyclic voltammetry (CV) and density functional theory (DFT) calculations, the Eu-MOF has been explored different luminescence mechanisms with variational total charges. The constructed ECL biosensor based on the Eu-MOF realized sensitive detection of trenbolone under wide pH range (In order to maintain the biological activity of antigen and antibody, the studied pH value is 5-8.5), in which the limits of detection were 3.95 fg/mL (pH = 5.0), 2.36 fg/mL (pH = 7.4) and 5.48 fg/mL (pH = 8.5) respectively. This work provides a considerable method to realize efficient trace detection of steroid estrogens under the wide or even whole pH conditions.

Hollow Double-Shell CuCo2O4@Cu2O Heterostructures as a Highly Efficient Coreaction Accelerator for Amplifying NIR Electrochemiluminescence of Gold Nanoclusters in Immunoassay.

The evolution of electrochemiluminescence (ECL) emission amplified by coreaction accelerator in near-infrared (NIR) area has been overwhelmingly anticipated for ultrasensitive detection of disease biomarkers. Herein, the hollow double-shell CuCo2O4@Cu2O (HDS-CuCo2O4@Cu2O) heterostructures were conveniently prepared and utilized as an attractive coreaction accelerator to improve the NIR ECL performance of gold nanoclusters (AuNCs) for the first time. Benefiting from perfect-matched lattice spacing, unique Cu2O nanoparticles (NPs) were formed in situ on the layered-hollow CuCo2O4 nanospheres (NSs) to obtain HDS-CuCo2O4@Cu2O heterostructures. The formed heterojunctions supplied shorter charge transfer distance and better interfacial charge transfer efficiency as well as more effective separation performance. Consequently, HDS-CuCo2O4@Cu2O heterostructures as an admirable electroactive substrate could significantly promote the formation of sufficient coreactant intermediate radicals to react with AuNCs cationic radicals, realizing about 3-folds stronger NIR ECL response than that of individual AuNCs. In addition, the AuNCs templated by l-methionine (l-Met) exhibited NIR ECL emission around 830 nm, which could decrease the photochemical damage to even realize a nondestructive detection with improved susceptibility and circumambient adaptability. Subsequently, a well site-oriented fixation strategy utilizing HWRGWVC heptapeptide as the specific antibody immobilizer was introduced to further preserve the bioactivity of antibody on the HDS-CuCo2O4@Cu2O and AuNCs surface along with enhancing the incubation performance markedly. In view of the progressive sensing mechanism, a NIR immunosensor was obtained for the ultrasensitive analysis of CYFRA21-1, which achieved a broad linear ranging from 2 fg/mL to 50 ng/mL and a low limit of detection (LOD) of 0.67 fg/mL (S/N = 3).

Associations Between Abdominal Obesity Indices and Nonalcoholic Fatty Liver Disease: Chinese Visceral Adiposity Index.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver metabolic disease worldwide. Up to 70%-80% of patients with NAFLD were obese, especially abdominal obesity. Many indicators of abdominal obesity have been reported, including waist circumference (WC), visceral obesity index (VAI), lipid accumulation (LAP), and Chinese VAI (CVAI). However, few studies investigated the associations between these indices with NAFLD. This present study aims to explore the associations between abdominal obesity indices with NAFLD. A total of 7,238 participants were involved in the cross-sectional study, and 1,584 participants were included in the longitudinal study from Jidong communities. NAFLD was assessed by abdominal ultrasonography. The trajectory of WC, VAI, LAP, and CVAI during 2013-2016 was identified by a group-based trajectory model. The logistic regression and Cox proportional hazards models analyzed the correlations and causality between abdominal obesity indices with NAFLD. In this study, the prevalence and incidence of NAFLD are approximately 44% and 26%, respectively. In the cross-sectional study, WC, VAI, LAP, and CVAI are associated with NAFLD. After adjustment for potential confounders, the moderate-rising and high-rising groups of CVAI had the highest risk of NAFLD in longitudinal analysis (hazard ratio (HR): 3.903, 95%CI: 2.434-6.259; HR: 5.694 95%CI: 3.098-10.464, respectively). Receiving operating characteristic curves show that CVAI has the best diagnostic value for NAFLD (area under the curve (AUC) = 0.868). CVAI is independently associated with the risk of NAFLD and may also have an important value to the diagnosis of NAFLD.

