Potential causal links of long-term exposure to PM2.5 and its chemical components with the risk of nasopharyngeal carcinoma recurrence: A 10-year cohort study in South China.

There is a lack of evidence from cohort studies on the causal association of long-term exposure to ambient fine particulate matter (PM2.5) and its chemical components with the risk of nasopharyngeal carcinoma (NPC) recurrence. Based on a 10-year prospective cohort of 1184 newly diagnosed NPC patients, we comprehensively evaluated the potential causal links of ambient PM2.5 and its chemical components including black carbon (BC), organic matter (OM), sulfate (SO4 2-), nitrate (NO3 -), and ammonium (NH4 +) with the recurrence risk of NPC using a marginal structural Cox model adjusted with inverse probability weighting. We observed 291 NPC patients experiencing recurrence during the 10-year follow-up and estimated a 33% increased risk of NPC recurrence (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 1.02-1.74) following each interquartile range (IQR) increase in PM2.5 exposure. Each IQR increment in BC, NH4 +, OM, NO3 -, and SO4 2- was associated with HRs of 1.36 (95%CI: 1.13-1.65), 1.35 (95%CI: 1.07-1.70), 1.33 (95%CI: 1.11-1.59), 1.32 (95%CI: 1.06-1.64), 1.31 (95%CI: 1.08-1.57). The elderly, patients with no family history of cancer, no smoking history, no drinking history, and those with severe conditions may exhibit a greater likelihood of NPC recurrence following exposure to PM2.5 and its chemical components. Additionally, the effect estimates of the five components are greater among patients who were exposed to high concentration than in the full cohort of patients. Our study provides solid evidence for a potential relationship between long-term exposure to PM2.5 and its components and the risk of NPC recurrence.

Death receptors 4/5 mediate tumour sensitivity to natural killer cell-mediated cytotoxicity in mismatch repair deficient colorectal cancer.

BACKGROUND: Identifying the target of natural killer (NK) cells in colorectal cancer (CRC) is critical for optimising the clinical use of NK cell-mediated immunotherapy. Mismatch repair deficiency (dMMR) is associated with high immune cell infiltration and MHC Class I defects. Whether dMMR CRC responses to NK cell therapy remains unclear. METHODS: MLH1, DR4, and DR5 knockout cell lines were established using CRISPR-Cas9 system. NK92-MI or NK cell isolated from BABL/C mice were used as effector cells against tumour cells. Inflammatory cytokines secretion by CRC cells was assessed via cytokine analysis. NK-cell-deficient/proficient animal models were used to validate the NK cell sensitivity. RESULTS: We observed that dMMR CRC cells were more sensitive to NK cell-mediated cytotoxicity than were mismatch-repair-proficient (pMMR) CRC cells. In dMMR CRC, Death receptor (DR)4/5 was upregulated and mediated sensitivity to NK cell-mediated cytotoxicity. DR4/5-mediated secretion of interleukin -12 sustained NK cell viability in dMMR CRC. NK cell depletion induced dMMR CRC tumour growth, and NK cell transfer inhibited lung metastasis of dMMR CRC with DR4/5 expression in vivo. TP53 upregulated DR4/DR5 expression in dMMR CRC. CONCLUSIONS: dMMR associated with increased sensitivity to NK cell-mediated cytotoxicity in CRC. DR4/DR5 sensitise dMMR CRC to NK cell-mediated cytotoxicity.

The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis.

BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC  plus cisplatin CCRT ) for LANPC patients. METHODS: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors. RESULTS: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064). CONCLUSION: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Systematic Review and Meta-Analysis: Impact of Various Hemostasis Methods on Ovarian Reserve Function in Laparoscopic Cystectomy for Ovarian Endometriomas.

