Effects of emissions caps on the costs and feasibility of low-carbon hydrogen in the European ammonia industry.

The European ammonia industry emits 36 million tons of carbon dioxide annually, primarily from steam methane reforming (SMR) hydrogen production. These emissions can be mitigated by producing hydrogen via water electrolysis using dedicated renewables with grid backup. This study investigates the impact of decarbonization targets for hydrogen synthesis on the economic viability and technical feasibility of retrofitting existing European ammonia plants for on-site, semi-islanded electrolytic hydrogen production. Results show that electrolytic hydrogen cuts emissions, on average, by 85% (36%-100% based on grid price and carbon intensity), even without enforcing emission limits. However, an optimal lifespan average well-to-gate emission cap of 1 kg carbon dioxide equivalent (CO2e)/kg H2 leads to a 95% reduction (92%-100%) while maintaining cost-competitiveness with SMR in renewable-rich regions (mean levelized cost of hydrogen (LCOH) of 4.1 euro/kg H2). Conversely, a 100% emissions reduction target dramatically increases costs (mean LCOH: 6.3 euro/kg H2) and land area for renewables installations, likely hindering the transition to electrolytic hydrogen in regions with poor renewables and limited land. Increasing plant flexibility effectively reduces costs, particularly in off-grid plants (mean reduction: 32%). This work guides policymakers in defining cost-effective decarbonization targets and identifying region-based strategies to support an electrolytic hydrogen-fed ammonia industry.

Silencing KPNA2 Promotes Ferroptosis in Laryngeal Cancer by Activating the FoxO Signaling Pathway.

We aim to clarify the specific role of Karyopherin α2 (KPNA2) in the progression of laryngeal cancer, a kind of malignant tumor with a poor curative effect. We performed the bioinformatic analysis to obtain the ferroptosis-related differentially expressed genes. KPNA2 was screened out. Then the CCK-8 assay, wound healing assay, and transwell assay were used to clarify the changes in the proliferation, migration, and invasion abilities of laryngeal cancer cells after silencing KPNA2. The concentrations of iron ions, glutathione, superoxide dismutase, and malondialdehyde were evaluated by the corresponding detection kits. The expression levels of cyclooxygenase 2, Acyl-CoA synthetase long-chain family member 4, glutathione peroxidase 4, forkhead box O (FoxO)1a and FoxO3a were determined by Western Blot. A total of 45 ferroptosis-related differentially expressed genes in laryngeal cancer were obtained, and KPNA2 was selected after bioinformatic analysis. In ferroptosis-induced laryngeal cancer cells, the cell viability, migration rate, invasion ability, and the expression of glutathione peroxidase 4, glutathione, and superoxide dismutase were further decreased and the expression of cyclooxygenase 2, Acyl-CoA synthetase long-chain family member 4, iron ions, and malondialdehyde were further increased after silencing KPNA2. The expression levels of FoxO1a and FoxO3a in laryngeal cancer cells were increased by silencing KPNA2. KPNA2 may be a promising therapeutic target for laryngeal cancer. Down-regulation of KPNA2 can promote ferroptosis in laryngeal cancer by stimulating the FoxO signaling pathway.

Assessing runoff control of low impact development in Hong Kong's dense community with reliable SWMM setup and calibration.

Low impact development (LID) is a sustainable practice to managing urban runoff. However, its effectiveness in densely populated areas with intense rainfall, such as Hong Kong, remains unclear due to limited studies with similar climate conditions and urban patterns. The highly mixed land use and complicated drainage network present challenges for preparing a Storm Water Management Model (SWMM). This study proposed a reliable framework for setting up and calibrating SWMM by integrating multiple automated tools to address these issues. With a validated SWMM, we examined LID's effects on runoff control in a densely built catchment of Hong Kong. A designed full-scale LID implementation can reduce total and peak runoffs by around 35-45% for 2, 10 and 50-year return rainfalls. However, LID alone may not be adequate to handle the runoff in densely built areas of Hong Kong. As the rainfall return period increases, total runoff reduction increases, but peak runoff reduction remains close. Percentages of reduction in total and peak runoffs decline. The marginal control diminishes for total runoff while remaining constant for peak runoff when increasing the extent of LID implementation. In addition, the study identifies the crucial design parameters of LID facilities using global sensitivity analysis. Overall, our study contributes to accelerating the reliable application of SWMM and deepening the understanding of the effectiveness of LID in ensuring water security in densely built urban communities located near the humid-tropical climate zone, such as Hong Kong.

