The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy.

Epilepsy is a multifaceted neurological syndrome characterized by recurrent, spontaneous, and synchronous seizures. The pathogenesis of epilepsy, known as epileptogenesis, involves intricate changes in neurons, neuroglia, and endothelium, leading to structural and functional disorders within neurovascular units and culminating in the development of spontaneous epilepsy. Although current research on epilepsy treatments primarily centers around anti-seizure drugs, it is imperative to seek effective interventions capable of disrupting epileptogenesis. To this end, a comprehensive exploration of the changes and the molecular mechanisms underlying epileptogenesis holds the promise of identifying vital biomarkers for accurate diagnosis and potential therapeutic targets. Emphasizing early diagnosis and timely intervention is paramount, as it stands to significantly improve patient prognosis and alleviate the socioeconomic burden. In this review, we highlight the changes and molecular mechanisms of the neurovascular unit in epileptogenesis and provide a theoretical basis for identifying biomarkers and drug targets.

Charge-Reversal NaCl/G-Quartets for Aggregation-Induced Mitochondrial MicroRNA Imaging and Ion-Interference Therapy.

Mitochondrial therapy is a promising new strategy that offers the potential to achieve precise disease diagnosis or maximum therapeutic response. However, versatile mitochondrial theranostic platforms that integrate biomarker detection and therapy have rarely been exploited. Here, we report a charge-reversal nanomedicine activated by an acidic microenvironment for mitochondrial microRNA (mitomiR) detection and ion-interference therapy. The transporter liposome (DD-DC) was constructed from a pH-responsive polymer and a positively charged phospholipid, encapsulating NaCl nanoparticles with coloading of the aggregation-induced emission (AIE) fluorogens AIEgen-DNA/G-quadruplexes precursor and brequinar (NAB@DD-DC). The negatively charged nanomedicine ensured good blood stability and high tumor accumulation, while the charge-reversal to positive in response to the acidic pH in the tumor microenvironment (TME) and lysosomes enhanced the uptake by tumor cells and lysosome escape, achieving accumulation in mitochondria. The subsequently released Na+ in mitochondria not only contributed to the formation of mitomiR-494 induced G-quadruplexes for AIE imaging diagnosis but also led to an osmolarity surge that was enhanced by brequinar to achieve effective ion-interference therapy.

Fabrication of hyaluronic acid-altered gold complex delivery for head and neck squamous cell carcinoma therapy with high antitumor efficacy and low in vivo toxicity.

The use of multifunctional nanomedicines in the treatment of tumors is gaining popularity. Here, we constructed a nanodrug delivery system (HA/Au-PDA@CZT) that targets tumors and responds to pH and near-infrared (NIR) dual stimuli. By precisely interacting with an overexpressed CD44 receptor in specific cancer cells, hyaluronic acid (HA) is coated on the Au-PDA NP surface for tumor-targeting abilities. When exposed to NIR radiation, polydopamine (PDA) and gold nanoshells exhibit exceptional photothermal performance that has the potential to both accelerate and kill HLAC 78 head and neck squamous cell carcinoma cells. Antitumor investigations conducted in vivo and in vitro demonstrated that nanomedicine had remarkable synergistic benefits with chemotherapy and photothermal treatment. Only 25.2% of the cells in the HA/Au-PDA@CZT with a NIR irradiation group were viable. Any group's lowest tumor volume was shown in the tumor mice subjected to HA/Au-PDA@CZT with NIR at 0.3 ± 0.1. Consequently, for synergistic chemo-photothermal therapy, our logically designed nanoplatform would be the potential for a head and neck squamous tumor-targeting drug delivery system.

Mapping of cytosol-facing organelle outer membrane proximity proteome by proximity-dependent biotinylation in living Arabidopsis cells.

