Titanium surfaces loaded with puerarin and exosomes derived from adipose stem cells promote the proliferation and differentiation of pre-osteoblasts.

The study is to evaluate the effects of collagen/hyaluronic acid coating with or without puerarin and exosomes (Exos) derived from adipose stem cells (ADSCs-Exos) on pre-osteoblast proliferation and differentiation on the surface of titanium materials. Titanium materials with different coatings were prepared by layer-by-layer technique, evaluating the surface characterization. Cell functions were assessed by cell biology experiments. Related genes and proteins were assessed by RT-qPCR and Western blot. Puerarin or ADSCs-Exos coating had better effects on promoting the adhesion, proliferation and differentiation of pre-osteoblasts, and the strongest effect was found after their co-coatings, manifesting as the up-regulations of alkaline phosphatase (ALP) activity, collagen type I alpha 1 (Col1a1), runt-related transcription factor 2 (Runx2), osterix and activating transcription factor-2 (ATF-2). Levels of phosphorylated-P38 (p-P38) and p-ATF-2 were up-regulated in pre-osteoblasts grown on puerarin and ADSCs-Exos-loaded titanium surfaces. Titanium surfaces loaded with puerarin and ADSCs-Exos promotes the proliferation and differentiation of pre-osteoblasts.

Power imbalance in hospital dual management system and its impact on turnover.

Introduction: With the deepening of the healthcare reform in China, the competition in the sector is becoming fiercer leading to several unintended consequences such as talent turnover, which highly affect hospital development. Taking the case of a specialized university-affiliated stomatology hospital in Guangzhou, this thesis aims to analyze the main factors that contribute to talent turnover in this type of hospitals. The loss of talents in the field of stomatology is not unique to China and represents a significant problem in both developed and developing countries. Methods: The data for the study were collected from post facto live interviews conducted with 21 resigners to understand their feelings and motivations after the passage of time. The data were coded and concepts refined using MAXQDA software to form 18 sub-categories and six aggregate dimensions leading to the construction of two theoretical models. Results: The balance of power embedded in the dual leadership system characteristic of Chinese organizations and corresponding leadership style and behavior, deeply affect the turnover of talents. The more unbalanced the power, the greater the impact on turnover. Conclusion: Based on the situation studied, a power imbalance allowed for individual behaviors that determined the development of the hospital and directly affected institutional fairness, culture, working atmosphere and ultimately led to turnover.

Growth and physiological metabolic regulation mechanisms of the dominant plant Leymus secalinus in alpine meadow under nitrogen deposition.

Nitrogen (N) deposition is an important pathway that affects the growth and development of alpine grassland plants. Under N deposition, Leymus secalinus has become the most dominant species in the alpine meadow of the Qinghai-Tibetan Plateau. However, its adaptive mechanisms to N deposition are still unknown. Therefore, we analyzed the physiological indices of Leymus secalinus under different N deposition levels (CK, 0 kg N ha-1 yr-1; N1, 8 kg N ha-1 yr-1; N3, 40 kg N ha-1 yr-1; N5, 72 kg N ha-1 yr-1) and focused on its growth and metabolism. The results indicated that the leaf carbon (C), N, amino acid (AA), and photosynthetic pigment contents in Leymus secalinus were significantly increased under N deposition, its endogenous hormone levels were regulated and the activities of N metabolism-related enzymes were enhanced. Metabolomics analysis further showed that the metabolites changed significantly and were mostly enriched in the amino acid metabolic pathway. Among them, glutamine and aspartic acid played key roles in N deposition for dominant growth of Leymus secalinus by regulating N and amino acid metabolism. These analyses unveiled the physiological and biochemical changes of dominant species in response to N deposition, identifying critical metabolites involved in this process. Furthermore, these findings provide substantial evidence explaining the ecological phenomenon of Leymus secalinus emerging as a dominant species under N deposition, serving as a data reference for understanding the physiological response and adaptation to N deposition in alpine grassland plants.

Polysialic acid driving cardiovascular targeting co-delivery 1,8-cineole and miR-126 to synergistically alleviate lipopolysaccharide-induced acute cardiovascular injury.

