Genomics insights into flowering and floral pattern formation: regional duplication and seasonal pattern of gene expression in Camellia.

BACKGROUND: The formation and domestication of ornamental traits are influenced by various aspects, such as the recognition of esthetic values and cultural traditions. Camellia japonica is widely appreciated and domesticated around the world mainly due to its rich variations in ornamental traits. Ornamental camellias have a diverse range of resources, including different bud variations from Camellia spp. as well as inter- and intra- specific hybridization. Despite research on the formation of ornamental traits, a basic understanding of their genetics and genomics is still lacking. RESULTS: Here, we report the chromosomal-level reference genome of C. japonica through combining multiple DNA-sequencing technologies and obtain a high-density genetic linkage map of 4255 markers by sequencing 98 interspecific F1 hybrids between C. japonica and C. chekiangoleosa. We identify two whole-genome duplication events in C. japonica: one is a shared ancient γ event, and the other is revealed to be specific to genus Camellia. Based on the micro-collinearity analysis, we find large-scale segmental duplication of chromosome 8, resulting to two copies of the AGAMOUS loci, which may play a key role in the domestication of floral shapes. To explore the regulatory mechanisms of seasonal flowering, we have analyzed year-round gene expression patterns of C. japonica and C. azalea-a sister plant of continuous flowering that has been widely used for cross breeding. Through comparative analyses of gene co-expression networks and annual gene expression patterns, we show that annual expression rhythms of some important regulators of seasonal growth and development, including GIGANTEA and CONSTANS of the photoperiod pathway, have been disrupted in C. azalea. Furthermore, we reveal that the distinctive expression patterns of FLOWERING LOCUS T can be correlated with the seasonal activities of flowering and flushing. We demonstrate that the regulatory module involved in GIGANTEA, CONSTANS, and FLOWERING LOCUS T is central to achieve seasonality. CONCLUSIONS: Through the genomic and comparative genomics characterizations of ornamental Camellia spp., we propose that duplication of chromosomal segments as well as the establishment of gene expression patterns has played a key role in the formation of ornamental traits (e.g., flower shape, flowering time). This work provides a valuable genomic platform for understanding the molecular basis of ornamental traits.

RENAL nephrometry scoring system in bilateral Wilms tumor: predictive application.

AIM: This study aims to explore the application of RENAL nephrometry scoring system in bilateral Wilms tumor (BWT). METHODS: A retrospective review of patients with BWT from January 2010 to June 2022 was performed. Each kidney unit of the BWT was evaluated independently and scored according to RENAL nephrometry scoring system by 2 blinded reviewers, and reviewers were blinded to what surgery the patients ultimately had. Discrepancies were evaluated by a third reviewer to reach a consensus. Tumor anatomical characteristics were summarized and compared. RESULTS: 29 patients with 53 kidney units were included in the study. 53 kidney units included 12 (22.6%) low-complexity, 9 (17.0%) intermediate-complexity, and 32 (60.4%) high-complexity. 2 kidney units (3.8%) had tumor thrombus, and 14 (26.4%) had multiple lesions. A total of 42 kidney units (79.2%) underwent initial nephron-sparing surgery (NSS) and 11 (20.8%) underwent radical nephrectomy. Less complexity tumors were observed in the NSS group. Of the 42 kidney units undergoing initial NSS, 26 were performed in vivo and 16 ex vivo via autotransplantation. The latter group featured a higher complexity. During follow-up, 22 patients survived and 7 died, no statistically significant tumor complexity was observed between the two groups. CONCLUSIONS: The anatomical characteristics of BWT are complex. Despite this study did not indicate that the complexity correlates with prognosis, low-complexity tumors were candidates for NSS, and kidney autotransplantation provided a feasible procedure for high-complexity tumors. A refined system is required due to multiple lesions and tumor thrombus.

Comparative efficacy and safety of drug treatment for premature ejaculation: A systemic review and Bayesian network meta-analysis.

