siRNA nanoparticle targeting Usp20 lowers lipid levels and ameliorates metabolic syndrome in mice.

Atherosclerotic cardiovascular disease is closely correlated with elevated low density lipoprotein-cholesterol. In feeding state, glucose and insulin activate mammalian target of rapamycin 1 that phosphorylates the deubiquitylase ubiquitin-specific peptidase 20 (USP20). USP20 then stabilizes HMG-CoA reductase, thereby increasing lipid biosynthesis. In this study, we applied clinically approved lipid nanoparticles to encapsulate the siRNA targeting Usp20. We demonstrated that silencing of hepatic Usp20 by siRNA decreased body weight, improved insulin sensitivity, and increased energy expenditure through elevating UCP1. In Ldlr-/- mice, silencing Usp20 by siRNA decreased lipid levels and prevented atherosclerosis. This study suggests that the RNAi-based therapy targeting hepatic Usp20 has a translational potential to treat metabolic disease.

A wearable non-enzymatic sensor for continuous monitoring of glucose in human sweat.

To enhance personalized diabetes management, there is a critical need for non-invasive wearable electrochemical sensors made from flexible materials to enable continuous monitoring of sweat glucose levels. The main challenge lies in developing glucose sensors with superior electrochemical characteristics and high adaptability. Herein, we present a wearable sensor for non-enzymatic electrochemical glucose analysis. The sensor was synthesized using hydrothermal and one-pot preparation methods, incorporating gold nanoparticles (AuNPs) functionalized onto aminated multi-walled carbon nanotubes (AMWCNTs) as an efficient catalyst, and crosslinked with carboxylated styrene butadiene rubber (XSBR) and PEDOT:PSS. The sensors were then integrated onto screen-printed electrodes (SPEs) to create flexible glucose sensors (XSBR-PEDOT:PSS-AMWCNTs/AuNPs/SPE). Operating under neutral conditions, the sensor exhibits a linear range of 50 µmol/L to 600 µmol/L, with a limit of detection limit of 3.2 µmol/L (S/N = 3), enabling the detection of minute glucose concentrations. The flexible glucose sensor maintains functionality after 500 repetitions of bending at a 180° angle, without significant degradation in performance. Furthermore, the sensor exhibits exceptional stability, repeatability, and resistance to interference. Importantly, we successfully monitored changes in sweat glucose levels by applying screen-printed electrodes to human skin, with results consistent with normal physiological blood glucose fluctuations. This study details the fabrication of a wearable sensor characterized by ease of manufacture, remarkable flexibility, high sensitivity, and adaptability for non-invasive blood glucose monitoring through non-enzymatic electrochemical analysis. Thus, this streamlined fabrication process presents a novel approach for non-invasive, real-time blood glucose level monitoring.

Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers.

BACKGROUND: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. METHODS: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. RESULTS: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10-7) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10-6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. CONCLUSION: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

Hyperactivation of SREBP induces pannexin-1-dependent lytic cell death.

Sterol-regulatory element binding proteins (SREBPs) are a conserved transcription factor family governing lipid metabolism. When cellular cholesterol level is low, SREBP2 is transported from the endoplasmic reticulum to the Golgi apparatus where it undergoes proteolytic activation to generate a soluble N-terminal fragment, which drives the expression of lipid biosynthetic genes. Malfunctional SREBP activation is associated with various metabolic abnormalities. In this study, we find that overexpression of the active nuclear form SREBP2 (nSREBP2) causes caspase-dependent lytic cell death in various types of cells. These cells display typical pyroptotic and necrotic signatures, including plasma membrane ballooning and release of cellular contents. However, this phenotype is independent of the gasdermin family proteins or mixed lineage kinase domain-like (MLKL). Transcriptomic analysis identifies that nSREBP2 induces expression of p73, which further activates caspases. Through whole-genome CRISPR-Cas9 screening, we find that Pannexin-1 (PANX1) acts downstream of caspases to promote membrane rupture. Caspase-3 or 7 cleaves PANX1 at the C-terminal tail and increases permeability. Inhibition of the pore-forming activity of PANX1 alleviates lytic cell death. PANX1 can mediate gasdermins and MLKL-independent cell lysis during TNF-induced or chemotherapeutic reagents (doxorubicin or cisplatin)-induced cell death. Together, this study uncovers a noncanonical function of SREBPs as a potentiator of programmed cell death and suggests that PANX1 can directly promote lytic cell death independent of gasdermins and MLKL.