Hypoxia formation triggered by the organic matter from subsurface chlorophyll maximum in a large estuary-shelf system.

This study reports, for the first time, the role of shoreward transport of organic matter (OM) from subsurface chlorophyll maximum (SCM) in triggering hypoxia off the Pearl River Estuary (PRE, an outstanding example of typical estuary-shelf systems) based on field measurements. Compared to frequently observed hypoxia driven by surface eutrophication and terrestrial OM during large river discharge, we demonstrate that the upslope-transported SCM played a critical role in forming offshore hypoxia during low river discharge. Together with the plume-sourced OM trapped below the surface plume front, upslope-transported OM originating from the SCM accumulated underneath the pycnocline and consumed dissolved oxygen (DO), enhancing the bottom hypoxia. The DO consumption induced by the SCM-associated OM was estimated to contribute ∼ 26% (±23%) of the DO depletion under the pycnocline. Based on coherent and consistent physical and biogeochemical evidence and reasoning, this study reveals the contribution of SCM to bottom hypoxia off the PRE, which is unreported and likely occurs in other coastal hypoxic systems.

Multi-stage planning of LID-GREI urban drainage systems in response to land-use changes.

Long-term planning of urban drainage systems aimed at maintaining the sustainability of urban hydrology remains challenging. In this study, an innovative multi-stage planning framework involving two adaptation pathways for optimizing hybrid low impact development and grey infrastructure (LID-GREI) layouts in opposing chronological orders was explored. The Forward Planning and Backward Planning are adaptation pathways to increase LID in chronological order based on the initial development stage of an urban built-up area and reduce LID in reverse chronological order based on the final development stage, respectively. Two resilience indicators, which considered potential risk scenarios of extreme storms and pipeline failures, were used to evaluate the performance of optimized layouts when land-use changed and evolved over time. Compared these two pathways, Forward Planning made the optimized layouts more economical and resilient in most risk scenarios when land-use changed, while the layouts optimized by Backward Planning showed higher resilience only in the initial stage. Furthermore, a decentralized scheme in Forward Planning was chosen as the optimal solution when taking costs, reliability, resilience, and land-use changes into an overall consideration. Nevertheless, this kind of reverse optimization order offers a novel exploration in planning pathways for discovering the alternative optimization schemes. More comprehensive solutions can be provided to decision-makers. The findings will shed a light on the exploration of optimized layouts in terms of spatial configuration and resilience performance in response to land-use changes. This framework can be used to support long-term investment and planning in urban drainage systems for sustainable stormwater management.

Hidden challenges behind ecosystem services improvement claims.

Substantial evidence indicates that China's afforestation statistically contributed to the ecosystem services (ES) improvement. However, we found the potential challenges behind this improvement, especially in water-limited areas. We propose an attribution analysis method, which can assess the specific contribution of natural, human and cognition degree drivers to ES dynamics. The results found that the ratio of natural and human drivers in the area north of China's 400 mm precipitation isopleth is 2:7. This means local vegetation capacity has already exceeded water limitation, implying a conflict between nature and humans. However, the natural contribution in the area between 400 and 800 mm precipitation isopleth is negative, whereas the human contribution is 91%. This means this area has fragile natural conditions and needs more flexible policies. The ratio of natural and human drivers in the region south of 800 mm precipitation isopleth is 6:3, suggesting the ecological policies here can be maintained.

