Tumor microenvironment-modulated nanoparticles with cascade energy transfer as internal light sources for photodynamic therapy of deep-seated tumors.

Photodynamic therapy (PDT) is an appealing modality for cancer treatments. However, the limited tissue penetration depth of external-excitation light makes PDT impossible in treating deep-seated tumors. Meanwhile, tumor hypoxia and intracellular reductive microenvironment restrain the generation of reactive oxygen species (ROS). To overcome these limitations, a tumor-targeted self-illuminating supramolecular nanoparticle T-NPCe6-L-N is proposed by integrating photosensitizer Ce6 with luminol and nitric oxide (NO) for chemiluminescence resonance energy transfer (CRET)-activated PDT. The high H2O2 level in tumor can trigger chemiluminescence of luminol to realize CRET-activated PDT without exposure of external light. Meanwhile, the released NO significantly relieves tumor hypoxia via vascular normalization and reduces intracellular reductive GSH level, further enhancing ROS abundance. Importantly, due to the different ROS levels between cancer cells and normal cells, T-NPCe6-L-N can selectively trigger PDT in cancer cells while sparing normal cells, which ensured low side effect. The combination of CRET-based photosensitizer-activation and tumor microenvironment modulation overcomes the innate challenges of conventional PDT, demonstrating efficient inhibition of orthotopic and metastatic tumors on mice. It also provoked potent immunogenic cell death to ensure long-term suppression effects. The proof-of-concept research proved as a new strategy to solve the dilemma of PDT in treatment of deep-seated tumors.

GLTSCR1 deficiency promotes colorectal cancer development through regulating non-homologous end joining.

Non-homologous end joining (NHEJ), as one major pathway of DNA double-strand break (DSB) repair, could cause genomic instability, which plays pivotal roles in cancer development. While, chromatin remodeling complexes dictate the selection and orchestration of DSB repair pathways by regulating chromatin dynamics. However, the crosstalk between NHEJ and chromatin remodeling in cancer progress remains unclear. In this study, deficiency of GLTSCR1 causes resistance to DNA damage in colorectal cancer (CRC) cells by promoting NHEJ repair efficiency. Mechanistically, GLTSCR1 interacts with BRD9 to engage in the assembly of the non-canonical BAF complex (GBAF). However, GLTSCR1 deficiency disrupts GBAF and triggers the ubiquitination degradation of BRD9. Furthermore, GLTSCR1 deficiency causes aberrant opening in the promoter region of NHEJ repair-associated genes, which promotes CRC development. While, GLTSCR1 and its binding partner BRD9 are not directly involved in assembling NHEJ repair machinery; instead, they regulate the DNA accessibility of NHEJ repair-associated genes. Collectively, our findings confirm GLTSCR1 deficiency as a critical regulatory event of the NHEJ pathway in CRC development, which might require different therapeutic strategy for GLTSCR1 wild-type and mutant CRC.

[Caries experience and its correlation with caries activity of 4-year-old children in Miyun District of Beijing].