Background: Ovarian endometriomas, resulting from the invasion of endometriosis into ovarian tissue, can significantly affect ovarian reserve, potentially leading to infertility. When conservative treatments fail, it may further aggravate ovarian reserve decline by invading the ovarian cortex and, in severe cases, result in premature ovarian failure and infertility. Objective: This study aimed to investigate the impact of various hemostasis methods on ovarian reserve function in cases of laparoscopic cystectomy for ovarian endometriomas. Methods: We conducted a systematic review and meta-analysis to assess the effects of different hemostasis techniques used during laparoscopic cystectomy for ovarian endometriomas. A comprehensive analysis of relevant literature was performed, focusing on the impact of bipolar electrocoagulation, ultrasonic scalpel, and suture hemostasis on ovarian reserve function. The evaluation criteria included Anti-Müllerian hormone levels and antral follicle counts. Results: Our analysis revealed significant variations in the impact of hemostasis methods on ovarian reserve function. While all methods aimed to stop bleeding during surgery, the thermal damage to surrounding tissues differed. Bipolar electrocoagulation, ultrasonic scalpel, and suture hemostasis showed varying effects on ovarian reserve, with implications for post-operative fertility. Conclusions: The choice of the hemostasis method in laparoscopic cystectomy for ovarian endometriomas has a crucial influence on ovarian reserve function. Our findings emphasize the need to consider the potential consequences of thermal damage when selecting a hemostasis technique. Clinicians should weigh the benefits and risks of each method to protect ovarian reserve function effectively. This study offers valuable insights for guiding clinical practice, ensuring optimal outcomes for patients facing endometrioma-related fertility challenges.

Identification of an N6-methyladenosine-mediated positive feedback loop that promotes Epstein-Barr virus infection.

N6-methyladenosine (m6A) is among the most abundant mRNA modifications, particularly in eukaryotes, and is found in mammals, plants, and even some viruses. Although essential for the regulation of many biological processes, the exact role of m6A modification in virus-host interaction remains largely unknown. Here, using m6A -immunoprecipitation and sequencing, we find that Epstein-Barr virus (EBV) infection decreases the m6A modification of transcriptional factor KLF4 mRNA and subsequently increases its protein level. Mechanistically, EBV immediate-early protein BZLF1 interacts with the promoter of m6A methyltransferase METTL3, inhibiting its expression. Subsequently, the decrease of METTL3 reduces the level of KLF4 mRNA m6A modification, preventing its decay by the m6A reader protein YTHDF2. As a result, KLF4 protein level is upregulated and, in turn, promotes EBV infection of nasopharyngeal epithelial cells. Thus, our results suggest the existence of a positive feedback loop formed between EBV and host molecules via cellular mRNA m6A levels, and this feedback loop acts to facilitate viral infection. This mechanism contains multiple potential targets for controlling viral infectious diseases.

The prognostic value of weight loss during radiotherapy among patients with nasopharyngeal carcinoma: a large-scale cohort study.

BACKGROUND: We aim to investigate the prognostic value of weight loss during radiotherapy (RT) among patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 1149 NPC patients who received radical RT were retrospectively analyzed. Patients' weight were measured at initiation of RT (WPre-RT) and every week during RT (WRT1,2,3,4,5,6,7). Percentage of weight loss (PWL) at 1st, 2nd, 3rd, 4th, 5th, 6th, and 7th week of RT (RT-PWL1,2,3,4,5,6,7) were calculated using the following equation: (WPre-RT -WRT1,2,3,4,5,6,7)/WPre-RT × 100%. The optimal threshold of RT-PWL7 was determined by recursive partitioning analyses (RPAs). Our endpoints included disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS). RESULTS: The median RT-PWLs were 0, 0, 1.5, 2.9, 4.1, 5.5, 6.6% at 1st, 2nd, 3rd, 4th, 5th, 6th, and 7th week of RT, respectively. RT-PWL7 optimal threshold with respect to DFS was 5.3% based on RPAs. Therefore, a consistent threshold of 5% (<5% vs > ≥5%) was selected to classify NPC patients into low RT-PWL7 and high RT-PWL7 groups for survival analysis. Compared to high RT-PWL7 (≥5%), patients with low RT-PWL7 (< 5%) had significantly better ten-year DFS (61.2% vs 78.8%; P < 0.001), OS (70.1% vs 86.6%; P < 0.001), and DMFS (80.2% vs 88.5%; P = 0.007). However, no difference was observed between LRRFS groups (91.7% vs 94.3%; P = 0.173). In multivariate analysis, high RT-PWL7 was an independent risk factor for DFS (HR, 1.56; 95%CI, 1.19-2.03; P = 0.001), OS (HR, 1.54; 95%CI, 1.11-2.15; P = 0.011), and DMFS (HR, 1.47; 95%CI, 1.03-2.10; P = 0.033) in patients with NPC. In addition, treatment strategy, plasma Epstein-Barr virus DNA, and N stage were associated with weight loss. CONCLUSIONS: High RT-PWL7 was significantly associated with decreased DFS, OS, and DMFS for NPC patients. Clinicians should continuously inform patients on the health impact of minimizing RT-PWL7 under 5% during radiotherapy.

