Application of organoids in otolaryngology: head and neck surgery.

PURPOSE: The purpose of this review is to systematically summarize the application of organoids in the field of otolaryngology and head and neck surgery. It aims to shed light on the current advancements and future potential of organoid technology in these areas, particularly in addressing challenges like hearing loss, cancer research, and organ regeneration. METHODS: Review of current literature regrading organoids in the field of otolaryngology and head and neck surgery. RESULTS: The review highlights several advancements in the field. In otology, the development of organoid replacement therapies offers new avenues for treating hearing loss. In nasal science, the creation of specific organoid models aids in studying nasopharyngeal carcinoma and respiratory viruses. In head and neck surgery, innovative approaches for squamous cell carcinoma prediction and thyroid regeneration using organoids have been developed. CONCLUSION: Organoid research in otolaryngology-head and neck surgery is still at an early stage. This review underscores the potential of this technology in advancing our understanding and treatment of various conditions, predicting a transformative impact on future medical practices in these fields.

Research progress and application of single-cell sequencing in head and neck malignant tumors.

Single-cell sequencing (SCS) is a technology that separates thousands of cells from the organism and accurately analyzes the genetic material expressed in each cell using high-throughput sequencing technology. Unlike the traditional bulk sequencing approach, which can only provide the average value of a cell population and cannot obtain specific single-cell data, single-cell sequencing can identify the gene sequence and expression changes of a single cell, and reflects the differences between genetic material and protein between cells, and ultimately the role played by the tumor microenvironment. single-cell sequencing can further explore the pathogenesis of head and neck malignancies from the single-cell biological level and provides a theoretical basis for the clinical diagnosis and treatment of head and neck malignancies. This article will systematically introduce the latest progress and application of single-cell sequencing in malignant head and neck tumors.

Mechanism and treatment of olfactory dysfunction caused by coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the start of the pandemic, olfactory dysfunction (OD) has been reported as a common symptom of COVID-19. In some asymptomatic carriers, OD is often the first and even the only symptom. At the same time, persistent OD is also a long-term sequela seen after COVID-19 that can have a serious impact on the quality of life of patients. However, the pathogenesis of post-COVID-19 OD is still unclear, and there is no specific treatment for its patients. The aim of this paper was to review the research on OD caused by SARS-CoV-2 infection and to summarize the mechanism of action, the pathogenesis, and current treatments.

T cell effects and mechanisms in immunotherapy of head and neck tumors.

Head and neck tumors (HNCs) are a common tumor in otorhinolaryngology head and neck surgery, accounting for 5% of all malignant tumors in the body and are the sixth most common malignant tumor worldwide. In the body, immune cells can recognize, kill, and remove HNCs. T cell-mediated antitumor immune activity is the most important antitumor response in the body. T cells have different effects on tumor cells, among which cytotoxic T cells and helper T cells play a major killing and regulating role. T cells recognize tumor cells, activate themselves, differentiate into effector cells, and activate other mechanisms to induce antitumor effects. In this review, the immune effects and antitumor mechanisms mediated by T cells are systematically described from the perspective of immunology, and the application of new immunotherapy methods related to T cells are discussed, with the objective of providing a theoretical basis for exploring and forming new antitumor treatment strategies. Video Abstract.

The role and mechanism of action of tRNA-derived fragments in the diagnosis and treatment of malignant tumors.

Cancer is a leading cause of morbidity and death worldwide. While various factors are established as causing malignant tumors, the mechanisms underlying cancer development remain poorly understood. Early diagnosis and the development of effective treatments for cancer are important research topics. Transfer RNA (tRNA), the most abundant class of RNA molecules in the human transcriptome, participates in both protein synthesis and cellular metabolic processes. tRNA-derived fragments (tRFs) are produced by specific cleavage of pre-tRNA and mature tRNA molecules, which are highly conserved and occur widely in various organisms. tRFs were initially thought to be random products with no physiological function, but have been redefined as novel functional small non-coding RNA molecules that help to regulate RNA stability, modulate translation, and influence target gene expression, as well as other biological processes. There is increasing evidence supporting roles for tRFs in tumorigenesis and cancer development, including the regulation of tumor cell proliferation, invasion, migration, and drug resistance. Understanding the regulatory mechanisms by which tRFs impact these processes has potential to inform malignant tumor diagnosis and treatment. Further, tRFs are expected to become new biological markers for early diagnosis and prognosis prediction in patients with tumors, as well as a targets for precision cancer therapies. Video abstract.

