Mechanisms of traditional Chinese medicine overcoming of radiotherapy resistance in breast cancer.

Breast cancer stands as the most prevalent malignancy among women, with radiotherapy serving as a primary treatment modality. Despite radiotherapy, a subset of breast cancer patients experiences local recurrence, attributed to the intrinsic resistance of tumors to radiation. Therefore, there is a compelling need to explore novel approaches that can enhance cytotoxic effects through alternative mechanisms. Traditional Chinese Medicine (TCM) and its active constituents exhibit diverse pharmacological actions, including anti-tumor effects, offering extensive possibilities to identify effective components capable of overcoming radiotherapy resistance. This review delineates the mechanisms underlying radiotherapy resistance in breast cancer, along with potential candidate Chinese herbal medicines that may sensitize breast cancer cells to radiotherapy. The exploration of such herbal interventions holds promise for improving therapeutic outcomes in the context of breast cancer radiotherapy resistance.

Tunable-bias based optical neural network for reinforcement learning in path planning.

Owing to the high integration, reconfiguration and strong robustness, Mach-Zehnder interferometers (MZIs) based optical neural networks (ONNs) have been widely considered. However, there are few works adding bias, which is important for neural networks, into the ONNs and systematically studying its effect. In this article, we propose a tunable-bias based optical neural network (TBONN) with one unitary matrix layer, which can improve the utilization rate of the MZIs, increase the trainable weights of the network and has more powerful representational capacity than traditional ONNs. By systematically studying its underlying mechanism and characteristics, we demonstrate that TBONN can achieve higher performance by adding more optical biases to the same side beside the inputted signals. For the two-dimensional dataset, the average prediction accuracy of TBONN with 2 biases (97.1%) is 5% higher than that of TBONN with 0 biases (92.1%). Additionally, utilizing TBONN, we propose a novel optical deep Q network (ODQN) algorithm to complete path planning tasks. By implementing simulated experiments, our ODQN shows competitive performance compared with the conventional deep Q network, but accelerates the computation speed by 2.5 times and 4.5 times for 2D and 3D grid worlds, respectively. Further, a more noticeable acceleration will be obtained when applying TBONN to more complex tasks. Also, we demonstrate the strong robustness of TBONN and the imprecision elimination method by using on-chip training.

Diatom Cribellum-Inspired Hierarchical Metamaterials: Unifying Perfect Absorption Toward Subwavelength Color Printing.

Diatom exoskeletons, known as frustules, exhibit a unique multilayer structure that has attracted considerable attention across interdisciplinary research fields as a source of biomorphic inspiration. These frustules possess a hierarchical porous structure, ranging from millimeter-scale foramen pores to nanometer-scale cribellum pores. In this study, this natural template for nanopattern design is leveraged to showcase metamaterials that integrates perfect absorption and subwavelength color printing. The cribellum-inspired hierarchical nanopatterns, organized in a hexagonal unit cell with a periodicity of 300 nm, are realized through a single-step electron beam lithography process. By employing numerical models, it is uncovered that an additional induced collective dipole mode is the key mechanism responsible for achieving outstanding performance in absorption, reaching up to 99%. Analysis of the hierarchical organization reveals that variations in nanoparticle diameter and inter-unit-cell distance lead to shifts and broadening of the resonance peaks. It is also demonstrated that the hierarchical nanopatterns are capable of color reproduction with high uniformity and fidelity, serving as hexagonal pixels for high-resolution color printing. These cribellum-inspired metamaterials offer a novel approach to multifunctional metamaterial design, presenting aesthetic potential applications in the development of robotics and wearable electronic devices, such as smart skin or surface coatings integrated with energy harvesting functionalities.

Comparing the efficacy of traditional Chinese exercises and general aerobic exercises in university students with sleep disorders: A systematic review and meta-analysis.