OBJECTIVE: To investigate the prevalence of dental caries of 4-year-old children in Miyun District of Beijing by international caries detection and assessment system (ICDAS), to detect the caries activity Cariostat value and to analyze the correlation between the Cariostat value and dental caries. METHODS: Totally 815 children aged 4 years in 7 kindergartens in Miyun District of Beijing were recruited. The clinical examination of all children was conducted by one examiner using ICDAS. The oral de-birs and plaques were collected by one doctor who recorded the Cariostat scores. The results of clinical examination were compared between genders. At the same time, the prevalence of dental caries, the mean d3-6ft/d3-6fs and d1-6ft/d1-6fs among high Cariostat scores group (2.0-3.0), medium Cariostat scores group (1.5) and low Cariostat scores group (0-1.0) were compared. The distributions of incipient caries in different Cariostat scores groups were compared among children with incipient caries only. RESULTS: All the children had incipient caries, and 78.3% of the children had cavitated caries with ICDAS score of 3 or above. The mean d1-2t scores were 9.76±3.65, the mean d3-6ft scores was 4.64±4.43 and the mean d1-6ft scores were 14.41±3.42. The incipient caries with ICDAS score of 1-2 were widely distributed, accounting for 67.7% of the total numbers of caries. There was no significant diffe-rence in caries prevalence and caries experience between genders (P>0.05). The proportion of children with high Cariostat scores in boys (43.6%) was higher than that in girls (33%) and the difference was statistically significant (P<0.05). With the increase of Cariostat scores, the prevalence of cavitated caries, the mean d3-6ft/d3-6fs and d1-6ft/d1-6fs scores in children was on the increase and the difference among the three groups was statistically significant (P<0.05). For children with incipient caries only, the distribution of incipient caries in different Cariostat scores groups was no significant difference (P>0.05). CONCLUSION: ICDAS can detect early enamel demineralization of deciduous teeth in children. The prevalence of dental caries among 815 4-year-old children in Miyun District of Beijing is more serious, and incipient caries is widely distributed in children. Cariostat value reflects the status of cavi-tated caries and has no correlation with the distribution of incipient caries. Therefore, the combined application of ICDAS and Cariostat caries activity detection method is helpful for the detection of incipient caries and screening of caries high-risk children, which has great significance for the comprehensive ma-nagement of caries in children and the formulation of early preventive measures.

Function Impairment Screening Tool predicts eight-year mortality in older adults: Beijing Longitudinal Study of Aging.

PURPOSE: Function impairment is an early stage of disability in older adults and requires timely intervention. We have previously developed Function Impairment Screening Tool (FIST) based on the Delphi method, which has good reliability and validity, but the predictive effect is unknown. Therefore, we aimed to explore the role of FIST in predicting long-term mortality in community-dwelling older adults. PARTICIPANTS AND METHODS: Data were from the Beijing Longitudinal Study of Aging. A total of 1,833 older adults with 8 years of follow-up were included. Function impairment was assessed using FIST. Cox proportional hazards model was used to calculate the predictive effect of FIST on 8-year all-cause mortality. RESULTS: According to FIST, approximately half of the older adults had function impairment (47.6%). The prevalence of function impairment varied across populations. Logistic regression analysis showed that age, female, rural, poor health satisfaction, not drinking tea, and low Mini-Mental State Examination and intrinsic capacity score were associated with function impairment. Furthermore, function impairment was associated with poor physical function and high mortality. Cox analysis showed that FIST could predict 8-year mortality (hazard ratio [HR] = 3.26, 95% confidence interval [CI] 2.74-3.87), and this relationship persisted after adjusting for age, sex, area, marital status, live alone, educational level, smoking, drinking alcohol, and chronic diseases (HR = 1.79, 95% CI 1.45-2.17). DISCUSSION: FIST can predict 8-year mortality in community-dwelling older adults. More attention should be paid to older adults with function impairment and early intervention should be provided.

Urchin-like NiCo-based bimetallic hydroxide decorated with DOPO as highly hydrophobic flame retardant for remarkably reducing fire hazard of poly (L-lactic acid).

Designing high-performance flame retardants for poly (L-lactic acid) (PLA) materials and exploring a simple and scalable strategy have been hot topics in research. In this work, a novel and highly efficient flame retardant, that is, 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) decorated urchin-like NiCo-based bimetallic hydroxide (NiCo-BH@DOPO), was synthesized and incorporated into PLA to prepare PLA and NiCo-BH@DOPO (PLA/NiCo-BH@DOPO) composite. Benefiting from the DOPO organic modification, NiCo-BH@DOPO had superb hydrophobicity and presented excellent dispersion in the PLA matrix. When 20 wt% NiCo-BH@DOPO was added, the LOI value of PLA/NiCo-BH@DOPO composites reached 33.2 %, passed the V-0 level of UL-94 grade, and its maximum peak heat release rate (PHRR) and total heat release (THR) were reduced by 13.2 % and 17.3 %, respectively, compared with PLA/NiCo-BH composites. Furthermore, the residue of PLA/NiCo-BH@DOPO at 800 °C reached 19.8 wt% and the T10% (temperature at 10 % weight loss) increased by 33 °C. More importantly, the residual PLA/NiCo-BH@DOPO char exhibits a significantly reduced presence of large cracks compared to PLA/NiCo-BH, indicating a more compact formation of residual char. NiCo-BH@DOPO endowed PLA with outstanding flame retardancy, thermal stability and carbonization properties, which were owing to the multi-coordinating effect transition metal (NiCo-BH) catalyzed the char formation to form a char layer barrier and DOPO free radicals captured to inhibit the combustion reaction chain. This investigation provided a facile strategy for the novel multi-function NiCo-based bimetallic hydroxide flame retardant, expanding NiCo-BH potential applications in PLA.

