Molecular and biological characterization of a bunyavirus infecting the brown planthopper (Nilaparvata lugens).

A negative-strand symbiotic RNA virus, tentatively named Nilaparvata lugens Bunyavirus (NLBV), was identified in the brown planthopper (BPH, Nilaparvata lugens). Phylogenetic analysis indicated that NLBV is a member of the genus Mobuvirus (family Phenuiviridae, order Bunyavirales). Analysis of virus-derived small interfering RNA suggested that antiviral immunity of BPH was successfully activated by NLBV infection. Tissue-specific investigation showed that NLBV was mainly accumulated in the fat-body of BPH adults. Moreover, NLBV was detected in eggs of viruliferous female BPHs, suggesting the possibility of vertical transmission of NLBV in BPH. Additionally, no significant differences were observed for the biological properties between NLBV-infected and NLBV-free BPHs. Finally, analysis of geographic distribution indicated that NLBV may be prevalent in Southeast Asia. This study provided a comprehensive characterization on the molecular and biological properties of a symbiotic virus in BPH, which will contribute to our understanding of the increasingly discovered RNA viruses in insects.

Mesenchymal stromal cells and their small extracellular vesicles in allergic diseases: From immunomodulation to therapy.

Mesenchymal stromal cells (MSCs) have long been considered a potential tool for treatment of allergic inflammatory diseases, owing to their immunomodulatory characteristics. In recent decades, the medical utility of MSCs has been evaluated both in vitro and in vivo, providing a foundation for therapeutic applications. However, the existing limitations of MSC therapy indicate the necessity for novel therapies. Notably, small extracellular vesicles (sEV) derived from MSCs have emerged rapidly as candidates instead of their parental cells. The acquisition of abundant and scalable MSC-sEV is an obstacle for clinical applications. The potential application of MSC-sEV in allergic diseases has attracted increasing attention from researchers. By carrying biological microRNAs or active proteins, MSC-sEV can modulate the function of various innate and adaptive immune cells. In this review, we summarise the recent advances in the immunomodulatory properties of MSCs in allergic diseases, the cellular sources of MSC-sEV, and the methods for obtaining high-quality human MSC-sEV. In addition, we discuss the immunoregulatory capacity of MSCs and MSC-sEV for the treatment of asthma, atopic dermatitis, and allergic rhinitis, with a special emphasis on their immunoregulatory effects and the underlying mechanisms of immune cell modulation.

METTL3-mediated m6A methylation of SLC38A1 stimulates cervical cancer growth.

The objective of this study was to better characterize the role of the glutamine transporter SLC38A1 in cervical cancer and explore the underlying mechanisms. Data from public databases and clinical cervical cancer tissue samples were used to assess the expression of SLC38A1 and its prognostic significance. Immunohistochemical staining, qRT-PCR, and Western blotting were used to evaluate the expression of relevant genes and proteins. Cell viability, cell cycle, apoptosis, and intracellular glutamine content were measured using CCK-8, flow cytometry, and biochemical assays. Additionally, the RNA immunoprecipitation (RIP) assay was used to examine the impact of METTL3/IGF2BP3 on the m6A modification of the SLC38A1 3'UTR. Both cervical cancer specimens and cells showed significantly increased expression of SLC38A1 and its expression correlated with an unfavorable prognosis. Knockdown of SLC38A1 inhibited cell viability and cell cycle progression, induced apoptosis, and suppressed tumor growth in vivo. Glutaminase-1 inhibitor CB-839 reversed the effects of SLC38A1 overexpression. METTL3 promoted m6A modification of SLC38A1 and enhanced its mRNA stability through IGF2BP3 recruitment. Moreover, METTL3 silencing inhibited cell viability, cell cycle progression, intracellular glutamine content, and induced apoptosis, but these effects were reversed by SLC38A1 overexpression. In conclusion, METTL3-mediated m6A methylation of SLC38A1 stimulates cervical cancer progression. SLC38A1 inhibition is a potential therapeutic strategy for cervical cancer.

Radiogenomic analysis for predicting lymph node metastasis and molecular annotation of radiomic features in pancreatic cancer.

