Search

Periodontitis, a prevalent chronic oral disease, poses a significant threat to periodontal tissues, often resulting in substantial attachment loss and tooth shedding. Leveraging the principles of bone affinity and the mechanism underlying tetracycline pigmentation of teeth, this study strategically employed tetracycline (TC) as a bone-affinity group. We modified TC on the surface of polylactic- co -glycolic acid copolymer (PLGA) microspheres (MSs) through covalent binding, and then loaded berberine (BBR) MSs into a thermosensitive self-healing hydrogel delivery system (BBR/TC-MS). It was verified that the BBR/TC-MS gel rapidly formed an in situ reservoir in the periodontal pocket upon injection, and the chelation between TC and cementum in the periodontal pocket enhanced the anchoring effect of the TC-modified microspheres on cementum, preventing their loss through gingival crevicular fluid. Subsequently, we proved in vitro and in vivo that the BBR/TC-MS gel has excellent bacteriostatic effects against the periodontal pathogenic bacteria Fusobacterium necrophorum ( Fn ), anti-inflammation property in periodontal and gingival tissues, and osteogenic effect by regulating the RANKL-RANK-OPG pathway to diminish osteoclast activity, thus continuously exerting antibacterial, anti-inflammatory, osteogenic, and anti-osteoclastic effects. This innovative approach holds promise as a targeted and effective strategy for combating multifaceted challenges posed by periodontitis.

The G-quadruplex (GQ) formed by guanine-rich DNA strands exhibits superior thermal stability and electric properties, which have generated substantial interest in applying GQ DNA to bioelectric interfaces. However, single G-wires formed by GQs have not yet surpassed the μm length due to the lack of an optimal assembly protocol and understanding of assembly mechanisms that limit application. Herein, we optimized a self-assembly protocol for a short 4-nt oligonucleotide (dG4) to achieve micrometer lengths of G-wires, including the buffer composition, incubation process and surface assembly. Furthermore, both theoretical modeling and chemical modifications were applied to unveil the atomic-level detail of GQ monomer interfaces and indicated that the assembly process follows a stepwise mechanism from nucleation to grow into oligomers and nanowires.

Indole, a compound in Chinese stinky tofu (ST), acts as a ligand for the aryl hydrocarbon receptor (AHR). Despite extensive research on prebiotic compounds, indole's specific role in ST remains unexplored. This study used an ethanol gavage method to create an ALD (alcoholic liver disease) mouse model and investigate dietary indole's effects on the intestinal barrier. Our findings indicate that after 6 weeks of being fed ST, the indole present (2 mg/day) robustly activated the intestinal AHR, upregulating its target gene, CYP1A1 (cytochrome P450 1A1 enzyme). This activation significantly reduced intestinal permeability, mitigated alcohol-induced oxidative stress and inflammation, and restored intestinal barrier function. Consequently, the study demonstrates that foodborne indole substantially reduces alcohol absorption and lowers the expression levels of liver inflammation-related factors, thereby slowing the progression of ALD. These results highlight indole's therapeutic potential for treating ALD and its role in developing functional foods.

Background: The relationship between gut microbiota and osteoarthritis (OA) occurrence remains unclear. Existing research needs to clearly understand how basal metabolic rate (BMR) regulates this relationship. Therefore, using a two-step bidirectional Mendelian Randomization approach, our study aims to investigate whether BMR levels mediate the causal relationship between gut microbiota and OA., Methods: In this study, we examined publicly available summary statistics from Genome-Wide Association Studies (GWAS) to determine the correlation between gut microbiota and OA. The analysis included one primary dataset and two secondary datasets. Initially, a two-step, two-sample, and reverse MR analysis was performed to identify the causal relationship between gut microbiota and OA. Subsequently, a two-step MR analysis revealed that the relationship between microbiota and OA is mediated by BMR. Sensitivity analyses confirmed the robustness of the study results., Results: In our analysis of the primary dataset, we discovered a positive correlation between three taxa and the outcome of OA, and eight taxa exhibited a negative correlation with the OA outcome. Through comparisons with the secondary dataset and multiple testing corrections, we found a negative association between the class Actinobacteria (OR=0.992886277, p -value = 0.003) and the likelihood of OA occurrence. Notably, knee osteoarthritis (KOA) and hip osteoarthritis (HOA) had a strong negative correlation (OR = 0.927237553/0.892581219). Our analysis suggests that BMR significantly mediates the causal pathway from Actinobacteria to OA, with a mediated effect of 2.59%. Additionally, BMR mediates 3.98% of the impact in the path from the order Bifidobacteriales and the family Bifidobacteriaceae to OA. Besides these findings, our reverse analysis did not indicate any significant effect of OA on gut microbiota or BMR., Conclusion: Our research results indicate that an increase in the abundance of specific gut microbial taxa is associated with a reduced incidence of OA, and BMR levels mediate this causal relationship. Further large-scale randomized controlled trials are necessary to validate the causal impact of gut microbiota on the risk of OA. This study provides new insights into the potential prevention of OA by modulating the gut microbiota., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Liang, Liu, Sun and Sun.)

The particle-particle random phase approximation (ppRPA) within the hole-hole channel was recently proposed as an efficient tool for computing excitation energies of point defects in solids [ J. Phys. Chem. Lett. 2024, 15, 2757-2764]. In this work, we investigate the application of ppRPA within the particle-particle channel for predicting correlated excited states of point defects, including the carbon-vacancy (VC) in diamond, the oxygen-vacancy (VO) in magnesium oxide (MgO), and the carbon dimer defect (C B C N ) in two-dimensional hexagonal boron nitride (h-BN). Starting from a density functional theory calculation of the ( N - 2)-electron ground state, vertical excitation energies of the N -electron system are obtained as the differences between the two-electron addition energies. We show that active-space ppRPA with the B3LYP functional yields accurate excitation energies, with errors mostly smaller than 0.1 eV for tested systems compared to available experimental values. We further develop a natural transition orbital scheme within ppRPA, which provides insights into the multireference character of defect states. This study, together with our previous work, establishes ppRPA as a low-cost and accurate method for investigating excited-state properties of point defect systems.

Reducing VOCs can effectively reduce the concentration of PM 2.5 and O 3 . Different gasoline compositions can impact the VOC species emitted by GDI and PFI vehicles. In this study, VOC species emitted from GDI and PFI vehicles combusting gasoline with different compositions (i.e., G1-market #92 gasoline, G2-high alkane gasoline, and G3-high heavy aromatic gasoline) were tested, and the influence of VOC species on O 3 formation were investigated. The results indicated that the GDI vehicle consistently exhibited higher VOC emissions than the PFI vehicle in combusting three types of gasolines. The presence of short-chain alkanes and alkenes in the exhaust of combusting G2 and ethyne among the aromatics of combusting G3 resulted in higher VOC emissions from combusting G2 and G3 than from combusting G1 in the GDI vehicle. High alkane gasoline exhibited larger reductions of VOC emissions in the PFI vehicle but increased the proportions of propene, 1-butene, and ethyne emissions. High heavy aromatic gasoline increased the proportion of ethyne emissions in the GDI vehicle and increased the proportion of toluene, formaldehyde, and propane emissions in the PFI vehicle. The overall emission variation of ozone formation potential (OFP) was similar to those of VOC emissions. Alkene (C2-C6), monocyclic aromatic hydrocarbons (MAHs) and aldehydes had high contribution to O 3 formation. Further research is needed to optimize fuel upgrading for GDI vehicles to ensure effective emission reduction. The results would help reduce vehicle emissions and provide support for achieving synergistic prevention and control of PM 2.5 and O 3 pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The pseudorabies virus (PRV) causes severe and fatal acute respiratory disease in pigs. During PRV proliferation, the enzyme deoxyuridine 5'-triphosphate nucleotide hydrolase (dUTPase) plays a pivotal role in maintaining a low dUTP/dTTP ratio, thereby ensuring the accuracy of viral DNA replication. However, its structure and catalytic mechanisms have not been fully elucidated. Here, we report the crystal structure of PRV dUTPase at a 2.24 Å resolution and demonstrate an unprecedented dimeric architecture, with a conserved enzyme activity center of the herpesvirus family. The enzyme activity center is located in a cavity between the two domains, forming a pocket for binding substrate dUMP and magnesium ions. Remarkably, the exquisite interface of the dimer is primarily composed of four antiparallel β-sheets, which form 11 hydrogen bonds between the residues P33-V36 and R242-A248 to maintain protein stability. To the best of our knowledge, this is the first report demonstrating that dUTPase exists as a dimer in the herpesvirus family. These findings not only present a novel fold dimeric structure but also deepen the scope of our comprehension of structural diversity in dUTPase family., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

The efficiency of silicon solar cells is still lower than theoretical values, partly due to their inability to utilize the ultraviolet and infrared portions of the solar spectrum. Herein, a novel method using a KCa 2 Mg 2 (VO 4 ) 3 phosphor with a down-shift effect to improve the photovoltaic performance of silicon solar cells and enhance the utilization of UV light in standard p-type silicon solar cells is proposed. The synthesized phosphors were mixed with an ethylene vinyl acetate (EVA) copolymer and pressed into a film, which was subsequently encapsulated in monocrystalline silicon solar cells. The results show that the addition of this film notably enhanced the photovoltaic performance of the silicon solar cells; the current density was increased by 2.89% (from 33.20 to 34.16 mA cm -2 ), and the photovoltaic conversion efficiency was improved by 5.69% (from 15.11% to 15.97%) at the optimal concentration compared to bare cells.