Infection-induced cardiovascular damage is the primary pathological mechanism underlying septic cardiac dysfunction. This condition affects the majority of patients in intensive care unit and has an unfavorable prognosis due to the lack of effective therapies available. Vascular cell adhesion molecule-1 (VCAM-1) plays a vital role in coordinating the inflammatory response and recruitment of leukocytes in cardiac tissue, making it a potential target for developing novel therapies. MicroRNA-126 (miR-126) has been shown to downregulate VCAM-1 expression in endothelial cells, reducing leukocyte adhesion and exerting anti-inflammatory effects. Therefore, this work described a polysialic acid (PSA) modified ROS-responsive nanosystem to targeted co-delivery 1,8-Cineole and miR-126 for mitigating septic cardiac dysfunction. The nanosystem consists of 1,8-Cineole nanoemulsion (CNE) conjugated with PEI/miR126 complex by a ROS-sensitive linker, with PSA on its surface to facilitate targeted delivery via specific interactions with selectins on endothelial cells. CNE has demonstrated protective effects against inflammation in the cardiovascular system and synergistic anti-inflammatory effects when combined with miR-126. The targeted nanosystem successfully delivered miR-126 and 1,8-Cineole to the injured heart tissues and vessels, reducing inflammatory responses and improving cardiac function. In summary, this work provides a promising therapy for alleviating the inflammatory response in sepsis while boosting cardiovascular protection.

Multifunctional Photothermal Nanorods for Targeted Treatment of Drug-Resistant Bacteria-Induced Wound Healing.

The challenge of drug-resistant bacteria-induced wound healing in clinical and public healthcare settings is significant due to the negative impacts on surrounding tissues and difficulties in monitoring the healing progress. We developed photothermal antibacterial nanorods (AuNRs-PU) with the aim of selectively targeting and combating drug-resistant Pseudomonas aeruginosa (P. aeruginosa). The AuNRs-PU were engineered with a bacterial-specific targeting polypeptide (UBI29-41) and a bacterial adhesive carbohydrate polymer composed of galactose and phenylboronic acid. The objective was to facilitate sutureless wound closure by specially distinguishing between bacteria and nontarget cells and subsequently employing photothermal methods to eradicate the bacteria. AuNRs-PU demonstrated high photothermal conversion efficiency in 808 nm laser and effectively caused physical harm to drug-resistant P. aeruginosa. By integrating the multifunctional bacterial targeting copolymer onto AuNRs, AuNRs-PU showed rapid and efficient bacterial targeting and aggregation in the presence of bacteria and cells, consequently shielding cells from bacterial harm. In a diabetic rat wound model, AuNRs-PU played a crucial role in enhancing healing by markedly decreasing inflammation and expediting epidermis formation, collagen deposition, and neovascularization levels. Consequently, the multifunctional photothermal therapy shows promise in addressing the complexities associated with managing drug-resistant infected wound healing.

ROS-Responsive Nanoparticles with Antioxidative Effect for the treatment of Diabetic Retinopathy.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes necessitating early intervention to impede progression, despite current clinical treatments focusing on advanced stages. Essential oils from Fructus Alpiniae zerumbet (EOFAZ) have demonstrated efficacy in protecting against high glucose (HG)-induced Müller cell activation and DR development. This study introduced a reactive oxidative species (ROS)-responsive drug delivery system (NPSPHE@EOFAZ) targeting early DR stages and oxidative stress. Our engineered nanoparticles effectively deliver EOFAZ into HG-exposed Müller cells by detecting and responding to elevated oxidative stress levels. The NPSPHE@EOFAZ significantly inhibited abnormal cell growth, reduced oxidative stress, and alleviated inflammation in vitro. In vivo experiments on diabetic mice with DR revealed that NPSPHE@EOFAZ mitigated early pathological changes by reducing oxidative stress and inflammation while also alleviating organ damage in the heart, liver, spleen, lung, and kidney. These findings underscore the potential of NPSPHE@EOFAZ as a promising antioxidant for early intervention in DR pathogenesis.

The SIX2/PFN2 feedback loop promotes the stemness of gastric cancer cells.