Association between Dietary Inflammatory Index (DII) and sarcopenia in ischemic heart disease: an 1999-2004 NHANES study of 1088 US individuals.

BACKGROUND: The aim of this study was to investigate the relationship between DII and sarcopenia in individuals with ischemic heart disease (IHD). METHODS: This was a retrospective study utilizing data of the National Health and Nutrition Examination Survey (NHANES) from 1999-2004. Adults aged ≥50 years diagnosed with IHD, having complete 24-hour dietary recall data, and dual energy X-ray absorptiometry (DEXA)-measured muscle mass were eligible for inclusion. Association between DII and sarcopenia, defined by reduced appendicular skeletal muscle mass, was determined by the logistic regression analyses. RESULTS: Data of 1088 individuals were analyzed, with the mean age of 68.1±0.5 years. Significantly higher DII was observed in the sarcopenic group compared to the non-sarcopenic group (0.24 vs. -0.17, P=0.020). After adjusting for relevant confounders in the multivariable analysis, each unit increase in DII was significantly associated with higher odds of sarcopenia (adjusted odd ratio [aOR]=1.07, 95% confidence interval: 1.00-1.14, P value = 0.040). In stratified analyses, among patients with a Body Mass Index (BMI) ≥30 kg/m2, both DII tertile 2 and tertile 3 were significantly associated with greater odds of sarcopenia (tertile 2 vs. tertile 1: aOR=2.85, 95% CI: 1.56-5.23, P=0.001; tertile 3 vs. tertile 1: aOR=3.11, 95% CI: 1.53-6.31, P=0.002), whereas no significant associations was observed among patients with a BMI<30 kg/m2. CONCLUSIONS: This study has established a significant independent association between a higher DII and an increased risk of sarcopenia in US adults with IHD regardless of type of IHD. BMI appears as a moderating factor in this association.

Pulmonary alveolar microlithiasis combined with gastric mucosal calcification: a case report.

Background: Pulmonary alveolar microlithiasis (PAM) is a rare disease whose clinical and imaging manifestations are non-specific, characterized by the deposition of microliths, which primarily consist of calcium and phosphorus, within the alveoli. In the cases of PAM, patients combined with calcification of other organs such as gastric mucosal calcification are less common. Case presentation: A 59-year-old woman was admitted to our hospital due to cough producing white, foamy sputum, accompanied by dyspnea and fever for 20 days. The CT scan showed diffuse ground-glass opacities and calcification of the gastric mucosa. Lung tissue biopsy revealed the presence of calcification and granulomatous foreign bodies in the interstitium and alveolar cavity. In the later stages, she developed painful skin petechiae. For this patient, the diagnosis of PAM, gastric mucosal calcification, and purpura fulminans was made. However, the genetic test results hinted that the patient and her son had a heterozygous mutation in the FBN1 gene, but her daughter's genetic test results were normal. Although the patient received anti-infection treatment, steroids, and oxygen therapy, her condition did not improve. Conclusion: We reported a rare case of PAM combined with calcification of other organs and purpura fulminans. Treatment of steroids did not show any benefit. The causative mechanism and effective treatment of this disease remain unclear. More treatments need to be explored.

Leukocyte immunoglobulin-like receptor B2: A promising biomarker for colorectal cancer.

According to the latest global cancer statistics, colorectal cancer (CRC) has emerged as the third most prevalent malignant tumor across the globe. In recent decades, the medical field has implemented several levels of CRC screening tests, encompassing fecal tests, endoscopic examinations, radiological examinations and blood tests. Previous studies have shown that leukocyte immunoglobulin-like receptor B2 (LILRB2) is involved in inhibiting immune cell function, immune evasion, and promoting tumor progression in acute myeloid leukemia and non-small cell lung cancer. However, its interaction with CRC has not been reported yet. Recently, a study published in the World Journal of Gastroenterology revealed that LILRB2 and its ligand, angiopoietin-like protein 2, are markedly overexpressed in CRC. This overexpression is closely linked to tumor progression and is indicative of a poor prognosis. The study highlights the potential of utilizing the concentration of LILRB2 in serum as a promising biomarker for tumors. However, there is still room for discussion regarding the data processing and analysis in this research.

