Oral colon-targeted pH-responsive polymeric nanoparticles loading naringin for enhanced ulcerative colitis therapy.

An oral colon-targeted drug delivery system holds great potential in preventing systemic toxicity and preserving the therapeutic benefits of ulcerative colitis (UC) treatment. In this study, we developed a negatively charged PLGA-PEG nanoparticle system for encapsulating naringin (Nar). Additionally, chitosan and mannose were coated on the surface of these nanoparticles to enhance their mucosal adsorption and macrophage targeting abilities. The resulting nanoparticles, termed MC@Nar-NPs, exhibited excellent resistance against decomposition in the strong acidic gastrointestinal environment and specifically accumulated at inflammatory sites. Upon payload release, MC@Nar-NPs demonstrated remarkable efficacy in alleviating colon inflammation as evidenced by reduced levels of pro-inflammatory cytokines in both blood and colon tissues, as well as the scavenging of reactive oxygen species (ROS) in the colon. This oral nanoparticle delivery system represents a novel approach to treating UC by utilizing Chinese herbal ingredient-based oral delivery and provides a theoretical foundation for local and precise intervention in specific UC treatment.

Hinge Modes of Surface Arcs in a Synthetic Weyl Phononic Crystal.

Chiral bulk Landau levels and surface arcs, as the two distinctive features unique to Weyl semimetals, have each attracted enormous interest. Recent works have revealed that surface-arc modes can support one-sided chiral hinge modes, a hallmark of the three-dimensional quantum Hall effect, as a combined result of chiral Landau levels of bulk states and magnetic response of surface arcs. Here, we exploit a two-dimensional phononic crystal to construct an ideal Weyl semimetal under a pseudomagnetic field, in which a structural parameter is combined to construct a synthetic three-dimensional space. By directly measuring the acoustic pressure fields, we have not only visualized the one-sided chiral hinge modes, but also observed the quantized Landau level modes. The results pave the way to explore the high-dimensional quantum Hall physics in low-dimensional phononic platforms.

Spin-Dependent Localization of Helical Edge States in a Non-Hermitian Phononic Crystal.

As a distinctive feature unique to non-Hermitian systems, non-Hermitian skin effect displays fruitful exotic phenomena in one or higher dimensions, especially when conventional topological phases are involved. Among them, hybrid skin-topological effect is theoretically proposed recently, which exhibits anomalous localization of topological boundary states at lower-dimensional boundaries accompanied by extended bulk states. Here, we experimentally realize the hybrid skin-topological effect in a non-Hermitian phononic crystal. The phononic crystal, before tuning to be non-Hermitian, is an ideal acoustic realization of the Kane-Mele model, which hosts gapless helical edge states at the boundaries. By introducing a staggered distribution of loss, the spin-dependent edge modes pile up to opposite corners, leading to a direct observation of the spin-dependent hybrid skin-topological effect. Our Letter highlights the interplay between topology and non-Hermiticity and opens new routes to non-Hermitian wave manipulations.

Photothermal and host immune activated therapy of cutaneous tuberculosis using macrophage targeted mesoporous polydopamine nanoparticles.

Tuberculosis (TB) remains the leading cause of deaths among infectious diseases worldwide. Cutaneous Tuberculosis (CTB), caused by Mycobacterium tuberculosis (Mtb) infection in the skin, is still a harmful public health issue that requires more effective treatment strategy. Herein, we introduced mannose-modified mesoporous polydopamine nanosystems (Man-mPDA NPs) as the macrophage-targeted vectors to deliver anti-TB drug rifampicin and as photothermal agent to facilitate photothermal therapy (PTT) against Mtb infected macrophages for synergistic treatment of CTB. Based on the selective macrophage targeting effects, the proposed Rif@Man-mPDA NPs also showed excellent photothermal properties to develop Rif@Man-mPDA NPs-mediated PTT for intracellular Mtb killings in macrophages. Importantly, Rif@Man-mPDA NPs could inhibit the immune escape of Mtb by effectively chelating intracellular Fe2+ and inhibiting lipid peroxidation, and up-regulating GPX4 expression to inhibit ferroptosis of Mtb infected macrophages through activating Nrf2/HO-1 signaling. Moreover, Rif@Man-mPDA NPs-mediated PTT could effectively activate host cell immune responses by promoting autophagy of Mtb infected macrophages, which thus synergizes targeted drug delivery and ferroptosis inhibition for more effective intracellular Mtb clearance. This Rif@Man-mPDA NPs-mediated PTT strategy could also effectively inhibit the Mtb burdens and alleviate the pathological lesions induced by Mtb infection without significant systemic side effects in mouse CTB model. These results indicate that Rif@Man-mPDA NPs-mediated PTT can be served as a novel anti-TB strategy against CTB by synergizing macrophage targeted photothermal therapy and host immune defenses, thus holding promise for more effective treatment strategy development against CTB.