BACKGROUND: The roles of the transcriptional factor SIX2 have been identified in several tumors. However, its roles in gastric cancer (GC) progression have not yet been revealed. Our objective is to explore the impact and underlying mechanisms of SIX2 on the stemness of GC cells. METHODS: Lentivirus infection was employed to establish stable expression SIX2 or PFN2 in GC cells. Gain- and loss-of-function experiments were conducted to detect changes of stemness markers, flow cytometry profiles, tumor spheroid formation, and tumor-initiating ability. ChIP, RNA-sequencing, tissue microarray, and bioinformatics analysis were performed to reveal the correlation between SIX2 and PFN2. The mechanisms underlying the SIX2/PFN2 loop-mediated effects were elucidated through tissue microarray analysis, RNA stability assay, IP-MS, Co-Immunoprecipitation, and inhibition of the JNK signaling pathway. RESULTS: The stemness of GC cells was enhanced by SIX2. Mechanistically, SIX2 directly bound to PFN2's promoter and promoted PFN2 activity. PFN2, in turn, promoted the mRNA stability of SIX2 by recruiting RNA binding protein YBX-1, subsequently activating the downstream MAPK/JNK pathway. CONCLUSION: This study unveils the roles of SIX2 in governing GC cell stemness, defining a novel SIX2/PFN2 regulatory loop responsible for this regulation. This suggests the potential of targeting the SIX2/PFN2 loop for GC treatment (Graphical Abstracts).

Spatial and temporal differentiation and its driving factors of air quality in the economic circle of Shandong Province during 2013-2020.

As the negative repercussions of environmental devastation, such as air quality decline and air pollution, become more apparent, environmental consciousness is growing across the world, forcing nations to take steps to mitigate the damage. China pledged to achieve air quality improvement goal to combat global environment issue, yet the spatial-temporal differentiation and its driving factors of environment-meteorology-economic index for air quality are not fully analysed. To promote regional collaborative control of air pollution and achieve sustainable urban development, spatial and temporal different and its driving factors of air quality in Shandong Province during 2013-2020. Results revealed that concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), particulate matter 2.5 (PM2.5), particulate matter 10 (PM10), and carbon monoxide (CO-95per) exhibited decreasing trend (SO2 concentrations decreasing 84 % and CO-95per concentrations decreasing 90 %). Air quality was improved from inland areas to coastal areas. Pollutant indicators of SO2, NO2, PM10, PM2.5, and CO-95per demonstrated significant positive correlation (P < 0.05). Air temperature and precipitation are significantly negatively correlated with concentrations of SO2, NO2, PM10, PM2.5, and CO-95per but significantly positively correlated with ozone (O3-8 h). SO2, NO2, PM2.5, PM10, CO-95per, and proportion of days with heavy pollution are strongly positively correlated with proportion of secondary industry but strongly negatively correlated with proportion of tertiary industry and volume of household waste. Except for O3-8 h, pollutant index of Provincial Capital Economic Circle (PCEC) and Southern Shandong Economic Circle (SSEC) has significant negative correlation (P < 0.05) with regional gross domestic product and investment in environmental protection; however, investment in environmental protection of Eastern Shandong Economic Circle (ESEC) has no significant correlation with air pollution index. There was significant negative correlation between vegetable sowing area and SSEC pollutant index. The relationship between pollution emission and investment in environmental protection has shifted from high pollution-low investment to low pollution-low investment in PCEC, ESEC and SSEC, and the inflection point was in 2020 for PCEC, 2019 for ESEC, and 2020 for SSEC. Those results provide empirical evidence and theoretical support for the improvement of regional air quality, aiming to achieve high-quality development. According to these findings, it has been found that meteorological elements, pollutant emission, socio-economic factors and agricultural data affect air quality. Those results could provide meaningful and significant supporting for synergistic regulation of diverse pollutants.

Primary cilia signaling in astrocytes mediates development and regional-specific functional specification.

Astrocyte diversity is greatly influenced by local environmental modulation. Here we report that the majority of astrocytes across the mouse brain possess a singular primary cilium localized to the cell soma. Comparative single-cell transcriptomics reveals that primary cilia mediate canonical SHH signaling to modulate astrocyte subtype-specific core features in synaptic regulation, intracellular transport, energy and metabolism. Independent of canonical SHH signaling, primary cilia are important regulators of astrocyte morphology and intracellular signaling balance. Dendritic spine analysis and transcriptomics reveal that perturbation of astrocytic cilia leads to disruption of neuronal development and global intercellular connectomes in the brain. Mice with primary ciliary-deficient astrocytes show behavioral deficits in sensorimotor function, sociability, learning and memory. Our results uncover a critical role for primary cilia in transmitting local cues that drive the region-specific diversification of astrocytes within the developing brain.