Isolation and characterization of wheat ice recrystallisation inhibition gene promoter involved in low temperature and methyl jasmonate responses.

It is well known that plant growth, development, survival and geographical distribution are constrained by extreme climatic conditions, especially extreme low temperature. Under cold stress, cold-inducible promoters were identified as important molecular switches to transcriptionally regulate the initiation of genes associated with cold acclimation processes and enhance the adaptability of plants to cold stimulation. Wheat (Triticum aestivum L.) is one of the most dominating food crops in the world, and wheat crops are generally overwintering with strong cold resistance. Our previous study already proved that heterologous expression of wheat ice recrystallization inhibition (IRI) genes enhanced freezing tolerance in tobacco. However, the upstream regulatory mechanisms of TaIRI are ambiguous. In this study, the space-time specific expression of TaIRI genes in wheat was analyzed by quantitative real-time PCR (qRT-PCR), and results showed that the expression of TaIRI in all tissues was cold-induced and accelerate by exogenous methyl jasmonate (MeJA). Three promoters of TaIRI genes were isolated from wheat genome, and various 5'-deletion fragments of TaIRIp were integrated into ß-glucuronidase (GUS) within vector pCAMBIA1301. The promoter activity of TaIRI genes was determined through transient expression system of tobacco and stable expression of Arabidopsis thaliana. Results revealed that the GUS activity were significantly strengthened by cold and MeJA treatments. This study will provide insights into elucidating the transcription-regulatory mechanism of IRI proteins responding to low temperature.

The predictive value of body mass index on prognosis and adverse events of cancers treated with immunotherapy: a systematic review and meta-analysis.

OBJECTIVE: High body mass index (BMI) greater than 25 kg/m2 has a complex relationship with cancers. The aim of this systematic review and meta-analysis is to explore controversy over whether BMI is correlated with outcomes including survival and immunotherapy-related adverse events (irAEs) in cancer patients treated with immunotherapy. METHODS: We searched PubMed, Embase, Web of Science, and The Cochrane Library for relevant studies published up to June 2020. Title/abstract screening, full-text review, data extraction, and quality assessment were performed independently. Subgroup analysis was based on sex, treatment lines, the status of programmed death-ligand 1 (PD-L1), and tumor types. Sensitivity analysis was performed by synthesizing studies that adjusted for certain covariates or studies with good quality. Statistical heterogeneity was evaluated by the I2 value. Meta-analysis was performed with hazard ratio (HR) / odds ratio (OR) and 95% confidence intervals (CIs) as the effect measures. RESULTS: Twenty studies were included for survival and irAEs analyses. Patients with high BMI who underwent immunotherapy had longer overall survival (OS) (pooled hazard ratio, pHR = 0.71 [95% CI: 0.59-0.85]) and progression-free survival (PFS) (pHR = 0.76 [95% CI: 0.65-0.88]) than those with low BMI; at the same time, high-BMI patients had increased irAEs (OR = 2.54 [95% CI: 1.12-5.79]). CONCLUSION: In general, high BMI was correlated with improved OS and PFS in patients treated with immunotherapy along with a high risk of irAEs. However, discrepant findings from subgroup analyses urgently call for further analysis.

Impact of cumulative cisplatin dose in childhood nasopharyngeal carcinoma based on neoadjuvant chemotherapy response in the intensity-modulated radiotherapy era: a real-world study.