Konjac Mannan Oligosaccharides enhanced intestinal barrier function to improve alcoholic nervous injury / 中国药理学通报

Aim Excessive cerebral inflammation caused by chronic alcohol intake is an important risk factor for central nervous system injury. The purpose of this study was to explore the protective effect of konjac mannan oligosaccharide (KMOS) on central nervous system inflammation in alcohol-fed mice and its mechanism. Methods The chronic alcohol fed model of C57BL/6J mice was established using Gao-binge method. And the different doses of KMOS were gavaged every day for 6 weeks. The neuronal damage and microglia activation were evaluated in cerebral cortex and hippocampus. The damage of colon tissue was assessed and serum LPS concentrations were measured. In vitro, Caco-2 cells were stimulated with LPS to establish intestinal mucosal injury model. Results Chronic alcohol intake can cause brain neuron damage in mice, and different doses of KMOS effectively reduced the activation state of microglia, decreased the expression of inflammatory factors caused by the activation of the NLRP3 inflammasome and alleviated neuronal damage in the brain tissue of alcohol-fed mice. The results of colon tissue analysis showed that the use of KMOS effectively reduced the concentration of endotoxin LPS in serum of alcohol-fed mice, alleviated the pathological injury and inflammatory response of colon tissue, and enhanced the expression of Occludin in intestinal tissue. In vitro experiments also showed that KMOS significantly inhibited the inflammatory reaction of Caco-2 cells exposed to alcohol and increased the expression of Occludin protein. Conclusions KMOS treatment effectively inhibited intestinal inflammation caused by alcohol intake, repaired intestinal barrier to prevent the entry of intestinal LPS into brain tissue, decreased the activation of microglia, and then improved brain neuron damage. KMOS had the potential to prevent alcoholic nerve injury.

High-Temperature Polymer Dielectrics Designed Using an Invertible Molecular Graph Generative Model.

Generating new molecules with the desired physical or chemical properties is the key challenge of computational material design. Deep learning techniques are being actively applied in the field of data-driven material informatics and provide a promising way to accelerate the discovery of innovative materials. In this work, we utilize an invertible graph generative model to generate hypothetical promising high-temperature polymer dielectrics. A molecular graph generative model based on the invertible normalizing flow is trained on a data set containing 250k polymer molecular graphs (mostly generated by an RNN-based generative model) to learn the invertible transformations between latent distributions and molecular graph structures. When generating molecular graphs, a sample vector is drawn from the latent space, and then an adjacency tensor and node attribute matrix are generated through two invertible flows in two steps and assembled into a molecular graph. The model has the merits of exact likelihood training and an efficient one-shot generation process. The learned latent space is used to generate polymers with a high glass-transition temperature (Tg) and a wide band gap (Eg) for the application of high-temperature energy storage film capacitors. This work contributes to the efficient design of high-temperature polymer dielectrics by using deep generative models.

Interaction between SlMAPK3 and SlASR4 regulates drought resistance in tomato (Solanum lycopersicum L.).

Tomato is a leading vegetable in modern agriculture, and with global warming, drought has become an important factor threatening tomato production. Mitogen-activated protein kinase 3 (MAPK3) plays an important role in plant disease and stress resistance. To clarify the downstream target proteins of SlMAPK3 and the mechanism of stress resistance in tomato, this study was conducted with the SlMAPK3-overexpressing lines OE-1 and OE-2 and the CRISPR/Cas9-mediated mutant lines slmapk3-1 and slmapk3-2 under PEG 6000-simulated drought. The results of yeast two-hybrid (Y2H), pull-down, and coimmunoprecipitation (Co-IP) assays confirmed that SlASR4 (NP_001269248.1) interacted with SlMAPK3. Analyses of the SlASR4 protein structure and SlASR4 expression under PEG 6000 and BTH stress revealed that SlASR4 has a highly conserved protein structural domain involved in the drought stress response under PEG 6000 treatment. The function of the SlASR4 and SlMAPK3 downstream target protein, in drought resistance in tomato plants, was identified by virus-induced gene silencing (VIGS). This study clarified that SlMAPK3 interacts with SlASR4 to positively regulate drought resistance in tomato plants.