The cytosol-facing outer membrane (OM) of organelles communicates with other cellular compartments to exchange proteins, metabolites, and signaling molecules. Cellular surveillance systems also target OM-resident proteins to control organellar homeostasis and ensure cell survival under stress. However, the OM proximity proteomes have never been mapped in plant cells since using traditional approaches to discover OM proteins and identify their dynamically interacting partners remains challenging. In this study, we developed an OM proximity labeling (OMPL) system using biotin ligase-mediated proximity biotinylation to identify the proximity proteins of the OMs of mitochondria, chloroplasts, and peroxisomes in living Arabidopsis (Arabidopsis thaliana) cells. Using this approach, we mapped the OM proximity proteome of these three organelles under normal conditions and examined the effects of the ultraviolet-B (UV-B) or high light (HL) stress on the abundances of OM proximity proteins. We demonstrate the power of this system with the discovery of cytosolic factors and OM receptor candidates potentially involved in local protein translation and translocation. The candidate proteins that are involved in mitochondrion-peroxisome, mitochondrion-chloroplast, or peroxisome-chloroplast contacts, and in the organellar quality control system are also proposed based on OMPL analysis. OMPL-generated OM proximity proteomes are valuable sources of candidates for functional validation and suggest directions for further investigation of important questions in cell biology.

Chemical and Structural Engineering of Gelatin-Based Delivery Systems for Therapeutic Applications: A Review.

As a biodegradable and biocompatible protein derived from collagen, gelatin has been extensively exploited as a fundamental component of biological scaffolds and drug delivery systems for precise medicine. The easily engineered gelatin holds great promise in formulating various delivery systems to protect and enhance the efficacy of drugs for improving the safety and effectiveness of numerous pharmaceuticals. The remarkable biocompatibility and adjustable mechanical properties of gelatin permit the construction of active 3D scaffolds to accelerate the regeneration of injured tissues and organs. In this Review, we delve into diverse strategies for fabricating and functionalizing gelatin-based structures, which are applicable to gene and drug delivery as well as tissue engineering. We emphasized the advantages of various gelatin derivatives, including methacryloyl gelatin, polyethylene glycol-modified gelatin, thiolated gelatin, and alendronate-modified gelatin. These derivatives exhibit excellent physicochemical and biological properties, allowing the fabrication of tailor-made structures for biomedical applications. Additionally, we explored the latest developments in the modulation of their physicochemical properties by combining additive materials and manufacturing platforms, outlining the design of multifunctional gelatin-based micro-, nano-, and macrostructures. While discussing the current limitations, we also addressed the challenges that need to be overcome for clinical translation, including high manufacturing costs, limited application scenarios, and potential immunogenicity. This Review provides insight into how the structural and chemical engineering of gelatin can be leveraged to pave the way for significant advancements in biomedical applications and the improvement of patient outcomes.

Surgical treatment and prognosis of recurrent and radiotherapy insensitive nasopharyngeal carcinoma.

OBJECTIVE: To explore the effect of surgical treatment and related prognostic factors for recurrent Nasopharyngeal Carcinoma (NPC) after radiotherapy and the pathological types of nasopharyngeal carcinoma insensitive to radiotherapy. METHODS: A total of 70 NPC patients who underwent surgery at the Department of Otolaryngology, head and neck surgery, from January 2005 to December 2020 were retrospectively included: 41 males and 29 females, aged 21-75 years, 47 patients were pathologically classified as NPC (nonkeratinizing, undifferentiated type), 10 patients as adenoid cystic carcinoma, 13 patients as other types, 45 patients had received radiotherapy preoperatively, and 25 patients had not received radiotherapy preoperatively. All patients underwent surgical treatment under general anesthesia. Fifty-six patients underwent nasoendoscopic NPC resection, seven patients underwent open surgery, and seven patients underwent combined nasoendoscopic and open surgery. The median follow-up was 39 months. Tumor volume, extent of involvement, lymph node metastasis, imaging characteristics, surgical approach and efficacy, postoperative complications, and 2-, 3-, and 5-year postoperative survival rates were calculated for all patients. Statistical analysis was performed using spss22 Kaplan Meier survival analysis and Cox regression analysis were performed. RESULTS: Among the 70 patients, the overall 2-year survival rate was 93.4%, the 3-year survival rate was 90.8%, and the 5-year survival rate was 80.3%. Multivariate analysis showed that TNM stage and age at onset were independent prognostic factors for NPC outcome. CONCLUSION: Depending on the size and location of the tumor, endoscopic surgery, open surgery, and combined open surgery with nasoendoscopy may be considered for recurrent and radiotherapy insensitive NPC. LEVEL OF EVIDENCE: Level 4.

