A high level of uric acid is associated with long-term adverse cardiovascular outcomes in patients who received fractional flow reserve with coronary intermediate stenosis.

BACKGROUND AND AIMS: The role of fractional flow reserve (FFR) in coronary intermediate lesions is widely recommended by guidelines. The effect of uric acid (UA) on cardiovascular events is also well known. However, the relationship between UA and long-term cardiovascular outcomes in patients who received FFR with intermediate lesions remains unknown. METHODS AND RESULTS: We retrospectively included 428 patients who underwent both coronary angiography (CAG) and FFR. Participants were stratified into two groups based on the median UA. The primary endpoint was the composite of major adverse cardiovascular and cerebrovascular events (MACCEs), including repeat revascularization, nonfatal stroke, nonfatal myocardial infarction, and all-cause death. A Cox proportional hazards model was utilized to analyze the association between UA and the prevalence of MACCEs. During a median follow-up of 5.8 years, a higher MACCEs rate occurred in the high UA group compared to the low UA group (16.8% vs. 5.1%, p log-rank<0.01). Elevated UA was independently linked to a higher incidence of MACCEs, whether UA was treated as a categorical or continuous variable (hazard ratio [HR] 2.76, 95% confidence interval [CI] 1.27-6.03 or HR 1.01, 95% CI 1.01-1.02). The restricted cubic spline (RCS) analysis illustrated that the HR for MACCEs increased with increasing UA. CONCLUSION: The present study demonstrates that UA is associated with MACCEs risk and suggests that UA is a reliable predictor of long-term cardiovascular events in coronary intermediate stenosis patients.

Triglyceride to high-density lipoprotein cholesterol ratio associated with long-term adverse clinical outcomes in patients deferred revascularization following fractional flow reserve.

BACKGROUND: Guidelines on coronary intermediate lesions strongly recommend deferred revascularization after detecting a normal fractional flow reserve (FFR). Researches about triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) on cardiovascular diseases has also been well conducted. However, the association of TG/HDL-C and long-term adverse clinical outcomes remains unknown for patients deferred revascularization following FFR. METHODS: This study retrospectively included 374 coronary artery disease (CAD) patients with non-significant coronary lesions diagnosed by coronary angiography (CAG) and FFR. The main outcome measure was the combination of major adverse cardiovascular and cerebrovascular events (MACCEs). All patients were categorized into three subgroups in terms of TG/HDL-C tertiles (T1 < 0.96, 0.96 ≤ T2 < 1.58, T3 ≥ 1.58). Three different Cox regression models were utilized to reveal the association between TG/HDL-C and prevalence of MACCEs. RESULTS: 47 MACCEs were recorded throughout a median monitoring period of 6.6 years. The Kaplan-Meier survival curves showed a higher MACCEs rate occurred in the higher TG/HDL-C group (5.6% vs. 12.9% vs. 19.4%, log-rank P < 0.01). After adjustment, patients in T3 suffered a 2.6-fold risk compared to the T1 group (T3 vs. T1: HR 2.55, 95% CI 1.05-6.21, P = 0.038; T2 vs. T1: HR 1.71, 95% CI 0.65-4.49, P = 0.075; P for trend = 0.001). The restricted cubic spline (RCS) analysis demonstrated that the HR for MACCEs rose as TG/HDL-C increased. Both the receiver operating characteristic (ROC) and time-dependent ROC proved the excellent predictive ability of TG/HDL-C. CONCLUSION: The study illustrates that TG/HDL-C correlates with the risk of MACCEs in CAD patients deferred revascularization following FFR. TG/HDL-C could serve as a dependable predictor of cardiovascular events over the long term in this population.

Alloying-Induced Synthesis of Amorphous PdZnS Hollow Spheres as Enhanced Oxygen Reduction Catalysts.

