A novel strategy to enhance inhibition of Hela cervical cancer by combining Lentinus ß-glucan and autophagic flux blockage.

Lentinus ß-D-glucan (LNT), derived from artificially cultured mushrooms of Lentinus edodes, shows an important yet incompletely understood biological functions in cancer. In this work, the chemical structure of the refined LNT comprising a ß-D-(1, 6)-branched ß-D-(1,3)-glucan was further clarified via 1D- and 2D-NMR with high resolution, and its drug resistance resulted from autophagy in human cervical cancer (CC) Hela cells besides its anti-cancer function were revealed in vitro and in vivo. In detail, LNT destroyed cellular homeostasis by significantly increasing the intracellular Ca2+ levels and promoted autophagic flux in vitro Hela cells, which was found to at least partially depend on the PI3K/Akt/mTOR-mediated pathway by up-regulating LC3-II levels and down-regulating the expression of p62, PI3K, p-Akt, and mTOR in Hela cells-transplanted BALB/c nude mice. In particular, LNT-induced autophagy led to a drug resistance against LNT-induced proliferation inhibition and apoptosis in Hela cells, and the co-treatment of autophagy inhibitors and LNT significantly enhanced the inhibition of Hela cells and tumor growth in vitro and in vivo. Therefore, the combination of LNT and autophagy inhibitors will be a novel therapeutic strategy to reduce the resistance and improve the prognosis of CC patients in the clinical.

Ultrathin BSA-Stabilized Black Phosphorous Nanoreactor Boosts Mild-Temperature Photothermal Therapy Through Modulation of Cellular Self-Defense Fate.

Mild-temperature photothermal therapy (mild-PTT, 42-45 °C) offers a higher level of biosafety. However, its therapeutic effects are compromised by the heat shock response (HSR), a cellular self-defense mechanism, which triggers the overexpression of heat shock proteins (HSPs) with the capacity of repairing the damaged tumor cells. Herein, this work fabricates a novel nanoreactor by incorporating up-conversion nanoparticles (UCNPs), chlorin e6 (Ce6), and glucose oxidase (GOx) onto the ultrathin black phosphorus nanosheet (BPNS) (denoted as GOx-BUC). This nanoreactor amplifies mild-PTT effects under irradiation with an 808 nm laser, modulating HSPs-mediated cellular self-defense fate. On one hand, upon irradiation with a 980 nm laser, UCNPs can transfer energy to excite Ce6, leading to the generation of ROS burst, which achieves indiscriminate damage to HSPs activity in deeper tumor tissues. On the other hand, GOx can consume glucose, thereby depleting the ATP energy supply and further suppressing HSPs expression. Consequently, GOx-BUC exhibits excellent anti-tumor efficacy under mild temperature in a human colorectal cancer mouse model, resulting in complete tumor inhibition with negligible side effects. This black phosphorous nanoreactor, featuring dual-track HSPs destruction functionality, introduces novel perspectives for enhancing mild-PTT effectiveness while maintaining high biosafety.

Research on the mechanism of HOPX-HDAC2 interaction inducing differentiation blockage in acute myeloid leukemia.

Homeodomain-only protein homeobox (HOPX) mainly exerts its transcriptional repression by physically sequestering the serum co-repressor and recruiting histone deacetylase (HDAC), possessing important potential as a prognostic gene in acute myeloid leukemia (AML). HDACs play crucial roles in cell growth, gene regulation, and metabolism, and they are also important factors in promoting AML progression. Therefore, this project attempts to investigate whether HOPX affects AML progression by interacting with HDAC2 protein. Bioinformatics analysis was employed to identify potential prognostic genes in AML. Flow cytometry and MTT assays were performed to analyze the cellular biological functions of the AML prognostic marker HOPX. The interaction network of HOPX was analyzed using the Search Tool for the Retrieval of Interacting Genes database, and the interaction between HOPX and HDAC2 was observed using endogenous and exogenous immunoprecipitation. HOPX is highly expressed in AML cells. Further research uncovered that low expression of HOPX can repress the proliferation activity, anti-apoptotic ability, and differentiation blockage of AML cells. Moreover, mechanistically, HOPX induced AML differentiation blockage and malignant progression through interaction with HDAC. HOPX can serve as a prognostic marker for AML and can interact with HDAC2 to induce AML differentiation blockage and malignant progression.

