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BACKGROUND: Human papillomavirus (HPV) infection has become an important etiological driver of oropharyngeal squamous cell carcinoma (OPSCC), leading to unique tumor characteristics. However, the interplay between HPV-associated tumor cells and tumor microenvironment (TME) remains an enigma. METHODS: We performed a single-cell RNA-sequencing (scRNA-seq) on HPV-positive (HPV+) and HPV-negative (HPVâ) OPSCC tumors, each for three samples, and one normal tonsil tissue. Ex vivo validation assays including immunofluorescence staining, cell line co-culture, and flow cytometry analysis were used to test specific subtypes of HPV+ tumor cells and their communications with T cells. RESULTS: Through a comprehensive single-cell transcriptome analysis, we uncover the distinct transcriptional signatures between HPV+ and HPVâ OPSCC. Specifically, HPV+ OPSCC tumor cells manifest an enhanced interferon response and elevated expression of the major histocompatibility complex II (MHC-II), potentially bolstering tumor recognition and immune response. Furthermore, we identify a CXCL13+CD4+ T cell subset that exhibits dual features of both follicular and pro-inflammatory helper T cells. Noteworthily, HPV+ OPSCC tumor cells embrace extensive intercellular communications with CXCL13+CD4+ T cells. Interaction with HPV+ OPSCC tumor cells amplifies CXCL13 and IFNγ release in CD4+T cells, fostering a pro-inflammatory TME. Additionally, HPV+ tumor cells expressing high MHC-II and CXCL13+CD4+ T cell prevalence are indicative of favorable overall survival rates in OPSCC patients. CONCLUSIONS: Together, our study underscores a synergistic inflammatory immune response orchestrated by highly immunogenic tumor cells and CXCL13+CD4+ T cells in HPV+ OPSCC, offering useful insights into strategy development for patient stratification and effective immunotherapy in OPSCC.
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Linfocitos T CD4-Positivos , Quimiocina CXCL13 , Inmunoterapia , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Microambiente Tumoral , Humanos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Quimiocina CXCL13/metabolismo , Quimiocina CXCL13/genética , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase II/metabolismo , Inmunoterapia/métodos , Activación de Linfocitos , Neoplasias Orofaríngeas/inmunología , Neoplasias Orofaríngeas/virología , Neoplasias Orofaríngeas/terapia , Papillomaviridae , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicacionesRESUMEN
Introduction: A meta-analysis was performed to examine the effects of wound catheter (WC) local anaesthetic infiltration (LAI) and epidural analgesia (EA) in open hepatectomy (OH). Material and methods: A systematic literature review was performed, which found 350 subjects with OH at the baseline of the studies; 159 of them were treated with WC local anaesthetic infiltration, and 191 used EA. Results: WC LAI substantially reduced the functional recovery time (MD = -0.64; 95% CI, -1.02 to -0.26, p < 0.001) and increased the pain score on the second postoperative day (MD = 0.25; 95% CI: 0.10-0.40, p < 0.001) compared to EA in OH patients. WC LAI did not vary from EA in OH patients in second postoperative opiate use (MD = -14.86; 95% CI: -32.88 to 3.16, p = 0.11) or overall complication rate (OR = 0.66; 95% CI: 0.41-1.04, p = 0.07). Conclusions: WC LAI showed a non-significant difference in opiate consumption on the second postoperative day and in the overall complication rate, compared with EA, but it showed a lower functional recovery time and higher pain score.
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BACKGROUND: N1-Methyladenosine (m1A) is an abundant modification of transcripts regulating mRNA structure and translation efficiency. However, the characteristics and biological functions of mRNA m1A modification in adult hippocampal neurogenesis remain enigmatic. RESULTS: We found that m1A demethylase Alkbh3 was dramatically enriched in neurons and neuronal genesis. Functionally, depletion of Alkbh3 in neural stem cells (NSCs) significantly decreased m1A modification, neuronal differentiation and proliferation coupling with increasing gliogenesis, whereas overexpressing Alkbh3 facilitated neuronal differentiation and proliferation. Mechanistically, the m1A demethylation of Mmp15 mRNA by Alkbh3 improved its RNA stability and translational efficacy, which promoted neurogenesis. Therapeutically, the silencing of Alkbh3 reduced hippocampal neurogenesis and impaired spatial memory in the adult mice. CONCLUSIONS: We reveal a novel function of m1A demethylation on Mmp15 mRNA in Alkbh3-mediated neurogenesis, which shed light on advancing Alkbh3 regulation of neurogenesis as a novel neurotherapeutic strategy.
