CELLULOSE SYNTHASE-LIKE C proteins modulate cell wall establishment during ethylene-mediated root growth inhibition in rice.

The cell wall shapes plant cell morphogenesis and affects the plasticity of organ growth. However, the way in which cell wall establishment is regulated by ethylene remains largely elusive. Here, by analyzing cell wall patterns, cell wall composition and gene expression in rice (Oryza sativa, L.) roots, we found that ethylene induces cell wall thickening and the expression of cell wall synthesis-related genes, including CELLULOSE SYNTHASE-LIKE C1, 2, 7, 9, 10 (OsCSLC1, 2, 7, 9, 10) and CELLULOSE SYNTHASE A3, 4, 7, 9 (OsCESA3, 4, 7, 9). Overexpression and mutant analyses revealed that OsCSLC2 and its homologs function in ethylene-mediated induction of xyloglucan biosynthesis mainly in the cell wall of root epidermal cells. Moreover, OsCESA-catalyzed cellulose deposition in the cell wall was enhanced by ethylene. OsCSLC-mediated xyloglucan biosynthesis likely plays an important role in restricting cell wall extension and cell elongation during the ethylene response in rice roots. Genetically, OsCSLC2 acts downstream of ETHYLENE-INSENSITIVE3-LIKE1 (OsEIL1)-mediated ethylene signaling, and OsCSLC1, 2, 7, 9 are directly activated by OsEIL1. Furthermore, the auxin signaling pathway is synergistically involved in these regulatory processes. These findings link plant hormone signaling with cell wall establishment, broadening our understanding of root growth plasticity in rice and other crops.

A nanofluidic spiking synapse.

Currently, the nanofluidic synapse can only perform basic neuromorphic pulse patterns. One immediate problem that needs to be addressed to further its capability of brain-like computing is the realization of a nanofluidic spiking device. Here, we report the use of a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate membrane to achieve bionic ionic current-induced spiking. In addition to the simulation of various electrical pulse patterns, our synapse could produce transmembrane ionic current-induced spiking, which is highly analogous to biological action potentials with similar phases and excitability. Moreover, the spiking properties could be modulated by ions and neurochemicals. We expect that this work could contribute to biomimetic spiking computing in solution.

Photoresponsive Hydrogen-Bonded Organic Frameworks-Enabled Organic Photoelectrochemical Transistors for Sensitive Bioanalysis.

A facile route for exponential magnification of transconductance (gm) in an organic photoelectrochemical transistor (OPECT) is still lacking. Herein, photoresponsive hydrogen-bonded organic frameworks (PR-HOFs) have been shown to be efficient for gm magnification in a typical poly(ethylene dioxythiophene):poly(styrenesulfonate) OPECT. Specifically, 450 nm light stimulation of 1,3,6,8-tetrakis (p-benzoic acid) pyrene (H4TBAPy)-based HOF could efficiently modulate the device characteristics, leading to the considerable gm magnification over 78 times from 0.114 to 8.96 mS at zero Vg. In linkage with a DNA nanomachine-assisted steric hindrance amplification strategy, the system was then interfaced with the microRNA-triggered structural DNA evolution toward the sensitive detection of a model target microRNA down to 0.1 fM. This study first reveals HOFs-enabled efficient gm magnification in organic electronics and its application for sensitive biomolecular detection.

Dual Engine Boosts Organic Photoelectrochemical Transistor for Enhanced Modulation and Bioanalysis.

Organic photoelectrochemical transistor (OPECT) has shown substantial potential in the development of next-generation bioanalysis yet is limited by the either-or situation between the photoelectrode types and the channel types. Inspired by the dual-photoelectrode systems, we propose a new architecture of dual-engine OPECT for enhanced signal modulation and its biosensing application. Exemplified by incorporating the CdS/Bi2S3 photoanode and Cu2O photocathode within the gate-source circuit of Ag/AgCl-gated poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) channel, the device shows enhanced modulation capability and larger transconductance (gm) against the single-photoelectrode ones. Moreover, the light irritation upon the device effectively shifts the peak value of gm to zero gate voltage without degradation and generates larger current steps that are advantageous for the sensitive bioanalysis. Based on the as-developed dual-photoelectrode OPECT, target-mediated recycling and etching reactions are designed upon the CdS/Bi2S3, which could result in dual signal amplification and realize the sensitive microRNA-155 biodetection with a linear range from 1 fM to 100 pM and a lower detection limit of 0.12 fM.