Integration of multi-objective spatial optimization and data-driven interpretation to direct the city-wide sustainable promotion of building-based decentralized water technologies.

Decentralized water technologies such as rainwater harvesting (RWH) and greywater recycling (GWR) can supplement centralized urban water systems, helping reduce water withdrawal and improve water reliability. These benefits only emerge when decentralized water technologies are widely implemented. Several decision-supporting frameworks have been developed to identify suitable locations for deploying decentralized water technologies in a city. Yet, the support remains inadequate regarding: (1) the evaluation of the trade-off between environmental benefits and economic costs in selecting locations, and (2) the interpretation of the transition of optimal selections from low to high investment to assist in the promotion. This study presents an integrated analytic framework that combines multi-objective optimization and data-driven interpretation to direct the city-wide sustainable promotion of building-based decentralized water technologies. We select single-family houses in the city of Boston and apply the framework to study the promotion of building-based RWH and GWR. The framework starts with multi-objective spatial optimization to identify the non-dominant optimal selections (i.e., Pareto-front) of houses and technologies at the trade-off between maximizing energy savings and minimizing financial investment. Then, we evaluate the impact of the initial selection setting and the community-based maximum water saving constraint on the Pareto-optimal front. The spatial optimization shows that RWH is much more applicable than GWR for single-family house communities in Boston. When interpreting the Pareto-front, two clusters of census blocks stand out based on the change in the percentages of houses selected to invest RWH and GWR in each census block along with different investment levels. One cluster demonstrates its priority of being first selected to deploy RWH. Using Random Forest, critical features explain why one cluster should be selected first for promotion, including the larger demand for non-potable water use, longer distance from the centralized facilities, and larger rooftop for collecting rainwater. Finally, we discuss possible future improvements of the proposed spatial optimization and interpretation framework. Overall, our study can be useful to promote decentralized water technologies in cities.

Predictors of Thyroid Gland Invasion in Total Laryngectomy for Advanced Laryngeal Squamous Cell Carcinoma.

Objectives: Thyroidectomy for advanced laryngeal squamous cell carcinoma (LSCC) is controversial. This study aimed to identify predictors of thyroid gland invasion in patients with LSCC and management of the thyroid gland during total laryngectomy. Patients and Methods: Clinical data and pathological characteristics of 113 patients, who underwent laryngectomy with thyroidectomy for advanced LSCC in Guangdong Provincial People's Hospital between 2009 and 2019, were retrospectively analyzed. The incidence and predictors of thyroid gland invasion were analyzed, and a new predictor was proposed using a parallel test. Results: Of 113 patients, 25.7% exhibited thyroid invasion. A new predictor that combined the lower third of thyroid cartilage invasion and thyroid gland invasion on computed tomography/magnetic resonance imaging (CT/MRI) was associated with pathological thyroid gland invasion (P = 0.001; sensitivity, 88.2%; negative predictive value, 95%). Conclusion: Thyroidectomy may be required during total laryngectomy in those with invasion of the lower third of thyroid cartilage and/or thyroid gland invasion revealed on CT/MRI instead of being performed routinely.

Designing coupled LID-GREI urban drainage systems: Resilience assessment and decision-making framework.

As flooding risks rise in urban areas, research suggests combining low impact development (LID) and grey infrastructure (GREI) in urban drainage systems. Several frameworks have been proposed to plan such coupled systems, but there is not a comprehensive framework to assess their resilience under diverse failure scenarios and sources of uncertainty. This study proposes a framework which considers both technological and operational resilience. Technological resilience has to do with the performance of the system under extreme loads. Operational resilience has to do with the performance and long-term efficiency of the system after structural damage or degradation, using appropriate probability distributions to quantify the likelihood of failures. The proposed framework is based on an optimization and multi-criteria decision-making platform. It improves on previous research, which lacked consideration of uncertainty in resilience over the life span. We also apply the proposed framework to a real-world test case, and find that in a high-density urban area, a coupled system is more cost-effective than GREI alone. Furthermore, decentralized systems with greater flexibility show significantly better technological and operational resilience. The proposed framework can better support decision-making for planning robust and cost-effective urban drainage systems, particularly in highly urbanized areas.