Background: Ischemic stroke leads a primary cause of mortality in human diseases, with a high disability rate worldwide. This study aims to investigate the function of β-1,4-galactosyltransferase 1 (B4galt1) in mouse brain ischemia/reperfusion (I/R) injury., Methods: Recombinant human B4galt1 (rh-B4galt1) was intranasally administered to the mice model of middle cerebral artery occlusion (MCAO)/reperfusion. In this study, the impact of rh-B4galt1 on cerebral injury assessed using multiple methods, including the neurological disability status scale, 2,3,5-triphenyltetrazolium chloride (TTC), Nissl and TUNEL staining. This study utilized laser speckle Doppler flowmeter to monitor the cerebral blood flow. Western blotting was performed to assess the protein expression levels, and fluorescence-labeled dihydroethidium method was performed to determine the superoxide anion generation. Assay kits were used for the measurement of iron, malondialdehyde (MDA) and glutathione (GSH) levels., Results: We demonstrated that rh-B4galt1 markedly improved neurological function, reduced cerebral infarct volume and preserved the completeness of blood-brain barrier (BBB) for preventing damage. These findings further illustrated that rh-B4galt1 alleviated oxidative stress, lipid peroxidation, as well as iron deposition induced by I/R. The vital role of ferroptosis was proved in brain injury. Furthermore, the rh-B4galt1 could increase the levels of TAZ, Nrf2 and HO-1 after I/R. And TAZ-siRNA and ML385 reversed the neuroprotective effects of rh-B4galt1., Conclusions: The results indicated that rh-B4galt1 implements neuroprotective effects by modulating ferroptosis, primarily via upregulating TAZ/Nrf2/HO-1 pathway. Thus, B4galt1 could be seen as a promising novel objective for ischemic stroke therapy., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Metallo-β-lactamases (MβLs) hydrolyze and inactivate β-lactam antibiotics, are a pivotal mechanism conferring resistance against bacterial infections. SMB-1, a novel B3 subclass of MβLs from Serratia marcescens could deactivate almost all β-lactam antibiotics including ampicillin (AMP), which has posed a serious threat to public health. To illuminate the mechanism of recognition and interaction between SMB-1 and AMP, various fluorescence spectroscopy techniques and molecular dynamics simulation were employed. The results of quenching spectroscopy unraveled that AMP could make SMB-1 fluorescence quenching that mechanism was the static quenching; the synchronous and three-dimensional fluorescence spectra validated that the microenvironment and conformation of SMB-1 were altered after interaction with AMP. The molecular dynamics results demonstrated that the whole AMP enters the binding pocket of SMB-1, even though with a relatively bulky R1 side chain. Loop1 and loop2 in SMB-1 undergo significant fluctuations, and α2 (71-73) and local α5 (186-188) were turned into random coils, promoting zinc ion exposure consistent with circular dichroism spectroscopy results. The binding between them was driven by a combination of enthalpy and entropy changes, which was dominated by electrostatic force in agreement with the fluorescence observations. The present study brings structural insights and solid foundations for the design of new substrates for β-lactamases and the development of effective antibiotics that are resistant to superbugs., (© 2024 John Wiley & Sons Ltd.)

Introduction: Accurate evaluation of exacerbation frequency is an essential part of COPD assessment. But relying on just the prior-year exacerbation history may not capture the full picture of risk given the inherent year-to-year fluctuations in exacerbation rates. This study aimed to evaluate the predictive performance of models incorporating the 3-year exacerbation history based on electronic medical record., Materials and Methods: This retrospective cohort study included 86,501 COPD hospitalized patients in Beijing from 2008 to 2014. The annual frequency of COPD exacerbation hospitalizations over a 3-year period after the index hospitalization was calculated, with patients segmented into seven distinct exacerbation trajectory groups. Logistic regression was used to evaluate the predictive capability of the 3-year exacerbation history for exacerbation readmission in the fourth year. Predictors included age, sex, comorbidities, and exacerbation hospitalization in previous 1-3 years. Model performance was evaluated using area under the receiver operating characteristic curve (AUC)., Results: Of the studied patients, 56.5% were men, and the mean age (SD) was 73.8 (10.3) years. The overall readmission rate for COPD exacerbation was 0.31 per person-year, with only 3.8% of patients persistently readmitted over three consecutive years. The 3-year trajectory of exacerbation frequency was associated with exacerbation risk in the fourth year. Compared to just the prior year, the inclusion of a 3-year exacerbation hospitalization history notably improved prediction accuracy, with AUC elevating from 0.731 (0.724-0.739) to 0.786 (0.779-0.792)., Conclusion: These results unveil the fluctuating nature of COPD exacerbation hospitalization frequency across years and demonstrate that integrating a more comprehensive 3-year exacerbation history significantly refines the prediction model for future risk, thus providing a more nuanced and actionable insight for clinical care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Current research in cancer therapy focuses on personalized therapies, through nanotechnology-based targeted drug delivery systems. Particularly, controlled drug release with nanoparticles (NPs) can be designed to safely transport various active agents, optimizing delivery to specific organs and tumors, minimizing side effects. The use of microfluidics (MFs) in this field has stood out against conventional methods by allowing precise control over parameters like size, structure, composition, and mechanical/biological properties of nanoscale carriers. This review compiles applications of microfluidics in the production of core-shell NPs (CSNPs) for cancer therapy, discussing the versatility inherent in various microchannel and/or micromixer setups and showcasing how these setups can be utilized individually or in combination, as well as how this technology allows the development of new advances in more efficient and controlled fabrication of core-shell nanoformulations. Recent biological studies have achieved an effective, safe, and controlled delivery of otherwise unreliable encapsulants such as small interfering RNA (siRNA), plasmid DNA (pDNA), and cisplatin as a result of precisely tuned fabrication of nanocarriers, showing that this technology is paving the way for innovative strategies in cancer therapy nanofabrication, characterized by continuous production and high reproducibility. Finally, this review analyzes the technical, biological, and technological limitations that currently prevent this technology from becoming the standard., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

This investigation explores the impact of various fermentation techniques and the inoculation of Bacillus subtilis spores on the physicochemical properties and principal flavor profiles of Huangjiu. Employing sensory analysis, headspace solid-phase microextraction, gas chromatography-tandem mass spectrometry (HS-SPME-GC-MS), and orthogonal partial least squares discriminant analysis (OPLS-DA), we observed that these variables significantly alter the physicochemical attributes of Huangjiu. Our analysis, integrating volatile organic compounds (VOCs) with odor activity values (OAV), revealed that while B. subtilis inoculation modifies the concentrations of key flavor compounds, it does not affect their types. Notably, the inoculation enhances the concentrations of 13 primary flavor compounds, thereby enriching floral and fruity notes while reducing higher alcohol levels. These findings contribute valuable insights into the flavor formation mechanisms of Huangjiu and guide the optimization of fermentation processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Behcet's syndrome (BS) is a vasculitis characterized by immune dysregulation. Biomarkers are valuable for assessing clinically atypical pathogenesis. We aimed to investigate the distribution of different biomarkers and their effects on the clinical features of patients with BS in a large-scale, real-world study. This is a retrospective, single-center study. In total, 502 patients diagnosed with BS were enrolled in this study. We analyzed the clinical features of this cohort and divided patients' symptoms into six categories, including mucocutaneous, articular, neurological, gastrointestinal, vascular, and ocular involvements. HLA-B51 cells, autoantibodies, and subsets of immune cells from the patients were tested. Pearson's correlation, Wilcoxon rank sum test and multivariate logistic regression were used for data analysis. Various autoantibodies were detected in the serum of 40.8% of patients with BS. The positivity rate of anti-endothelial cell antibodies (AECA) was the highest among autoantibodies and was found in 23.5% (118/502) of patients with BS. The positivity rate of HLA-B51 in patients with BS was 27.1%. Tumor necrosis factor (TNF)-α, IL-2, and IL-4 producing CD4 + T cells were positively correlated with the gastrointestinal BS. Increased IL-4 + CD4 + T cell was a risk factor for gastrointestinal BS (P = 0.006, Overall rate [OR] = 2.491, 95% Confidence interval [CI]: [1.317, 5.100]). Various autoantibodies can be detected in patients with BS. HLA-B51 and AECA are the most common biomarkers. Increased IL-4 + CD4 + T cell was a risk factor for gastrointestinal involvement in BS., (© 2024. The Author(s).)