Application of prolonged submental perforator flap to repair the postoperative defect of upper airway malignancy.

OBJECTIVES: To explore the feasibility of making a submental perforator flap distal to the connecting line between the mastoid and the sternoclavicular joint under the guidance of neck-enhanced CT and repairing the postoperative defect of upper airway malignancy. MATERIALS AND METHODS: This study retrospectively analysed 19 cases of upper airway malignant tumours treated in our department from January 2021 to September 2022, including 17 males and 2 females, aged 43-70 years. SITE OF LESIONS: 15 cases were in the laryngopharynx, 2 cases in the nasal cavity and paranasal sinus and 2 cases on the soft palate. All the lesions were malignant and at stages T2-4N0-2M0. SURGICAL METHOD: The extended submental perforator flap (size 22-15 × 6-7 cm) was prefabricated distal to the connecting line between the mastoid and the sternoclavicular joint. After tumour resection, the flap was used to repair the postoperative defect. Fifteen cases of laryngopharyngeal malignant tumours were repaired using the extended submental perforator flap with the vascular pedicle located on the opposite side of the tumour body. Two cases of nasal cavity and paranasal sinus tumours were repaired using the extended submental perforator flap combined with the temporalis muscle flap. The soft palate was completely removed in two patients with soft palate cancer and repaired using the folded extended submental perforator flap. RESULTS: Before the surgery, the reflux vein was observed by neck-enhanced CT, including 12 cases returning to the internal jugular vein and 7 cases to the external jugular vein. All 19 cases in which flaps were used survived, and 1 case had a postoperative infection. All the patients had nasal feeding removed after surgery. The tracheal cannula was removed from the patients with laryngeal preservation, and the pronunciation was satisfactory. Among them, patients with soft palate cancer repair had mild nasal reflux symptoms with smooth breathing. During the follow-up period of 4-24 months, 18 patients had no tumour recurrence or metastasis, and 1 patient had cervical lymph node metastasis. CONCLUSIONS: This study highlights the use of a submental perforator flap distal to the connecting line between the mastoid and the sternoclavicular joint to repair postoperative defects for upper airway malignancy as an innovative surgical approach that provides more tissue and good arteriovenous blood supply to adjacent sites. This method has high clinical value and provides an effective option for repairing postoperative defects of upper airway malignancy.

A hierarchical porous aerohydrogel for enhanced water evaporation.

Natural solar-powered steam generation provides a promising strategy to deal with deteriorating water resources. However, the practical applications of this strategy are limited by the tedious manufacturing of structures at micro-nano levels to concentrate heat and transport water to heat-localized regions. Herein, this work reports the fabrication of hierarchically porous aerohydrogel with enhanced light absorption and thermal localization at the air-solid interface. This aerohydrogel steam generator is fabricated by a simple yet controllable micropore generation approach to assemble air and hydrogel into hierarchically porous gas-solid hybrids. The tunable micropore size in a wide range from 99±49µm to 316±58µm not only enables contrasting sunlight absorptance (0.2 - 2.5µm) by reducing the reflection of solar light but also harnesses water transportation to the heating region via a capillary force-driven liquid flow. Therefore, a solar-vapor conversion efficiency of 91.3% under one sun irradiation was achieved using this aerohydrogel evaporator, reaching a ready evaporation rate of 2.76kg m-2 h-1 and 3.71kg m-2 h-1 under one and two sun irradiations, respectively. Our work provides a versatile and scalable approach to engineering porous hydrogels for highly efficient steam generation and opens an avenue for other potential practical applications based on this aerohydrogel.