Impact of implementation timing on the effectiveness of stay-at-home requirement under the COVID-19 pandemic: Lessons from the Italian Case.

When a new infectious outbreak emerges, governments must initially rely on non-pharmaceutical interventions (NPIs) to mitigate the impact of the pathogen. Although a strict stay-at-home requirement (i.e., lockdown) presents high effectiveness in reducing patients hospitalized in intensive care units (ICUs), it comes with unintended physical, psychological, and economic damages for the citizens. Using how Italy managed the COVID-19 outbreak from February to September 2020 on a national basis, this study aims at understanding the impact of implementation timing on the effectiveness of NPIs. Our findings may be helpful to avoid the implementation of stay-at-home requirements when it is not strictly necessary. A compartmental SEICRD model was developed to create the baseline scenario without NPIs. Generalized Poisson regressions were applied to study the change in effectiveness over-time of NPIs on Avoided ICUs for each one of the Italian regions. Our study suggests that although the stay-at-home requirement is the most effective measure in reducing ICU hospitalizations in regions encountering the outbreak early, its effectiveness decreases in regions encountering the outbreak later, where a set of other NPIs are more effective. We developed a reference of daily new cases when lockdown should be implemented or avoided, accordingly. Our findings could be useful to support policymakers in contrasting the pandemic and in limiting the societal and economic impact of stringent NPIs.

Exploring the response patterns of strong-flavor baijiu brewing microecosystem to fortified Daqu under different pit ages.

The fermentation of strong-flavor baijiu depends largely on the evolution of the microbial community that originated from Daqu and pit mud (PM). Applying fortified Daqu (FD) has been proven to be an effective strategy to improve the quality and yield of baijiu. However, it is unclear what the effects of FD on the liquor brewing microecosystem under different pit ages because of the temporal heterogeneity of the PM community. Taking 2-year (new) and 40-year (aged) pits as the objects, the influence of FD on the metabolic profile, physicochemical parameters, and community diversity in Zaopei and PM was investigated by polyphase detecting approaches. Present results showed that the metabolic profiles of Zaopei were significantly improved by FD, whereas those of PM were mainly dependent on pit age. Aspergillus, Caproiciproducens, and Methanosarcina were more abundant in the aged pit, while Kazachstania, Lactobacillus, and Sphingomonas dominated in the new pit, whether in Zaopei or in PM. The interaction relationships among the communities were also altered by FD, and the co-occurrence network, especially the increased links between archaea and bacteria in the new pit. Notably, this interaction in the aged pit distinctly affected the hexanoic acid content based on the Mantel test. The results of PICRUSt2 analysis inferred that FD perhaps improved the interspecies hydrogen transfer in the new pit and increased the carbon flow of hexanoic acid production during chain elongation in the aged pit. These results provide new insights into the production of high-quality strong-flavor baijiu and the aging of PM.

Thyroid gland invasion in total laryngectomy: A systematic review and meta-analysis.