Artificial olfactory memory system based on conductive metal-organic frameworks.

The olfactory system can generate unique sensory memories of various odorous molecules, guiding emotional and cognitive decisions. However, most existing electronic noses remain constrained to momentary concentration, failing to trigger specific memories for different smells. Here, we report an artificial olfactory memory system utilizing conductive metal-organic frameworks (Ce-HHTP) that integrates sensing and memory and exhibits short- and long-term memory responses to alcohols and aldehydes. Experiments and theoretical calculations show that distinct memories are derived from the specific combinations of Ce-HHTP with O atoms in different guest. An unmanned aircraft equipped with this system realized the sensory memories in established areas. Moreover, the fusion of portable detection boxes and wearable flexible electrodes demonstrated the immense potential in off-site pollution monitoring and health management. This work represents an artificial olfactory memory system with two specific sensory memories under simultaneous conditions, laying the foundation for bionic design with qualities of human olfactory memory.

Efficient synthesis of lactic acid from cellulose through the synergistic effect of zinc chloride hydrate and metal salts.

The chemocatalystic conversion of cellulose, the main component of lignocellulosic biomass, to building-block chemicals in water under mild conditions, is an ideal but highly challenging process due to the robust crystal structure of cellulose. It is also the key to establishing a sustainable biomass-based chemical process. Here, we present a highly efficient and selective chemocatalytic hydrolysis of cellulose using ZnCl2·3H2O hydrate as the pretreatment reagent and water-compatible metal salts - ErCl3 as the catalyst, into lactic acid (LA), which is an important chemical building-block widely utilized in the food industry and in the production of chemicals and biodegradable plastic. With 94.0 % conversion of cellulose, an impressive LA yield of 84.6 % was achieved at 170 °C after 4 h under ambient air pressure in water. High yields of LA were also obtained from other carbohydrates, such as fructose (68.3 %), glucose (52.7 %), starch (54.4 %), and inulin (67 %). A series of experiments demonstrated that Er(III) combination with water catalyzed cascading steps of soluble cellulose into LA after ZnCl2·3H2O hydrate disrupted the hydrogen bonds in the cellulose, Zn(II) played an indirect role by promoting LA formation through inhibition of side reactions. A plausible mechanism was proposed for the chemocatalytic conversion of cellulose to LA.

Improving High-Voltage Cycling Stability and High-Rate Capability of Sodium-Ion Layered Cathode Oxides through Trace Amounts of Low-Valence Metals.

With the increasing demand for clean energy sources, the need for large-scale energy storage systems to ensure the stable output of renewable energy sources, such as wind and solar, has also increased. Sodium-ion batteries have emerged as a potential solution for these storage systems owing to their high energy density, abundance in the Earth's crust, and low cost. However, the larger atomic radius of sodium ions results in higher energy barriers for ion migration in cathode materials, which can affect the cycle life and rate performance of the battery. Therefore, developing a suitable structure that facilitates rapid sodiation and desodiation and maintains good cycling stability remains a significant challenge. This study aimed to reduce the content of trivalent manganese ions and minimize the impact of the Jahn-Teller effect to enhance the capacity retention of manganese-based layered oxides. Additionally, a series of P2-type Na0.78Li0.1ZnxNi0.15-xMn0.75O2 compounds were successfully synthesized through doping with divalent zinc ions. Structural analyses of the doped material indicated that Zn doping did not alter the crystal structure but increased the interlayer distance of the transition metals. Electrochemical performance tests revealed that appropriate Zn2+ doping promoted sodium-ion diffusion and improved the reversible capacity of the battery. This study provides a promising approach for developing sodium-ion batteries with rapid charging and discharging capabilities.