Dynamically blocking leakage current in molecular tunneling junctions.

Molecular tunneling junctions based on self-assembled monolayers (SAMs) have demonstrated rectifying characteristics at the nanoscale that can hardly be achieved using traditional approaches. However, defects in SAMs result in high leakage when applying bias. The poor performance of molecular diodes compared to silicon or thin-film devices limits their further development. In this study, we show that incorporating "mixed backbones" with flexible-rigid structures into molecular junctions can dynamically block tunneling currents, which is difficult to realize using non-molecular technology. Our idea is achieved by the interaction between interfacial dipole moments and electric field, triggering structured packing in SAMs. Efficient blocking of leakage by more than an order of magnitude leads to a significant enhancement of the rectification ratio to the initial value. The rearrangement of supramolecular structures has also been verified through electrochemistry and electroluminescence measurements. Moreover, the enhanced rectification is extended to various challenging environments, including endurance measurements, bending of electrodes, and rough electrodes, thus demonstrating the feasibility of the dynamic behavior of molecules for practical electronic applications.

Calculus bovis inhibits M2 tumor-associated macrophage polarization via Wnt/ß-catenin pathway modulation to suppress liver cancer.

BACKGROUND: Calculus bovis (CB), used in traditional Chinese medicine, exhibits anti-tumor effects in various cancer models. It also constitutes an integral component of a compound formulation known as Pien Tze Huang, which is indicated for the treatment of liver cancer. However, its impact on the liver cancer tumor microenvironment, particularly on tumor-associated macrophages (TAMs), is not well understood. AIM: To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/ß-catenin pathway modulation. METHODS: This study identified the active components of CB using UPLC-Q-TOF-MS, evaluated its anti-neoplastic effects in a nude mouse model, and elucidated the underlying mechanisms via network pharmacology, transcriptomics, and molecular docking. In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs, and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. RESULTS: This study identified 22 active components in CB, 11 of which were detected in the bloodstream. Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth. An integrated approach employing network pharmacology, transcriptomics, and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization. In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/ß-catenin pathway activation. The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001, confirming its pathway specificity. CONCLUSION: This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/ß-catenin pathway, contributing to the suppression of liver cancer growth.

Genome-wide identification of R2R3-MYB transcription factor subfamily genes involved in salt stress in rice (Oryza sativa L.).

BACKGROUND: R2R3-MYB transcription factors belong to one of the largest gene subfamilies in plants, and they are involved in diverse biological processes. However, the role of R2R3-MYB transcription factor subfamily genes in the response of rice (Oryza sativa L.) to salt stress has been rarely reported. RESULTS: In this study, we performed a genome-wide characterization and expression identification of rice R2R3-MYB transcription factor subfamily genes. We identified a total of 117 R2R3-MYB genes in rice and characterized their gene structure, chromosomal location, and cis-regulatory elements. According to the phylogenetic relationships and amino acid sequence homologies, the R2R3-MYB genes were divided into four groups. qRT-PCR of the R2R3-MYB genes showed that the expression levels of 10 genes significantly increased after 3 days of 0.8% NaCl treatment. We selected a high expression gene OsMYB2-115 for further analysis. OsMYB2-115 was highly expressed in the roots, stem, leaf, and leaf sheath. OsMYB2-115 was found to be localized in the nucleus, and the yeast hybrid assay showed that OsMYB2-115 has transcriptional activation activity. CONCLUSION: This result provides important information for the functional analyses of rice R2R3-MYB transcription factor subfamily genes related to the salt stress response and reveals that OsMYB2-115 may be an important gene associated with salt tolerance in rice.

Lexical tone recognition in multi-talker babbles and steady-state noise by Mandarin-speaking children with unilateral cochlear implants or bimodal hearing.