BACKGROUND: We aimed to comprehensively investigate the optimal cumulative cisplatin dose during concurrent chemoradiotherapy (CC-CCD) for locoregionally advanced nasopharyngeal carcinoma (CA-LANPC) with different tumor responses after neoadjuvant chemotherapy (NAC). METHODS: Patients with CA-LANPC who underwent NAC followed by cisplatin-based concurrent chemoradiotherapy were retrospectively analyzed. Evaluation of tumor response in patients was conducted by Response Evaluation Criteria for Solid Tumor (RECIST) 1.1 after two to four cycles NAC. Multivariate Cox proportional hazards models were used for prognosis. Recursive partitioning analysis (RPA) was conducted to classify participates and predict disease-free survival (DFS). RESULTS: One hundred and thirty-two patients with favorable response after NAC were included. The median CC-CCD was 163 mg/m2 (IQR, 145-194 mg/m2), and 160 mg/m2 was selected as the cutoff point to group patients into low and high CC-CCD groups (< 160 vs. ≥ 160 mg/m2). There was significant improvement in 5-year DFS (91.2% vs. 72.6%; P = 0.003) for patients receiving high CC-CCD compared to those receiving low CC-CCD. Multivariate analysis revealed that CC-CCD, T stage, and Epstein-Barr virus (EBV) DNA were independent prognostic factors for DFS (P < 0.05 for all). Patients were further categorized into two prognostic groups by RPA: the low-risk group (T1-3 disease with regardless of EBV DNA, and T4 disease with EBV DNA < 4000 copy/mL), and the high-risk group (T4 disease with EBV DNA ≥ 4000 copy/mL). Significant 5-year DFS improvement was observed for the high-risk group (P = 0.004) with high CC-CCD. However, DFS improvement was relatively insignificant in the low-risk group (P = 0.073). CONCLUSIONS: CC-CCD was a positive prognostic factor for responders after NAC in CA-LANPC. Furthermore, CC-CCD ≥ 160 mg/m2 could significantly improve DFS in the high-risk group with CA-LANPC, but the benefit of high CC-CCD in the low-risk group needs further study.

Characterization of ZmCOLD1, novel GPCR-Type G Protein genes involved in cold stress from Zea mays L. and the evolution analysis with those from other species.

Maize is one of the most vital staple crops worldwide. G proteins modulate plentiful signaling pathways, and G protein-coupled receptor-type G proteins (GPCRs) are highly conserved membrane proteins in plants. However, researches on maize G proteins and GPCRs are scarce. In this study, we identified three novel GPCR-Type G Protein (GTG) genes from chromosome 10 (Chr 10) in maize, designated as ZmCOLD1-10A, ZmCOLD1-10B and ZmCOLD1-10C. Their amino acid sequences had high similarity to TaCOLD1 from wheat and OsCOLD1 from rice. They contained the basic characteristics of GTG/COLD1 proteins, including GPCR-like topology, the conserved hydrophilic loop (HL) domain, DUF3735 (domain of unknown function 3735) domain, GTPase-activating domain, and ATP/GTP-binding domain. Subcellular localization analyses of ZmCOLD1 proteins suggested that ZmCOLD1 proteins localized on plasma membrane (PM) and endoplasmic reticulum (ER). Furthermore, amino acid sequence alignment verified the conservation of the key 187th amino acid T in maize and other wild maize-relative species. Evolutionary relationship among plants GTG/COLD1 proteins family displayed strong group-specificity. Expression analysis indicated that ZmCOLD1-10A was cold-induced and inhibited by light. Together, these results suggested that ZmCOLD1 genes had potential value to improve cold tolerance and to contribute crops growth and molecular breeding.

The role of histogram analysis in diffusion-weighted imaging in the differential diagnosis of benign and malignant breast lesions.

