Prognostic significance of adjuvant therapy and specific radiation dosages in Taiwanese patients with oral cavity cancer and extra-nodal extension: a nationwide cohort study.

BACKGROUND: The evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE. METHODS: A retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted. RESULTS: Multivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p < 0.0001), OS (42% versus 18%, p < 0.0001); after PS matching (n = 111 in each group), DSS (52% versus 30%, p = 0.0016), OS (38% versus 21%, p = 0.0019). For patients who underwent CRT, the 5-year outcomes for different radiation dose groups (6600 - 7000 cGy, n = 1155 versus 6000 - 6500 cGy, n = 199) were as follows: before PS matching, DSS (52% versus 54%, p = 0.1904), OS (43% versus 46%, p = 0.1610); after PS matching (n = 199 in each group), DSS (55% versus 54%, p = 0.8374), OS (46.5% versus 46.3%, p = 0.7578). CONCLUSIONS: For OCSCC patients with ENE, our study shows CRT improved survivals than RT alone, underscoring the clinical significance of chemotherapy. Patients undergoing CRT with irradiation doses ranging from 6000 to 6500 cGy exhibited comparable survival outcomes to those receiving doses of 6600-7000 cGy. This observation suggests that irradiation doses exceeding the 6600 cGy may not confer the survival advantage in these patients. Further research is needed to confirm our results and explore the optimal irradiation dose for managing these patients.

Anti-Jamming Resource-Allocation Method in the EH-CIoT Network through LWDDPG Algorithm.

In the Energy-Harvesting (EH) Cognitive Internet of Things (EH-CIoT) network, due to the broadcast nature of wireless communication, the EH-CIoT network is susceptible to jamming attacks, which leads to a serious decrease in throughput. Therefore, this paper investigates an anti-jamming resource-allocation method, aiming to maximize the Long-Term Throughput (LTT) of the EH-CIoT network. Specifically, the resource-allocation problem is modeled as a Markov Decision Process (MDP) without prior knowledge. On this basis, this paper carefully designs a two-dimensional reward function that includes throughput and energy rewards. On the one hand, the Agent Base Station (ABS) intuitively evaluates the effectiveness of its actions through throughput rewards to maximize the LTT. On the other hand, considering the EH characteristics and battery capacity limitations, this paper proposes energy rewards to guide the ABS to reasonably allocate channels for Secondary Users (SUs) with insufficient power to harvest more energy for transmission, which can indirectly improve the LTT. In the case where the activity states of Primary Users (PUs), channel information and the jamming strategies of the jammer are not available in advance, this paper proposes a Linearly Weighted Deep Deterministic Policy Gradient (LWDDPG) algorithm to maximize the LTT. The LWDDPG is extended from DDPG to adapt to the design of the two-dimensional reward function, which enables the ABS to reasonably allocate transmission channels, continuous power and work modes to the SUs, and to let the SUs not only transmit on unjammed channels, but also harvest more RF energy to supplement the battery power. Finally, the simulation results demonstrate the validity and superiority of the proposed method compared with traditional methods under multiple jamming attacks.

Synergetic Modulation of Steric Hindrance and Excited State for Anti-Quenching and Fast Spin-Flip Multi-Resonance Thermally Activated Delayed Fluorophore.