Lungs can undergo facultative regeneration, but handicapped regeneration often leads to fibrosis. How microenvironmental cues coordinate lung regeneration via modulating cell death remains unknown. Here, we reveal that the neurotransmitter dopamine modifies the endothelial niche to suppress ferroptosis, promoting lung regeneration over fibrosis. A chemoproteomic approach shows that dopamine blocks ferroptosis in endothelial cells (ECs) via dopaminylating triosephosphate isomerase 1 (TPI1). Suppressing TPI1 dopaminylation in ECs triggers ferroptotic angiocrine signaling to aberrantly activate fibroblasts, leading to a transition from lung regeneration to fibrosis. Mechanistically, dopaminylation of glutamine (Q) 65 residue in TPI1 directionally enhances TPI1's activity to convert dihydroxyacetone phosphate (DHAP) to glyceraldehyde 3-phosphate (GAP), directing ether phospholipid synthesis to glucose metabolism in regenerating lung ECs. This metabolic shift attenuates lipid peroxidation and blocks ferroptosis. Restoring TPI1 Q65 dopaminylation in an injured endothelial niche overturns ferroptosis to normalize pro-regenerative angiocrine function and alleviate lung fibrosis. Overall, dopaminylation of TPI1 balances lipid/glucose metabolism and suppresses pro-fibrotic ferroptosis in regenerating lungs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The risk of developing dementia is higher in individuals who suffer from perioperative neurocognitive disorder (PND), including postoperative cognitive dysfunction (POCD) and delirium. Recent studies have indicated correlations between anesthesia, surgery and PND. Acute metabolic changes induced by anesthesia and surgery may be related to cognitive impairments. Despite a paucity of research on acute metabolic changes in the hippocampus during surgery, there are conflicting about specific metabolites., Methods: We developed a mouse model of cognitive impairment induced by isoflurane anesthesia and unilateral nephrectomy. Cognition was evaluated by Y maze and fear conditioning test (FCT). The hippocampus was harvested after the surgery. LC-MS (liquid chromatography-mass spectrometry) was performed. The differential metabolites involved in lipid, amino acid, nucleotide, carbohydrate metabolism were analyzed., Results: Anesthesia and surgery exposure induced cognition decline. A total of 49 metabolites were significantly up-regulated and 122 down-regulated. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the metabolites identified purine, glutathione, nicotinate and nicotinamide metabolism. Metabolites involved in lipid, amino acid, nucleotide, carbohydrate metabolism were identified including nicotinamide adenine dinucleotide (NAD), 1-Methylnicotinamide, propionic acid, histidine, adenosine, and guanosine cyclic monophosphate. Some metabolites exhibited a consistent change trend in the hippocampus of aging mice., Conclusions: The study indicates that anesthesia and surgery can induce acute alterations in hippocampal metabolomics, including metabolites involved in lipid, amino acid, nucleotide, and carbohydrate metabolism. These metabolites may play a role in modulating PND through the regulation of neuroinflammation, oxidative stress, blood-brain barrier (BBB) permeability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Emerging evidence indicates a significant role of remnant cholesterol in contributing to the residual risk associated with major adverse cardiovascular events (MACE). This study aims to evaluate the dose-response relationship between remnant cholesterol and the risk of MACE. PubMed, Embase and Cochrane databases were reviewed to identify cohort studies published in English up to 1 August 2023. Twenty-eight articles were selected. Pooled hazard ratios (HR) and their 95% confidence intervals (CIs) were calculated using fixed or random-effects models to evaluate the association between remnant cholesterol and the risk of MACE. The dose-response relationship between remnant cholesterol levels and the risk of MACE was analyzed using the linear model and restricted cubic spline regression models. For calculated remnant cholesterol levels, the pooled HR (95% CI) of MACE for per 1-SD increase was 1.13 (1.08, 1.17); HR (95% CI) for the second quartile (Q2), the third quartile (Q3) and the highest quartile (Q4) of remnant cholesterol levels were 1.14 (1.03, 1.25), 1.43 (1.23, 1.68) and 1.68 (1.44, 1.97), respectively, compared with the lowest quartile (Q1). For measured remnant cholesterol levels, the pooled HR (95% CI) of MACE per 1-SD increase was 1.67 (1.39, 2.01). The dose-response meta-analysis showed a dose-response relationship between remnant cholesterol levels and the risk of MACE, both on a linear trend (P < 0.0001) and a nonlinear trend (P < 0.0001). The risk of MACE is associated with increased levels of remnant cholesterol, and the dose-response relationship between remnant cholesterol levels and the risk of MACE showed both linear and nonlinear trends., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The intensive use of antibiotics has resulted in strong natural selection for the evolution of antimicrobial resistance (AMR), but whether, and under what circumstances, the removal of antibiotics would result in a rapid reduction in AMR has been insufficiently explored. We aimed to test the hypothesis that in the simple, yet common, case of AMR conferred by a single gene, removing antibiotics would quickly reduce the prevalence of resistance if the AMR gene imposes a high fitness cost and costless resistance is extremely rare among its proximal mutants., Methods: In this genetic study, to test our hypothesis, we used the mcr-1 gene in Escherichia coli, which confers resistance to the last-resort antibiotic colistin, as a model. A high-throughput reverse genetics approach was used to evaluate mcr-1 variants for their fitness cost and resistance levels relative to a non-functional construct, by measuring relative growth rates in colistin-free media and at 2 μg/mL and 4 μg/mL colistin. We identified costless resistant mcr-1 mutants, and examined their properties within the context of the sequential organisation of mcr-1's functional domains as well as the evolutionary accessibility of these mutations. Finally, a simple population genetic model incorporating the measured fitness cost was constructed and tested against previously published real-world data of mcr-1 prevalence in colonised inpatients in China since the 2017 colistin ban in fodder additives., Findings: We estimated the relative growth rates of 14 742 mcr-1 E coli variants (including the wild type), 3449 of which were single-nucleotide mutants. E coli showed 73·8% less growth per 24 h when carrying wild-type mcr-1 compared with the non-functional construct. 6252 (42·4%) of 14 741 mcr-1 mutants showed colistin resistance accompanied by significant fitness costs, when grown under 4 μg/mL colistin selection. 43 (0·3%) mcr-1 mutants exhibited costless resistance, most of which contained multiple mutations. Among the 3449 single mutants of mcr-1, 3433 (99·5%) had a fitness cost when grown in colistin-free media, with a mean relative growth of 0·305 (SD 0·193) compared with the non-functional variant. 3059 (88·7%) and 1833 (53·1%) of 3449 single mutants outgrew the non-functional mcr-1 in the presence of 2 μg/mL and 4 μg/mL colistin, respectively. Single mutations that gave rise to costless mutants were rare in all three domains of mcr-1 (transmembrane domain, flexible linker, and catalytic domain), but the linker domain was enriched with cost-reducing and resistance-enhancing mutations and depleted with cost-increasing mutations. The population genetics model based on the experimental data accurately predicts the rapid decline in mcr-1 prevalence in real-world data., Interpretation: Many identified costless resistant variants that consist of multiple mutations are unlikely to evolve easily in nature. These findings for colistin and mcr-1 might be applicable to other cases in which AMR entails a substantial fitness cost that cannot be mitigated in proximal mutants., Funding: National Natural Science Foundation of China, and National Key Research and Development Program of China., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Dynamical mean-field theory (DMFT) and its cluster extensions provide an efficient Green's function formalism to simulate spectral properties of periodic systems at the quantum many-body level. However, traditional cluster DMFT breaks translational invariance in solid-state materials, and the best strategy to capture non-local correlation effects within cluster DMFT remains elusive. In this work, we investigate the use of overlapping atom-centered impurity fragments in recently-developed ab initio all-orbital DMFT, where all local orbitals within the impurity are treated with high-level quantum chemistry impurity solvers. We demonstrate how the translational symmetry of the lattice self-energy can be restored by designing symmetry-adapted embedding problems, which results in an improved description of spectral functions in two-dimensional boron nitride monolayers and graphene at the levels of many-body perturbation theory (GW) and coupled-cluster theory. Furthermore, we study the convergence of self-energy and density of states as the embedding size is systematically expanded in one-shot and self-consistent DMFT calculations.