Blockage at cross-drainage hydraulic structures - Advances, challenges and opportunities.

Blockage of cross-drainage hydraulic structures is a significant concern in water resources and civil engineering projects, particularly in urban areas experiencing increased debris supply. During storms or floods, debris can accumulate and restrict the flow capacity of these structures, leading to potential failures and adverse impacts on flood levels. While some argue that blockage at culverts is a non-issue, scientific research supports its significance in specific regions. However, in context of rivers and dams, blockage by Large Wood (LW) is an established issue with plenty of research in terms of its hydraulic impacts, dynamics, modeling and scouring impacts. Specifically in Australasia the Australian Rainfall and Runoff (ARR) initiative recognized the importance of studying blockage at culverts and introduced guidelines incorporating it into design and modeling. These guidelines also included post flood visual inspections of structures to understand blockage, however, this approach has been criticized by hydraulic engineers arguing that post flood visuals can not be considered as the representation of the peak floods blockage. Recently, an approach of using visual information to interpret the blockage has been adopted as a new dimension to the problem. This paper, therefore, highlights the advances, challenges, and opportunities in studying blockage, emphasizing the need for data-driven approaches and interdisciplinary collaboration. Understanding and addressing blockage are crucial for ensuring the efficient operation and longevity of hydraulic structures and promoting the resilience of infrastructure systems in the face of evolving environmental conditions.

Black phosphorus nanosheets induce autophagy dysfunction by a size- and surface modification-related impairment of lysosomes in macrophages.

The widespread application of black phosphorus nanosheets (BPNSs) raises concerns about their potential impact on human health. Although that the autophagy-inducing properties of BPNSs in cancer cells are documented, their effects on macrophages-key components of the immune system and the mechanisms involved remain obscure, especially in terms of the influences of BPNS the size and surface modifications on the autophagic process. This study investigated the effects of bare BPNSs and PEGylated BPNSs (BP-PEG) on macrophage autophagy and its underlying mechanisms by comprehensive biochemical analyses. The results indicated that both BPNSs and BP-PEG are internalized by RAW264.7 cells through phagocytosis and caveolin-dependent endocytosis, leading to lysosomal accumulation. The internalized BPNSs induced mitochondrial dysfunction, which subsequently elevated the NAD+/NADH ratio and activated the SIRT-1 pathway, initiating autophagy. However, BPNSs disrupted the autophagic flux by impairing autolysosome formation, leading to apoptosis in a size-dependent manner. In contrast, BP-PEG preserved lysosomal integrity, maintaining autophagic activity and cell viability. These findings deepen our understanding of the influence of nanosheet size and surface modifications on macrophage autophagy, contributing to the formulation of regulatory guidelines to minimize the potential adverse effects and health risks associated with BPNS utilization in various applications.

Causative mechanisms limiting the removal efficiency of short-chain per- and polyfluoroalkyl substances (PFAS) by activated carbon.

Short-chain per and polyfluoroalkyl substances (PFAS) have been found to be relatively high in water treatment systems compared to long-chain PFAS because of the unsatisfactory adsorption efficiency of short-chain PFAS. Knowledge about why short-chain PFAS are less removed by porous carbon is very limited. The study focused on providing causal mechanisms that link the low adsorption of short-chain PFAS and proposing an improved method for removing both short- and long-chain PFAS. The long-chain PFAS with higher hydrophobicity diffused more quickly than the short-chain PFAS due to stronger partitioning driving forces. In the initial adsorption stage, therefore, pores of activated carbon were blocked by long-chain PFAS, which makes it difficult for the short-chain PFAS to enter the internal pores. Although several short-chain PFAS diffuse into the pores, the relatively more hydrophilic short-chain congeners cannot be fully adsorbed on activated carbon due to limited positively charged sites. Moreover, compared to larger particle sizes, smaller activated carbon particles have shorter pore channels near the surface, reducing the risk of pore-blocking and ensuring the pores remain accessible for more efficient adsorption. Additionally, these smaller particles offer a greater external surface area and more functional groups, which enhance the adsorption capacity. It indicates that the smaller particle size of activated carbon would have a positive effect on the short-chain PFAS removal.

