Explore the vast range of titles available.

The poor sensitivity of clear cell renal cell carcinoma (ccRCC) to conventional chemotherapy and radiotherapy makes its treatment challenging. The Ndc80 kinetochore complex component (NUF2) is involved in the development and progression of several cancers. However, its role in ccRCC remains unclear. In this study, we investigated the biological functions and underlying mechanism of NUF2 in ccRCC. We found that NUF2 expression was increased in ccRCC and associated with poor prognosis. Altering NUF2 level affected cell proliferation, migration, and invasion. Moreover, NUF2 acted as a potential oncogene to promote the progression of ccRCC through epigenetic activation of high-mobility group AT-hook 2 (HMGA2) transcription by suppressing lysine demethylase 2A expression and affecting its occupancy on the promoter region to regulate histone H3 lysine 36 di-methylation modification. In addition, Kaplan-Meier and multivariate analysis revealed that patients whose NUF2 and HMGA2 were both elevated showed the shortest survival; and the number of upregulated markers acted as an independent predictor to evaluate survival probability. Thus, our results demonstrate that NUF2 promotes ccRCC progression, at least partly by epigenetically regulating HMGA2 transcription, and that the NUF2-HMGA2 axis could be an ideal therapeutic target and a promising prognostic indicator for ccRCC.

Transmembrane protein 52B (TMEM52B), a newly identified tumor‐related gene, has been reported to regulate various tumors, yet its role in nasopharyngeal carcinoma (NPC) remains unclear. Transcriptomic analysis of NPC cell lines reveals frequent overexpression of TMEM52B, and immunohistochemical results show that TMEM52B is associated with advanced tumor stage, recurrence, and decreased survival time. Depleting TMEM52B inhibits the proliferation, migration, invasion, and oncogenesis of NPC cells in vivo. TMEM52B encodes two isoforms, TMEM52B‐P18 and TMEM52B‐P20, differing in their N‐terminals. While both isoforms exhibit similar pro‐oncogenic roles and contribute to drug resistance in NPC, TMEM52B‐P20 differentially promotes metastasis. This functional discrepancy may be attributed to their distinct subcellular localization; TMEM52B‐P18 is confined to the cytoplasm, while TMEM52B‐P20 is found both at the cell membrane and in the cytoplasm. Mechanistically, cytoplasmic TMEM52B enhances AKT phosphorylation by interacting with phosphoglycerate kinase 1 (PGK1), fostering NPC growth and metastasis. Meanwhile, membrane‐localized TMEM52B‐P20 promotes E‐cadherin ubiquitination and degradation by facilitating its interaction with the E3 ubiquitin ligase NEDD4, further driving NPC metastasis. In conclusion, the TMEM52B‐P18 and TMEM52B‐P20 isoforms promote the metastasis of NPC cells through different mechanisms. Drugs targeting these TMEM52B isoforms may offer therapeutic benefits to cancer patients with varying degrees of metastasis. TMEM52B represents a promising biomarker for early diagnosis and prognostic prediction in nasopharyngeal carcinoma (NPC). Mechanistically, cytoplasmic TMEM52B‐P18 and TMEM52B‐P20 promote AKT phosphorylation by interacting with PGK1, thereby activating AKT signaling and driving NPC Carcinoma. On the other hand, membrane‐bound TMEM52B‐P20 induces the ubiquitination of E‐cadherin by NEDD4 and degrades it, thus promoting metastasis.

Bladder cancer poses severe threats to human health due to its aggressive nature and resistance to drug treatment; however, the underlying mechanisms have not been fully investigated. In the present study, we identify SBSPON (Somatomedin B and Thrombospondin Type 1 Domain Containing) as a novel tumor suppressor. The expression of SBSPON was downregulated in bladder cancer and correlated with poor overall survival. SBSPON suppressed the proliferation and migration ability of bladder cancer cells , and inhibited tumor growth of bladder cancer cells . Genetic ablation of in mice significantly accelerated the progression of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) induced bladder cancer. Mechanistically, SBSPON is a novel HSPA5 binding glycoprotein. SBSPON functioned through binding to HSPA5 and inhibiting its membrane translocation, resulting in an inactivated AKT signaling pathway. More importantly, SBSPON inhibited the cisplatin resistance of bladder cancer cells by reducing the inhibitory effect of HSPA5 on apoptosis. In summary, the novel glycoprotein SBSPON functions as a tumor suppressor and inhibits resistance to cisplatin in bladder cancer. This may provide novel therapeutic strategies for bladder cancer treatment.