The Bethe-Salpeter equation using the GW approximation to the self-energy (BSE@ GW ) is a computationally attractive method for studying electronic excitation from first principles within the many-body Green's function theory framework. We examine its dependence on the underlying exchange-correlation (XC) approximation as well as on the GW approximation for predicting the charge transfer exciton formation at representative type-II interfaces between molecular systems of tetrachloro-1,2-benzoquinone (TCBQ) and acene derivatives. For the XC approximation, we consider several widely used generalized gradient approximation (GGA) and hybrid GGA functionals. For the GW self-energy approximation, we examine the recently proposed renormalized singles approach by Yang and coauthors [ J. Phys. Chem. Lett. 2019 , 10 (3), 447-452; J. Chem. Theory Comput. 2022 , 18, 7570-7585] in addition to other commonly employed approximated GW schemes. We demonstrate a reliable prediction of the charge transfer exciton within the BSE@ GW level of theory.

Introduction: We evaluated the impact of heating conventional cigarettes with a novel heated tobacco product (HTP) device on biomarkers and cigarette use patterns in Chinese adult smokers unwilling to quit smoking., Methods: In this pilot randomized controlled trial, 50 eligible participants were allocated to either Control group (smoking conventional cigarettes) or HTP device group (switching to using heated conventional cigarettes by the HTP device). Participants in the HTP device group went through a 2-day run-in period then used heated conventional cigarettes exclusively for 5 days, followed by flexible use for 14 days. Five biomarkers of exposure (BoEs) were measured at baseline and on Day 7. Thirteen biomarkers of biological effect (BoBEs) were measured at baseline and on Day 21. Safety, daily cigarette consumption, craving, withdrawal symptoms, and device acceptability, were assessed., Results: BoE levels decreased by 26.4 % to 71.4% from baseline in the HTP device group, while BoBE levels did not significantly change in either group. In the HTP group, 56% exclusively used heated conventional cigarettes during the flexible use period, experiencing reduced cravings and withdrawal symptoms, while dual users consumed more cigarettes. Mild to moderate device-related reactions were reported in 36% of users. Satisfaction, taste, and harm reduction belief scores averaged 7.4, 6.6, and 8.7 (out of 10), respectively., Conclusions: Switching to heated cigarettes with the HTP device may reduce short-term exposure to smoke toxicants. However, it can lead to increased tobacco use among dual users. Further investigation is needed to confirm these preliminary findings., Implications: This study is the first to evaluate the impact of heating conventional cigarettes with a novel heated tobacco product (HTP) device on health-related biomarkers and cigarette use patterns among Chinese adult smokers. This novel HTP device can directly heat conventional cigarettes without the necessity for specifically designed tobacco products, avoiding potential additive risks of traditional HTPs. If the results of this study could be further verified by randomized controlled clinical trials with larger sample sizes, this novel HTP device could serve as a short-term harm reduction alternative for smokers unwilling to quit., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The cost of annual energy consumption in buildings in the United States exceeds 430 billion dollars ( Science 2019, 364 (6442), 760-763), of which about 48% is used for space thermal management (https://www.iea.org/reports/global-status-report-for-buildings-and-construction-2019), revealing the urgent need for efficient thermal management of buildings and dwellings. Radiative cooling technologies, combined with the booming photonic and microfabrication technologies ( Nature 2014, 515 (7528), 540-544), enable energy-free cooling by radiative heat transfer to outer space through the atmospheric transparent window ( Nat. Commun. 2024, 15 (1), 815). To pursue all-season energy savings in climates with large temperature variations, switchable and tunable radiative coolers (STRC) have emerged in recent years and quickly gained broad attention. This Perspective introduces the existing STRC technologies and analyzes their benefits and challenges in future large-scale applications, suggesting ways for the development of future STRCs.

For first-order phase transitions, the second derivatives of Gibbs free energy (specific heat and compressibility) diverge at the transition point, resulting in an effect known as super-elasticity along the pressure axis, or super-thermicity along the temperature axis. Here we report a chemical analogy of these singularity effects along the atomic doping axis, where the second derivative of Gibbs free energy (chemical susceptibility) diverges at the transition point, leading to an anomalously high energy barrier for dopant diffusion in co-existing phases, an effect we coin as super-susceptibility. The effect is realized in hydrogen diffusion in vanadium dioxide (VO 2 ) with a metal-insulator transition (MIT). We show that hydrogen faces three times higher energy barrier and over one order of magnitude lower diffusivity when it diffuses across a metal-insulator domain wall in VO 2 . The additional energy barrier is attributed to a volumetric energy penalty that the diffusers need to pay for the reduction of latent heat. The super-susceptibility and resultant retarded atomic diffusion are expected to exist universally in all phase transformations where the transformation temperature is coupled to chemical composition, and inspires new ways to engineer dopant diffusion in phase-coexisting material systems., (© 2024. The Author(s).)

Background: The apoptosis-resistant pulmonary arterial endothelial cells (PAECs) are known to be major players in the pulmonary remodeling of pulmonary arterial hypertension (PAH) and exhibit an abnormal metabolic profile with mitochondrial dysfunction. Mitochondrial fission has been shown to regulate the apoptosis of several cell types, but this is largely unexplored in the PAECs., Objective: The roles of mitochondrial fission control by Dynamin related protein-1 (DRP1) in the development of PAECs apoptosis suppression were investigated in present study and the potential mechanisms behind this were furtherly explored., Methods: The mitochondrial morphology was investigated in PAECs from PAH rats with the pulmonary plexiform lesions, and the relations of it with DRP1 expression and apoptosis were furtherly identified in apoptosis-resistant PAECs induced by hypoxia. PAECs were isolated from rats with severe PAH and from normal subjects, the apoptotic-resistant PAECs were induced by hypoxia. DRP1 gene knockdown was achieved via DRP1-siRNA, DRP1 and STAT3 phosphorylation were blocked using its inhibitors, respectively. Apoptosis was analyzed by flow cytometry, and mitochondrial morphology was investigated by transmission electron microscope and confocal microscopy., Results: The PAECs isolated from PAH rats with the pulmonary plexiform-like lesions and displayed lower apoptotic rate with increased DRP1 expression and mitochondrial fragmentation. In addition, similar observations were achieved in apoptosis-resistant PAECs induced by hypoxia. Targeting DRP1 using siRNA and pharmacologic blockade prevented the mitochondrial fission and subsequent apoptotic resistance in PAECs under hypoxia. Mechanistically, STAT3 phosphorylation at Tyr705 was shown to be activated in both PAH and hypoxia-treated PAECs, leading to the regulation of DRP1 expression. Of importance, targeting STAT3Tyr705 phosphorylation prevented DRP1 disruption on apoptosis in PAECs under hypoxia., Conclusions: These data indicated that STAT3 phosphorylation at Tyr705 impacted DRP1-controlled mitochondrial fission during the development of apoptosis-resistance in PAECs, suggesting mitochondrial dynamics may represent a therapeutic target for PAH., (© 2024. The Author(s).)