BACKGROUND: To provide a preoperative prediction model for lymph node metastasis in pancreatic cancer patients and provide molecular information of key radiomic features. METHODS: Two cohorts comprising 151 and 54 pancreatic cancer patients were included in the analysis. Radiomic features from the tumor region of interests were extracted by using PyRadiomics software. We used a framework that incorporated 10 machine learning algorithms and generated 77 combinations to construct radiomics-based models for lymph node metastasis prediction. Weighted gene coexpression network analysis (WGCNA) was subsequently performed to determine the relationships between gene expression levels and radiomic features. Molecular pathways enrichment analysis was performed to uncover the underlying molecular features. RESULTS: Patients in the in-house cohort (mean age, 61.3 years ± 9.6 [SD]; 91 men [60%]) were separated into training (n = 105, 70%) and validation (n = 46, 30%) cohorts. A total of 1,239 features were extracted and subjected to machine learning algorithms. The 77 radiomic models showed moderate performance for predicting lymph node metastasis, and the combination of the StepGBM and Enet algorithms had the best performance in the training (AUC = 0.84, 95% CI = 0.77-0.91) and validation (AUC = 0.85, 95% CI = 0.73-0.98) cohorts. We determined that 15 features were core variables for lymph node metastasis. Proliferation-related processes may respond to the main molecular alterations underlying these features. CONCLUSIONS: Machine learning-based radiomics could predict the status of lymph node metastasis in pancreatic cancer, which is associated with proliferation-related alterations.

Geminivirus C4 proteins inhibit GA signaling via prevention of NbGAI degradation, to promote viral infection and symptom development in N. benthamiana.

The phytohormone gibberellin (GA) is a vital plant signaling molecule that regulates plant growth and defense against abiotic and biotic stresses. To date, the molecular mechanism of the plant responses to viral infection mediated by GA is still undetermined. DELLA is a repressor of GA signaling and is recognized by the F-box protein, a component of the SCFSLY1/GID2 complex. The recognized DELLA is degraded by the ubiquitin-26S proteasome, leading to the activation of GA signaling. Here, we report that ageratum leaf curl Sichuan virus (ALCScV)-infected N. benthamiana plants showed dwarfing symptoms and abnormal flower development. The infection by ALCScV significantly altered the expression of GA pathway-related genes and decreased the content of endogenous GA in N. benthamiana. Furthermore, ALCScV-encoded C4 protein interacts with the DELLA protein NbGAI and interferes with the interaction between NbGAI and NbGID2 to prevent the degradation of NbGAI, leading to inhibition of the GA signaling pathway. Silencing of NbGAI or exogenous GA3 treatment significantly reduces viral accumulation and disease symptoms in N. benthamiana plants. The same results were obtained from experiments with the C4 protein encoded by tobacco curly shoot virus (TbCSV). Therefore, we propose a novel mechanism by which geminivirus C4 proteins control viral infection and disease symptom development by interfering with the GA signaling pathway.

Tomato and lemon extracts synergistically improve cognitive function by increasing brain-derived neurotrophic factor levels in aged mice.

Brain ageing, the primary risk factor for cognitive impairment, occurs because of the accumulation of age-related neuropathologies. Identifying effective nutrients that increase cognitive function may help maintain brain health. Tomatoes and lemons have various bioactive functions and exert protective effects against oxidative stress, ageing and cancer. Moreover, they have been shown to enhance cognitive function. In the present study, we aimed to investigate the effects of tomato and lemon ethanolic extracts (TEE and LEE, respectively) and their possible synergistic effects on the enhancement of cognitive function and neurogenesis in aged mice. The molecular mechanisms underlying the synergistic effect of TEE and LEE were investigated. For the in vivo experiment, TEE, LEE or their mixture was orally administered to 12-month-old mice for 9 weeks. A single administration of either TEE or LEE improved cognitive function and neurogenesis in aged mice to some extent, as determined using the novel object recognition test and doublecortin immunohistochemical staining, respectively. However, a significant enhancement of cognitive function and neurogenesis in aged mice was observed after the administration of the TEE + LEE mixture, which had a synergistic effect. N-methyl-d-aspartate receptor 2B, postsynaptic density protein 95, and brain-derived neurotrophic factor (BDNF) levels and tropomyosin receptor kinase B (TrkB)/extracellular signal-regulated kinase (ERK) phosphorylation also synergistically increased after the administration of the mixture compared with those in the individual treatments. In conclusion, compared with their separate treatments, treatment with the TEE + LEE mixture synergistically improved the cognitive function, neurogenesis and synaptic plasticity in aged mice via the BDNF/TrkB/ERK signalling pathway.

Recombinant human adenovirus type 5 promotes anti-tumor immunity via inducing pyroptosis in tumor endothelial cells.