Association of DOK3 and infiltrated tumor-associated macrophages with risk for the prognosis of Porphyromonas gingivalis-infected oral cancer: a 12-year data analysis of 200 patients from a tertiary teaching hospital, Urumqi, China.

BACKGROUND: While there is an understanding of the association between the expression of Porphyromonas gingivalis (P. gingivalis) and prognosis of oral squamous cell carcinoma (OSCC), significance specially to address the relevance between different immunohistochemical intensities of P. gingivalis and tumor-associated macrophages (TAMs) in OSCC tissue and related clinicopathologic characteristics has not been well investigated. The present study aimed to investigate the pathological features related to M2-TAM in P. gingivalis-infected OSCC and ascertain its clinical relevance with patients' prognosis. METHODS: A prospective cohort study was designed to comparatively analyze 200 patients from June 2008 to June 2020. Bioinformatics analyses were implemented to identify DOK3 as a key molecule and to appraise immunocyte infiltration using Gene Expression Omnibus and The Cancer Genome Atlas databases. Immunohistochemical evaluation was performed to analyze the association between the expression levels of P. gingivalis, DOK3, and M2-TAM and clinicopathological variables using Fisher's exact test or Pearson's chi-square test. Cox analysis was used to calculate hazard ratios (HR) with corresponding 95% confidence interval (CI) for various clinicopathological features. The Kaplan-Meier approach and log-rank test were used to plot the survival curves. RESULTS: The expression level of P. gingivalis was positively associated with DOK3 and M2-TAMs expression level (P < 0.001). Parameters, including body mass index, clinical stage, recurrence, tumor differentiation, and P. gingivalis, DOK3, and M2-TAM immunoexpression levels, affected the prognosis of patients with OSCC (all P < 0.05). In addition, P. gingivalis (HR = 1.674, 95%CI 1.216-4.142, P = 0.012), DOK3 (HR = 1.881, 95%CI 1.433-3.457, P = 0.042), and M2-TAM (HR = 1.649, 95%CI 0.824-3.082, P = 0.034) were significantly associated with the 10-year cumulative survival rate. CONCLUSIONS: Elevated expression of P. gingivalis and DOK3 indicates M2-TAM infiltration and unfavorable prognosis of OSCC, and could be considered as three novel independent risk factors for predicting the prognosis of OSCC.

Knowledge, attitudes, and practice related to tooth loss and dentures among patients with dental arch deficiencies.

BACKGROUND: Tooth loss is a common problem that affects many people worldwide. Exploring knowledge, attitude, and practice (KAP) among patients can identify barriers and challenges in following recommended practices, providing valuable insights for dental healthcare providers, policymakers, and researchers. This study aimed to explore the KAP of patients with dental arch deficiencies regarding tooth loss and dentures. METHODS: This web-based, cross-sectional study was conducted among patients with dental arch deficiencies using a self-designed questionnaire. RESULT: 3166 valid questionnaires were included. Participants' mean KAP scores were 6.84 ± 2.27 (possible range: 0 ~ 12), 39.4 ± 3.72 (possible range: 9 ~ 45), and 27.7 ± 4.36 (possible range: 8 ~ 40), respectively. Multivariable logistic regression analysis showed that knowledge (OR = 1.383), employed (OR = 1.805), family history (OR = 2.158), and treatment (OR = 1.683) were independently associated with attitude. Moreover, knowledge (OR = 1.239), attitude (OR = 1.250), female (OR = 0.619), age (OR = 0.967), college/bachelor (OR = 0.373), and master and above degree (OR = 0.418), employed (OR = 0.554) or student (OR = 0.434), with 10,001-20,000 Yuan household income per month (OR = 0.492), have been married (OR = 0.609), smoking (OR = 0.595), drinking (OR = 0.397), disease duration (OR = 0.972), with family history (OR = 1.676), and with treatment (OR = 3.492) were independently associated with practice (all P < 0.05). CONCLUSION: Patients with dental arch deficiencies have insufficient knowledge, positive attitudes, and moderate practice toward tooth loss and dentures, which might be affected by multiple demographic factors.