Dumbbell Plate-Shaped AIEgen-Based Luminescent MOF with High Quantum Yield as Self-Enhanced ECL Tags: Mechanism Insights and Biosensing Application.

It is widely known that high-performance electrochemiluminescence (ECL) emitters play a crucial part in improving the detection sensitivity of the ECL strategy. Through the combination of aggregation-induced emission luminogens (AIEgens), 1,1,2,2-tetra(4-carboxylbiphenyl)ethylene (H4 TCBPE) with Zr(IV) cations, a dumbbell plate-shaped metal-organic framework (MOF) with high luminous efficiency is synthesized as ECL tags. The resultant MOF exhibits stronger ECL activity than those of H4 TCBPE monomers and aggregates. Herein, this phenomenon is defined as the coordination-triggered electrochemiluminescence (CT-ECL) enhancement effect. Furthermore, the nearly matched ECL and photoluminescence (PL) spectra imply the bandgap emission mechanism. Remarkably, polyethyleneimine (PEI) as the coreactant is covalently connected with MOF to form the uniquely self-enhanced ECL complex of Zr-TCBPE-PEI, where the robust ECL signal is captured owing to the intramolecular-like coreaction acceleration. Based on the resonance energy transfer (RET) behavior, the AuPd@SiO2 composite is designed as the high-efficiency quencher. In this manner, an innovative and ultrasensitive ECL sensor is constructed for neuron-specific enolase (NSE) detection through sandwich-type immunoreaction, with the detection limit down to 52 fg ml-1 . The present study has gone some way toward designing MOF-based self-luminescent ECL materials, thus paving a new avenue to expand the late-model ECL emitters for immunoassay.

Delay of initial radioactive iodine therapy beyond 3 months has no effect on clinical responses and overall survival in patients with thyroid carcinoma: A cohort study and a meta-analysis.

BACKGROUND: More than a third of thyroid carcinoma (TC) patients require treatment with radioactive iodine (RAI), but the timing of initial RAI therapy after thyroidectomy remains controversial. METHODS: We included 1224 differentiated thyroid carcinoma (DTC) patients during 2015-2019, divided them into the early (≤3 months) and the delayed (>3 months) groups based on the interval between surgery and the initial RAI. Clinical outcomes were assessed within 6-8 months of treatment with RAI, including excellent response (ER), indeterminate response (IDR), biochemical incomplete (BIR) and structural incomplete response (SIR). Further transformed them into dichotomous outcomes, we therefore introduced the ordered/binary logistic regression to assess the relation of time interval and quaternary/dichotomous outcomes, respectively. Finally, we conducted a meta-analysis for cohort study to investigate the effect of timing of RAI therapy on the prognosis of TC. RESULTS: Delay RAI therapy beyond 3 months reduced the IR (BIR + SIR) rate in the present cohort study (RR = 0.67, 95% CI: 0.49-91). Following meta-analysis including 38,688 DTC patients confirmed these results (RR = 0.77, 95% CI: 0.66-0.91), further revealed the duration of treatment does not influence OS (pooled RR = 1.05, 95% CI: 0.83-1.33). CONCLUSION: Delayed initial RAI therapy beyond 3 months but no later than 6 months did not impair the prognosis of TC.

Cysteine Modification of Glutathione-Stabilized Au Nanoclusters to Red-Shift and Enhance the Electrochemiluminescence for Sensitive Bioanalysis.

