Cost-effectiveness and cost-utility analyses of three different gargles in the treatment of chronic periodontitis.

OBJECTIVE: This study aimed to investigate the economics of three different gargles in the treatment of chronic periodontitis. METHODS: A total of 108 patients with periodontitis received one of the following three gargles: xipayi, compound chlorhexidine, or Kangfuxin gargle. The basic information of the patients, the costs of the gargles, the periodontal indexes before and after treatment, and the scores of the 3-level version of the EuroQol Five Dimensions Questionnaire were collected. The cost-effectiveness and cost-utility of the various gargles were determined. RESULTS: The cost-effectiveness ratios (CER) of the three groups after treatment were 1828.75, 1573.34, and 1876.92 RMB, respectively. The utility values before treatment were 0.92, 0.90, and 0.91, respectively, and the utility values after treatment were 0.98, 0.98, and 0.97, respectively. The cost-utility ratios (CURs) were 213.43, 195.61, and 301.53 RMB, respectively. CONCLUSIONS: For each increase in effective rate and quality-adjusted life years, the treatment cost of periodontitis patients was lower than the gross domestic product per capita of Jiangsu Province, indicating that the treatment cost is completely worth it. The CER and CUR results were the same, and the compound chlorhexidine group was the lowest, demonstrating that when the same therapeutic effect was achieved, it cost the least.

TNIK depletion induces inflammation and apoptosis in injured renal proximal tubule epithelial cells.

In the aftermath of acute kidney injury (AKI), surviving proximal tubule epithelia repopulate injured tubules to promote repair. However, a portion of cells fail to repair [termed failed-repair proximal tubule cells (FR-PTCs)] and exert ongoing proinflammatory and profibrotic effects. To better understand the molecular drivers of the FR-PTC state, we reanalyzed a mouse ischemia-reperfusion injury single-nucleus RNA-sequencing (snRNA-seq) atlas to identify Traf2 and Nck interacting kinase (Tnik) to be exclusively expressed in FR-PTCs but not in healthy or acutely injured proximal tubules after AKI (2 and 6 wk) in mice. We confirmed expression of Tnik protein in injured mouse and human tissues by immunofluorescence. Then, to determine the functional role of Tnik in FR-PTCs, we depleted TNIK with siRNA in two human renal proximal tubule epithelial cell lines (primary and immortalized hRPTECs) and analyzed each by bulk RNA-sequencing. Pathway analysis revealed significant upregulation of inflammatory signaling pathways, whereas pathways associated with differentiated proximal tubules such as organic acid transport were significantly downregulated. TNIK gene knockdown drove reduced cell viability and increased apoptosis, including differentially expressed poly(ADP-ribose) polymerase (PARP) family members, cleaved PARP-1 fragments, and increased annexin V binding to phosphatidylserine. Together, these results indicate that Tnik upregulation in FR-PTCs acts in a compensatory fashion to suppress inflammation and promote proximal tubule epithelial cell survival after injury. Modulating TNIK activity may represent a prorepair therapeutic strategy after AKI.NEW & NOTEWORTHY The molecular drivers of successful and failed repair in the proximal tubule after acute kidney injury (AKI) are incompletely understood. We identified Traf2 and Nck interacting kinase (Tnik) to be exclusively expressed in failed-repair proximal tubule cells after AKI. We tested the effect of siTNIK depletion in two proximal tubule cell lines followed by bulk RNA-sequencing analysis. Our results indicate that TNIK acts to suppress inflammatory signaling and apoptosis in injured renal proximal tubule epithelial cells to promote cell survival.

Analysis of public opinion on employment issues using a combined approach: a case study in China.