BACKGROUND AND OBJECTIVES: Lexical tone presents challenges to cochlear implant (CI) users especially in noise conditions. Bimodal hearing utilizes residual acoustic hearing in the contralateral side and may offer benefits for tone recognition in noise. The purpose of the present study was to evaluate tone recognition in both steady-state noise and multi-talker babbles by the prelingually-deafened, Mandarin-speaking children with unilateral CIs or bimodal hearing. METHODS: Fifty-three prelingually-deafened, Mandarin-speaking children who received CIs participated in this study. Twenty-two of them were unilateral CI users and 31 wore a hearing aid (HA) in the contralateral ear (i.e., bimodal hearing). All subjects were tested for Mandarin tone recognition in quiet and in two types of maskers: speech-spectrum-shaped noise (SSN) and two-talker babbles (TTB) at four signal-to-noise ratios (-6, 0, +6, and +12 dB). RESULTS: While no differences existed in tone recognition in quiet between the two groups, the Bimodal group outperformed the Unilateral CI group under noise conditions. The differences between the two groups were significant at SNRs of 0, +6, and +12 dB in the SSN conditions (all p < 0.05), and at SNRs of +6 and +12 dB of TTB conditions (both p < 0.01), but not significant at other conditions (p > 0.05). The TTB exerted a greater masking effect than the SSN for tone recognition in the Unilateral CI group as well as in the Bimodal group at all SNRs tested (all p < 0.05). Among demographic or audiometric variables, only age at implantation showed a weak but significant correlation with the mean tone recognition performance under the SSN conditions (r = -0.276, p = 0.045). However, when Bonferroni correction was applied to the correlation analysis results, the weak correlation became not significant. CONCLUSION: Prelingually-deafened children with CIs face challenges in tone perception in noisy environments, especially when the noise is fluctuating in amplitude such as the multi-talker babbles. Wearing a HA on the contralateral side when residual hearing permits is beneficial for tone recognition in noise.

Electrically Driven Deterministic Plasmon Light Sources Based on Arrays of Molecular Tunnel Junctions.

Surface plasmons excited via inelastic tunnelling have led to plasmon light sources with small footprints and ultrafast response speeds, which are favored by integrated optical circuits. Self-assembled monolayers of organic molecules function as highly tunable tunnel barriers with novel functions. However, limited by the low effective contact between the liquid metal electrode and the self-assembled monolayers, it is quite challenging to obtain molecular plasmon light sources with high density and uniform emission. Here, by combining lithographic patterning with a solvent treatment method, we have demonstrated electrically driven deterministic plasmon emission from arrays of molecular tunnel junctions. The solvent treatment could largely improve the effective contact from 9.6% to 48% and simultaneously allow the liquid metal to fill into lithographically patterned micropore structures toward deterministic plasmon emission with desired patterns. Our findings open up new possibilities for tunnel junction-based plasmon light sources, laying the foundation for electrically driven light-emitting metasurfaces.

A survey of breastfeeding among women with previous surgery for benign breast disease: a descriptive exploratory study.

BACKGROUND: Surgery is the primary treatment for benign breast disease and causes some disruption to the normal physiology of the breast, even when this disruption is localised, it remains unclear whether it affects women's ability to breastfeed. There are only a few studies describing the experience of breastfeeding in women who have undergone benign breast disease (BBD) surgery. METHODS: We retrospectively analysed data from patients aged 20-40 years in Guangdong, China, who underwent breast lumpectomy for BBD in our department between 01 January 2013 and 30 June 2019, with a follow-up date of 01 February 2022. Patients were included who had a history of childbirth between the time of surgery and the follow-up date. By collecting general information about this group of patients and information about breastfeeding after surgery, we described the breastfeeding outcomes of women of a fertile age who had previously undergone surgery for benign breast disease. RESULTS: With a median follow-up of 5.9 years, a total of 333 patients met the inclusion criteria. From the breastfeeding data of the first child born postoperatively, the mean duration of 'exclusive breastfeeding' was 5.1 months, and the mean duration of 'any breastfeeding' was 8.8 months. The rate of 'ever breastfeeding' is 91.0%, which is lower than the national average of 93.7%, while the exclusive breastfeeding rate at six months was 40.8%, was higher than the 29.2% national average. The any breastfeeding rate at 12 months was 30.0%, which was well below the 66.5% national average. The common reason for early breastfeeding cessation was insufficient breast milk. A total of 29.0% of patients who had ever breastfed after surgery voluntarily reduced the frequency and duration of breastfeeding on the operated breast because of the surgery. CONCLUSIONS: There are some impacts of BBD surgery on breastfeeding and some may be psychological. Institutions should provide more facilities for mothers who have undergone breast surgery to help them breastfeed, such as conducting community education on breastfeeding after breast surgery, training professional postoperative lactation consultants in hospitals, and extending maternity leave. Families should encourage mothers to breastfeed with both breasts instead of only the non-operated breast.