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INTRODUCTION AND IMPORTANCE: Direct carotid-cavernous fistulas (CCF) are primarily caused by head trauma. Some cases have also been attributed to iatrogenic injuries during endovascular procedures. However, the reports of functional endoscopic sinus surgery (FESS) associated with direct CCFs are extremely rare. PRESENTATION OF CASE: A 52-year-old male worker, who suffered from chronic sinusitis and underwent functional endoscopic sinus surgery (FESS) performed by an otolaryngologist. Intra-operative finding indicated a left sphenoid sinus wall injury without internal carotid artery bleeding, which was repaired using mucosa and tissue glue. One month after discharge, he began experiencing tinnitus, headache and swelling in his left eye. Cerebral angiography revealed a direct carotid-cavernous fistula (CCF) on the left side. The patient underwent transarterial and transvenous stent-assisted coiling using detachable coils and Onyx, which alleviated his symptoms. CLINICAL DISCUSSION: A cavernous-carotid fistula following FESS is an exceedingly rare occurrence first reported by Karaman et al. in 2009. The incidence of internal carotid artery injury during FESS or endonasal endoscopic surgery (EES) is estimated to be between 0 and 0.1 %. Currently, there is no definitive explanation for the development of a carotid-cavernous fistula (CCF) post-FESS. Previous studies suggest that procedures like transsphenoidal surgery and EES can induce pseudoaneurysms in the internal carotid artery. If the cavernous pseudoaneurysm ruptures, it could lead to the formation of a CCF. CONCLUSION: A direct cavernous-carotid fistula following functional endoscopic sinus surgery is a very rare. Consequently, when encountering patients with a carotid-cavernous fistula, relevant procedure history should be considered.
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Oxidative stress, characterized by an imbalance between oxidative and antioxidant processes, results in excessive accumulation of intracellular reactive oxygen species. Among these responses, the regulation of intracellular hydroxyl radicals (â¢OH) and glutathione (GSH) is vital for physiological processes. Real-time in situ monitoring these two opposing bioactive species and their redox interactions is essential for understanding physiological balance and imbalance. In this study, we developed a dual-site fluorescence chemosensor OG-3, which can independently image both exogenous and endogenous â¢OH and GSH in separate channels both within cells and in vivo, eliminating issues of spatiotemporal inhomogeneous distribution and cross-interference. With its imaging capabilities of monitoring â¢OH-GSH redox, OG-3 elucidated two different pathways for ferroptosis induction: (i) inhibition of system xc- to block cystine uptake (extrinsic pathway) and (ii) GPX4 inactivation, leading to the loss of antioxidant defense (intrinsic pathway). Moreover, we assessed the antiferroptotic function and effects of ferroptosis inhibitors by monitoring â¢OH and GSH fluctuations during ferroptosis. This method provides a reliable platform for identifying potential ferroptosis inhibitors, contributing to our understanding of relevant metabolic and physiological mechanisms. It shows potential for elucidating the regulation of ferroptosis mechanisms and investigating further strategies for therapeutic applications.
