Search

Fungal infection possesses the characteristics of high invasion depth and easy formation of a biofilm under the skin, which greatly hinders the treatment process. Here, traditional Chinese medicine moxa is carbonized and modified with zinc oxide (ZnO) nanosheets to synthesize carbonized moxa@ZnO (CMZ) with the dual response properties of yellow light (YL) and ultrasound (US) for synergistic antifungal therapy. CMZ with narrow bandgap can respond to long-wavelength YL that is highly safe and helpful for skin repair. Simultaneously, CMZ with a piezoelectric effect can further enhance the photocatalytic efficiency under the stimulation of US with high tissue penetration. Gene mechanism investigation indicates that when exposed to US and YL irradiation, CMZ-based therapy can adjust the expression of genes associated with fungal virulence, metabolic activity, mycelial growth and biofilm development, thus efficaciously eradicating planktonic Candida albicans(C. albicans) and mature biofilm. Importantly, despite the 1.00 cm thick tissue barrier, CMZ can rapidly eliminate 99.9% of C. albicanswithin 4 min, showing a satisfactory deep fungicidal efficacy. The in vivotherapeutic effect of this strategy is demonstrated in both open wound and deep cutaneous infection tests, speaking of dramatically better efficacy than the traditional fungicide ketoconazole (KTZ).

The development of biodegradable Zn alloys with comprehensive performance for biomedical applications is still challenging. Hence, the nanocrystalline Zn–Cu–Sr–Li alloys were prepared by alloying design and multi-pass high-speed hot rolling. The Zn–3Cu-0.2Sr-0.4Li alloy achieved nanoscale microstructures, resulting in high strength and an ideal corrosion rate that is more suitable for tissue repair cycles. Scanning Kelvin probe force microscopy analysis revealed the potential from high to low was ranked as: ε phase > SrZn13phase > Zn grains > β phase. The nanoscale Zn grains and β particles formed numerous microcells, enhancing the microgalvanic corrosion effect. The Sr ions could be released more efficiently during the degradation in Li-containing alloys, which endowed the alloys with outstanding biocompatibility. Besides, the synergistic release of Zn ions and Cu ions during alloy degradation endowed the alloy with excellent antimicrobial ability against Staphylococcus aureus(inhibition zone diameter ≈ 7.5 mm). The antimicrobial ability of Zn–3Cu–0.2Sr–0.4Li alloy was superior among the reported biodegradable Zn alloys. These results demonstrated nanocrystalline Zn–Cu–Sr–Li alloys have comprehensive performance and broad application prospects in biodegradable bone implants, providing the experimental and theoretical basis for future research in the biomedical field.

The crystal growth kinetics is crucial for the controllable preparation and performance modulation of metal nanocrystals (NCs). However, the study of growth mechanisms is significantly limited by characterization techniques, and it is still challenging to in situcapture the growth process. Real-time and real-space imaging techniques at the atomic scale can promote the understanding of microdynamics for NC growth. Herein, the growth of Pd NCs on monolayer MoS2under different atmospheres was in situstudied by environmental transmission electron microscopy. Introducing carbon monoxide can modulate the diffusion of Pd monomers, resulting in the epitaxial growth of Pd NCs with a uniform orientation. The electron energy loss spectroscopy and theoretical calculations showed that the CO adsorption assured the specific exposed facets and good uniformity of Pd NCs. The insight into the gas–solid interface interaction and the microscopic growth mechanism of NCs may shed light on the precise synthesis of NCs on two-dimensional (2D) materials.