BACKGROUND: Although guidelines indicate that thyroidectomy should be performed routinely during total laryngectomy in patients with advanced laryngeal cancer, its clinical indications remain controversial. Some researchers believe that thyroid invasion is uncommon and that thyroid preservation should be considered in most cases. OBJECTIVE: This study aimed to identify the incidence and predictors of thyroid invasion in patients with laryngeal cancer to facilitate decision-making regarding whether to perform thyroidectomy during total laryngectomy. MATERIALS AND METHODS: The author conducted a systematic review and meta-analysis of all published articles retrieved from a search of the MEDLINE (1982-2020) and EMBASE (1971-2020) databases. The published studies of advanced laryngeal cancer with total laryngectomy and partial or total thyroidectomy for laryngeal cancer were selected. The incidence and predictors of thyroid invasion were analyzed. RESULTS: We analyzed 25 studies (2177 cases), of which 176 people (8.08%) had thyroid invasion. Subglottic tumors (odds ratio [OR], 3.74; 95% CI, 1.75-7.99), T4 stage tumors (OR, 2.39; 95% CI, 1.20-4.75), subglottic extension (OR, 3.85; 95% CI,2.09-7.11), and thyroid cartilage invasion (OR, 3.98; 95% CI, 1.47-10.75) are risk factors for thyroid invasion, and no statistically significant difference was noted between recurrent tumor and thyroid invasion. CONCLUSION: The risk of thyroid invasion was significantly higher when advanced laryngeal cancer involved subglottic tumors, T4 stage tumors, subglottic extension, and thyroid cartilage invasion. The overall incidence of thyroid gland invasion was low; therefore, thyroidectomy may be performed for cases deemed risky rather than as a routine measure of total laryngectomy. RESEARCH REGISTRY UIN: reviewregistry1226.

Effect of minocycline hydrochloride combined with photodynamic therapy on skin barrier function of patients with acne.

OBJECTIVE: The aim of this study is to evaluate the effects of minocycline hydrochloride combined with photodynamic therapy on skin barrier function of patients with acne. METHODS: Eighty-eight acne patients admitted to our hospital were randomized into research group (n=44, photodynamic therapy on the basis of minocycline hydrochloride) and control group (n=44, minocycline hydrochloride). The clinical efficacy, skin barrier function indexes (transdermal water loss (TEWL), stratum corneum water content, pH value), scores of GAGS and Acne-QOL, cosmetic satisfaction and adverse reaction rates of the two groups were compared. RESULTS: The total effective rate of research group was higher than that of control group (P<0.05). After treatment, TEWL, cuticle water content and pH value were improved compared with those before treatment, and the research group was superior to the control group (all P<0.05). After treatment, the GAGS scores of both groups were lower than those before treatment, and the research group was lower than that of the control group (all P<0.05). The cosmetic satisfaction in the research group was higher than that in the control group (P<0.05). There was no marked difference in the incidence of adverse reactions between the two groups (P>0.05). After treatment, the quality of life scores of patients were higher than before treatment, and the research group was higher than that of the control group (all P<0.05). CONCLUSION: Minocycline hydrochloride combined with photodynamic therapy can effectively improve the skin barrier function of patients, relieve clinical symptoms, and enhance the overall efficacy and quality of life. It is also safe and patients are highly satisfied with the cosmetic effect.

HTR7 promotes laryngeal cancer growth through PI3K/AKT pathway activation.

BACKGROUND: Laryngeal cancer is a common malignancy of the head and neck, it's important to find novel targets for its therapy. The 5-hydroxytryptamine receptor 7 (HTR7) belongs to the G protein-coupled receptors (GPCRs) family which are easily druggable in diseases; however, its role in laryngeal cancer remains unknown. METHODS: Colony formation assay, Soft agar growth assay, BrdU incorporation assay and MTT assay were used to analyze the effect of HTR7 on laryngeal cancer cell proliferation. Xenograft tumors in nude mice was used to analyze the effect of HTR7 on laryngeal cancer growth. Luciferase reporter assay was used to analyze the effect of HTR7 on phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT) pathway activity. RESULTS: We found that HTR7 was significantly upregulated in laryngeal cancer tissues and cells, and patients with high HTR7 expression had shorter survival time than those with low HTR7 expression. Univariate and multivariate Cox regression models showed that HTR7 was an independent predictive factor for the prognosis of patients with laryngeal cancer. Cell proliferation assays and an animal model showed that HTR7 overexpression promoted laryngeal cancer proliferation and growth, while HTR7 knockdown inhibited laryngeal cancer proliferation and growth. Further analysis showed HTR7 activated the PI3K/AKT pathway, characterized by increased phosphorylation of AKT, luciferase reporter activity of forkhead box O (FOXO) factors, and target expression. Inhibition of the PI3K/AKT pathway in HTR7-overexpressing cells suppressed proliferation and growth, suggesting that HTR7 promotes laryngeal cancer proliferation and growth by activating the PI3K/AKT pathway. CONCLUSIONS: HTR7 is not only a target for laryngeal cancer therapy but also a prognostic factor for the prognosis of patients with laryngeal cancer.

