Integrative analysis of the transcriptome and proteome reveals the molecular responses of tobacco to boron deficiency.

BACKGROUND: Boron (B) is an essential micronutrient for plants. Inappropriate B supply detrimentally affects the productivity of numerous crops. Understanding of the molecular responses of plants to different B supply levels would be of significance in crop improvement and cultivation practices to deal with the problem. RESULTS: We conducted a comprehensive analysis of the transcriptome and proteome of tobacco seedlings to investigate the expression changes of genes/proteins in response to different B supply levels, with a particular focus on B deficiency. The global gene and protein expression profiles revealed the potential mechanisms involved in the responses of tobacco to B deficiency, including up-regulation of the NIP5;1-BORs module, complex regulation of genes/proteins related to cell wall metabolism, and up-regulation of the antioxidant machinery. CONCLUSION: Our results demonstrated that B deficiency caused severe morphological and physiological disorders in tobacco seedlings, and revealed dynamic expression changes of tobacco genes/proteins in response to different B supply levels, especially to B deficiency, thus offering valuable insights into the molecular responses of tobacco to B deficiency.

Prognostic effects of previous cancer history on patients with major salivary gland cancer.

OBJECTIVES: To explore the prognostic effects of previous cancer history on patients with major salivary gland cancer (SGC). SUBJECTS AND METHODS: SGC patients with (sec-SGC) and without (one-SGC) a previous cancer from the SEER database were identified. Cox proportional hazards regression (CoxPH) models were used to compare the prognosis between sec-SGC and one-SGC patients. Subgroup analyses for sec-SGC patients by gender, previous cancer types, previous cancer histology, and cancer diagnosis interval (CDI) were performed. Two CoxPH models were constructed to distinguish sec-SGC patients with different prognostic risks. RESULTS: 9098 SGC patients were enrolled. Overall, sec-SGC patients (adjusted HR [aHR] = 1.26, p < 0.001), especially those with a CDI ≤ 5 years (aHR = 1.47, p < 0.001), had worse overall survival (OS) than one-SGC patients. In subgroup analysis, only sec-SGC patients with a previous head and neck cancer who were female (aHR = 2.38, p = 0.005), with a CDI ≤ 5 years (aHR = 1.65, p = 0.007) or with a previous squamous cell carcinoma (aHR = 6.52, p < 0.001) had worse OS. Our models successfully differentiated all sec-SGC patients into high-, intermediate- and low-risk groups with different prognosis. CONCLUSIONS: Sec-SGC patients with different previous cancer types, gender, CDI and previous cancer histology had varied prognosis. The models we constructed could help differentiate the prognosis of sec-SGC patients with different risks.

Comparison of the Efficacy of Endoscopic Radial Incision and Cutting Procedure and Endoscopic Balloon Dilation for Benign Anastomotic Stricture After Low Anterior Resection Combined With Preventive Loop Ileostomy in Rectal Cancer.

BACKGROUND: Endoscopic radial incision and cutting procedure is a notable technique in the treatment of benign anastomotic strictures after low anterior resection in rectal cancer. However, the efficacy and safety of the endoscopic radial incision and cutting procedure and traditional endoscopic balloon dilation remain unknown. OBJECTIVE: To compare the efficacy and safety of the endoscopic radial incision and cutting procedure and endoscopic balloon dilation in patients with anastomotic stricture after low anterior resection. DESIGN: Rectal cancer patients with anastomotic stricture after low anterior resection combined with synchronous preventive loop ileostomy between January 2014 and June 2021 were retrospectively collected. These patients underwent the endoscopic radial incision and cutting procedure or endoscopic balloon dilation as an initial treatment. The clinicopathological baseline data of the patients, endoscopic surgery success rate, complications, and restricture rate were analyzed. SETTINGS: This study was conducted at Nanfang Hospital in China. PATIENTS: A total of 30 patients were eligible after reviewing the medical records. Twenty patients underwent endoscopic balloon dilation, and 10 patients underwent endoscopic radial incision and cutting procedure. MAIN OUTCOME MEASURES: The adverse event rate and stricture recurrence rate. RESULTS: There were no significant differences in patient demographics or clinical features. No adverse events occurred in either of the 2 groups. The mean operation time was 18.9 ± 3.6 minutes in the endoscopic balloon dilation group and 10.2 ± 3.3 minutes in the endoscopic radial incision and cutting procedure group ( p < 0.001). The stricture recurrence rates between the endoscopic balloon dilation group and the endoscopic radial incision and cutting procedure group were significantly different (44.4% vs 0%; p = 0.025). LIMITATIONS: This was a retrospective study. CONCLUSIONS: The endoscopic radial incision and cutting procedure is safe and more efficacious than endoscopic balloon dilation for anastomotic stricture after low anterior resection combined with synchronous preventive loop ileostomy in rectal cancer.