Declined intrinsic capacity predicts long-term mortality in Chinese older adults: Beijing Longitudinal Study of Aging.

BACKGROUND: Intrinsic capacity reflects an individual's functions and capacities across their lifetime. There are few studies on whether the level of intrinsic capacity can predict long-term mortality in Chinese populations. OBJECTIVE: To explore the effects of intrinsic capacity on long-term outcomes in older Chinese adults. METHODS: Data were obtained from the Beijing Longitudinal Study of Aging. Overall, 1699 community-dwelling adults aged ≥60 years were included and followed up for 8 years. Intrinsic capacity was determined according to the World Health Organization definition. The predictive ability for adverse outcomes was assessed using the age- and sex-adjusted Cox proportional hazards model. RESULTS: A decline in intrinsic capacity domains was observed in 729 (42.9 %) participants. Declines in the mobility, cognition, vitality, sensory and psychology domains were observed in 21.8 %, 15.1 %, 11.4 %, 9.10 %, and 14.2 % of the participants, respectively. Low intrinsic capacity was associated with worse physical performance, frailty, social frailty, chronic diseases, fracture, and falls. A greater decline in intrinsic capacity predicted an elevated 8-year mortality rate (decline in overall intrinsic capacity hazard ratio 2.91, 95 % confidence interval 2.44-3.47, P < 0.001; decline in one domain hazard ratio 2.11, 95 % confidence interval 1.71-2.61, P < 0.001; decline in two domains hazard ratio 3.54, 95 % confidence interval 2.81-4.45, P < 0.001; decline in three or more domains hazard ratio 5.30, 95 % confidence interval 4.09-6.87, P < 0.001); adjusted models did not affect prediction performance. Among the five domains of intrinsic capacity, cognition was the strongest predictor of mortality (hazard ratio 3.17, 95 % confidence interval 2.63-3.81, P < 0.001). CONCLUSIONS: Intrinsic capacity is useful in identifying older adults at higher risk of adverse outcomes, presenting significant implications for healthcare policies in China.

A nomogram and risk stratification system for predicting survival in T1-2N0-1 breast cancer patients with liver metastasis in females: a population-based study.

PURPOSE: Liver was one of the most common distant metastatic sites in breast cancer. Patients with distant metastasis were identified as American Joint Committee on Cancer (AJCC) stage IV indicating poor prognosis. However, few studies have predicted the survival in females with T1-2N0-1 breast cancer who developed liver metastasis. This study aimed to explore the clinical features of these patients and establish a nomogram to predict their overall survival. RESULTS: 1923 patients were randomly divided into training (n = 1154) and validation (n = 769) cohorts. Univariate and multivariate analysis showed that age, marital status, race, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), chemotherapy, surgery and bone metastasis, brain metastasis were considered the independent prognostic indicators. We developed a nomogram according to these ten parameters. The consistency index (c-index) was 0.72 (95% confidence interval CI 0.70-0.74) in the training cohort, 0.72 (95% CI 0.69-0.74) in the validation cohort. Calibration plots indicated that the nomogram-predicted survival was consistent with the recorded 1-, 3- and 5-year prognoses. Decision curve analysis curves in both the training and validation cohorts demonstrated that the nomogram showed better prediction than the AJCC TNM (8th) staging system. Kaplan Meier curve based on the risk stratification system showed that the low-risk group had a better prognosis than the high-risk group (P < 0.001). CONCLUSIONS: A predictive nomogram and risk stratification system were constructed to assess prognosis in T1-2N0-1 breast cancer patients with liver metastasis in females. The risk model established in this study had good predictive performance and could provide personalized clinical decision-making for future clinical work.