To analyze the public opinion related to the employment situation, a combined approach is proposed to study the valuable ideas from social media. Firstly, the popularity of public opinion was analyzed according to the time series from a statistical point of view. Secondly, the feature extraction was carried out on the public opinion information, and the thematic analysis of the employment environment was carried out based on the Latent Dirichlet Allocation model. Thirdly, the Bert model was used to analyze the sentiment classification and trend of the employment-related public opinion data. Finally, the employment public opinion texts in different regions were studied based on the spatial sequence popularity analysis, keyword difference analysis. A case study in China is conducted to verify the effectiveness of proposed combined approach. Results shown that the popularity of employment public opinion reached the highest level in March 2022. Public opinions towards employment situation are negative. There is a specific relationship between the popularity of employment public opinion in different provinces.

Biological evaluation of 9-thioansamitocin P3.

Highly cytotoxic maytansine derivatives are widely used in targeted tumor delivery. Structure-activity studies published earlier suggested the C9 carbinol to be a key element necessary to retain the potency. However, in 1984 a patent was published by Takeda in which the synthesis of 9-thioansamitocyn (AP3SH) was described and its activity in xenograft models was shown. In this article we summarize the results of an extended study of the anti-tumor properties of AP3SH. Like other maytansinoids, it induces apoptosis and arrests the cell cycle in the G2/M phase. It is metabolized in liver microsomes predominately by C3A4 isoform and doesn't inhibit any CYP isoforms except CYP3A4 (midazolam, IC50 7.84 µM). No hERG inhibition, CYP induction or mutagenicity in Ames tests were observed. AP3SH demonstrates high antiproliferative activity against 25 tumor cell lines and tumor growth inhibition in U937 xenograft model. Application of AP3SH as a cytotoxic payload in drug delivery system was demonstrated by us earlier.

Dexmedetomidine modulates neuronal activity of horizontal limbs of diagonal band via α2 adrenergic receptor in mice.

BACKGROUND AND OBJECTIVES: Dexmedetomidine (DEX) is widely used in clinical sedation which has little effect on cardiopulmonary inhibition, however the mechanism remains to be elucidated. The basal forebrain (BF) is a key nucleus that controls sleep-wake cycle. The horizontal limbs of diagonal bundle (HDB) is one subregions of the BF. The purpose of this study was to examine whether the possible mechanism of DEX is through the α2 adrenergic receptor of BF (HDB). METHODS: In this study, we investigated the effects of DEX on the BF (HDB) by using whole cell patch clamp recordings. The threshold stimulus intensity, the inter-spike-intervals (ISIs) and the frequency of action potential firing in the BF (HDB) neurons were recorded by application of DEX (2 µM) and co-application of a α2 adrenergic receptor antagonist phentolamine (PHEN) (10 µM). RESULTS: DEX (2 µM) increased the threshold stimulus intensity, inhibited the frequency of action potential firing and enlarged the inter-spike-interval (ISI) in the BF (HDB) neurons. These effects were reversed by co-application of PHEN (10 µM). CONCLUSION: Taken together, our findings revealed DEX decreased the discharge activity of BF (HDB) neuron via α2 adrenergic receptors.

Observation of non-superconducting phase changes in nitrogen doped lutetium hydrides.

The recent report of near-ambient superconductivity and associated color changes in pressurized nitrogen doped lutetium hydride has triggered worldwide interest and raised major questions about the nature and underlying physics of these latest claims. Here we report synthesis and characterization of high-purity nitrogen doped lutetium hydride LuH2±xNy. We find that pressure conditions have notable effects on Lu-N and Lu-NH chemical bonding and the color changes likely stem from pressure-induced electron redistribution of nitrogen/vacancies and interaction with the LuH2 framework. No superconducting transition is found in all the phases at temperatures 1.8-300 K and pressures 0-38 GPa. Instead, we identify a notable temperature-induced resistance anomaly of electronic origin in LuH2±xNy, which is most pronounced in the pink phase and may have been erroneously interpreted as a sign of superconducting transition. This work establishes key benchmarks for nitrogen doped lutetium hydrides, allowing an in-depth understanding of its novel pressure-induced phase changes.