Impact of altered groundwater depth on soil microbial diversity, network complexity and multifunctionality.

Understanding the effects of groundwater depth on soil microbiota and multiple soil functions is essential for ecological restoration and the implementation of groundwater conservation. The current impact of increased groundwater levels induced by drought on soil microbiota and multifunctionality remains ambiguous, which impedes our understanding of the sustainability of water-scarce ecosystems that heavily rely on groundwater resources. This study investigated the impacts of altered groundwater depths on soil microbiota and multifunctionality in a semi-arid region. Three groundwater depth levels were studied, with different soil quality and soil moisture at each level. The deep groundwater treatment had negative impacts on diversity, network complexity of microbiota, and the relationships among microbial phylum unites. Increasing groundwater depth also changed composition of soil microbiota, reducing the relative abundance of dominant phyla including Proteobacteria and Ascomycota. Increasing groundwater depth led to changes in microbial community characteristics, which are strongly related to alterations in soil multifunctionality. Overall, our results suggest that groundwater depth had a strongly effect on soil microbiota and functionality.

Induction chemotherapy-based organ-preservation protocol improve the function preservation compared with immediate total laryngectomy for locally advanced hypopharyngeal cancer-Results of a matched-pair analysis.

BACKGROUND: We performed a paired analysis to compare the therapeutic effect between the induction chemotherapy-based organ-preservation approach and immediate total laryngectomy in hypopharyngeal squamous cell carcinoma patients requiring total laryngectomy. METHODS: 351 patients who were treated with organ-preservation approach were compared with 110 patients who were treated with total laryngectomy. The main measures and outcomes were progression-free survival (PFS), overall survival (OS), and larynx function preservation survival (LFPS). RESULTS: No statistical difference was observed for 3-, 5-, and 10-year PFS and OS in two groups. In the organ-preservation group, the 3-, 5-, and 10-year LFPS was 30.7%, 23.3%, and 16.6%, respectively. The LFPS of Stage III > Stage IV, N0 > N1 > N2 > N3, T2 > T3 > T4, CR > PR > SD > PD patients (all p values <0.05). CONCLUSIONS: Survival outcomes did not significantly differ between the two groups. The organ-preservation approach allowed more than 70% of the survivors to retain their larynx function.

Integrating molybdenum into zinc vanadate enables Zn3V2MoO8 as a high-capacity Zn-supplied cathode for Zn-metal free aqueous batteries.

The commercialization of aqueous zinc-ion batteries (AZIBs) has been hindered by the obsession with Zn-metal anode, just like the early days of lithium-ion batteries. Developing Zn-metal free aqueous batteries (ZFABs) with superior Zn-supplied cathodes is a promising way to escape this predicament. Herein, a novel mixed transition-metal spinel, Zn3V2MoO8, has been synthesized via a sol-gel technique and proposed as a Zn-supplied cathode material. Utilizing the synergistic effect of vanadium and molybdenum, Zn3V2MoO8 can provide a high capacity of 360.3 mA h g-1 at 100 mA g-1, which is the state-of-the-art in existing Zn-supplied cathodes, and the capacity retention is 82% over 700-4500 cycles at 10 A g-1. The mechanism is that Zn3V2MoO8 undergoes a phase transition to Zny(V,Mo)2O5-x·nH2O in the initial charge, and then protons and zinc ions intercalate/deintercalate concurrently into/from the new host. To construct ZFABs with a Zn3V2MoO8 cathode, two non-zinc materials (brass and 9,10-anthraquinone) are used as anodes. Thereby, the Zn3V2MoO8||9,10AQ battery reveals a more satisfactory electrochemical performance, with a stable capacity of 100.4 mA h g-1 lasting for 200 cycles, which provides a feasible scheme for the practical application of AZIBs.