Physiologically Based Pharmacokinetic Modeling of Vancomycin in Critically Ill Neonates: Assessing the Impact of Pathophysiological Changes.

Dosing vancomycin for critically ill neonates is challenging owing to substantial alterations in pharmacokinetics (PKs) caused by variability in physiology, disease, and clinical interventions. Therefore, an adequate PK model is needed to characterize these pathophysiological changes. The intent of this study was to develop a physiologically based pharmacokinetic (PBPK) model that reflects vancomycin PK and pathophysiological changes in neonates under intensive care. PK-sim software was used for PBPK modeling. An adult model (model 0) was established and verified using PK profiles from previous studies. A neonatal model (model 1) was then extrapolated from model 0 by scaling age-dependent parameters. Another neonatal model (model 2) was developed based not only on scaled age-dependent parameters but also on quantitative information on pathophysiological changes obtained via a comprehensive literature search. The predictive performances of models 1 and 2 were evaluated using a retrospectively collected dataset from neonates under intensive care (chictr.org.cn, ChiCTR1900027919), comprising 65 neonates and 92 vancomycin serum concentrations. Integrating literature-based parameter changes related to hypoalbuminemia, small-for-gestational-age, and co-medication, model 2 offered more optimized precision than model 1, as shown by a decrease in the overall mean absolute percentage error (50.6% for model 1; 37.8% for model 2). In conclusion, incorporating literature-based pathophysiological changes effectively improved PBPK modeling for critically ill neonates. Furthermore, this model allows for dosing optimization before serum concentration measurements can be obtained in clinical practice.

Bioaerosols emission from source facilities in a wastewater treatment plant: Critical exposure time and sensitivity analysis.

Overexposure of sewage workers to bioaerosol released from wastewater treatment plants (WWTPs) can cause serious infections, but practical method for controlling their health risk is lacking. In this study, reverse quantitative microbial risk assessment was used to estimate the daily critical exposure time (CET) of sewage workers exposing to Staphylococcus aureus bioaerosol emitted by three emission sources facilities in a WWTP based on either U.S. EPA or WHO benchmark, and sensitivity analysis was conducted to analyze the influence of various parameters on the outcomes of CET. The results showed that the CET of females was always 1.12-1.29 times that of males. In addition, the CET after wearing face masks was 28.28-52.37 times as long as before. The working time can be determined based on the CET results of male workers wearing face masks exposed to the inverted-umbrella aeration tank (14.73-550.98 min for U.S. EPA benchmark and 55.07-1972.24 min for WHO benchmark). In each scenario, the variable parameter exposure concentration (ec) always showed the most influence on the CET results. After wearing the face masks, the removal fraction by employing face masks also had a significant effect on the results, only second to ec. Therefore, the wearing of face mask is the most convenient and effective measure to prolong the CET. Furthermore, practical methods to reducing bioaerosol concentration in WWTPs exposure are also necessary to extend CET and safeguard worker health. This study enriches the application range of reverse quantitative microbial risk assessment framework and provides theoretical support for stakeholders to establish reasonable working time threshold guidelines, and practical method and novel perspective to protect the on-site health risks of sewage workers exposing to various facilities.

Nitroxide radical conjugated ovalbumin theranostic nanosystem for enhanced dendritic cell-based immunotherapy and T1 magnetic resonance imaging.