BACKGROUND: The objective of this study was to compare the impact of traditional Chinese exercise (TCEs) and general aerobic exercise (GAEs) on the sleep quality of university students and to determine which exercise is more effective in improving sleep quality in this specific population. METHODS: We utilized Review Manager 5.3 to analyze data from 21 randomized controlled trials (RCTs), which included a total of 1252 participants. Effect sizes of TCEs and GAEs were compared using a random-effects model. Subgroup analyses were conducted on 3 modulating variables: times per session, frequency per week, and period. RESULTS: A Meta-analysis of 14 RCTs showed that both TCEs (standard mean difference [SMD] = -0.89, 95% CI: -1.18 to -0.61; P < .00001) and GAEs (SMD = -1.53, 95% CI: -2.10 to -0.97; P < .00001) can significantly improve the sleep of university students, with a significant difference between TCEs and GAEs (P = .05). Both GAEs and TCEs had positive effects on various aspects of sleep quality, including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication, and daytime dysfunction. A subgroup analysis of aerobic exercise showed that the effect size was larger in the 40 to 60 minutes group compared to the 60 to 90 minutes group (SMD = -1.89; 95% CI: -2.19 to -1.59; P < .00001). Furthermore, the effect size was larger in the 3 to 5 times per week group compared to the 2 times per week group (SMD = -1.56; 95% CI: -2.33 to -0.80; P < .0001). The effect size was also found to be larger in a period of 2 to 4 weeks compared to 6 to 18 weeks (SMD = -1.85; 95% CI: -2.17 to -1.54; P < .00001). CONCLUSION: GAEs is more effective than TCEs in improving the sleep quality of university students. An optimal aerobic exercise regimen for enhancing sleep quality among university students involves engaging in sessions lasting 40~60 minutes, 3~5 times per week, over a duration of 4 weeks.

Facile synthesis of Cu-based catalysts from Cu3Si and their catalysis properties study.

Supported copper species are well-known for their remarkable catalytic properties across numerous reactions. However, the current preparation methods pose challenges for large-scale production. In this study, we present a cost-effective method for the facile preparation of a series of copper-silicon composites using Cu3Si@Si particles as precursors. We evaluate the catalytic properties of these composites in the conversion of 4-nitrophenol to 4-amionphenol. Notably, the Cu@SiOx/Si composite exhibits exceptional catalytic performance, attributed to the synergy effect between Cu and Si, and the formation of a metastable Si-H2 complex that enhances the reaction kinetics. This research introduces a novel approach for creating efficient and stable catalysts for hydrogenation reactions.

Twin Strep-Tag Modified CPT1A Mitochondrial Membrane Chromatography in Screening Lipid Metabolism Regulators.

Mitochondrial Membrane Chromatography (MMC) is a bioaffinity chromatography technique developed to study the interaction between target proteins embedded in the mitochondrial membrane and their ligand compounds. However, the MMC stationary phases (MMSP) prepared by chemical immobilization are prone to nonspecific binding in candidate agent screening inevitably. To address these challenges, Twin Strep-Tag/Strep Tactin was employed to establish a specific affinity system in the present study. We prepared a carnitine palmitoyltransferase 1A (CPT1A) MMSP by specifically linking Strep-tactin-modified silica gel with the Twin Strep-Tag on the CPT1A-oriented mitochondrial membrane. This Twin Strep-Tag/Strep Tactin modified CPT1A/MMC method exhibited remarkably better retention behavior, longer stationary phase lifespan, and higher screening specificity compared with previous MMC systems with glutaraldehyde immobilization. We adopted the CPT1A-specific MMC system in screening CPT1A ligands from traditional Chinese medicines, and successfully identified novel candidate ligands: ononin, isoliquiritigenin, and aloe-emodin, from Glycyrrhiza uralensis Fisch and Senna tora (L.) Roxb extracts. Biological assessments illustrated that the compounds screened promote CPT1A enzyme activity without affecting CPT1A protein expression, as well as effectively reduce the lipid droplets and triglyceride levels in the high fat induction HepG2 cells. The results suggest that we have developed an MMC system, which is promising for studying the bioaffinity of mitochondrial membrane proteins to candidate compounds. This system provides a platform for a key step in mitochondrial medicine discovery, especially for bioactive molecule screening from complex herbal extracts.

Enhanced flotation removal of polystyrene nanoplastics by chitosan modification: Performance and mechanism.