Amorphous alloys have multiple advantages in electrocatalysis, yet the isotropic nature makes their syntheses a great obstacle in application. In this work, it is shown that the Zn2+ can interfere with the crystallization of Pd-base structures to form amorphous alloy materials. By simply adjusting the Zn2+ content, unique PdZnS amorphous hollow spheres (AHS) with various compositions and degrees of crystallinity can be obtained through a facile one-pot wet chemical method. Owing to both the amorphous nature and hollow morphologies, the PdZnS AHSs possess appealing activities and stabilities as oxygen reduction catalysts. Typically, the Pd20 ZnS10 AHSs exhibit the highest half-wave potential (E1/2 ) of 0.940 V (vs reversible hydrogen electrode), and such E1/2 only negatively shifts 25 mV after 60 000 cycles.

Facile Synthesis of Pd and PdPtNi Trimetallic Nanosheets as Enhanced Oxygen Reduction Electrocatalysts.

While bimetallic 2D metallic nanomaterials are widely synthesized and used as electrocatalysts with enhanced performance, trimetallic 2D structures are less commonly reported. In this work, a facile wet chemical method for synthesizing Pd nanosheets and PdPtNi trimetallic alloy nanosheets is developed. Without the introduction of gaseous CO and pressurized equipment, Pd nanosheets with a thickness of ≈2.85 nm and sizes in the range of 1-2 µm can be obtained. The facile synthesis conditions allow for a comprehensive study of the nanosheet growth mechanism. It is found that 2D growth is closely related to the product of solvent decomposition and the additive ligand diethylenetriamine. Further, by depositing Pt and Ni onto the Pd nanosheets, trimetallic nanosheets with tunable compositions can be obtained and applied as oxygen reduction reaction electrocatalysts. Typically, the Pd9 Pt1 Ni1 nanosheets have the highest half-wave potential of 0.928 V (vs reversible hydrogen electrode), which is 34 mV higher than that of commercial Pt/C and 28 mV higher than that of Pd/C, and also have high durability.

Uric Acid to High-Density Lipoprotein Cholesterol Ratio is a Novel Marker to Predict Functionally Significant Coronary Artery Stenosis.

Background: Intermediate coronary stenosis (ICS) is defined as a visually estimated percentage of diameter stenosis ranging between 40% and 70% by conventional coronary angiography (CAG). Whether to perform percutaneous coronary intervention (PCI) for these lesions is a challenge in clinical practice. The fractional flow reserve (FFR) can guide treatment by determining the functional significance of ICS. Studies have shown that some clinical indicators can be used to predict FFR. However, there is little research on this in the Chinese population. Methods: We retrospectively analyzed 690 patients who underwent FFR measurements to determine the functional significance of a single ICS. Patients were divided into 2 groups: FFR ≤0.8 (n = 280) and FFR >0.8 (n = 410). We compared the clinical factors between the two groups and performed multivariate logistic regression analyses to explore the risk factors. In addition, receiver-operating characteristic (ROC) curves were constructed for FFR ≤0.8 diagnoses. Results: The mean UHR (uric acid to high-density lipoprotein cholesterol ratio) level was significantly higher in the FFR ≤0.8 group (p < 0.001). UHR corrects negatively with FFR (r = -0.44, p < 0.001). High-level UHR was an independent risk factor for the FFR ≤0.8 (OR = 7.17, 95% CI 4.17-12.34). The area under the curve (AUC) of the UHR diagnostic capacity for the FFR ≤0.8 is 0.77, with 77.3% sensitivity and 68.2% specificity. Conclusion: UHR levels were significantly increased in patients with hemodynamically significant coronary lesions. UHR is a novel predictor of functionally significant lesions in patients with a single-vessel disease of ICS.

De novo transcriptome sequencing and anthocyanin metabolite analysis reveals leaf color of Acer pseudosieboldianum in autumn.

