Transcriptional programs of Pitx2 and Tfap2a/Tfap2b controlling lineage specification of mandibular epithelium during tooth initiation.

How the dorsal-ventral axis of the vertebrate jaw, particularly the position of tooth initiation site, is established remains a critical and unresolved question. Tooth development starts with the formation of the dental lamina, a localized thickened strip within the maxillary and mandibular epithelium. To identify transcriptional regulatory networks (TRN) controlling the specification of dental lamina from the naïve mandibular epithelium, we utilized Laser Microdissection coupled low-input RNA-seq (LMD-RNA-seq) to profile gene expression of different domains of the mandibular epithelium along the dorsal-ventral axis. We comprehensively identified transcription factors (TFs) and signaling pathways that are differentially expressed along mandibular epithelial domains (including the dental lamina). Specifically, we found that the TFs Sox2 and Tfap2 (Tfap2a/Tfap2b) formed complimentary expression domains along the dorsal-ventral axis of the mandibular epithelium. Interestingly, both classic and novel dental lamina specific TFs-such as Pitx2, Ascl5 and Zfp536-were found to localize near the Sox2:Tfap2a/Tfap2b interface. To explore the functional significance of these domain specific TFs, we next examined loss-of-function mouse models of these domain specific TFs, including the dental lamina specific TF, Pitx2, and the ventral surface ectoderm specific TFs Tfap2a and Tfap2b. We found that disruption of domain specific TFs leads to an upregulation and expansion of the alternative domain's TRN. The importance of this cross-repression is evident by the ectopic expansion of Pitx2 and Sox2 positive dental lamina structure in Tfap2a/Tfap2b ectodermal double knockouts and the emergence of an ectopic tooth in the ventral surface ectoderm. Finally, we uncovered an unappreciated interface of mesenchymal SHH and WNT signaling pathways, at the site of tooth initiation, that were established by the epithelial domain specific TFs including Pitx2 and Tfap2a/Tfap2b. These results uncover a previously unknown molecular mechanism involving cross-repression of domain specific TFs including Pitx2 and Tfap2a/Tfap2b in patterning the dorsal-ventral axis of the mouse mandible, specifically the regulation of tooth initiation site.

Absolute Structures of a Mirror Pair of Infinite Na(H2O)4 + -Connected ε-Keggin-Al13 Species.

The absolute structures of a pair of infinite Na(H2O)4+-connected ε-Keggin-Al13 species (Na-ε-K-Al13) that were inversion structures and mirror images of each other were determined. Single crystals obtained by adding A2SO4 (A = Li, Na, K, Rb, or Cs) solution to NaOH-hydrolyzed AlCl3 solution were subjected to X-ray structure analyses. The statistical results for 36 single crystals showed that all the crystals had almost the same unit cell parameter, belonged to the same F4̅3m space group, and possessed the same structural formula [Na(H2O)4AlO4Al12(OH)24(H2O)12](SO4)4·10H2O. However, the crystals had two inverse absolute structures (denoted A and B), which had a crystallization ratio of 1:1. From Li+ to Cs+, with increasing volume of the cation coexisting in the mother solution, the degree of disorder of the four H2O molecules in the Na(H2O)4+ hydrated ion continuously decreased; they became ordered when the cation was Cs+. Absolute structures A and B are the first two infinite aluminum polycations connected by statistically occupied [(Na1/4)4(H2O)4]+ hydrated ions. The three-dimensional structure of the infinite Na-ε-K-Al13 species can be regarded as the assembly of finite ε-K-Al13 species linked by [(Na1/4)4(H2O)4]+ in a 1:1 ratio. In this assembly, each [(Na1/4)4(H2O)4]+ is connected to four ε-K-Al13 and each ε-K-Al13 is also connected to four [(Na1/4)4(H2O)4]+ in tetrahedral orientations to form a continuous rigid framework structure, which has an inverse spatial orientation between absolute structure A and B. This discovery clarifies that the ε-K-Al13 (or ε-K-GaAl12) species in Na[MO4Al12(OH)24(H2O)12](XO4)4·nH2O (M = Al, Ga; X = S, Se; n = 10-20) exists as discrete groups and deepens understanding of the formation and evolution process of polyaluminum species in forcibly hydrolyzed aluminum salt solution. The reason why Na+ statistically occupies the four sites was examined, and a formation and evolution mechanism of the infinite Na-ε-K-Al13 species was proposed.