Glycogen synthase kinase 3 activity enhances liver inflammation in MASH.

Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by excessive circulating toxic lipids, hepatic steatosis, and liver inflammation. Monocyte adhesion to liver sinusoidal endothelial cells (LSECs) and transendothelial migration (TEM) are crucial in the inflammatory process. Under lipotoxic stress, LSECs develop a proinflammatory phenotype known as endotheliopathy. However, mediators of endotheliopathy remain unclear. Methods: Primary mouse LSECs isolated from C57BL/6J mice fed chow or MASH-inducing diets rich in fat, fructose, and cholesterol (FFC) were subjected to multi-omics profiling. Mice with established MASH resulting from a choline-deficient high-fat diet (CDHFD) or FFC diet were also treated with two structurally distinct GSK3 inhibitors (LY2090314 and elraglusib [9-ING-41]). Results: Integrated pathway analysis of the mouse LSEC proteome and transcriptome indicated that leukocyte TEM and focal adhesion were the major pathways altered in MASH. Kinome profiling of the LSEC phosphoproteome identified glycogen synthase kinase (GSK)-3ß as the major kinase hub in MASH. GSK3ß-activating phosphorylation was increased in primary human LSECs treated with the toxic lipid palmitate and in human MASH. Palmitate upregulated the expression of C-X-C motif chemokine ligand 2, intracellular adhesion molecule 1, and phosphorylated focal adhesion kinase, via a GSK3-dependent mechanism. Congruently, the adhesive and transendothelial migratory capacities of primary human neutrophils and THP-1 monocytes through the LSEC monolayer under lipotoxic stress were reduced by GSK3 inhibition. Treatment with the GSK3 inhibitors LY2090314 and elraglusib ameliorated liver inflammation, injury, and fibrosis in FFC- and CDHFD-fed mice, respectively. Immunophenotyping using cytometry by mass cytometry by time of flight of intrahepatic leukocytes from CDHFD-fed mice treated with elraglusib showed reduced infiltration of proinflammatory monocyte-derived macrophages and monocyte-derived dendritic cells. Conclusion: GSK3 inhibition attenuates lipotoxicity-induced LSEC endotheliopathy and could serve as a potential therapeutic strategy for treating human MASH. Impact and Implications: LSECs under lipotoxic stress in MASH develop a proinflammatory phenotype known as endotheliopathy, with obscure mediators and functional outcomes. The current study identified GSK3 as the major driver of LSEC endotheliopathy, examined its pathogenic role in myeloid cell-associated liver inflammation, and defined the therapeutic efficacy of pharmacological GSK3 inhibitors in murine MASH. This study provides preclinical data for the future investigation of GSK3 pharmacological inhibitors in human MASH. The results of this study are important to hepatologists, vascular biologists, and investigators studying the mechanisms of inflammatory liver disease and MASH, as well as those interested in drug development.

Synergetic effects during co-pyrolysis of waste textiles and Ca/Fe-rich industrial sewage sludge: Reaction kinetics and product distribution.

Co-pyrolysis is a promising technology for industrial organic waste to utilize their unique resource and energy properties for efficient conversion into valuable products. This study was the first time to characterize the co-pyrolysis of waste textiles with Ca-rich industrial sludge and Fe-rich industrial sludge on a laboratory-scale fixed bed. The properties, mechanisms, gas, oil and carbon production were investigated as a function of temperature and mixing type. Co-pyrolysis increased the total weight loss from 50.05 % to 69.81 % for Ca-rich industrial sludge mixed with 50 % waste textiles and from 49.13 % to 70.01 % for Fe-rich industrial sludge mixed with 50 % waste textiles. The activation energy of co-pyrolysis was approximately 50 % lower compared to the pyrolysis of waste textiles alone. The optimal reaction model for the different reaction stages for all samples was three diffusion (D3). Co-pyrolysis resulted in lower CO and CO2 emission temperatures of about 25-110 °C and produced more short-chain organic compounds (C < 10). Co-pyrolysis produced more aldehydes and ketones organics. Moreover, co-pyrolysis char exhibited an elevated level of fatty alkyl side chains and bridge branching, as well as higher degrees of aromatization and stability. This study offers valuable insights into the potential application of pyrolysis for the management of Ca/Fe-rich industrial sludge and waste textiles, thereby serving as a basis for future utilization endeavors.