Melanoma, known for its aggressive metastatic nature, presents a formidable challenge in cancer treatment, where conventional therapies often fall short. This study introduces a pioneering approach utilizing metal-free nanosystem as tumor vaccines, spotlighting their potential in revolutionizing melanoma treatment. This work employed organic nitroxides, specifically 4-carboxy-TEMPO, in combination with chitosan (CS), to create a novel nanocomposite material - the CS-TEMPO-OVA nanovaccines. This composition not only improves biocompatibility and extends blood circulation time of TEMPO but also marks a significant departure from traditional gadolinium-based contrast agents in MRI technology, addressing safety concerns. CS-TEMPO-OVA nanovaccines demonstrate excellent biocompatibility at both the cellular and organoid level. They effectively stimulate bone marrow-derived dendritic cells (BMDCs), which in turn promote the maturation and activation of T cells. This ultimately leads to a strong production of essential cytokines. These nanovaccines serve a dual purpose as both therapeutic and preventive. By inducing an immune response, activating cytotoxic T cells, and promoting macrophage M1 polarization, they effectively inhibit melanoma growth and enhance survival in mouse models. When combined with αPD-1, the CS-TEMPO-OVA nanovaccines significantly bolster the infiltration of cytotoxic T lymphocytes (CTLs) within tumors, sparking a powerful systemic antitumor response that effectively curbs tumor metastasis. The ability of these nanovaccines to control both primary (subcutaneous) and metastatic B16-OVA tumors highlights their remarkable efficacy. Furthermore, the CS-TEMPO-OVA nanovaccine can be administered in vivo via both intravenous and intramuscular routes, both of which effectively enhance the T1 contrast of magnetic resonance imaging in tumor tissue. This study offers invaluable insights into the integrated application of these nanovaccines in both clinical diagnostics and treatment, marking a significant stride in cancer research and patient care.

Elaborating the Fluorescence Regulation and Quenching Mechanism of Sulfur-for-Oxygen Replacement for Fluorophores.

Thio-caged fluorophores can be effectively desulfurized into their oxygenated derivatives through visible light, thereby restoring the strong emission of fluorophores, and are applied in the field of live cell super-resolution imaging. Herein, we theoretically investigated the reasons for the low fluorescence quantum yields of a series of thio-caged fluorophores and the underlying reasons for the differences in fluorescence quantum yields of their oxygenated derivatives. The calculation results show that the S atom on the thiocarbonyl group is more likely to excite n electrons to form the nπ* state, which reduces the energy of the nπ* state and leads to fluorescence quenching. In contrast, the O atom on the carbonyl group is more likely to excite π electrons to form ππ* state, which is the main reason for restoring the strong emission of fluorophore. Meanwhile, the calculation results show that the difference of fluorescence intensity caused by oxygenated derivatives is determined by the number of the carbonyl group, which affects the vibronic coupling between ππ* and nπ* states and thereby leads to fluorescence quenching. These results can effectively reveal the fluorescence quenching mechanism of thio-caged fluorophores and the luminescence mechanism of their oxygenated derivatives, and provide correct and guiding design strategies for the development of new thio-caged fluorophores.

AFDN Deficiency Promotes Liver Tropism of Metastatic Colorectal Cancer.

Liver metastasis is a major cause of morbidity and mortality in patients with colorectal cancer. A better understanding of the biological mechanisms underlying liver tropism and metastasis in colorectal cancer could help to identify improved prevention and treatment strategies. In this study, we performed genome-wide CRISPR loss-of-function screening in a mouse colorectal cancer model and identified deficiency of AFDN, a protein involved in establishing and maintaining cell-cell contacts, as a driver of liver metastasis. Elevated AFDN expression was correlated with prolonged survival in patients with colorectal cancer. AFDN-deficient colorectal cancer cells preferentially metastasized to the liver but not in the lungs. AFDN loss in colorectal cancer cells at the primary site promoted cancer cell migration and invasion by disrupting tight intercellular junctions. Additionally, CXCR4 expression was increased in AFDN-deficient colorectal cancer cells via the JAK-STAT signaling pathway, which reduced the motility of AFDN-deficient colorectal cancer cells and facilitated their colonization of the liver. Collectively, these data shed light on the mechanism by which AFDN deficiency promotes liver tropism in metastatic colorectal cancer. Significance: A CRISPR screen reveals AFDN loss as a mediator of liver tropism in colorectal cancer metastasis by decreasing tight junctions in the primary tumor and increasing interactions between cancer cells and hepatocytes.

Customized Vascular Repair Microenvironment: Poly(lactic acid)-Gelatin Nanofibrous Scaffold Decorated with bFGF and Ag@Fe3O4 Core-Shell Nanowires.

