Retinoic acid receptor gamma is required for proliferation of pancreatic cancer cells.

Despite the expectation that retinoic acid receptor could be the potential therapeutic targets for pancreatic cancers, there has been the lack of information about the role and the impact of retinoic acid receptor gamma (RARγ, RARG) on pancreatic cancer, unlike other two RARs. Herein, we applied TCGA and GEO database to show that the expression and prognosis of RARG is closely related to pancreatic cancer, which demonstrates that RARG is commonly overexpressed in human pancreatic cancer and is an independent diagnostic marker predicting the poor prognosis of pancreatic cancer patients. In addition, we demonstrated that the reduction in the expression of RARG in human pancreatic cancer cells dramatically suppress their proliferation and tumor growth in vivo, partially attributable to the downregulation of tumor-supporting biological processes such as cell proliferation, antiapoptosis and metabolism and the decreased expression of various oncogenes like MYC and STAT3. Mechanistically, RARG binds on the promoters of MYC, STAT3, and SLC2A1 which is distinguished from well-known conventional Retinotic acid response elements (RAREs) and that the binding is likely to be responsible for the epigenetic activation in the level of chromatin, assessed by the measurement of deposition of the gene activation marker histone H3 K27 acetylation (H3K27ac) using ChIP-qPCR. In this study, we reveal that RARG plays important role in the tumorigenesis of pancreatic cancer and represents new therapeutic targets for human pancreatic cancer.

Dissociation of FK506-binding protein 12.6 kD from ryanodine receptor in bronchial smooth muscle cells in airway hyperresponsiveness in asthma.

Airway hyperresponsiveness (AHR) in asthma is predominantly caused by increased sensitivity of bronchial smooth muscle cells (BSMCs) to stimuli. The sarcoplasmic reticulum (SR)-Ca(2+) release channel, known as ryanodine receptor (RyR), mediates the contractive response of BSMCs to stimuli. FK506-binding protein 12.6 kD (FKBP12.6) stabilizes the RyR2 channel in a closed state. However, the interaction of FKBP12.6 with RyR2 in AHR remains unknown. This study examined the interaction of FKBP12.6 with RyR2 in BSMCs in AHR of asthma. The interaction of FKBP12.6 with RyR2 and FKBP12.6 expression was determined in a rat asthma model and in BSMCs treated with inflammatory cytokines. The calcium responses to contractile agonists were determined in BSMCs with overexpression and knockdown of FKBP12.6. Asthmatic serum, IL-5, IL-13, and TNF-α enhance the calcium response of BSMCs to contractile agonists and cause dissociation of FKBP12.6 from RyR2 and a decrease in FKBP12.6 gene expression in BSMCs in culture and in ovalbumin (OVA)-sensitized and -challenged rats. Knockdown of FKBP12.6 in BSMCs causes a decrease in the association of RyR2 with FKBP12.6 and an increase in the calcium response of BSMCs. Overexpression of FKBP12.6 increases the association of FKBP12.6 with RyR2, decreases the calcium response of BSMCs, and normalizes airway responsiveness in OVA-sensitized and -challenged rats. Dissociation of FKBP12.6 from RyR2 in BSMCs is responsible for the increased calcium response contributing to AHR in asthma. Manipulating the interaction of FKBP12.6 with RyR2 might be a novel and useful treatment for asthma.

[Retracted] MicroRNA­15a­5p­targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell invasion assay data shown in Fig. 3A and B on p. 1306 were strikingly similar to data appearing in different form in a paper by different authors at a different research institute that had already been submitted for publication. Owing to the fact that the contentious data in the above article had already been submitted for publication prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 46: 1301­1310, 2020; DOI: 10.3892/ijmm.2020.4704].

miR-425-5p Regulates Proliferation of Bovine Mammary Epithelial Cells by Targeting TOB2.