Nanoplastics are difficult to remove from water using conventional flotation processes due to their stability and resistance to biodegradation. Here, polystyrene nanoplastics (PSNPs) were selected as the object of study. In addition, chitosan (CTS), an environmentally friendly natural cationic polymer, was selected to modify the air flotation process to improve the separation of PSNPs using air flotation. Adding chitosan effectively enhanced the removal of PSNPs using air flotation from 3.1 % to 96.7 %. The residual concentration decreased from 9.69 mg/L to 0.33 mg/L. Removal of PSNPs by CTS-modified air flotation was maintained at 92.8 % even when the air flotation time was significantly shortened. The zeta potential alterations demonstrated robust electrostatic attraction within the CTS-modified air flotation process. The contact angle measurements indicated that incorporating CTS could enhance the hydrophobic interaction between bubbles and PSNPs. PSNPs particles around 100 nm agglomerated to form floating flocs with a particle size of more than 4500 nm. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) images confirmed the presence of tight adhesion between PSNPs and CTS, indicating the presence of bridging adsorption during the process. The major PSNPs removal mechanisms included electrostatic attraction, enhancement of hydrophobicity, and bridging adsorption. Increasing the aeration volume could improve the removal rate, but this improvement was finite. Weakly acidic and low ionic strength conditions favored PSNPs removal. The CTS-modified air flotation process showed great potential for PSNPs removal from real water bodies.

Co-Mutations and Possible Variation Tendency of the Spike RBD and Membrane Protein in SARS-CoV-2 by Machine Learning.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, SARS-CoV-2 variants capable of breakthrough infections have attracted global attention. These variants have significant mutations in the receptor-binding domain (RBD) of the spike protein and the membrane (M) protein, which may imply an enhanced ability to evade immune responses. In this study, an examination of co-mutations within the spike RBD and their potential correlation with mutations in the M protein was conducted. The EVmutation method was utilized to analyze the distribution of the mutations to elucidate the relationship between the mutations in the spike RBD and the alterations in the M protein. Additionally, the Sequence-to-Sequence Transformer Model (S2STM) was employed to establish mapping between the amino acid sequences of the spike RBD and M proteins, offering a novel and efficient approach for streamlined sequence analysis and the exploration of their interrelationship. Certain mutations in the spike RBD, G339D-S373P-S375F and Q493R-Q498R-Y505, are associated with a heightened propensity for inducing mutations at specific sites within the M protein, especially sites 3 and 19/63. These results shed light on the concept of mutational synergy between the spike RBD and M proteins, illuminating a potential mechanism that could be driving the evolution of SARS-CoV-2.

Molecular Insights into Macromolecules Structure, Function, and Regulation.

Macromolecules exhibit ordered structures and complex functions in an aqueous environment with strong thermodynamic fluctuations [...].

In situ densification and heparin immobilization of bacterial cellulose vascular patch for potential vascular applications.

Nowadays, developing vascular grafts (e.g., vascular patches and tubular grafts) is challenging. Bacterial cellulose (BC) with 3D fibrous network has been widely investigated for vascular applications. In this work, different from BC vascular patch cultured with the routine culture medium, dopamine (DA)-containing culture medium is employed to in situ synthesize dense BC fibrous structure with significantly increased fiber diameter and density. Simultaneously, BC fibers are modified by DA during in situ synthesis process. Then DA on BC fibers can self-polymerize into polydopamine (PDA) accompanied with the removal of bacteria in NaOH solution, obtaining PDA-modified dense BC (PDBC) vascular patch. Heparin (Hep) is subsequently covalently immobilized on PDBC fibers to form Hep-immobilized PDBC (Hep@PDBC) vascular patch. The obtained results indicate that Hep@PDBC vascular patch exhibits remarkable tensile and burst strength due to its dense fibrous structure. More importantly, compared with BC and PDBC vascular patches, Hep@PDBC vascular patch not only displays reduced platelet adhesion and improved anticoagulation activity, but also promotes the proliferation, adhesion, spreading, and protein expression of human umbilical vein endothelial cells, contributing to the endothelialization process. The combined strategy of in situ densification and Hep immobilization provides a feasible guidance for the construction of BC-based vascular patches.

Photocatalytic CO2 reduction with iron porphyrin catalysts and anthraquinone dyes.