BACKGROUND: Leaf color is an important ornamental trait of colored-leaf plants. The change of leaf color is closely related to the synthesis and accumulation of anthocyanins in leaves. Acer pseudosieboldianum is a colored-leaf tree native to Northeastern China, however, there was less knowledge in Acer about anthocyanins biosynthesis and many steps of the pathway remain unknown to date. RESULTS: Anthocyanins metabolite and transcript profiling were conducted using HPLC and ESI-MS/MS system and high-throughput RNA sequencing respectively. The results demonstrated that five anthocyanins were detected in this experiment. It is worth mentioning that Peonidin O-hexoside and Cyanidin 3, 5-O-diglucoside were abundant, especially Cyanidin 3, 5-O-diglucoside displayed significant differences in content change at two periods, meaning it may be play an important role for the final color. Transcriptome identification showed that a total of 67.47 Gb of clean data were obtained from our sequencing results. Functional annotation of unigenes, including comparison with COG and GO databases, yielded 35,316 unigene annotations. 16,521 differentially expressed genes were identified from a statistical analysis of differentially gene expression. The genes related to leaf color formation including PAL, ANS, DFR, F3H were selected. Also, we screened out the regulatory genes such as MYB, bHLH and WD40. Combined with the detection of metabolites, the gene pathways related to anthocyanin synthesis were analyzed. CONCLUSIONS: Cyanidin 3, 5-O-diglucoside played an important role for the final color. The genes related to leaf color formation including PAL, ANS, DFR, F3H and regulatory genes such as MYB, bHLH and WD40 were selected. This study enriched the available transcriptome information for A. pseudosieboldianum and identified a series of differentially expressed genes related to leaf color, which provides valuable information for further study on the genetic mechanism of leaf color expression in A. pseudosieboldianum.

An All-Ceramic, Anisotropic, and Flexible Aerogel Insulation Material.

To exploit the high-temperature superinsulation potential of anisotropic thermal management materials, the incorporation of ceramic aerogel into the aligned structural networks is indispensable. However, the long-standing obstacle to exploring ultralight superinsulation ceramic aerogels is the inaccessibility of its mechanical elasticity, stability, and anisotropic thermal insulation. In this study, we report a recoverable, flexible ceramic fiber-aerogel composite with anisotropic lamellar structure, where the interfacial cross-linking between ceramic fiber and aerogel is important in its superinsulation performance. The resulting ultralight aerogel composite exhibits a density of 0.05 g/cm3, large strain recovery (over 50%), and low thermal conductivity (0.0224 W m-1 K-1), while its hydrophobicity is achieved by in situ trichlorosilane coating with the water contact angle of 135°. The hygroscopic tests of such aerogel composites demonstrate a reversible thermal insulation. The mechanical elasticity and stability of the anisotropic composites, with its soundproof performance, shed light on the low-cost superelastic aerogel manufacturing with scalability for energy saving building applications.

A capillary electrophoresis strategy to sensitively detect dynamic properties of coiled coil polypeptides.

The self-assembly behavior of polypeptides plays an essential role to form biological and functional macromolecules, which have attracted a lot of attention due to their excellent characters. Understanding the polypeptide self-assembly systems and dynamic behaviors is fundamental to improve the potential of biomedical applications. In this work, coiled coil polypeptides PC10 and PC10 P were designed and biosynthesized. PC10 and PC10 P could form nanogels when the concentration of polypeptides was less than 2% (m/v). The dynamic behaviors of PC10 and PC10 P were measured by Förster resonance energy transfer method based on a capillary electrophoresis system. The Förster resonance energy transfer efficiency of this system was 60.4%, and the distance of self-assembled domains in the polypeptides was calculated as 6.14 nm, demonstrating that the exchange behavior occurred between two different polypeptides containing the same coiled coil region.

Hollow gold nanoshells-incorporated injectable genetically engineered hydrogel for sustained chemo-photothermal therapy of tumor.