Inhibitory Activities of Five Fungicides on Alternaria suffruticosae and Their Field Control Efficacy Against Tree Peony Black Spot.

Tree peony black spot (TPBS), mainly caused by Alternaria suffruticosae, is a common leaf disease on the ornamental peony, which poses a great threat to the flower buds in the current year and the flowering quality in the next year. However, there is only one fungicide registered for the control of this disease, difenoconazole. In order to avoid the severe problem of pathogen resistance caused by long-term use of difenoconazole, it is necessary to screen more chemical fungicides for the prevention and control of TPBS. In this study, the biological activities of flutolanil, phenamacril, pyraclostrobin, and boscalid on mycelial growth, conidial germination, germ tube elongation, and sporulation quantity of A. suffruticosae were determined, and the field control efficacy was tested to evaluate the preventive and therapeutic activities. Difenoconazole was used as a control simultaneously. The results showed that pyraclostrobin had the strongest inhibitory effects on the conidial germination, mycelium growth, germ tube elongation, and sporulation quantity, with the average EC50 values of 0.0517, 0.5343, 0.0008, and 0.8068 µg/ml, respectively. The inhibitory activity of flutolanil on the four developmental stages of A. suffruticosae was weaker than that of the other three fungicides. Compared with flutolanil, boscalid, the other succinate dehydrogenase inhibitor, had more strong inhibitory effects on the mycelial growth and sporulation quantity, with the average EC50 values of 3.8603 and 1.4760 µg/ml, respectively. Phenamacril had a moderate inhibitory level and had more inhibitory activity on conidial germination and germ tube elongation, with the average EC50 values of 31.5349 and 5.2597 µg/ml, respectively. All of the four fungicides had no significant effects on the shape of spores and germ tubes. The control fungicide difenoconazole had the strongest inhibitory activity on mycelial growth, and the average EC50 value was only 0.3297 µg/ml. However, its inhibitory activity on the other three growth stages was not high. In the field trials, pyraclostrobin had high control efficacy on TPBS even at low concentrations, reaching a minimum of 62.6293%, which was higher than that of difenoconazole. The other three fungicides had higher control efficacy at high concentrations but decreased significantly at low concentrations. Considering the dosage and control efficacy, pyraclostrobin was the first choice for the control of TPBS. Pyraclostrobin is the preferred alternative fungicide to difenoconazole for the prevention and control of TPBS in production.

Optimization strategy of power purchase and sale for electricity retailers in a two-tier market.

Against the backdrop of the gradual advancement of China's electricity market reform, the number of Power Trading Companies in China has been increasing year by year, and as of October 2022, the number has reached more than 10,000. As an important hub connecting the electricity market and users, electricity retailers face double risks from downstream user load fluctuations and electricity market price fluctuations. Therefore, a reasonable power purchase and sale strategy is very important for an electricity retailer. In this study, a block bidding mechanism is adopted to optimize the clearing of the medium-to long-term market and a DA-RBF neural network is established for spot electricity price forecasting model based on numerical feature similarity to improve the accuracy of electricity price forecasting. Furthermore, the model considers the differences in user demand responses and investigates the optimal power purchase and sale strategy, guided by differentiated time-of-use electricity pricing. The case study analysis demonstrated that the proposed power purchase and sale optimization strategy yields favorable results, improving profitability and enhancing the stability of the power system.

Appraising the value of CircRNAs for the diagnosis and prognosis of esophageal squamous cell cancer: An updated meta-analysis.