Herein we studied visible-light-driven CO2 reduction using a series of tetra-phenylporphyrin iron catalysts and inexpensive anthraquinone dyes. Varying the functional groups on the phenyl moieties of the catalysts significantly enhances the photocatalytic activity, achieving an optimal turnover number (TON) of 10 476 and a selectivity of 100% in the noble-metal-free systems. The highest activity found in a bromo-substituted catalyst is attributed to favorable electron transfer from the photosensitizer to the iron porphyrin.

[Analysis of clinical treatment of acute respiratory distress syndrome assisted by artificial intelligence].

OBJECTIVE: To evaluate the clinical practice of intensive care unit (ICU) physicians at Hebei General Hospital in identifying patients meeting the diagnostic criteria for acute respiratory distress syndrome (ARDS) and the current status of invasive mechanical ventilation management and adjunctive therapy in these patients, and to analyze the incidence and clinical outcomes of ARDS. METHODS: A retrospective cohort study was conducted. The patients who were hospitalized in the ICU of Hebei General Hospital from April 10, 2017 to June 30, 2022 and met the Berlin definition diagnostic criteria for ARDS were enrolled as study subjects. Artificial intelligence (AI) technology was applied to search the basic information (age, gender, height, body weight, etc.), auxiliary examination, electronic medical record, non-drug doctor's advice, drug doctor's advice, critical report, scoring system, monitoring master table and other data of the above medical records in the electronic medical record system of the hospital. The first set of laboratory indicators sequentially retrieved from the system daily from 05:00 to 10:00 and vital signs and mechanical ventilation-related parameters recorded in the "critical care report" at 06:00 daily were extracted, and outcome indicators of the patients were collected. RESULTS: After screening and analysis, a total of 255 patients who met the ARDS diagnostic criteria were finally enrolled. The overall incidence of ARDS in the ICU accounted for 3.4% (255/7 434) of the total number of ICU patients, of which mild, moderate and severe ARDS accounted for 22.4% (57/255), 49.0% (125/255), and 28.6% (73/255), respectively, while the recognition rates of clinical doctors were 71.9% (41/57), 58.4% (73/125) and 71.2% (52/73), respectively. During the ICU stay, 250 patients (98.0%) received only invasive mechanical ventilation, while 5 patients (2.0%) received both non-invasive and invasive mechanical ventilation. The tidal volume/ideal body weight of ARDS patients was 7.64 (6.49, 9.01) mL/kg, and the positive end-expiratory pressure (PEEP) was 8.0 (5.0, 10.0) cmH2O (1 cmH2O ≈ 0.098 kPa). In addition, during the diagnosis and detection of ARDS, only 7 patients were recorded the platform pressure and 6 patients were recorded the drive pressure. Regarding adjunctive therapies, 137 patients (53.7%) received deep sedation, 26 patients (10.2%) underwent lung recruitment, 55 patients (21.6%) received prone ventilation, 42 patients (16.5%) were treated with high-dose steroids, 19 patients (7.5%) were treated with neuromuscular blockade, and 8 patients (3.1%) were treated with extracorporeal membrane oxygenation (ECMO). Finally, 70 patients (27.5%) were discharged automatically, while 50 patients (19.6%) died in the ICU, of which the ICU mortality of mild, moderate, and severe ARDS patients were 15.8% (9/57), 22.4% (28/125), and 17.8% (13/73), respectively. After follow-up, it was found that all 70 patients discharged automatically died within 28 days after discharge, and the overall ICU mortality adjusted accordingly was 47.1% (120/255). CONCLUSIONS: The overall incidence of ARDS in ICU patients at Hebei General Hospital is relatively low, with a high recognition rate by clinical physicians. Despite the high level of compliance and implementation of lung protective ventilation strategies and auxiliary treatment measures, it is still necessary to further improve the level of standardization in the implementation of small tidal volume and respiratory mechanics monitoring. For the implementation of auxiliary measures such as prone ventilation, it is necessary to further improve the enthusiasm of medical staff. The mortality in ICU is relatively low in ARDS patients, while the rate of spontaneous discharge is relatively high.

Heterointerface engineering of layered double hydroxide/MAPbBr3 heterostructures enabling tunable synapse behaviors in a two-terminal optoelectronic device.