Multi-resonance thermally activated delayed fluorescence (MR-TADF) materials hold great promise for advanced high-resolution organic light-emitting diode (OLED) displays. However, persistent challenges, such as severe aggregation-caused quenching (ACQ) and slow spin-flip, hinder their optimal performance. We propose a synergetic steric-hindrance and excited-state modulation strategy for MR-TADF emitters, which is demonstrated by two blue MR-TADF emitters, IDAD-BNCz and TIDAD-BNCz, bearing sterically demanding 8,8-diphenyl-8H-indolo[3,2,1-de]acridine (IDAD) and 3,6-di-tert-butyl-8,8-diphenyl-8H-indolo[3,2,1-de]acridine (TIDAD), respectively. These rigid and bulky IDAD/TIDAD moieties, with appropriate electron-donating capabilities, not only effectively mitigate ACQ, ensuring efficient luminescence across a broad range of dopant concentrations, but also induce high-lying charge-transfer excited states that facilitate triplet-to-singlet spin-flip without causing undesired emission redshift or spectral broadening. Consequently, implementation of a high doping level of IDAD-BNCz resulted in highly efficient narrowband electroluminescence, featuring a remarkable full-width at half-maximum of 34 nm and record-setting external quantum efficiencies of 34.3 % and 31.8 % at maximum and 100 cd m-2, respectively. The combined steric and electronic effects arising from the steric-hindered donor introduction offer a compelling molecular design strategy to overcome critical challenges in MR-TADF emitters.

Exploring the diagnostic value, prognostic value, and biological functions of NPC gene family members in hepatocellular carcinoma based on a multi-omics analysis.

Liver cancer is a cunning malignancy with a high incidence and mortality rate among cancers worldwide. The NPC gene family members (NPCs: NPC1, NPC2, and NPC1L1) are closely linked to the development of multiple cancers, but their role in liver cancer remains unclear. As a result, we must investigate their functions in liver hepatocellular carcinoma (LIHC). NPCs were significantly differentially expressed between normal and LIHC tissues, with a high mutation frequency in LIHC. The ROC curve analysis revealed that NPC1/NPC2 had high diagnostic and prognostic values in LIHC. NPC1 expression was also found to be negatively correlated with its methylation level. The differentially expressed genes between high and low NPC1 expression groups in LIHC were mainly related to channel activity, transporter complexes, and plasma membrane adhesion molecules. Additionally, NPC1 expression was significantly associated with multiple immune cells and immunization checkpoints. It was hypothesized that a TUG1/SNHG4-miR-148a-3p-NPC1 regulatory axis is associated with hepatocarcinogenesis. Finally, the protein expression of NPC1 in LIHC tissues and paraneoplastic tissues was detected, and NPC1-knockdown HepG2 cells (NPC1KO) inhibited the proliferation, migration, and invasion. This study helped to identify new prognostic markers and potential immunotherapeutic targets for LIHC and revealed the molecular mechanisms underlying NPC1 regulation in LIHC. The NPCs play a key role in the prognosis and diagnosis of LIHC and may be an important indicator for LIHC prognosis and diagnosis; NPC1 might be a potential therapeutic target in LIHC.

The relationship of nutritional status with anticancer immunity and its prognostic value for head and neck cancer.

Malnutrition has been reported to be associated with reduced survival and deficient anticancer immunity, and undernourishment is a frequent comorbidity in head and neck cancer (HNC) patients. In this study, we evaluated the relationship between nutritional status and immunologic factors, and its prognostic value for HNC. We retrospectively reviewed 212 HNC patients who had undergone a nutrition evaluation based on the Patient-Generated Subjective Global Assessment (PG-SGA) and curative radiotherapy (RT). The role of nutritional status in the prognosis of HNC and its correlation with anticancer immune response was assessed in HNC patients, and in the 4-nitroquinoline 1-oxide (4NQO)-induced tongue tumor animal model. Our data revealed that malnutrition (high PG-SGA scores) was significantly associated with more advanced disease, lower body mass index, lower RT completion rates, and reduced survival. Patients in the group with high PG-SGA scores had a higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived suppressor cells (MDSCs), and elevated IL-6 levels in the peripheral circulation. Patients with increased PG-SGA scores following treatment were more likely to developing locoregional failure. In the 4NQO-induced tumor model, nutritional supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. Following ectopic tumor implantation in an immunocompetent host, nutrition supplements decreased tumor growth in association with attenuated MDSC recruitment and lower IL-6 expression. In conclusion, malnutrition by PG-SGA was associated with poor prognosis in HNC patients. Based on the data of HNC patients and the 4NQO-tumor model, adequate nutritional supplementation might improve the prognosis associated with augmented anticancer immunity.