Triple-negative breast cancer (TNBC) is a heterogeneous breast cancer subtype and accounts for approximately 15–20% of breast cancer cases. In this study, we identified KLHL29, which is an understudied member of the Kelch-like gene family, as a crucial tumor suppressor that regulates chemosensitivity in TNBC. KLHL29 expression was significantly downregulated in breast cancer tissues compared with adjacent normal tissues, and low levels of KLHL29 were associated with unfavorable prognoses. Ectopic KLHL29 suppressed, while depleting KLHL29 promoted, the growth, proliferation, migration, and invasion of TNBC. Mechanistically, KLHL29 recruited the CUL3 E3-ligase to the RNA-binding protein DDX3X, leading to the proteasomal degradation of the latter. This downregulation of DDX3X resulted in the destabilization of CCND1 mRNA and the consequent cell cycle arrest at G0/G1 phase. Remarkably, the DDX3X inhibitor RK33 combined with platinum-based chemotherapy can synergistically suppress TNBC that usually expresses low levels of KLHL29 and high levels of DDX3X using cancer cell-derived xenograft and patient-derived organoids models. Altogether, we uncovered the potential role for the KLHL29-DDX3X signaling cascade in the regulation of TNBC progression, thus providing a promising combination strategy for overcoming TNBC chemoresistance.

Caries is considered to be the most prevalent non-communicable disease in humans, mainly deriving from acidogenic bacterial biofilm and resulting in the demineralization and decomposition of hard dental tissue. Herein, a composite responsive foam brace loaded with magnesium organic framework (MPC) is designed for caries prevention and tooth remineralization. MPC can intelligently release organic antibacterial molecules (gallic acid) and mineralized ions (Mg2+, Ca2+and PO43−) under acidic conditions (pH < 5.5) of biofilm infection, regulating pH and killing bacteria. Additionally, due to the excellent photothermal conversion efficiency, MPC can further enhance the destruction of bacterial biofilm by inhibiting virulence genes and destroying bacterial adhesion under near-infrared light irradiation (808 nm). More importantly, MPC can not only reverse the cariogenic environment at both pH and microbial levels, but also promote self-healing of demineralized teeth in terms of both the micro-structure and mechanical properties.

Periodontitis is a chronic inflammatory disease deriving from dental plaque, characterized by the excessive accumulation of reactive oxygen species (ROS), matrix metalloproteinase (MMP) and other substances, resulting in the destruction of periodontal tissues. At present, the main therapeutic modalities, such as local mechanical debridement and antibiotic delivery, are not only difficult to solve the intractable bacterial biofilm effectively but also tricky to ameliorate the excessive inflammatory response as well as regenerate the impaired periodontal tissues. Herein, we have proposed the TM/BHT/CuTA hydrogel system formed by the self-assembly of the copper-based nanozyme (copper tannic acid coordination nanosheets, CuTA NSs) and the triglycerol monostearate/2,6-di-tert-butyl-4-methylphenol (TM/BHT) hydrogel. The negatively charged TM/BHT/CuTA can retain at the inflammation sites with a positive charge through electrostatic adsorption and hydrolyze in response to the increasing MMP of periodontitis, realizing the on-demand release of the CuTA nanozyme. The released CuTA nanozyme has antibacterial and antiplaque properties. Meanwhile, as a metal-phenolic nanozyme, it can scavenge multiple ROS by simulating the cascade process of superoxide dismutase (SOD) and catalase (CAT). Further, the CuTA nanozyme can modulate the macrophage polarization from M1 phenotype to M2 phenotype through the Nrf2/NF-κB pathway, which reduces the pro-inflammatory cytokines, increases the anti-inflammatory cytokines, and promotes the expression of osteogenetic genes successively, thus relieving the inflammation and accelerating the tissue regeneration of periodontitis. Altogether, this multifunctional nanozyme on-demand release platform (TM/BHT/CuTA) provides a desirable strategy for the treatment of periodontitis.

High resolution (HR) 3D medical image segmentation is vital for an accurate diagnosis. However, in the field of medical imaging, it is still a challenging task to achieve a high segmentation performance with cost-effective and feasible computation resources. Previous methods commonly use patch-sampling to reduce the input size, but this inevitably harms the global context and decreases the model's performance. In recent years, a few patch-free strategies have been presented to deal with this issue, but either they have limited performance due to their over-simplified model structures or they follow a complicated training process. In this study, to effectively address these issues, we present Adaptive Decomposition (A-Decomp) and Shared Weight Volumetric Transformer Blocks (SW-VTB). A-Decomp can adaptively decompose features and reduce their spatial size, which greatly lowers GPU memory consumption. SW-VTB is able to capture long-range dependencies at a low cost with its lightweight design and cross-scale weight-sharing mechanism. Our proposed cross-scale weight-sharing approach enhances the network's ability to capture scale-invariant core semantic information in addition to reducing parameter numbers. By combining these two designs together, we present a novel patch-free segmentation framework named VolumeFormer. Experimental results on two datasets show that VolumeFormer outperforms existing patch-based and patch-free methods with a comparatively fast inference speed and relatively compact design.