Solution-processable semiconductor heterostructures enable scalable fabrication of high performance electronic and optoelectronic devices with tunable functions via heterointerface control. In particular, artificial optical synapses require interface manipulation for nonlinear signal processing. However, the limited combinations of materials for heterostructure construction have restricted the tunability of synaptic behaviors with simple device configurations. Herein, MAPbBr3 nanocrystals were hybridized with MgAl layered double hydroxide (LDH) nanoplates through a room temperature self-assembly process. The formation of such heterostructures, which exhibited an epitaxial relationship, enabled effective hole transfer from MAPbBr3 to LDH, and greatly reduced the defect states in MAPbBr3. Importantly, the ion-conductive nature of LDH and its ability to form a charged surface layer even under low humidity conditions allowed it to attract and trap holes from MAPbBr3. This imparted tunable synaptic behaviors and short-term plasticity (STP) to long-term plasticity (LTP) transition to a two-terminal device based on the LDH-MAPbBr3 heterostructures. The further neuromorphic computing simulation under varying humidity conditions showcased their potential in learning and recognition tasks under ambient conditions. Our work presents a new type of epitaxial heterostructure comprising metal halide perovskites and layered ion-conductive materials, and provides a new way of realizing charge-trapping induced synaptic behaviors.

Four Parallel Pathways in T4 Ligase-Catalyzed Repair of Nicked DNA with Diverse Bending Angles.

The structural diversity of biological macromolecules in different environments contributes complexity to enzymological processes vital for cellular functions. Fluorescence resonance energy transfer and electron microscopy are used to investigate the enzymatic reaction of T4 DNA ligase catalyzing the ligation of nicked DNA. The data show that both the ligase-AMP complex and the ligase-AMP-DNA complex can have four conformations. This finding suggests the parallel occurrence of four ligation reaction pathways, each characterized by specific conformations of the ligase-AMP complex that persist in the ligase-AMP-DNA complex. Notably, these complexes have DNA bending angles of ≈0°, 20°, 60°, or 100°. The mechanism of parallel reactions challenges the conventional notion of simple sequential reaction steps occurring among multiple conformations. The results provide insights into the dynamic conformational changes and the versatile attributes of T4 DNA ligase and suggest that the parallel multiple reaction pathways may correspond to diverse T4 DNA ligase functions. This mechanism may potentially have evolved as an adaptive strategy across evolutionary history to navigate complex environments.

Corporate political acuity and carbon - efficiency synergies.

RESEARCH QUESTION: In the context of global low-carbon emission reduction, how to achieve green and high-quality development has become a major issue for the Communist Party of China (CPC) and the Chinese government recently. Based on the data of China's listed companies from 2013 to 2020, this paper uses Python to implement text analysis of annual reports, and explores the relationship between political acuity and carbon-efficiency synergies (CES) from the perspective of enterprise initiative. RESEARCH FINDINGS: We found that (1) political acuity positively affects carbon-efficiency synergies. (2) Increased political acuity can reduce carbon emissions, but the effect on economic efficiency is not obvious. That is, low carbon takes the lead in raising the level of carbon-efficiency synergies. (3) Environmental regulations can positively regulate the relationship between political acuity and carbon-efficiency synergies. (4) Political acuity in southern China, carbon neutral and non-state-owned enterprises (NSOEs) will have a more pronounced effect on carbon-efficiency synergies. ACADEMIC IMPLICATIONS: From the perspective of the root causes of political linkages, we find the synergies between formal and informal institutions, and the key factors for policy implementation. POLICY IMPLICATIONS: This paper is helpful for enterprises to improve the synergies of emission reduction and efficiency promotion, and has practical implications for the government to promote green and high-quality development.

Super-resolution imaging for in situ monitoring sub-cellular micro-dynamics of small molecule drug.