To assess the comparative efficacy and safety of drug treatments for premature ejaculation. A systemic review and Bayesian network meta-analysis were executed on randomised controlled trials of drug interventions for premature ejaculation. Intravaginal ejaculation latency time and related adverse effects were outcome measures. A total of 44 RCTs with 11,008 patients were included in our NMA. In therapy <8 weeks, the ranking of drug efficacy was topical creams >selective serotonin reuptake inhibitor (SSRI)+ phosphodiesterase 5 inhibitor (PDE5i) > PDE5i > sertraline > clomipramine > paroxetine > dapoxetine 60 milligram (mg) > dapoxetine 30 mg > fluoxetine>citalopram > duloxetine>placebo. In therapy ≥ 8 weeks, the ranking of drug efficacy was SSRI + PDE5i > topical creams > paroxetine > tramadol > PDE5i > fluoxetine > dapoxetine 60 mg > dapoxetine 30 mg > clomipramine>citalopram > placebo. For total adverse events, clomipramine, dapoxetine 30 mg, dapoxetine 60 mg, paroxetine, PDE5i, SSRI + PDE5i and tramadol had a higher risk than placebo. In conclusion, in ≥8 weeks of therapy, the drug combination of SSRI + PDE5i was the most effective PE therapy. In <8 weeks of therapy, the efficacy of local anaesthetics was best. All drug treatments were ranked better than placebo. In general, drugs with better effects had more obvious side effects.

NCK1 promotes the angiogenesis of cervical squamous carcinoma via Rac1/PAK1/MMP2 signal pathway.

OBJECTIVE: The study was to explore the roles of Nck1 in the angiogenesis of cervical squamous cell carcinoma (CSCC). METHODS: mRNA and protein levels were evaluated with real-time quantitative PCR and immunohistochemisty/western blotting respectively. The cancer microvessel density (MVD) was assayed with CD34 endothelial labeling. Nck1 gene knock-in (SiHa-Nck1+) and knock-down (SiHa-Nck1-) were achieved by gene transfection and siRNA respectively. Protein level from cellular supernatant was measured with ELISA. Proliferation, migration and tube formation of the Human Umbilical Vein Endothelial cells (HUVECs) were evaluated by CCK-8 cell viability assay, transwell chamber assay and in vitro Matrigel tubulation assay respectively. RESULTS: Nck1 level gradually increased from normal cervical epithelia to high-grade CIN, overexpressed in CSCC and was associated with cancer MVD. The ability of proliferation, migration and tube formation of HUVECs was enhanced in SiHa-Nck1+-treated while decreased in SiHa-NcK1--treated cells compared to SiHa-control-treated cells. Mechanistically, RAC1-GTP, p-PAK1 and MMP2 were increased in SiHa-NCK1+ cells and pretreatment with the Rac1 inhibitor (NSC23766) significantly decreased their levels. Furthermore, inhibition of PAK1 reduced MMP2 level in SiHa-Nck1+ cells whereas the level of Rac1-GTP was unaltered. Also, inhibition of Rac1 or PAK1 impaired angiogenesis-inducing capacity of cancer cells. CONCLUSIONS: Nck1 promotes the angiogenesis-inducing capacity of CSCC via the Rac1/PAK1/MMP2 signal pathway.

[Corrigendum] Celecoxib inhibits the epithelial­to­mesenchymal transition in bladder cancer via the miRNA­145/TGFBR2/Smad3 axis.

Following the publication of the above article, an interested reader drew to the authors' attention that, for the Transwell migration assays shown in Figs. 1B and 3B on p. 685 and p. 688 respectively, the images selected for the '5637 / DMSO' experiment in Fig. 1B and the DMSO experiment in Fig. 3B were apparently the same, such that these data appeared to have been derived from the same original source. After having consulted their original data, the authors have realized that the 5637 DMSO data panel in Fig. 3B had been selected incorrectly. The revised version of Fig. 3, showing the correct data for the DMSO experiment in Fig. 3B, is shown on the next page. The authors regret that these errors went unnoticed prior to the publication of this article, and thank the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they also apologize to the readership of the journal for any inconvenience caused. [International Journal of Molecular Medicine 44: 683­683, 2019; DOI: 10.3892/ijmm.2019.4241].