Macrophage targeted graphene oxide nanosystem synergize antibiotic killing and host immune defense for Tuberculosis Therapy.

Tuberculosis (TB), a deadly disease caused by Mycobacterium tuberculosis (Mtb) infection, remains one of the top killers among infectious diseases worldwide. How to increase targeting effects of current anti-TB chemotherapeutics and enhance anti-TB immunological responses remains a big challenge in TB and drug-resistant TB treatment. Here, mannose functionalized and polyetherimide protected graphene oxide system (GO-PEI-MAN) was designed for macrophage-targeted antibiotic (rifampicin) and autophagy inducer (carbamazepine) delivery to achieve more effective Mtb killings by combining targeted drug killing and host immunological clearance. GO-PEI-MAN system demonstrated selective uptake by in vitro macrophages and ex vivo macrophages from macaques. The endocytosed GO-PEI-MAN system would be transported into lysosomes, where the drug loaded Rif@Car@GO-PEI-MAN system would undergo accelerated drug release in acidic lysosomal conditions. Rif@Car@GO-PEI-MAN could significantly promote autophagy and apoptosis in Mtb infected macrophages, as well as induce anti-bacterial M1 polarization of Mtb infected macrophages to increase anti-bacterial IFN-γ and nitric oxide production. Collectively, Rif@Car@GO-PEI-MAN demonstrated effectively enhanced intracellular Mtb killing effects than rifampicin, carbamazepine or GO-PEI-MAN alone in Mtb infected macrophages, and could significantly reduce mycobacterial burdens in the lung of infected mice with alleviated pathology and inflammation without systemic toxicity. This macrophage targeted nanosystem synergizing increased drug killing efficiency and enhanced host immunological defense may be served as more effective therapeutics against TB and drug-resistant TB.

Intratracheal delivery of macrophage targeted Celastrol-loaded PLGA nanoparticles for enhanced anti-inflammatory efficacy in acute lung injury mice.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common causes of respiratory failure in critically ill patients. There is still a lack of definitive and effective treatment options, and the mortality rate remains as high as 30% to 40%. Effective therapeutics for ALI/ARDS are greatly hindered by the side effects resulting from inefficient delivery to the disease lesions and off-targeting biodistribution of drugs. Macrophages play an integral role in maintaining the steady state of the immune system and are involved in inflammation processes. Thus, nanodrug to accurately target macrophages have the potential to transform disease treatment. Here, we developed an mannosylated drug delivery system to target and deliver celastrol (Cel) to the alveolar macrophages for enhanced alleviating the cytokines in LPS-induce ALI mice. In vitro data demonstrated that the as-synthesized Man@Cel-NPs significantly improved the targeting of Cel into the inflammatory macrophages via mannose receptor-mediated phagocytosis. In vivo experiments further showed that intratracheal delivery of Man@Cel-NPs can improve the dysregulation of inflammatory response in LPS-induced mice by inhibiting the release of inflammatory cytokines and increasing autophagy and decreasing apoptosis in lungs. This work provides a potential NP platform for the locally tracheal delivery of herbal ingredients and exhibits promising clinical potential in the treatment of numerous respiratory diseases, including ALI/ARDS.

Inhaled tea polyphenol-loaded nanoparticles coated with platelet membranes largely attenuate asthmatic inflammation.