Owing to stringent vehicle emission regulations and the shifting automotive landscape towards clean-energy vehicles, the emission of non-exhaust tire-wear particles and its implications for microplastic contamination have garnered substantial attention, emerging as a focal point of research interest. Unlike traditional source apportionment methods involving direct environmental sampling, this study focuses on the physical and chemical attributes of tire treads, the tread temperature changes, and the tire-wear particle emissions of three light-duty vehicles manufactured between 2011 and 2021. This study advances the understanding of the effects of tire properties on particle emissions, which provides preliminary information on low-wear tires. The results show that tire-wear particle emissions, mainly composed of ultrafine particles in terms of number, heavily depend on the elevated tread temperatures. The change in tread temperature is influenced not only by the initial tread temperature but also by tread pyrolysis characteristics. Ca, Mg, and Zn are abundantly contained in the tire tread and tire-wear particles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We develop a functional derivative approach to calculate the chemical potentials of second-order perturbation theory (MP2). In the functional derivative approach, the correlation part of the MP2 chemical potential, which is the derivative of the MP2 correlation energy with respect to the occupation number of frontier orbitals, is obtained from the chain rule via the noninteracting Green's function. First, the MP2 correlation energy is expressed in terms of the noninteracting Green's function, and its functional derivative to the noninteracting Green's function is the second-order self-energy. Then, the derivative of the noninteracting Green's function to the occupation number is obtained by including the orbital relaxation effect. We show that the MP2 chemical potentials obtained from the functional derivative approach agree with that obtained from the finite difference approach. The one-electron Hamiltonian, defined as the derivative of the MP2 energy with respect to the one particle density matrix, is also derived using the functional derivative approach, which can be used in the self-consistent calculations of MP2 and double-hybrid density functionals. The developed functional derivative approach is promising for calculating the chemical potentials and the one-electron Hamiltonian of approximate functionals and many-body perturbation approaches dependent explicitly on the noninteracting Green's function.

The strategy of parallel factor analysis, combined with the internal standard method, has been increasingly applied to the qualitative and quantitative analysis of three-dimensional fluorescence spectra of unknown mixed fluorophores. Nevertheless, the disparity in the number of fluorophores included in the internal standard sample set and the number included in test samples may impact the qualitative and quantitative outcomes of parallel factor analysis. In this work, we systematically established the framework of the parallel factor analysis with internal standard sample embedding (ISSE-PARAFAC) strategy. We applied this framework to six datasets representing two scenarios and a real dataset and conducted a detailed discussion on the effects of the disparity between the number of fluorophores in the internal standard sample set and the number in the test set on both qualitative and quantitative results. Additionally, we introduced an enhancement to PARAFAC by aggregating fluorophores with similar emission wavelengths, corresponding to the peaks of emission loadings (spectra) obtained from PARAFAC, as a single fluorophore. This aggregation aimed to mitigate the strong correlation between similar fluorophores. The results imply that the presence of irrelevant fluorophores in the internal standard sample set, whether increased or decreased, does not significantly affect the qualitative and quantitative analysis of target fluorophores in the test set. Moreover, we demonstrated that the improved parallel factor analysis with internal standard sample embedding not only fully decomposes the uncorrelated mixed fluorophores for qualitative analysis but also allows the established linear concentration model for fluorescent components to predict the corresponding fluorophore concentration of test samples, enabling quantitative analysis at the ppm level (mg/L)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving multidrug resistance. To uncover the mechanism of hMRP5, we determine six distinct cryo-EM structures, revealing an autoinhibitory N-terminal peptide that must dissociate to permit subsequent substrate recruitment. Guided by these molecular insights, we design an inhibitory peptide that could block substrate entry into the transport pathway. We also identify a regulatory motif, comprising a positively charged cluster and hydrophobic patches, within the first nucleotide-binding domain that modulates hMRP5 localization by engaging with membranes. By integrating our structural, biochemical, computational, and cell biological findings, we propose a model for hMRP5 conformational cycling and localization. Overall, this work provides mechanistic understanding of hMRP5 function, while informing future selective hMRP5 inhibitor development. More broadly, this study advances our understanding of the structural dynamics and inhibition of ABC transporters., (© 2024. The Author(s).)

Background: Mobile health (mHealth) is an emerging mobile communication and networking technology for health care systems. The integration of mHealth in medical education is growing extremely rapidly, bringing new changes to the field. However, no study has analyzed the publication and research trends occurring in both mHealth and medical education., Objective: The aim of this study was to summarize the current application and development trends of mHealth in medical education by searching and analyzing published articles related to both mHealth and medical education., Methods: The literature related to mHealth and medical education published from 2003 to 2023 was searched in the Web of Science core database, and 790 articles were screened according to the search strategy. The HistCite Pro 2.0 tool was used to analyze bibliometric indicators. VOSviewer, Pajek64, and SCImago Graphica software were used to visualize research trends and identify hot spots in the field., Results: In the past two decades, the number of published papers on mHealth in medical education has gradually increased, from only 3 papers in 2003 to 130 in 2022; this increase became particularly evident in 2007. The global citation score was determined to be 10,600, with an average of 13.42 citations per article. The local citation score was 96. The United States is the country with the most widespread application of mHealth in medical education, and most of the institutions conducting in-depth research in this field are also located in the United States, closely followed by China and the United Kingdom. Based on current trends, global coauthorship and research exchange will likely continue to expand. Among the research journals publishing in this joint field, journals published by JMIR Publications have an absolute advantage. A total of 105 keywords were identified, which were divided into five categories pointing to different research directions., Conclusions: Under the influence of COVID-19, along with the popularization of smartphones and modern communication technology, the field of combining mHealth and medical education has become a more popular research direction. The concept and application of digital health will be promoted in future developments of medical education., (© Yuanhang He, Zhihong Xie, Jiachen Li, Ziang Meng, Dongbo Xue, Chenjun Hao. Originally published in JMIR Medical Education (https://mededu.jmir.org).)

Rifampicin is the most powerful first-line antibiotic for tuberculosis, which is caused by Mycobacterium tuberculosis. Although accumulating evidence from sequencing data of clinical M. tuberculosis isolates suggested that mutations in the rifampicin-resistance-determining region (RRDR) are strongly associated with rifampicin resistance, the comprehensive characterisation of RRDR polymorphisms that confer this resistance remains challenging. By incorporating I-SceI sites for I-SceI-based integrant removal and utilizing an L5 swap strategy, we efficiently replaced the integrated plasmid with alternative alleles, making mass allelic exchange feasible in mycobacteria. Using this method to establish a fitness-related gain-of function screen, we generated a mutant library that included all single-amino-acid mutations in the RRDR, and identified the important positions corresponding to some well-known rifampicin-resistance mutations (Q513, D516, S522, H525, R529, S531). We also detected a novel two-point mutation located in the RRDR confers a fitness advantage to M. smegmatis in the presence or absence of rifampicin. Our method provides a comprehensive insight into the growth phenotypes of RRDR mutants and should facilitate the development of anti-tuberculosis drugs., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Because of global warming, people have paid more attention to greenhouse gas emitted by vehicles. To quantify the impact of temperature on vehicle CO 2 emissions, this study was conducted using the world light vehicle test cycle on two light-duty E10 gasoline vehicles at ambient temperatures of -10, 0, 23, and 40℃, and found that CO 2 emission factors of Vehicle 1 in the low-speed phase were 22.07% and 20.22% higher than those of Vehicle 2 at cold start and hot start under -10℃. The reason was vehicle 1 had a larger displacement and more friction pairs than vehicle 2. There was the highest CO 2 emission at the low-speed phase due to low average speed, frequent acceleration, and deceleration. The CO 2 temperature factor and the ambient temperature had a strong linear correlation (R 2 = 0.99). According to CO 2 temperature factors and their relationships, CO 2 emission factors of other ambient temperatures could be calculated when the CO 2 emission factor of 23℃ was obtained, and the method also could be used to obtain the CO 2 temperature factors of different vehicles. To separate the effect of load setting and temperature variation on CO 2 emission quantitatively, a method was proposed. And results showed that the load setting was dominant for the CO 2 emission variation. Compared with 23℃, the CO 2 emission for vehicle 1 caused by load setting variation were 62.83 and 47.42 g/km, respectively at -10 and 0℃, while those for vehicle 2 were 45.01 and 35.63 g/km, respectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Tracking and imaging immune cells in vivo non-invasively would offer insights into the immune responses induced by vaccination. Here we report a cancer vaccine consisting of polymer-coated NaErF 4 /NaYF 4 core-shell down-conversion nanoparticles emitting luminescence in the near-infrared spectral window IIb (1,500-1,700 nm in wavelength) and with surface-conjugated antigen (ovalbumin) and electrostatically complexed adjuvant (class-B cytosine-phosphate-guanine). Whole-body wide-field imaging of the subcutaneously injected vaccine in tumour-bearing mice revealed rapid migration of the nanoparticles to lymph nodes through lymphatic vessels, with two doses of the vaccine leading to the complete eradication of pre-existing tumours and to the prophylactic inhibition of tumour growth. The abundance of antigen-specific CD8 + T lymphocytes in the tumour microenvironment correlated with vaccine efficacy, as we show via continuous-wave imaging and lifetime imaging of two intravenously injected near-infrared-emitting probes (CD8 + -T-cell-targeted NaYbF 4 /NaYF 4 nanoparticles and H-2K b /ovalbumin 257-264 tetramer/PbS/CdS quantum dots) excited at different wavelengths, and by volumetrically visualizing the three nanoparticles via light-sheet microscopy with structured illumination. Nanoparticle-based vaccines and imaging probes emitting infrared light may facilitate the design and optimization of immunotherapies., (© 2023. The Author(s).)