Role of exosomal competitive endogenous RNA (ceRNA) in diagnosis and treatment of malignant tumors.

Malignant tumors are a threat to human health, thus it is critical to better understand the mechanism of tumor occurrence and development and to find key therapeutic targets. Competitive endogenous RNA (ceRNA) is a type of RNA molecule that includes mRNA of coding-protein, pseudogenes, long non-coding RNA (lncRNA), and circular RNA (circRNA) etc. It is created through a competitive combination of common small RNA (miRNA) and has an inhibitory effect on mRNA translation. ceRNA regulate the post transcriptional expression of genes by competitively binding to common microRNAs (miRNAs).Studies have shown that cernas are involved in tumor cell proliferation, invasion and migration, drug resistance, angiogenesis, as well as tumor immunity, and so on, affecting the progression of tumor development. This article reviews the reported roles of exosomal ceRNA in the diagnosis and treatment of malignant tumors and the mechanisms underlying these.

Roles and clinical application of exosomal circRNAs in the diagnosis and treatment of malignant tumors.

Exosomes are microvesicles secreted by cells. They contain a variety of bioactive substances with important roles in intercellular communication. Circular RNA (circRNA), a type of nucleic acid molecule found in exosomes, forms a covalently bonded closed loop without 5' caps or 3' poly(A) tails. It is structurally stable, widely distributed, and tissue specific. CircRNAs mainly act as microRNA sponges and have important regulatory roles in gene expression; they are superior to other non-coding RNAs as molecular diagnostic markers and drug treatment targets. Exosomal-derived circRNAs in the body fluids of tumor patients can modulate tumor proliferation, invasion, metastasis, and drug resistance. They can be used as effective biomarkers for early non-invasive diagnosis and prognostic evaluation of tumors, and also represent ideal targets for early precision therapeutic intervention. This review provides a theoretical basis for exploring the applications of exosomal circRNAs in malignant tumor diagnosis and treatment. We describe the biological functions of exosomal circRNAs in the occurrence and development of malignant tumors, their potential utility in diagnosis and treatment, and possible mechanisms.

Research Progress of Olfactory Nerve Regeneration Mechanism and Olfactory Training.

The olfactory nerve (ON) is the only cranial nerve exposed to the external environment. Hence, it is susceptible to damage from head trauma, viral infection, inflammatory stimulation, and chemical toxins, which can lead to olfactory dysfunction. However, compared with all other cranial nerves, the ON is unique due to its inherent ability to regenerate. This characteristic provides a theoretical basis for treatment of olfactory dysfunction. Olfactory training (OT) is one of the main treatments for olfactory dysfunction. It is easy to apply and has few side-effects, and has been shown to be efficacious for patients with olfactory dysfunction of various causes. To further understand the application value of ON regeneration and OT on olfactory dysfunction, we review the research progress on the mechanism of ON regeneration and OT.

A holistic understanding of cobalt cycling and limiting roles in the eutrophic Lake Taihu.

Cobalt (Co) cycling is often dominated by its role as a micronutrient in marine, while little is known on its cycling in a shallow eutrophic lake. Monthly sampling was performed in eutrophic Meiliang Bay of Lake Taihu, combining two laboratory control experiments and in situ Co limitation bioassay experiments. The high-resolution dialysis and the diffusive gradients in thin films technique were used to detect dissolved and labile Co, respectively. The positive correlations between dissolved/labile Co and Mn in the sediments for 6 or 7 months demonstrated that the mobility of Co in the sediments was primarily controlled by Mn redox cycling in the field. However, it is unexpected that the dissolved and labile Co only showed a small change over one year irrespective of the significant fluctuation in dissolved/labile Mn, with the concentrations being as low as 1.08 ± 0.22 µg/L and 0.246 ± 0.091 µg/L for dissolved and labile Co in the surface 20 mm sediment, respectively. Cyanobacterial bloom simulation and aerobic-anaerobic-cyanobacterial addition experiments indicated that the level of Co in the sediment-overlying water system was strongly regulated by cyanobacterial uptake, followed by the degradation of Co-enriched cyanobacterial biomass, which offset the influence of Mn redox cycling on Co mobility in the sediment. The significant enhancement of Microcystis spp. biomass by Co addition further indicated that Co was the potential limiting nutrient for cyanobacterial blooms. This work provides new ideas for better management strategies of eutrophication in shallow lakes.