Modified Kramers-Kronig receiver based on memory polynomial compensation for photonics-assisted millimeter-wave communications.

Photonics-assisted millimeter-wave (MMW) wireless communications are advancing rapidly driven by the escalating congestion in the lower-band spectrum and the growing demand for higher data rates. Concurrently, Kramers-Kronig (KK) receivers provide an economical solution ideally suited for cost-sensitive deployment and application. However, the conventional KK receiver is subject to performance degradation due to the nonlinearity and memory effects introduced by practical electronic devices. In this work, the performance degradation of the conventional KK receiver is investigated and quantitatively simulated, showing that the KK receiver exhibits greater sensitivity to nonlinearity and memory effects compared to the conventional coherent receiver. To enhance the performance of KK receivers deployed in MMW communication systems, we propose a modified KK receiver employing memory polynomial compensation, namely MP-KK receiver, capable of effectively compensating memory effects whilst simultaneously addressing nonlinearity. Crucially, the memory polynomial model is employed prior to the KK algorithm to prevent further signal degradation caused by the nonlinear operator in the KK algorithm in the scenario of photonics-assisted MMW wireless communication based on the KK receiver. For verification, we present a 95 GHz W-band MMW wireless transmission demonstration with 20 Gb/s QPSK and 40 Gb/s 16-QAM signals. The experimental results indicate that the MP-KK receiver can achieve more than 3.5 dB improvement in EVM and 71.25% reduction in BER compared to the conventional approaches.

Response to programmed cell death protein 1 antibody in patients with Epstein-Barr virus-associated intrahepatic cholangiocarcinoma.

AIM: Epstein-Barr virus-associated intrahepatic cholangiocarcinoma (EBVaICC) has a distinct genomic profile and increased CD3+ and CD8+ T cells infiltration. However, the efficacy of immunotherapy in EBVaICC remains largely unknown. This study aimed to assess the efficacy of programmed cell death protein 1 (PD-1) antibody therapy in EBVaICC. METHODS: Patients with metastatic biliary tract cancer (BTC) diagnosed at Sun Yat-sen University Cancer Center from January 2016 to December 2021 were identified. In situ hybridisation was performed to detect EBV. Overall survival (OS) and progression-free survival (PFS) were measured. RESULTS: A total of 698 patients with metastatic BTC were identified, of whom 39 (5.6%) had EBVaICC. Among the 136 patients who were not administered PD-1 antibody, the OS was similar between patients with EBVaICC and EBV-negative ICC (median OS 12.5 versus 9.5 months, respectively; P = 0.692). For the 205 patients who were administered PD-1 antibody, patients with EBVaICC had significantly longer OS than patients with EBV-negative ICC (median OS 24.9 versus 11.9 months, respectively; P = 0.004). Seventeen patients with EBVaICC were administered PD-1 antibody. Eight patients (47%) achieved a partial response, and 17 patients achieved disease control. The median PFS was 17.5 months. CONCLUSIONS: This study identified a clinically actionable subset of patients with EBVaICC with a promising response to the PD-1 antibody.

A Fully Integrated RFID Reader SoC.

The traditional RFID reader module relies on a discrete original design. This design integrates a microcontroller, high-frequency RFID reader IC and other multiple chips onto a PCB board, leading to bottlenecks in cost, power consumption, stability and reliability. To align with the trend towards high integration, miniaturization and low power consumption in RFID reader, this paper introduces a fully integrated RFID Reader SoC. The SoC employs the open-source Cortex-M0 core to integrate the RF transceiver, analog circuits, baseband protocol processing, memory and interface circuits into one chip. It's compatible with ISO/IEC 14443 A-type and B-type and ISO/IEC 15693 transmission protocols and rates. Manufactured using a 0.18 µm process, the chip is compatible with multiple standards. The optimized design of the digital baseband control circuit results in a chip area of only 11.95 mm2 offering clear advantages in both area and integration compared to similar work.