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Ferroptosis , Colorantes Fluorescentes , Glutatión , Radical Hidroxilo , Oxidación-Reducción , Ferroptosis/efectos de los fármacos , Glutatión/metabolismo , Glutatión/análisis , Humanos , Radical Hidroxilo/metabolismo , Animales , Colorantes Fluorescentes/química , Ratones , Imagen ÓpticaRESUMEN
BACKGROUND: Hyperpigmentation is a skin disorder characterized by a localized darkening of the skin due to increased melanin production. When patients fail first line topical treatments, secondary treatments such as chemical peels and lasers are offered. However, these interventions are not devoid of risks and are associated with postinflammatory hyperpigmentation. In the quest for novel therapeutic potentials, this study aims to investigate computational methods in the identification of new targeted therapies in the treatment of hyperpigmentation. METHODS: We used a comprehensive approach, which integrated text mining, interpreting gene lists through enrichment analysis and integration of diverse biological information (GeneCodis), protein-protein association networks and functional enrichment analyses (STRING), and plug-in network centrality parameters (Cytoscape) to pinpoint genes closely associated with hyperpigmentation. Subsequently, analysis of drug-gene interactions to identify potential drugs (Cortellis) was utilized to select drugs targeting these identified genes. Lastly, we used Deep Learning Based Drug Repurposing Toolkit (DeepPurpose) to conduct drug-target interaction predictions to ultimately identify candidate drugs with the most promising binding affinities. RESULTS: Thirty-four hyperpigmentation-related genes were identified by text mining. Eight key genes were highlighted by utilizing GeneCodis, STRING, Cytoscape, gene enrichment, and protein-protein interaction analysis. Thirty-five drugs targeting hyperpigmentation-associated genes were identified by Cortellis, and 29 drugs, including 16 M2PK1 inhibitors, 11 KRAS inhibitors, and 2 BRAF inhibitors were recommended by DeepPurpose. CONCLUSIONS: The study highlights the promise of advanced computational methodology for identifying potential treatments for hyperpigmentation.
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Aprendizaje Profundo , Reposicionamiento de Medicamentos , Hiperpigmentación , Humanos , Hiperpigmentación/genética , Hiperpigmentación/tratamiento farmacológico , Medicina de Precisión/métodos , Biología Computacional/métodos , Minería de DatosRESUMEN
The detection of anions using carbon dots (CDs) has received less attention compared to cations. Therefore, the present study aimed to develop a fluorescence sensor based on carbon dots (CDs) capable of detecting S2- in real water samples. The CDs were successfully prepared from the residues of a traditional Chinese herb, Gardenia, which emitted green photoluminescence (PL) under ultraviolet light irradiation. The as-prepared CDs were quasi-spherical in shape and ranged in size from 10 to 30 nm. Different detailed analyses proved that the CDs had good morphology, various functional groups, high water solubility, great optical features, and excellent stability under diverse environmental conditions. The ion detection showed that only Ag+ had the strongest fluorescence quenching effect on the CDs, however, the addition of S2- could recover their fluorescence. Based on these results, an "off-on" fluorescence sensor was achieved to selectively detect the concentration of S2- in real water samples with a limit of detection (LOD) of 39 µM, which further expanded the application of residues from traditional Chinese herbal medicine.
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Carbono , Gardenia , Puntos Cuánticos , Azufre , Carbono/química , Azufre/química , Puntos Cuánticos/química , Gardenia/química , Espectrometría de Fluorescencia/métodos , Límite de Detección , Contaminantes Químicos del Agua/análisisRESUMEN
[This corrects the article DOI: 10.1039/D2RA03435B.].
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Managing severe chronic pain is a challenging task, given the limited effectiveness of available pharmacological and non-pharmacological treatments. This issue continues to be a significant public health concern, requiring a substantial therapeutic response. Ziconotide, a synthetic peptide initially isolated from Conus magus in 1982 and approved by the US Food and Drug Administration and the European Medicines Agency in 2004, is the first-line intrathecal method for individuals experiencing severe chronic pain refractory to other therapeutic measures. Ziconotide produces powerful analgesia by blocking N-type calcium channels in the spinal cord, which inhibits the release of pain-relevant neurotransmitters from the central terminals of primary afferent neurons. However, despite possessing many favorable qualities, including the absence of tolerance development, respiratory depression, and withdrawal symptoms (largely due to the absence of a G-protein mediation mechanism), ziconotide's application is limited due to factors such as intrathecal administration and a narrow therapeutic window resulting from significant dose-related undesired effects of the central nervous system. This review aims to provide a comprehensive and clinically relevant summary of the literatures concerning the pharmacokinetics and metabolism of intrathecal ziconotide. It will also describe strategies intended to enhance clinical efficacy while reducing the incidence of side effects. Additionally, the review will explore the current efforts to refine the structure of ziconotide for better clinical outcomes. Lastly, it will prospect potential developments in the new class of selective N-type voltage-sensitive calcium-channel blockers.