In recent years, rising temperatures have caused heat stress (HS), which has had a significant impact on livestock production and growth, presenting considerable challenges to the agricultural industry. Research has shown that miR-425-5p regulates cellular proliferation in organisms. However, the specific role of miR-425-5p in bovine mammary epithelial cells (BMECs) remains to be determined. The aim of this study was to investigate the potential of miR-425-5p in alleviating the HS-induced proliferation stagnation in BMECs. The results showed that the expression of miR-425-5p significantly decreased when BMEC were exposed to HS. However, the overexpression of miR-425-5p effectively alleviated the inhibitory effect of HS on BMEC proliferation. Furthermore, RNA sequencing analysis revealed 753 differentially expressed genes (DEGs), comprising 361 upregulated and 392 downregulated genes. Some of these genes were associated with proliferation and thermogenesis through enrichment analyses. Further experimentation revealed that TOB2, which acts as a target gene of miR-425-5p, is involved in the regulatory mechanism of BMEC proliferation. In summary, this study suggests that miR-425-5p can promote the proliferation of BMECs by regulating TOB2. The miR-425-5p/TOB2 axis may represent a potential pathway through which miR-425-5p ameliorates the proliferation stagnation of BMECs induced by HS.

Dynamical interplay between superconductivity and pseudogap in cuprates as revealed by terahertz third-harmonic generation spectroscopy.

We report on nonlinear terahertz third-harmonic generation (THG) measurements on YBa2Cu3O6+x thin films. Different from conventional superconductors, the THG signal starts to appear in the normal state, which is consistent with the crossover temperature T* of pseudogap over broad doping levels. Upon lowering the temperature, the THG signal shows an anomaly just below Tc in the optimally doped sample. Notably, we observe a beat pattern directly in the measured real-time waveform of the THG signal. We elaborate that the Higgs mode, which develops below Tc, couples to the mode already developed below T*, resulting in an energy level splitting. However, this coupling effect is not evident in underdoped samples. We explore different potential explanations for the observed phenomena. Our research offers valuable insight into the interplay between superconductivity and pseudogap.

Phonon promoted charge density wave in topological kagome metal ScV6Sn6.

Charge density wave (CDW) orders in vanadium-based kagome metals have recently received tremendous attention, yet their origin remains a topic of debate. The discovery of ScV6Sn6, a bilayer kagome metal featuring an intriguing [Formula: see text] CDW order, offers a novel platform to explore the underlying mechanism behind the unconventional CDW. Here, we combine high-resolution angle-resolved photoemission spectroscopy, Raman scattering and density functional theory to investigate the electronic structure and phonon modes of ScV6Sn6. We identify topologically nontrivial surface states and multiple van Hove singularities (VHSs) in the vicinity of the Fermi level, with one VHS aligning with the in-plane component of the CDW vector near the [Formula: see text] point. Additionally, Raman measurements indicate a strong electron-phonon coupling, as evidenced by a two-phonon mode and new emergent modes. Our findings highlight the fundamental role of lattice degrees of freedom in promoting the CDW in ScV6Sn6.

[Operative strategies for bilateral brain contusion and laceration].

OBJECTIVE: To explore the operative strategies for bilateral brain contusion and laceration and evaluate their clinical significance. METHODS: Based on the clinical manifestations, computed tomography (CT) and intracranial pressure (ICP), different operative strategies were applied to 25 cases of bilateral brain contusion and laceration. The strategies were classified into 6 types according to the principles of decompression and brain protection.All cases received routine treatments at neurosurgical intensive care unit (ICU) ward. And the occurrences of operative complications and 6-month Glasgow outcome scale (GOS) were statistically analyzed. RESULTS: Type 1:4 cases of unilateral decompressive craniectomy without resection of contusion focus; Type 2:8 cases of unilateral decompressive craniectomy with resection of bilateral contusion focus; Type 3:5 cases of bilateral decompressive craniectomy with resection of unilateral brain contusion; Type 4:5 cases of bilateral decompressive craniectomy; Type 5:1 case of bilateral brain contusion resection; Type 6:2 cases of bilateral decompressive craniectomy and brain contusion resection.Postoperative complications such as epilepsy, expanding contusion foci, brain infarction, encephalocele, incisional CSF leakage, intracranial infection, subdural hydroma and hydrocephalus were rare. The 6-month GOS revealed 6 cases of good outcome (n = 6), moderate disability (n = 8), severe disability (n = 3) and vegetative status (n = 5) and death (n = 3). CONCLUSION: Different operative strategies may be applied for severe brain contusion and laceration according to their clinical manifestations, CT findings and ICP values. And the efficacies are improved by operative strategies based on the principles of ICP control, prevention of secondary injury and brain function preservation.