BACKGROUND: Combined therapy has demonstrated to be an effective strategy for cancer therapy. Herein, an injectable hydrogel based on the genetically engineered polypeptide and hollow gold nanoshells (HAuNS) has been developed for chemo-photothermal therapy of HepG2 tumor. METHODS: PC10A/DOX/HAuNS nanogel was prepared with layer-by-layer through the adsorption of DOX and PC10A successively. DOX with positive charge and PC10A with negative charge were coated step by step onto the surface of negatively charged HAuNS. The multifunctional hydrogel PC10A/DOX/HAuNS were prepared via dissolving hybrid PC10A/DOX/HAuNS nanogel in polypeptide PC10A. Chemotherapy drug DOX in the PC10A/DOX/HAuNS hydrogel was absorbed on the HAuNS and directly embedded in the PC10A hydrogel, which contributes to sequentially release of the drug. Specifically, DOX adsorbed on the HAuNS could be released slowly for sustainable chemotherapy. RESULTS: The PC10A/DOX/HAuNS hydrogel could pass 26-gauge needle without clogging, indicating that it is injectable. In addition, the PC10A/DOX/HAuNS hydrogel possessed outstanding photothermal effect and photothermal stability. In both in vitro cell and in vivo tumor-bearing mice experiments, a remarkably enhance tumor inhibition was observed by the combined therapy of chemo-photothermal therapy compared with photothermal therapy or chemotherapy alone. CONCLUSIONS: The combined chemotherapy and photothermal therapy of PC10A/DOX/HAuNS hydrogels could significantly improve the therapeutic effect. Therefore, the multifunctional hydrogel PC10A/DOX/HAuNS is promising to provide a new strategy for sustained chemo-photothermal therapy.

Factors associated with stigma attitude towards people living with HIV among general individuals in Heilongjiang, Northeast China.

BACKGROUND: HIV-related stigma always is major obstacles to an effective HIV response worldwide. The effect of HIV-related stigma on HIV prevention and treatment is particularly serious in China. This study was to examine stigma attitude towards people living with HIV/AIDS (PLWHA) among general individuals in Heilongjiang Province, Northeast China and the factors associated with stigma attitude, including socio-demographic factors and HIV/AIDS Knowledge. METHODS: A cross-sectional survey was carried out in Heilongjiang Province, China. A total of 4050 general individuals with age 15-69 years in four villages in rural areas and two communities in urban areas were drawn using stratified cluster sampling. Standardized questionnaire interviews were administered. Univariate and multivariate log-binomial regression were performed to assess factors affecting stigma attitude towards PLWHA. RESULTS: The proportions of participants holding stigma attitude towards PLWHA were 49.6% among rural respondents and 37.0% among urban respondents (P < 0.001). Multivariate log binomial regression analysis among both rural participants (RR = 0.89, 95% CI: 0.87-0.91, P < 0.001) and urban participants (RR = 0.89, 95% CI: 0.87-0.91, P < 0.001) showed that greater knowledge of HIV transmission misconceptions was significantly associated with lower stigma attitude towards people living with HIV. And among urban participants, higher education level (high school vs. primary school or less: RR = 0.73, 95%CI: 0.62-0.87, P < 0.001; middle school vs. primary school or less: RR = 0.83, 95%CI: 0.71-0.97, P = 0.018) were also significantly associated with lower stigma attitude towards PLWHA. CONCLUSIONS: The level of stigma attitude towards PLWHA is higher in rural areas than in urban areas in Heilongjiang. Meanwhile, individuals who better were aware of HIV/AIDS transmission misconceptions may hold lower stigma attitude toward PLWHA whether among rural or urban residents.

A facile method to in situ fabricate three dimensional gold nanoparticle micropatterns in a cell-resistant hydrogel.

A facile method for in situ fabrication of three-dimensional gold nanoparticle micropatterns in a cell-resistant polyethylene glycol hydrogel has been developed by combining photochemical synthesis of gold nanoparticles with photolithography technology. The gold nanoparticle micropatterns were further bio-modified with cell integrated polypeptide NcysBRGD based on a gold-thiol bond to improve cell behaviors. Primary cell tests showed that NcysBRGD can enhance cell adhesion very well on the surface of gold nanoparticle micropatterns.