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Over the past two decades, immunotherapies have increasingly been considered as first-line treatments for most cancers. One such treatment is immune checkpoint blockade (ICB), which has demonstrated promising results against various solid tumors in clinical trials. Monoclonal antibodies (mAbs) are currently available as immune checkpoint inhibitors (ICIs). These ICIs target specific immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Clinical trial results strongly support the feasibility of this immunotherapeutic approach. However, a substantial proportion of patients with cancer develop resistance or tolerance to treatment, owing to tumor immune evasion mechanisms that counteract the host immune response. Consequently, substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1, anti-programmed cell death ligand 1 (anti-PD-L1), and anti-CTLA-4 treatments. Recently, several immune checkpoint molecular targets have been identified, such as T cell immunoreceptor with Ig and ITIM domains (TIGIT), mucin domain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), V-domain immunoglobulin suppressor of T cell activation (VISTA), B and T lymphocyte attenuator (BTLA), and signal-regulatory protein α (SIRPα). Functional mAbs targeting these molecules are under development. CTLA-4, PD-1/PD-L1, and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of research. This review discusses these structures, as well as clinical progress in mAbs targeting these immune checkpoint molecules and their potential applications.
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Inhibidores de Puntos de Control Inmunológico , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/métodos , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , AnimalesRESUMEN
Developing precise tumor cell-specific mitochondrial ferroptosis-related inhibition miRNA imaging methods holds enormous potential for anticancer drug screening and cancer treatment. Nevertheless, traditional amplification methods still tolerated the limited tumor specificity because of the "off-tumor" signal leakage resulting from their "always-active" sensing mode. To overcome this limitation, we herein developed a dual (exogenous 808 nm NIR light and endogenous APE1) activated nanoladder for precise imaging of mitochondrial ferroptosis-related miRNA with tumor cell specificity and improved imaging resolution. Exogenous NIR light-activation can regulate the ferroptosis-related inhibition miRNA imaging signals within mitochondria, and endogenous enzyme-activation can confine signals to tumor cells. Based on this dual activation design, off-tumor signals were greatly reduced and tumor-to-background contrast was enhanced with an improved tumor/normal discrimination ratio, realizing tumor cell-specific precise imaging of mitochondrial ferroptosis-related inhibition miRNA.
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Ferroptosis , MicroARNs , Mitocondrias , Ferroptosis/efectos de los fármacos , Humanos , MicroARNs/metabolismo , MicroARNs/análisis , Mitocondrias/metabolismo , Animales , Ratones , Imagen Óptica , Línea Celular Tumoral , Rayos Infrarrojos , Nanopartículas/químicaRESUMEN
Background: Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is an evolving and growing disease, especially in developing countries. However, the clinical characteristics of HPV-associated HNSCC in regard to HPV infection rates, patient features, and prognosis are under-reported in the Asian population. Methods: In this study, we retrospectively enrolled a 400-case cohort of HNSCC with p16 immunochemistry and analyzed with long-term follow-up. We investigate the current HPV prevalence of HNSCC, unique HPV-associated patient clinical characteristics, and patient prognosis in the southern China population. Results: HPV infection exhibited a 15% prevalence in all HNSCC cases, notably higher in oropharyngeal cases (30.7%), followed by oral cavity (11.8%), laryngeal (10.1%), and hypopharyngeal (2.5%). HPV status, gender, old age, and location of tumor were significantly associated with the patient's survival. Tonsil invasion was found more frequent in HPV-positive oropharyngeal HNSCC than in HPV-negative cases. HPV-associated HNSCC patients tend to possess stronger tobacco and alcohol habits, which were correlated to poor survival. HPV status's correlation with gender, age, and anatomical location is associated intricately with patient survival. The secondary primary tumor rate was found higher within the HPV-negative group, compared to the HPV-positive group (9.12% versus 1.67%). Conclusion: Our study provided a current picture of HPV-associated HNSCC in the southern China population and elaborated the understanding of key factors that correlate to HNSCC prognosis. Our findings indicated a strong susceptibility of HPV-associated oropharyngeal HNSCC in the tonsil and the difference in secondary primary tumor rates associated with HPV status.
HPV in head and neck cancer In this study, we retrospectively enrolled a 400-case cohort of HNSCC with p16 immunochemistry and analyzed with long-term follow-up. We investigate the current HPV prevalence of HNSCC, unique HPV-associated patient characteristics, along with patient prognosis in southern China population. Our findings indicated a strong susceptibility of HPV-associated oropharyngeal HNSCC in tonsil and difference of secondary primary tumor associated with HPV status. Our study provided a current picture of HPV-associated HNSCC in southern China population and elaborated the understanding of key factors that correlate to HNSCC prognosis.