Vascular defects caused by trauma or vascular diseases can significantly impact normal blood circulation, resulting in serious health complications. Vascular grafts have evolved as a popular approach for vascular reconstruction with promising outcomes. However, four of the greatest challenges for successful application of small-diameter vascular grafts are (1) postoperative anti-infection, (2) preventing thrombosis formation, (3) utilizing the inflammatory response to the graft to induce tissue regeneration and repair, and (4) noninvasive monitoring of the scaffold and integration. The present study demonstrated a basic fibroblast growth factor (bFGF) and oleic acid dispersed Ag@Fe3O4 core-shell nanowires (OA-Ag@Fe3O4 CSNWs) codecorated poly(lactic acid) (PLA)/gelatin (Gel) multifunctional electrospun vascular grafts (bAPG). The Ag@Fe3O4 CSNWs have sustained Ag+ release and exceptional photothermal capabilities to effectively suppress bacterial infections both in vitro and in vivo, noninvasive magnetic resonance imaging (MRI) modality to monitor the position of the graft, and antiplatelet adhesion properties to promise long-term patency. The gradually released bFGF from the bAPG scaffold promotes the M2 macrophage polarization and enhances the recruitment of macrophages, endothelial cells (ECs) and fibroblast cells. This significant regulation of diverse cell behavior has been proven to be beneficial to vascular repair and regeneration both in vitro and in vivo. Therefore, this study supplies a method to prepare multifunctional vascular-repair materials and is expected to represent a significant guidance and reference to the development of biomaterials for vascular tissue engineering.

ADAMTS16 Suppression by MicroRNA-25 Leads to Oncogenic Properties in Renal Cell Carcinoma.

INTRODUCTION: Increasing evidence indicates that microRNAs (miRNAs) play a crucial role in modulating tumor growth. This study is centered on investigating the contribution of miR-25 to the progression of Renal Cell Carcinoma (RCC). METHODS: The investigators examined the expression levels of miR-25 and ADAMTS16 in RCC samples and cell lines. The association between miR-25 and ADAMTS16 was validated via a luciferase reporter assay. Cell viability, apoptosis, migration, and invasion were evaluated utilizing CCK-8 and flow cytometry techniques, while the expression levels of ADAMTS16, ß-catenin, GSK-3ß, and p-GSK-3ß were assessed through western blot analysis. RESULTS: The investigation revealed elevated expression levels of miR-25 in RCC tissues. Subsequently, ADAMTS16 was identified as a target of miR-25. Increased miR-25 levels were associated with decreased expression of ADAMTS16, resulting in enhanced cell viability and diminished apoptosis. Conversely, inhibition of miR-25 led to decreased cell viability, proliferation, and migration. Additionally, the researchers observed that miR-25 triggered the phosphorylation of GSK-3ß and ß-catenin while leaving the total GSK-3ß level unaffected. CONCLUSION: This study suggests that miR-25 regulates the expression of ADAMTS16 through the Wnt/ß-catenin signaling pathway, providing new insights into the cause and potential treatment of RCC.

Yolk-shelled silver nanowire@amorphous metal-organic framework for controlled drug delivery and light-promoting infected wound healing.