An engineered coiled-coil polypeptide assembled onto quantum dots for targeted cell imaging.

Quantum dot (QD)-polypeptide probes have been developed through the specific metal-affinity interaction between polypeptides appended with N-terminal polyhistidine sequences and CdSe/ZnS core-shell QDs. The size and charge of a QD-polypeptide can be tuned by using different coiled-coil polypeptides. Compared to glutathione-capped QDs (QD-GSH), QD-polypeptide probes showed an approximately two- to three-fold luminescence increase, and the luminescence increase was not obviously related to the charge of the polypeptide. QD-polypeptide probes with different charge have a great effect on nonspecific cellular uptake. QD-polypeptide probes with negative charge exhibited lower nonspecific cellular uptake in comparison to the QD-GSH, while positively charged QD-polypeptide probes presented higher cellular uptake than the QD-GSH. A targeted QD-ARGD probe can obviously increase targeted cellular uptake in α v ß 3 overexpressing HeLa cells compared to QD-A. In addition, QD-polypeptide probes showed lower in vitro cytotoxicity compared to the original QDs. These results demonstrate that these QD-polypeptide probes with high specific cellular uptake, high fluorescence intensity and low background noise are expected to have great potential applications in targeted cell imaging.

Single-center study of familial papillary thyroid cancer in China: surgical considerations.

BACKGROUND: Whether familial papillary thyroid cancer (FPTC) is more aggressive than sporadic counterpart remains elusive, and the optimal clinical approach for FPTC is yet to be established. In this study, we investigated familial occurrence of PTC in China and reviewed our experience of its surgical treatment. METHODS: The clinical records of 248 consecutive patients with an established diagnosis of PTC who were admitted to Nanfang Hospital for thyroidectomy between January 2011 and June 2013 were analyzed in this study. Patients included 66 males and 182 females, aged 11 to 76 years. RESULTS: Twenty-two patients (8.9%) with a positive family history were confirmed. Patients with FPTC had a predilection for female subjects and tended to be younger than other patients, but the difference was not significant (P = 0.0514 and P = 0.168). They were more likely to present large tumors (P = 0.0024), multifocality (familial vs. sporadic: 54.50% vs. 26.50%; P < 0.006), local invasion (81.8% vs. 23.9%; P < 0.001), and malignant lymph nodes (63.6% vs. 33.6%; P = 0.005). Univariate and multivariate analyses identified that a positive family history was an independent risk factor for local invasion (OR: 5.683; 95% CI: 2.056 to 15.707; P = 0.001), malignant lymph nodes (OR: 3.005; 95% CI: 1.046 to 8.630; P = 0.041) in FPTC patients. Kaplan-Meier survival curves revealed that an aggressive surgical strategy was associated with a better relapse-free survival than conventional one (P = 0.032). CONCLUSIONS: FPTC is more likely to possess aggressive features than sporadic counterparts. Thus, screening of at-risk families is essential to aid in earlier recognition. An aggressive surgical strategy appeared to be the more effective therapy. However, sufficient detailed interrogation and long-term follow-up of the patients and their family are necessary for providing individualized recommendations for clinical management.

[Impact of exogenous fibroblast growth factor 21 on atherosclerosis in apolipoprotein E deficient mice].