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Background: To compare and analyze the presence of CD4+ and CD8 + lymphocyte infiltrates in Oral squamous cell carcinoma (OSCC) tissue versus adjacent tissue and their clinical significance. Methods: We enrolled a total of 152 patients diagnosed with OSCC, all of whom had confirmed diagnoses through pathological reports. Clinical and demographics data were extracted from medical records. Tissue microarrays were constructed and immunohistochemical staining for CD4 and CD8 was performed. Findings: The average number of infiltrating CD4+ T cells in OSCC tumor tissue was 1026.22±1163.36 cells/mm2, which did not significantly differ from the count in adjacent tissue, which was 1163.36±1013.23 cells/mm2. However, the number of CD8+ T cell infiltration in tumor tissue was significantly higher than in adjacent tissue (655.25±705.70 vs 504.56±659.26 cells/mm2, p = 0.026). We observed that, among patients who consumed alcohol, the CD4+ T cell infiltration in tumor tissue being significantly lower than that in adjacent tissue (P=0.036). Moreover, the CD8+ T cell infiltration in cancer tissue was significantly higher than in adjacent tissue for T1-2 patients (p=0.005). Patients with higher CD8+ T cell in tumor tissue exhibited significantly improved overall survival (p = 0.043). Multivariate analyses revealed that alcohol consumption had a significant impact on the number of CD4+T lymphocytes in tumor tissue (OR = 0.403, P = 0.033) while T stage was the independent factor affecting CD8+ T lymphocyte infiltration in tumor tissue (OR = 0.459, P = 0.031). Interpretation: OSCC patients with a higher number of CD8+ T lymphocyte infiltration in tumor tissue exhibited an improved prognosis.
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The basic leucine zipper (bZIP) transcription factor (TF) family is one of the biggest TF families identified so far in the plant kingdom, functioning in diverse biological processes including plant growth and development, signal transduction, and stress responses. For Perilla frutescens, a novel oilseed crop abundant in polyunsaturated fatty acids (PUFAs) (especially α-linolenic acid, ALA), the identification and biological functions of bZIP members remain limited. In this study, 101 PfbZIPs were identified in the perilla genome and classified into eleven distinct groups (Groups A, B, C, D, E, F, G, H, I, S, and UC) based on their phylogenetic relationships and gene structures. These PfbZIP genes were distributed unevenly across 18 chromosomes, with 83 pairs of them being segmental duplication genes. Moreover, 78 and 148 pairs of orthologous bZIP genes were detected between perilla and Arabidopsis or sesame, respectively. PfbZIP members belonging to the same subgroup exhibited highly conserved gene structures and functional domains, although significant differences were detected between groups. RNA-seq and RT-qPCR analysis revealed differential expressions of 101 PfbZIP genes during perilla seed development, with several PfbZIPs exhibiting significant correlations with the key oil-related genes. Y1H and GUS activity assays evidenced that PfbZIP85 downregulated the expression of the PfLPAT1B gene by physical interaction with the promoter. PfLPAT1B encodes a lysophosphatidate acyltransferase (LPAT), one of the key enzymes for triacylglycerol (TAG) assembly. Heterogeneous expression of PfbZIP85 significantly reduced the levels of TAG and UFAs (mainly C18:1 and C18:2) but enhanced C18:3 accumulation in both seeds and non-seed tissues in the transgenic tobacco lines. Furthermore, these transgenic tobacco plants showed no significantly adverse phenotype for other agronomic traits such as plant growth, thousand seed weight, and seed germination rate. Collectively, these findings offer valuable perspectives for understanding the functions of PfbZIPs in perilla, particularly in lipid metabolism, showing PfbZIP85 as a suitable target in plant genetic improvement for high-value vegetable oil production.