The Outcome of Transplanting Kidneys From Very Small Pediatric Deceased Donors.

BACKGROUND: Kidneys from very small pediatric donors (VSPDs, aged <2 y) are underutilized. Concerns regarding potentially inferior outcomes hinder the use in pediatric recipients. METHODS: All pediatric kidney-only transplants from <18-year-old donors between January 2012 and May 2021 in our center were included in this study. Outcomes were compared between VSPD and normal pediatric donor (NPD, aged 2-18 y) groups, and 3-y death-censored graft survival was assessed by the multivariable Cox proportional hazard model. RESULTS: Of all 252 enrolled patients, 149 (59.1%) received kidneys from NPDs and 103 (40.9%) from VSPDs. The 3-y graft survival rates of the NPD and VSPD groups were 91.2% and 88.6%, respectively ( P = 0.385). The adjusted hazard ratio of 3-y graft loss was 1.2 (95% confidence interval, 0.6-2.5; P = 0.659) for the VSPD group compared with the NPD group. There was no significant difference in estimated glomerular filtration rate at 3 y posttransplant observed between NPD and VSPD groups (86.9 ± 26.8 versus 87 ± 27.9 mL/min/1.73 m 2 ; P = 0.991). Patients (n = 12, 4.8%) who received kidneys from donors <5 kg contributed 5 (5/39, 12.8%) with delayed graft function and the sole primary nonfunction in our cohort. CONCLUSIONS: Although attention to preventing complications is necessary, especially for kidneys from donors <5 kg, kidneys from VSPDs did not appear to impart added risk for 3-y graft loss and renal function.

Single planar photonic chip with tailored angular transmission for multiple-order analog spatial differentiator.

Analog spatial differentiation is used to realize edge-based enhancement, which plays an important role in data compression, microscopy, and computer vision applications. Here, a planar chip made from dielectric multilayers is proposed to operate as both first- and second-order spatial differentiator without any need to change the structural parameters. Third- and fourth-order differentiations that have never been realized before, are also experimentally demonstrated with this chip. A theoretical analysis is proposed to explain the experimental results, which furtherly reveals that more differentiations can be achieved. Taking advantages of its differentiation capability, when this chip is incorporated into conventional imaging systems as a substrate, it enhances the edges of features in optical amplitude and phase images, thus expanding the functions of standard microscopes. This planar chip offers the advantages of a thin form factor and a multifunctional wave-based analogue computing ability, which will bring opportunities in optical imaging and computing.

Feature generation and contribution comparison for electronic fraud detection.

Modern money transfer services are convenient, attracting fraudulent actors to run scams in which victims are deceived into transferring funds to fraudulent accounts. Machine learning models are broadly applied due to the poor fraud detection performance of traditional rule-based approaches. Learning directly from raw transaction data is impractical due to its high-dimensional nature; most studies construct features instead by extracting patterns from raw transaction data. Past literature categorizes these features into recency, frequency, monetary, and anomaly detection features. We use various machine learning algorithms to examine the performance of features in these four categories with real transaction data; we compare them with the performance of our feature generation guideline based on the statistical perspectives and characteristics of (non)-fraudulent accounts. The results show that except for the monetary category, other feature categories used in the literature perform poorly regardless of which machine learning algorithm is used; anomaly detection features perform the worst. We find that even statistical features generated based on financial knowledge yield limited performance on a real transaction dataset. Our atypical detection characteristic of normal accounts improves the ability to distinguish them from fraudulent accounts and hence improves the overall detection results, outperforming other existent methods.

Serum Soluble B Cell-Activating Factor Is a Non-Invasive Biomarker of Antibody-Mediated Rejection in Kidney Allograft With Satisfactory Risk Stratification Performance But Negligible Diagnostic Value.