Polymeric PD1/PDL1 bispecific antibody enhances immune checkpoint blockade therapy.

Immune checkpoint blockade (ICB) therapy, particularly PD1/PDL1 inhibition, has demonstrated success in bolstering durable responses in patients. However, the response rate remains below 30 %. In this study, we developed a polymeric bispecific antibody (BsAb) targeting PD1/PDL1 to enhance ICB therapy. Specifically, poly(L-glutamic acid) (PGLU) was conjugated with a double cyclic Fc binding peptide, Fc-III-4C, through condensation reactions between the -COOH group of PGLU and the -NH2 group of Fc-III-4C. This conjugate was then mixed with αPD1 and αPDL1 monoclonal antibodies (mAbs) in an aqueous solution. Mechanistically, the PD1/PDL1 BsAb (BsAbαPD1+αPDL1) acts as a bridge between tumor cells and CD8+ T cells, continuously activating CD8+ T cells to a greater extent. This leads to significantly suppressed tumor growth and prolonged survival in a mouse model of colon cancer compared to treatment with either a single mAb or a mixture of free mAbs. The tumor suppression rate achieved by the BsAbαPD1+αPDL1 was 90.1 %, with a corresponding survival rate of 83.3 % after 48 days. Thus, this study underscores the effectiveness of the BsAbαPD1+αPDL1 as a synchronizing T cell engager and dual ICBs, offering theoretical guidance for clinical ICB therapy.

Efficacy of endolymphatic duct blockage in treating Ménière's disease. / å† æ·‹å·´ç®¡å¤¹é—­æœ¯æ²»ç–—æ¢ å°¼åŸƒç— çš„æ•ˆæžœ.

OBJECTIVES: Ménière's disease (MD) is an idiopathic inner ear disorder characterized by recurrent episodes of episodic rotational vertigo, fluctuating hearing loss, tinnitus, and a feeling of ear stuffiness. Endolymphatic sac (ES)-related surgery is used primarily in patients with MD who have failed to respond to pharmacologic therapy. Endolymphatic duct blockage (EDB) is a new procedure for the treatment of MD, and related clinical studies are still scarce. This study aims to investigate the dynamic changes in endolymphatic hydrops (EH) and the long-term surgical outcomes in MD patients undergoing EDB, and to evaluate the impact of different types of ES on the surgical efficacy. METHODS: A retrospective analysis was conducted on 33 patients with refractory MD who underwent EDB. Based on the morphology of their endolymphatic sacs, patients were divided into a normal-type group (n=14) and an atrophic-type group (n=19). The frequency of vertigo symptoms, hearing, vestibular function, and the dynamic changes of gadolinium-enhanced MRI of the inner ear were compared were compared before and after surgery between the 2 groups. RESULTS: Compared with the atrophic-type group, the patients in the normal-type group had a higher rate of complete vertigo control, better cochlear and vestibular function, and a lower endolymph to vestibule volume ratio (all P<0.05). In addition, 7 patients in the normal-type group were found to have reversal of EH, while no reversal of EH was detected in the atrophic-type group after surgery. CONCLUSIONS: The response to EDB treatment varies between normal and atrophic MD patients, suggesting that the 2 pathological types of endolymphatic sacs may have different underlying mechanisms of disease.

Endometriosis affects natural and ART fertility in different ways: let's look at the whole patient and not at the single lesion.