What Is Already Known on This Topic?: Smoking is the primary risk factor for a poor prognosis in chronic respiratory disease (CRD). Current tobacco surveillance efforts in China focus on the general population and do not adequately cover CRD patients., What Is Added by This Report?: We employed electronic medical records (EMR) to track smoking habits in 28,334 hospitalized CRD patients at Beijing Chao-Yang Hospital. The rates of former and current smokers were 30.7% and 18.0%, respectively. Both former and current smokers exhibited an increased risk of respiratory symptoms and extended hospital stays., What Are the Implications for Public Health Practice?: These results underscore the importance of implementing smoking monitoring and targeted cessation interventions for hospitalized patients with CRDs., Competing Interests: No conflicts of interest., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2024.)

Cells are the fundamental units of life. The cell membrane primarily composed of two layers of phospholipids (a bilayer) structurally defines the boundary of a cell, which can protect its interior from external disturbances and also selectively exchange substances and conduct signals from the extracellular environment. The complexity and particularity of transmembrane proteins provide the foundation for versatile cellular functions. Nanomedicine as an emerging therapeutic strategy holds tremendous potential in the healthcare field. However, it is susceptible to recognition and clearance by the immune system. To overcome this bottleneck, the technology of cell membrane coating has been extensively used in nanomedicines for their enhanced therapeutic efficacy, attributed to the favorable fluidity and biocompatibility of cell membranes with various membrane-anchored proteins. Meanwhile, some engineering strategies of cell membranes through various chemical, physical and biological ways have been progressively developed to enable their versatile therapeutic functions against complex diseases. In this review, we summarized the potential clinical applications of four typical cell membranes, elucidated their underlying therapeutic mechanisms, and outlined their current engineering approaches. In addition, we further discussed the limitation of this technology of cell membrane coating in clinical applications, and possible solutions to address these challenges.

Purpose: Neoadjuvant chemotherapy (NCT) is the standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Some studies reported neoadjuvant immunochemotherapy (NICT) could improve pathological response with manageable safety. However, few studies have compared the efficacy and safety of NICT and NCT, especially survival outcomes. In this study, we compared the efficacy and safety of NICT and NCT after a median follow-up of 36.0 months., Methods: This was a retrospective study with a 1:1 propensity score matching (PSM). Locally advanced ESCC patients treated with neoadjuvant sintilimab plus chemotherapy or chemotherapy followed by esophagectomy were reviewed. The primary outcome was recurrence-free survival (RFS)., Results: Forty-five patients were identified in each group by PSM. The pathological complete response (pCR) rate in NICT and NCT group were 28.9% and 8.9% (P = 0.02). The hazard ratio (HR) was 0.396 (95% CI 0.171-0.919, p = 0.025) for RFS and 0.377 (95% CI 0.145-0.981, p = 0.038) for overall survival (OS), 3-year RFS was 80.6% and 62.1%, 3-year OS was 86.2% and 68.1%. Patients with pCR, MPR or downstaging had better 3-year RFS and 3-year OS. The incidences of postoperative complications and treatment-related adverse events (TRAEs) were similar., Conclusion: This trial preliminarily shows that NICT improves pathological and survival outcomes over NCT for resectable locally advanced ESCC, with acceptable and manageable safety., (© 2024. The Author(s).)

What we believe to be a novel reconfigurable multi-channel microwave photonic (MWP) receiver for multi-band RF signal is demonstrated for the first time, to the best of our knowledge. A reconfigurable MWP signal processing chip based on two cascaded microring filter banks is employed in the proposed receiver, which slices the multi-band RF input into several narrow band signals and selects optical frequency comb lines for frequency converting of each channel. Due to the significant reconfigurability of the signal processing chip, the proposed receiver can flexibly choose the output frequency band of each channel, and thus different frequency components of the multi-band RF input can be down converted to the intermediate frequency (IF) band for receiving or converted to other frequency band for forwarding. A multi-band RF signal composed of a linear frequency modulation (LFM) signal with 2 GHz bandwidth and a quad-phase shift keyed (QPSK) signal with 100 Mbit/s rate is experimentally received and reconstructed by the proposed receiver, where the reconstructed LFM component exhibits a signal to noise ratio (SNR) of 10.2 dB, and the reconstructed QPSK component reaches a high SNR of 26.1 dB and a great error vector magnitude (EVM) of 11.73%. On the other hand, the QPSK component of the multi-band RF signal centered at 13.5 GHz is successfully converted to 3.1 GHz.

The recent discovery of ferroelectricity in pure ZrO 2 has drawn much attention, but the information storage and processing performances of ferroelectric ZrO 2 -based nonvolatile devices remain open for further exploration. Here, a ZrO 2 (∼8 nm)-based ferroelectric capacitor using RuO 2 oxide electrodes is fabricated, and the ferroelectric orthorhombic phase evolution under electric field cycling is studied. A ferroelectric remnant polarization (2 P r ) of >30 μC/cm 2 , leakage current density of ∼2.79 × 10 -8 A/cm 2 at 1 MV/cm, and estimated polarization retention of >10 years are achieved. When the ferroelectric capacitor is connected with a transistor, a memory window of ∼0.8 V and eight distinct states can be obtained in such a ferroelectric field-effect transistor (FeFET). Through the conductance manipulation of the FeFET, a high object image recognition accuracy of ∼93.32% is achieved on the basis of the CIFAR-10 dataset in the convolutional neural network (CNN) simulation, which is close to the result of ∼94.20% obtained by floating-point-based CNN software. These results demonstrate the potential of ferroelectric ZrO 2 devices for nonvolatile memory and artificial neural network computing.

Category-level pose tracking methods can continuously track the pose of objects without requiring any prior knowledge of the specific shape of the tracked instance. This makes them advantageous in augmented reality and virtual reality applications. The key challenge is how to train neural networks to accurately predict the poses of objects they have never seen before and exhibit strong generalization performance. We propose a novel category-level 6D pose tracking method Corr-Track, which is capable of accurately tracking objects belonging to the same category from depth video streams. Our approach utilizes direct soft correspondence constraints to train a neural network, which estimates bidirectional soft correspondences between sparsely sampled point clouds of objects in two frames. We first introduce a soft correspondence matrix for pose tracking tasks and establish effective constraints through direct spatial point-to-point correspondence representations in the sparse point cloud correspondence matrix. We propose the "point cloud expansion" strategy to address the "point cloud shrinkage" problem resulting from soft correspondences. This strategy ensures that the corresponding point cloud accurately reproduces the shape of the target point cloud, leading to precise pose tracking results. We evaluated our approach on the NOCS-REAL275 and Wild6D dataset and observed superior performance compared to previous methods. Additionally, we conducted cross-category experiments that further demonstrated its generalization capability.