Objectives: B cell-activating factor (BAFF), which is critical in the activation and differentiation of B cells, is a candidate diagnostic and predictive biomarker for antibody-mediated rejection (ABMR). We aimed to investigate the value of serum soluble BAFF (sBAFF) for the diagnosis and risk stratification of ABMR after kidney transplantation. Methods: In the diagnostic study, sBAFF level among ABMR (n = 25), T cell-mediated rejection (TCMR) (n = 14), 4 other pathological lesions (n = 21), and stable allograft function group (n = 15) were compared. In the nested case-control study, kidney allograft recipients with de novo donor-specific antibody (DSA) or ABMR (n = 16) vs. stable allograft function (n = 7) were enrolled, and sBAFF was measured preoperatively, at D7, M1, M3, M6, M9, M12, M18 posttransplant and at allograft biopsy. Results: There was no significant difference in sBAFF level at biopsy between ABMR and non-ABMR groups. Longitudinal study showed that the sBAFF levels decreased dramatically at D7 in both groups. The sBAFF level in the DSA group started to increase within M1, while in the stable group, it maintained a low level until M3 and M6. The sBAFF levels of the DSA group were significantly higher than that of the stable group at M1 [1,013.23 (633.97, 1,277.38) pg/ml vs. 462.69 (438.77, 586.48) pg/ml, P = 0.005], M3 [1,472.07 (912.79, 1,922.08) pg/ml vs. 561.63 (489.77, 630.00) pg/ml, P = 0.002], and M6 [1,217.95 (965.25, 1,321.43) pg/ml vs. 726.93 (604.77, 924.60) pg/ml, P = 0.027]. sBAFF levels at M3 had the best predictive value for the DSA/ABMR with the area under the receiver operating characteristic (AUROC) curve value of 0.908. The predictive performance of the maximum (max) change rate from D7 to the peak within M3 was also excellent (AUROC 0.949, P = 0.580). Conclusion: We clarified by a diagnostic study that sBAFF is not a diagnostic biomarker for ABMR in kidney transplantation and revealed by a nested case-control study that sBAFF values at M3 posttransplant and dynamic changes in sBAFF within M3 posttransplant have a good predictive value for the DSA/ABMR. It provides a useful tool for early screening of low-risk patients with negative preoperative DSA for the risk of developing postoperative DSA in kidney allograft recipients.

Single kidney transplantation from pediatric deceased donors in China: the outcomes and risk factors of graft survival.

Background: Pediatric deceased donors offer great potential for expanding the organ donor pool. The utilization of pediatric donor kidneys has been explored by numerous transplant centers; however, the transplant outcome and risk factors have not been well elucidated. The aim of this study was to demonstrate the safety and risk factors of transplant outcome from pediatric deceased donors. Methods: We retrospectively analyzed 484 cases of single kidney transplantation (SKT) with pediatric donor kidneys performed at our center from January 2012 to March 2021. The recipients were grouped by age: child (≤12 years; n=143), adolescents (12-18 years; n=86), and adults (≥18 years; n=255). The overall prognosis of the recipients was analyzed, and the post-transplant outcomes were compared among the three groups and assessed by univariate and multivariate analyses using the Cox proportional risk model. Results: The median follow-up time was 26.7 months. The 1- and 3-year patient survival rates were 98.7% and 96.8%, respectively. The 1- and 3-year death-censored graft survival (DCGS) was 96.1% and 92.7%, respectively. The overall estimated glomerular filtration rates (eGFRs) at 1 and 3 years were 80.0±24.5 and 84.2±25.2 mL/min/1.73 m2; the 3-year eGFR of the three groups were comparable and all were over 80 mL/min/1.73 m2. Rejection was an independent risk factor for death-censored graft failure within 3 years after transplantation [hazard ratio (HR) =3.85; P=0.001], and was the primary cause of graft losses in the adolescent group. Thrombosis was more common within 1-month post-transplant in the child recipients (P<0.05), and its incidence was higher in recipients with donor body weight (DBW) ≤11 kg. Conclusions: SKT from pediatric donors could achieve decent outcomes. Rejection was an independent risk factor of graft survival, especially for adolescent recipients. Child recipients may compromise early transplant outcomes due to vascular thrombosis, which might be related to small (DBW ≤11 kg) pediatric donors.