Combined toxic effects of polyethylene microplastics and lambda-cyhalothrin on gut of zebrafish (Danio rerio).

Microplastics (MPs), which are prevalent and increasingly accumulating in aquatic environments. Other pollutants coexist with MPs in the water, such as pesticides, and may be carried or transferred to aquatic organisms, posing unpredictable ecological risks. This study sought to assess the adsorption of lambda-cyhalothrin (LCT) by virgin and aged polyethylene MPs (VPE and APE, respectively), and to examine their influence on LCT's toxicity in zebrafish, specifically regarding acute toxicity, oxidative stress, gut microbiota and immunity. The adsorption results showed that VPE and APE could adsorb LCT, with adsorption capacities of 34.4 mg∙g-1 and 39.0 mg∙g-1, respectively. Compared with LCT exposure alone, VPE and APE increased the acute toxicity of LCT to zebrafish. Additionally, exposure to LCT and PE-MPs alone can induce oxidative stress in the zebrafish gut, while combined exposure can exacerbate the oxidative stress response and intensify intestinal lipid peroxidation. Moreover, exposure to LCT or PE-MPs alone promotes inflammation, and combined exposure leads to downregulation of the myd88-nf-κb related gene expression, thus impacting intestinal immunity. Furthermore, exposure to APE increased LCT toxicity to zebrafish more than VPE. Meanwhile, exposure to PE-MPs and LCT alone or in combination has the potential to affect gut microbiota function and alter the abundance and diversity of the zebrafish gut flora. Collectively, the presence of PE-MPs may affect the toxicity of pesticides in zebrafish. The findings emphasize the importance of studying the interaction between MPs and pesticides in the aquatic environment.

Accurate and robust auto-segmentation of head and neck organ-at-risks based on a novel CNN fine-tuning workflow.

PURPOSE: Obvious inconsistencies in auto-segmentations exist among various AI software. In this study, we have developed a novel convolutional neural network (CNN) fine-tuning workflow to achieve precise and robust localized segmentation. METHODS: The datasets include Hubei Cancer Hospital dataset, Cetuximab Head and Neck Public Dataset, and Québec Public Dataset. Seven organs-at-risks (OARs), including brain stem, left parotid gland, esophagus, left optic nerve, optic chiasm, mandible, and pharyngeal constrictor, were selected. The auto-segmentation results from four commercial AI software were first compared with the manual delineations. Then a new multi-scale lightweight residual CNN model with an attention module (named as HN-Net) was trained and tested on 40 samples and 10 samples from Hubei Cancer Hospital, respectively. To enhance the network's accuracy and generalization ability, the fine-tuning workflow utilized an uncertainty estimation method for automatic selection of candidate samples of worthiness from Cetuximab Head and Neck Public Dataset for further training. The segmentation performances were evaluated on the Hubei Cancer Hospital dataset and/or the entire Québec Public Dataset. RESULTS: A maximum difference of 0.13 and 0.7 mm in average Dice value and Hausdorff distance value for the seven OARs were observed by four AI software. The proposed HN-Net achieved an average Dice value of 0.14 higher than that of the AI software, and it also outperformed other popular CNN models (HN-Net: 0.79, U-Net: 0.78, U-Net++: 0.78, U-Net-Multi-scale: 0.77, AI software: 0.65). Additionally, the HN-Net fine-tuning workflow by using the local datasets and external public datasets further improved the automatic segmentation with the average Dice value by 0.02. CONCLUSION: The delineations of commercial AI software need to be carefully reviewed, and localized further training is necessary for clinical practice. The proposed fine-tuning workflow could be feasibly adopted to implement an accurate and robust auto-segmentation model by using local datasets and external public datasets.