OBJECTIVE: To explore the effects and related mechanisms of exogenous fibroblast growth factor (FGF) 21 on atherosclerosis in apolipoprotein E deficient (apoE-/-) mice. METHODS: Male 17-week-old C57BL/6J mice and apoE-/- mice were randomly divided into three groups (n = 12 each): blank control group (C vehicle), atherosclerosis group without FGF21 (apoE-/- vehicle) and apoE-/- plus FGF21 (100 µg × kg⁻¹ × d⁻¹ subcutaneously treatment) . All mice were fed with high-fat diet for 4 weeks. After 4 weeks treatments, atherosclerotic lesions in aortic arch and inner diameter of abdominal aorta were measured by ultrasonography. Plasma lipid profiles, CRP and TNFα were measured. The whole aorta and aortic root were prepared for HE and oil red O staining to analyze lesion areas. RESULTS: There was no evident plaque in C vehicle group. TC/HDL-C, LDL-C/HDL-C, non-HDL-C, expression of CRP and TNFα were significantly higher in apoE-/- vehicle group than in C vehicle group (all P < 0.05). IMT of aorta [(156.4 ± 17.6)µm vs. (57.8 ± 7.4)µm] were significantly higher in apoE-/- vehicle group than in C vehicle group (all P < 0.05). While FGF21 significantly reduced the lesion area in aorta arch [(1.42 ± 0.16) mm² vs. (2.30 ± 0.10) mm², P < 0.05] and the inner diameter of abdominal aorta [(0.97 ± 0.03) mm vs. (0.75 ± 0.18) mm, P < 0.05] compared to apoE-/- vehicle group. Similarly, TC/HDL-C(5.11 ± 0.70), LDL-C/HDL-C(3.90 ± 0.76), non-HDL-C[(6.33 ± 1.22)mmol/L], plasma CRP[(4.20 ± 1.03)mmol/L] and plasma TNFα[(1.29 ± 0.47)mmol/L] were also reduced by FGF21( all P < 0.05 vs. apoE-/- vehicle). Moreover, FGF21 decreased the IMT[(107.2 ± 33.5)µm vs. (156.4 ± 17.6)µm], lesion area of aorta [(14.26 ± 3.5)%] vs. [(23.06 ± 4.16)%] and plaque size of aorta root [(21.75 ± 7.14)% vs. (38.03 ± 5.76)%] (all P < 0.05 vs. apoE-/- vehicle). CONCLUSIONS: FGF21 can protect apoE-/- mice from atherosclerosis by modifying lipid profiles and downregulating CRP and TNFα expressions.

Transition-Metal-Oxide-Based Nanozymes for Antitumor Applications.

Transition metal oxide (TMO)-based nanozymes have appeared as hopeful tools for antitumor applications due to their unique catalytic properties and ability to modulate the tumor microenvironment (TME). The purpose of this review is to provide an overview of the latest progress made in the field of TMO-based nanozymes, focusing on their enzymatic activities and participating metal ions. These nanozymes exhibit catalase (CAT)-, peroxidase (POD)-, superoxide dismutase (SOD)-, oxidase (OXD)-, and glutathione oxidase (GSH-OXD)-like activities, enabling them to regulate reactive oxygen species (ROS) levels and glutathione (GSH) concentrations within the TME. Widely studied transition metals in TMO-based nanozymes include Fe, Mn, Cu, Ce, and the hybrid multimetallic oxides, which are also summarized. The review highlights several innovative nanozyme designs and their multifunctional capabilities. Despite the significant progress in TMO-based nanozymes, challenges such as long-term biosafety, targeting precision, catalytic mechanisms, and theoretical supports remain to be addressed, and these are also discussed. This review contributes to the summary and understanding of the rapid development of TMO-based nanozymes, which holds great promise for advancing nanomedicine and improving cancer treatment.

Association of D-dimer to albumin ratio with adverse cardiovascular outcomes in ischaemic heart failure patients with diabetes mellitus: a retrospective cohort study.