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Regulación de la Expresión Génica de las Plantas , Perilla frutescens , Proteínas de Plantas , Arabidopsis/genética , Arabidopsis/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Regulación hacia Abajo/genética , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-3/biosíntesis , Perilla frutescens/genética , Perilla frutescens/metabolismo , Filogenia , Aceites de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genéticaRESUMEN
This study investigates the influence of the quality of the "deep squat" movement, adapted from the Functional Movement Screen (FMS) system, on the lower extremity movement pattern during baseball throwing, and its potential impact on throwing performance and propulsion efficiency. Twenty-two baseball players were recruited and categorized into two groups: 13 in the high-score squat group (HSS) and 9 in the low-score squat group (LSS), based on their deep squat screening results. This research explored disparities in ball velocity, propulsion efficiency, propulsion ground reaction force (GRF) characteristics, and throwing kinematics between these two groups. The findings revealed no significant difference in ball velocity between the groups. However, the LSS group demonstrated a lower propulsion GRF efficiency (p < 0.030, ES = 0.46), along with a higher vertical peak GRF (p < 0.002, ES = 0.66). In the pivot leg, the HSS group exhibited significantly lower impulse forces in the Impulse Fresultant (p < 0.035, ES = 0.45), throwing direction (p < 0.049, ES = 0.42), and vertical direction (p < 0.048, ES = 0.42). Additionally, the contribution to the ball velocity of the pivot leg was significantly greater in the HSS group, along with significantly better efficiency in Impulse Fresultant (p < 0.035, ES = 0.45), throwing direction (p < 0.053, ES = 0.41), and vertical direction (p < 0.032, ES = 0.46). In the leading leg, the HSS group demonstrated significantly lower impulse forces in the Impulse Fresultant (p < 0.001, ES = 0.69), throwing direction (p < 0.007, ES = 0.58), and vertical direction (p < 0.001, ES = 0.70). Moreover, the contribution to the ball velocity of the leading leg was significantly greater in the HSS group, accompanied by significantly better efficiency in Impulse Fresultant (p < 0.003, ES = 0.63), throwing direction (p < 0.005, ES = 0.60), and vertical direction (p < 0.021, ES = 0.49). In conclusion, this study suggests that squat screening is a valuable tool for assessing propulsion efficiency. Coaches and trainers should be mindful of players with low squat quality but high throwing performance, as they may face increased impact and injury risks in the future.
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This study aims to investigate the different ground reaction force (GRF) characteristics from different stride types. This study included 30 Taiwanese elite college and professional baseball pitchers. Each pitcher was classified into one of the following stride types: tall and fall (TF), dip and drive (DD), or mixed (MX). Our findings indicated that DD pitchers pressed their bodies forward earlier than TF pitchers. In contrast, the GRF of the pivot leg of TF pitchers increased slowly in the first half of the stride phase and continued to increase even after the stride leg touched the ground. This type of continuous pressing in TF was different from that in DD and MX pitchers, which decreased rapidly into the arm-cocking & acceleration phases. We conclude that the lower extremities were used differently by TF, DD and MX pitchers. This information could serve as a training guideline for coaches and pitchers to enhance training effectiveness, while simultaneously lowering injury risks.
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Developing accurate tumor-specific molecular imaging approaches holds great potential for evaluating cancer progression. However, traditional molecular imaging approaches still suffer from restricted tumor specificity due to the "off-tumor" signal leakage. In this work, we proposed light and endogenous APE1-triggered plasmonic antennas for accurate tumor-specific subcellular molecular imaging with enhanced spatial resolution. Light activation ensures subcellular molecular imaging and endogenous enzyme activation ensures tumor-specific molecular imaging. In addition, combined with the introduction of plasmon enhanced fluorescence (PEF), off-tumor signal leakage at the subcellular level was effectively reduced, resulting in the significantly enhanced discrimination ratio of tumor/normal cells (â¼11.57-fold) which is better than in previous reports, demonstrating great prospects of these plasmonic antennas triggered by light and endogenous enzymes for tumor-specific molecular imaging at the subcellular level.