Different responses of two maize cultivars to Spodoptera frugiperda (Lepidoptera: Noctuidae) larvae infestation provide insights into their differences in resistance.

Spodoptera frugiperda (Lepidoptera: Noctuidae), a pest with an amazing appetite, damages many crops and causes great losses, especially maize. Understanding the differences in different maize cultivars' responses to S. frugiperda infestation is very important for revealing the mechanisms involved in the resistance of maize plants to S. frugiperda. In this study, a comparative analysis of two maize cultivars, the common cultivar 'ZD958' and the sweet cultivar 'JG218', was used to investigate their physico-biochemical responses to S. frugiperda infestation by a pot experiment. The results showed that the enzymatic and non-enzymatic defense responses of maize seedlings were rapidly induced by S. frugiperda. Frist, the hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents of infested maize leaves were significantly increased and then decreased to the level of the control. Furthermore, compared with the control leaves, the puncture force values and the total phenolics, total flavonoids, and 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one contents of infested leaves were significantly increased within a certain time. The superoxide dismutase and peroxidase activities of infested leaves were significantly increased in a certain period of time, while the catalase activities decreased significantly and then increased to the control level. The jasmonic acid (JA) levels of infested leaves were significantly improved, whereas the salicylic acid and abscisic acid levels changed less. Signaling genes associated with phytohormones and defensive substances including PAL4, CHS6, BX12, LOX1, and NCED9 were significantly induced at certain time points, especially LOX1. Most of these parameters changed greater in JG218 than in ZD958. Moreover, the larvae bioassay showed that S. frugiperda larvae weighed more on JG218 leaves than those on ZD958 leaves. These results suggested that JG218 was more susceptible to S. frugiperda than ZD958. Our findings will make it easier to develop strategies for controlling S. frugiperda for sustainable maize production and breeding of new maize cultivars with increased resistance to herbivores.

Dysregulated Polycomb Repressive Complex 2 contributes to chronic obstructive pulmonary disease by rewiring stem cell fate.

Aberrant lung cell differentiation is a hallmark of many lung diseases including chronic obstructive pulmonary disease (COPD). The EZH2-containing Polycomb Repressive Complex 2 (PRC2) regulates embryonic lung stem cell fate, but its role in adult lung is obscure. Histological analysis of patient tissues revealed that loss of PRC2 activity was correlated with aberrant bronchiolar cell differentiation in COPD lung. Histological and single-cell RNA-sequencing analyses showed that loss of EZH2 in mouse lung organoids led to lowered self-renewal capability, increased squamous morphological development, and marked shifts in progenitor cell populations. Evaluation of in vivo models revealed that heterozygosity of Ezh2 in mice with ovalbumin-induced lung inflammation led to epithelial cell differentiation patterns similar to those in COPD lung. We also identified cystathionine-ß-synthase as a possible upstream factor for PRC2 destabilization. Our findings suggest that PRC2 is integral to facilitating proper lung stem cell differentiation in humans and mice.

Unusual Dual-Site Substitution Adjusts the Degree of Stacking Disorder in Honeycomb Na3Ni2SbO6 Cathode for Sodium-Ion Batteries.