Bamboo-like dual-phase nanostructured copper composite strengthened by amorphous boron framework.

Grain boundary engineering is a versatile tool for strengthening materials by tuning the composition and bonding structure at the interface of neighboring crystallites, and this method holds special significance for materials composed of small nanograins where the ultimate strength is dominated by grain boundary instead of dislocation motion. Here, we report a large strengthening of a nanocolumnar copper film that comprises columnar nanograins embedded in a bamboo-like boron framework synthesized by magnetron sputtering co-deposition, reaching the high nanoindentation hardness of 10.8 GPa among copper alloys. The boron framework surrounding copper nanograins stabilizes and strengthens the nanocolumnar copper film under indentation, benefiting from the high strength of the amorphous boron framework and the constrained deformation of copper nanocolumns confined by the boron grain boundary. These findings open a new avenue for strengthening metals via construction of dual-phase nanocomposites comprising metal nanograins embedded in a strong and confining light-element grain boundary framework.

Core Electron Count as a Versatile and Accurate New Descriptor for Sorting Mechanical Properties of Diverse Transition Metal Compounds.

Transition-metal light-element compounds show superb mechanical, chemical, and thermal properties, and accurate descriptors are important to sorting targeted properties among this vast class of materials. Valence electron concentration (VEC) can track broad trends of mechanical properties, but this widely used descriptor suffers low accuracy with sorted data strongly scattered along trendlines, necessitating an improved sorting strategy. Here, elastic parameters from first-principles calculations are examined for 81 ternary transition-metal nitrides (TMN) in cubic structure and 81 ternary transition-metal diborides (TMB2 ) in hexagonal structure and identify core electron count (CEC) of the solvent atoms as a new descriptor. Combined with VEC, the composite VEC-CEC descriptor exhibits greatly improved ability to sort elastic parameters of distinct TMN and TMB2 compounds. Unregulated property variations under the VEC description are well-captured by CEC, which tends to enhance ductility and reduce strength at fixed VEC and rising CEC. By invoking a full-electron consideration, the VEC-CEC descriptor accounts for the impact on bonding behaviors by both core and valence electrons with much-improved accuracy and versatility in sorting mechanical properties of diverse TM compounds compared to many other commonly used descriptors, opening a fresh path for rational design and optimization of TM compounds with tailored performance benchmarks.

A viable mechanism to form boron-bearing diamonds in deep Earth.

Boron is considered extremely depleted inside Earth's mantle. It is therefore a great challenge to elucidate the prevalence of boron impurity seen in sublithospheric diamonds, especially in identifying the boron source and the mechanism for its incorporation into these enigmatic diamonds. Here, we unveil a pathway for the crystallization of boron-bearing diamonds via redox reactions of carbonates and borides at pressure-temperature conditions relevant to the Earth's lower mantle. We present computational results along with pertinent experimental evidence for a genesis of boron-bearing diamonds via the redox reaction of CaCO3 and FeB at 22.5 GPa and 2100 K, corresponding to the geological conditions at the top of the lower mantle. The present findings offer a viable mechanism for the formation of boron-bearing diamonds deep inside the Earth's mantle.

Adjuvant DNA vaccine pNMM promotes enhanced specific immunity and anti-tumor effects.

DNA vaccines containing only antigenic components have limited efficacy and may fail to induce effective immune responses. Consequently, adjuvant molecules are often added to enhance immunogenicity. In this study, we generated a tumor vaccine using a plasmid encoding NMM (NY-ESO-1/MAGE-A3/MUC1) target antigens and immune-associated molecules. The products of the vaccine were analyzed in 293 T cells by western blotting, flow cytometry, and meso-scale discovery electrochemiluminescence. To assess the immunogenicity obtained, C57BL/6 mice were immunized using the DNA vaccine. The results revealed that following immunization, this DNA vaccine induced cellular immune responses in C57BL/6 mice, as evaluated by the release of IFN-γ, and we also detected increases in the percentages of nonspecific lymphocytes, as well as those of antigen-specific T cells. Furthermore, immunization with the pNMM vaccine was found to significantly inhibit tumor growth and prolonged the survival of mice with B16-NMM+-tumors. Our data revealed that pNMM DNA vaccines not only confer enhanced immunity against tumors but also provide a potentially novel approach for vaccine design. Moreover, our findings provide a basis for further studies on vaccine pharmacodynamics and pharmacology, and lay a solid foundation for clinical application.