CCL18 enhances migration, invasion and EMT by binding CCR8 in bladder cancer cells.

Increased expression of CCL18 has been observed in various malignancies and in the urine samples of patients with bladder cancer (BC). However, the roles of CCL18 in the development, progression and metastasis of BC remain unclear. The present study demonstrated that CCL18 expression was significantly associated with advanced clinical stages of BC. Furthermore, exogenous CCL18 promoted cell invasion and migration, and induced cell epithelial­mesenchymal transition (EMT) in BC cells. Western blotting demonstrated that E­cadherin, an epithelial marker, was decreased, whereas matrix metalloproteinase (MMP)­2 and vascular endothelial growth factor (VEGF)­C were increased in CCL18­treated cells. Blocking CCR8 via a small molecule inhibitor or short hairpin (sh)RNA mitigated the decrease in E­cadherin, and increase in MMP­2 and VEGF­C, caused by human recombinant (r)CCL18. CCR8 knockdown by shRNA reversed rCCL18­induced cancer cell invasion, migration and EMT. In conclusion, these data suggested that CCL18 may promote migration, invasion and EMT by binding CCR8 in BC cells. Inhibition of CCL18 activity by blocking CCR8 could be a potential therapeutic strategy for preventing the progression of BC.

Celecoxib inhibits the epithelial-to-mesenchymal transition in bladder cancer via the miRNA-145/TGFBR2/Smad3 axis.

Celecoxib, a selective cyclooxygenase­2 inhibitor, has chemo­preventive activity against different cancer types, including bladder cancer (BC). However, the mechanisms by which celecoxib exerts its cancer preventative effects have yet to be completely understood. In the present study, the effect of celecoxib on the epithelial­to­mesenchymal transition (EMT) of BC cells and its potential molecular mechanisms were investigated. The results of the present study demonstrated that celecoxib inhibited the proliferation, migration, invasion and EMT of BC cells. Further investigation of the underlying mechanism revealed that celecoxib inhibited EMT by upregulating microRNA (miR)­145 and downregulating the expression of transforming growth factor ß receptor 2 and SMAD family member 3. Furthermore, the combination of celecoxib with miR­145 mimics demonstrated an additive migration and invasion­inhibitory effect in BC cell lines.

Isoform-selective substrates of nitric oxide synthase.

Because of the double-edged nature of NO, the development of isoform-selective NOS substrates is a highly desirable goal. Given the striking similarity in the heme active sites of the three NOS isoforms, it presents an challenging problem. Several N-aryl-N'-hydroxyguanidines have recently been shown as substrates that are selective for iNOS over nNOS. Here, we report the first success that 3 is a good substrate for nNOS (70% activity of NOHA, K(m) approximately 40 +/- 6 microM) over iNOS.

Cross-linked surface-grafted glycopolymer for multivalent recognition of lectin.

An alpha-link mannose-conjugated acrylamide monomer was synthesized. This monomer was polymerized by free radical polymerization with acrylamide, a cross-linker, and a surface linker directly on the gold surface. The surface linker, with an active carbon-carbon double bond, was preimmobilized on the gold surface by the thiol anchor. Thus, a cross-linked mannose-conjugated polymer thin layer was grafted onto a gold surface. This thin layer of polymer showed high binding sensitivity and excellent selectivity to its target lectin, concanavalin A (Con A), surpassing the formerly used linear glycopolymer and self-assembled glycol monolayers, validated by the techniques of quartz crystal microbalance, atomic force microscopy, and surface plasmon resonance. Remarkable response was observed to Con A at a concentration as low as 5 x 10(-10) M. The response is proportional to the Con A concentration up to 10(-7) M in phosphate-buffered saline. The use of cross-linked polymer decreased the flexibility of the polymer backbone between the carbohydrate binding sites. Therefore, the cost of conformational entropy for multivalent binding was minimized. The binding constants of the so-prepared cross-linked polymer with Con A were measured to be between 2.5 x 10(6) and 3.2 x 10(6) M(-1). These values are significantly larger than that obtained in our early study with a carbohydrate self-assembled monolayer. In addition to the carbohydrate-lectin recognition, additional selectivity may be achieved by controlling the degree of cross-linking.