O'3-Na3Ni2SbO6 with a honeycomb cation order, as a potential cathode, presents simplified phase-transition steps and a high average voltage. To mitigate the intrinsic phase irreversibility, Mg, Zn, and Co have been introduced to displace part of the Ni, which inevitably reduces the theoretical capacity related to the Ni2+/Ni3+ redox reaction. In this work, an unusual dual-site substitution is carried out to increase the P'3-O'3 structure reversibility without sacrificing the practical capacity. In addition, it is found that special stacking faults along the c-axis direction can be induced by doping to result in incomplete Sb/Ni disorder, though the honeycomb order remains in every TM (transition-metal) layer. The codoped Na2.85Cs0.15Ni1.9Mg0.1SbO6 has a high degree of disorder, which breaks the ideal monoclinic symmetry (C2/m) and partly upgrades its structure to higher-symmetry models. Profiting from the influence of stacking disorder and doping ions on the coordination environment around Na, more gradual and smaller variations of the lattice parameters appear upon Na-ion extraction/insertion. Consequently, this cathode displays a high initial discharge capacity (120 mAh g-1), long-term cycling stability, and excellent rate performance (66 mAh g-1 under 10 C). These findings reveal that not only a full TM-disordered arrangement but also this incomplete stacking disorder can effectively improve the performance of a layered cathode.

Hydrogen Peroxide Promotes the Production of Radiation-Derived EVs Containing Mitochondrial Proteins.

In spite of extensive successes, cancer recurrence after radiation treatment (RT) remains one of the significant challenges in the cure of localized prostate cancer (PCa). This study focuses on elucidating a novel adaptive response to RT that could contribute to cancer recurrence. Here, we used PC3 cell line, an adenocarcinoma from a bone metastasis and radio-resistant clone 695 cell line, which survived after total radiation dose of 66 Gy (2 Gy × 33) and subsequently regrew in nude mice after exposure to fractionated radiation at 10 Gy (2 Gy × 5). Clone 695 cells not only showed an increase in surviving fraction post-radiation but also an increase in hydrogen peroxide (H2O2) production when compared to PC3 cells. At the single cell level, confocal microscope images coupled with IMARIS rendering software demonstrate an increase in mitochondrial mass and membrane potential in clone 695 cells. Utilizing the Seahorse XF96 instrument to investigate mitochondrial respiration, clone 695 cells demonstrated a higher basal Oxygen Consumption Rate (OCR), ATP-linked OCR, and proton leak compared to PC3 cells. The elevation of mitochondrial function in clone 695 cells is accompanied by an increase in mitochondrial H2O2 production. These data suggest that H2O2 could reprogram PCa's mitochondrial homeostasis, which allows the cancer to survive and regrow after RT. Upon exposure to RT, in addition to ROS production, we found that RT induces the release of extracellular vesicles (EVs) from PC3 cells (p < 0.05). Importantly, adding H2O2 to PC3 cells promotes EVs production in a dose-dependent manner and pre-treatment with polyethylene glycol-Catalase mitigates H2O2-mediated EV production. Both RT-derived EVs and H2O2-derived EVs carried higher levels of mitochondrial antioxidant proteins including, Peroxiredoxin 3, Glutathione Peroxidase 4 as well as mitochondrial-associated oxidative phosphorylation proteins. Significantly, adding isolated functional mitochondria 24 h prior to RT shows a significant increase in surviving fractions of PC3 cells (p < 0.05). Together, our findings reveal that H2O2 promotes the production of EVs carrying mitochondrial proteins and that functional mitochondria enhance cancer survival after RT.

A novel strategy via electrode catalysis induced nano transformation for lithiated-bimetallic-oxides to avoid the long activation process of advanced lithium-ion batteries.

Improving the anode materials for lithium-ion batteries with a long activation process, poor cycle stability, and low Coulomb efficiency is of great significance for developing novel high-performance anode materials. Orthorhombic LiVMoO5 with high specific capacity was applied to the anode field of lithium-ion battery for the first time. However, the activation process led to its poor cyclic performance. By adopting a novel nano-transformation treatment process in a water and oxygen environment, we effectively avoided the long-term activation process. The specially treated LiVMoO5 electrode (STLVME) exhibited excellent reversible specific capacity (∼1100 mA h g-1) and rate cycle stability (capacity retention rate ∼100%). Furthermore, GITT and EIS also showed that compared with the primitive LiVMoO5 electrode (LVME), smaller internal resistance and a higher Li+ diffusion coefficient were caused using the novel treatment process, significantly improving the rate cycle stability. Using in situ XRD and ex situ characterization, we illustrated the lithium storage mechanism of LVME and STLVME. In addition, the practical application potential of LVME and STLVME was also explored by assembling the full cells. Because the long-term activation process was effectively avoided, the full-cell exhibited amazing cycle stability, indicating that STLVME can be considered a promising potential anode for practical applications in energy storage devices.

