Actin-bundling protein fimbrin serves as a new auxin biosynthesis orchestrator in Arabidopsis root tips.

Plants delicately regulate endogenous auxin levels through the coordination of transport, biosynthesis, and inactivation, which is crucial for growth and development. While it is well-established that the actin cytoskeleton can regulate auxin levels by affecting polar transport, its potential role in auxin biosynthesis has remained largely unexplored. Using LC-MS/MS-based methods combined with fluorescent auxin marker detection, we observed a significant increase in root auxin levels upon deletion of the actin bundling proteins AtFIM4 and AtFIM5. Fluorescent observation, immunoblotting analysis, and biochemical approaches revealed that AtFIM4 and AtFIM5 affect the protein abundance of the key auxin synthesis enzyme YUC8 in roots. AtFIM4 and AtFIM5 regulate the auxin synthesis enzyme YUC8 at the protein level, with its degradation mediated by the 26S proteasome. This regulation modulates auxin synthesis and endogenous auxin levels in roots, consequently impacting root development. Based on these findings, we propose a molecular pathway centered on the 'actin cytoskeleton-26S proteasome-YUC8-auxin' axis that controls auxin levels. Our findings shed light on a new pathway through which plants regulate auxin synthesis. Moreover, this study illuminates a newfound role of the actin cytoskeleton in regulating plant growth and development, particularly through its involvement in maintaining protein homeostasis via the 26S proteasome.

Short-term associations between ambient PM1, PM2.5, and PM10 and hospital admissions, length of hospital stays, and hospital expenses for patients with cardiovascular diseases in rural areas of Fuyang, East China.

Evidence on the impacts of PM1, PM2.5, and PM10 on the hospital admissions, length of hospital stays (LOS), and hospital expenses among patients with cardiovascular disease (CVD) is still limited in China, especially in rural areas. This study was performed in eight counties of Fuyang from 1 January 2015 to 30 June 2017. We use a three-stage time-series analysis to explore the effects of short-term exposure to PM1, PM2.5, and PM10 on hospital admissions, LOS, and hospital expenses for CVDs. An increment of 10 ug/m3 in PM1, PM2.5, and PM10 corresponded to an increment of 1.82% (95% CI: 1.34, 2.30), 0.96% (95% CI: 0.44, 1.48), and 0.79% (95% CI: 0.63%, 0.95%) in CVD hospital admissions, respectively. We observed that daily concentrations of PMs were associated with an increase in hospital admissions, LOS, and expenses for CVDs. Sustained endeavors are required to reduce air pollution so as to attenuate disease burdens from CVDs.

The association between the essential metal mixture and fasting plasma glucose in Chinese community-dwelling elderly people.

BACKGROUND: Epidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people. METHODS: The study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: In multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (ß = - 0.016, 95 % CI: - 0.030 to - 0.003 for V; ß = - 0.021, 95 % CI: - 0.033 to - 0.009 for Mg), and urine Se was positively related to the FPG levels (ß = 0.024, 95 % CI: 0.014-0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women. CONCLUSIONS: Both Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings.

Lipid Nanoparticles for mRNA Delivery to Enhance Cancer Immunotherapy.

Messenger RNA (mRNA) is being developed by researchers as a novel drug for the treatment or prevention of many diseases. However, to enable mRNA to fully exploit its effects in vivo, researchers need to develop safer and more effective mRNA delivery systems that improve mRNA stability and enhance the ability of cells to take up and release mRNA. To date, lipid nanoparticles are promising nanodrug carriers for tumor therapy, which can significantly improve the immunotherapeutic effects of conventional drugs by modulating mRNA delivery, and have attracted widespread interest in the biomedical field. This review focuses on the delivery of mRNA by lipid nanoparticles for cancer treatment. We summarize some common tumor immunotherapy and mRNA delivery strategies, describe the clinical advantages of lipid nanoparticles for mRNA delivery, and provide an outlook on the current challenges and future developments of this technology.

Determination of nine nucleosides in Rhizoma Paridis by quantitative analysis of multi-components via a single marker method.