Alkanethiol containing glycopolymers: a tool for the detection of lectin binding.

Glycopolymers are useful macromolecules with a non-carbohydrate backbone for presenting saccharides in multivalent form. Here, glycopolymers containing mannose and alkanethiol linker were synthesized through substituting preactivated poly [N-(acryloyloxy) succinimide] (pNAS) with amine-containing monomer. With the obtained glycopolymers, a glycosurface was generated on the gold surface of quartz crystal microbalance (QCM) through self-assembled strategy by the use of alkanethiol functional group. Furthermore, the resulting glycosurface was used to detect the binding of mannose specific lectin concanavalin A (Con A).

Nonlabeled quartz crystal microbalance biosensor for bacterial detection using carbohydrate and lectin recognitions.

High percentages of harmful microbes or their secreting toxins bind to specific carbohydrate sequences on human cells at the recognition and attachment sites. A number of studies also show that lectins react with specific structures of bacteria and fungi. In this report, we take advantage of the fact that a high percentage of microorganisms have both carbohydrate and lectin binding pockets at their surface. We demonstrate here for the first time that a carbohydrate nonlabeled mass sensor in combination with lectin-bacterial O-antigen recognition can be used for detection of high molecular weight bacterial targets with remarkably high sensitivity and enhanced specificity. A functional mannose self-assembled monolayer in combination with lectin concanavalin A (Con A) was used as molecular recognition elements for the detection of Escherichia coli W1485 using a quartz crytsal microbalance (QCM) as a transducer. The multivalent binding of Con A to the E. coli surface O-antigen favors the strong adhesion of E. coli to the mannose-modified QCM surface by forming bridges between these two. As a result, the contact area between cell and QCM surface that increases leads to rigid and strong attachment. Therefore, it enhances the binding between E. coli and the mannose. Our results show a significant improvement of the sensitivity and specificity of the carbohydrate QCM biosensor with a experimental detection limit of a few hundred bacterial cells. The linear range is from 7.5 x 10(2) to 7.5 x 10(7) cells/mL, which is four decades wider than the mannose-alone QCM sensor. The change of damping resistances for E. coli adhesion experiments was no more than 1.4%, suggesting that the bacterial attachment was rigid, rather than a viscoelastic behavior. Little nonspecific binding was observed for Staphylococcus aureus and other proteins (fetal bovine serum, Erythrina cristagalli lectin). Our approach not only overcomes the challenges of applying QCM technology for bacterial detection but also increases the binding of bacteria to their carbohydrate receptor through bacterial surface binding lectins that significantly enhanced specificity and sensitivity of QCM biosensors. Combining carbohydrate and lectin recognition events with an appropriate QCM transducer can yield sensor devices highly suitable for the fast, reversible, and straightforward on-line screening and detection of bacteria in food, water, and clinical and biodefense areas.

A study of heart sound and lung sound separation by independent component analysis technique.

In the hospital, using percussion and auscultation are the most common ways for physical examination. Recently, in order to develop tele-medicine and home care system and to assist physician getting better auscultation results; electric stethoscope and computer analysis have become an inevitable trend. However, two important physical signals heart sound and lung sound recorded from chest overlap on spectrum chart. Therefore, in order to reduce human factor (ex. misplace or untrained of using) and minimize correlated effect in computer analysis; it's necessary for separated heart sound and lung sound. Independent component analysis can divide these sounds efficiency. In this paper, we use two microphones to collect signals from left and right chest. We have successfully divide heart and lung sounds by fast ICA algorithm. Therefore, it can assist physician examine and also using on tele-medicine and home care by this way.