Intramolecular Cyclization: A Convenient Strategy to Realize Efficient BT.2020 Blue Multi-Resonance Emitter for Organic Light-Emitting Diodes.

Rationally tuning the emission position and narrowing the full width at half-maximum (FWHM) of an emitter is of great importance for many applications. By synergistically improving rigidity, strengthening the resonant strength, inhibiting molecular bending and rocking, and destabilizing the HOMO energy level, a deep-blue emitter (CZ2CO) with a peak wavelength of 440 nm and an ultranarrow spectral FWHM of 16 nm (0.10 eV) was developed via intramolecular cyclization in a carbonyl/N resonant core (QAO). The dominant υ0-0 transition character of CZ2CO gives a Commission Internationale de I'Éclairage coordinates (CIE) of (0.144, 0.042), nicely complying with the BT.2020 standard. Moreover, a hyper-fluorescent device based on CZ2CO shows a high maximum external quantum efficiency (EQEmax ) of 25.6 % and maintains an EQE of 22.4 % at a practical brightness of 1000 cd m-2 .

Photo-controllable Luminescence from Radicals Leading to Ratiometric Emission Switching via Dynamic Intermolecular Coupling.

The development of photoinduced luminescent radicals with dynamic emission color is still challenging. Herein we report a novel molecular radical system (TBIQ) that shows photo-controllable luminescence, leading to a wide range of ratiometric color changes via light excitation. The conjugated skeleton of TBIQ is decorated with steric-demanding tertiary butyl groups that enable appropriate intermolecular interaction to make dynamic intermolecular coupling possible for controllable behaviors. We reveal that the helicenic pseudo-planar conformation of TBIQ experiences a planarization process after light excitation, leading to more compactly stacked supermolecules and thus generating radicals via intermolecular charge transfer. The photo-controllable luminescent radical system is employed for a high-level information encryption application. This study may offer unique insight into molecular dynamic motion for optical manufacturing and broaden the scope of smart-responsive materials for advanced applications.

Near-Infrared Thermally Activated Delayed Fluorescence Nanoparticle: A Metal-Free Photosensitizer for Two-Photon-Activated Photodynamic Therapy at the Cell and Small Animal Levels.

Thermally activated delayed fluorescence (TADF) materials with extremely small singlet-triplet energy offsets have opened new horizons for the development of metal-free photosensitizers for photodynamic therapy (PDT) in recent years. However, the exploration of near-infrared (NIR) TADF emitters for efficient two-photon-excited (TPE) PDT is still a formidable challenge, thus it has not been reported yet. In this study, purely organic photosensitizers (PSs) based on the TADF nanoparticles (NIR-TADF NPs) are designed for efficient TPE-PDT, which show excellent singlet oxygen generation ability. Thanks to the intrinsic two-photon excitation and NIR emission characteristics, the NIR-TADF NPs demonstrate promising potential in both single-photon-excited (SPE) and TPE NIR imaging. More importantly, the anti-tumor efficiency and biosafety of TADF-based PSs at the small animal level are confirmed in A549 tumor xenograft models under TPE laser irradiance, which will facilitate the practical biomedical applications of TADF materials. This work not only provides a promising strategy to develop metal-free PSs, but also expands the applied scope of TADF-based nanotherapeutics and advances their possible clinical translation in cancer therapy.

Optimizing Intermolecular Interactions and Energy Level Alignments of Red TADF Emitters for High-Performance Organic Light-Emitting Diodes.