Treatment plan complexity quantification for predicting gamma passing rates in patient-specific quality assurance for stereotactic volumetric modulated arc therapy.

PURPOSE: To investigate the beam complexity of stereotactic Volumetric Modulated Arc Therapy (VMAT) plans quantitively and predict gamma passing rates (GPRs) using machine learning. METHODS: The entire dataset is exclusively made of stereotactic VMAT plans (301 plans with 594 beams) from Varian Edge LINAC. The GPRs were analyzed using Varian's portal dosimetry with 2%/2 mm criteria. A total of 27 metrics were calculated to investigate the correlation between metrics and GPRs. Random forest and gradient boosting models were developed and trained to predict the GPRs based on the extracted complexity features. The threshold values of complexity metric were obtained to predict a given beam to pass or fail from ROC curve analysis. RESULTS: The three moderately significant values of Spearman's rank correlation to GPRs were 0.508 (p < 0.001), 0.445 (p < 0.001), and -0.416 (p < 0.001) for proposed metric LAAM, the ratio of the average aperture area over jaw area (AAJA) and index of modulation, respectively. The random forest method achieved 98.74% prediction accuracy with mean absolute error of 1.23% using five-fold cross-validation, and 98.71% with 1.25% for gradient boosting regressor method, respectively. LAAM, leaf travelling distance (LT), AAJA, LT modulation complexity score (LTMCS) and index of modulation, were the top five most important complexity features. The LAAM metric showed the best performance with AUC value of 0.801, and threshold value of 0.365. CONCLUSIONS: The calculated metrics were effective in quantifying the complexity of stereotactic VMAT plans. We have demonstrated that the GPRs could be accurately predicted using machine learning methods based on extracted complexity metrics. The quantification of complexity and machine learning methods have the potential to improve stereotactic treatment planning and identify the failure of QA results promptly.

An enzymatic reaction-based SERS saliva analysis microporous array chip for chiral differentiation and high-throughput detection of D-amino acids.

A Raman-active boronate modified surface-enhanced Raman scattering (SERS) microporous array chip based on the enzymatic reaction was constructed for reliable, sensitive, and quantitative monitoring of D-Proline (D-Pro) and D-Alanine (D-Ala) in saliva. Initially, 3-mercaptophenylboronic acid (3-MPBA) was bonded to Au-coated Si nanocrown arrays (Au/SiNCA) via Au-S bonding. Following this, H2O2 obtained from D-amino acid oxidase (DAAO)-specific catalyzed D-amino acids (D-AAs) further reduced 3-MPBA to 3-hydroxythiophenol (3-HTP) with a new Raman peak at 882 cm-1. Meanwhile, the original characteristic peak at 998 cm-1 remained unchanged. Therefore, the I882/I998 ratio increased with increasing content of D-AAs in the sample to be tested, allowing D-AAs to be quantitatively detected. The Au/SiNCA with large-area periodic crown structure prepared provided numerous, uniform "hot spots," and the microporous array chip with 16 detection units was employed as the platform for SERS analysis, realizing high-throughput, high sensitivity, high specificity and high-reliability quantitative detection of D-AAs (D-Pro and D-Ala). The limits of detection (LOD) were down to 10.1 µM and 13.7 µM throughout the linear range of 20-500 µM. The good results of the saliva detection suggested that this SERS sensor could rapidly differentiate between early-stage gastric cancer patients and healthy individuals.