Background: Latinx populations have experienced disproportionately high case rates of COVID-19 across the USA. Latinx communities in non-traditional migration areas may experience greater baseline day-to-day challenges such as a lack of resources for immigrants and insufficient language services. These challenges may be exacerbated by the COVID-19 pandemic. Objective: This article describes the results of an initial community health needs assessment to better understand the prevention and care of COVID-19 infection in the Cincinnati Latinx community. Methods: We used convergent mixed methods to examine barriers and facilitators to COVID-19 prevention and care for those with infection. Results: Latinx adults ≥ 18 years old completed 255 quantitative surveys and 17 qualitative interviews. Overarching mixed methods domains included knowledge, prevention, work, challenges, and treatment. Quantitative results largely reinforced qualitative results (confirmation). Certain quantitative and qualitative results, however, diverged and expanded insights related to caring for COVID-19 infection among Latinx adults (expansion). There were infrequent contradictions between quantitative and qualitative findings (discordance). Primary barriers for the Latinx community during the COVID-19 pandemic included insecurities in food, jobs, housing, and immigration. Key facilitators included having trusted messengers of health-related information. Conclusion: Public health interventions should be centered on community partnerships and the use of trusted messengers. Wraparound services (including resources for immigrants) are essential public health services. Close partnership with employers is essential as lack of sick leave and mask supplies were more frequent barriers than knowledge. These findings emerged from experiences during the COVID-19 pandemic but likely generalize to future public health crises.

Purpose To identify associations between age of onset of overweight/obesity, a child’s sociodemographic characteristics, and characteristics of a child’s home census tract.Design Retrospective electronic health record review of children with overweight/obesity.Setting Three primary care centers associated with a free-standing, tertiary-care pediatric institution in Cincinnati.Subjects Patients born between August 1, 2013 and July 31, 2014, who had a body mass index (BMI) ≥85th percentile before 5 years of age (n = 794).Measures Primary outcome was the patient’s age at the first encounter when BMI was ≥85th percentile. Patient-level predictors were sex, age, race/ethnicity, health insurance, and number of moves captured in the health record. Census tract-level predictors were density of bus stops, presence of grocery stores, and a Socioeconomic Deprivation Index.Analysis Multivariable linear regression models assessed for independent associations between age of onset of overweight/obesity and predictors.Results Patients were 55.8% female, 73.6% black, and 79.1% publicly insured. Each additional move per year was associated with onset of overweight/obesity occurring 4.05 months earlier (P< .0001). No significant associations between age of onset of overweight/obesity and census tract-level density of bus stops (P= .82), presence of grocery stores (P= .39), and socioeconomic deprivation (P= .53) were demonstrated.Conclusion Public policy efforts toward improving access to grocery stores or public transportation may not be sufficient to prevent childhood obesity. Population-level interventions related to improving housing may also reduce obesity.

Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need. Here, we summarize our current knowledge of biomarkers developed for cellular, organ, and organismal levels of aging, comprising six pillars: physiological characteristics, medical imaging, histological features, cellular alterations, molecular changes, and secretory factors. To fulfill all these requisites, we propose that aging biomarkers should qualify for being specific, systemic, and clinically relevant.