Nucleoside deaminases: the key players in base editing toolkit.

The development of nucleoside deaminase-containing base editors realized targeted single base change with high efficiency and precision. Such nucleoside deaminases include adenosine and cytidine deaminases, which can catalyze adenosine-to-inosine (A-to-I) and cytidine-to-uridine (C-to-U) conversion respectively. These nucleoside deaminases are under the spotlight because of their vast application potential in gene editing. Recent advances in the engineering of current nucleoside deaminases and the discovery of new nucleoside deaminases greatly broaden the application scope and improve the editing specificity of base editors. In this review, we cover current knowledge about the deaminases used in base editors, including their key structural features, working mechanisms, optimization, and evolution.

Derepression of the USP22-FASN axis by p53 loss under oxidative stress drives lipogenesis and tumorigenesis.

Overproduction of reactive oxygen species (ROS) and aberrant lipid metabolism are established hallmarks of cancer; however, the role of ROS in lipid synthesis during tumorigenesis is almost unknown. Herein, we show that ROS regulates lipid synthesis and thus controls colorectal tumorigenesis through a p53-dependent mechanism. In p53 wild-type colorectal cancer (CRC) cells, hydrogen peroxide (H2O2)-induced p53 expression represses the transcription of deubiquitinase USP22, which otherwise deubiquitinates and stabilizes Fatty Acid Synthase (FASN), and thus inhibits fatty acid synthesis. Whereas, in p53-deficient CRC cells, ROS-mediated inhibition of USP22 is relieved, leading to FASN stabilization, which thus promotes lipid synthesis and tumor growth. In human CRC specimens, USP22 expression is positively correlated with FASN expression. Our study demonstrates that ROS critically regulates lipid synthesis and tumorigenesis through the USP22-FASN axis in a p53-dependent manner, and targeting the USP22-FASN axis may represent a potential strategy for the treatment of colorectal cancer.

Dynamic changes of hematological indices in oropharyngeal cancer patients treated with radiotherapy.

BACKGROUND: Hematological indices assist in predicting clinical outcomes. OBJECTIVES: To explore changes of hematological indices on oropharynx squamous cell carcinoma (OPSCC) patients received radiotherapy and their association with survival. MATERIAL AND METHODS: The white blood cell count (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), hemoglobin (Hb), platelet (Plt), albumin (Alb), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline, 1-, 3-, 6- and 12-months follow-up were retrospectively collected. The trajectory of indices was described. A linear model with random effects was to describe indices' changing rate and trend. Univariable Cox analysis was to assess the correlation between indices and survival. RESULTS: Of the 85 patients, WBC and ALC dropped during acute phase and gradually recovered, while NLR and PLR increased during acute phase and subsequently declined (all p < .01). Higher absolute value of nutritional indices (Alb and Hb) was associated with better prognosis (p < .05). In contrast, patients with higher absolute value or upward trend of inflammatory indices (ANC, Plt, NLR and PLR) had worse survival (p < .05). CONCLUSIONS AND SIGNIFICANCE: The short- and long-term changes of indices differed in OPSCC patients received radiotherapy, and absolute values and dynamic changes of indices had the potential to be prognostic factors.

Cost-effectiveness analysis of pembrolizumab for patients with advanced esophageal cancer at PD-L1 combined positive score ≥10.

Aim: Due to the high price of pembrolizumab, it is still unknown whether the use of pembrolizumab for advanced esophageal cancer would be a cost-effective option for patients whose PD-L1 combined positive score is ≥10. Methods: A Markov simulation model was performed based on clinical trial KEYNOTE-181. Incremental cost-effectiveness ratios were calculated to compare the two treatments. Results: The total costs were US$193,575.60 and $8789.24 for pembrolizumab and chemotherapy treatment, respectively. The pembrolizumab group produced 0.93 quality-adjusted life years (QALYs), while the chemotherapy group produced 0.58 QALYs. Thus, patients in the pembrolizumab group spent an additional US$184,786.36 and produced 0.35 QALYs more than the chemotherapy group, which resulted in an incremental cost-effectiveness ratio of US$527,961.03 per QALY. Conclusion: For patients with advanced esophageal cancer whose PD-L1 combined positive score is ≥10, pembrolizumab is not a cost-effective second-line therapy versus chemotherapy from the US payer perspective.