OBJECTIVE: The purpose of this study was to thoroughly assess the relevance of circular RNAs (circRNAs) in the diagnosis and prognosis of esophageal squamous cell carcinoma (ESCC)， and design a systematic review and meta-analysis. METHODS: Using Stata 14.0 software, a meta-analysis was carried out by looking for pertinent studies up to February 20, 2023, in the online databases PubMed, Embase, Web of Science, and CNKI. The clinicopathologic and prognostic data were evaluated using the combined advantage ratio (OR) and combined hazard ratio (HR), respectively. The threshold effects and publication bias were quantified using Spearman's correlation and the Deeks funnel plot asymmetry tests, respectively. RESULTS: A total of 36 pertinent studies with a literature quality score of 7 or above were included in this study. Of them, 22 papers dealt with clinicopathological characterization, 15 dealt with prognostic analysis, and 13 dealt with diagnostic analysis. The findings demonstrated that high expression of upregulated circRNAs was associated with worse clinicopathological features (tumor size: OR=3.61, 95% CI:1.45-5.78; TNM stage: OR=2.12, 95% CI:1.41-2.83; lymph node metastasis: OR=2.87, 95% CI:1.67-4.07) and worse OS (HR=1.49, 95% CI:1.26-1.77). High downregulated circRNAs expression was linked to improved clinicopathologic characteristics (TNM staging: OR=0.35, 95% CI:0.13- 0.95) and longer survival (HR=0.48, 95% CI:0.27-0.84); combined sensitivity was 0.77 (95% CI: 0.71-0.82), specificity was 0.80 (95% CI:0.74-0.86), and area under the subject operating characteristic curve (AUC) was 0.86 (95% CI:0.82- 0.88). CONCLUSION: CircRNAs are useful for ESCC patient diagnosis and prognosis, and they are anticipated to be unique potential biomarkers for ESCC clinical diagnosis.

THGNCDA: circRNA-disease association prediction based on triple heterogeneous graph network.

Circular RNAs (circRNAs) are a class of noncoding RNA molecules featuring a closed circular structure. They have been proved to play a significant role in the reduction of many diseases. Besides, many researches in clinical diagnosis and treatment of disease have revealed that circRNA can be considered as a potential biomarker. Therefore, understanding the association of circRNA and diseases can help to forecast some disorders of life activities. However, traditional biological experimental methods are time-consuming. The most common method for circRNA-disease association prediction on the basis of machine learning can avoid this, which relies on diverse data. Nevertheless, topological information of circRNA and disease usually is not involved in these methods. Moreover, circRNAs can be associated with diseases through miRNAs. With these considerations, we proposed a novel method, named THGNCDA, to predict the association between circRNAs and diseases. Specifically, for a certain pair of circRNA and disease, we employ a graph neural network with attention to learn the importance of its each neighbor. In addition, we use a multilayer convolutional neural network to explore the relationship of a circRNA-disease pair based on their attributes. When calculating embeddings, we introduce the information of miRNAs. The results of experiments show that THGNCDA outperformed the SOTA methods. In addition, it can be observed that our method gives a better recall rate. To confirm the significance of attention, we conducted extensive ablation studies. Case studies on Urinary Bladder and Prostatic Neoplasms further show THGNCDA's ability in discovering known relationships between circRNA candidates and diseases.

K-N Bridge-Mediated charge separation in hollow g-C3N4 Frameworks: A bifunctional photocatalysts towards efficient H2 and H2O2 production.

The development of bifunctional photocatalysts for enhancing hydrogen (H2) and hydrogen peroxide (H2O2) production from water is essential in addressing environmental and energy issues. However, the practical implementation of photocatalytic technology is still constrained by the inadequate separation of photo-generated charge carriers. Herein, potassium (K) atoms are introduced into the interlayers of graphitic carbon nitride (g-C3N4) with a hollow hexagonal structure (K-TCN) and are coordinated with N atoms in adjacent layers. The presence of K-N coordination serves as a layer bridge, facilitating the separation of charge carriers. The hollow hexagonal structure reduces the distance over which photogenerated electrons migrate to the surface, thereby enhancing the reaction kinetics. Consequently, the optimized K-TCN exhibits a dramatically improved photocatalytic H2 (941.6 µmol g-1h-1 with platinum (Pt) as the cocatalyst) and H2O2 (347.6 µmol g-1h-1) generation as compared to hollow g-C3N4 (TCN) and bulk g-C3N4 nanosheet (CN) without K-N bridge under visible light irradiation. The unique design holds promising potential for developing highly efficient bifunctional photocatalysts towards producing renewable fuels and value-added chemicals.

Achieving high carrier separation over Bi4O5I2through Ni doping for improved photocatalytic CO2reduction.