BACKGROUND: The present study aims to investigate the role of histogram analysis of intravoxel incoherent motion (IVIM) in the differential diagnosis of benign and malignant breast lesions. METHODS: The magnetic resonance imaging and clinical data of 55 patients (63 lesions) were retrospectively analyzed. The multi-b-valued diffusion-weighted imaging image was processed using the MADC software to obtain the gray-scaled maps of apparent diffusion coefficient (ADC)-slow, ADC-fast and f. The MaZda software was used to extract the histogram metrics of these maps. Combined with the conventional sequence images, the region of interest (ROI) was manually drawn along the edge of the lesion at the maximum level of the gray-scale image, and the difference of the data was analyzed between the benign and malignant breast lesions. RESULTS: There were 29 patients with 37 benign lesions, which included 23 fibroadenomas, 6 adenosis, 1 breast cysts, 4 intraductal papillomas, and 3 inflammations of breast. Furthermore, 26 malignant lesions in 26 patients, which included 20 non-specific invasive ductal carcinomas, 5 intraductal carcinomas and 1 patient with squamous cell carcinoma. The ADC-slow (mean and the 50th percentile) and f (minimum, mean, kurtosis, the 10th percentile and 50th percentile) of these malignant breast lesions were significantly lower than those of benign lesions (P < 0.05), while ADC-fast (kurtosis) and f (variance, skewness) of these malignant breast lesions were significantly higher than those of benign lesions (P < 0.05). CONCLUSION: The histogram analysis of ADC-slow (mean and the 50th percentile), ADC-fast (kurtosis) and f (minimum, mean, kurtosis, the 10th percentile and 50th percentile. Variance, skewness) can provide a more objective and accurate basis for the differential diagnosis of benign and malignant breast lesions.

Monoexponential, Biexponential, and stretched-exponential models using diffusion-weighted imaging: A quantitative differentiation of breast lesions at 3.0T.

BACKGROUND: Diffusion-weighted imaging (DWI) plays an important role in the differentiation of malignant and benign breast lesions. PURPOSE: To investigate the utility of various diffusion parameters obtained from monoexponential, biexponential, and stretched-exponential DWI models in the differential diagnosis of breast lesions. STUDY TYPE: Prospective. POPULATION: Sixty-one patients (age range: 25-68 years old; mean age: 46 years old) with 31 malignant lesions, 42 benign lesions, and 28 normal breast tissues diagnosed initially by clinical palpation, ultrasonography, or conventional mammography were enrolled in the study from January to September 2016. FIELD STRENGTH: 3.0T MR scanner, T1 WI, T2 WI, DWI (conventional and multi-b values), dynamic contrast-enhanced. ASSESSMENT: The apparent diffusion coefficient (ADC) was calculated by monoexponential analysis. The diffusion coefficient (ADCslow ), pseudodiffusion coefficient (ADCfast ), and perfusion fraction (f) were calculated using the biexponential model. The distributed diffusion coefficient (DDC) and water molecular diffusion heterogeneity index (α) were obtained using a stretched-exponential model. All parameters were compared for malignant tumors, benign tumors, and normal breast tissues. A receiver operating characteristic curve was used to compare the ability of these parameters, in order to differentiate benign and malignant breast lesions. STATISTICAL TESTS: All statistical analyses were performed using statistical software (SPSS). RESULTS: ADC, ADCslow , f, DDC, and α values were significantly lower in malignant tumors when compared with normal breast tissues and benign tumors (P < 0.05). However, ADC and f had higher area under the receiver operating characteristic curve (AUC) values (0.889 and 0.919, respectively). DATA CONCLUSION: The parameters derived from the biexponential and stretched-exponential DWI could provide additional information for differentiating between benign and malignant breast tumors when compared with conventional diffusion parameters. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;50:1461-1467.

The detrimental effects of radiotherapy interruption on local control after concurrent chemoradiotherapy for advanced T-stage nasopharyngeal carcinoma: an observational, prospective analysis.