OBJECTIVE: To determine the association of D-dimer to albumin ratio (DAR) with major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) in ischaemic heart failure patients with diabetes mellitus. DESIGN: A retrospective observational cohort study. SETTING: Single centre in Beijing, China, conducted at one of the largest cardiology centres in China. PARTICIPANTS: From June 2017 to June 2019, 3707 patients with heart failure and concomitant multiple vessel disease undergoing elective PCI were screened. A total 1021 of patients were enrolled after exclusion and the follow-up period was up to 36 months. PRIMARY AND SECONDARY OUTCOME MEASURES: The MACE was the primary measured outcome. The secondary outcomes were all-cause mortality, non-fatal myocardial infarction and any revascularisation. METHODS: These participants were grouped according to DAR tertiles. The cumulative incidence functions, Cox regression, restricted cubic spline and receiver operating characteristic curves were used to determine the association between DAR and outcomes. The subgroup analysis was also performed. RESULTS: After follow-up, MACE occurred in 404 (39.6%) participants. The cumulative hazards curve manifested significant differences in MACE, all-cause mortality and any revascularisation (log-rank test: all p<0.001). In adjusted models, DAR was an independent risk factor of MACE (tertile 2: HR 1.82, 95% CI 1.37 to 2.42; tertile 3: HR 1.74, 95% CI 1.28 to 2.36) and all-cause mortality (tertile 2: HR 2.04, 95% CI 1.35 to 3.11; tertile 3: HR 1.89, 95% CI 1.20 to 2.98). The optimal cut-off of DAR was 1.2. In the stratified analysis, sex, age, hypertension, hypercholesterolaemia, total revascularisation and any interfered vessel did not affect the independent predictive ability. CONCLUSION: Higher DAR was independently associated with MACE and all-cause mortality after PCI in ischaemic heart failure patients with diabetes mellitus.

Copper peroxide loaded gelatin/oxide dextran hydrogel with temperature and pH responsiveness for antibacterial and wound healing activity.

Bacterial infection and tissue hypoxia always prevent wound healing, so multifunctional platforms with antimicrobial and oxygen-supplying functions were developed. However, they face many difficulties such as complex preparation and low oxygen release. To address this challenge, a copper peroxide loaded gelatin/oxide dextran hydrogel (CGO) was prepared. Surprisingly, CGO hydrogel as a wound dressing not only had good biocompatibility, injectivity, and mechanical properties, but also exhibited mild photothermal properties, temperature responsiveness, and pH responsiveness. After being applied to wounds infected with bacteria, CGO hydrogel released copper peroxide under near-infrared laser irradiation, which produced copper ions and hydrogen peroxide, combined with PTT to kill bacteria. After the bacteria were cleared from the wound and the pH of the wound was changed to be acidic, CGO hydrogel released copper peroxide via pH response. Copper ions and oxygen produced from copper peroxide accelerated wound healing by promoting angiogenesis. The multi-responsive and multi-mode treatment platform provided a potential strategy for treating bacteria-infected wounds.

Flavan-3-ol monomers intake is associated with osteoarthritis risk in Americans over 40 years of age: results from the National Health and Nutritional Examination Survey database.

Objectives: Osteoarthritis (OA) stands as the prevailing progressive musculoskeletal disease, serving as the primary cause of chronic pain and activity limitations among adults over 40. Flavan-3-ols, common polyphenolic compounds, are believed to harbor anti-inflammatory and anti-aging properties. This study explores the relationship between flavan-3-ol intake and osteoarthritis risk in individuals over the age of 40 in the US. Methods: This study included 7452 participants over the age of 40 from three cycles (2007-2008, 2009-2010, and 2017-2018) of the National Health and Nutrition Examination Survey. Information on OA history was obtained via home surveys. Information on flavan-3-ol monomers intake was obtained using a survey from the Food and Nutrient Database for Dietary Studies. We used a logistic regression model and restricted cubic spline to analyze the relationships between flavan-3-ol monomers and OA. Stratified analyses were also conducted in this study. Results: There were 1056 participants with OA and 6396 without OA. Compared to the first tertile (T1) group, the adjusted odds ratio with a 95% confidence interval (CI) of logistic regression model 2 for the flavan-3-ol T2 group was 1.296 (0.979-1.715) (p = 0.068), the OR for (-)-epigallocatechin was 1.292 (1.025-1.629) (p = 0.032), and the OR for (-)-epicatechin 3-gallate was 1.348 (1.013, 1.793) (p = 0.042). A dose-response curve indicated a non-linear association (p for non-linearity <0.05) between OA and total flavan-3-ol monomers (nadir point: 483.29 mg, 95% CI: 0.61-0.90). No interaction effects were found in the subgroup analysis. Conclusions: In individuals over 40 in the US, the average daily dietary intake of flavan-3-ol monomers manifests a J-shaped relationship with OA risk.