Photocatalytic CO2reduction is considered to be an appealing way of alleviating environmental pollution and energy shortages simultaneously under mild condition. However, the activity is greatly limited by the poor separation of the photogenerated carriers. Ion doping is a feasible strategy to facilitate the charge transfer. In this work, Ni-doped Bi4O5I2photocatalyst is successfully fabricated using a one-pot hydrothermal method. A few doping levels appear in the energy band of Bi4O5I2after Ni doping, which are used as springboards for electrons transition, thus promoting photoexcited electrons and holes separation. As a consequence, a remarkably enhanced yield of CO and CH4(6.2 and 1.9µmol g-1h-1) is obtained over the optimized Bi4O5I2-Ni15, which is approximately 2.1 and 3.8 times superior to pure Bi4O5I2, respectively. This work may serve as a model for the subsequent research of Bi-based photocatalysts to implement high-performance CO2photoreduction.

Metal-Insulator Transition of Single-Crystal V2O3 through van der Waals Interface Engineering.

Strongly correlated electron materials harbor interesting materials physics, such as high-Tc superconductivity, colossal magnetoresistance, and metal-insulator transition. These physical properties can be greatly influenced by the dimensionality and geometry of the hosting materials and their interaction strengths with underlying substrates. In a classic strongly correlated oxide vanadium sesquioxide (V2O3), the coexistence of a metal-insulator and paramagnetic-antiferromagnetic transitions at ∼150 K makes this material an excellent platform for exploring basic physics and developing future devices. So far, most studies have been focused on epitaxial thin films in which the strongly coupled substrate has a pronounced effect on V2O3, leading to the observations of intriguing phenomena and physics. In this work, we unveil the kinetics of a metal-insulator transition of V2O3 single-crystal sheets at nano and micro scales. We show the presence of triangle-like alternating metal/insulator phase patterns during phase transition, which is drastically different from the epitaxial film. The observation of single-stage metal-insulator transition in V2O3/graphene compared to the multistage in V2O3/SiO2 evidence the importance of sheet-substrate coupling. Harnessing the freestanding form of the V2O3 sheet, we show that the phase transition of V2O3 sheet can generate a large dynamic strain to monolayer MoS2 and tune its optical property based on the MoS2/V2O3 hybrid structure. The demonstration of the capability in tuning phase transition kinetics and phase patterns using designed hybrid structure of varied sheet-substrate coupling strengths suggests an effective knob in the design and operation of emerging Mott devices.

Impact of Phenamacril on the Growth and Development of Fusarium pseudograminearum and Control of Crown Rot of Wheat.

Fusarium pseudograminearum is the dominant pathogen causing Fusarium crown rot (FCR) of wheat. Phenamacril is a 2-cyanoacrylate fungicide, having a control effect on diseases caused by Fusarium spp. The objective of this study was to investigate the inhibitory effect of phenamacril on F. pseudograminearum and its control efficacy against FCR. The results showed that phenamacril had a strong inhibitory effect on the mycelial growth of F. pseudograminearum, EC50 values of phenamacril to 63 tested strains were in the range of 0.0998 to 0.5672 µg/ml, and the average EC50 value was 0.3403 ± 0.0872 µg/ml and could be used as the baseline sensitivity of F. pseudograminearum to phenamacril. Phenamacril reduced the germination rate of conidia of F. pseudograminearum, and the EC50 value was 5.0273 to 26.4814 µg/ml. In addition, we found that phenamacril had a teratogenic effect on conidia and blastotubules, which increased the ratio of conidial germination from the middle cells and showed high efficacy on the sporulation quantity of F. pseudograminearum with an EC50 value in the range of 0.0770 to 0.1064 µg/ml. There was no significant correlation between the sensitivity of F. pseudograminearum to phenamacril and its sensitivity to fludioxonil, carbendazim, tebuconazole, and kresoxim-methyl. In vitro and greenhouse assays showed that the treatment with 0.125 µl of active ingredient per gram recorded the best control effect on wheat crown rot, reaching 87.8 and 77.3%, respectively. In two experimental sites in Luoyang, phenamacril also had great control effect against FCR, reaching 83.9%. It was proven that phenamacril has a superior control effect against FCR. This study has laid a foundation for the study of the mechanism of action of phenamacril against F. pseudograminearum and provided a theoretical basis for the application of phenamacril to control FCR.

Facile Synthesis of TiO2/MoS2 Composites with Co-Exposed High-Energy Facets for Enhanced Photocatalytic Performance.