Evidence for an emergent anomalous metallic state in compressed titanium.

The anomalous metallic state (AMS) emerging from a quantum superconductor-to-metal transition is a subject of great current interest since this exotic quantum state exhibits unconventional transport properties that challenge the core physics principles of Fermi liquid theory. As the AMS concept is historically derived from disordered two-dimensional (2D) systems, related studies have predominately concentrated on 2D materials. The AMS behaviors in three-dimensional (3D) systems have been rarely reported to date, which raises intriguing questions on the fundamental nature of pertinent physics. Here, we report experimental evidence for a 3D AMS in highly compressed titanium metal that exhibits superconductivity with a critical temperature (Tc) reaching near-record 25.1 K among elemental superconductors, offering a favorable material template for exploring 3D AMS. At sufficiently strong magnetic fields, unusual transport behaviors set in over a wide pressure range, showcasing AMS hallmarks of a low-temperature saturation resistance below the Drude value and giant positive magnetoresistance. These findings reveal a 3D AMS in simple elemental systems and, more importantly, provide a fresh platform for probing the decades-long enigmatic underlying physics.

Mechanism Regulating Self-Intercalation in Layered Materials.

Recent experimental breakthrough demonstrated a powerful synthesis approach for intercalating the van der Waals gap of layered materials to achieve property modulation, thereby opening an avenue for exploring new physics and devising novel applications, but the mechanism governing intercalant assembly patterns and properties remains unclear. Based on extensive structural search and energetics analysis by ab initio calculations, we reveal a Sabatier-like principle that dictates spatial arrangement of self-intercalated atoms in transition metal dichalcogenides. We further construct a robust descriptor quantifying that strong intercalant-host interactions favor a monodispersing phase of intercalated atoms that may exhibit ferromagnetism, while weak interactions lead to a trimer phase with attenuated or quenched magnetism, which further evolves into tetramer and hexagonal phases at increasing intercalant density. These findings elucidate the mechanism underpinning experimental observations and paves the way for rational design and precise control of self-intercalation in layered materials.

Solving Strength-Toughness Dilemma in Superhard Transition-Metal Diborides via a Distinct Chemically Tuned Solid Solution Approach.

Solid solution strengthening enhances hardness of metals by introducing solute atoms to create local distortions in base crystal lattice, which impedes dislocation motion and plastic deformation, leading to increased strength but reduced ductility and toughness. In sharp contrast, superhard materials comprising covalent bonds exhibit high strength but low toughness via a distinct mechanism dictated by brittle bond deformation, showcasing another prominent scenario of classic strength-toughness tradeoff dilemma. Solving this less explored and understood problem presents a formidable challenge that requires a viable strategy of tuning main load-bearing bonds in these strong but brittle materials to achieve concurrent enhancement of the peak stress and related strain range. Here, we demonstrate a chemically tuned solid solution approach that simultaneously enhances hardness and toughness of superhard transition-metal diboride Ta1-x Zr x B2. This striking phenomenon is achieved by introducing solute atom Zr that has lower electronegativity than solvent atom Ta to reduce the charge depletion on the main load-bearing B-B bonds during indentation, leading to prolonged deformation that gives rise to notably higher strain range and the corresponding peak stress. This finding highlights the crucial role of properly matched contrasting relative electronegativity of solute and solvent atoms in creating concurrent strengthening and toughening and opens a promising avenue for rational design of enhanced mechanical properties in a large class of transition-metal borides. This strategy of concurrent strength-toughness optimization via solute-atom-induced chemical tuning of the main load-bearing bonding charge is expected to work in broader classes of materials, such as nitrides and carbides.