Cyclometalated Ir(III) complexes with high electrochemiluminescence (ECL) efficiency and appropriate bioconjugation sites are urgently needed in ECL immunoassays (ECLIA). Herein, we report the synthesis, photophysics, electrochemistry, and ECL of six new Ir(III) complexes bearing naphthyl (nap) or adamantane phenyl (adap) substitutions, four of which emit cyan, green, or red light and display 1.7- to 7.5-fold increases in ECL intensity. In combination with DFT/TDDFT calculations, this enhancement is rationalized to the augmented radiative rate that arises from both the strengthened spin-orbit coupling (SOC) and the increased transition dipole moment. In addition, the adap-based Ir(III) complex shows high binding affinity with β-cyclodextrin (β-CD) due to the strong hydrophobic interaction, which enables us to develop a modular strategy for the labeling of Ir(III) complexes with biomolecules and to use hydrophobic luminophores in the aqueous-phase detection. As demonstrated, a novel ECLIA is built up and exhibits a wide linear range from 1 ng/mL to 10 μg/mL and a detection limit of 72 pg/mL for the determination of C-reactive protein (CRP). These findings provide new insights into the design, synthesis, and bio-labeling of highly emissive Ir(III) complexes and pave the way for the development of novel ECLIA based on host–guest recognition motifs.

Oral mucosal ulcer is the most prevalent oral mucosal lesion, affecting the quality of life. Due to the moist and highly dynamic oral lining, the existing oral mucoadhesives are unable to serially address the challenges of residency, hemorrhage, bacterial infection and inflammatory reaction. Herein, a dual-light defined oral mucoadhesive (ZPTA-G/HMA) was proposed, with a methacrylate gelatin-methacrylate hyaluronic acid (GelMA-HAMA, G/HMA) double network hydrogel as a matrix, tannic acid (TA) as a high content anchor moiety provider for the moist oral mucosa, and polydopamine modified zinc oxide (ZnO@PDA, ZP) as a photocatalytic antibacterial substance. This platform had good adhesive and hemostatic properties both in vitroand in vivo. Under 520 nm green light (GL) irradiation, ZPTA-G/HMA would anchor to the wet mucosa surface by crosslinking and exert broad-spectrum antibacterial ability (even including Candida albicans) by in situproducing reactive oxygen species (ROS). Moreover, under 808 nm near-infrared (NIR) irradiation, the increased release of TA combined with the photothermal effect of ZP endowed ZPTA-G/HMA with enhanced anti-inflammatory and pro-healing performance. Collectively, ZPTA-G/HMA could be switched by light sources to achieve the dual-mode real-time adjustment of in situanti-bacterial function and controlled anti-inflammation, combined with ideal mucosal residence, thus promising in developing personalized sequential strategies for varied oral mucosal lesions.

AbstractThe rapid growth in defence expenditure in China raises the concern that investments in the defence sector crowd out investments in social sectors, i.e., the ‘guns for butter’ argument. This article resorts to the bubble testing method to study the trade-off between defence and utilities sectors in the Chinese capital market. Based upon the generalized sup Augmented Dickey-Fuller (GSADF) test, this paper captures and date stampings explosive behaviors in defence and utilities industries using stock indexes. Empirical results reveal bubbles for defence and utilities sectors in similar time periods, thus indicating that the factors driving explosive movements are alike for both sectors. However, bubbles in a certain sector do not necessarily crowd out investments in the other sector. Through testing bubbles in the ratio of stock indexes of two sectors, we find that the explosive episodes vanish. The results indicate that the crowding-out effect between defence and utilities sectors does not exist in the Chinese capital market. Increases in the military expenditure in China are necessary to safeguard the national security because of frequent geopolitical conflicts and terrorism. However, the defence to utilities ratio is increasing rapidly, implying the possibility that excessive growth in military expenditure may generate the ‘guns for butter’ problem, which can be detrimental to economic growth.

AbstractUncertainty is an economically important risk factor in the banking sector. Using a sample of Chinese listed commercial banks over the period 2005 − 2018, this research conducted pooled OLS and found evidence that economic uncertainty significantly increases bank risk and lowers profitability. Furthermore, we constructed a partial equilibrium model to explain how risk governance alters the risk-increasing effect and profit-decreasing effect of economic uncertainty on bank risk and profitability. Consistent with theory, empirical results suggested the effects of economic uncertainty on bank risk and performance tend to be considerably weaker when there exists a strong risk governance mechanism. These findings stand when subjected to several endogeneity and robustness checks. Risk governance plays a key role in weakening the detrimental consequences of economic uncertainty on banks and promoting a sustainable growth of the banking sector. A financial regulator entity should require banks to establish a sound risk governance system in order to mitigate financial systemic risk and safeguard overall financial stability.