Adequately harvesting all excitons in a single molecule and inhibiting exciton losses caused by intermolecular interactions are two important factors for achieving high efficiencies thermally activated delayed fluorescence (TADF). One potential approach for optimizing these is to tune alignment of various excited state energy levels by using different doping concentrations. Unfortunately, emission efficiencies of most TADF emitters decrease rapidly with concentrations which limits the window for energy level tunning. In this work, by introducing a spiro group to increase steric hindrance of a TADF emitter (BPPXZ) with a phenoxazine and a dibenzo[a,c]phenazine, emission efficiency of the resulting molecule (BPSPXZ) is much less affected by concentration increase. This enables exploitation of the concentration effects to tune energy levels of its excited states for obtaining simultaneously small singlet-triplet energy offset and large spin-orbital coupling, leading to high-efficiency reverse intersystem crossing. With these merits, organic light-emitting diodes (OLEDs) using the BPSPXZ emitter from 5 to 60 wt% doping can all deliver EQE of over 20%. More importantly, record-high EQEs of 33.4% and 15.8% are respectively achieved in the optimized and nondoped conditions. This work proposes a strategy for developing red TADF emitters by optimizing the intermolecular interaction and energy level alignments to facilitate exciton utilization over wide doping concentrations.

Clinical Outcomes of Taiwanese Patients with Resected Oral Cavity Squamous Cell Carcinoma Who Underwent Reconstruction with Free Versus Local Flaps.

BACKGROUND: We sought to compare the clinical outcomes of Taiwanese patients with resected oral cavity squamous cell carcinoma (OCSCC) who underwent reconstruction with free versus local flaps. METHODS: From 2011 to 2017, we examined 8646 patients with first primary OCSCC who received surgery either with or without adjuvant therapy. Of these patients, 7297 and 1349 received free and local flap reconstruction, respectively. Two propensity score-matched groups of patients who underwent free versus local flap (n = 1268 each) reconstructions were examined. Margin status was not included as a propensity score-matched variable. RESULTS: Compared with local flaps, patients who received free flaps had a higher prevalence of the following variables: male sex, age < 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm, margin > 4 mm, extranodal extension (ENE), and adjuvant therapy (all p < 0.0001). Multivariable analysis identified the reconstruction method (local vs. free flaps, only overall survival [OS]), age ≥ 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm (only OS), margins ≤ 4 mm, and ENE as independent adverse prognosticators for disease-specific survival (DSS) and OS. The results of propensity score-matched analyses revealed that, compared with free flaps, patients who underwent local flap reconstruction showed less favorable 5-year DSS (hazard ratio [HR] 1.26, 82%/77%; p = 0.0100) and OS (HR 1.21, 73%/68%; p = 0.0079). CONCLUSIONS: After adjusting for covariates using multivariate models, and also by propensity score modeling, OCSCC patients who underwent free flap reconstruction showed a higher frequency of clear margins and a significant survival advantage compared with those who received local flaps.

Modulating the intersystem crossing mechanism of anthracene carboxyimide-based photosensitizers via structural adjustments and application as a potent photodynamic therapeutic reagent.

Herein, a series of compact anthracene carboxyimide (ACI) based donor-acceptor dyads were prepared by substituting bulky aryl moieties with various electron-donating ability to study the triplet-excited state properties. The ISC mechanism and triplet yield of the dyads were successfully tuned via structural manipulation. Efficient ISC (ΦΔ ≈ 99%) and long-lived triplet state (τT ≈ 122 µs) was observed for the orthogonal anthracene-labeled ACI derivative compared to the Ph-ACI and NP-ACI dyads, which showed fast triplet state decay (τT ≈ 7.7 µs). Femtosecond transient absorption study demonstrated the ultrafast charge separation (CS) and efficient charge recombination (CR) in the orthogonal dyads and ISC occurring via spin-orbit charge transfer (SOCT) mechanism (AN-ACI: τCS = 355 fs, τCR = 2.41 ns; PY-ACI: τCS = 321 fs, τCR = 1.61 ns), while in Ph-ACI and NP-ACI dyads triplet populate following the normal ISC channel (nπ* → ππ* transition), no CS was observed. We found that the attachment of suitable aryl donor moiety (AN- or PY-) to the ACI core can ensure the insertion of the intermediate triplet state, resulting in a small energy gap among charge separated state (CSS) and triplet state, which leads to efficient ISC in these derivatives. The SOCT-ISC-based AN-ACI dyad was confirmed to be a potent photodynamic therapeutic reagent; an ultra-low IC50 value (0.27 nM) that was nearly 214 times lower than that of the commercial Rose Bengal photosensitizer (57.8 nM) was observed.