When considering the typical lesions associated with endometriosis, such as endometriomas, and pelvic adherences involving the tubes, it is very clear how this pathology may impair both natural and assisted reproductive technology (ART) fertility. It may be more difficult for clinicians to recognize that endometriosis can reduce female fertility potential through other mechanisms which may be independent of direct damage to ovarian reserve and tubal function. The most recent clinical studies have shown that endometriosis is associated with increased risk of infertility, independent of the type of endometriosis (ovarian, peritoneal and deep endometriosis). In the IVF setting, the cumulative live birth rate in women with endometriosis has been reported to be significantly lower compared with women without endometriosis. Endometriosis is a complex, multifactorial condition that encompasses not only the presence of endometriotic lesions, but also involves women's sexuality, uterine and ovarian compartment. Endometriosis should always be considered a severe risk factor for infertility and ART failure.

Investigation of Enzyme Immobilization and Clogging Mechanisms in the Enzymatic Synthesis of Amoxicillin.

This study investigated the blocking mechanism of immobilized penicillin G acylase (PGA) during the enzymatic synthesis of amoxicillin. Laboratory observations revealed that the primary cause of clogging was the crystallization of the substrate and product on the enzyme surface. Adjusting key parameters can significantly reduce clogging and improve catalytic efficiency. Methanol can decrease enzyme activity, but isopropyl alcohol cleaners can effectively remove clogs and protect enzyme activity. These findings provide an experimental foundation for optimizing the PGA immobilization process, which is crucial for achieving high efficiency and sustainability in industrial production.

Investigating small sized metal blockage effects at 60 and 100 GHz using measurements and modeling approaches.

Millimeter wave (mmWave) technologies at 60 GHz and 100 GHz bands are currently gaining significant attention for its potential to meet the demanding needs of next-generation networks. These include ultra-high data rate, ultra-low latency, high spectral efficiency, and high end-to-end reliability. However, mmWave signals' blockage remains a critical issue that affects the reliability of mmWave at 60 GHz and at 100 GHz bands due to the significant attenuations induced by the blockers (BLs). Not only blockers that have the size of a human body or even larger can affect the signal, but also smaller objects with much narrower dimensions, as narrow as 4 cm, can severely affect the signal strength and introduce an attenuation that reaches up to 12 dB at 100 GHz. In this paper we have conducted new measurements and presented results for three small copper sheets at each frequency band, aiming to investigate the blockage effect of small-sized metal objects on signal strength at these two frequency bands. Also, we have examined the performance of the knife-edge diffraction (KED) blockage model of the third-generation partnership project (3GPP) standards body and its evolved version named the mmMAGIC blockage model in such scenarios. Furthermore, we investigated the applicability of the two blockage models in capturing the attenuation characteristics of other materials-such as wood and glass. Experimental results supported by numerical models have shown that the induced peak attenuations are 5(12) dB, 10(23) dB, 23(23) dB for 4 × 4 cm, 8 × 8 cm, 16 × 16 cm copper blockers, respectively, at 60(100) GHz mmWave bands. Also, we have shown that both the 3GPP and mmMAGIC simulation models fail to accurately capture the attenuation characteristics of materials other than copper. The findings of this work highlight the importance of considering the dimensions and types of blockages when deploying reliable mmWave and sub-THz communications.

A retrospective study of prognostic factors and prostate-specific antigen dynamics in Japanese patients with metastatic hormone-sensitive prostate cancer who received combined androgen blockade therapy with bicalutamide.

BACKGROUND: This retrospective observational study explored the therapeutic potential of combined androgen blockade (CAB) with bicalutamide (Bic-CAB) as an initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC) in Japan. METHODS: The electronic health records of 159 patients with mHSPC from three Japanese institutions who received initial treatment with Bic-CAB between 2007 and 2017 were analyzed. The time to prostate-specific antigen (PSA) progression, duration of Bic-CAB treatment, and overall survival (OS), with various definitions for PSA progression, were assessed. A multivariate Cox proportional hazards model was constructed using clinical parameters to predict time to the end of Bic-CAB treatment and OS. RESULTS: The median observation period was 46.4 months, and the median age of patients at diagnosis was 71 years. A total of 46.5% patients experienced PSA progression with a median survival duration of 29 months (according to Prostate Cancer Clinical Trials Working Group 3 criteria), and 49.1% patients achieved a PSA nadir < 0.2 ng/mL in a median time of 4.7 months. When stratified by PSA nadir and PSA change, patients at low risk for disease progression with a small PSA change due to low initial PSA had a 5-year OS of 100% and a 10-year OS of 75%. The OS during the observation period was 72.9 months. CONCLUSION: These findings highlight the potential effect of Bic-CAB in patients with mHSPC who were at low risk for disease progression. Initial treatment with Bic-CAB and adjusting treatment early based on PSA dynamics may be a reasonable treatment plan for these patients.