MicroRNA-125a-3p Modulate Amyloid ß-Protein through the MAPK Pathway in Alzheimer's Disease.

BACKGROUND: MicroRNA (miR)-125a-3p is reported to play an important role in some central nervous system diseases, such as Alzheimer's disease (AD). However, a study has not been conducted on the mechanism of miR-125a-3p in the pathological process of AD. METHODS: First, we assessed the expression of miR-125a-3p in AD cohort. Subsequently, we altered the expressions of miR-125a-3p to assess its role in cell viability, cell apoptosis, amyloid-ß (Aß) metabolism, and synaptic activity. Finally, we identified its potential mechanism underlying AD pathology. RESULTS: This study unveiled the potential function of miR-125a-3p through modulating amyloid precursor protein processing. Additionally, miR-125a-3p influenced cell survival and activated synaptic expression through the modulation of Aß metabolism in the mitogen-activated protein kinase (MAPK) pathway via fibroblast growth factor receptor 2. CONCLUSION: Our study indicates that targeting miR-125a-3p may be an applicable therapy for AD in the future. However, more in vitro and in vivo studies with more samples are needed to confirm these results.

Measurement of the Thermic Effect of Food in a Chinese Mixed Diet in Young People.

Objective: To determine the thermic effect of food (TEF) in a Chinese mixed diet in young people. Methods: During the study, the participants were weighed and examined for body composition every morning. The total energy expenditure (TEE) of the participants was measured by the doubly labeled water method for 7 days, and during this period, basal energy expenditure was measured by indirect calorimetry and physical activity energy expenditure was measured by an accelerometer. The value obtained by subtracting basal energy expenditure and physical activity energy expenditure from TEE was used to calculate TEF. Results: Twenty healthy young students (18-30 years; 10 male) participated in the study. The energy intake of the participants was not significantly different from the Chinese Dietary Reference Intake of energy ( P > 0.05). The percentage of energy from protein, fat and carbohydrate were all in the normal range. The intakes of fruits, milk and dietary fiber of the participants were significantly lower than those in the Chinese Dietary Guidelines ( P < 0.05). There was no significant difference in the body weight of the participants during the experiment ( P > 0.05). When adjusted for body weight, there was no significant difference in either TEE or basal energy expenditure between the male and female participants ( P > 0.05). In addition, there was no significant difference in physical activity energy expenditure and TEF between the male and female participants ( P > 0.05). The percentage of TEF in TEE was 8.73%. Conclusion: The percentage of TEF in TEE in a Chinese mixed diet in young people was significantly lower than 10% ( P < 0.001). A value of 10% is usually considered to be the TEF in mixed diets as a percentage of TEE.

Identification of an LDLR variant in a Chinese familial hypercholesterolemia and its relation to ROS/NLRP3-Mediated pyroptosis in hepatic cells.

BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant hereditary disease. Its early diagnosis and intervention significantly improve the patient's quality of life. However, there are few types of research on the FH pathogenic genes in China. METHODS: In this study, we recruited a family diagnosed with FH and used whole exome sequencing (WES) to analyze the proband variants. Intracellular cholesterol level, reactive oxygen species (ROS) level, and the expression of pyroptosis-related genes were detected after overexpression of wild-type or variant LDLR in L02 cells. RESULTS: A heterozygous missense variant predicted to be deleterious to LDLR (c.1879G > A, p.Ala627Thr) was identified in the proband. Mechanistically, intracellular cholesterol level, ROS level, and the expression of pyroptosis-related genes, nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome and components (caspase 1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and NLRP3), gasdermin D (GSDMD), interleukin (IL) -18, IL-1ß was elevated in the variant LDLR group, which was attenuated by inhibition of ROS. CONCLUSIONS: FH is associated with a variant (c.1879G>A, p.Ala627Thr) in the LDLR gene. Regarding the mechanism, the ROS/NLRP3-mediated pyroptosis in hepatic cells may contribute to the pathogenesis of the LDLR variant.