The impact of different states of type 2 diabetes when stratified by baseline HbA1c on the periodontal outcomes of non-surgical periodontal treatment: A systematic review and network meta-analysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been considered by many studies to have a bidirectional relationship with periodontitis. This systematic review and network meta-analysis aimed to investigate the impact of different states of T2DM when stratified by baseline HbA1c on the clinical outcomes of non-surgical periodontal treatment (NSPT). METHODS: This study followed the Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines and involved an electronic literature search (from inception to the 2nd of January 2023). The study included at least two groups of patients: chronic periodontitis only (No-DM) or periodontitis and well-controlled/poorly controlled type 2 diabetes mellitus (WC/PC-T2DM). Clinical outcomes included probing depth (PD) reduction, bleeding on probing reduction, and clinical attachment level (CAL) gain. Direct and indirect comparisons between groups were assessed by network meta-analysis, thus allowing us to establish a treatment ranking. RESULTS: Ten prospective cohort studies (11 data sets) were included for qualitative analysis and network meta-analysis. The data included in this study had high consistency; in addition, a funnel plot and Egger's test showed that the articles had low publication bias. Network meta-analysis showed that the effect of NSPT in the No-DM group was significantly better than the WC-T2DM group [weighted mean difference (WMD) = 0.09, 95% confidence interval (CI) (0.01, 0.18)] and the PC-T2DM group [WMD = 0.09, 95% CI (0.01, 0.18)] in terms of CAL gain and better than the PC-T2DM group [WMD = 0.15, 95% CI (0.02, 0.28)] in terms of PD reduction. According to the surface under the cumulative ranking value, the No-DM group had the highest probability of achieving the best outcome following NSPT. CONCLUSIONS: Collectively, our analyses show that T2DM exerts significant effects on the outcomes of NSPT.

Dual Functional Conjugated Acetylenic Polymers: High-Efficacy Modulation for Organic Photoelectrochemical Transistors and Structural Evolution for Bioelectronic Detection.

Conjugated acetylenic polymers (CAPs) have emerged as a unique class of metal-free semiconductors with tunable electrical and optical properties yet their full potential remains largely unexplored. Organic bioelectronics is envisioned to create more opportunities for innovative biomedical applications. Herein, we report a poly(1,4-diethynylbenzene) (pDEB)/NiO gated enhancement-mode poly(ethylene dioxythiophene)-poly(styrene sulfonate) organic photoelectrochemical transistor (OPECT) and its structural evolution toward bioelectronic detection. pDEB was synthesized via copper-mediated Glaser polycondensation of DEB monomers on the NiO/FTO substrate, and the as-synthesized pDEB/NiO/FTO can efficiently modulate the enhancement-mode device with a high current gain. Linking with a sandwich immunoassay, the labeled alkaline phosphatase can catalyze sodium thiophosphate to generate H2S, which will react with the diacetylene group in pDEB through the Michael addition reaction, resulting in an altered molecular structure and thus the transistor response. Exemplified by HIgG as the model target, the developed biosensor achieves highly sensitive detection with a linear range of 70 fg mL-1-10 ng mL-1 and a low detection limit of 28.5 fg mL-1. This work features the dual functional CAP-gated OPECT, providing not only a novel gating module but also a structurally new rationale for bioelectronic detection.

Chemical Redox Cycling in an Organic Photoelectrochemical Transistor: Toward Dual Chemical and Electronic Amplification for Bioanalysis.

The organic photoelectrochemical transistor (OPECT) has been proven to be a promising platform to study the rich light-matter-bio interplay toward advanced biomolecular detection, yet current OPECT is highly restrained to its intrinsic electronic amplification. Herein, this work first combines chemical amplification with electronic amplification in OPECT for dual-amplified bioanalytics with high current gain, which is exemplified by human immunoglobulin G (HIgG)-dependent sandwich immunorecognition and subsequent alkaline phosphatase (ALP)-mediated chemical redox cycling (CRC) on a metal-organic framework (MOF)-derived BiVO4/WO3 gate. The target-dependent redox cycling of ascorbic acid (AA) acting as an effective electron donor could lead to an amplified modulation against the polymer channel, as indicated by the channel current. The as-developed bioanalysis could achieve sensitive HIgG detection with a good analytical performance. This work features the dual chemical and electronic amplification for OPECT bioanalysis and is expected to stimulate further interest in the design of CRC-assisted OPECT bioassays.

Microplastics Enhance the Prevalence of Antibiotic Resistance Genes in Anaerobic Sludge Digestion by Enriching Antibiotic-Resistant Bacteria in Surface Biofilm and Facilitating the Vertical and Horizontal Gene Transfer.