In this work, a new quantitative analysis method of multi-components analysis via a single marker strategy coupled with high-performance liquid chromatography (HPLC) analysis, was proposed to analyze nine nucleosides (cytidine, uridine, 2'-deoxyuridine, inosine, guanosine, 2'-deoxyguanosine, thymidine, adenosine, and 2'-deoxyadenosine) as quality control markers in Rhizoma Paridis. Guanosine was set as the internal reference substance, whose content in Rhizoma Paridis was determined using conventional external standard method. Then, relative correction factors between guanosine and the other eight nucleosides were measured respectively. The amounts of the other eight components were calculated according to the relative correction factors by the quantitative analysis of multi-components via a single marker method. Finally, the result of vector angle cosine analysis showed that there was no significant difference of the contents between the external standard method and the quantitative analysis of multi-components via a single marker method, indicating that the quantitative analysis of multi-components via a single marker method can be applied for the quality control of Rhizoma Paridis. As far as we know, this is also the first report to analyze nucleosides by the quantitative analysis of multi-components via a single marker method, providing an efficient and promising quality assessment method for other traditional Chinese medicine containing nucleosides.

Postnatal nectin-3 knockdown induces structural abnormalities of hippocampal principal neurons and memory deficits in adult mice.

The early postnatal stage is a critical period of hippocampal neurodevelopment and also a period of high vulnerability to adverse life experiences. Recent evidence suggests that nectin-3, a cell adhesion molecule, mediates memory dysfunction and dendritic alterations in the adult hippocampus induced by postnatal stress. But it is unknown whether postnatal nectin-3 reduction alone is sufficient to alter hippocampal structure and function in adulthood. Here, we down regulated hippocampal expression of nectin-3 and its heterophilic adhesion partner nectin-1, respectively, from early postnatal stage by injecting adeno-associated virus (AAV) into the cerebral lateral ventricles of neonatal mice (postnatal day 2). We found that suppression of nectin-3, but not nectin-1, expression from the early postnatal stage impaired hippocampus-dependent novel object recognition and spatial object recognition in adult mice. Moreover, AAV-mediated nectin-3 knockdown significantly reduced dendritic complexity and spine density of pyramidal neurons throughout the hippocampus, whereas nectin-1 knockdown only induced the loss of stubby spines in CA3. Our data provide direct evidence that nectins, especially nectin-3, are necessary for postnatal hippocampal development of memory functions and structural integrity.

Bevacizumab and risk of intracranial hemorrhage in patients with brain metastases: a meta-analysis.

Administration of bevacizumab to patients with brain metastases (BM) is controversial due to concerns about the increased risk of intracranial hemorrhage (ICH). This meta-analysis assessed whether the risk of ICH increases in BM patients receiving treatments that contain bevacizumab versus without. PubMed, Embase, Cochrane Library and annual meeting abstracts of the American Society of Clinical Oncology up to 13 November 2016 were searched for studies that referred to ICH complications due to bevacizumab in patients with BM. Eight studies involving 8713 patients were included in this analysis. Compared with the control arm without bevacizumab, the bevacizumab treatment arm did not exhibit a significant increase in ICH [odds ratio (OR) 1.20; 95% confidence intervals (CI) 0.69-2.09; P = 0.53]. Subgroup analyses with retrospective studies showed a similar result, although subgroup analyses with prospective studies failed. This meta-analysis revealed that bevacizumab does not significantly increase the risk of ICH in solid tumor patients with BM.

Prevention of Atrial Fibrillation by Using Sarcoplasmic Reticulum Calcium ATPase Pump Overexpression in a Rabbit Model of Rapid Atrial Pacing.

BACKGROUND Recent research suggests that abnormal Ca2+ handling plays a role in the occurrence and maintenance of atrial fibrillation (AF). Therefore, Ca2+ release and ingestion depend on properties of the ryanodine receptor (RyR) and sarcoplasmic reticulum Ca2+ATPase2a (SERCA2a). This study aimed to detect whether SERCA2a gene overexpression has a preventive effect on atrial fibrillation caused by rapid pacing right atrium. MATERIAL AND METHODS Forty-eight New Zealand white rabbits were randomly divided into a control group, AF group, AAV9/GFP group, and AAV9/SERCA2a group. The right atrium was rapidly paced at 600 beats/min for 30 days after an intraperitoneal injection of an adeno-associated virus expressing the SERCA2a gene and GFP. The AF induction rate and the effective refraction period (ERP) were measured after 0, 4, 8, 12, and 24 h of pacing. Western blot analysis was used to test for the expression of SERCA2a. Changes in atrial tissue structure were observed by H&E staining and electron microscopy. RESULTS The AF induction rate was higher in the AF groups than in the AAV9/SERCA2a group at different time points of pacing. After 12 h of pacing, ERP was significantly prolonged in the AAV9/SERCA2a group compared to the AF and AAV9/GFP groups (p<0.05). SERCA2a protein expression was significantly lower in the AF and AAV9/GFP groups compared to the control group (p<0.05), while expression was significantly higher in the AAV9/SERCA2a group than in the AF and AAV9/GFP groups (p<0.05). The myocardial structure of the AAV9/SERCA2a group was significantly improved compared with the AF group, indicating that SERCA2a overexpression relieved the structural remodeling of atrial fibrillation. CONCLUSIONS SERCA2a overexpression is capable of suppressing ERP shortening and AF induced by rapid pacing atrium. SERCA2a gene therapy is expected to be a new anti-atrial fibrillation strategy.

