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Austenite reversion has been widely used in the traditional heat treatment of steels, and recently, it has been used in the fabrication of advanced high-strength steels. The microstructure of reverted austenite significantly influences the final microstructure and properties of steel; thus, it is crucial to understand the formation of globular austenite to accurately grasp its reversion behavior. In this paper, an Fe–2.5Mn–1.5Si–0.35C alloy was chosen as the research object, and the evolution of intragranular globular austenite and finally transformed austenite grain size were studied under different pre-tempering conditions using a metallographic optical microscope, scanning electron microscope, and electron backscatter diffraction. It was found that as the pre-tempering temperature was increased from 350 ℃ to 650 ℃, the volume fraction of intragranular globular austenite first increased and then rapidly decreased. At the pre-tempering temperature of 400 ℃, the volume fraction of intragranular globular austenite initially increased and remained stable thereafter, when the pre-tempering duration was increased from 1 to 10 h. Fine cementite particles were primarily formed immediately before the reversion in the non-tempered or low-temperature pre-tempered initial structures. This provided less effective nucleation sites for the formation of intragranular globular austenite. Therefore, lesser intragranular globular austenite grains were formed, thereby resulting in relatively coarse finally transformed austenite grains after reversion. The cementite particles were gradually coarsened as the pre-tempering temperature was increased to 550 ℃, thereby increasing the number of effective nucleation sites for the formation of intragranular globular austenite. Conversely, when the martensite samples were pre-tempered at a high temperature of 650 ℃, Mn is seriously enriched into the cementite particles before the reversion, largely reducing the driving force for reversion. This resulted in the growth of intragranular globular austenite under the partitioning local equilibrium mode, with a slow growth rate, resulting in a low volume fraction. Therefore pre-tempering can effectively promote the formation of intragranular globular austenite. Owing to its multiple orientations, increased intragranular globular austenite formation resulted in significantly refined austenite grains after reversion. This study provided a new strategy to regulate the formation of intragranular globular austenite and finally transformed austenite grain size by controlling the size and composition of cementite particles through pre-tempering without changing the chemical composition of the steel.

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 (β = − 0.016, 95 % CI: − 0.030 to − 0.003 for V; β = − 0.021, 95 % CI: − 0.033 to − 0.009 for Mg), and urine Se was positively related to the FPG levels (β = 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.

BackgroundThe 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.Methods20 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.ResultsWith 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.ConclusionOur 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.

The pathogenesis of intervertebral disc degeneration (IDD) is complex, and a better understanding of IDD pathogenesis may provide a better method for the treatment of IDD. Exosomes are 40–100 nm nanosized vesicles that are released from many cell types into the extracellular space. We speculated that exosome-transported circular RNAs (circRNAs) could regulate IDD. Exosomes from different degenerative grades were isolated and added to nucleus pulposus cells (NPCs), and indicators of proliferation and apoptosis were detected. Based on the previous circRNA microarray results, the top 10 circRNAs were selected. PCR was performed to determine the circRNA with the maximum upregulation. Competing endogenous RNA (ceRNA) analysis was carried out, and the sponged microRNA (miRNA) was identified. Further functional verification of the selected circRNA was carried out in vivo and in vitro. NPCs of different degenerative grades secreted exosomes, which could regulate IDD. circRNA_0000253 was selected as having the maximum upregulation in degenerative NPC exosomes. ceRNA analysis showed that circRNA_0000253 could adsorb miRNA-141-5p to downregulate SIRT1. circRNA_0000253 was confirmed to increase IDD by adsorbing miRNA-141-5p and downregulating SIRT1 in vivo and in vitro. Exosomal circRNA_0000253 owns the maximum upregulation in degenerative NPC exosomes and could promote IDD by adsorbing miRNA-141-5p and downregulating SIRT1.

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.