BACKGROUND: Previous studies have reported radiotherapy interruption (RTI) is associated with poor local control in two-dimensional radiotherapy (2DRT) era. However, it remains unclear whether RTI still affects local control for advanced T stage (T3-4) in the intensity-modulated radiation therapy (IMRT) era. We aim to evaluate whether RTI affects local control for T3-4 NPC treated with definitive IMRT. METHODS: In this observational prospective study, 447 T3-4 NPC patients treated with IMRT plus concurrent chemotherapy were included. All patients completed the planned radiotherapy course, and RTI was defined as the actual time taken to finish the prescribed course of radiotherapy minus the planned radiotherapy time. Receiver operating characteristic (ROC) curve was used for determined the cutoff point of RTI. The effects of RTI on local control were analyzed in multivariate analysis. RESULTS: At 5 years, the local relapse-free survival (LRFS) and overall survival (OS) rates were 93.7 and 85.7%, respectively. The cutoff RTI for LRFS was 5.5 days by ROC curve. Compared to patients with RTI >  5 days, patients with RTI ≤ 5 days had a significantly lower rate of LRFS (97% vs. 83%; P < 0.001). In multivariate analysis, RTI was a risk factor independently associated with LRFS (HR = 9.64, 95% CI, 4.10-22.65), but not for OS (HR = 1.09, 95% CI, 0.84-1.64). CONCLUSIONS: The current analysis demonstrates a significant correlation between prolonged RTI and local control in NPC, even when concurrent chemotherapy is used. We consider that attention to RTI seems to be warranted for patients with advanced T-stage NPC in the era of IMRT.

Synthesis of zwitterionic N-chlorohydantoins for antibacterial applications.

Two novel zwitterionic N-chlorohydantoin biocides, containing an N-chlorohydantoin unit and a sulfobetaine unit or a carboxybetaine unit, were chemically synthesized and characterized. Using the quaternary ammonium N-chlorohydantoin as control, the antibacterial activity of synthetic zwitterionic N-chlorohydantoins was challenged and the antibacterial data showed that carboxybetaine N-chlorohydantoin exhibited distinctively higher biocidal efficacy than QA counterpart, while sulfobetaine N-chlorohydantoin displayed slightly inferior antimicrobial efficacy. Our results may inspire further exploration of more zwitterionic N-chlorohydantoin analogs for antibacterial application.

Identification of genes from the ICE-CBF-COR pathway under cold stress in Aegilops-Triticum composite group and the evolution analysis with those from Triticeae.

Adverse environmental conditions limit various aspects of plant growth, productivity, and ecological distribution. To get more insights into the signaling pathways under low temperature, we identified 10 C-repeat binding factors (CBFs), 9 inducer of CBF expression (ICEs) and 10 cold-responsive (CORs) genes from Aegilops-Triticum composite group under cold stress. Conserved amino acids analysis revealed that all CBF, ICE, COR contained specific and typical functional domains. Phylogenetic analysis of CBF proteins from Triticeae showed that these CBF homologs were divided into 11 groups. CBFs from Triticum were found in every group, which shows that these CBFs generated prior to the divergence of the subfamilies of Triticeae. The evolutionary relationship among the ICE and COR proteins in Poaceae were divided into four groups with high multispecies specificity, respectively. Moreover, expression analysis revealed that mRNA accumulation was altered by cold treatment and the genes of three types involved in the ICE-CBF-COR signaling pathway were induced by cold stress. Together, the results make CBF, ICE, COR genes family in Triticeae more abundant, and provide a starting point for future studies on transcriptional regulatory network for improvement of chilling tolerance in crop.

Prognostic value of serum Epstein-Barr virus antibodies in patients with nasopharyngeal carcinoma and undetectable pretreatment Epstein-Barr virus DNA.

Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC). Serum IgA antibodies against early antigen (EA-IgA) and viral capsid antigen (VCA-IgA) are the most commonly used to screen for NPC in endemic areas. However, the prognostic value of serum EA-IgA and VCA-IgA in patients with NPC is less clear. We hypothesize that serum EA-IgA and VCA-IgA levels have prognostic impact for survival outcomes in NPC patients with undetectable pretreatment EBV (pEBV) DNA. In this series, 334 patients with non-metastatic NPC and undetectable pEBV DNA were included. Serum EA-IgA and VCA-IgA were determined by ELISA. After analysis, serum EA-IgA and VCA-IgA loads correlated positively with T, N, and overall stage (all P < 0.05). Serum EA-IgA was not associated with survival outcome in univariable analyses. But patients with serum VCA-IgA >1:120 had significantly inferior 5-year progression-free survival (80.4% vs 89.6%, P = 0.025), distant metastasis-free survival (88.4% vs 94.8%, P = 0.050), and locoregional relapse-free survival (88.4% vs 95.6%, P = 0.023; log-rank test). Multivariable analyses revealed that N stage was the only independent prognostic factor (all P < 0.05), but the VCA-IgA became insignificant. Further analyses revealed that serum VCA-IgA was not an independent prognostic factor in early N (N0-1) or advanced N (N2-3) stage NPC. In summary, although both EA-IgA and VCA-IgA correlate strongly with TNM stage, our analyses do not suggest that these antibodies are prognostic biomarkers in patients with NPC and undetectable pEBV DNA.