The Prognostic Prediction Value of Positive Lymph Nodes Numbers for the Hypopharyngeal Squamous Cell Carcinoma.

Background: The current American Joint Committee on Cancer (AJCC) system only considered the importance of the size and laterality of lymph nodes while not the positive lymph node number (PLNN) for hypopharyngeal squamous cell carcinoma (HPSCC). Methods: A total of 973 patients with HPSCC from the Surveillance, Epidemiology, and End Results database (2004-2015) were identified. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic effects. We applied six Cox regression models to compare the survival prognostic values of PLNN and AJCC systems. Results: Positive lymph node number showed a significant association with overall survival (OS) and cancer-specific survival (CSS) (P < 0.001) in univariate and multivariable analyses. The increased PLNN of HPSCC gave rise to poor OS and CSS. The survival model incorporating a composite of PLNN and TNM classification (C-index for OS:0.682, C-index for CSS:0.702) performed better than other models. Conclusions: A positive lymph node number could serve as a survival predictor for patients with HPSCC and a complement to enhance the prognostic assessment effects of TNM cancer staging systems.

Epithelial chemerin-CMKLR1 signaling restricts microbiota-driven colonic neutrophilia and tumorigenesis by up-regulating lactoperoxidase.

Intestinal barrier immunity is essential for controlling gut microbiota without eliciting harmful immune responses, while its defect contributes to the breakdown of intestinal homeostasis and colitis development. Chemerin, which is abundantly expressed in barrier tissues, has been demonstrated to regulate tissue inflammation via CMKLR1, its functional receptor. Several studies have reported the association between increased expression of chemerin-CMKLR1 and disease severity and immunotherapy resistance in inflammatory bowel disease (IBD) patients. However, the pathophysiological role of endogenous chemerin-CMKLR1 signaling in intestinal homeostasis remains elusive. We herein demonstrated that deficiency of chemerin or intestinal epithelial cell (IEC)-specific CMKLR1 conferred high susceptibility to microbiota-driven neutrophilic colon inflammation and subsequent tumorigenesis in mice following epithelial injury. Unexpectedly, we found that lack of chemerin-CMKLR1 signaling specifically reduced expression of lactoperoxidase (LPO), a peroxidase that is predominantly expressed in colonic ECs and utilizes H2O2 to oxidize thiocyanates to the antibiotic compound, thereby leading to the outgrowth and mucosal invasion of gram-negative bacteria and dysregulated CXCL1/2-mediated neutrophilia. Importantly, decreased LPO expression was causally linked to aggravated microbiota-driven colitis and associated tumorigenesis, as LPO supplementation could completely rescue such phenotypes in mice deficient in epithelial chemerin-CMKLR1 signaling. Moreover, epithelial chemerin-CMKLR1 signaling is necessary for early host defense against bacterial infection in an LPO-dependent manner. Collectively, our study reveals that the chemerin-CMKLR1/LPO axis represents an unrecognized immune mechanism that potentiates epithelial antimicrobial defense and restricts harmful colonic neutrophilia and suggests that LPO supplementation may be beneficial for microbiota dysbiosis in IBD patients with a defective innate antimicrobial mechanism.

Association between fish oil supplementation and cancer risk according to fatty fish consumption: A large prospective population-based cohort study using UK Biobank.