Diagnostic Approaches in Nuclear Medicine for Reproductive Health Assessment: Hysterosalpingography in Radiology versus hysterosalpingoscintigraphy.

Background: Infertility is a significant aspect of reproductive health and evaluating degree of tubal pathology is essential for determining appropriate management plans. Aims and Objectives: To assess the role of hysterosalpingoscintigraphy (HSSG) as a tubal patency test in nuclear medicine and compare it with hysterosalpingography (HSG) in radiology in infertile women and study pain perception in both tests as well. Materials and Methods: A prospective study was conducted on 50 infertility patients undergoing infertility evaluation at a tertiary care hospital. Both HSG and HSSG procedures were performed during proliferative phase of menstrual cycle. Results: Our study demonstrated the potential of HSSG as a tool for evaluating tubal patency in infertility workup. It showed good accuracy in detecting tubal patency compared to HSG. Conclusion: HSG is a radiological procedure valued for its ability to provide detailed anatomical information of uterus and patency of fallopian tubes. In contrast, HSSG provides dynamic information on the functional aspects of the reproductive system using nuclear medicine techniques. Both HSG and HSSG are vital tools in the diagnostic armamentarium for assessing female reproductive health, offering complementary information that aids in comprehensive patient management.

Rosai Dorfman Disease of Nose and Paranasal Sinuses: An Incidental Discovery.

Rosai Dorfman disease is a benign lymphoproliferative disorder. Isolated extranodal involvement is rarely encountered. The causation has not been attributed to any particular factor and the clinical progress of the disease is varied. Treatment options range from observation to medical therapy to surgical excision. Long term follow up is advocated. We report an elderly female with complaints of nasal obstruction who underwent ESS and was diagnosed with this disease on account of histopathology. Follow up period has been uneventful. The case report illustrated here is aimed at highlighting high index of suspicion as well as creating awareness regarding diagnosis and management of a rarely seen pathology.

Mechanisms of well iron clogging in groundwater heat pump systems: Insights from video imaging, hydrogeochemical analysis, and geochemical modeling.

Groundwater heat pump (GWHP) systems are increasingly popular as low-carbon and environmentally friendly technologies, but well clogging induced by iron remains a significant issue. This study investigated the clogging characteristics and biogeochemistry of three typical wells (pumping, injection, and observation wells) in an operating GWHP system using video imaging, sampling, and analysis of hydrogeochemical and microbial data. The results revealed that iron-induced well clogging is a complex process involving physical, chemical, and microbial factors. Pumping wells experience clogging due to water mixing with varying redox conditions, resulting in hematite-based iron oxide deposits. Injection wells exhibit higher clogging severity, with transformed oxidation and accumulation of reduced iron minerals at the solid-liquid interface, resulting in darker colored clogs with magnetite. Clogging in both extraction and injection wells is closely related to iron-rich aquifer sections, where severe clogging occurs. Shallow clogging due to iron oxide is limited and attributed to the oxidation of zero-valent iron in well casing material. Iron-oxidizing bacteria and iron-reducing bacteria were detected in the consolidated deposits of clogged wells, indicating their involvement in the clogging formation process. Moreover, a strong correlation was observed between the presence of nitrate-reducing bacteria in the water phase and the severity of clogging, suggesting a possible link between iron oxidation and nitrate reduction in the system. Geochemical modeling results further supported the observed clogging severity in GWHP systems and confirmed varying clogging mechanisms in different wells and depths. These findings contribute to the understanding of clogging in GWHP operations, aiding in robust water utilization and energy-saving efforts, and supporting global carbon reduction initiatives.