Upregulation of Long Noncoding RNA_GAS5 Suppresses Cell Proliferation and Metastasis in Laryngeal Cancer via Regulating PI3K/AKT/mTOR Signaling Pathway.

BACKGROUND: Laryngeal cancer is one of the most common malignant tumors among head and neck cancers. Accumulating studies have indicated that long noncoding RNAs (lncRNAs) play an important role in laryngeal cancer occurrence and progression, however, the functional roles and relative regulatory mechanisms of lncRNA growth arrest-specific transcript 5 (GAS5) in laryngeal cancer progression remain unclear. METHODS: The expression of lncRNA GAS5 in both laryngeal cancer tissues and cell lines was evaluated using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay. The relationships between lncRNA GAS5 expression and clinical parameters were also analyzed. To determine the biological function of lncRNA GAS5, a lncRNA GAS5-specific plasmid was first transfected into laryngeal cancer cells using lentiviral technology. Cell counting kit-8 assay, flow cytometry, and Transwell assays were used to detect in vitro cell proliferation, apoptosis, cycle distribution, and metastasis abilities, respectively. Furthermore, in vivo cell growth experiments were also performed using nude mice. Additionally, western blotting was performed to identify the underlying regulatory mechanism. RESULTS: In the current study, lncRNA GAS5 was downregulated in laryngeal cancer tissues and its low expression was closely associated with poor tumor differentiation, advanced TNM stage, lymph node metastasis, and shorter overall survival time. In addition, lncRNA GAS5 upregulation significantly inhibited laryngeal cancer cell proliferation both in vitro and in vivo. Moreover, in response to lncRNA GAS5 overexpression, more laryngeal cancer cells were arrested at the G2/M stage, accompanied by increased cell apoptosis rates and suppressed migration and invasion capacities. Mechanistically, our data showed that the overexpression of lncRNA GAS5 significantly regulated the PI3K/AKT/mTOR signaling pathway. CONCLUSION: LncRNA GAS5 might act as a suppressor gene during laryngeal cancer development, as it suppressed cell proliferation and metastasis by regulating the PI3K/AKT/mTOR signaling pathway; thus, lncRNA GAS5 is a promising therapeutic biomarker for the treatment of laryngeal cancer.

Characteristics of pharyngeal paraesthesia symptoms in patients with obstructive sleep apnoea.