Prognostic value of primary gross tumor volume and standardized uptake value of 18F-FDG in PET/CT for distant metastasis in locoregionally advanced nasopharyngeal carcinoma.

Distant metastasis has become the predominant model of treatment failures in patients with locoregionally advanced nasopharyngeal carcinoma. Effort should therefore be made to stratify locoregionally advanced nasopharyngeal carcinoma patients into different groups based on the risk of metastasis to improve prognosis and tailor individualized treatments. This study aims to assess the value of primary gross tumor volume and the maximum standardized uptake value for predicting distant metastasis-free survival of patients with locoregionally advanced nasopharyngeal carcinoma. A total of 294 locoregionally advanced nasopharyngeal carcinoma patients who were identified from prospectively maintained database and underwent fluor-18-fluorodeoxyglucose positron emission tomography/computed tomography imaging before treatment were included. The maximum standardized uptake value was recorded for the primary tumor (SUVmax-P) and neck lymph nodes (SUVmax-N). Computed tomography-derived primary gross tumor volume was measured using the summation-of-area technique. At 5 years, the distant metastasis-free survival rate was 83.7%. The cut-off of the SUVmax-P, SUVmax-N, and primary gross tumor volume for distant metastasis-free survival was 8.95, 5.75, and 31.3 mL, respectively, by receiver operating characteristic curve. In univariate analysis, only SUVmax-N (hazard ratio: 7.01; 95% confidence interval: 1.70-28.87; p < 0.01) and clinical stage (hazard ratio: 3.03; 95% confidence interval: 1.67-5.47; p = 0.007) were confirmed as independent predictors of distant metastasis-free survival. A prognostic model was derived by SUVmax-N and clinical stage: low risk (SUVmax-N < 5.75 regardless of clinical stage), medium risk (stage III and SUVmax-N ≥ 5.75), and high risk (stage IV and SUVmax-N ≥ 5.75). Multivariate analysis revealed that SUVmax-N and the prognostic model remained independent prognostic factors for distant metastasis-free survival (p = 0.023 and p < 0.001, respectively), but the clinical stage became insignificant (p = 0.133). Furthermore, the adjusted hazard ratios for the prognostic model were higher than SUVmax-N (hazard ratio = 6.27 vs 5.21, respectively). In summary, compared with SUVmax-P, SUVmax-N may be a better predictor of distant metastasis-free survival for patients with locoregionally advanced nasopharyngeal carcinoma. Combining SUVmax-N with clinical stage gives a more precise picture in predicting distant metastasis.

Gene Regulation and Signal Transduction in the ICE-CBF-COR Signaling Pathway during Cold Stress in Plants.

Low temperature is an abiotic stress that adversely affects the growth and production of plants. Resistance and adaptation of plants to cold stress is dependent upon the activation of molecular networks and pathways involved in signal transduction and the regulation of cold-stress related genes. Because it has numerous and complex genes, regulation factors, and pathways, research on the ICE-CBF-COR signaling pathway is the most studied and detailed, which is thought to be rather important for cold resistance of plants. In this review, we focus on the function of each member, interrelation among members, and the influence of manipulators and repressors in the ICE-CBF-COR pathway. In addition, regulation and signal transduction concerning plant hormones, circadian clock, and light are discussed. The studies presented provide a detailed picture of the ICE-CBF-COR pathway.