AbstractInflation expectations of firms affect their micro-decision-making behaviors and therefore impact the macro-economy. Thus, a deep understanding of how firms form inflation expectations benefits the achievement of central bank’s policy objectives on macro-economic sustainability and development. In this paper, we focus on the inflation expectations of firms from surveys. Specifically, the Naïve Expectation, Adaptive Expectation, Rational Expectation, VAR, and Heterogeneous Static Expectation formation models are adopted to test the models being used by firms to form inflation expectations. Empirically, this paper reveals the heterogeneity between the formation mechanisms of households and firms. Then, empirical results reject the rational expectation hypothesis of firms’ inflation expectations, which means that they are not perfectly rational. Finally, we find that the inflation perception is a non-negligible factor in forming firms’ inflation expectations. Therefore, central banks’ monetary policies that aiming to formulate firms’ inflation perceptions can be a useful tool in regulating their inflation expectations, which are expected to benefit the stability of the macro-economy.

Tribocatalysis, as a new approach in environmental purification, has drawn increasing attention in the past few years. In this work, we successfully convert mechanical energy to chemical energy by Bi12TiO20, which was synthesized by a hydrothermal method. Under magnetic stirring, electrons transfer from the surface of Bi12TiO20to the polytetrafluoroethylene-sealed magnetic bar due to their friction. Moreover, the holes that remain on Bi12TiO20provide oxidation properties in the process for organic matter degradation. According to a series of tests, it is noticed that the shape of the stirring bar and the material of the reaction vessel have a remarkable influence on the removal efficiency of contaminants. Simultaneously, multiple tests reveal the high stability of Bi12TiO20. A great potential for Bi12TiO20to control water pollutants under dark conditions during collection of ambient mechanical energy was clearly demonstrated in this study.

Metastasis of breast cancer represents the major reason for its poor prognosis, leading to high mortality. In breast cancer, a tumor suppressor gene TP53is commonly mutated. TP53mutation leads to an altered expression of various genes, an event that is associated with aggressive tumor and is a strong independent marker for survival. In this study, we identified a novel p53 target gene, immunoglobulin superfamily 9 (IGSF9). IGSF9 is generally down-regulated in breast cancer tissues. Loss of IGSF9 is associated with frequent metastasis and poor prognosis of breast cancer patients. Wild-type p53, but not R175H mutant, trans-activates the transcription of IGSF9 via binding to its promoter (−137 to −131 bp), inhibits epithelial-mesenchymal transition (EMT), consequently the inhibition of breast cancer cells migration and invasion. IGSF9 interacts with focal adhesion kinase (FAK) and inhibits FAK/AKT signaling activity. PND1186, FAK inhibitor, inhibits breast cancer metastasis induced by IGSF9knockdown in vitro and in vivo. Taken together, IGSF9 is trans-activated by p53 and inhibits breast cancer metastasis by modulating FAK/AKT signaling pathway. IGSF9 could serve as a prognostic marker and potential therapeutic target for breast cancer.

Precise prediction on vacant parking space (VPS) information plays a vital role in intelligent transportation systems for it helps drivers to find the parking space quickly to reduce unnecessary waste of time and excessive environmental pollution. By analyzing the historical zone-wise VPS data, we find that for the number of VPSs, there is not only a solid temporal correlation within each parking lot, but also an obvious spatial correlation among different parking lots. Given this, this paper proposes a hybrid deep learning framework, known as the dConvLSTM-DCN (dual Convolutional Long Short-Term Memory with Dense Convolutional Network), to make short-term (within 30 min) and long-term (over 30 min) predictions on the VPS availability zone-wisely. Specifically, the temporal correlations of different time scales, namely the 5-min and daily-wise temporal correlations of each parking lot, and the spatial correlations among different parking lots can be effectively captured by the two parallel ConvLSTM components, and meanwhile, the dense convolutional network is leveraged to further improve the propagation and reuse of features in the prediction process. Besides, a two-layer linear network is used to extract the meta-info features to promote the prediction accuracy. For long-term predictions, two methods, namely the direct and iterative prediction methods, are developed. The performance of the prediction model is extensively evaluated with practical data collected from nine public parking lots in Santa Monica. The results show that the dConvLSTM-DCN framework can achieve considerably high accuracy in both short-term and long-term predictions.