CuCo2S4 Nanoparticles Embedded in Carbon Nanotube Networks as Sulfur Hosts for High Performance Lithium-Sulfur Batteries.

Rational design of sulfur hosts for lithium-sulfur (Li-S) batteries is essential to address the shuttle effect and accelerate reaction kinetics. Herein, the composites of bimetallic sulfide CuCo2S4 loaded on carbon nanotubes (CNTs) are prepared by hydrothermal method. By regulating the loading of CuCo2S4 nanoparticles, it is found that when Cu2+ and CNT are prepared in a 10:1 ratio, the CuCo2S4 nanoparticles loaded on the CNT are relatively uniformly distributed, avoiding the occurrence of agglomeration, which improves the electrical conductivity and number of active sites. Through a series of electrochemical performance tests, the S/CuCo2S4-1/CNT presents a discharge specific capacity of 1021 mAh g-1 at 0.2 C after 100 cycles, showing good cycling stability. Even at 1 C, the S/CuCo2S4-1/CNT cathode delivers a discharge capacity of 627 mAh g-1 after 500 cycles. This study offers a promising strategy for the design of bimetallic sulfide-based sulfur hosts in Li-S batteries.

A combined microinvasive trans-submandibular and nasendoscopy surgical approach to dissect recurrent or radiotherapy-insensitive nasopharyngeal carcinoma.

Objective: To investigate a novel combined microinvasive trans-submandibular and nasendoscopy surgical approach for nasopharyngeal carcinoma involving the parapharyngeal space. Methods: Seven patients diagnosed with nasopharyngeal carcinoma involving the parapharyngeal space between May 2018 and April 2021, two males and five females, aged 37-63 years.Six of the 7 patients underwent submental flap preparation and dissection of the lymph nodes in the upper neck and parapharyngeal space on the lesion side. The nasopharynx lesions and tumor margins were dissected under nasal endoscopy. The medial boundary of internal carotid artery separated by open cervical approach was used as the lateral boundary of the tumor to realize en bloc resection of the tumor. Results: The patients were preoperatively diagnosed with T2~3N0M0 nasopharyngeal carcinoma, including mucoepidermoid carcinoma (n=2), papillary adenocarcinoma (n=1), and nonkeratinizing squamous cell carcinoma (n=4). The tumors were removed completely, and patients achieved primary healing of the incision. No recurrence and no serious complications were recorded during the 13-48 month follow-up. Conclusion: Complete resection of the tumor was obtained in the 7 patients without recurrence and serious complications during the follow-up. The findings of this cohort study suggest that, patients with recurrent nasopharyngeal carcinoma after radiotherapy and radiotherapy-insensitive types of nasopharyngeal carcinoma, the combined microinvasive trans-submandibular and nasendoscopy surgical approach may be considered as an surgical options. The results of this study provide an additional option for surgical treatment of NPC in the clinic.

Prognostic significance of myocardial salvage assessed by cardiac magnetic resonance in reperfused ST-segment elevation myocardial infarction.