Effects of anesthetic adjunctive agents on postoperative cognitive dysfunction in elderly patients undergoing noncardiac surgery: A Bayesian network meta-analysis.

BACKGROUND: Elderly patients are prone to postoperative cognitive dysfunction (POCD). The comparison of the effects of anesthetic adjuvant drugs on POCD in elderly patients undergoing noncardiac surgery remains controversial. METHODS: The final search took place on June 10, 2023. Randomized controlled trials including ketamine, ulinastatin, dexmedetomidine, parecoxib, and midazolam on the prevention and treatment of POCD in elderly undergoing noncardiac surgery were collected. A Bayesian network meta-analysis was performed to quantitatively combine the evidence. RESULTS: A total of 35 randomized trials were finally included in this systematic review, and the overall risk of bias is Allocation concealment. These anesthetic adjuvant drugs did not show significant differences in preventing POCD on postoperative days 1 and 7 compared with each other, but ulinastatin may be more effective in preventing POCD than dexmedetomidine [odds ratio (OR) = 0.28, 95% confidence interval (CI) = (0.10, 0.71)] and parecoxib [OR = 0.3, 95% CI = (0.10, 0.82 on postoperative day 3. The efficiency ranking results also find that ulinastatin and ketamine might provide better effects regarding POCD prevention. CONCLUSIONS: Ketamine and ulinastatin might have better effects in preventing POCD in elderly patients undergoing noncardiac surgery. Our meta-analysis provided evidence for the use of ulinastatin and ketamine in the prevention of POCD in elderly patients undergoing noncardiac surgery.

An ultrasmall PVP-Fe-Cu-Ni-S nano-agent for synergistic cancer therapy through triggering ferroptosis and autophagy.

Photothermal therapy (PTT) is an emerging field where photothermal agents could convert visible or near-infrared (NIR) radiation into heat to kill tumor cells. However, the low photothermal conversion efficiency of photothermal agents and their limited antitumor activities hinder the development of these agents into monotherapies for cancer. Herein, we have fabricated an ultrasmall polyvinylpyrrolidone (PVP)-Fe-Cu-Ni-S (PVP-NP) nano-agent via a simple hot injection method with excellent photothermal conversion efficiency (∼96%). Photothermal therapy with this nano-agent effectively inhibits tumor growth without apparent toxic side-effects. Mechanistically, our results demonstrated that, after NIR irradiation, PVP-NPs can induce ROS/singlet oxygen generation, decrease the mitochondrial membrane potential, release extracellular Fe2+, and consume glutathione, triggering autophagy and ferroptosis of cancer cells. Moreover, PVP-NPs exhibit excellent contrast enhancement according to magnetic resonance imaging (MRI) analysis. In summary, PVP-NPs have a high photothermal conversion efficiency and can be applied for MRI-guided synergistic photothermal/photodynamic/chemodynamic cancer therapy, resolving the bottleneck of existing phototherapeutic agents.

PSMD2 contributes to the progression of esophageal squamous cell carcinoma by repressing autophagy.