Contrasting effects of different light regimes on the photoreactivities of allochthonous and autochthonous chromophoric dissolved organic matter.

Chromophoric dissolved organic matter (CDOM) plays an important role in ultraviolet (UV) light absorption in the ocean. CDOM is known to originate from either an allochthonous or autochthonous source and has varying compositions and levels of reactivity; however, the effects of individual radiation treatments and the combined effects of UVA and UVB on allochthonous and autochthonous CDOM remain poorly understood. Thus, here, we measured changes in the common optical properties of CDOM collected from China's marginal seas and the Northwest Pacific, using full-spectrum, UVA (315-400 nm), and UVB (280-315 nm) irradiation to induce photodegradation over the same time period (60 h). Excitation-emission matrices (EEMs) combined with parallel factor analysis (PARAFAC) identified four components: marine humic-like C1, terrestrial humic-like C2, soil fulvic-like C3, and tryptophan-like C4. Although the behaviours of these components during full-spectrum irradiation exhibited similar decreasing tendencies, three components (C1, C3, and C4) underwent direct photodegradation under UVB exposure, whereas C2 was more susceptible to UVA degradation. The diverse photoreactivities of the source-dependent components to different light treatments led to differing photochemical behaviours of other optical indices [aCDOM(355), aCDOM(254), SR, HIX, and BIX]. The results indicate that irradiation preferentially reduced the high humification degree or humic substance content of allochthonous DOM, and promoted the transformation from the allochthonous humic DOM components to recently produced components. Although values for the samples from different sources overlapped frequently, principal component analysis (PCA) indicated that the overall optical signatures could be linked to the original CDOM source features. The degradation of CDOM humification, aromaticity, molecular weight, and autochthonous fractions under exposure can drive the CDOM biogeochemical cycle in marine environments. These findings can aid in a better understanding of the effects of different combinations of light treatments and CDOM characteristics on CDOM photochemical processes.

Mesoporous TiO2 Coatings Regulate ZnO Nanoparticle Loading and Zn2+ Release on Titanium Dental Implants for Sustained Osteogenic and Antibacterial Activity.

Two major issues are currently hindering the clinical practice of titanium dental implants for the lack of biological activities: immediate/early loading risks and peri-implantitis. To solve these issues, it is urgent to develop multifunctional implants modified with effective osteogenic and antibacterial properties. Zinc oxide nanoparticles (ZnO NPs) possess superior antibacterial activity; however, they can rapidly release Zn2+, causing cytotoxicity. In this study, a potential dental implant modification was creatively developed as ZnO nanoparticle-loaded mesoporous TiO2 coatings (nZnO/MTC-Ti) via the evaporation-induced self-assembly method (EISA) and one-step spin coating. The mesoporous TiO2 coatings (MTCs) regulated the synthesis and loading of ZnO NPs inside the nanosized pores. The synergistic effects of MTC and ZnO NPs on nZnO/MTC-Ti not only controlled the long-term steady-state release of Zn2+ but also optimized the charge distribution on the surface. Therefore, the cytotoxicity of ZnO NPs was resolved without triggering excessive reactive oxygen species (ROS). The increased extracellular Zn2+ further promoted a favorable intracellular zinc ion microenvironment through the modulation of zinc transporters (ZIP1 and ZnT1). Owing to that, the adhesion, proliferation, and osteogenic activity of bone mesenchymal stem cells (BMSCs) were improved. Additionally, nZnO/MTC-Ti inhibited the proliferation of oral pathogens (Pg and Aa) by inducing bacterial ROS production. For in vivo experiments, different implants were implanted into the alveolar fossa of Sprague-Dawley rats immediately after tooth extraction. The nZnO/MTC-Ti implants were found to possess a higher capability for enhancing bone regeneration, antibiosis, and osseointegration in vivo. These findings suggested the outstanding performance of nZnO/MTC-Ti implants in accelerating osseointegration and inhibiting bacterial infection, indicating a huge potential for solving immediate/early loading risks and peri-implantitis of dental implants.