Abstract. Background:. Exposure to adverse experiences in early life may profoundly reshape the neurodevelopmental trajectories of the brain and lead to long-lasting behavioral and neural alterations. One deleterious effect of early-life stress that manifests in later life is sleep disturbance, but this has not been examined in aged mice and the underlying neural mechanisms remain unknown. Considering the important role of the nucleus accumbens (NAc) in the sleep-wake regulation, this study aimed to assess the effects of early-life stress on the sleep behaviors in aged mice and the potential involvement of the NAc in stress-induced sleep abnormalities. Methods:. Twenty aged male C57BL/6 mice (>16 months, n = 10 per group) were used in this study. During post-natal days 2 to 9, dams were provided with either sufficient (control) or a limited nesting and bedding materials (stressed). When the mice were 16 to 17 months old, their sleep-wake behaviors were recorded over 24 h using electroencephalogram and electromyelogram. The amount of each sleep-wake stage, mean duration, and stage transition was analyzed. Then, five animals were randomly chosen from each group and were used to measure the expression levels of vesicular glutamate transporter-1 (VGluT1) and vesicular transporters of γ-aminobutyric acid (VGAT) in the NAc using immunohistochemistry. Group comparisons were carried out using Student t test or analysis of variances when appropriate. Results:. Compared with the control mice, the early-life stressed aged mice spent less time awake over 24 h (697.97 ± 77.47 min vs. 631.33 ± 34.73 min, t17 = 2.376, P = 0.030), accordingly, non-rapid eye movement sleep time was increased (667.37 ± 62.07 min vs. 723.54 ± 39.21 min, t17 = 2.326, P = 0.033) and mean duration of rapid eye movement sleep was prolonged (73.00 ± 8.98 min vs. 89.39 ± 12.69 min, t17 = 3.277, P = 0.004). Meanwhile, we observed decreased VGluT1/VGAT ratios in the NAc in the stressed group (F(1, 16) = 81.04, P

Abstract. Background:. Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods. In this study, we examined the effects of adolescent chronic social stress in aged mice on depressive behaviors and the excitatory-inhibitory (E/I) balance in stress-sensitive regions of the brain. Methods:. Sixty-four adolescent, male C57BL/6 mice were randomly assigned to either the 7-week (from post-natal days 29 to 77) social instability stress (stress group, n = 32) or normal housing conditions (control group, n = 32). At 15 months of age, 16 mice were randomly selected from each group for a series of behavioral tests, including two depression-related tasks (the sucrose preference test and the tail suspension test). Three days following the last behavioral test, eight mice were randomly selected from each group for immunohistochemical analyses to measure the cell density of parvalbumin (PV+)- and calretinin (CR+)-positive gamma-aminobutyric-acid (GABA)ergic inhibitory inter-neurons, and the expression levels of vesicular transporters of glutamate-1 (VGluT1) and vesicular GABA transporter (VGAT) in three stress-sensitive regions of the brain (the medial pre-frontal cortex [mPFC], hippocampus, and amygdala). Results:. Behaviorally, compared with the control group, adolescent chronic stress increased depression-like behaviors as shown in decreased sucrose preference (54.96 ± 1.97% vs. 43.11 ± 2.85%, t(22) = 3.417, P = 0.003) and reduced latency to immobility in the tail suspension test (92.77 ± 25.08 s vs. 33.14 ± 5.95 s, t(25) = 2.394, P = 0.025), but did not affect anxiety-like behaviors and pre-pulse inhibition. At the neurobiologic level, adolescent stress down-regulated PV+, not CR+, inter-neuron density in the mPFC (F(1, 39) = 19.30, P 10.09, all P