BACKGROUND: Tea polyphenols (TPs), prominent constituents of green tea, possess remarkable antioxidant and anti-inflammatory properties. However, their therapeutic potential is limited due to low absorption and poor bioavailability. To address this limitation and enhance their efficacy, we developed a biomimetic nanoplatform by coating platelet membrane (PM) onto poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) to create targeted delivery vehicles for TPs (PM@TP/NPs) to the inflamed tissues in asthma. METHODS: After synthesizing and characterizing PM@TP/NPs, we assessed their biocompatibility and biosafety through cell viability assays, hemolysis tests, and inflammation analysis in vivo and in vitro. The therapeutic effect of PM@TP/NPs on asthma was then evaluated using a mouse model of HDM-induced asthma. Additionally, PM@TP/NPs-mediated reactive oxygen species (ROS) scavenging capacity, as well as the activation of signaling pathways, were analyzed in HBE cells and asthmatic mice via flow cytometry, RT-qPCR, and western blotting. RESULTS: Compared with free TPs, PM@TP/NPs demonstrated excellent biocompatibility and safety profiles in both in vitro and in vivo, as well as enhanced retention in inflamed lungs. In HDM-induced mouse asthma model, inhaled PM@TP/NPs largely attenuated lung inflammation and reduced the secretion of type 2 pro-inflammatory cytokines in the lungs compared to free TPs. The therapeutic effects of PM@TP/NPs on asthma might be associated with an enhanced ROS scavenging capacity, increased activation of the Nrf2/HO-1 pathway, and decreased activation of the CCL2/MAPK and TLR4/NF-κB pathway in the lungs. CONCLUSIONS: Our findings demonstrate that inhalation of PM@TP/NPs largely attenuated lung inflammation in HDM-induced asthmatic mice. These results suggest that PM@TP/NPs might be a novel therapeutic strategy for asthma.

Congenital Cutaneous Sinus at the Sternoclavicular Joint.

A 32-year-old female patient presented with chronic discharging sinus with recurrent infection at the left sternoclavicular joint. What is your diagnosis?

Topological Network Modes in a Twisted Moiré Phononic Crystal.

Twisted moiré materials, a new class of layered structures with different twist angles for neighboring layers, are attracting great attention because of the rich intriguing physical phenomena associated with them. Of particular interest are the topological network modes, first proposed in the small angle twisted bilayer graphene under interlayer bias. Here we report the observations of such topological network modes in twisted moiré phononic crystals without requiring the external bias fields. Acoustic topological network modes that can be constructed in a wide range of twist angles are both observed in the domain walls with and without reconstructions, which serve as the analogy of the lattice relaxations in electronic moiré materials. Topological robustness of the topological network modes is observed by introducing valley-preserved defects to the network channel. Furthermore, the network can be reconfigured into two-dimensional patterns with any desired connectivity, offering a unique prototype platform for acoustic applications.

Doughnut-shaped bimetallic Cu-Zn-MOF with peroxidase-like activity for colorimetric detection of glucose and antibacterial applications.

Metal-organic frameworks (MOFs), especially bimetallic MOFs, have attracted widespread attention for simulating the structure and function of natural enzymes. In this study, different morphologies of bimetallic Cu-Zn-MOF with different peroxidase (POD)-like activities were prepared by simply controlling the molar ratio of Cu2+ and Zn2+. Among them, the doughnut-shaped Cu9-Zn1-MOF exhibited the largest POD-like activity. Cu9-Zn1-MOF was combined with glucose oxidase to construct a sensitive and selective glucose colorimetric biosensor with a linear detection range of 10-300 µM and a detection limit of 7.1 µm. Furthermore, Cu9-Zn1-MOF can efficiently convert hydrogen peroxide (H2O2) into hydroxyl radicals that effectively kill both gram-negative and gram-positive bacteria at low H2O2 level. The results of this study may promote the synthesis of bimetallic MOFs and broaden their applications in the biomedical field.

Propensity Score Matching Analysis of the Influence of Waiting Time Satisfaction on Community Resident's Satisfaction With Medical Institutions: An Extensive Survey of Outpatient Population in Shantou City of Southern China.