BACKGROUND: The ubiquitin-proteasome and autophagy-lysosomal systems collaborate in regulating the levels of intracellular proteins. Dysregulation of protein homeostasis is a central feature of malignancy. The gene encoding 26S proteasome non-ATPase regulatory subunit 2 (PSMD2) of the ubiquitin-proteasome system is an oncogene in various types of cancer. However, the detailed role of PSMD2 in autophagy and its relationship to tumorigenesis in esophageal squamous cell carcinoma (ESCC) remain unknown. In the present study, we have investigated the tumor-promoting roles of PSMD2 in the context of autophagy in ESCC. METHODS: Molecular approaches including DAPgreen staining, 5-Ethynyl-2'-deoxyuridine (EdU), cell counting kit 8 (CCK8), colony formation, transwell assays, and cell transfection, xenograft model, immunoblotting and Immunohistochemical analysis were used to investigate the roles of PSMD2 in ESCC cells. Data-independent acquisition (DIA) quantification proteomics analysis and rescue experiments were used to study the roles of PSMD2 in ESCC cells. RESULTS: We demonstrate that the overexpression of PSMD2 promotes ESCC cell growth by inhibiting autophagy and is correlated with tumor progression and poor prognosis of ESCC patients. DIA quantification proteomics analysis shows a significant positive correlation between argininosuccinate synthase 1 (ASS1) and PSMD2 levels in ESCC tumors. Further studies indicate that PSMD2 activates the mTOR pathway by upregulating ASS1 to inhibit autophagy. CONCLUSIONS: PSMD2 plays an important role in repressing autophagy in ESCC, and represents a promising biomarker to predict prognosis and a therapeutic target of ESCC patients.

Revealing the frequency-dependent oscillations in the nonlinear terahertz response induced by the Josephson current.

Nonlinear responses of superconductors to intense terahertz radiation has been an active research frontier. Using terahertz pump-terahertz probe spectroscopy, we investigate the c-axis nonlinear optical response of a high-temperature superconducting cuprate. After excitation by a single-cycle terahertz pump pulse, the reflectivity of the probe pulse oscillates as the pump-probe delay is varied. Interestingly, the oscillatory central frequency scales linearly with the probe frequency, a fact widely overlooked in pump-probe experiments. By theoretically solving the nonlinear optical reflection problem on the interface, we show that our observation is well explained by the Josephson-type third-order nonlinear electrodynamics, together with the emission coefficient from inside the material into free space. The latter results in a strong enhancement of the emitted signal whose physical frequency is around the Josephson plasma edge. Our result offers a benchmark for and new insights into strong-field terahertz spectroscopy of related quantum materials.

Propensity score matching comparing short-term nerve electrical stimulation to pulsed radiofrequency for herpes zoster-associated pain: A retrospective study.

Background: Zoster-associated pain (ZAP) is notoriously difficult to treat. Pulsed radiofrequency (PRF) and short-term nerve electrical stimulation (st-NES) have been proven effective treatments for ZAP. However, it is still unclear which technique provides improved analgesia in ZAP. This study is based on a large-scale, long-term follow-up to evaluate the efficacy and safety between st-NES and PRF. Materials and methods: All eligible ZAP patients treated with st-NES or PRF in our department were enrolled. Cohorts were divided into the st-NES group and the PRF group. A 1:1 ratio propensity score matching (PSM) was used to balance the baseline characteristics. The PS-matched cohort was adopted to investigate the efficacy and safety of the two treatments. The ordinal regression analysis was performed to determine the variables affecting the treatment effect of ZAP. Results: A total of 226 patients were included after PSM. The numerical rating scale (NRS) scores in st-NES and PRF groups considerably reduced compared to baseline levels after treatment. The NRS scores in the st-NES group were obviously lower than those in the PRF group at discharge, 1, 3, 6, 12, and 24 months. During the follow-up period, the NRS reduction rate remained higher in the st-NES group than in the PRF group (P < 0.01). The dosage of medication, Pittsburgh Sleep Quality Index (PSQI) score, and the number of patients with aggravated pain after discharge in the st-NES group were significantly less than in the PRF group after treatment. Conclusion: Short-term nerve electrical stimulation has been shown to be more advantageous than PRF for pain relief and quality of life improvement for ZAP patients.

Unveiling the Degradation Mechanism of High-Temperature Superconductor Bi2Sr2CaCu2O8+δ in Water-Bearing Environments.