Enhancing the Properties of Water-Soluble Copolymer Nanocomposites by Controlling the Layer Silicate Load and Exfoliated Nanolayers Adsorbed on Polymer Chains.

Novel polymer nanocomposites of methacryloyloxy ethyl dimethyl hexadecyl ammonium bromide-modified montmorillonite (O-MMt) with acrylamide/sodium p-styrene sulfonate/methacryloyloxy ethyl dimethyl hexadecyl ammonium bromide (ASD/O-MMt) were synthesized via in situ polymerization. The molecular structures of the synthesized materials were confirmed using Fourier-transform infrared and 1H-nuclear magnetic resonance spectroscopy. X-ray diffractometry and transmission electron microscopy revealed well-exfoliated and dispersed nanolayers in the polymer matrix, and scanning electron microscopy images revealed that the well-exfoliated nanolayers were strongly adsorbed on the polymer chains. The O-MMt intermediate load was optimized to 1.0%, and the exfoliated nanolayers with strongly adsorbed chains were controlled. The properties of the ASD/O-MMt copolymer nanocomposite, such as its resistance to high temperature, salt, and shear, were significantly enhanced compared with those obtained under other silicate loads. ASD/1.0 wt% O-MMt enhanced oil recovery by 10.5% because the presence of well-exfoliated and dispersed nanolayers improved the comprehensive properties of the nanocomposite. The large surface area, high aspect ratio, abundant active hydroxyl groups, and charge of the exfoliated O-MMt nanolayer also provided high reactivity and facilitated strong adsorption onto the polymer chains, thereby endowing the resulting nanocomposites with outstanding properties. Thus, the as-prepared polymer nanocomposites demonstrate significant potential for oil-recovery applications.

College students' screening early warning factors in identification of suicide risk.

This study aimed to explore the main influencing factors of suicide risk among Chinese students and establish an early warning model to provide interventions for high-risk students. We conducted surveys of students in their first and third years from a cohort study at Jining Medical College. Logistic regression models were used to screen the early warning factors, and four machine learning models were used to establish early warning models. There were 8 factors related to suicide risk that were eventually obtained through screening, including age, having a rough father, and CES-D, OHQ, ASLEC-4, BFI-Neuroticism, BFI-Openness, and MMC-AF-C scores. A random forest model with SMOTE was adopted, and it verified that these 8 early warning signs, for suicide risk can effectively predict suicide risk within 2 years with an AUC score of 0.947. Among the factors, we constructed a model that indicated that different personality traits affected suicide risk by different paths. Moreover, the factors obtained by screening can be used to identify college students in the same year with a high risk of suicide, with an AUC score that reached 0.953. Based on this study, we suggested some interventions to prevent students going high suicide risk.

Development and function of tissue-resident memory B cells.

Barrier tissues are the primary site of infection for pathogens likely to cause future pandemics. Tissue-resident lymphocytes can rapidly detect pathogens upon infection of barrier tissues and are critical in preventing viral spread. However, most vaccines fail to induce tissue-resident lymphocytes and are instead reliant on circulating antibodies to mediate protective immunity. Circulating antibody titers wane over time following vaccination leaving individuals susceptible to breakthrough infections by variant viral strains that evade antibody neutralization. Memory B cells were recently found to establish tissue residence following infection of barrier tissues. Here, we summarize emerging evidence for the importance of tissue-resident memory B cells in the establishment of protective immunity against viral and bacterial challenge. We also discuss the role of tissue-resident memory B cells in regulating the progression of non-infectious diseases. Finally, we examine new approaches to develop vaccines capable of eliciting barrier immunity.

Record high Tc element superconductivity achieved in titanium.