Prognostic Significance of Neoadjuvant Rectal Scores in Preoperative Short-Course Radiotherapy and Long-Course Concurrent Chemoradiotherapy for Patients with Locally Advanced Rectal Cancer.

BACKGROUND: This study aimed to investigate the prognostic factors and the utility of the neoadjuvant rectal (NAR) score for patients who have locally advanced rectal cancer (LARC) treated with preoperative short-course radiotherapy (SRT) or long-course concurrent chemoradiotherapy (CRT). METHODS: Of 314 consecutive stage 2 or 3 rectal cancer patients enrolled from January 2006 to December 2017, 205 underwent preoperative SRT (2500 cGy/5 fractions), and 109 underwent preoperative CRT (4200-5080 cGy/21-28 fractions) after total mesorectal excision (TME). The study calculated NAR scores using the following equation: [5 pN - 3(cT - pT) + 12]2/9.61. RESULTS: The multivariate analysis showed that age above 65 years, pT4, pN2, NAR scores higher than 16, and distance from anal verges (< 8 cm) were significant prognostic factors for overall survival (OS), whereas, pN2, NAR scores lower than 16, and distance from anal verges (< 8 cm) were significant prognostic factors for disease-free survival (DFS) and distant metastasis (DM). The patients with an NAR score higher than 16, had a 5-year OS rate of 67.6%, a DFS rate of 56.9%, a locoregional recurrence (LRR) rate of 7.7%, and a DM rate of 35% compared with corresponding rates of 87.6%, 76.7%, 5.4%, and 7.2% for the patients with an NAR score of 16 or lower (p < 0.001 for OS, < 0.001 for DFS, 0.25 for LRR, and < 0.001 for DM). CONCLUSIONS: For patients who undergo SRT or CRT for LARC, a higher NAR score is associated with worse OS and DFS and higher DM rates at 5 years. The NAR score could be used as a short-term surrogate end point after neoadjuvant therapy for LARC.

Treatment patterns and survival outcomes of advanced hypopharyngeal squamous cell carcinoma.

BACKGROUND: This study evaluated the treatment outcomes of the primary surgery (PS) or concurrent chemoradiotherapy (CCRT) as the initial treatment for hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: This retrospective cohort study included patients with stages III-IV HPSCC from four tertiary referral centers consecutively enrolled from 2003 to 2012; of them, 213 (32.6%) and 439 (67.4%) had received PS and CCRT as their primary treatments, respectively. The 5-year overall survival (OS) and disease-free survival (DFS) rates were analyzed using the Kaplan-Meier method and Cox regression models. RESULTS: In patients undergoing PS and CCRT, OS rates were 45.0% and 33.1% (p < 0.001), respectively, and DFS rates were 36.2% and 28.9% (p = 0.003), respectively. In subgroup analysis, in patients with stage IVA HPSCC, PS was associated with higher OS rate (p = 0.002), particularly in those with T4 or N2 classification (p = 0.021 and 0.002, respectively). Multivariate analysis indicated that stage IVA HPSCC, stage IVB HPSCC, and CCRT were independent adverse prognostic factors for OS rate (p = 0.004, < 0.001, and 0.014, respectively). Furthermore, in patients with stage IVA HPSCC aged ≥ 65 years and with N2 classification, CCRT was significantly associated with lower OS rates than was PS (p = 0.027 and 0.010, respectively). CONCLUSIONS: In patients with advanced HPSCC, PS was significantly associated with better prognosis than CCRT. PS could be a favorable primary treatment modality for the management of patients with stage IVA HPSCC, particularly those aged ≥ 65 years and with T4 and N2 classification.