Small molecule drugs play a pivotal role in the arsenal of anticancer pharmacological agents. Nonetheless, their small size poses a challenge when directly visualizing their localization, distribution, mechanism of action (MOA), and target engagement at the subcellular level in real time. We propose a strategy for developing triple-functioning drug beacons that seamlessly integrate therapeutically relevant bioactivity, precise subcellular localization, and direct visualization capabilities within a single molecular entity. As a proof of concept, we have meticulously designed and constructed a boronic acid fluorescence drug beacon using coumarin-hemicyanine (CHB). Our CHB design includes three pivotal features: a boronic acid moiety that binds both adenosine triphosphate (ATP) and adenosine diphosphate (ADP), thus depleting their levels and disrupting the energy supply within mitochondria; a positively charged component that targets the drug beacon to mitochondria; and a sizeable conjugated luminophore that emits fluorescence, facilitating the application of structured illumination microscopy (SIM). Our study indicates the exceptional responsiveness of our proof-of-concept drug beacon to ADP and ATP, its efficacy in inhibiting tumor growth, and its ability to facilitate the tracking of ADP and ATP distribution around the mitochondrial cristae. Furthermore, our investigation reveals that the micro-dynamics of CHB induce mitochondrial dysfunction by causing damage to the mitochondrial cristae and mitochondrial DNA. Altogether, our findings highlight the potential of SIM in conjunction with visual drug design as a potent tool for monitoring the in situ MOA of small molecule anticancer compounds. This approach represents a crucial advancement in addressing a current challenge within the field of small molecule drug discovery and validation.

The role of HDAC6 in enhancing macrophage autophagy via the autophagolysosomal pathway to alleviate legionella pneumophila-induced pneumonia.

Legionella pneumophila (L. pneumophila) is a prevalent pathogenic bacterium responsible for significant global health concerns. Nonetheless, the precise pathogenic mechanisms of L. pneumophila have still remained elusive. Autophagy, a direct cellular response to L. pneumophila infection and other pathogens, involves the recognition and degradation of these invaders in lysosomes. Histone deacetylase 6 (HDAC6), a distinctive member of the histone deacetylase family, plays a multifaceted role in autophagy regulation. This study aimed to investigate the role of HDAC6 in macrophage autophagy via the autophagolysosomal pathway, leading to alleviate L. pneumophila-induced pneumonia. The results revealed a substantial upregulation of HDAC6 expression level in murine lung tissues infected by L. pneumophila. Notably, mice lacking HDAC6 exhibited a protective response against L. pneumophila-induced pulmonary tissue inflammation, which was characterized by the reduced bacterial load and diminished release of pro-inflammatory cytokines. Transcriptomic analysis has shed light on the regulatory role of HDAC6 in L. pneumophila infection in mice, particularly through the autophagy pathway of macrophages. Validation using L. pneumophila-induced macrophages from mice with HDAC6 gene knockout demonstrated a decrease in cellular bacterial load, activation of the autophagolysosomal pathway, and enhancement of cellular autophagic flux. In summary, the findings indicated that HDAC6 knockout could lead to the upregulation of p-ULK1 expression level, promoting the autophagy-lysosomal pathway, increasing autophagic flux, and ultimately strengthening the bactericidal capacity of macrophages. This contributes to the alleviation of L. pneumophila-induced pneumonia.

Efficacy of 1-hour postload plasma glucose as a suitable measurement in predicting type 2 diabetes and diabetes-related complications: A post hoc analysis of the 30-year follow-up of the Da Qing IGT and Diabetes Study.