OBJECTIVE: This study was designed to perform a nuanced analysis of the multifaceted association between community residents' satisfaction and their perceived satisfaction concerning the visit duration at medical facilities, that could be harnessed to enhance and streamline the process of hierarchical diagnosis and treatment, thereby augmenting healthcare outcomes and patient experiences. METHODS: Respondents who had utilized services from medical institutions were invited to fill out questionnaires by scanning QR codes. Additionally, surveys also distributed questionnaires through WeChat groups of community residents in densely populated areas of the community, as well as WeChat groups for patients who had previously visited local hospitals. To balance differences between groups, propensity score matching was applied to analyze the contrast between residents satisfied and dissatisfied with their medical visits. After eliminating the interference of confounding factors, a comparative analysis was conducted on the relationship between resident satisfaction and medical institution experience.After eliminating the interference of confounding factors, a comparative analysis was conducted to delve deeply into the relationship between residents' satisfaction and their experiences at medical facilities. RESULTS: The study incorporated a large dataset encompassing 2356 community residents. Upon successful propensity score matching, logistic regression analysis elucidated several determinants of overall resident satisfaction. Notably, the grade of the medical institution (χ2 = 8.226, P < .05), satisfaction with the time invested in the registration process (χ2 = 11.04, P < .05), satisfaction with the waiting duration for consultation (χ2 = 15.759, P < .05), and satisfaction with the travel time to the hospital (χ2 = 45.157, P < .05) each exerted significant influence on the holistic satisfaction of residents with their medical experience. CONCLUSION: Factors such as the grade of the medical institution, satisfaction related to registration and waiting durations, and travel time to the hospital emerged as crucial determinants shaping community residents' holistic satisfaction with their medical encounters. These findings underscore the exigency for strategic allocation and optimization of medical resources, refinement of the classification system, and enhancement of public health education on the graded diagnosis and treatment schema. The study also demonstrates the value of employing advanced propensity score matching and predictive modelling techniques in health services research.

Brillouin Klein space and half-turn space in three-dimensional acoustic crystals.

The Bloch band theory and Brillouin zone (BZ) that characterize wave-like behaviors in periodic mediums are two cornerstones of contemporary physics, ranging from condensed matter to topological physics. Recent theoretical breakthrough revealed that, under the projective symmetry algebra enforced by artificial gauge fields, the usual two-dimensional (2D) BZ (orientable Brillouin two-torus) can be fundamentally modified to a non-orientable Brillouin Klein bottle with radically distinct manifold topology. However, the physical consequence of artificial gauge fields on the more general three-dimensional (3D) BZ (orientable Brillouin three-torus) was so far missing. Here, we theoretically discovered and experimentally observed that the fundamental domain and topology of the usual 3D BZ can be reduced to a non-orientable Brillouin Klein space or an orientable Brillouin half-turn space in a 3D acoustic crystal with artificial gauge fields. We experimentally identify peculiar 3D momentum-space non-symmorphic screw rotation and glide reflection symmetries in the measured band structures. Moreover, we experimentally demonstrate a novel stacked weak Klein bottle insulator featuring a nonzero Z2 topological invariant and self-collimated topological surface states at two opposite surfaces related by a nonlocal twist, radically distinct from all previous 3D topological insulators. Our discovery not only fundamentally modifies the fundamental domain and topology of 3D BZ, but also opens the door towards a wealth of previously overlooked momentum-space multidimensional manifold topologies and novel gauge-symmetry-enriched topological physics and robust acoustic wave manipulations beyond the existing paradigms.

Neutrophils in Cancer immunotherapy: friends or foes?

Neutrophils play a Janus-faced role in the complex landscape of cancer pathogenesis and immunotherapy. As immune defense cells, neutrophils release toxic substances, including reactive oxygen species and matrix metalloproteinase 9, within the tumor microenvironment. They also modulate the expression of tumor necrosis factor-related apoptosis-inducing ligand and Fas ligand, augmenting their capacity to induce tumor cell apoptosis. Their involvement in antitumor immune regulation synergistically activates a network of immune cells, bolstering anticancer effects. Paradoxically, neutrophils can succumb to the influence of tumors, triggering signaling cascades such as JAK/STAT, which deactivate the immune system network, thereby promoting immune evasion by malignant cells. Additionally, neutrophil granular constituents, such as neutrophil elastase and vascular endothelial growth factor, intricately fuel tumor cell proliferation, metastasis, and angiogenesis. Understanding the mechanisms that guide neutrophils to collaborate with other immune cells for comprehensive tumor eradication is crucial to enhancing the efficacy of cancer therapeutics. In this review, we illuminate the underlying mechanisms governing neutrophil-mediated support or inhibition of tumor progression, with a particular focus on elucidating the internal and external factors that influence neutrophil polarization. We provide an overview of recent advances in clinical research regarding the involvement of neutrophils in cancer therapy. Moreover, the future prospects and limitations of neutrophil research are discussed, aiming to provide fresh insights for the development of innovative cancer treatment strategies targeting neutrophils.