Aims: Myocardial salvage index (MSI) is attracting increasing attention for predicting prognosis in acute myocardial infarction (AMI); however, the evaluation of MSI is mainly based on contrast agent-dependent cardiac magnetic resonance (CMR) scanning sequences. This study aims to investigate the prognostic value of MSI in reperfused ST-segment elevation myocardial infarction (STEMI) through the contrast agent-free CMR technique. Methods and results: Nighty-two patients with acute STEMI, who underwent CMR after primary percutaneous coronary intervention (PPCI), were finally enrolled. Patients were subcategorized into two groups according to median MSI. T1 and T2 mapping were conducted for measuring infarct size (IS) and area at risk (AAR). IS was significantly larger in < median MSI group than ≥ median MSI group (P < 0.001). AAR between the two groups showed no obvious differences (P = 0.108). Left ventricular ejection fraction (LVEF) was lower in < median MSI group than ≥ median MSI group (P = 0.014). There was an obvious inverse correlation between MSI and reperfusion time (R = -0.440, P < 0.001) and a strong inverse correlation between MSI and IS (R = -0.716, P = 0.011). As for the relationship LVEF, MSI showed positive but weak correlation (R = 0.2265, P < 0.001). Over a median follow-up period of 263 (227-238) days, prevalence of MACEs was significantly higher in the < median MSI group [HR: 0.15 (0.04-0.62); Log-rank P = 0.008]. The univariate Cox regression analysis revealed that LVEF, IS, and MSI were significant predictors for major adverse cardiovascular events (MACEs) (all P < 0.05). In the stepwise multivariate Cox regression analysis, LVEF and MSI were identified as independent parameters for predicting MACEs (both P < 0.05). In the receiver-operating characteristic analysis, LVEF, IS, and MSI showed prognostic value in predicting MACEs with AUCs of 0.809, 0.779, and 0.896, respectively, all (P < 0.05). A combination of MSI with LVEF showed the strongest prognostic value of MACEs (AUC: 0.901, sensitivity: 77.78%, specificity: 98.80%, P < 0.001). Delong's test showed that the combination of LVEF with MSI had an incremental value than LVEF itself in predicting MACEs (P = 0.026). Conclusion: Contrast agent-free CMR technique provides a reliable evaluation of MSI, which contributes to assessing the efficacy of reperfusion therapy and predicting the occurrence of MACEs.

Validating a Major Quantitative Trait Locus and Predicting Candidate Genes Associated With Kernel Width Through QTL Mapping and RNA-Sequencing Technology Using Near-Isogenic Lines in Maize.

Kernel size is an important agronomic trait for grain yield in maize. The purpose of this study was to validate a major quantitative trait locus (QTL), qKW-1, which was identified in the F2 and F2:3 populations from a cross between the maize inbred lines SG5/SG7 and to predict candidate genes for kernel width (KW) in maize. A major QTL, qKW-1, was mapped in multiple environments in our previous study. To validate and fine map qKW-1, near-isogenic lines (NILs) with 469 individuals were developed by continuous backcrossing between SG5 as the donor parent and SG7 as the recurrent parent. Marker-assisted selection was conducted from the BC2F1 generation with simple sequence repeat (SSR) markers near qKW-1. A secondary linkage map with four markers, PLK12, PLK13, PLK15, and PLK17, was developed and used for mapping the qKW-1 locus. Finally, qKW-1 was mapped between the PLK12 and PLK13 intervals, with a distance of 2.23 cM to PLK12 and 0.04 cM to PLK13, a confidence interval of 5.3 cM and a phenotypic contribution rate of 23.8%. The QTL mapping result obtained was further validated by using selected overlapping recombinant chromosomes on the target segment of maize chromosome 3. Transcriptome analysis showed that a total of 12 out of 45 protein-coding genes differentially expressed between the two parents were detected in the identified qKW-1 physical interval by blasting with the Zea_Mays_B73 v4 genome. GRMZM2G083176 encodes the Niemann-Pick disease type C, and GRMZM2G081719 encodes the nitrate transporter 1 (NRT1) protein. The two genes GRMZM2G083176 and GRMZM2G081719 were predicted to be candidate genes of qKW-1. Reverse transcription-polymerase chain reaction (RT-qPCR) validation was conducted, and the results provide further proof of the two candidate genes most likely responsible for qKW-1. The work will not only help to understand the genetic mechanisms of KW in maize but also lay a foundation for further cloning of promising loci.