Mild hyperthermia-assisted chitosan hydrogel with photothermal antibacterial property and CAT-like activity for infected wound healing.

Infected wounds pose a serious threat to public health and pose a significant challenge and financial burden worldwide. The treatment of infected wounds is now an urgent problem to be solved. Herein, mild hyperthermia-assisted hydrogels composed of carboxymethyl chitosan (CMCs), oxidized dextran (Odex), epigallocatechin gallate (EGCG) and PtNPs@PVP (CAT-like nanoenzymes) were proposed for the repair of infected wounds. The incorporation of PtNPs@PVP nanoenzymes give the hydrogels excellent photothermal property and CAT-like activity. When the temperature is maintained at 42-45 °C under 808 nm near infrared (NIR) exposure, the CMCs/Odex/EGCG/Nanoenzymes (COEN2) hydrogel demonstrated highly enhanced antibacterial ability (95.9 % in vivo), hydrogen peroxide (H2O2) scavenging ratio (85.1 % in vitro) and oxygen supply (20.7 mg/L in vitro). Furthermore, this mild-heat stimulation also promoted angiogenesis in the damaged skin area. Overall, this multifunctional hydrogel with antibacterial, antioxidant, oxygen supply, hemostasis, and angiogenesis capabilities has shown great promise in the repair of infected wounds. This study establishes the paradigm of enhanced infected wound healing by mild hyperthermia-assisted H2O2 scavenging, oxygen supplemental, and photothermal antibacterial hydrogels.

Identification of Reduced mTOR T1262 Phosphorylation as a Novel Mechanism and Therapeutic Target of Apoptosis in Senescent Cardiomyocytes: Aging and Cardiomyocyte Apoptosis.

The mechanisms through which aging increases heart injury remain partially understood. Protein phosphorylation plays a critical regulatory role in cell survival and death. Using an unbiased phosphoproteomics approach, we aimed to identify the proteins whose phosphorylation could be causatively related to aging-related cardiomyocyte apoptosis and elucidate the underlying mechanisms. Comparative phosphoproteomics was conducted on cardiac tissues obtained from young (8 weeks) and aged (24 months) mice. Our findings revealed that the Mammalian Target of Rapamycin phosphorylation at T1262 (mTORT1262) was reduced in the aging heart. Immunohistochemical and Western blot analyses confirmed these findings in aging myocardia and D-galactose-induced senescent AC16 cardiomyocytes. In hypoxia/reoxygenation cardiomyocytes, mTORT1262 phosphorylation deficiency (mTORT1262A, lentivirus-mediated transfection) inhibited AKT1, suppressed NF-κB, activated FOXO1/3a signaling, and ultimately exacerbated apoptosis. Conversely, mTORT1262 pseudophosphorylation (mTORT1262E) exhibited opposite effects. Through bioinformatics and CO-IP, purinergic receptor P2X4 (P2X4R) was found to be the possible receptor responsible for mTORT1262 phosphorylation. Knockdown of P2X4R increased apoptosis, whereas its overexpression decreased it. In senescent cardiomyocytes, P2X4R expression and mTORT1262 and AKT1S473 phosphorylation were reduced, NF-κB signaling was suppressed, and FOXO1/3a signaling was activated. We demonstrated that P2X4R downregulation and the subsequent reduction of mTORT1262 phosphorylation is a novel mechanism contributing to cardiomyocyte apoptosis in aging hearts. The P2X4R-mTOR-AKT1 signaling pathway represents a potential therapeutic target against accelerated cardiac injury in aging.