Abstract. Background:. Endothelial dysfunction, the initial pathogenic factor in atherosclerosis, can be alleviated via transient limb ischemia. We observed the effects of regular transient limb ischemia (RTLI) on atherosclerosis in hypercholesterolemic rabbits. Methods:. Twenty-eight rabbits were randomized to control, cholesterol, sham, ischemia groups (n = 7 each) between October 2010 and March 2011. They were fed a normal diet in the control group and hypercholesterolemic diet in other groups for 12 weeks. Six cycles of RTLI were performed once per day on the ischemia group. Serum samples were prepared to measure the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) before the experiment (W0), at the end of weeks 4, 8, 12 (W4, W8, W12). The whole aorta was harvested at W12 and stained using Sudan IV to identify the plaque. The plaque area was measured using Image J. Results were analyzed by analysis of variance or rank sum test. Results:. Concentrations of TC in the cholesterol group were higher than those in the control group at W4 (29.60 [23.75, 39.30] vs. 1.00 [0.80, 1.55], Z = –2.745, P = 0.006), W8 (41.78 [28.08, 47.37] vs. 0.35 [0.10, 0.68], Z = –2.739, P = 0.006), W12 (48.32 [40.04, 48.95] vs. 0.61 [0.50, 0.86], Z = –2.739, P = 0.006). Similar results were obtained for HDL-C and LDL-C. Serum concentrations of TC, HDL-C, and LDL-C in the hypercholesterolemic groups had no differences (all P > 0.05). The percentage of plaque area in the cholesterol group was higher than that in the control group (47.22 ± 23.89% vs. 0, Z = –2.986, P = 0.003). Square root of the percentage of plaque area was smaller in the ischemia group than that in the cholesterol (0.44 ± 0.13 vs. 0.67 ± 0.18, P = 0.014) or sham groups (0.44 ± 0.13 vs. 0.61 ± 0.12, P = 0.049). Conclusion:. In hypercholesterolemic rabbits, RTLI might prevent atherosclerosis progression by reducing the percentage of plaque area.

Objective: The objective was to study the effect of total flavonoids of Herba Taxilli (TFHT) on osteoporotic (OP) rats induced by retinoic acid (RA) and explore its mechanism. Methods: Three-month-old female Sprague Dawley rats were randomly divided into six groups, each with ten rats, i.e. normal control group, model group, and positive control group and three TFHT groups (at high-, middle-, and low-doses). Except the normal control group, rats of all the other groups were administered RA by gavage (70 mg/kg/day) every morning for 14 days to establish an OP model; at the same time, all the rats were given Corresponding therapeutic drug by gavage for 28 days: rats in the three TFHT groups were given TFHT (400, 200, and 100 mg/kg/day, respectively) and rats in the positive control group were given Long mu Zhuang gu Granule 300 mg/kg/day. Rats in the model group and normal group were given an equal volume of 1% sodium carboxymethyl cellulose sodium suspension. After the experiment, blood was taken to measure the levels of serum calcium (Ca2+), alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP); the spleen, uterus, and ovary were dissected to determine the organ coefficient; the left hind limb femur was dissected to determine bone mineral density (BMD), bone dry weight (BDW), bone wet weight (BWW), bone diameter (BD), bone length (BL), bone dry weight/rat weight (BDW/W), bone wet weight/rat weight (BWW/W), bone dry weight/bone wet weight (BDW/BWW), bone dry weight/bone length (BDW/L), and bone wet weight/bone diameter (BWW/D); and the right hind limb femur was dissected to observe the bone path morphological changes. Results: Compared with the model group, the serum Ca2+ content, uterus plus ovary coefficient, BMD, BDW, BDW/W, BWW/W, BDW/BWW, BDW/L, and BWW/D in the TFHT groups increased, whereas the spleen coefficient, ALP, and TRAP decreased in the TFHT groups, and the differences were statistically significant (P < 0.05 orP < 0.01). Conclusion: TFHT was found effective in treating OP in rats induced by RA; the main mechanisms were increasing the serum Ca2+ content and reducing the level of ALP and TRAP.

Spinal disease: A roundabout route to disc degeneration ‘RNA sponges’ may provoke lower back pain by soaking up regulatory RNAs that normally protect the protein infrastructure surrounding cells in intervertebral discs. Many people suffer from lower back pain arising from disc degeneration (IDD). A team led by Fei-Zou and Jian-Yuan Jiang at Fudan University, Shanghai, China set out to identify molecular mechanisms that might contribute to IDD. They focused on circular RNAs, non-protein coding RNAs that have been linked to a variety of diseases. The researchers learned that IDD is associated with strongly elevated expression of a circular RNA that acts as an ‘RNA sponge’, binding to and thereby inactivating other RNA molecules. This inactivation ultimately results in the excessive production of an enzyme that can damage the protein matrix that supports cells within spinal discs, potentially setting up the conditions for IDD.