Screening new electrochemiluminescence (ECL) emitters for the design of sensitive detection strategies with even long emission wavelength is intensively anticipated in ECL evolution. Herein, a promising modification strategy for improving the ECL performance of Au nanoclusters (AuNCs) as a water-soluble luminophore was proposed. Upon the introduction of l-cysteine (l-Cys) onto the surface of glutathione (GSH)-stabilized AuNCs (GSH-AuNCs), the dual-thiol bond between l-Cys and GSH was formed to limit the intramolecular motion and nonradiative relaxation of the excited state from the capping agents, which resulted in the enhancement of monochromatic ECL emission of GSH-AuNCs with a red-shifted wavelength. By utilizing triethylamine as a coreactant, the ECL of l-Cys/GSH-AuNCs was about 1.5-fold stronger than that of GSH-AuNCs, and the emission wavelength red-shifted from 660 to 780 nm at a relatively low potential, which could decrease the interference in bioassay and the photochemical damage in nondestructive detection. As a proof of application, a sandwich-type immunosensing method for CYFRA 21-1 was proposed with l-Cys/GSH-AuNCs as the signal tag, which displayed a wide linear ranging from 0.2 fg/mL to 2 ng/mL and a limit of detection down to 0.067 fg/mL at 3S/N. This work provides a wonderful strategy for promoting the performance of ECL emitters.

Mothers caring experiences of children with congenital hand or foot abnormalities: A phenomenological study.

PURPOSE: To explore the mothers' caring experiences of children with congenital hand or foot abnormalities, and to inform the development of tailored intervention strategies to improve the mothers' well-being. DESIGN AND METHODS: A qualitative study design was used. A purposive sample of 23 women whose children had congenital abnormalities of the hand or foot were enrolled. Semi-structured, in-depth interviews were conducted from December 2019 to May 2020. The Colaizzi's phenomenological approach was used for data analysis. RESULTS: Data analysis revealed four main themes: (a) dynamic negative affect; (b) low health literacy; (c) mothers' need for support; and (d) the shift in social activity and family role. Eleven subthemes were involved in these themes. CONCLUSIONS: Women whose children have abnormal hands or feet have complicated care experiences and are under tremendous psychological pressure. Some mothers also encounter financial difficulties. PRACTICE IMPLICATIONS: This study assessed the psychological impact on mothers of children with congenital hand or foot abnormalities. Our findings illustrate the needs of mothers, and call attention to this specific group. The findings may help inform healthcare and social interventions to facilitate the recovery of the affected children and cater to the needs of these families. Healthcare providers should provide adequate instructions to the parents regarding the provision of home management care following discharge from the hospital.

TRIM7 suppresses cell invasion and migration through inhibiting HIF-1α accumulation in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one frequent form of urologic malignancy characterized by deregulated hypoxia-inducible factor signaling, genetic and epigenetic alterations. Metastasis is the leading cause of mortality from ccRCC, and understanding the underlying mechanism of this event will provide better strategies for its management. Here, we identify tripartite motif containing 7 (TRIM7) as a tumor suppressor in ccRCC cells, which negatively regulates hypoxia-inducible factor 1α (HIF-1α) signaling through targeting the proto-oncogene Src. We observed the downregulated expression of TRIM7 in clinical ccRCC tissues and its correlation with the poor prognosis. In Caki-1 cells, depletion of TRIM7 increased cell migration and invasion under normoxic and hypoxic conditions. TRIM7 markedly reduced the abundance of Src protein via the ubiquitin-proteasome pathway. Further study showed that TRIM7 affected HIF-1α accumulation through targeting either the Src-triggered PI3K/AKT/mTOR signaling pathway or reactive oxygen species production. Overall, our findings highlight a novel mechanism for negative regulation of HIF-1 signaling pathway by TRIM7 and define a promising therapeutic strategy for ccRCC by modulating TRIM7.

Copper doped terbium metal organic framework as emitter for sensitive electrochemiluminescence detection of CYFRA 21-1.