AIM: To evaluate whether 1-hour plasma glucose (1hPG) can be a comparable measurement to 2-hour plasma glucose (2hPG) in identifying individuals at high risk of developing diabetes. METHODS: A total of 1026 non-diabetic subjects in the Da Qing IGT and Diabetes Study were included and classified according to baseline postload 1hPG. The participants were followed up and assessed at 6-, 20- and 30year follow-up for outcomes including diabetes, all-cause and cardiovascular mortality, cardiovascular disease (CVD) events, and microvascular disease. We then conducted a proportional hazards analysis in this post hoc study to determine the risks of developing type 2 diabetes and its complications in a '1hPG-normal' group (1hPG <8.6 mmol/L) and a '1hPG-high' group (≥8.6 mmol/L). The predictive values of 1hPG and 2hPG were evaluated using a time-dependent receiver-operating characteristic (ROC) curve. RESULTS: Compared with the 1hPG-normal group, the 1hPG-high group had increased risk of diabetes (hazard ratio [HR] 4.45, 95% CI 3.43-5.79), all-cause mortality (HR 1.46, 95% CI 1.07-2.01), CVD mortality (HR 1.84, 95% CI 1.16-2.95), CVD events (HR 1.39, 95% CI 1.03-1.86) and microvascular disease (HR 1.70, 95% CI: 1.03-2.79) after adjusting for confounders. 1hPG exhibited a higher area under the ROC curve (AUC) for predicting diabetes than 2hPG during the long-term follow-up (AUC [1hPG vs. 2hPG]: 10 years: 0.86 vs. 0.84, p = 0.08; 20 years: 0.88 vs. 0.87, p = 0.04; 30 years: 0.85 vs. 0.82, p = 0.009). CONCLUSIONS: Elevated 1hPG level (≥8.6 mmol/L) was associated with increased risk of developing type 2 diabetes and its long-term complications, and could be considered as a suitable measurement for identifying individuals at high risk of type 2 diabetes.

Dang-Gui-Bu-Xue decoction improves wound healing in diabetic rats by the activation of Notch signaling.

Diabetes serves as a severe chronic disease that severely affects the normal life of human beings. Diabetes causes the complication of diabetic wound dysfunction, which is characterized by sustained inflammation, altered angiogenesis, delayed epithelialization and abnormal secretion of protease. Dang-Gui-Bu-Xue decoction (DBD) is a Chinese traditional medicine that comprises Radix Astragali and Radix Angelicae sinensis and is widely applied in treatment of multiple diseases owing to its functions against inflammation, lipid peroxidation and oxidative stress. Nevertheless, the impact of DBD on diabetic wound healing remains elusive. In this study, we aimed to explore the function of DBD in the regulation of wound healing. We observed that the gavage administration of DBD reduced the wound area, inflammatory infiltration, inflammatory factor levesl, and enhanced granulation tissue formation, wound extracellular matrix (ECM) production, and CD31 accumulation in the diabetic rat wound model, and the co-treatment of gavage administration and the external administration of gauze containing DBD further improved the wound healing effect, while the combination of Notch signaling inhibitor DAPT ((N- [N- (3, 5-difluorophenacetyl)-l-alanyl]-s-phenylglycinet-butyl ester)) could attenuate the improvement. Regarding to the mechanism, the expression levels of Notch1, Delta-like canonical Notch ligand 4 (Dll4), Jagged1, and Hairy Enhancer of Split-1 (Hes1) were increased by DBD, while the treatment of DAPT impaired the effect in the rats. Furthermore, we found that the high glucose (HG)-inhibited viability and tube formation were induced by DBD in human umbilical vein endothelial cells (HUVECs), in which DAPT could reverse this effect. Therefore, we concluded that DBD contributed to wound healing by the activation of Notch signaling. Our finding provides new insight into the potential role of DBD in promoting diabetic wound healing.

Sonic hedgehog-heat shock protein 90ß axis promotes the development of nonalcoholic steatohepatitis in mice.

Sonic hedgehog (SHH) and heat shock protein 90ß (HSP90ß) have been implicated in nonalcoholic steatohepatitis (NASH) but their molecular mechanisms of action remain elusive. We find that HSP90ß is a key SHH downstream molecule for promoting NASH process. In hepatocytes, SHH reduces HSP90ß ubiquitylation through deubiquitylase USP31, thus preventing HSP90ß degradation and promoting hepatic lipid synthesis. HSP90ß significantly increases in NASH mouse model, leading to secretion of exosomes enriched with miR-28-5p. miR-28-5p directly targetes and decreases Rap1b levels, which in turn promotes NF-κB transcriptional activity in macrophages and stimulates the expression of inflammatory factors. Genetic deletion, pharmacological inhibition of the SHH-HSP90ß axis, or delivery of miR-28-5p to macrophages in the male mice liver, impairs NASH symptomatic development. Importantly, there is a markedly higher abundance of miR-28-5p in NASH patient sera. Taken together, the SHH-HSP90ß-miR-28-5p axis offers promising therapeutic targets against NASH, and serum miR-28-5p may serve as a NASH diagnostic biomarker.