Objective To explore the relation between abnormal functional connectivity of substantia nigra and impairment of movement and cognition in patients with rapid eye movement sleep behavior disorder (RBD). Methods A total of 22 subjects, including 14 patients with RBD and 8 sex, age, education-matched healthy controls, were enrolled in this study according to international diagnostic criteria. Unified Parkinson's Disease Rating Scale Ⅲ (UPDRS Ⅲ) and Hoehn-Yahr Stage were used to evaluate motor function. Digit Ordering Test - Attention (DOT - A), Symbol Digit Modalities Test (SDMT), Stroop Color-Word Test (SCWT), Trail Making Test (TMT), Rey-Osterrieth Complex Figure Test (ROCFT), Clock Drawing Test (CDT), Boston Naming Test (BNT) and Auditory Verbal Learning Test (AVLT) were used to evaluate cognitive function. The functional connectivity from left and right substantia nigra to brain region were examined. Results There were no statistical differences of UPDRSⅢ and Hoehn?Yahr Stage between 2 groups (P > 0.05, for all). In comparison with control group, SDMT (P = 0.001), ROCFT-copy (P = 0.013) and AVLT-N2 (P = 0.032) were significantly lower, while TMT-B test was significantly higher (P =0.005) in RBD group. Compared with control group, the functional connectivity of right substantia nigra to left precentral gyrus (P < 0.005) and right angular gyrus (P < 0.005) were all decreased in RBD group. Conclusions The results suggest that cognitive impairment occurs earlier than movement disorders in RBD, and there are abnormal functional connectivity from right substantia nigra to left precentral gyrus and right angular gyrus, proving that abnormal functional connectivity is the base of behavior disorders in RBD. DOI: 10.3969/j.issn.1672-6731.2017.09.005

Abstract Macrosclereid cells, which are a layer in the seed coat of Medicago truncatula, accumulate large amounts of phytochemicals during their development. But little is known about the complex and dynamic changes during macrosclereid cell development. To characterize the phytochemicals and the related gene expression during the development of M. truncatula macrosclereid cells, a high performance liquid chromatography-mass spectrometry (HPLC-MS) assay and microarray study were conducted on transcriptome changes from macrosclereid cell during seed development. A total of 16 flavonoids by HPLC-MS and 4861 genes exhibited significant differences at transcript levels by microarray analysis were identified for macrosclerid cells at six different time points during seed development. 815 abiotic and biotic stress genes, 223 transcriptional factors (TFs), and 155 annotated transporter proteins exhibited differential expression during the development of macrosclereid cells. A total of 102 genes were identified as involved in flavonoid biosynthesis, phenypropanoid biosynthesis, and flavone and flavonol biosynthesis. We performed a weighted gene co-regulatory network (WGCNA) to analyze the gene-flavonoid association and rebuilt the gene regulatory network during macrosclereid cell development. Our studies revealed that macrosclereid cells are, beside as the first barrier of defense against diseases, an excellent model system to investigate the regulatory network that governs flavonoid biosynthesis.

Objective To investigate the structure of corpus striatum and the integrity of white matter fiber in patients with Parkinson's disease (PD) and idiopathic rapid eye movement sleep behavior disorder (iRBD). Methods Twelve patients with iRBD, 12 patients with PD and 10 healthy subjects that were well matched in gender, age and education were enrolled in this study. Head MRI examination was performed to all subjects to observe the changes of corpus striatum structure (the gray matter volume) and the integrity of white matter fiber [fractional anisotropy (FA)] by combining voxel?based morphometry (VBM) and diffusion tensor imaging (DTI). Results Compared with healthy subjects, the gray matter volume of left caudate nucleus was significantly decreased (P < 0.005), and FA values of left caudate nucleus (P < 0.005), right caudate nucleus (P < 0.001) and right putamen (P < 0.05) were all significantly reduced in iRBD patients; FA value of right putamen was significantly decreased in PD patients (P < 0.05). Compared with PD patients, the gray matter volume of left caudate nucleus of iRBD patients was significantly reduced (P < 0.001), FA values of left caudate nucleus (P < 0.01) and right caudate nucleus (P < 0.005) of iRBD patients were significantly reduced. Conclusions There is atrophy of gray matter volume and extensive white matter fiber impairment in corpus striatum of patients with iRBD, and the white matter fiber impairment was similar to PD, which provides an anatomical evidence for iRBD being presymptom of PD. DOI: 10.3969/j.issn.1672-6731.2017.05.008