The physical properties of copper oxide high-temperature superconductors have been studied extensively, such as the band structure and doping effects of Bi2Sr2CaCu2O8+δ (Bi-2212). However, some chemical-related properties of these superconductors are rarely reported, such as their stability in water-bearing environments. Herein, we report experiments combined with ab initio calculations that address the effects of water in contact with Bi-2212. The evolution of Bi-2212 flakes with exposure to water for different time intervals was tested and characterized by optical microscopy (OM), atomic force microscopy (AFM), Raman spectroscopy, transmission electron microscopy (TEM), and electrical measurements. The thickness of Bi-2212 flakes is gradually decreased in water, and some thin flakes can be completely etched away after a few days. The stability of Bi-2212 in other solvents is also evaluated, including alcohol, acetone, HCl, and KOH. The morphology of Bi-2212 flakes is relatively stable in organic solvents. However, the flakes are etched relatively quick in HCl and KOH, especially in an acidic environment. Our results imply that hydrogen ions are primarily responsible for the deterioration of their properties. Both TEM and calculation results demonstrate that the atoms in the Bi-O plane are relatively stable when compared to the inner atoms in Sr-O, Ca-O, and Cu-O planes. This work contributes toward understanding the chemical stability of a Bi-2212 superconducting device in environmental medium, which is important for both fundamental studies and practical applications of copper oxide high-temperature superconductors.

Fully Integrated Self-Powered Electrical Stimulation Cell Culture Dish for Noncontact High-Efficiency Plasmid Transfection.

Plasmid DNA transfection of mammalian cells is widely used in biomedical research and genetic drug delivery, but low transfection efficiency, especially in the context of the primary cells, limits its application. To improve the efficiency of plasmid transfection, a fully integrated self-powered electrical stimulation cell culture dish (SESD) has been developed to provide self-powered electrical stimulation (ES) of adherent cells, significantly improving the efficiency of plasmid transfection into mammalian cells and cell survival by the standard lipofectamine transfection method. Mechanistically, ES can safely increase the intracellular calcium concentration by opening calcium-ion channels, leading to a higher efficiency of plasmid transfection. Therefore, SESD has the potential to become an effective platform for high-efficiency plasmid DNA transfection in biomedical research and drug delivery.

Core-Shell-Like Structured Co3O4@SiO2 Catalyst for Highly Efficient Catalytic Elimination of Ozone.

Co3O4 is an environmental catalyst that can effectively decompose ozone, but is strongly affected by water vapor. In this study, Co3O4@SiO2 catalysts with a core-shell-like structure were synthesized following the hydrothermal method. At 60% relative humidity and a space velocity of 720,000 h-1, the prepared Co3O4@SiO2 obtained 95% ozone decomposition for 40 ppm ozone after 6 h, which far outperformed that of the 25wt% Co3O4/SiO2 catalysts. The superiority of Co3O4@SiO2 is ascribed to its core@shell structure, in which Co3O4 is wrapped inside the SiO2 shell structure to avoid air exposure. This research provides important guidance for the high humidity resistance of catalysts for ozone decomposition.

Discovery of a Series of 1,2,3-Triazole-Containing Erlotinib Derivatives With Potent Anti-Tumor Activities Against Non-Small Cell Lung Cancer.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are emerging at the vanguard of therapy for non-small-cell lung cancer (NSCLC) patients with EGFR-activating mutations. However, the increasing therapeutic resistance caused by novel mutations or activated bypass pathways has impaired their performance. In this study, we link one of the commercial EGFR-TKIs, Erlotinib, to different azide compounds to synthesize a novel class of 1,2,3-triazole ring-containing Erlotinib derivatives. We discovered that several new compounds show robust antiproliferation activity against diverse NSCLC cells in vitro including PC-9, H460, H1975 and A549. Two of the most potent compounds, e4 and e12 have been found to be more efficient than Erlotinib in all NSCLC cell lines except PC-9. They significantly induce apoptosis and cell cycle arrest in PC-9 and H460 cells. The antitumor efficacy of compound e4 in vivo is close to that of Erlotinib in a PC-9 xenograft mouse model. Most Erlotinib-1,2,3-triazole compounds exhibit moderate to good inhibitory activities toward wild-type EGFR as indicated by enzyme-linked immunosorbent assay (ELISA), and the EGFR phosphorylation was inhibited in H460 and PC-9 cells exposed to e4 or e12. These data suggest that these Erlotinib-1,2,3-triazole compounds are suitable candidates for use against NSCLC and more unknown mechanisms merit further investigation.

Deep Learning for Retail Product Recognition: Challenges and Techniques.