Cu(II)-Mediated C(sp(2))-H Hydroxylation.

A Cu(II)-mediated ortho-C-H hydroxylation using a removable directing group has been developed. The reaction exhibits considerable functional group tolerance. The use of O2 as an oxidant is crucial for the reactivity. Water is also found to significantly improve this reaction.

Cu(II)-mediated ortho C-H alkynylation of (hetero)arenes with terminal alkynes.

Cu(II)-promoted ortho alkynylation of arenes and heteroarenes with terminal alkynes has been developed to prepare aryl alkynes. A variety of arenes and terminal alkynes bearing different substituents are compatible with this reaction, thus providing an alternative disconnection to Sonogashira coupling.

Exceedingly fast copper(II)-promoted ortho C-H trifluoromethylation of arenes using TMSCF3.

The direct ortho-trifluoromethylation of arenes, including heteroarenes, with TMSCF3 has been accomplished by a copper(II)-promoted C-H activation reaction which completes within 30 minutes. Mechanistic investigations are consistent with the involvement of C-H activation, rather than a simple electrophilic aromatic substitution (SE Ar), as the key step.

P(O)R2-directed Pd-catalyzed C-H functionalization of biaryl derivatives to synthesize chiral phosphorous ligands.

Chiral phosphorus ligands have been widely used in transition metal-catalyzed asymmetric reactions. Herein, we report a new synthesis approach of chiral biaryls containing a phosphorus moiety using P(O)R2-directed Pd-catalyzed C-H activation; the functionalized products are produced with good enantioselectivity.

Fluoxetine reverses early-life stress-induced depressive-like behaviors and region-specific alterations of monoamine transporters in female mice.

The sex difference that females are more vulnerable to depression than males has been recently replicated in an animal model of early-life stress (ES) called the limited bedding and nesting material (LBN) paradigm. Adopting this animal model, we have previously examined the effects of ES on monoamine transporter (MATs) expression in stress-related regions in adult female mice, and the reversal effects of a novel multimodal antidepressant, vortioxetine. In this study, replacing vortioxetine with a classical antidepressant, fluoxetine, we aimed to replicate the ES effects in adult female mice and to elucidate the commonality and differences between fluoxetine and vortioxetine. We found that systemic 30-day treatment with fluoxetine successfully reversed ES-induced depression-like behaviors (especially sucrose preference) in adult female mice. At the molecular level, we largely replicated the ES effects, such as reduced serotonin transporter (SERT) expression in the amygdala and increased norepinephrine transporter (NET) expression in the medial prefrontal cortex (mPFC) and hippocampus. Similar reversal effects of fluoxetine and vortioxetine were observed, including SERT in the amygdala and NET in the mPFC, whereas different reversal effects were observed for NET in the hippocampus and vesicular monoamine transporters expression in the nucleus accumbens. Overall, these results demonstrate the validity of the LBN paradigm to induce depression-like behaviors in female mice, highlight the involvement of region-specific MATs in ES-induced depression-like behaviors, and provide insights for further investigation of neurobiological mechanisms, treatment, and prevention associated with depression in women.

IiAGL6 participates in the regulation of stamen development and pollen formation in Isatis indigotica.

The AGL6 (AGMOUSE LIKE 6) gene is a member of the SEP subfamily and functions as an E-class floral homeotic gene in the development of floral organs. In this study, we cloned IiAGL6, the orthologous gene of AGL6 in Isatis indigotica. The constitutive expression of IiAGL6 in Arabidopsis thaliana resulted in a late-flowering phenotype and the development of curly leaves during the vegetative growth period. Abnormal changes in floral organ development were observed during the reproductive stage. In woad plants, suppression of IiAGL6 using TRV-VIGS (tobacco rattle virus-mediated virus-induced gene silencing) decreased the number of stamens and led to the formation of aberrant anthers. Similar changes in stamen development were also observed in miRNA-AGL6 transgenic Arabidopsis plants. Yeast two-hybrid and BiFC tests showed that IiAGL6 can interact with other MADS-box proteins in woad; thus, playing a key role in defining the identities of floral organs, particularly during stamen formation. These findings might provide novel insights and help investigate the biological roles of MADS transcription factors in I. indigotica.