In this work, with the the H2TiO3 colloidal suspension and MoS2 as the precursors, TiO2/MoS2 composites composed of anatase TiO2 nanocrystals with co-exposed {101} and [111]-facets (nanorod and nanocuboid), {101} and {010} facets (nanospindle), and MoS2 microspheres constructed by layer-by-layer self-assembly of nanosheets were hydrothermally synthesized under different pH conditions. The characterization has been performed by combining X-ray powder diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), high resolution TEM (HRTEM), X-ray photoelectron spectroscopy (XPS), photoluminescence (PL) spectra, and UV-visible absorption spectrum analyses. The photocatalytic degradation of rhodamine B (RhB) in an aqueous suspension was employed to evaluate the photocatalytic activity of the as-prepared pHx-TiO2/MoS2 composites. The photocatalytic degradation efficiency of pH3.5-TiO2/MoS2 composite was the highest (99.70%), which was 11.24, 2.98, 1.48, 1.21, 1.09, 1.03, 1.10, and 1.14 times that of Blank, MoS2, CM-TiO2, pH1.5-TiO2/MoS2, pH5.5-TiO2/MoS2, pH7.5-TiO2/MoS2, pH9.5-TiO2/MoS2, pH11.5-TiO2/MoS2, respectively. The pH3.5-TiO2/MoS2 composite exhibited the highest photocatalytic degradation rate, which may be attributed to the synergistic effects of its large specific surface area, suitable heterojunction structure, and favorable photogenerated charge-separation efficiency. This work is expect to provide primary insights into the photocatalytic effect of TiO2/MoS2 composite with co-exposed high-energy facets, and make a contribution to designing more efficient and stable photocatalysts.

Potential value of cerebrospinal fluid α-synuclein in the identification of postoperative delirium undergoing knee/hip arthroplasty: The perioperative neurocognitive disorder and biomarker lifestyle study.

Objective: Postoperative delirium (POD) is a common postoperative complication, which may be associated with α-synuclein (α-syn). The purpose of this study was to explore the association between the expression level of α-syn in cerebrospinal fluid (CSF) and POD. Methods: We conducted a prospective observational cohort study, which involved in 740 participants (mean age of 61.86 years, range 40-90 years; 40% female) from the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE) study in the final analysis. POD was diagnosed using the Confusion Assessment Scale (CAM), and its severity was measured using the Memorial Delirium Assessment Scale (MDAS). Enzyme-linked immune-sorbent assay (ELISA) was used to detect the concentrations of α-syn, Aß40, Aß42, T-tau, and P-tau in CSF. Results: The incidence of POD was 11.22% (83/740). The logistic regression analysis showed that the increased concentrations of CSF α-syn (OR = 1.005, 95%CI 1.004-1.006, P < 0.001), P-tau (OR = 1.093, 95%CI 1.071-1.115, P < 0.001), and T-tau (OR = 1.008, 95%CI 1.006-1.009, P < 0.001) were risk factors of POD. Linear regression showed that CSF α-syn had positive correlations with P-tau (ß = 0.480, P < 0.001), T-tau (ß = 0.334, P < 0.001), while negative correlations with Aß40 (ß = -0.378 P < 0.001), Aß42 (ß = -0.800, P = 0.001) in POD patients. Mediation analyses showed the association between α-syn and POD was partially mediated by tau pathologies (proportion: 16-17%). Conclusion: CSF α-syn is one of the preoperative risk factors for POD, which may be mediated through tau pathologies. Clinical trial registration: [www.ClinicalTrials.gov], identifier [ChiCTR20 00033439].

Cluster Alignment With Target Knowledge Mining for Unsupervised Domain Adaptation Semantic Segmentation.

Unsupervised domain adaptation (UDA) carries out knowledge transfer from the labeled source domain to the unlabeled target domain. Existing feature alignment methods in UDA semantic segmentation achieve this goal by aligning the feature distribution between domains. However, these feature alignment methods ignore the domain-specific knowledge of the target domain. In consequence, 1) the correlation among pixels of the target domain is not explored; and 2) the classifier is not explicitly designed for the target domain distribution. To conquer these obstacles, we propose a novel cluster alignment framework, which mines the domain-specific knowledge when performing the alignment. Specifically, we design a multi-prototype clustering strategy to make the pixel features within the same class tightly distributed for the target domain. Subsequently, a contrastive strategy is developed to align the distributions between domains, with the clustered structure maintained. After that, a novel affinity-based normalized cut loss is devised to learn task-specific decision boundaries. Our method enhances the model's adaptability in the target domain, and can be used as a pre-adaptation for self-training to boost its performance. Sufficient experiments prove the effectiveness of our method against existing state-of-the-art methods on representative UDA benchmarks.