The Predictive Value of Pretreatment Neutrophil-To-Lymphocyte Ratio in Esophageal Squamous Cell Carcinoma.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been reported to be both a prognostic biomarker for cancer and associated with inflammation, but its predictive role in tumor immunity is not clear. The present study examined the correlations of the NLR and immune suppression with the prognoses in patients with esophageal squamous cell carcinoma (ESCC). METHODS: We performed a retrospective review of 1168 patients who were newly diagnosed with stage T1N(+) and T2-T4 ESCC at our hospital. The NLR of each ESCC patient prior to treatment was calculated, and the associations of the NLR with various clinicopathological parameters and prognoses were then examined. In addition, correlations of the proportion of myeloid-derived suppressor cells (MDSCs) and level of interleukin (IL)-6 with the NLR were assessed in 242 ESCC patients. RESULTS: An elevated NLR was significantly correlated with advanced-stage disease and reduced overall survival (OS) of ESCC patients. Furthermore, the levels of IL-6 in tumors and MDSCs in the peripheral circulation were significantly correlated with the prognoses of ESCC, and the NLR was positively correlated with MDSC levels in the circulation and IL-6 staining intensity in tumor specimens. Moreover, a high NLR was significantly associated with reduced OS in the 926 patients treated with concomitant chemoradiotherapy, but not in the 242 patients who underwent surgical intervention. CONCLUSION: The NLR may represent a clinically useful biomarker to guide ESCC treatment decisions. Patients with a higher NLR may be an optimal subgroup for IL-6- and MDSC-targeted therapy.

Long-Term Taste Impairment after Intensity-Modulated Radiotherapy to Treat Head-and-Neck Cancer: Correlations with Glossectomy and the Mean Radiation Dose to the Oral Cavity.

We explored the effects of various parameters on taste impairments (TIs) in head-and-neck (H&N) cancer patients receiving intensity-modulated radiotherapy (IMRT). From January 2014 to September 2017, 88 H&N cancer patients subjected to curative or postoperative IMRT were enrolled in this prospective study. All patients underwent at least 1 year of follow-up after IMRT. Quality-of-life assessments in terms of patient-reported gustatory function were measured using the taste-related questions of the European Organization for Research and Treatment of Cancer H&N35 questionnaires. At a median follow-up time of 27 months, 27 of 88 patients (30.7%) reported long-term TIs. In multivariate analyses, glossectomy most significantly predicted TIs (P = 0.04). The percentage of TIs (61.5%) was significantly (P = 0.03) higher in patients who underwent partial or total glossectomy than in patients who did not undergo surgery (28.0%) and those who underwent radical surgery without glossectomy (20.0%). When we excluded surgical patients from analyses, the mean radiation dose to the oral cavity was of borderline significance in terms of TI prediction (P = 0.05). Only 10.5% of patients suffered from TIs when the mean radiation dose was <5000 cGy compared with 38.7% when the mean dose was ≥5000 cGy. In conclusion, glossectomy is the major cause of long-term TIs in H&N cancer patients receiving IMRT. In patients who do not undergo glossectomy, reduction of the mean radiation dose to the oral cavity may reduce TIs after IMRT.

[Impacts of aluminum on sperm quality and sperm mitochondria in male rats].