Mobility of chromium in sediments dominated by macrophytes and cyanobacteria in different zones of Lake Taihu.

To study the mechanisms of chromium (Cr) mobilization in sediments of lakes with different ecotypes, seasonal sampling was performed in the macrophyte-dominated East Taihu (MDET) and cyanobacteria-dominated Meiliang Bay (CDMB) in Lake Taihu. Concentrations of labile Cr(VI) and dissolved Cr were assessed using diffusive gradients in thin films (DGT) and high-resolution dialysis passive sampling devices, respectively. Results indicated that in pore water the dissolved Cr concentrations and in sediments total Cr and Cr fractions concentrations (dissolved, exchangeable and carbonate fraction (F1), Fe-Mn oxide fraction (F2), organic/sulfide fraction (F3)) were lower in MDET than in CDMB. However, the highly toxic DGT-labile Cr(VI) concentrations were higher in MDET sediments than in CDMB sediments. In the two lake zones, the seasonal variations in concentrations of dissolved Cr and DGT-labile Cr(VI) were significant, while total Cr and Cr fractions showed negligible changes (except F1 fraction). In summer, the high mobility of dissolved Cr (MDET: 103.42±10.82µg/L; CDMB: 108.99±4.24µg/L) were mainly caused by dissolved organic matter complexing with Cr(III). In winter the high mobility of dissolved Cr (MDET: 100.27±22.04µg/L; CDMB: 102.01±8.81µg/L) and DGT-labile Cr(VI) (MDET: 28.26±3.73µg/L; CDLZ: 25.82±2.26µg/L) were primarily caused by the oxidization of Cr (III) by Mn(III/IV) oxides. This study establishes the mechanisms for seasonal variation of Cr mobilization in different lake ecological zones, highlighting the urgent need for remediation of Cr pollution, especially in macrophyte-dominated lake zones.

Peak Chromium Pollution in Summer and Winter Caused by High Mobility of Chromium in Sediment of a Eutrophic Lake: In Situ Evidence from High Spatiotemporal Sampling.

To study the mechanisms of chromium (Cr) mobilization in sediments of eutrophic lakes, monthly sampling was performed in the Meiliang Bay of Lake Taihu, China, combined with laboratory experiments. High-resolution dialysis and diffusive gradients in thin film (DGT) sampling techniques were used. Results indicated that in July 2016 and January 2017, the concentrations of soluble Cr and DGT-labile Cr(VI) in the overlying water exceeded both drinking and fishery water quality standards, resulting from the high mobility of Cr in sediments. In July (summer), the high concentration of soluble Cr (134.04 ± 7.20 µg/L) detected in the anaerobic sediments was primarily caused by the complexation of Cr(III) with dissolved organic matter (DOM). This mechanism was supported by an observed simultaneous increase of soluble Cr and DOM under simulated anaerobic conditions. In January (winter), the high concentrations of soluble Cr (97.55 ± 9.65 µg/L) and DGT-labile Cr(VI) (25.83 ± 1.25 µg/L) in aerobic sediments were primarily caused by reoxidation of Cr(III) by Mn(III/IV) oxides as evidenced by the lowest concentrations of soluble and DGT-labile Mn(II). This study sheds light on the full-year variation and mechanisms of Cr mobilization in eutrophic lake sediments and suggests the urgent need for remediation of Cr pollution especially for winter.

Efficacy of dredging engineering as a means to remove heavy metals from lake sediments.