Safety and efficacy of histotripsy delivery through overlying gas-filled small bowel in an ex vivo swine model.

PURPOSE: To evaluate the safety and efficacy of performing histotripsy through overlying gas-filled bowel in an ex vivo swine model. METHODS: An ex vivo model was created to simulate histotripsy treatment of solid organs through gas-filled bowel. Spherical 2.5 cm histotripsy treatments were performed in agar phantoms for each of five treatment groups: 1) control with no overlying bowel (n = 6), 2) bowel 0 cm above phantom (n = 6), 3) bowel 1 cm above phantom (n = 6), 4) bowel 2 cm above phantom (n = 6), and 5) bowel 0 cm above the phantom with increased treatment amplitude (n = 6). Bowel was inspected for gross and microscopic damage, and treatment zones were measured. A ray-tracing simulation estimated the percentage of therapeutic beam path blockage by bowel in each scenario. RESULTS: All histotripsy treatments through partial blockage were successful (24/24). No visible or microscopic damage was observed to intervening bowel. Partial blockage resulted in a small increase in treatment volume compared to controls (p = 0.002 and p = 0.036 for groups with bowel 0 cm above the phantom, p > 0.3 for bowel 1 cm and 2 cm above the phantom). Gas-filled bowel was estimated to have blocked 49.6%, 35.0%, and 27.3% of the therapeutic beam at 0, 1, and 2 cm, respectively. CONCLUSION: Histotripsy has the potential to be applied through partial gas blockage of the therapeutic beam path, as shown by this ex vivo small bowel model. Further work in an in vivo survival model appears indicated.

Peppermint essential oil enhances the vase life of Dendrobium orchids.

To extend the vase life of cut flowers, there is now a trend of using plant essential oils in place of synthetic chemicals, as they are fully biodegradable, more eco-friendly, and safer. The objective of this study was to examine the possible application and postharvest quality effects of three plant essential oils namely, ginger (Zingiber officinale Roscoe), peppermint (Mentha piperita L.), and citronella (Cymbopogon nardus Rendle), as natural vase solution for cut Dendrobium flowers. Peppermint essential oil showed promise as a holding solution for extending the vase life of Dendrobium orchids. To confirm vase life extension, emulsions containing peppermint essential oil at concentrations of 50 and 100 µg mL-1 combined with 4 % glucose to formulate holding solutions applied to Dendrobium orchids. Vase life, some biochemical changes, electrolyte leakage, total microbial count in the holding solution, and physical condition via scanning electron microscopy (SEM) were evaluated over a period of 25 days. The three major compounds in peppermint essential oil were identified as menthol (33.24 %), 1-menthone (18.91 %) and menthofuran (14.85 %). The essential oil was applied in emulsion form as a holding solution. Treatment with 4 % glucose and either 50 or 100 µg mL-1 peppermint essential oil prolonged the vase life of Dendrobium orchids to up to 28 days. Scanning electron microscopy on Day 7 showed that the xylem vessels of treated orchids remained clear, suggesting reduced microbial plugging at the stalk end. Similarly, on Day 20, a reduced microbial cell count was observed for treated orchids (<1 log CFU mL-1) in comparison with controls (7.20 ± 0.04 log CFU mL-1). Finally, the essential oil improved flower quality by helping preserve petal membrane stability and petal anthocyanin content. Our results suggest the application of peppermint essential oil as a novel alternative to chemicals used in holding solutions for extending the vase life of Dendrobium orchids.

Antiproliferative and Pro-Apoptotic Activity and Tubulin Dynamics Modulation of 1H-Benzimidazol-2-yl Hydrazones in Human Breast Cancer Cell Line MDA-MB-231.