PURPOSE: This study aimed to investigate pharyngeal paraesthesia symptoms in patients with obstructive sleep apnoea (OSA). MATERIAL AND METHODS: Patients with snoring and suspected OSA as well as age-matched controls were recruited. All participants underwent nocturnal polysomnography (PSG) and pharyngeal paraesthesia assessment using the Glasgow-Edinburgh throat scale (GETS). The incidence and severity of pharyngeal paraesthesia symptoms were compared between the groups. RESULTS: A total of 280 patients who snored or were suspected of having OSA and 35 healthy, age-matched controls were recruited. The total pharyngeal paraesthesia symptom score was significantly higher in the OSA group than in the healthy group (12 [5, 23] vs. 3 [0, 9]; p < 0.001). The most frequent pharyngeal paraesthesia symptoms in the snore patients were Q7 (catarrh down the throat) and Q3 (discomfort/irritation in the throat), which are related to the irritability of the throat. The incidence of Q7 (OSA, 58% vs. controls, 14%; χ2 = 23.66; p < 0.001), Q3 (OSA, 46% vs. controls, 3%; χ2 = 23.07; p < 0.001), Q1 (feeling of something stuck in the throat; OSA, 33% vs. controls, 6%; χ2 = 11.00; p = 0.001), Q6 (swelling in the throat; OSA, 31% vs. controls, 0%; χ2 = 14.53; p < 0.001), Q9 (want to swallow all the time; OSA, 20% vs. controls, 6%; χ2 = 6.28; p = 0.012), Q5 (throat closing off; OSA, 24% vs. controls, 6%; χ2 = 6.16; p = 0.013), and Q2 (pain in the throat; OSA, 23% vs. controls, 6%; χ2 = 5.32; p = 0.021) was significantly higher in the OSA group than in the controls CONCLUSIONS: Patients with obstructive sleep apnoea have higher pharyngeal paraesthesia symptoms scores and tend to have irritated throats compared to healthy controls. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03506178.

MiR-125a-5p inhibits cell proliferation, cell cycle progression, and migration while promoting apoptosis in head and neck cancers by targeting ERBB3.

OBJECTIVE: Head and neck cancer is one of the most common cancer types worldwide. MicroRNAs play a vital regulatory role in the occurrence and development of cancer. The objective of this study is to explore the mechanism of miR-125a-5p in the proliferation, migration and apoptosis of head and neck cancer cells and define its target genes. METHODS: The effects of miR-125a-5p on head and neck cancer cells proliferation, cell cycle distribution, apoptosis and migration were evaluated by colony formation, BrdU assay, flow cytometry and transwell assays. The potential target gene of miR-125a-5p was determined by luciferase activity assay and western blot analysis. RESULTS: In this study, overexpression of miR-125a-5p significantly inhibited the proliferation of head and neck cancer cells, whereas inhibition of miR-125a-5p enhanced their proliferation. BrdU assay and flow cytometry revealed that miR-125a-5p might inhibit the proliferation of cancer cells by causing cell cycle arrest. Cell apoptosis assay and Transwell assay indicated that miR-125a-5p induced cell apoptosis and inhibited cell migration of cancer cells. Other experiments confirmed that miR-125a-5p could significantly downregulate its expression by binding to ERBB3 to inhibit proliferation and ERBB3 could at least partially mediate the inhibition of miR-125a-5p on the proliferation of head and neck cancer cells. CONCLUSION: The findings of this study suggested that the miR-125a-5p/ERBB3 axis might play a role in the proliferation, regulation of cell cycle, migration and apoptosis of head and neck cancer cells, potentially offering a new target for treatments of head and neck cancers.

Association between single nucleotide polymorphisms of IL-6 and susceptibility to skin cancer: a meta-analysis and systematic review.