Dredging is used worldwide to remove polluted sediments from water bodies. However, the dredging efficacy remains hard to identify. Here, we studied the efficacy of dredging engineering as a means to remove Cu, Cd, and Pb from polluted lake sediments, after six years of completion. Dissolved metals and DGT-labile metals were quantified in the non-dredged and post-dredged sediments by high-resolution dialysis (HR-Peeper) and diffusive gradients (DGT) in thin films techniques. April and July measurements showed that dredging was effectively remediate the polluted sediments. The dissolved Pb, Cd, and Cu contents decreased up to 30%, 44%, and 26%, and the DGT-labile contents decreased up to 51%, 27%, and 33% compared with the contents in the non-dredged zone. Dredging was thus proven efficient in decreasing the labile metal fractions, increasing the capacity of available solids to bind metals, and slowing the leaching of metals from available solids in the post-dredged sediments. In October and January, the dredging efficacy was counteracted by the decomposition of algae, which increased the dissolved and DGT-labile metal concentrations in the post-dredged zone.

Seasonal changes of lead mobility in sediments in algae- and macrophyte-dominated zones of the lake.

This study examined lead (Pb) pollution in algae- and macrophytes-dominated sediments, using diffusive gradient in thin films (DGT) and dialysis (HR-Peeper) techniques. Lead pollution varied by season in the two different ecotype sediments. In the algae-dominated zone, the highest concentrations of DGT-labile Pb and dissolved Pb occurred in April and July, respectively. The reductive dissolution of Fe/Mn oxides was identified as an important driver for Pb releases in April and July. This was supported by the decrease of the reducible fraction of Pb in sediments during those sampling periods. Furthermore, dissolved organic matter (DOM) complexation with Pb in sediments also significantly increased the dissolved Pb concentrations in July. The Pb-DOM complexes accounted for 95% of the total chemical species of Pb in pore water, calculated by Visual MINTEQ 3.1 model. Low concentrations of labile and dissolved Pb were observed in October and January; these resulted from the formation of Pb-sulfide precipitates and adsorption by Fe/Mn oxides. It was supported by the high rate of Pb(HS)2 precipitation (saturation index > 0), at 36%, in October samples and the high reducible fraction of Pb in sediments in January samples. In the macrophytes-dominated region, there was a decrease of labile and dissolved Pb concentrations in April and July. It is likely because of the uptake of Pb by submerged macrophyte roots and the Fe/Mn plaques in the root surface. High concentrations of labile and dissolved Pb were observed in October and January, likely resulting from the DOM complexation with Pb in sediments. This was supported by the fact that the Pb-DOM complexes accounted for 90% and 87% of the total chemical species of Pb in October and January, respectively.

Long-term effectiveness of sediment dredging on controlling the contamination of arsenic, selenium, and antimony.

This study assessed the effectiveness of dredging in controlling arsenic (As), selenium (Se), and antimony (Sb) contamination in sediments, by examining contaminant concentrations in sediments six years after dredging was completed. High-resolution diffusive gradients in thin films (DGT) and dialysis (HR-Peeper) techniques were used to monitor the concentrations of DGT-labile metalloids and soluble metalloids in sediments, respectively. Results revealed that dredging effectively remediated metalloid contamination in sediments only in April, July and/or January. Compared to non-dredged sediments, the concentrations of soluble and DGT-labile As, Se, and Sb in dredged sediments decreased on average by 42%, 52%, and 43% (soluble), and 54%, 50%, and 53% (DGT), respectively. The effectiveness of the dredging was primarily due to the transformation of metalloids from labile to inert fractions, which increased the ability of the sediments to retain the metalloids, and the slowed rate of resupplied metalloids from available solid pools. In contrast, negligible/negative effects of dredging were seen in October, and the concentrations of soluble and DGT-labile metalloids even increased in some profiles of dredged sediments. This was mainly caused by a release of the metalloids from algal degradation, which may offset the dredging effectiveness.

High resolution spatiotemporal sampling as a tool for comprehensive assessment of zinc mobility and pollution in sediments of a eutrophic lake.