Objective:The prognosis of malignant tumors with peritoneal metastases and cancerous ascites has generally been poor, with limited treatment options. The PRaG regimen, which comprised of hypofractionated radiotherapy, programmed cell death-1 (PD-1) inhibitor, and granulocyte-macrophage colony-stimulating factor (GM-CSF), showed a survival advantage in patients with advanced solid tumors who failed at least the first line of standard systemic treatment. Intraperitoneal infusion of PD-1 inhibitors may be a novel therapeutic strategy for managing malignant ascites. Integrating the PRaG regimen with intraperitoneal perfusion of a PD-1 inhibitor might control malignant ascites and provide further survival benefits in these patients. This proposed study aims to investigate the safety and efficacy of intraperitoneal infusion of serplulimab in combination with the PRaG regimen in patients with simultaneous advanced solid tumors and cancerous ascites who fail at least the first-line treatment. Methods:This proposed study is a prospective, single-arm, open-label, multicenter clinical trial. All eligible patients will receive 2 cycles of intensive treatment, a combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor. The patients who are beneficially treated with intensive treatment will receive consolidation treatment every 2 weeks until ascites disappear, disease progression occurs, intolerable toxicity occurs, or for up to 1 year. Phase I of this study will be conducted using a modified 3 + 3 design. The dose of intraperitoneal infusion of PD-1 inhibitor for phase II will be determined according to dose-limiting toxicity evaluation in the phase I study. Conclusion:This prospective, open-label, multicenter study will potentially lead to intraperitoneal perfusion of a PD-1 inhibitor being a new strategy for malignant ascites patients and provide a meaningful efficacy and safety of the combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor for these patients.

ABSTRACTChange detection methods include model-driven methods and data-driven methods. Model-driven methods are rigorous in theory but have difficulties in establishing accurate models for complex problems. Data-driven methods have strong learning abilities, but it is difficult to interpret their mechanism. In order to comprehensively utilize their advantages to highlight changes in multi-temporal remote sensing images. We proposed a change detection method for remote sensing images based on deep coupled sparse representation learning, in which the coupled sparse representation learning is implicitly expressed by convolutional neural networks (CNNs). A coupled sparse representation learning method is first proposed, and then it is unfolded into a CNNs network, the coupled sparse coefficient and dictionary are learned from the training data. Unlike fully data-driven CNNs, auxiliary coupled sparse representation is utilized to guide CNNs to identify the changed areas. Finally, the experiments on two datasets verified the validity of the proposed method.

•Modal and departure time shift behaviors in new daily travel conditions.•Choice models from both small (questionnaire) and big ([3D] geo-spatial) data.•A case study in a multi-layered city – Hong Kong.•Efficient and comfortable walking environment promotes different shift behaviors.

Biofilm-driven caries and tooth discoloration are two major problems in oral health care. The current methods have the disadvantages of insufficient biofilm targeting and irreversible enamel damage. Herein, an injectable sodium alginate hydrogel membrane doped with bismuth oxychloride (Bi12O17Cl2) and cubic cuprous oxide (Cu2O) nanoparticles was designed to simultaneously achieve local tooth whitening and biofilm removal through a photodynamic dental therapy process. This fast cross-linked hydrogel could form a biofilm removal coating on the target tooth surface precisely. Afterward, reactive oxygen species was effectively released on demand under green light, which could not only eradicate the biofilm but also whiten the tooth non-destructively in a facile manner without significant damage to both the enamel and biological cells. After the usage, the removal of this hydrogel can also enhance the effect of biofilm destruction and caries prevention.