Antibiotic resistance genes (ARGs) and microplastics (MPs) are recognized as emerging contaminants and threats to global human health. Despite both of them being significantly detected in their "hotspots", i.e., waste activated sludge (WAS), rare studies on how MPs affect ARGs and antibiotic-resistant bacteria (ARB) in anaerobic sludge digestion are available. Herein, the fate of ARGs and ARB after exposure to MPs of three dosages (10, 30, and 80 particles/g-TS), three polymer types (LDPE, PET, and PS), and three branching extents (LDPE, LLDPE, and HDPE) in anaerobic sludge digestion was investigated. Metagenomic results indicated that all variants of MPs resulted in an increase of the relative abundance of ARGs in the digester compared to the control. The abundance of ARGs demonstrated a dosage-dependent relationship within the range from 10 to 80 particles/g-TS, resulting in an increase from 4.5 to 27.9% compared to the control. Branching structure and polymer type influence ARG level in the sludge digester as well. Mechanism studies revealed that LDPE selectively enriched potential ARB and ARGs in the surface biofilm, possibly creating a favorable environment for ARB proliferation and ARG exchange. Furthermore, vertical transfer of ARGs was facilitated by LDPE through increasing bacterial cell proliferation accompanied by the enhancement of relevant functional genes. The elevated abundance of mobile genetic elements (MGEs) and ARGs-carrying plasmids also demonstrated that MGE-mediated horizontal transfer was promoted by LDPE at 80 particles/g-TS. This effect was compounded by increased oxidative stress, cell membrane permeability, and cell cohesion, collectively facilitating horizontal ARG transfer. Consequently, both vertical and horizontal transfer of ARGs could be concurrently promoted by LDPE an in anaerobic sludge digester.

Simultaneous Dissemination of Nanoplastics and Antibiotic Resistance by Nematode Couriers.

Nanoplastics (NPs) are increasingly recognized as a newly emerging pollutant in the environment. NPs can enable the colonization of microbial pathogens on their surfaces and adsorb toxic pollutants, such as heavy metals and residual antibiotics. Although the dissemination of plastic particles in water bodies and the atmosphere is widely studied, the dissemination of NPs and adsorbed pollutants on land, via biological means, is poorly understood. Since soil animals, such as the bacterivorous nematode Caenorhabditis elegans (C. elegans), are highly mobile, this raises the possibility that they play an active role in disseminating NPs and adsorbed pollutants. Here, we established that antibiotic-resistant bacteria could aggregate with antibiotic-adsorbed NPs to form antibiotic-adsorbed NP-antibiotic resistant bacteria (ANP-ARB) aggregates, using polymyxins (colistin) as a proof-of-concept. Colistin-resistant mcr-1 bearing Escherichia coli from a mixed population of resistant and sensitive bacteria selectively aggregate with colistin-ANPs. In the soil microcosm, C. elegans fed on ANP-ARB clusters, resulting in the rapid spread of ANP-ARB by the nematodes across the soil at a rate of 40-60 cm per day. Our work revealed insights into how NPs could still disseminate across the soil faster than previously thought by "hitching a ride" in soil animals and acting as agents of antibiotic-resistant pathogens and antibiotic contaminants. This poses direct risks to ecology, agricultural sustainability, and human health.

A GP130-Targeting Small Molecule, LMT-28, Reduces LPS-Induced Bone Resorption around Implants in Diabetic Models by Inhibiting IL-6/GP130/JAK2/STAT3 Signaling.

In this study, we examined the effect of the GP130-targeting molecule, LMT-28, on lipopolysaccharide- (LPS-) induced bone resorption around implants in diabetic models using in vitro and rat animal experiments. First, LMT-28 was added to osteoblasts stimulated by LPS and advanced glycation end products (AGEs), and nuclear factor-κB receptor-activating factor ligand (RANKL) and associated pathways were evaluated. Then, LMT-28 was administered by gavage at 0.23 mg/kg once every 5 days for 2 weeks to type 2 diabetic rats with peri-implantitis induced by LPS injection and silk ligature. The expression of IL-6 and RANKL was evaluated by immunohistochemistry, and the bone resorption around implants was evaluated by microcomputed tomography. The results showed that LMT-28 downregulated the expression of RANKL through the JAK2/STAT3 signaling pathway in osteoblasts stimulated by LPS and AGEs, reduced bone resorption around implants with peri-implantitis, decreased the expression of IL-6 and RANKL, and decreased osteoclast activity in type 2 diabetic rats. This study confirmed the ability of LMT-28 to reduce LPS-induced bone resorption around implants in diabetic rats.