Lanthanide metal organic frameworks (L-MOFs) are emerging as promising electrochemiluminescence (ECL) emitters for bioanalysis. This work proposed a copper doped terbium MOF as a luminescent tag for construction of a "signal-on" ECL immunosensing method. The Tb-Cu-PA MOF was prepared using Tb3+ and Cu2+ ions as metal linkers and m-phthalic acid as bridge ligand, and exhibited strong ECL emission with K2S2O8 as a coreactant. The immunosensor was prepared by immobilizing capture antibody on Pd nanoparticles modified Ni-Co layered double hydroxide (Pd-ZIF-67@LDH) nanoboxes, which showed strong electrocatalytic activity toward the reduction of S2O82- for amplifying the ECL signal. Upon the sandwich-typed immunoreactions, Tb-Cu-PA MOF labeled antibody was introduced onto the immunosensor for sensitive ECL detection of target protein. Using cytokeratin 19 fragment 21-1 (CYFRA21-1), a representative lung cancer biomarker, as target model, the ECL immunosensing method showed a linear range of 0.01-100 ng/mL and a detection limit of 2.6 pg/mL (S/N = 3). This immunosensing strategy highlighted the advances of using luminescent and electroactive MOFs in the developments of highly efficient immunosensors for bioanalysis.

Burden of Thyroid Cancer From 1990 to 2019 and Projections of Incidence and Mortality Until 2039 in China: Findings From Global Burden of Disease Study.

Projecting the burden of thyroid cancer (TC) over time provides essential information to effectively plan measures for its management and prevention. This research obtained data from the Global Burden of Disease (GBD) Study from between 1990 and 2019 to model how TC will affect China until 2039 by conducting the Bayesian age-period-cohort analysis. The number of new TC cases in China was 10,030 in 1990, 39,080 in 2019, and is projected to be 47,820 in 2039. This corresponds to 3,320, 7,240, and 4,160 deaths, respectively. Disability-adjusted life years (DALYs) cases increased from 103,490 in 1990 to 187,320 in 2019. The age-standardized rate (ASR) of incidence increased from 1.01 to 2.05 during 1990-2019 and was projected to increase to 3.37 per 100,000 person-years until 2039. The ASR of mortality (ASMR) remained stable during the study period and was projected to have a mild decline from 0.39 to 0.29/100,000 during 2020-2039. Although the ASMR in male patients has maintained increasing at a rate of 2.2% per year over the past 30 years, it is expected to decline at a rate of 1.07% per year in 2019-2039. The most significant increase in crude incidence occurred in people aged 45-65 from 1990 to 2019, however, this will shift into young people aged 10-24 from 2020 to 2039. In addition, the proportion of deaths and DALYs caused by obesity increased from 1990 to 2019 and affected men more than women. In conclusion, a substantial increase in counts of incidence of TC in China is projected over the next two decades, combined with the slightly declining mortality, indicating that rational health policies are needed in the future to cope with the increasing number of TC patients, especially among males and adolescents.

Lymph node metastases >5 and metastatic lymph node ratio >0.30 of differentiated thyroid cancer predict response to radioactive iodine.

PURPOSE: The study was designed to elucidate the predictive value of the number of lymph node metastases (LNMs) and lymph node ratio (LNR) for response to therapy restratification system (RTRS). METHODS: From December 2015 to December 2019, 1228 patients who accepted radioactive iodine (RAI) were collected in the study. After 6-8 months, response to RAI was evaluated as complete response (excellent response) and incomplete response (indeterminate, biochemical, and structural incomplete response). The study developed classification tree to determine the optimum LNMs and LNR that predicted response to RAI. Multivariate logistic regression analyses were further analyzed to find independent factors of response to RAI. RESULT: The mean age of patients was 44 ± 12 and 71.09% (873/1228) were females. The best cutoff value of LNMs to affect RAI treatment response determined by classification tree was 5. Further in 388 patients with LNMs >5, the best cutoff value of LNR to affect RAI treatment response determined by classification tree was 0.30. With multivariate analysis, the study found that LNMs (>5), gender, lymph node dissection, and American Thyroid Association (ATA) risk classification were independent predictors of response to RAI for all 1228 patients; and LNR (>0.30), gender, and ATA risk classification for 388 patients with LNMs >5. The sensitivity analysis indicated that whether patients with LNM or not were included, the multivariate logistic regression model was kept stable. On subgroup analysis, no significant interactions were observed between the effect of LNMs/LNR and gender, N stage, ATA risk classification, lymph node dissection, or T stage. CONCLUSIONS: With classification tree, the study found that LNMs and LNR could predict initial response to RAI, and their optimal cutoff values were 5 and 0.30, separately.