The effect of neostigmine on postoperative delirium after colon carcinoma surgery: a randomized, double-blind, controlled trial.

BACKGROUND: Postoperative delirium (POD) is a critical complication in patients accepting colon carcinoma surgery. Neostigmine, as a cholinesterase inhibitor, can enhance the transmission of cholinergic transmitters in synaptic space, and play an important role in maintaining the normal level of cognition, attention and consciousness. The objective of this study was to investigate the effect of neostigmine on POD and clinical prognosis. METHODS: A randomized, double-blind controlled trial was implemented in Qingdao Municipal Hospital Affiliated to Qingdao University. A total of 454 patients aged 40 to 90 years old accepted colon carcinoma surgery were enrolled between June 7, 2020, and June 7, 2021, with final follow-up on December 8, 2021. Patients were randomly assigned to two groups: the neostigmine group (group N) and the placebo group (group P), the patients in group N were injected with 0.04 mg/kg neostigmine and 0.02 mg/kg atropine intravenously. The primary endpoint was the incidence of POD, researchers evaluated the occurrence of POD by the Confusion Assessment Method (CAM) twice daily (at 10 a.m. and 2 p.m.) during the first 7 postoperative days, POD severity was assessed by the Memorial Delirium Assessment Scale (MDAS). The secondary endpoints were the extubating time, postanesthesia care unit (PACU) time, the incidence of various postoperative complications, length of hospital stays, and 6 months postoperative mortality. RESULTS: The incidence of POD was 20.20% (81/401), including 19.39% (38/196) in group N and 20.98% (43/205) in group P. There was no significant statistical significance in the incidence of POD between group N and group P (P > 0.05); Compared to group P, the extubating time and PACU time in group N were significantly reduced (P < 0.001), the incidence of postoperative pulmonary complications (POPCs) decreased significantly in group N (P < 0.05), while no significant differences were observed in postoperative hospital stay and mortality in 6 months between the two groups (P > 0.05). CONCLUSION: For patients accepted colon carcinoma surgery, neostigmine did not significantly reduce the incidence of POD, postoperative mortality and postoperative hospital stay, while it indeed reduced the extubating time, PACU time and the incidence of POPCs. TRIAL REGISTRATION: The randomized, double-blind, controlled trial was registered retrospectively at www.chictr.org.cn on 07/06/2020 (ChiCTR2000033639).

Debulking different Corona (SARS-CoV-2 delta, omicron, OC43) and Influenza (H1N1, H3N2) virus strains by plant viral trap proteins in chewing gums to decrease infection and transmission.

Because oral transmission of SARS-CoV-2 is 3-5 orders of magnitude higher than nasal transmission, we investigated debulking of oral viruses using viral trap proteins (CTB-ACE2, FRIL) expressed in plant cells, delivered through the chewing gum. In omicron nasopharyngeal (NP) samples, the microbubble count (based on N-antigen) was significantly reduced by 20 µg of FRIL (p < 0.0001) and 0.925 µg of CTB-ACE2 (p = 0.0001). Among 20 delta or omicron NP samples, 17 had virus load reduced below the detection level of spike protein in the RAPID assay, after incubation with the CTB-ACE2 gum powder. A dose-dependent 50% plaque reduction with 50-100 ng FRIL or 600-800 µg FRIL gum against Influenza strains H1N1, H3N2, and Coronavirus HCoV-OC43 was observed with both purified FRIL, lablab bean powder or gum. In electron micrographs, large/densely packed clumps of overlapping influenza particles and FRIL protein were observed. Chewing simulator studies revealed that CTB-ACE2 release was time/dose-dependent and release was linear up to 20 min chewing. Phase I/II placebo-controlled, double-blinded clinical trial (IND 154897) is in progress to evaluate viral load in saliva before or after chewing CTB-ACE2/placebo gum. Collectively, this study advances the concept of chewing gum to deliver proteins to debulk oral viruses and decrease infection/transmission.