Land scarcity has become the prominent obstacle on the way to sustainable development for China. Under the constraints of land shortage, how to allocate the finite land resources to the multiple land users in China considering various political, environmental, ecological and economic conditions have become research topics with great significance. In this study, an interval fuzzy national-scale land-use model（IFNLM） was developed for optimizing land systems of China. IFNLM is based on an integration of existing interval linear programming（ILP）, and fuzzy flexible programming（FFP） techniques. IFNLM allows uncertainties expressed as discrete interval values and fuzzy sets to be incorporated within a general optimization framework. It can also facilitate national-scale land-use planning under various environmental, ecological, social conditions within a multi-period and multi-option context. Then, IFNLM was applied to a real case study of land-use planning in China. The satisfaction degree of environmental constraints is between 0.69 and 0.97, the system benefit will between 198.25 × 1012 USD and 229.67 × 1012 USD. The results indicated that the hybrid model can help generate desired policies for land-use allocation with a maximized economic benefit and minimized environmental violation risk. Optimized land-use allocation patterns can be generated from the proposed IFNLM.

Melatonin (MT) plays integral roles in regulating several biological processes including plant growth, seed germination, flowering, senescence, and stress responses. This study investigated the effects of MT on adventitious root formation (ARF) of de-rooted tomato seedlings. Exogenous MT positively or negatively influenced ARF, which was dependent on the concentration of MT application. In the present experiment, 50 μM MT showed the best effect on inducing ARF. Interestingly, exogenous MT promoted the accumulation of endogenous nitric oxide (NO) by down-regulating the expression of S-nitrosoglutathione reductase (GSNOR). To determine the interaction of MT and NO in ARF, MT synthesis inhibitor p-chlorophenylalanine, NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt as well as GSNOR-overexpression plants with low NO levels were used. The function of MT was removed by NO scavenger or GSNOR-overexpression plants. However, application of MT synthesis inhibitor did little to abolish the function of NO. These results indicate that NO, as a downstream signal, was involved in the MT-induced ARF. Concentrations of indole-3-acetic acid and indole-3-butyric acid, as well as the expression of several genes related to the auxin signaling pathway (PIN1, PIN3, PIN7, IAA19, and IAA24), showed that MT influenced auxin transport and signal transduction as well as auxin accumulation through the NO signaling pathway. Collectively, these strongly suggest that elevated NO levels resulting from inhibited GSNOR activity and auxin signaling were involved in the MT-induced ARF in tomato plants. This can be applied in basic research and breeding.

Efficacious interventions are urgently needed for the treatment of COVID-19. Here, we report a monoclonal antibody (mAb), MW05, with SARS-CoV-2 neutralizing activity by disrupting the interaction of receptor binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2) receptor. Crosslinking of Fc with FcγRIIB mediates antibody-dependent enhancement (ADE) activity by MW05. This activity is eliminated by introducing the LALA mutation to the Fc region (MW05/LALA). Potent prophylactic and therapeutic effects against SARS-CoV-2 are observed in rhesus monkeys. A single dose of MW05/LALA blocks infection of SARS-CoV-2 in prophylactic treatment and clears SARS-CoV-2 in three days in a therapeutic treatment setting. These results pave the way for the development of MW05/LALA as an antiviral strategy for COVID-19. Here the authors characterize a monoclonal antibody from a COVID-19 convalescent patient that interferes with SARS-CoV-2 spike binding to ACE2 and has prophylactic and therapeutic activity in non-human primates. Antibody-dependent enhancement of infection is prevented by mutating the Fc region of the antibody.

Consumers and marketers use facial information to make important inferences about others in many business contexts. However, consumers and firms are increasingly concerned about privacy and discrimination. To address privacy–perception trade-offs, the authors propose a novel contour-as-face (CaF) framework that transforms face images into contour images incorporating both the nonoutline and outline features of facial parts. In three empirical studies, the authors (1) compare human perceptions of face and contour images along 15 dimensions commonly assessed in marketing contexts; (2) investigate the effectiveness of contour images for protecting anonymity related to identity, age, and gender; and (3) implement the CaF framework in a real-life online dating context. Results show that the CaF framework effectively resolves privacy–perception trade-off problems by preserving the information that is useful for humans to make inferences about many relevant perceptual dimensions in marketing while making it virtually impossible for humans to infer identity and very difficult to infer age and gender accurately—two critical discrimination factors. Results from the field implementation demonstrate the feasibility and value of using the CaF framework for real-life decision making.