Dorsal CA3 overactivation mediates witnessing stress-induced recognition memory deficits in adolescent male mice.

Witnessing violent or traumatic events is common during childhood and adolescence and could cause detrimental effects such as increased risks of psychiatric disorders. This stressor could be modeled in adolescent laboratory animals using the chronic witnessing social defeat (CWSD) paradigm, but the behavioral consequences of CWSD in adolescent animals remain to be validated for cognitive, anxiety-like, and depression-like behaviors and, more importantly, the underlying neural mechanisms remain to be uncovered. In this study, we first established the CWSD model in adolescent male mice and found that CWSD impaired cognitive function and increased anxiety levels and that these behavioral deficits persisted into adulthood. Based on the dorsal-ventral functional division in hippocampus, we employed immediate early gene c-fos immunostaining after behavioral tasks and found that CWSD-induced cognition deficits were associated with dorsal CA3 overactivation and anxiety-like behaviors were associated with ventral CA3 activity reduction. Indeed, chemogenetic activation and inhibition of dorsal CA3 neurons mimicked and reversed CWSD-induced recognition memory deficits (not anxiety-like behaviors), respectively, whereas both inhibition and activation of ventral CA3 neurons increased anxiety-like behaviors in adolescent mice. Finally, chronic administration of vortioxetine (a novel multimodal antidepressant) successfully restored the overactivation of dorsal CA3 neurons and the cognitive deficits in CWSD mice. Together, our findings suggest that dorsal CA3 overactivation mediates CWSD-induced recognition memory deficits in adolescent male mice, shedding light on the pathophysiology of adolescent CWSD-induced adverse effects and providing preclinical evidence for early treatment of stress-induced cognitive deficits.

Specific convulsions and brain damage in children hospitalized for Omicron BA.5 infection: an observational study using two cohorts.

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

The Nucleus Accumbens CRH-CRHR1 System Mediates Early-Life Stress-Induced Sleep Disturbance and Dendritic Atrophy in the Adult Mouse.

Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.

Ambient nitrogen dioxide and cardiovascular diseases in rural regions: a time-series analyses using data from the new rural cooperative medical scheme in Fuyang, East China.

Most of studies relating ambient nitrogen dioxide (NO2) exposure to hospital admissions for cardiovascular diseases (CVDs) were conducted among urban population. Whether and to what extent these results could be generalizable to rural population remains unknown. We addressed this question using data from the New Rural Cooperative Medical Scheme (NRCMS) in Fuyang, Anhui, China. Daily hospital admissions for total CVDs, ischaemic heart disease, heart failure, heart rhythm disturbances, ischaemic stroke, and haemorrhagic stroke in rural regions of Fuyang, China, were extracted from NRCMS between January 2015 and June 2017. A two-stage time-series analysis method was used to assess the associations between NO2 and CVD hospital admissions and the disease burden fractions attributable to NO2. In our study period, the average number (standard deviation) of hospital admissions per day were 488.2 (117.1) for total CVDs, 179.8 (45.6) for ischaemic heart disease, 7.0 (3.3) for heart rhythm disturbances, 13.2 (7.2) for heart failure, 267.9 (67.7) for ischaemic stroke, and 20.2 (6.4) for haemorrhagic stroke. The 10-µg/m3 increase of NO2 was related to an elevated risk of 1.9% (RR: 1.019, 95% CI: 1.005 to 1.032) for hospital admissions of total CVDs at lag0-2 days, 2.1% (1.021, 1.006 to 1.036) for ischaemic heart disease, and 2.1% (1.021, 1.006 to 1.035) for ischaemic stroke, respectively, while no significant association was observed between NO2 and hospital admissions for heart rhythm disturbances, heart failure, and haemorrhagic stroke. The attributable fractions of total CVDs, ischaemic heart disease, and ischaemic stroke to NO2 were 6.52% (1.87 to 10.94%), 7.31% (2.19 to 12.17%), and 7.12% (2.14 to 11.85%), respectively. Our findings suggest that CVD burdens in rural population are also partly attributed to short-term exposure to NO2. More studies across rural regions are required to replicate our findings.