Observation of 3D acoustic quantum Hall states.

Quantum Hall effect, the quantized transport phenomenon of electrons under strong magnetic fields, remains one of the hottest research topics in condensed matter physics since its discovery in 2D electronic systems. Recently, as a great advance in the research of quantum Hall effects, the quantum Hall effect in 3D systems, despite its big challenge, has been achieved in the bulk ZrTe5 and Cd3As2 materials. Interestingly, Cd3As2 is a Weyl semimetal, and quantum Hall effect is hosted by the Fermi arc states on opposite surfaces via the Weyl nodes of the bulk, and induced by the unique edge states on the boundaries of the opposite surfaces. However, such intriguing edge state distribution has not yet been experimentally observed. Here, we aim to reveal experimentally the unusual edge states of Fermi arcs in acoustic Weyl system with the aid of pseudo-magnetic field. Benefiting from the macroscopic nature of acoustic crystals, the pseudo-magnetic field is introduced by elaborately designed the gradient on-site energy, and the edge states of Fermi arcs on the boundaries of the opposite surfaces are unambiguously demonstrated in experiments. Our system serves as an ideal and highly tunable platform to explore the Hall physics in 3D system, and has the potential in the application of new acoustic devices.

Meta-analysis of machine learning models for the diagnosis of central precocious puberty based on clinical, hormonal (laboratory) and imaging data.

Background: Central precocious puberty (CPP) is a common endocrine disorder in children, and its diagnosis primarily relies on the gonadotropin-releasing hormone (GnRH) stimulation test, which is expensive and time-consuming. With the widespread application of artificial intelligence in medicine, some studies have utilized clinical, hormonal (laboratory) and imaging data-based machine learning (ML) models to identify CPP. However, the results of these studies varied widely and were challenging to directly compare, mainly due to diverse ML methods. Therefore, the diagnostic value of clinical, hormonal (laboratory) and imaging data-based ML models for CPP remains elusive. The aim of this study was to investigate the diagnostic value of ML models based on clinical, hormonal (laboratory) and imaging data for CPP through a meta-analysis of existing studies. Methods: We conducted a comprehensive search for relevant English articles on clinical, hormonal (laboratory) and imaging data-based ML models for diagnosing CPP, covering the period from the database creation date to December 2023. Pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), summary receiver operating characteristic (SROC) curve, and area under the curve (AUC) were calculated to assess the diagnostic value of clinical, hormonal (laboratory) and imaging data-based ML models for diagnosing CPP. The I2 test was employed to evaluate heterogeneity, and the source of heterogeneity was investigated through meta-regression analysis. Publication bias was assessed using the Deeks funnel plot asymmetry test. Results: Six studies met the eligibility criteria. The pooled sensitivity and specificity were 0.82 (95% confidence interval (CI) 0.62-0.93) and 0.85 (95% CI 0.80-0.90), respectively. The LR+ was 6.00, and the LR- was 0.21, indicating that clinical, hormonal (laboratory) and imaging data-based ML models exhibited an excellent ability to confirm or exclude CPP. Additionally, the SROC curve showed that the AUC of the clinical, hormonal (laboratory) and imaging data-based ML models in the diagnosis of CPP was 0.90 (95% CI 0.87-0.92), demonstrating good diagnostic value for CPP. Conclusion: Based on the outcomes of our meta-analysis, clinical and imaging data-based ML models are excellent diagnostic tools with high sensitivity, specificity, and AUC in the diagnosis of CPP. Despite the geographical limitations of the study findings, future research endeavors will strive to address these issues to enhance their applicability and reliability, providing more precise guidance for the differentiation and treatment of CPP.

Valley edge states as bound states in the continuum.