To assess zinc (Zn) pollution risk from sediments, this study investigated the monthly changes of dissolved Zn and labile Zn in sediment-overlying water profiles in a eutrophic bay (Meiliang Bay) of Lake Taihu (China) using high-resolution dialysis (HR-Peeper) and diffusive gradients in thin films (DGT) at a 4 mm vertical resolution. In February and March, Mn oxides reduction caused high concentrations of DGT-labile Zn (14 ∼ 235 µg L-1), as evidenced by the significant correlation between DGT-labile Zn and DGT-labile Mn in sediments. In June and July, algal blooms reduced concentrations of dissolved Zn via algal assimilation. From August through October, concentrations of dissolved Zn in overlying water (338 ∼ 1023 µg L-1) exceeded the water quality limit for fisheries in China (100 µg L-1). This was attributed to reductive dissolution of Mn oxides in sediments caused by algal degradation followed by complexation of dissolved organic matter (DOM), which was identified in a simulated algal bloom experiment. In the winter, decreased Zn mobility was mainly attributed to adsorption by Mn oxides. It was concluded that enhanced Zn pollution risk from sediments is worthy of concern especially during algal degradation in eutrophic lakes.

Long-term effects of sediment dredging on controlling cobalt, zinc, and nickel contamination determined by chemical fractionation and passive sampling.

Studies of dredging effectiveness, especially the ones that last for several years, are scarce. In this study, we evaluated effectiveness of dredging performed for six years on controlling cobalt (Co), zinc (Zn), and nickel (Ni) contamination of sediments. High-resolution dialysis (HR-Peeper) and diffusive gradients in thin films (DGT) methods were applied to analyze the non-dredged and post-dredging sediments. The soluble and DGT-labile Co and Ni content declined by 22% and 44% (soluble) and by 16% and 26% (labile) in April, July and October in the post-dredging region. In contrast, their concentrations increased by 105% and 9% (soluble) and 322% and 27% (labile) in January. These changes in the dredging effects were caused by the corresponding changes in the reducible and residual fractions of Co and the residual fraction of Ni in sediments in the dredged site, respectively. Soluble and DGT-labile Zn decreased on average by 23% and 29% in July and October and increased on average by 151% and 52% in April and January in the post-dredging region. The different Zn mobility in the post-dredging region was controlled by the reducible fraction of Zn. The results revealed positive influence of dredging engineering in summer, autumn and/or spring and negative one in winter. Therefore, an accurate assessment of dredging effectiveness should take its seasonal variation into consideration.

Different Influences of Bacterial Communities on Fe (III) Reduction and Phosphorus Availability in Sediments of the Cyanobacteria- and Macrophyte-Dominated Zones.

Little is known about the effects of bacterial community on iron (Fe) and phosphorus (P) cycles in sediments under different primary producer habitats in different seasons. Lake Taihu has both the cyanobacteria- and macrophyte-dominated lake zones. In this work, the abundance and structure of bacterial community was investigated using qPCR and 16S rRNA gene high throughput sequencing, respectively. Compared with the sediments in the cyanobacteria-dominated lake zone, sediments in the macrophyte-dominated lake zone had higher TP, TOC and TN contents but lower DO and Eh values. Dissolved reactive P, dissolved Fe, and their molar ratios (Fe/P) were lower in the sediments of the cyanobacteria-dominated lake zone than those in the macrophyte-dominated lake zone. Consistent with this was the significantly lower abundance of total and typical Fe redox transforming bacteria in the sediment of the cyanobacteria-dominated lake zone than those in the macrophyte-dominated lake zone. Correlation analyses also revealed positive influence of abundances of total bacteria and typical Fe reducing bacteria on dissolved Fe and Fe/P ratio. The results showed that, in the cyanobacteria-dominated open water zone, Acidimicrobiaceae was capable of Fe metabolism, contributing to higher P flux in summer. In the cyanobacteria-dominated bay, Sva0081 sediment group and Desulfobulbaceae could transform sulfate to sulfide, which resulted in the reduction of Fe (III), while in the macrophyte-dominated zones, Clostridium sensu stricto 1 could couple oxidation of organic carbon with the reduction of Fe (III). The present study adds new knowledge linking the bacterial communities with the physicochemical cycles of Fe and P in sediments under different primary producer habitats.

Internal phosphorus loading from sediments causes seasonal nitrogen limitation for harmful algal blooms.