The associations of non-essential metal mixture with fasting plasma glucose among Chinese older adults without diabetes.

The evidence about the effect of non-essential metal mixture on fasting plasma glucose (FPG) levels among older adults without diabetes is limited. This study aims to estimate the individual and joint relationship between five non-essential metals and FPG levels in Chinese older adults without diabetes. This study included 2362 older adults without diabetes. Urinary concentrations of five non-essential metals, i.e., cesium (Cs), aluminum (Al), thallium (Tl), cadmium (Cd), and arsenic (As), were detected by inductively coupled plasma mass spectrometry (ICP-MS). The associations of single metals and the metal mixture with FPG levels were assessed using linear regression and Bayesian kernel machine regression (BKMR) models, respectively. Adjusted single-metal linear regression models showed positive associations of urinary Al (ß = 0.016, 95%CI: 0.001-0.030) and Cs (ß = 0.018, 95%CI: 0.006-0.031) with FPG levels. When comparing the 2th, 3th, and 4th quartiles of urine Cs to its 1th quartile, the significant associations between Cs and FPG levels were found and presented as an "inverted U" trend (ßQ2 vs. Q1: 0.034; ßQ3 vs. Q1:0.054; ßQ4 vs. Q1: 0.040; all P<0.05). BKMR analyses showed urinary level of Cs exhibited an "inverted U" shape association with FPG levels. Moreover, the FPG levels increased linearly with the raised levels of the non-essential metal mixture, and the posterior inclusion probability (PIP) of Cs was the highest (0.92). Potential positive interaction of As and Cs on FPG levels was found in BKMR model. Stratified analysis displayed significant interactions of hyperlipidemia and urine Cs or Tl on FPG levels. An inverse U-shaped association between Cs and FPG was found, individually and as mixture. The FPG levels increased with the raised levels of the non-essential metal mixture, and Cs was the most contributor to FPG levels. Further research is required to confirm the correlation between non-essential metals and FPG levels and to clarify the underlying mechanisms.

Identification and validation of a novel signature based on cell-cell communication in head and neck squamous cell carcinoma by integrated analysis of single-cell transcriptome and bulk RNA-sequencing.

Background: The heterogeneous crosstalk between tumor cells and other cells in their microenvironment means a notable difference in clinical outcomes of head and neck squamous cell carcinoma (HNSCC). CD8+ T cells and macrophages are effector factors of the immune system, which have direct killing and phagocytosis effects on tumor cells. How the evolution of their role in the tumor microenvironment influences patients clinically remains a mystery. This study aims to investigate the complex communication networks in the HNSCC tumor immune microenvironment, elucidate the interactions between immune cells and tumors, and establish prognostic risk model. Methods: 20 HNSCC samples single-cell rna sequencing (scRNA-seq) data and bulk rna-seq data were derived from public databases. The "cellchat" R package was used to identify cell-to-cell communication networks and prognostic related genes, and then cell-cell communication (ccc) molecular subtypes were constructed by unsupervised clustering. Kaplan-Meier(K-M) survival analysis, clinical characteristics analysis, immune microenvironment analysis, immune cell infiltration analysis and CD8+T cell differentiation correlation analysis were performed. Finally, the ccc gene signature including APP, ALCAM, IL6, IL10 and CD6 was constructed based on univariate Cox analysis and multivariate Cox regression. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the model in the train group and the validation group, respectively. Results: With CD8+T cells from naive to exhaustion state, significantly decreased expression of protective factor (CD6 gene) is associated with poorer prognosis in patients with HNSCC. The role of macrophages in the tumor microenvironment has been identified as tumor-associated macrophage (TAM), which can promote tumor proliferation and help tumor cells provide more nutrients and channels to facilitate tumor cell invasion and metastasis. In addition, based on the strength of all ccc in the tumor microenvironment, we identified five prognostic ccc gene signatures (cccgs), which were identified as independent prognostic factors by univariate and multivariate analysis. The predictive power of cccgs was well demonstrated in different clinical groups in train and test cohorts. Conclusion: Our study highlights the propensity for crosstalk between tumors and other cells and developed a novel signature on the basis of a strong association gene for cell communication that has a powerful ability to predict prognosis and immunotherapy response in patients with HNSCC. This may provide some guidance for developing diagnostic biomarkers for risk stratification and therapeutic targets for new therapeutic strategies.