Objective: To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies (IIMs) patients receiving conventional treatment., Methods: Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were included. The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics, laboratory features, peripheral blood lymphocytes, immunological indicators, and therapeutic drugs., Results: Among the 635 patients included, 518 patients finished the follow-up, with an average time of 36.8 months. The total complete clinical response rate of IIMs was 50.0% (259/518). The complete clinical response rate of dermatomyositis (DM), anti-synthetase syndrome (ASS) and immune-mediated necrotizing myopathy (IMNM) were 53.5%, 48.9% and 39.0%, respectively. Fever ( P =0.002) and rapid progressive interstitial lung disease (RP-ILD) ( P =0.014) were observed much more frequently in non-complete clinical response group than in complete clinical response group. The aspartate transaminase (AST), lactate dehydrogenase (LDH), D-dimer, erythrocyte sedimentation rate (ESR), C-reaction protein (CRP) and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group. As for the treatment, the percentage of glucocorticoid received and intravenous immunoglobin (IVIG) were significantly higher in non-complete clinical response group than in complete clinical response group. Risk factor analysis showed that IMNM subtype ( P =0.007), interstitial lung disease (ILD) ( P =0.001), eleva-ted AST ( P =0.012), elevated serum ferritin ( P =0.016) and decreased count of CD4 + T cells in peripheral blood ( P =0.004) might be the risk factors for IIMs non-complete clinical response., Conclusion: The total complete clinical response rate of IIMs is low, especially for IMNM subtype. More effective intervention should be administered to patients with ILD, elevated AST, elevated serum ferritin or decreased count of CD4 + T cells at disease onset.

Background: Recent studies have suggested elevated blood eosinophils are independent predictors of response to corticosteroid therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Smoking status has been shown to affect corticosteroid response. Whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking has not been fully investigated so far., Objectives: This study aimed to assess whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking., Methods: We included 3402 inpatients with AECOPD treated with corticosteroids at Beijing Chao-Yang Hospital from July 2013 to June 2021. Blood eosinophil counts were measured within 24 hours of admission. An eosinophil percentage ≥2% was considered as high eosinophilic. Smokers in this study were defined as current or former smokers. Treatment failure was defined as a worsening of AECOPD that led to adverse clinical outcomes or required further treatment or an extended hospital stay or hospitalisation following the exacerbation. Multivariate-adjusted logistic models were used to estimate the OR and 95% CI associated with treatment failure., Results: There were 958 (28.2%) treatment failure events occurring. Patients with high eosinophils had a lower risk of treatment failure (OR 0.74, 95% CI 0.63 to 0.87) than patients with low eosinophils. Compared with never smoking and low eosinophilic group, the ORs for treatment failure were 0.70 (95% CI 0.52 to 0.96) for never smoking and high eosinophilic group, 0.82 (95% CI 0.64 to 1.05) for smoking and low eosinophilic group and 0.62 (95% CI 0.47 to 0.81) for smoking and high eosinophilic group. Furthermore, there was no significant interaction between eosinophils and smoking status in relation to treatment failure (p for interaction=0.73). Similar results were obtained from multiple secondary outcomes and subgroup analyses., Conclusion: Elevated blood eosinophils are associated with a lower rate of corticosteroid treatment failure, regardless of smoking status. Smoking does not modify the association between blood eosinophil level and corticosteroid treatment failure among inpatients with AECOPD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The big data era requires ultrafast, low-power, and silicon-compatible materials and devices for information storage and processing. Here, ferroelectric tunnel junctions (FTJs) based on SiO 2 /Hf 0.5 Zr 0.5 O 2 composite barrier and both conducting electrodes are designed and fabricated on Si substrates. The FTJ achieves the fastest write speed of 500 ps under 5 V (2 orders of magnitude faster than reported silicon-compatible FTJs) or 10 ns speed at a low voltage of 1.5 V (the lowest voltage among FTJs at similar speeds), low write current density of 1.3 × 10 4 A cm -2 , 8 discrete states, good retention > 10 5 s at 85 °C, and endurance > 10 7 . In addition, it provides a large read current (88 A cm -2 ) at 0.1 V, 2 orders of magnitude larger than reported FTJs. Interestingly, in FTJ-based synapses, gradually tunable conductance states (128 states) with high linearity (<1) are obtained by 10 ns pulses of <1.2 V, and a high accuracy of 91.8% in recognizing fashion product images is achieved by online neural network simulations. These results highlight that silicon-compatible HfO 2 -based FTJs are promising for high-performance nonvolatile memories and electrical synapses., (© 2024 Wiley‐VCH GmbH.)

Background: Autoimmune responses have been suggested to involvement in patients with Behcet's syndrome (BS). There has been growing attention towards the roles of cutaneous lymphocyte antigen (CLA) + regular T cells (Tregs) in autoimmune diseases. The role of CLA + Tregs in BS is still uncertain. This study aims to clarify the impact of CLA + Tregs on BS., Methods: We collected peripheral blood from a total of 107 patients with BS and 114 healthy controls (HCs). The number of CLA + Tregs, natural killer (NK) cells, B cells, and several subtypes of CD4 + T cells were detected using flow cytometry and compared between patients and HCs., Results: The absolute number and proportion of CLA + Tregs among CD4 + T lymphocytes and CD4 + Tregs were lower in patients with BS than in HCs. CLA + Tregs were positively related with NK cells (r = 0.500, P < 0.001) and B cells (r = 0.470, P < 0.001) and negatively related with effector T cells (r=-0.402, P < 0.001) in patients with BS. Patients with BS and arterial aneurysms had CLA + Treg cell deficiency. A decreased proportion of CLA + Tregs was associated with arterial aneurysms in patients with BS. The proportion of CLA + Tregs in patients with BS increased with corticosteroids and immunosuppressants., Conclusion: CLA + Tregs decrease in association with arterial aneurysm in patients with BS. CLA + Tregs may be a predictor of response to BS treatment., (© 2024. The Author(s).)

Background: An accurate assessment of isocitrate dehydrogenase (IDH) status in patients with glioma is crucial for treatment planning and is a key factor in predicting patient outcomes. In this study, we investigated the potential value of whole-tumor histogram metrics derived from synthetic magnetic resonance imaging (MRI) in distinguishing IDH mutation status between astrocytoma and glioblastoma., Methods: In this prospective study, 80 glioma patients were enrolled from September 2019 to June 2022. All patients underwent pre- and post-contrast synthetic MRI scan protocol. Immunohistochemistry (IHC) staining or gene sequencing were used to assess IDH mutation status in tumor tissue samples. Whole-tumor histogram metrics, including T1, T2, proton density (PD), etc., were extracted from the quantitative maps, while radiological features were assessed by synthetic contrast-weighted maps. Basic clinical features of the patients were also evaluated. Differences in clinical, radiological, and histogram metrics between IDH-mutant astrocytoma and IDH-wildtype glioblastoma were analyzed using univariate analyses. Variables with statistical significance in univariate analysis were included in multivariate logistic regression analysis to develop the combined model. Receiver operating characteristic (ROC) and area under the curve (AUC) were used to assess the diagnostic performance of metrics and models., Results: The histopathologic analysis revealed that of the 80 cases, 41 were classified as IDH-mutant astrocytoma and 39 as IDH-wildtype glioblastoma. Compared to IDH-wildtype glioblastoma, IDH-mutant astrocytoma showed significantly lower T1 [10th percentile (10th), mean, and median] and post-contrast PD (10th, 90th percentile, mean, median, and maximum) values as well as higher post-contrast T1 (cT1) (10th, mean, median, and minimum) values (all P<0.05). The combined model (T1-10th + cT1-10th + age) was developed by integrating the independent influencing factors of IDH-mutant astrocytoma using the multivariate logistic regression. The diagnostic performance of this model [AUC =0.872 (0.778-0.936), sensitivity =75.61%, and specificity =89.74%] was superior to the clinicoradiological model, which was constructed using age and enhancement degree (AUC =0.822 (0.870-0.898), P=0.035)., Conclusions: The combined model constructed using histogram metrics derived from synthetic MRI could be a valuable preoperative tool to distinguish IDH mutation status between astrocytoma and glioblastoma, and subsequently, could assist in the decision-making process of pretreatment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1288/coif). Y.X. and M.L., employees of GE healthcare, provided MRI technical guidance and writing guidance for this paper. The other authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

We present an efficient particle-particle random phase approximation (ppRPA) approach that predicts accurate excitation energies of point defects, including the nitrogen-vacancy (NV - ) and silicon-vacancy (SiV 0 ) centers in diamond and the divacancy center (VV 0 ) in 4H silicon carbide, with errors of ±0.2 eV compared with experimental values. Starting from the ( N + 2)-electron ground state calculated with density functional theory (DFT), the ppRPA excitation energies of the N -electron system are calculated as the differences between the two-electron removal energies of the ( N + 2)-electron system. We demonstrate that the ppRPA excitation energies converge rapidly with a few hundred canonical active-space orbitals. We also show that active-space ppRPA has weak DFT starting-point dependence and is significantly cheaper than the corresponding ground-state DFT calculation. This work establishes ppRPA as an accurate and low-cost tool for investigating excited-state properties of point defects and opens up new opportunities for applications of ppRPA to periodic bulk materials.