(1) Background: The aim of the work is the evaluation of in vitro antiproliferative and pro-apoptotic activity of four benzimidazole derivatives containing colchicine-like and catechol-like moieties with methyl group substitution in the benzimidazole ring against highly invasive breast cancer cell line MDA-MB-231 and their related impairment of tubulin dynamics. (2) Methods: The antiproliferative activity was assessed with the MTT assay. Alterations in tubulin polymerization were evaluated with an in vitro tubulin polymerization assay and a docking analysis. (3) Results: All derivatives showed time-dependent cytotoxicity with IC50 varying from 40 to 60 µM after 48 h and between 13 and 20 µM after 72 h. Immunofluorescent and DAPI staining revealed the pro-apoptotic potential of benzimidazole derivatives and their effect on tubulin dynamics in living cells. Compound 5d prevented tubulin aggregation and blocked mitosis, highlighting the importance of the methyl group and the colchicine-like fragment. (4) Conclusions: The benzimidazole derivatives demonstrated moderate cytotoxicity towards MDA-MB-231 by retarding the initial phase of tubulin polymerization. The derivative 5d containing a colchicine-like moiety and methyl group substitution in the benzimidazole ring showed potential as an antiproliferative agent and microtubule destabilizer by facilitating faster microtubule aggregation and disrupting cellular and nuclear integrity.

Endolymphatic duct blockage surgery vs. intratympanic steroids for treatment of refractory Ménière's disease.

PURPOSE: To compare the effectiveness of the Endolymphatic duct blockage (EDB) and intratympanic methylprednisolone(ITMP) injection to control refractory Ménière's disease(MD) symptoms and evaluate their impact on hearing level. STUDY DESIGN: Retrospective study in a tertiary care center. METHODS: 36 received ITMP injection and 52 EDB. Mean outcome measures at 24 months included vertigo control, tinnitus, aural fullness and hearing level: pure-tone average (PTA), bone conduction average(BCA) and speech discrimination score(SDS). RESULTS: At 24 months postoperatively, 90.4% of the EDB group had complete control of vertigo and 43.4% of the ITMP group (p = 0.001). There was no significant difference in tinnitus or aural fullness control (p = 0.34 and p 0.21 respectively). In each group, the drop in tinnitus and aural fullness frequency at 24 months were significant for EDB (p = 0.03; p < 0.001 respectively) and for ITMP group in tinnitus (p = 0.03) but not aural fullness (p = 0.063). At 24 months, PTA, BCA and SDS were significantly worst in the ITMP group when compared to preoperative levels (p = 0.038, p = 0.027, p = 0.016). PTA in the EDB group was stable with no difference compared to ITMP group (p = 0.48). BCA and SDS in the EDB group were stable and better than the ITMP group (p = 0.032; p = 0.036). In each group, vestibular paresis was not significantly different before (p = 0.06) and after treatment (p = 0.68). CONCLUSION: EDB is more effective than the ITMP for controlling the vertigo symptoms of Ménière's disease and in preserving hearing function. It is a novel surgical technique with promising results for a complete treatment of Ménière's disease. ITMP decreases the frequency and the severity of the symptoms but only control vertigo in 27.8% of cases.

Nanoparticle-Mediated Immunotherapy in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype with the worst prognosis and highest recurrence rates. The treatment choices are limited due to the scarcity of endocrine and HER2 targets, except for chemotherapy. However, the side effects of chemotherapy restrict its long-term usage. Immunotherapy shows potential as a promising therapeutic strategy, such as inducing immunogenic cell death, immune checkpoint therapy, and immune adjuvant therapy. Nanotechnology offers unique advantages in the field of immunotherapy, such as improved delivery and targeted release of immunotherapeutic agents and enhanced bioavailability of immunomodulators. As well as the potential for combination therapy synergistically enhanced by nanocarriers. Nanoparticles-based combined application of multiple immunotherapies is designed to take the tactics of enhancing immunogenicity and reversing immunosuppression. Moreover, the increasing abundance of biomedical materials holds more promise for the development of this field. This review summarizes the advances in the field of nanoparticle-mediated immunotherapy in terms of both immune strategies for treatment and the development of biomaterials and presents challenges and hopes for the future.