Taking time to identify expected products and waiting for the checkout in a retail store are common scenes we all encounter in our daily lives. The realization of automatic product recognition has great significance for both economic and social progress because it is more reliable than manual operation and time-saving. Product recognition via images is a challenging task in the field of computer vision. It receives increasing consideration due to the great application prospect, such as automatic checkout, stock tracking, planogram compliance, and visually impaired assistance. In recent years, deep learning enjoys a flourishing evolution with tremendous achievements in image classification and object detection. This article aims to present a comprehensive literature review of recent research on deep learning-based retail product recognition. More specifically, this paper reviews the key challenges of deep learning for retail product recognition and discusses potential techniques that can be helpful for the research of the topic. Next, we provide the details of public datasets which could be used for deep learning. Finally, we conclude the current progress and point new perspectives to the research of related fields.

Superconductivity related to the suppression of exciton formation in 1T-TiSe2.

In strongly correlated electron system, the impact of elementary substitution or intercalation plays a crucial role in determining electronic ground state among various macroscopic quantum phases such as charge order and superconductivity. Here, we report that simultaneous Cu intercalation and Ta substitution at Ti site in 1T-Cu x Ti0.8Ta0.2Se2 induce an intrinsic electronic phase diagram, characterized by an inherent superconducting transition in the x region of 0 ⩽ x ⩽ 0.12, with a maximum superconducting transition temperature T c of 2.5 K for x = 0.04, in contrast to the non-superconducting sample 1T-Cu0.04TiSe2. The increased density of free charge carriers screen the Coulomb interaction between electron-hole pairs effectively, promoting the occurrence of superconductivity favourably. Present results suggest that the Cu intercalation and the Ta substitution-induced suppression of the exciton condensation boost the superconductivity, shedding new light on the fundamental physics of the interplay between superconductivity, charge order, and electron correlation.

MicroRNA­15a­5p­targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells.

MicroRNAs (miRNAs) have been reported to have important regulatory roles in the progression of several types of cancer, including cervical cancer (CC). However, the biological roles and regulatory mechanisms of miRNAs in CC remain to be fully elucidated. The aim of the present study was to examine the functions of miRNAs in CC and the possible mechanisms. Using a microarray, it was identified that miRNA­15a­5p (miR­15a­5p) was one of the most downregulated miRNAs in CC tissues compared with adjacent noncancerous tissues. The low expression of miR­15a­5p was observed in CC tumor tissues with distant metastasis and in CC cell lines. In addition, the effects of miR­15a­5p upregulation on cell viability, apoptosis, invasion and migration of CC cells were investigated using CCK­8, flow cytometry, Transwell and wound healing assays, respectively. It was demonstrated that upregulation of miR­15a­5p significantly suppressed the viability, migration and invasion, and promoted the apoptosis of SiHa and C­33A cells. Furthermore, yes­associated protein 1 (YAP1), a well­known oncogene, was confirmed to be directly targeted by miR­15a­5p and was found to be negatively regulated by miR­15a­5p. Further correlation analysis indicated that miR­15a­5p expression was negatively correlated with YAP1 expression in CC tissues. Notably, overexpression of YAP1 abrogated the tumor suppressive effects of miR­15a­5p in CC cells. Taken together, these present findings indicated that the miR­15a­5p/YAP1 axis may provide a novel strategy for the clinical treatment of CC.

Pressure effect on the magnetoresistivity of topological semimetal RhSn.

RhSn is a topological semimetal with chiral fermions. At ambient pressure, it exhibits large positive magnetoresistance (MR) and field-induced resistivity upturn at low temperatures. Here we report on the electrical transport properties of RhSn single crystal under various pressures. We find that with increasing pressure the temperature-dependent resistivity ρ(T) of RhSn varies minutely, whereas the value of MR at low temperatures decreases significantly. The ρ(T) data was fitted with the Bloch-Grüneisen model and the Debye temperature was extracted. Analyses of the nonlinear Hall conductivity with two-band model indicate that the carrier concentrations do not change significantly with pressure, but the mobilities for both electron and hole carriers are reduced monotonically, which can account for the significant reduction of MR under high pressures.