BACKGROUND: As one of the most common body malignant cancers, skin cancers contain a group of highly heterogeneous tumors with different malignant potential, prognosis and treatment methods. Despite the progress in the treatment of skin cancers worldwide, the overall prognosis is still poor. Recent studies indicated single nucleotide polymorphisms (SNPs) of interleukin-6 (IL-6), including 174G/C and 597G/A, might be associated with susceptibility to skin cancer. This meta-analysis aims to clarify the relationship between IL-6 gene polymorphisms and skin cancers. METHODS: Eligible studies were identified from searching PubMed, Embase, Web of Science and Cochrane. Pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were obtained for the relationships between IL-6 174G/C and 597G/A polymorphisms and skin cancer using random-effects models. For the included studies, the Newcastle-Ottawa scale (NOS) score was calculated to assess study quality. Heterogeneity tests, sensitivity analysis, and publication bias assessments were also performed. Trim-and-fill method was used when publication bias existed aiming to adjusting OR. All data were analyzed in R (version 4.0.2). RESULTS: This meta-analysis included 1,705 cases and 1,987 controls for 174G/C polymorphism (10 publications), and 968 cases and 998 controls for 597G/A polymorphism (3 publications). No elevated risk of skin cancer was found in all comparisons for 174G/C polymorphism: CC vs. GC + GG, OR =1.03 (95% CI: 0.81-1.31); GC + CC vs. GG, OR =1.16 (95% CI: 0.96-1.39); CC vs. GG, OR =1.14 (95% CI: 0.86-1.53); GC vs. GG, OR =1.16 (95% CI: 0.99-1.37); C vs. G, OR =1.07 (95% CI: 0.92-1.24). Then we performed subgroup analysis based on publication year, the cancer type, sample size, NOS score. Significant differences were observed in the subgroup of publication year before 2010 (GC + CC vs. GG, OR =1.255, P=0.012; GC vs. GG, OR =1.277, P=0.01), while there is no statistical significance in the subgroup of publication year after 2010 (P>0.05 for all comparisons). After publication bias adjustment, the results further suggested that 174G/C polymorphism is not associated with the risk of skin cancer. No elevated risk of skin cancer was found in the comparisons for 597G/A polymorphism. DISCUSSION: Current evidence showed that IL-6 gene polymorphisms might not be associated with the susceptibility to skin cancer.

Azithromycin combined with doxycycline in non-gonococcal urethritis.

Non-gonococcal urethritis (NGU) is one of the most common sexually transmitted diseases caused by chlamydia or mycoplasma. The present study aimed to explore the clinical efficacy of azithromycin combined with doxycycline in patients with NGU and its effect on serum levels of inflammatory cytokine interleukin-6 (IL-6). A total of 98 patients with non-gonococcal urethritis were prospectively selected, of which 46 patients were assigned to an azithromycin group (treated with azithromycin alone), while the rest were assigned to a combination group (treated with azithromycin and doxycycline). The conditions of the patients were evaluated and compared between the two groups. The treatment efficacy in patients in the combination group was significantly better than that in the azithromycin group, and the time to symptom relief, period of medication, recurrence rate within 1 year of withdrawal and level of serum IL-6 in the combination group were significantly lower than those in the azithromycin group. The quality of life of patients in the combination group was significantly improved compared to those in the azithromycin group. However, there was no significant difference in the incidence of adverse reactions between the two groups. Azithromycin combined with doxycycline was revealed to be more effective than azithromycin monotherapy for NGU.

OTX1 exerts an oncogenic role and is negatively regulated by miR129-5p in laryngeal squamous cell carcinoma.

BACKGROUND: Orthodenticle homeobox 1 (OTX1) is a transcription factor that plays an important role in various human cancers. However, the function of OTX1 in laryngeal squamous cell carcinoma (LSCC) is largely unknown. We aimed to explore the roles of OTX1 in LSCC and its possible molecular mechanism. METHODS: The expression levels of OTX1 were assessed in LSCC cell lines and tissue samples. We further examined the effect of OTX1 on LSCC progression. The upstream regulator of OTX1 was identified using a computer algorithm and confirmed experimentally. RESULTS: OTX1 was highly expressed in 70.7% (70/99) of LSCC tissue samples. The OTX1 expression in LSCC was significantly correlated with lymph node metastasis. High OTX1 expression in patients with LSCC was correlated with poor prognosis. Knockdown of OTX1 inhibited proliferation, colony formation, migration and invasion in LSCC cells. Knockdown of OTX1 inhibited tumor growth in a xenograft mouse model. Mechanistically, OTX1 might act as a direct target of miR-129-5p. OTX1 enhanced tumorigenicity and tumor growth both in vitro and in vivo. CONCLUSIONS: Our findings support that OTX1 is an oncogene in LSCC tumorigenesis and progression. Furthermore, OTX1 is a direct target of miR-129-5p in LSCC cells. Taken together, OTX1 is a promising diagnostic and therapeutic marker for LSCC.