It is proposed that the internal loading of phosphorus (P) from sediments plays an important role in seasonal nitrogen (N) limitation for harmful algal blooms (HABs), although there is a lack of experimental evidence. In this study, an eutrophic bay from the large and shallow Lake Taihu was studied for investigating the contribution of internal P to N limitation over one-year field sampling (February 2016 to January 2017). A prebloom-bloom period was identified from February to August according to the increase in Chla concentration in the water column, during which the ratio of total N to total P (TN/TP) exponentially decreased with month from 43.4 to 7.4. High-resolution dialysis (HR-Peeper) and diffusive gradients in thin films (DGT) analysis showed large variations in the vertical distribution of mobile P (SRP and DGT-labile P) in sediments, resulting in the SRP diffusion flux at the sediment-water interface ranging from -0.01 to 6.76mg/m2/d (minus sign denotes downward flux). Significant and linear correlations existed between SRP and soluble Fe(II) concentrations in pore water, reflecting that the spatial-temporal variation in mobile P was controlled by microbe-mediated Fe redox cycling. Mass estimation showed that the cumulative flux of SRP from sediments accounted for 54% of the increase in TP observed in the water column during the prebloom-bloom period. These findings are supported by the significantly negative correlation (p<0.01) observed between sediment SRP flux and water column TN/TP during the same period. Overall, these results provide solid evidence for the major role of internal P loading in causing N limitation during the prebloom-bloom period.

Successful control of internal phosphorus loading after sediment dredging for 6years: A field assessment using high-resolution sampling techniques.

The effectiveness of sediment dredging for the control of internal phosphorus (P) loading, was investigated seasonally in the eutrophic Lake Taihu. The high-resolution dialysis (HR-Peeper) and diffusive gradients in thin films (DGT) techniques were used to measure the concentrations of soluble Fe(II) and soluble reactive P (SRP) as well as DGT-labile Fe/P in the non-dredging and post-dredging sediments. The P resupply kinetics from sediment solids were interpreted using DGT Induced Fluxes in Sediments (DIFS) modeling. The results showed no obvious improvement in water and sediment quality after dredging for 6years, due to their geographical proximity (a line distance of approximately 9km). However, dredging significantly decreased the concentrations of soluble Fe(II)/SRP and DGT-labile Fe/P in sediments, with effects varying at different depths below the sediment-water interface; More pronounced effects appeared in January and April. The diffusive flux of pore water SRP from sediments decreased from 0.746, 4.08 and 0.353mg/m2/d to 0.174, 1.58 and 0.048mg/m2/d in April, July and January, respectively. DIFS modeling indicated that the P retention capability of sediment solids was improved in April in post-dredging site. Positive correlations between pore water soluble Fe(II) and SRP as well as between DGT-labile Fe and P, reflect the key role of Fe redox cycling in regulating dredging effectiveness. This effect is especially important in winter and spring, while in summer and autumn, the decomposition of algae promoted the release of P from sediments and suppressed dredging effectiveness. Overall, the high-resolution HR-Peeper and DGT measurements indicated a successful control of internal P loading by dredging, and the post-dredging effectiveness was suppressed by algal bloom.

Submillimeter-scale heterogeneity of labile phosphorus in sediments characterized by diffusive gradients in thin films and spatial analysis.

Sediments have a heterogeneous distribution of labile redox-sensitive elements due to a drastic downward transition from oxic to anoxic condition as a result of organic matter degradation. Characterization of the heterogeneous nature of sediments is vital for understanding of small-scale biogeochemical processes. However, there are limited reports on the related specialized methodology. In this study, the monthly distributions of labile phosphorus (P), a redox-sensitive limiting nutrient, were measured in the eutrophic Lake Taihu by Zr-oxide diffusive gradients in thin films (Zr-oxide DGT) on a two-dimensional (2D) submillimeter level. Geographical information system (GIS) techniques were used to visualize the labile P distribution at such a micro-scale, showing that the DGT-labile P was low in winter and high in summer. Spatial analysis methods, including semivariogram and Moran's I, were used to quantify the spatial variation of DGT-labile P. The distribution of DGT-labile P had clear submillimeter-scale spatial patterns with significant spatial autocorrelation during the whole year and displayed seasonal changes. High values of labile P with strong spatial variation were observed in summer, while low values of labile P with relatively uniform spatial patterns were detected in winter, demonstrating the strong influences of temperature on the mobility and spatial distribution of P in sediment profiles.