Polystyrene microplastics enhanced copper-induced acute immunotoxicity in red swamp crayfish (Procambarus clarkii).

Microplastic pollution has attracted a lot of attention in recent years. Not only can it be ingested by animals, but it can easily become a carrier of other pollutants, forming a composite pollutant with potentially toxic effects on organisms. We investigated the effect of Cu on the accumulation of polystyrene microplastics (PS) in the gills of Procambarus clarkii and whether PS exacerbated the immune toxicity of Cu to P. clarkii were exposed to Cu, PS and PS+Cu for 48 h, the accumulation of PS in gill and hepatopancreas immune and antioxidant indices were analyzed. The objective was to investigate the toxic effects of Ps and Cu compound pollutants on P. clarkii and whether the accumulated pollutants would cause food safety problems. The results showed that microplastic particles adhered to each other and aggregated in the PS+Cu group, and the number of microplastic particles in gill in the PS+Cu group was significantly lower than that in the PS group. Compared with the other two treatment groups, SOD, CAT, GPx activities and MDA content increased significantly in the PS+Cu group and were relatively delayed. At 12 h, 24 h, 36 h and 48 h, the SOD mRNA expression levels in the PS+Cu group were all significantly lower than those in the Cu group (P < 0.05). At 24 h and 48 h, CAT mRNA expression in the PS+Cu group was significantly higher than that in the Cu group (P < 0.05). Crustin 4 mRNA expressions in the PS+Cu group was significantly higher than that in the Cu group at 12 h and 36 h (P < 0.05). The results demonstrate that the PS and Cu compound reduced the accumulation of microplastic particles in the gill. PS particles delayed Cu entry into P. clarkii for a short time (12 h) and reduced the toxic effect, but with the increase of exposure time (24 h and 48 h), the toxic effect of PS and Cu complexes on P. clarkii increases, and the large accumulation of PS and Cu complexes may cause food safety problems.

RGS10 negatively regulates apical periodontitis via TFEB-mediated autophagy in BABL/c mice model and in vitro.

AIM: Apical periodontitis is a prevalent oral inflammatory disease that has recently been linked to transcription factor EB (TFEB)-mediated autophagy. Regulator of G-protein signalling 10 (RGS10) is reported to be an effective regulator of the immune system and inflammation. This study aimed to investigate the involvement of RGS10 during the development of apical periodontitis through the TFEB-mediated autophagy signalling pathway. METHODOLOGY: Sixty BALB/c mice were randomly divided into four groups of 15 mice for the in vivo experiment. Rgs10 was locally overexpressed through eight injections of an adeno-associated virus vector. The model of apical periodontitis was established 21 days following pulp exposure, and the mice were euthanized to obtain mandibles for analysis. Micro-computed tomography was employed to assess alveolar bone destruction, and the levels of Rgs10, TFEB-mediated autophagy signalling factors and inflammatory factors were measured using quantitative reverse transcription polymerase chain reactions, western blotting, enzyme-linked immunosorbent assays, immunofluorescence and immunohistochemistry. All experimental results were displayed as images or graphs. For the in vitro experiments, we employed small interfering RNA (siRNA) to silence Rgs10 expression in RAW 264.7 cells. The data were analysed via one-way anova or Mann-Whitney U test/Kruskal-Wallis test of variance, where p < .05 or U > 1.96 was considered statistically significant. RESULTS: Local overexpression of Rgs10 reduced alveolar bone destruction within the apical periodontitis lesion and significantly decreased macrophage infiltration (p < .05). Meanwhile, the expression of TFEB-mediated autophagy signalling factors was upregulated, along with a decrease in inflammatory factor expression (p < .05). Lipopolysaccharide-stimulated RAW 264.7 cells exhibited decreased Rgs10 expression and TFEB-mediated autophagy signalling. siRNA-mediated silencing of Rgs10 further suppressed autophagy and concomitantly upregulated inflammatory factors (p < .05). CONCLUSIONS: Collectively, the findings revealed that RGS10 suppresses the inflammatory response and bone destruction through TFEB-mediated autophagy in apical periodontitis.