It is challenging to search for high Tc superconductivity (SC) in transition metal elements wherein d electrons are usually not favored by conventional BCS theory. Here we report experimental discovery of surprising SC up to 310 GPa with Tc above 20 K in wide pressure range from 108 GPa to 240 GPa in titanium. The maximum Tconset above 26.2 K and zero resistance Tczero of 21 K are record high values hitherto achieved among element superconductors. The Hc2(0) is estimated to be ∼32 Tesla with coherence length 32 Å. The results show strong s-d transfer and d band dominance, indicating correlation driven contributions to high Tc SC in dense titanium. This finding is in sharp contrast to the theoretical predications based on pristine electron-phonon coupling scenario. The study opens a fresh promising avenue for rational design and discovery of high Tc superconductors among simple materials via pressure tuned unconventional mechanism.

Direct H-He chemical association in superionic FeO2H2He at deep-Earth conditions.

Hydrogen and helium are known to play crucial roles in geological and astrophysical environments; however, they are inert toward each other across wide pressure-temperature (P-T) conditions. Given their prominent presence and influence on the formation and evolution of celestial bodies, it is of fundamental interest to explore the nature of interactions between hydrogen and helium. Using an advanced crystal structure search method, we have identified a quaternary compound FeO2H2He stabilized in a wide range of P-T conditions. Ab initio molecular dynamics simulations further reveal a novel superionic state of FeO2H2He hosting liquid-like diffusive hydrogen in the FeO2He sublattice, creating a conducive environment for H-He chemical association, at P-T conditions corresponding to the Earth's lowest mantle regions. To our surprise, this chemically facilitated coalescence of otherwise immiscible molecular species highlights a promising avenue for exploring this long-sought but hitherto unattainable state of matter. This finding raises strong prospects for exotic H-He mixtures inside Earth and possibly also in other astronomical bodies.

Robust Quantum Anomalous Hall States in Monolayer and Few-Layer TiTe.

Quantum anomalous Hall (QAH) insulators possess exotic properties driven by novel topological physics, but related studies and potential applications have been hindered by the ultralow temperatures required to sustain the operating mechanisms dictated by key material parameters. Here, using first-principles calculations, we predict a robust QAH state in monolayer TiTe that exhibits a high ferromagnetic Curie temperature of 650 K and a sizable band gap of 261 meV. These outstanding benchmark properties stem from the Te atom's large size that favors ferromagnetic kinetic exchange with the neighboring Ti atoms and strong spin-orbit coupling that creates a QAH state by adding a mass term to the Dirac half-semimetal state. Remarkably, the ferromagnetic order remains robust against interlayer stacking via the d-pz/py-pz-d super-super exchange, generating unprecedented QAH states in few-layer configurations with enhanced Curie temperatures and higher Chern numbers. These results signify layered TiTe to be a prime template for exploring novel QAH physics at ambient and higher temperatures.

Prediction of Above-Room-Temperature Superconductivity in Lanthanide/Actinide Extreme Superhydrides.

Achieving room-temperature superconductivity has been an enduring scientific pursuit driven by broad fundamental interest and enticing potential applications. The recent discovery of high-pressure clathrate superhydride LaH10 with superconducting critical temperatures (Tc) of 250-260 K made it tantalizingly close to realizing this long-sought goal. Here, we report a remarkable finding based on an advanced crystal structure search method of a new class of extremely hydrogen-rich clathrate superhydride MH18 (M: rare-earth/actinide atom) stoichiometric compounds stabilized at an experimentally accessible pressure of 350 GPa. These compounds are predicted to host Tc up to 330 K, which is well above room temperature. The bonding and electronic properties of these MH18 clathrate superhydrides closely resemble those of atomic metallic hydrogen, giving rise to the highest Tc hitherto found in a thermodynamically stable hydride compound. An in-depth study of these extreme superhydrides offers insights for elucidating phonon-mediated superconductivity above room temperature in hydrogen-rich and other low-Z materials.