Giant pyroelectricity in nanomembranes.

Pyroelectricity describes the generation of electricity by temporal temperature change in polar materials1-3. When free-standing pyroelectric materials approach the 2D crystalline limit, how pyroelectricity behaves remained largely unknown. Here, using three model pyroelectric materials whose bonding characters along the out-of-plane direction vary from van der Waals (In2Se3), quasi-van der Waals (CsBiNb2O7) to ionic/covalent (ZnO), we experimentally show the dimensionality effect on pyroelectricity and the relation between lattice dynamics and pyroelectricity. We find that, for all three materials, when the thickness of free-standing sheets becomes small, their pyroelectric coefficients increase rapidly. We show that the material with chemical bonds along the out-of-plane direction exhibits the greatest dimensionality effect. Experimental observations evidence the possible influence of changed phonon dynamics in crystals with reduced thickness on their pyroelectricity. Our findings should stimulate fundamental study on pyroelectricity in ultra-thin materials and inspire technological development for potential pyroelectric applications in thermal imaging and energy harvesting.

The application of the acoustic shadowing facilitates guidance in radial artery puncture and cannulation teaching in standardized training for residents: a randomized controlled trial.

BACKGROUND: Radial artery cannulation is a crucial investigative procedure for measuring patients' blood pressure invasively and serial blood gases. However, radial artery cannulation can be challenging for medical residents, and it is necessary to establish a facile and straightforward teaching strategy. This study aimed to evaluate the efficiency of acoustic shadowing-facilitated ultrasound guidance on radial artery cannulation teaching for medical residents. METHODS: A total of 116 medical postgraduates who underwent standardized residency training programs in the Department of Anesthesiology were randomly divided into a new ultrasound-guided teaching group and a traditional ultrasound-guided teaching group. In the new ultrasound-guided teaching group, radial artery puncture technique was taught by acoustic shadowing-facilitated ultrasound guidance. The training included both theoretical and practical components. After the training, the success rate of the first puncture attempt, the success rate of the catheterization, the ultrasonic positioning time, and the catheterization time of the two groups were compared in a unified manner. A questionnaire on the subjective evaluation of the various aspects of the program by participants was conducted at the end of the training period. RESULTS: The study included 101 medical residents. The success rate for radial artery puncture at the first attempt in the new ultrasound-guided teaching group was 78.43%. It was significantly higher than that of the traditional ultrasound-guided group (58.00%, odds ratio = 0.380; 95% CI = 0.159 to 0.908; p = 0.027). The success rate for the first arterial catheterization in the new ultrasound-guided teaching group was significantly higher than that of the traditional ultrasound-guided group (74.51% vs. 52.00%, odds ratio = 0.371; 95% CI = 0.160 to 0.858; p = 0.019). The ultrasonic positioning time and catheterization time in minutes in the new ultrasound-guided teaching group were significantly shorter than that of the traditional ultrasound-guided group (14.36 ± 3.31 vs. 18.02 ± 4.95, p < 0.001; 10.43 ± 2.38 vs. 14.78 ± 8.02, p = 0.012). However, no significant differences were observed in the incidence of local hematomas and teaching satisfaction scores between the two groups. CONCLUSION: Acoustic shadowing facilitates ultrasound-guided radial artery puncture and catheterization is beneficial in the standardized training and teaching of residents. It improves the success rate of the first attempt at radial artery puncture and catheterization and shortens the time of ultrasound location and catheterization. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry on 28 May 2021. REGISTRATION NUMBER: ChiCTR2100046833 .

Phenytoin Regulates Migration and Osteogenic Differentiation by MAPK Pathway in Human Periodontal Ligament Cells.