Combined impacts of microplastics and cadmium on the liver function, immune response, and intestinal microbiota of crucian carp (Carassius carassius).

Microplastics (MPs) and the heavy metal cadmium (Cd) have attracted global attention for their toxicological interactions in aquatic organisms. The purpose of this investigation was evaluating the effect of MPs (1 mg L-1) and Cd (5 mg L-1) on the liver function, immune response of crucian carp (Carassius carassius) after 96 h exposure, and intestinal microbiota after 21 days, respectively. Co-exposure to MPs and Cd significantly enhanced MP accumulation in the liver of the crucian carp compared to the accumulation with exposure to MPs alone. Co-exposure to MPs and Cd triggered notable histopathological alterations accompanied by increased hepatic cell necrosis and inflammation, and was associated with higher aspartate aminotransferase and alanine aminotransferase levels, lower superoxide dismutase and catalase activity levels, but higher malondialdehyde content and total antioxidant capacity in the liver. Moreover, the combined treatment of MPs and Cd led to the up-regulated transcription of genes related to immune response, such as interleukin 8 (il-8), il-10, il-1ß, tumor necrosis factor-α, and heat shock protein 70, both in the liver and spleen. Co-exposure to MPs and Cd reduced the variety and abundance of the intestinal microbiota in the crucian carp. Our research indicates that the combined exposure to MPs and Cd may exert synergistic toxic effects on crucian carp, which could impede the sustainable growth of the aquaculture industry and pose potential risks to food safety.

Long-circulating doxorubicin and Schizandrin A liposome with drug-resistant liver cancer activity: in vitro and in vivo evaluation.

Co-loading doxorubicin (DOX) and Schizandrin A (SchA) long-circulating liposome (SchA-DOX-Lip) have been confirmed to have good antitumor activity in vitro. However, in vivo pharmacodynamics, targeting, safety, and mechanism of action of SchA-DOX-Lip still need to be further verified. We investigated the tumor inhibition effect, targeting, safety evaluation, and regulation of tumor apoptosis-related proteins of the SchA-DOX-Lip. MTT assay was used to investigate the inhibitory effect of SchA-DOX-Lip on CBRH7919 cells. The drug uptake of CBRH7919 cells was observed by inverted fluorescence microscope. The tumor-bearing nude mice models of CBRH7919 were established, and the anti-tumor effect of SchA-DOX-Lip in vivo was evaluated by tumor biological observation, H&E staining, and TUNEL staining. The distribution and targeting of SchA-DOX-Lip in nude mice models were investigated by small animal imaging and tissue distribution experiment of CBRH7919. The biosafety of SchA-DOX-Lip was evaluated by blood routine parameters, biochemical indexes, and H&E staining. The expression of tumor-associated apoptotic proteins (Bcl-2, Bax, and Caspase-3) was detected by immunohistochemistry anvd western blotting. The results showed that SchA-DOX-Lip had cytotoxicity to CBRH7919 cells which effectively inhibited the proliferation of CBRH7919 cells, improved the uptake of drugs by CBRH7919 cells and the targeting effect of drugs on tumor site. H&E staining and biochemical detection results showed that SchA-DOX-Lip had high biosafety and did not cause serious damage to normal tissues. Western-blotting and TUNEL staining results showed that SchA-DOX-Lip could improve the regulatory effect of drugs on tumor apoptosis proteins. It was demonstrated that SchA-DOX-Lip had high safety and strong tumor inhibition effects, providing a new method for the clinical treatment of hepatocellular carcinoma (HCC).