Bound states in the continuum (BICs) are spatially localized states with energy embedded in the continuum spectrum of extended states. The combination of BICs physics and nontrivial band topology theory givs rise to topological BICs, which are robust against disorders and meanwhile, the merit of conventional BICs is attracting wide attention recently. Here, we report valley edge states as topological BICs, which appear at the domain wall between two distinct valley topological phases. The robustness of such BICs is demonstrated. The simulations and experiments show great agreement. Our findings of valley related topological BICs shed light on both BICs and valley physics, and may foster innovative applications of topological acoustic devices.

Wood-converted porous carbon decorated with MIL-101(Fe) derivatives for promoting photo-Fenton degradation of ciprofloxacin.

In response to the escalating concerns over antibiotics in aquatic environments, the photo-Fenton reaction has been spotlighted as a promising approach to address this issue. Herein, a novel heterogeneous photo-Fenton catalyst (Fe3O4/WPC) with magnetic recyclability was synthesized through a facile two-step process that included in situ growth and subsequent carbonization treatment. This catalyst was utilized to expedite the photocatalytic decomposition of ciprofloxacin (CIP) assisted by H2O2. Characterization results indicated the successful anchoring of MIL-101(Fe)-derived spindle-like Fe3O4 particles in the multi-channeled wood-converted porous carbon (WPC) scaffold. The as-synthesized hybrid photocatalysts, boasting a substantial specific surface area of 414.90 m2·g-1 and an excellent photocurrent density of 0.79 µA·cm-2, demonstrated superior photo-Fenton activity, accomplishing approximately 100% degradation of CIP within 120 min of ultraviolet-light exposure. This can be attributed to the existence of a heterojunction between Fe3O4 and WPC substrate that promotes the migration and enhances the efficient separation of photogenerated electron-hole pairs. Meanwhile, the Fe(III)/Fe(II) redox circulation and mesoporous wood carbon in the catalyst synergistically enhance the utilization of H2O and accelerate the formation of •OH radicals, leading to heightened degradation efficiency of CIP. Experiments utilizing chemical trapping techniques have demonstrated that •OH radicals are instrumental in the CIP degradation process. Furthermore, the study on reusability indicated that the efficiency in removing CIP remained at 89.5% even through five successive cycles, indicating the structural stability and excellent recyclability of Fe3O4/WPC. This research presented a novel pathway for designing magnetically reusable MOFs/wood-derived composites as photo-Fenton catalysts for actual wastewater treatment.

Inflammatory cytokines and risk of allergic rhinitis: A Mendelian randomization study.

BACKGROUND: Epidemiological and experimental evidences have implicated chronic inflammation in the association with allergic rhinitis (AR). However, it remains unclear whether specific circulating cytokines are the cause of AR or the consequence of bias. To examine whether genetic-predicted changes in circulating cytokine concentrations are related to the occurrence of AR, we conducted a two-sample Mendelian randomization (MR) analysis. METHODS: We investigated the causal effects of 26 circulating inflammatory cytokines on AR through MR analysis. The primary method employed in this study was the inverse variance-weighted (IVW) method. Sensitivity analyses were conducted using simple median, weighted median, penalized weighted median, and MR-Egger regression. RESULTS: Our study revealed suggestive evidence that higher levels of circulating IL-18 (OR per one standard deviation [SD] increase: 1.006; 95 % CI, 1.002 to 1.011; P = 0.006, PFDR = 0.067, random-effects IVW method) and Macrophage inflammatory protein-1α (MIP-1α) (OR per one SD increase: 1.015; 95 % CI, 1.004 to 1.026; P = 0.009, PFDR = 0.048, random-effects IVW method) were associated with an increased risk of AR. Conversely, higher levels of circulating TRAIL were associated with a decreased risk of AR (OR per one SD increase: 0.993; 95 % CI, 0.989 to 0.997; P = 4.58E-4, PFDR = 0.004, random-effects IVW method). Only the results of TRAIL exist after Bonferroni-correction (the p-value < 0.0019). Sensitivity analysis yielded directionally consistent results. No significant associations were observed between other circulating inflammatory cytokines and AR. CONCLUSION: Genetically predicted levels of IL-18, and MIP-1α are likely to associated with an increased risk of AR occurrence. Genetically predicted levels of TRAIL are statistically significant in reducing the risk of AR occurrence. However, the current research evidence does not support an impact of other inflammatory cytokines on the risk of AR. Future studies are needed to provide additional evidence to support the current conclusions.