Whether regular fish oil supplementation is associated with cancer risk is controversial. We aimed to evaluate the association of fish oil supplementation on cancer risk according to fatty fish consumption patterns. From the UK Biobank cohort, 470 804 participants with fish oil supplementation data were included. A total of 147 316 individuals with fish oil supplementation were in the exposed group; the other 323 488 were in the unexposed group. No association was found between self-report regular fish oil supplementation and overall cancer risk (hazard ratio [HR] = 0.97, 95% confidence intervals [CIs] = 0.95-1). Stratified by fatty fish consumption level, we found the association between fish oil supplementation and lower cancer risk in participants who consumed fatty fish less than two times per week, with association noted for both overall cancer (HR = 0.96, 95% CI = 0.94-0.99) and some specific cancers (colon cancer: HR = 0.84, 95% CI = 0.75-0.94; hepatobiliary cancer: HR = 0.74, 95% CI = 0.58-0.96; lung cancer: HR = 0.87, 95% CI = 0.78-0.98). On the contrary, a higher risk of breast cancer was observed (HR = 1.16, 95% CI = 1.01-1.32) in participants who consumed fatty fish at least two times per week. In conclusion, our findings underscore the need to refine recommendations for nutritional supplements according to inherent diet habits.

Two New Types of Homodiploid Fish and Polyploid Hybrids Derived from the Distant Hybridization of Female Koi Carp and Male Bighead Carp.

Bighead carps  (Hypophthalmichthys nobilis) and silver carps (Hypophthalmichthys molitrix) represent an important component of freshwater ichthiofauna in its native range, though they might become mass propagation in other systems (North America) and the reason of concern for fisheries management. Therefore, understanding their reproductive traits and particularly in the context of hybridization with other cyprinids was of value to explain their rapid propagation as well as potential benefits for aquaculture due to their unique diet, behavior, growth potential, and tolerance to deteriorating environmental conditions in freshwater ecosystems. Distant hybridization is an effective tool to create different ploidy offspring with changed phenotypes and genotypes. In this study, we reported distant hybridization of female koi carp (Cyprinus carpio haematopterus, KOC, 2n = 100) × male bighead carp (Hypophthalmichthys nobilis, BIC, 2n = 48) and the spontaneous occurrence of two new "crucian" carp-like homodiploid fish (2nGCC-L; 2nCCC-L; 2n = 100), a new type of triploid hybrid (3nKB, 3n = 124), and a new type of tetraploid hybrid (4nKB, 4n = 148). The body color of 2nGCC-L and 2nCCC-L were gray and multicolor, respectively. Both phenotypes were similar to the crucian carp (Carassius auratus). The difference was that their heads were rounder than those of the crucian carp and they had higher backs. Compared with the KOC with two pairs of barbels and BIC without barbel, 2nGCC-L, 2nCCC-L, and 4nKB had no barbel, but 3nKB had one pair of barbels. Microsatellite patterns and 5S rDNA sequences confirmed that 2nGCC-L, 2nCCC-L, and 3nKB were of hybrid origin. In regard to feeding, KOC was omnivorous and BIC was a typical filter-feeder. However, the 2nGCC-L, 2nCCC-L, and 3nKB were omnivorous. The formation of four kinds of new offspring is a groundbreaking finding in fish genetic breeding and evolutionary biology.

Hox genes reveal variations in the genomic DNA of allotetraploid hybrids derived from Carassius auratus red var. (female) × Cyprinus carpio L. (male).

BACKGROUND: Hox transcription factors are master regulators of animal development. Although highly conserved, they can contribute to the formation of novel biological characteristics when modified, such as during the generation of hybrid species, thus potentially serving as species-specific molecular markers. Here, we systematically studied the evolution of genomic sequences of Hox loci in an artificial allotetraploid lineage (4nAT, 4n = 200) derived from a red crucian carp (♀, RCC, 2n = 100) × common carp (♂, CC, 2n = 100) cross and its parents (RCC and CC). RESULTS: PCR amplification yielded 23 distinct Hox gene fragments from 160 clones in 4nAT, 22 fragments from 90 clones in RCC, and 19 fragments from 90 clones in CC. Sequence alignment of the HoxA3a and HoxC10a genes indicated both the inheritance and loss of paternal genomic DNA in 4nAT. The HoxA5a gene from 4nAT consisted of two subtypes from RCC and two subtypes from CC, indicating that homologous recombination occurred in the 4nAT hybrid genome. Moreover, 4nAT carried genomic pseudogenization in the HoxA10b and HoxC13a loci. Interestingly, a new type of HoxC9a gene was found in 4nAT as a hybrid sequence of CC and RCC by recombination in the intronic region. CONCLUSION: The results revealed the influence of Hox genes during polyploidization in hybrid fish. The data provided insight into the evolution of vertebrate genomes and might be benefit for artificial breeding programs.