In this paper, we propose an automated and scalable garment recommender system using real-time in-store videos that can improve the experiences of garment shoppers and increase product sales. The video-based automated recommender (VAR) system is based on observations that garment shoppers tend to try on garments and evaluate themselves in front of store mirrors. Combining state-of-the-art computer vision techniques with marketing models of consumer preferences, the system automatically identifies shoppers’ preferences based on their reactions and uses that information to make meaningful personalized recommendations. First, the system uses a camera to capture a shopper’s behavior in front of the mirror to make inferences about her preferences based on her facial expressions and the part of the garment she is examining at each time point. Second, the system identifies shoppers with preferences similar to the focal customer from a database of shoppers whose preferences, purchasing, and/or consideration decisions are known. Finally, recommendations are made to the focal customer based on the preferences, purchasing, and/or consideration decisions of these like-minded shoppers. Each of the three steps can be implemented with several variations, and a retailing chain can choose the specific configuration that best serves its purpose. In this paper, we present an empirical test that compares one specific type of VAR system implementation against two alternative, nonautomated personal recommender systems: self-explicated conjoint (SEC) and self-evaluation after try-on (SET). The results show that VAR consistently outperforms SEC and SET. A second empirical study demonstrates the feasibility of VAR in real-time applications. Participants in the second study enjoyed the VAR experience, and almost all of them tried on the recommended garments. VAR should prove to be a valuable tool for both garment retailers and shoppers. Data, as supplemental material, are available at http://dx.doi.org/10.1287/mksc.2016.0984 .

Electrical stimulation (ES) therapy has good effects in patients with nervous system injury-related diseases. ES promotes nerve cell regeneration and stimulates Schwann cells to express neurotrophic factors. The incidence of stress urinary incontinence (SUI) among elderly people is increasing. Some studies suggest that damage to the pudendal nerve is closely related to the pathogenesis of SUI. It has also been found that pelvic ES can reduce SUI symptoms in a rat model of SUI caused by pudendal nerve injury. Clinically, pelvic floor electrical stimulation is effective in patients with mild to moderate SUI. These studies indicate that ES may ameliorate damage to the pudendal nerve and thus achieve the goal of SUI treatment, although the mechanism of action of this treatment remains unclear. Therefore, the purpose of the present study was to clarify the relationships among ES, neural cells and Schwann cells at the cellular level. We applied ES to nerve cells at 100 mV/mm or 200 mV/mm for 0, 0.5, 1, or 2 h to investigate changes in nerve cell activity. We then co-cultured the nerve cells with Schwann cells to explore the influence of single-culture and co-culture conditions on the nerve cells. Compared to non-ES, ES of the nerve cells increased their activity. Compared to those in single culture, co-cultured nerve cells exhibited an additional increase in activity. We also found that Schwann cell derived exosomes could promote the activity of nerve cells, with glutamate and calcium ions playing a potential role in this process. These results suggest that the mutual regulation of neural cells and Schwann cells plays an important role in the process by which ES ameliorates neurological function, which may provide a basis for subsequent studies.

A molecular classification of diseases that accurately reflects clinical behaviour lays the foundation of precision medicine. The development of in silico classifiers coupled with molecular implementation based on DNA reactions marks a key advance in more powerful molecular classification, but it nevertheless remains a challenge to process multiple molecular datatypes. Here we introduce a DNA-encoded molecular classifier that can physically implement the computational classification of multidimensional molecular clinical data. To produce unified electrochemical sensing signals across heterogeneous molecular binding events, we exploit DNA-framework-based programmable atom-like nanoparticles with n valence to develop valence-encoded signal reporters that enable linearity in translating virtually any biomolecular binding events to signal gains. Multidimensional molecular information in computational classification is thus precisely assigned weights for bioanalysis. We demonstrate the implementation of a molecular classifier based on programmable atom-like nanoparticles to perform biomarker panel screening and analyse a panel of six biomarkers across three-dimensional datatypes for a near-deterministic molecular taxonomy of prostate cancer patients. The authors use a DNA-framework-based molecular classifier to perform biomarker panel screening and analyse six biomarkers across three-dimensional datatypes to obtain a molecular taxonomy for prostate cancer diagnosis.