Prognostic nutritional index and systemic immune-inflammation index are prognostic biomarkers for non-small-cell lung cancer brain metastases.

Aim: This research aimed to elucidate the prognosis values of prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) and clinical characteristics in NSCLC patients with brain metastases (BM) underwent radiotherapy. Materials & methods: Cut-off points of hematological indicators were determined by receiver operating characteristic curve. Overall survival was evaluated by Kaplan-Meier method and Cox proportional hazards model. Results: We retrospectively analyzed 214 patients from January 2009 to December 2018. The result demonstrated the independent prognostic values of PNI (hazard ratio: 0.600; p = 0.004) and SII (hazard ratio: 1.486; p = 0.019). The remaining clinicopathologic factors, including brain radiotherapy modality, smoking history, numbers of brain metastases, intracranial symptoms and Radiation Therapy Oncology Group - recursive partitioning analysis, were independently related to survival (p < 0.05). Conclusion: PNI and SII could be critical prognostic indicators for NSCLC patients with BM.

SLC34A2 Up-regulation And SLC4A4 Down-regulation Correlates With Invasion, Metastasis, And The MAPK Signaling Pathway In Papillary Thyroid Carcinomas.

Papillary thyroid carcinoma (PTC) is one of the fastest growing endocrine system malignant carcinomas detected over the past decade. Unfortunately, more than 25% of PTC patients are characterized by their aggressiveness and subsequent metastasis; these characteristics usually indicate poor prognosis. Recently, increasing evidence has suggested that solute carrier (SLC) transporters may play a pivotal role in the initiation, invasion and metastasis of human carcinoma. However, the expression and clinicopathological significance of SLC transporters in patients with PTC remains undetermined. In this study, we aimed to elucidate how the differential expression of SLC transporters affects clinicopathological features, as well as determine the possible regulatory signaling pathways involved. Three differentially expressed SLC transporters were screened from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database using a bioinformatics approach. The results indicated that high SLC34A2 and low SLC4A4 protein expression exhibited a higher percentage of capsular invasion and extra-thyroid metastasis in patients. Logistic regression analysis showed that high SLC34A2 expression in tumors was identified as an independent risk factor for capsular invasion [odds ratio (OR)=11.400, 95% confidence interval (CI)=1.733-74.995, P=0.011] and extra-thyroid metastasis (OR=4.920, 95%CI=1.234-19.623, P=0.024), while low SLC4A4 expression in tumors was only identified as independent risk factors for extra-thyroid metastasis (OR=8.568, 95%CI =1.186-61.906, P=0.033). Specifically, for tumors with capsular invasion and extra-thyroid metastasis, the protein expression staining of SLC34A2 was markedly enhanced in the cytoplasm of follicular epithelial cells, contrastingly, SLC4A4 expression was notably weakened in the cytomembrane and nucleus. Intriguingly, both high SLC34A2 and low SLC4A4 protein expression were significantly linked to a high urinary iodine concentration in patients with PTC. Mechanistically, compared with adjacent normal thyroids, p-ERK was significantly up-regulated by 17.8% in the invading tumor; p-ERK, p-JNK, and p-P38 were markedly up-regulated by 29.2%, 67.1%, and 38.9% for metastatic tumors, respectively. Importantly, SLC4A4 negatively correlated with p-JNK (r=-0.696, P= 0.004) and p-P38 (r=-0.534, P=0.049). In conclusion, we suggest that up-regulated SLC34A2 (mainly in the cytoplasm) and down-regulated SLC4A4 (mainly in the cytomembrane and nucleus), which might be attributed to excess iodine intake, were closely linked to extra-thyroid metastasis in PTCs. Furthermore, this effect of SLC4A4 may be through the activation of JNK/P38 MAPK signaling pathway. Future in vivo and in vitro gain- or loss-of-function experiments are needed to verify these findings and further elucidate the deeper molecular mechanisms.