Background: Local anesthetics (LAs) are generally considered as safe, but cytotoxicity has been reported for several local anesthetics used in humans, which is not well investigated. In the present study, the cytotoxicity of lidocaine, ropivacaine and the combination of lidocaine and ropivacaine were evaluated on human melanoma cell lines. Melphalan, a nitrogen mustard alkylating agent, was used as a control agent for comparison of cytotoxic activity. Methods: Melanoma cell lines, A375 and Hs294T, were exposed to 1 h to different concentrations of above agents. Cell-viability after exposure was determined by flow cytometry. Results: Investigated LAs showed detrimental cytotoxicity on studied melanoma cell lines in time- (p

Caustic esophageal stricture (CES) in children still occurs frequently in developing countries. We aimed to evaluate the long-term outcomes of endoscopic balloon dilatation (EBD) in treating CES in children and the influencing factors associated with outcome. We retrospectively reviewed the data of all patients who had a diagnosis of CES and underwent EBD from August 1, 2005, to December 31, 2014. The primary outcome was EBD success, which was defined as the maintenance of dysphagia-free status for at least 12 months after the last EBD. The secondary outcome was to analyze influencing factors associated with EBD success. Forty-three patients were included for analysis (29 males; mean age at first dilatation 44 months with range 121 months). 26 (60.5%) patients had long segment (>2 cm) stricture. A total of 168 EBD procedures were performed. Twenty-six (60.5%) patients were considered EBD success. Seventeen (39.5%) patients failed EBD and required stent placement and/or surgery. Patients in the EBD success group had significantly shorter stricture segments when compared to the EBD failure group (t=2.398, P=0.018, OR=3.206, 95% OR: 1.228–8.371). Seven (4.4%) esophageal perforations occurred in 6 patients after EBD. Stents were placed in 5 patients, and gastric tube esophagoplasty was performed in 14 patients. In conclusion, 26 (60.5%) of 43 children with CES had EBD success. Length of stricture was the main influencing factor associated with EBD treatment outcome.

Background: The concept of minimally invasive techniques is to make every effort to reduce tissue damage. Certainly, reducing skin incision is an important part of these techniques. This study aimed to investigate the clinical feasibility of Mast Quadrant-assisted modified transforaminal lumbar interbody fusion (TLIF) with a small single posterior median incision. Methods: During the period of March 2011 to March 2012, 34 patients with single-segment degenerative lumbar disease underwent the minimally invasive modified TLIF assisted by Mast Quadrant with a small single posterior median incision (single incision group). The cases in this group were compared to 37 patients with single-segment degenerative lumbar disease in the double incision group. The perioperative conditions of patients in these two groups were statistically analyzed and compared. The Oswestry Disability Index (ODI) scores, Visual Analog Scale (VAS) scores, and sacrospinalis muscle damage evaluation indicators before operation and 3, 12 months postoperation were compared. Results: A total of 31 and 35 cases in the single incision and double incision groups, respectively, completed at least 12 months of systemic follow-up. The differences in perioperative conditions between the two groups were not statistically significant. The incision length of the single incision group was significantly shorter than that of the double incision group (P < 0.01). The ODI and VAS scores of patients in both groups improved significantly at 3 and 12 months postoperation. However, these two indicators at 3 and 12 months postoperation and the sacrospinalis muscle damage evaluation indicators at 3 months postoperation did not differ significantly between the two groups (P ≥ 0.05). Conclusions: Mast Quadrant-assisted modified TLIF with a small single posterior median incision has excellent clinical feasibility compared to minimally invasive TLIF with a double paramedian incision.

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. [ABSTRACT FROM AUTHOR]

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.