Bacteria-infected wounds healing has been greatly hindered by antibiotic resistance and persistent inflammation. It is crucial to develop multifunctional nanocomposites that possess effective antibacterial properties and can simultaneously accelerate the wound healing process to overcome the above challenges. Herein, we prepared a yolk-shell structured Ag nanowires (NWs)@amorphous hollow ZIF-67 by etching ZIF-67 onto the Ag NWs for infected wound healing for the first time. The etched hollow structure of amorphous ZIF-67 in the nanocomposite makes it a promising platform for loading healing-promoting drugs. We extensively studied the antibacterial and healing-promoting properties of the curcumin (CCM)-loaded nanocomposite (Ag NWs@C-HZ67). Ag NWs, being noble metal materials with plasmonic effects, can absorb a broad range of natural light and convert it to thermal energy. This photothermal conversion further improves the release of antibacterial components and wound healing drugs when exposed to light. During the healing process of an infected wound, Ag and Co ions were released from Ag NWs@C-HZ67 upon direct contact with the wound exudate and under the influence of light irradiation. Simultaneously, the loaded CCM leaked out to repair the infected wound. The minimum inhibitory concentrations of the Ag NWs@C-HZ67 groups against Escherichia coli and Staphylococcus aureus bacteria decreased to 3 and 3 µg ml-1 when exposed to white light. Furthermore, an in vivo assessment of infected wound healing demonstrated that combining Ag NWs@C-HZ67 with light significantly accelerated the wound healing process, achieving 70% healing by the 6th day and almost complete healing by the 8th day. This advanced nanocomposite, consisting of components that possess antibacterial and growth-promoting properties, offers a safe, effective and clinically-translatable solution for accelerating the healing process of infected wounds.

Near-infrared-II responsive ovalbumin functionalized gold-genipin nanosystem cascading photo-immunotherapy of cancer.

Synergistic cancer therapies have attracted wide attention owing to their multi-mode tumor inhibition properties. Especially, photo-responsive photoimmunotherapy demonstrates an emerging cancer treatment paradigm that significantly improved treatment efficiency. Herein, near-infrared-II responsive ovalbumin functionalized Gold-Genipin nanosystem (Au-G-OVA NRs) was designed for immunotherapy and deep photothermal therapy of breast cancer. A facile synthesis method was employed to prepare the homogeneous Au nanorods (Au NRs) with good dispersion. The nanovaccine was developed further by the chemical cross-linking of Au-NRs, genipin and ovalbumin. The Au-G-OVA NRs outstanding aqueous solubility, and biocompatibility against normal and cancer cells. The designed NRs possessed enhanced localized surface plasmon resonance (LSPR) effect, which extended the NIR absorption in the second window, enabling promising photothermal properties. Moreover, genipin coating provided complimentary red fluorescent and prepared Au-G-OVA NRs showed significant intracellular encapsulation for efficient photoimmunotherapy outcomes. The designed nanosystem possessed deep photothermal therapy of breast cancer and 90% 4T1 cells were ablated by Au-G-OVA NRs (80µg ml-1concentration) after 1064 nm laser irradiation. In addition, Au-G-OVA NRs demonstrated outstanding vaccination phenomena by facilitating OVA delivery, antigen uptake, maturation of bone marrow dendritic cells, and cytokine IFN-γsecretion for tumor immunosurveillance. The aforementioned advantages permit the utilization of fluorescence imaging-guided photo-immunotherapy for cancers, demonstrating a straightforward approach for developing nanovaccines tailored to precise tumor treatment.

On the Use and Construction of Wi-Fi Fingerprint Databases for Large-Scale Multi-Building and Multi-Floor Indoor Localization: A Case Study of the UJIIndoorLoc Database.

Large-scale multi-building and multi-floor indoor localization has recently been the focus of intense research in indoor localization based on Wi-Fi fingerprinting. Although significant progress has been made in developing indoor localization algorithms, few studies are dedicated to the critical issues of using existing and constructing new Wi-Fi fingerprint databases, especially for large-scale multi-building and multi-floor indoor localization. In this paper, we first identify the challenges in using and constructing Wi-Fi fingerprint databases for large-scale multi-building and multi-floor indoor localization and then provide our recommendations for those challenges based on a case study of the UJIIndoorLoc database, which is the most popular publicly available Wi-Fi fingerprint multi-building and multi-floor database. Through the case study, we investigate its statistical characteristics with a focus on the three aspects of (1) the properties of detected wireless access points, (2) the number, distribution and quality of labels, and (3) the composition of the database records. We then identify potential issues and ways to address them using the UJIIndoorLoc database. Based on the results from the case study, we not only provide valuable insights on the use of existing databases but also give important directions for the design and construction of new databases for large-scale multi-building and multi-floor indoor localization in the future.