Preablative Stimulated Thyroglobulin and Thyroglobulin Reduction Index as Decision-Making Markers for Second Radioactive Iodine Therapy in Patients with Structural Incomplete Response.

PURPOSE: The aim of this study was to evaluate the value of preablative stimulated thyroglobulin (presTg) and thyroglobulin reduction index (TRI) to predict the different responses to second radioactive iodine (RAI) therapy in differentiated thyroid cancer (DTC) patients with structural incomplete response (SIR). PATIENTS AND METHODS: A single-center retrospective study analyzed the different clinical outcomes after second RAI therapy in 206 patients with SIR. PresTg1 and presTg2 were measured before first and second RAI management and TRI was the reduction index of presTg1 and presTg2. Cut-off values of presTg and TRI were obtained using receiver operating characteristic analysis. The univariate logistic regression analysis was performed to confirm these parameters as prognostic factors to predict different responses to second RAI therapy. RESULTS: Only ATA risk stratification, the post-therapy whole-body scanning (Rx-WBS) findings, presTg1, presTg2, TRI, were different in patients with SIR. After second RAI therapy, 28.2% (58/206) of patients with SIR initially were reclassified as excellent response (ER). PresTg1 <6.6 ng/mL, presTg2 <1.2ng/mL, and TRI >74.2% were excellent indications to predict ER from non-ER after second RAI treatment. PresTg1 >14.9 ng/mL, presTg2 >1.8ng/mL and TRI <66.5% were well markers to predict poor outcome (SIR). High risk and distant metastases could still be considered as risk factors. CONCLUSION: DTC patients with SIR could benefit through second RAI treatment. PresTg before each RAI therapy and TRI could be considered as effective decision-making markers for second RAI therapy and as predictive indications for clinical outcomes.

Research trends for papillary thyroid carcinoma from 2010 to 2019: A systematic review and bibliometrics analysis.

BACKGROUND: Thyroid carcinoma comprises the fastest rising incidence of carcinomas over the past decade. Papillary thyroid carcinoma (PTC) is the most predominant type of thyroid carcinoma. This study aimed to assess the research trends in the field of PTC. METHODS: Publications from January 2010 to December 2019 were retrieved from the Web of Science Core Collection database using Thompson Reuters. Searching strategies were determined according to Medical Subject Heading terms. Different kinds of bibliometrics software, such as HistCite and VOSviewer, and online bibliometrics analysis platforms were utilized to evaluate and visualize the results. RESULTS: A total of 8102 publications across 93 countries were identified, with the annual number of publications showing an increasing trend. The United States, China, and South Korea showed their dominant position in PTC publication outputs, H-index, total citations, and international collaborations. Thyroid was the most productive journal. Akira Miyauchi published the most articles, and the most productive institution was Yonsei University. The hotspots keywords proliferation, invasion and metastasis, diagnoses and prognoses, therapeutic resistance, recurrence, and microcarcinomas appeared earlier and were sustained over the last 3 years. CONCLUSIONS: This bibliometric study provides a comprehensive analysis delineating the scientific productivity, collaboration, and research hotspots within the PTC field, which will be very helpful when focusing on the direction of research over the next few years.