Accessing and exploring the unusual chemistry by radical SAM-RiPP enzymes.

Radical SAM enzymes involved in the biosynthesis of ribosomally synthesized and post-translationally modified peptides catalyze unusual transformations that lead to unique peptide scaffolds and building blocks. Several natural products from these pathways show encouraging antimicrobial activities and represent next-generation therapeutics for infectious diseases. These systems are uniquely configured to benefit from genome-mining approaches because minimal substrate and cognate modifying enzyme expression can reveal unique, chemically complex transformations that outperform late-stage chemical reactions. This report highlights the main strategies used to reveal these enzymatic transformations, which have relied mainly on genome mining using enzyme-first approaches. We describe the general biosynthetic components for rSAM enzymes and highlight emerging approaches that may broaden the discovery and study of rSAM-RiPP enzymes. The large number of uncharacterized rSAM proteins, coupled with their unpredictable transformations, will continue to be an essential and exciting resource for enzyme discovery.

Mitochondria-Targeted Natural Antioxidant Nanosystem for Diabetic Vascular Calcification Therapy.

The development of nanotherapy targeting mitochondria to alleviate oxidative stress is a critical therapeutic strategy for vascular calcification (VC) in diabetes. In this study, we engineered mitochondria-targeted nanodrugs (T4O@TPP/PEG-PLGA) utilizing terpinen-4-ol (T4O) as a natural antioxidant and mitochondrial protector, PEG-PLGA as the nanocarrier, and triphenylphosphine (TPP) as the mitochondrial targeting ligand. In vitro assessments demonstrated enhanced cellular uptake of T4O@TPP/PEG-PLGA, with effective mitochondrial targeting. This nanodrug successfully reduced oxidative stress induced by high glucose levels in vascular smooth muscle cells. In vivo studies showed prolonged retention of the nanomaterials in the thoracic aorta for up to 24 h. Importantly, experiments in diabetic VC models underscored the potent antioxidant properties of T4O@TPP/PEG-PLGA, as evidenced by its ability to mitigate VC and restore mitochondrial morphology. These results suggest that these nanodrugs could be a promising strategy for managing diabetic VC.

Cetuximab inhibits colorectal cancer development through inactivating the Wnt/ß-catenin pathway and modulating PLCB3 expression.

Colorectal cancer (CRC) often necessitates cetuximab (an EGFR-targeting monoclonal antibody) for treatment. Despite its clinical utility, the specific operative mechanism of cetuximab remains elusive. This research investigated the influence of PLCB3, a potential CRC oncogene, on cetuximab treatment. We extracted differentially expressed genes from the GSE140973, the overlapping genes combined with 151 Wnt/ß-Catenin signaling pathway-related genes were identified. Then, we conducted bioinformatics analysis to pinpoint the hub gene. Subsequently, we investigated the clinical expression characteristics of this hub gene, through cell experimental, scrutinized the impact of cetuximab and PLCB3 on CRC cellular progression. The study identified 26 overlapping genes. High expression of PLCB3, correlated with poorer prognosis. PLCB3 emerged as a significant oncogene associated with patient prognosis. In vitro tests revealed that cetuximab exerted a cytotoxic effect on CRC cells, with PLCB3 knockdown inhibiting CRC cell progression. Furthermore, cetuximab treatment led to a reduction in both ß-catenin and PLCB3 expression, while simultaneously augmenting E-cadherin expression. These findings revealed PLCB3 promoted cetuximab inhibition on Wnt/ß-catenin signaling. Finally, simultaneous application of cetuximab with a Wnt activator (IM12) and PLCB3 demonstrated inhibited CRC proliferation, migration, and invasion. The study emphasized the pivotal role of PLCB3 in CRC and its potential to enhance the efficacy of cetuximab treatment. Furthermore, cetuximab suppressed Wnt/ß-catenin pathway to modulate PLCB3 expression, thus inhibiting colorectal cancer progression. This study offered fresh perspectives on cetuximab mechanism in CRC.