Transcutaneous Electrical Acupoint Stimulation Improves Postoperative Sleep Quality in Patients Undergoing Laparoscopic Gastrointestinal Tumor Surgery: A Prospective, Randomized Controlled Trial.

INTRODUCTION: This study was conducted to observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the postoperative sleep quality of patients undergoing gastrointestinal tumor surgery and to verify the possible mechanism. METHODS: Eighty-three patients were allocated to the TEAS or Sham group. Patients in the TEAS group received TEAS treatment (disperse-dense waves; frequency, 2/100 Hz) on bilateral Shenmen (HT7), Neiguan (PC6) and Zusanli (ST36) points for 30 min each time, total three times in the perioperative period. In the Sham group, electrodes were placed; however, no current was given. Sleep quality was assessed on the day before surgery (P1) and the first and third days after surgery (D1 and D3) using the Pittsburgh Sleep Quality Index (PSQI) and Athens Insomnia Scale (AIS). Postoperative pain was assessed using visual analog scale (VAS) 72 h postoperatively. The incidences of abdominal distension, dizziness, postoperative nausea and vomiting (PONV) and pulmonary complications were recorded. Serum levels of inflammatory cytokines and the expression of key factors of oxidative stress and key molecules of the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signal pathway were measured. RESULTS: TEAS ameliorated sleep quality at D1 and D3 (PSQI P < 0.05, AIS P < 0.05) and decreased postoperative pain as demonstrated by lower VAS scores compared to the Sham group (P < 0.05). The incidences of abdominal distension and PONV were also lower in the TEAS group. Markers of oxidative stress were increased (P < 0.05), and the serum concentration of interleukin-6 (IL-6) was significantly lower in the TEAS group. The key mediators of the Nrf2/ARE pathway were enhanced after TEAS. CONCLUSION: Perioperative TEAS improved postoperative sleep quality, reduced postoperative pain and alleviated postoperative adverse effects in patients undergoing laparoscopic gastrointestinal tumor surgery resection. This may be associated with activating Nrf2/ARE signal pathway and decreasing its inflammatory actions. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx ), ChiCTR2100054971.

Xenogeneic collagen matrix versus free gingival graft for augmenting keratinized mucosa around posterior mandibular implants: a randomized clinical trial.

OBJECTIVES: To assess the clinical efficacy of xenogeneic collagen matrix (XCM) plus apically positioned flap (APF) in augmenting the keratinized mucosa (KM) width (KMW) and thickness (KMT) around posterior mandibular implants and compare it with free gingival graft (FGG) plus APF. MATERIAL AND METHODS: Thirty patients with KMW ≤ 2 mm in the posterior mandibular implant site were randomly allocated to the FGG group (FGG plus APF) or the XCM group (XCM plus APF). Clinical assessments, including KMW and KMT, shrinkage rate of established KM, and peri-implant soft tissue health, were evaluated during a 6-month follow-up. Additionally, the esthetic outcomes and patient-reported postoperative morbidity were investigated. RESULTS: At 6 months, the KMW measured 3.60 ± 0.79 mm in the FGG group and 3.28 ± 0.96 mm in the XCM group (p = 0.186). Both groups showed a tendency for graft contraction (FGG, 42.11%; XCM, 53.22%). The KMT measured 1.24 ± 0.34 mm in the FGG group and 0.95 ± 0.29 mm in the XCM group, with statistical difference (p = 0.002). No difference in the peri-implant soft tissue health was observed between the two groups (p > 0.05), but the esthetic outcomes were better in the XCM group (p < 0.05). CONCLUSIONS: XCM plus APF rendered a similar clinical efficacy in augmenting KMW as that with FGG plus APF, but with higher shrinkage. XCM plus APF was inferior with respect to FGG plus APF in augmenting KMT. The esthetic outcomes were better with XCM plus APF than FGG plus APF. Clinical relevance XCM plus APF graft was inferior with respect to FGG plus APF in augmenting KMT. TRIAL REGISTRATION: Trial registration number: ChiCTR2200058027 and date: 03/27/2022.