Purpose: Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) exhibit heterogeneous responses to corticosteroid treatment. We aimed to determine whether combining eosinophil levels with other routine clinical indicators can enhance the predictability of corticosteroid treatment outcomes and to come up with a scoring system., Patients and Methods: Consecutive patients admitted with AECOPD receiving corticosteroid treatment between July 2013 and March 2022 at Beijing Chao-Yang Hospital were retrospectively analyzed. Data on patients' demographics, smoking status, hospitalization for AECOPD in the previous year, comorbidities, blood laboratory tests, in-hospital treatment and clinical outcomes were collected. Least absolute shrinkage and selection operator (LASSO) regression and backward logistic regression were used for predictor selection, and predictive nomograms were developed. The discrimination and calibration of the nomograms were assessed using the area under the receiver operating curve (AUC) and calibration plots. Internal validation was performed using the 500-bootstrap method, and clinical utility was evaluated using decision curve analysis (DCA)., Results: Among the 3254 patients included, 804 (24.7%) had treatment failure. A nomogram of eosinophils, platelets, C-reactive protein (CRP), low density lipoprotein cholesterol, prognostic nutritional index (PNI), hospitalization for AECOPD in the previous year, ischemic heart diseases and chronic hepatic disease was developed to predict treatment failure for patients with a smoking history. For patients without a smoking history, a nomogram of CRP, PNI, ischemic heart diseases and chronic hepatic disease was developed. Although the AUCs of these two nomograms were only 0.644 and 0.647 respectively, they were significantly superior to predictions based solely on blood eosinophil levels., Conclusion: We developed easy-to-use comprehensive nomograms utilizing readily available clinical biomarkers related to inflammation, nutrition and immunity, offering modestly enhanced predictive value for treatment outcomes in corticosteroid-treated patients with AECOPD. Further investigations into novel biomarkers and additional patient data are imperative to optimize the predictive performance., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Feng et al.)

It has been predicted that the highly degenerate mammalian Y chromosome will be lost eventually. Indeed, Y was lost in the Ryukyu spiny rat Tokudaia osimensis, but the fate of the formerly Y-linked genes is not completely known. We looked for all 12 ancestrally Y-linked genes in a draft T. osimensis genome sequence. Zfy1, Zfy2, Kdm5d, Eif2s3y, Usp9y, Uty, and Ddx3y are putatively functional and are now located on the X chromosome, whereas Rbmy, Uba1y, Ssty1, Ssty2, and Sry are missing or pseudogenized. Tissue expressions of the mouse orthologs of the retained genes are significantly broader/higher than those of the lost genes, suggesting that the destinies of the formerly Y-linked genes are related to their original expressions. Interestingly, patterns of gene retention/loss are significantly more similar than by chance across four rodent lineages where Y has been independently lost, indicating a level of certainty in the fate of Y-linked genes even when the chromosome is gone., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Objective: To explore the effect of cognitive reserve (CR) on brain volume and cerebrospinal fluid (CSF) in patients with mild cognitive impairment (MCI) and healthy elders (HE)., Methods: 31 HE and 50 MCI patients were collected in this study to obtain structural MRI, cognitive function, and composite CR scores. Educational attainment, leisure time, and working activity ratings from two groups were used to generate cognitive reserve index questionnaire (CRIq) scores. The different volumes of brain regions and CSF were obtained using uAI research portal in both groups, which were taken as the regions of interest (ROI), the correlation analysis between ROIs and CRIq scores were conducted., Results: The scores of CRIq, CRIq-leisure time, and CRIq-education in HE group were significantly higher than patients in MCI group, and the montreal cognitive assessment (MoCA) and minimum mental state examination (MMSE) scores were positively correlated with the CRIq, CRIq-education in both groups, and were positively correlated with CRIq-leisure time in MCI group. The scores of auditory verbal learning test (AVLT) and verbal fluency test (VFT) were also positively correlated with CRIq, CRIq-leisure time, and CRIq-education in MCI group, but the score of AVLT was only positively correlated with CRIq in HE group. Moreover, in MCI group, the volume of the right middle cingulate cortex and the right parahippocampal gyrus were negatively correlated with the CRIq, and the volume of CSF, peripheral CSF, and third ventricle were positively correlated with the CRIq-leisure time score. The result of mediation analysis suggested that right parahippocampal gryus mediated the main effect of the relationship between CRIq and MoCA score in MCI group., Conclusion: People with higher CR show better levels of cognitive function, and MCI patients with higher CR showed more severe volume atrophy of the right middle cingulate cortex and the right parahippocampal gyrus, but more CSF at a given level of global cognition., Competing Interests: MZ was employed by Shanghai United Imaging Intelligence. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Yang, Liu, Li, Zhao, Liu and Zhang.)

Background: Insufficient understanding of the pathogenesis and tumor immunology of triple-negative breast cancer (TNBC) has limited the development of immunotherapy. The importance of tumor microenvironment (TME) in immunotyping, prognostic assessment and immunotherapy efficacy of cancer has been emphasized, however, potential immunogenic cell death (ICD) related genes function in TME of TNBC has been rarely investigated., Aims: To initially explore the role and related mechanisms of ICD in TNBC, especially the role played in the TME of TNBC, and to identify different relevant subtypes based on ICD, and then develop an ICD-related risk score to predict each TNBC patient TME status, prognosis and immunotherapy response., Methods and Results: In this study, we identified distinct ICD-related modification patterns based on 158 TNBC cases in the TCGA-TNBC cohort. We then investigated the possible correlation between ICD-related modification patterns and TME cell infiltration characteristics in TNBC. By using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis, we created a risk scoring system (ICD score) to quantifiably evaluate the impact of ICD-related modification patterns in individual TNBC patient. Two different ICD-related modification patterns were found with significant differences in immune infiltration. Lower ICD score was correlated with higher immune infiltration, tumor mutational burden and significantly enriched in immune-related pathways, indicating a strong ability to activate immune response, which might account for relatively favorable prognosis of TNBC patients and could serve as a predictor to select suitable candidates for immunotherapy. We used two independent cohorts, GSE58812 cohort and Metabric cohort to validate prognosis and immunohistochemistry for preliminary in vitro validation., Conclusion: This study evidenced that the ICD-related modification patterns might exert pivotal roles in the immune infiltration landscape of TNBC and ICD score might act as potential predictors of prognostic assessment and immunotherapy response. This research provides unique insights for individualize immune treatment strategies and promising immunotherapy candidates screening., (© 2024 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

RNA velocity is closely related with cell fate and is an important indicator for the prediction of cell states with elegant physical explanation derived from single-cell RNA-seq data. Most existing RNA velocity models aim to extract dynamics from the phase delay between unspliced and spliced mRNA for each individual gene. However, unspliced/spliced mRNA abundance may not provide sufficient signal for dynamic modeling, leading to poor fit in phase portraits. Motivated by the idea that RNA velocity could be driven by the transcriptional regulation, we propose TFvelo, which expands RNA velocity concept to various single-cell datasets without relying on splicing information, by introducing gene regulatory information. Our experiments on synthetic data and multiple scRNA-Seq datasets show that TFvelo can accurately fit genes dynamics on phase portraits, and effectively infer cell pseudo-time and trajectory from RNA abundance data. TFvelo opens a robust and accurate avenue for modeling RNA velocity for single cell data., (© 2024. The Author(s).)

Skeletal system disease (SSD) is defined as a class of chronic disorders of skeletal system with poor prognosis and causes heavy economic burden. m6A, methylation at the N6 position of adenosine in RNA, is a reversible and dynamic modification in posttranscriptional mRNA. Evidences suggest that m6A modifications play a crucial role in regulating biological processes of all kinds of diseases, such as malignancy. Recently studies have revealed that as the most abundant epigentic modification, m6A is involved in the progression of SSD. However, the function of m6A modification in SSD is not fully illustrated. Therefore, make clear the relationship between m6A modification and SSD pathogenesis might provide novel sights for prevention and targeted treatment of SSD. This article will summarize the recent advances of m6A regulation in the biological processes of SSD, including osteoporosis, osteosarcoma, rheumatoid arthritis and osteoarthritis, and discuss the potential clinical value, research challenge and future prospect of m6A modification in SSD., (© 2024. The Author(s).)