INTRODUCTION: Periodontal healing requires an adequate number of periodontal ligament (PDL) cells to rebuild the impaired tissue. Phenytoin (PHT) has been reported to promote wound healing and extracellular matrix deposition, which indicates its promising application of periodontal healing. However, the effects of PHT on PDL cells behavior and the underlying mechanism are still unknown. METHODS: Human PDL cells were cultured and identified. 20-100 µg/mL PHT were used in our study. The proliferation of PDL cells was determined by the EdU assay. A wound healing assay was used to detect cell migration. Matrix metalloproteinase (MMP)-1, MMP-2, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 expression were analyzed by real time-PCR. The protein expression of MMP-1 and phosphorylated mitogen-activated protein kinases (MAPKs) were detected by western blotting assay. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) staining. RESULTS: We found that 20-100 µg/mL of PHT did not affect PDL cells proliferation, whereas 50-100 µg/mL of PHT inhibited cell migration. The 50 or 100 µg/mL of PHT decreased the gene and protein expression of MMP-1, but increased the gene expression of TIMP-1. MMP-2 and TIMP-2 were not affected by 20-100 µg/mL of PHT. Further, 20-50 µg/mL of PHT increased ALP expression, but 100 µg/mL of PHT depressed ALP expression. The extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 were activated by PHT. JNK and ERK are involved in PHT-regulated migration. JNK plays an essential role in PHT-induced osteogenic differentiation. CONCLUSIONS: MAPK pathway involved in PHT-regulated migration and osteogenic differentiation in human PDL cells.

Ion Migration in Perovskite Light-Emitting Diodes: Mechanism, Characterizations, and Material and Device Engineering.

In recent years, perovskite light-emitting diodes (PeLEDs) have emerged as a promising new lighting technology with high external quantum efficiency, color purity, and wavelength tunability, as well as, low-temperature processability. However, the operational stability of PeLEDs is still insufficient for their commercialization. The generation and migration of ionic species in metal halide perovskites has been widely acknowledged as the primary factor causing the performance degradation of PeLEDs. Herein, this topic is systematically discussed by considering the fundamental and engineering aspects of ion-related issues in PeLEDs, including the material and processing origins of ion generation, the mechanisms driving ion migration, characterization approaches for probing ion distributions, the effects of ion migration on device performance and stability, and strategies for ion management in PeLEDs. Finally, perspectives on remaining challenges and future opportunities are highlighted.

The degradation of Rap1GAP via E6AP-mediated ubiquitin-proteasome pathway is associated with HPV16/18-infection in cervical cancer cells.

BACKGROUND: Cervical cancers are closely associated with persistent high-risk human papillomaviruses (HR HPV) infection. The main mechanism involves the targeting of tumor suppressors, such as p53 and pRB, for degradation by HR HPV-encoded oncoproteins, thereby leading to tumorigenesis. Rap1GAP, a tumor suppressor gene, is down-regulated in many cancers. Previous studies have revealed that down-regulation of Rap1GAP is correlated with HPV16/18 infection in cervical cancer. However, the molecular mechanism remains unclear. In this study, we aimed to address the degradation pathway of Rap1GAP in HPV-positive cervical cancer cells. METHODS: HPV-positive (HeLa and SiHa) and negative (C33A) cervical cancer cells were used to analyze the pathways of Rap1GAP degradation. MG132 (carbobenzoxy-leucyl-leucyl-leucine) was used to inhibit protein degradation by proteasome. Co-immunoprecipitation (co-IP) was used to detect the interaction between Rap1GAP and E6AP. siRNA for E6AP was used to silence the expression of E6AP. Rapamycin was used to induce cell autophagy. Western blotting was used to check the levels of proteins. RESULTS: Following treatment with MG132, the levels of Rap1GAP were increased in the HR HPV-positive HeLa and SiHa cells, but not in the HPV-negative C33A cells. Co-immunoprecipitation assay revealed ubiquitinated Rap1GAP protein in HeLa and SiHa cells, but not in C33A cells. E6-associated protein (E6AP) mediated the ubiquitination of Rap1GAP by binding to it in HeLa and SiHa cells, but not in C33A cells. However, the levels of Rap1GAP were decreased in HeLa and SiHa cells after knocking down E6AP by siRNA. Silencing of E6AP did not affect the levels of Rap1GAP in C33A cells. Autophagy marker p62 was decreased and LC3 II/LC3 I was increased after knocking down E6AP in HeLa cells, but not in C33A cells. The levels of Rap1GAP were decreased after treating the cells with rapamycin to induce cell autophagy in HeLa and C33A cells. CONCLUSION: Rap1GAP may be degraded by autophagy in cervical cancer cells, but HPV infection can switch the degradation pathway from autophagy to E6AP-mediated ubiquitin-proteasome degradation. E6AP may be a key component of the switch.