OBJECTIVE: To study the impacts of aluminum chloride (AlCl3) on the sperm quality, sperm mitochondrial membrane potential (MMP) and sperm mitochondrial membrane permeability transition pore (MPTP) function of male rats, and the possible mechanisms of AlCl3 inducing the declination of sperm quality. METHODS: According to the median lethal dose (LD50) of AlCl3・6H2O in drinking water, we randomly assigned 96 male Wistar rats weighing 180－200 g to four groups of equal number and fed them with AlCl3 aqueous drinking water at 256.72 mg/kg/d (1/5 LD50, high-dose group), 128.36 mg/kg/d (1/10 LD50, medium-dose group), 64.18 mg/kg/d (1/20 LD50, low-dose group) and 0 mg/kg/d (control group), respectively, all for 16 weeks. Then, we examined the quality of the epididymal sperm of the rats, observed the morphology of the sperm mitochondria under the transmission electron microscope, and determined the MMP level of the sperm mitochondria and the function of the MPTP by flow cytometry. RESULTS: The percentage of progressively motile sperm was significantly decreased in the low-, medium- and high-dose AlCl3 groups as compared with that in the control group (ï¼»46.49 ± 5.37ï¼½%, ï¼»33.50 ± 8.75ï¼½% and ï¼»16.94 ± 5.00ï¼½% vs ï¼»66.28 ± 5.68ï¼½%, P < 0.01), that of dead sperm was remarkably increased (ï¼»19.73 ± 5.57ï¼½%, ï¼»35.80 ± 5.90ï¼½% and ï¼»55.19 ± 4.97ï¼½% vs ï¼»12.71 ± 4.84ï¼½%, P < 0.01), and so was that of morphologically abnormal sperm (ï¼»19.06 ± 2.44ï¼½%, ï¼»23.78 ± 3.29ï¼½% and ï¼»32.06 ± 4.65ï¼½% vs ï¼»14.56 ± 1.62ï¼½%, P < 0.01). Sperm mitochondrial swelling was aggravated in the AlCl3-exposed rats in a dose-dependent manner. The sperm MMP level was significantly lower in the low-, medium- and high-dose AlCl3 groups than in the control (ï¼»60.88 ± 7.37ï¼½%, ï¼»51.54 ± 6.12ï¼½% and ï¼»37.70 ± 7.44ï¼½% vs ï¼»74.35±4.67ï¼½%, P < 0.01), with a negative correlation to the dose of AlCl3 (rs = －0.819, P < 0.01), while the pathologically open MPTP was markedly higher in the former three than in the latter group (ï¼»27.80 ± 5.74ï¼½%, ï¼»36.58 ± 6.67ï¼½% and ï¼»64.95 ± 8.07ï¼½% vs ï¼»15.37 ± 7.13ï¼½%, P < 0.01), with a positive correlation to the dose of AlCl3 (rs = 0.867, P < 0.01). CONCLUSIONS: Exposure to aluminum can cause sperm mitochondrial swelling, decrease the sperm MMP level, induce pathological opening of the MPTP, and consequently reduce sperm quality in male rats.

Red/Near-Infrared Thermally Activated Delayed Fluorescence OLEDs with Near 100 % Internal Quantum Efficiency.

Developing red thermally activated delayed fluorescence (TADF) emitters, attainable for both high-efficient red organic light-emitting diodes (OLEDs) and non-doped deep red/near-infrared (NIR) OLEDs, is challenging. Now, two red emitters, BPPZ-PXZ and mDPBPZ-PXZ, with twisted donor-acceptor structures were designed and synthesized to study molecular design strategies of high-efficiency red TADF emitters. BPPZ-PXZ employs the strictest molecular restrictions to suppress energy loss and realizes red emission with a photoluminescence quantum yield (ΦPL ) of 100±0.8 % and external quantum efficiency (EQE) of 25.2 % in a doped OLED. Its non-doped OLED has an EQE of 2.5 % owing to unavoidable intermolecular π-π interactions. mDPBPZ-PXZ releases two pyridine substituents from its fused acceptor moiety. Although mDPBPZ-PXZ realizes a lower EQE of 21.7 % in the doped OLED, its non-doped device shows a superior EQE of 5.2 % with a deep red/NIR emission at peak of 680 nm.