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The performance of zinc-ion batteries is severely hindered by the uncontrolled growth of dendrites and the severe side reactions on the zinc anode interface. To address these challenges, a weak-water-coordination electrolyte is realized in a peptone-ZnSO4 -based electrolyte to simultaneously regulate the solvation structure and the interfacial environment. The peptone molecules have stronger interaction with Zn2+ ions than with water molecules, making them more prone to coordinate with Zn2+ ions and then reducing the active water in the solvated sheath. Meantime, the peptone molecules selectively adsorb on the Zn metal surface, and then are reduced to form a stable solid-electrolyte interface layer that can facilitate uniform and dense Zn deposition to inhabit the dendritic growth. Consequently, the Zn||Zn symmetric cell can exhibit exceptional cycling performance over 3200 h at 1.0 mA cm-2 /1.0 mAh cm-2 in the peptone-ZnSO4 -based electrolyte. Moreover, when coupled with a Na2 V6 O16 ·3H2 O cathode, the cell exhibits a long lifespan of 3000 cycles and maintains a high capacity retention rate of 84.3% at 5.0 A g-1 . This study presents an effective approach for enabling simultaneous regulation of the solvation structure and interfacial environment to design a highly reversible Zn anode.
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BACKGROUND: The study aimed to investigate the efficacy and survival outcomes of neoadjuvant chemotherapy combined with programmed cell death protein 1 (PD-1) blockade (neoadjuvant chemoimmunotherapy) for patients with resectable head and neck squamous cell carcinoma (HNSCC). METHODS: A retrospective analysis was conducted. Patients with initially diagnosed, resectable HNSCCs who received the neoadjuvant chemoimmunotherapy and radical surgery were included. Correlation analysis between patients' clinical characteristics and pathological responses, and survival analysis were performed. RESULTS: A total of 79 patients were included. The majority of patients (55, 69.6%) were diagnosed at locally advanced stages and most of them (58, 73.4%) had tumor located at the oral cavity. Nearly half of patients (35, 44.3%) received two cycles of neoadjuvant chemoimmunotherapy and the rest had three or more cycles. The R0 resection rate was 98.7%. In the pathological evaluation, 53.1% of patients reached pathological complete responses or major pathological responses. After a median follow-up of 17.0 months, the 1-year disease-free survival (DFS) and overall survival (OS) rates were 87.2% and 97.4%, respectively. The pathological response showed a significantly positive association with survival benefits (p < 0.001). Patients with human papillomavirus (HPV)-positive oropharyngeal cancer had the best pathological response and survival outcomes. Besides, history of radiation at head and neck region and poor pathological response were found to be independent risk factors of DFS for patients receiving such treatments. CONCLUSION: Neoadjuvant chemoimmunotherapy of HNSCC showed high rate of pathological response and low recurrence rate, holding promise for becoming the new standard of care for resectable HNSCC.
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RATIONALE: Pancreatic ductal adenocarcinoma (PDAC) is the main type of pancreatic cancer with a poor prognosis. Rectal metastasis after radical resection of PDAC is comparatively rare, and the understanding of such cases is currently not unified. This study presents the entire process of diagnosis and treatment of a patient with PDAC metastasized to the rectal. We propose the viewpoint of exploring potential biomarkers or establishing effective predictive models to assist in the clinical decision-making of such cases. PATIENT CONCERNS: We present the case of a 71-year-old man with slight abdominal distension and dull pain. He underwent surgical treatment for a malignant tumor of the pancreatic body, which was discovered through computed tomography and magnetic resonance imaging examinations. Nine months after the pancreatectomy, a rectal mass was identified by digital rectal examination and diagnosed as a malignant lesion through a puncture biopsy. After a multidisciplinary joint consultation, the patient underwent radical surgery. It was later confirmed as rectal adenocarcinoma based on postoperative pathological results. DIAGNOSIS: The pathological result after pancreatic surgery was PDAC, which had invaded the peripheral nerves and abdominal arteries. A diagnosis of rectal metastasis was determined ultimately by combining with the medical history and immunohistochemical staining results. INTERVENTIONS AND OUTCOMES: Treatment of the PDAC included laparoscopic resection of the body and tail of the pancreas combined with splenectomy, and postoperative systemic chemotherapy. In addition, treatment of the rectal metastasis included laparoscopic radical resection and postoperative systemic chemotherapy. The patient's current living condition was good. LESSONS: As a rare metastatic site of PDAC, rectal metastasis should be avoided because of misdiagnosis and missed diagnosis. Surgical resection is still an effective treatment strategy for localized pancreatic tumors and isolated metastases. Furthermore, the mining of potential biomarkers or the establishment of predictive models for pancreatic cancer and its metastases may contribute to better clinical decision-making in the future.