Role of ALDH1 in the prognosis of esophageal cancer and its relationship with tumor microenvironment.

Aldehyde dehydrogenase 1 (ALDH1) is associated with tumorigenesis, and significantly increased in cancer stem-like cells. In the present study, the role of ALDH1 in esophageal squamous cell carcinoma (ESCC) was investigated. We retrospectively analyzed the clinical outcomes of 148 ESCC and examined its correlation with ALDH1 levels. Furthermore, we preformed cellular and animal experiments to investigate the role of ALDH1 in tumor progression and microenvironment. Our data revealed that ALDH1 staining was positively linked to a higher clinical stage, higher loco-regional failure rate, and shorter survival time. Furthermore, there was a positive link between ALDH1 expression and IL-6 signaling according to the data of clinical specimens and cellular experiments. Using animal model, ALDH1-positive tumors were associated with aggressive tumor growth, increased IL-6, augmented epithelial-mesenchymal transition (EMT), and activation of myeloid-derived suppressor cells (MDSCs). Blockade of COX-2 attenuated the aggressive tumor growth of ALDH1-positive cancer cells. In conclusion, our findings suggested that ALDH1 played an important role in tumor aggressiveness and associated with a tumor-promoting microenvironment in esophageal cancer. Directly targeting ALDH1 or using a COX-2 inhibitor could be a promising strategy for the treatment of ESCC.

Predictive Value of CD44 in Muscle-Invasive Bladder Cancer and Its Relationship with IL-6 Signaling.

BACKGROUND: CD44, a cancer stem cell surface marker, is associated with treatment resistance and prognosis in some cancers. In the present study, we examined the predictive value of CD44 in muscle-invasive bladder cancer (MIBC). METHODS: We retrospectively analyzed the clinical outcomes of 105 MIBC patients and correlated these outcomes with the expression of CD44. Furthermore, the bladder cancer cell lines HT1197 and MB49 were selected for cellular and animal experiments to investigate the correlation between CD44 and tumor aggressiveness. RESULTS: Analysis of clinical specimens indicated that CD44 staining was significantly associated with a higher clinical stage, higher locoregional failure rate, and lower disease-specific survival rate for MIBC patients. Using cellular experiments and orthotopic tumor models, we showed that CD44+ bladder cancer cells had a higher invasion ability and augmented epithelial-mesenchymal transition (EMT) compared with CD44 cells. There was a significant correlation between interleukin (IL)-6 and CD44 levels noted by in vitro testing, and clinical samples. Blockade of IL-6 attenuated the expression of CD44, cancer stem-cell-like properties, and aggressive tumor behavior in vitro and in vivo. The related changes included the attenuated STAT3 activation and EMT, and decreased programmed death ligand 1-mediated T-cell suppression. CONCLUSION: Our findings suggest that CD44 expression is positively associated with tumor aggressiveness in bladder cancer, and activated IL-6 signaling provides a suitable microenvironment for the induction of CD44 expression.

Manipulation of Molecular Aggregation States to Realize Polymorphism, AIE, MCL, and TADF in a Single Molecule.

Multifunctional emitting materials are scarce and need to be further explored. Now, a newly anthraquinone derivative, 2-(phenothiazine-10-yl)-anthraquinone (PTZ-AQ) was designed and synthesized and found to demonstrate polymorphism, multi-color emission, aggregation-induced emission (AIE), mechanochromic luminescence (MCL), and thermally activated delayed fluorescence (TADF) in its different solid forms. It is shown for the first time that TADF properties of a compound can be systematically tuned via its aggregation state. The optimized PTZ-AQ crystal shows a small singlet-triplet energy splitting of 0.01 eV and exhibits red TADF with a photoluminescence quantum yield as high as 0.848. This study shows that the unique multiple functions can be integrated into one single compound through controlling the aggregation states, which provides a new strategy for the investigation and application of multifunctional organic materials.