Recombinant human type 5 adenovirus (H101) is an oncolytic virus used to treat nasopharyngeal carcinoma. Owing to the deletion of the E1B-55kD and E3 regions, H101 is believed to selectively inhibit nasopharyngeal carcinoma. Whether H101 inhibits other type of tumors via different mechanisms remains unclear. In this study we investigated the effects of H101 on melanomas. We established B16F10 melanoma xenograft mouse model, and treated the mice with H101 (1 × 108 TCID50) via intratumoral injection for five consecutive days. We found that H101 treatment significantly inhibited B16F10 melanoma growth in the mice. H101 treatment significantly increased the infiltration of CD8+ T cells and reduced the proportion of M2-type macrophages. We demonstrated that H101 exhibited low cytotoxicity against B16F10 cells, but the endothelial cells were more sensitive to H101 treatment. H101 induced endothelial cell pyroptosis in a caspase-1/GSDMD-dependent manner. Furthermore, we showed that the combination of H101 with the immune checkpoint inhibitor PD-L1 antibody (10 mg/kg, i.p., every three days for three times) exerted synergic suppression on B16F10 tumor growth in the mice. This study demonstrates that, in addition to oncolysis, H101 inhibits melanoma growth by promoting anti-tumor immunity and inducing pyroptosis of vascular endothelial cells.

Intranasal delivery of small extracellular vesicles reduces the progress of amyotrophic lateral sclerosis and the overactivation of complement-coagulation cascade and NF-ĸB signaling in SOD1G93A mice.

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive motoneuron degeneration, and effective clinical treatments are lacking. In this study, we evaluated whether intranasal delivery of mesenchymal stem cell-derived small extracellular vesicles (sEVs) is a strategy for ALS therapy using SOD1G93A mice. In vivo tracing showed that intranasally-delivered sEVs entered the central nervous system and were extensively taken up by spinal neurons and some microglia. SOD1G93A mice that intranasally received sEV administration showed significant improvements in motor performances and survival time. After sEV administration, pathological changes, including spinal motoneuron death and synaptic denervation, axon demyelination, neuromuscular junction degeneration and electrophysiological defects, and mitochondrial vacuolization were remarkably alleviated. sEV administration attenuated the elevation of proinflammatory cytokines and glial responses. Proteomics and transcriptomics analysis revealed upregulation of the complement and coagulation cascade and NF-ĸB signaling pathway in SOD1G93A mouse spinal cords, which was significantly inhibited by sEV administration. The changes were further confirmed by detecting C1q and NF-ĸB expression using Western blots. In conclusion, intranasal administration of sEVs effectively delays the progression of ALS by inhibiting neuroinflammation and overactivation of the complement and coagulation cascades and NF-ĸB signaling pathway and is a potential option for ALS therapy.

Association of urinary and seminal plasma vanadium concentrations with semen quality: A repeated-measures study of 1135 healthy men.

Although animal studies have shown the reproductive toxicity of vanadium, less is known about its effects on semen quality in humans. Among 1135 healthy men who were screened as potential semen donors, we investigated the relationships of semen quality with urinary and seminal plasma vanadium levels via inductively coupled plasma-mass spectrometry (ICP-MS). Spearman rank correlation tests and linear regression models were used to assess the correlations between average urinary and within-individual pooled seminal plasma vanadium concentrations (n = 1135). We utilized linear mixed-effects models to evaluate the associations of urinary and seminal plasma vanadium levels (n = 1135) with repeated sperm quality parameters (n = 5576). Seminal plasma vanadium concentrations were not significantly correlated with urinary vanadium concentrations (r = 0.03). After adjusting for possible confounders, we observed inverse relationships of within-individual pooled seminal plasma vanadium levels with total count, semen volume, and sperm concentration (all P values for trend < 0.05). Specifically, subjects in the highest (vs. lowest) tertile of seminal plasma vanadium concentrations had - 11.3% (-16.4%, -5.9%), - 11.1% (-19.1%, -2.4%), and - 20.9% (-29.0%, -11.8%) lower sperm volume, concentration, and total count, respectively; moreover, urinary vanadium levels appeared to be negatively associated with sperm motility. These relationships showed monotonically decreasing dose-response patterns in the restricted cubic spline analyses. Our results demonstrated a poor correlation between urinary and seminal plasma levels of vanadium, and elevated vanadium concentrations in urine and seminal plasma may be adversely related to male semen quality.

Mesenchymal stromal cells-derived small extracellular vesicles modulate DC function to suppress Th2 responses via IL-10 in patients with allergic rhinitis.

Mesenchymal stromal cells (MSCs) are well known for their immunoregulatory roles on allergic inflammation particularly by acting on T cells, B cells, and dendritic cells (DCs). MSC-derived small extracellular vesicles (MSC-sEV) are increasingly considered as one of the main factors for the effects of MSCs on immune responses. However, the effects of MSC-sEV on DCs in allergic diseases remain unclear. MSC-sEV were prepared from the induced pluripotent stem cells (iPSC)-MSCs by anion-exchange chromatography, and were characterized with the size, morphology, and specific markers. Human monocyte-derived DCs were generated and cultured in the presence of MSC-sEV to differentiate the so-called sEV-immature DCs (sEV-iDCs) and sEV-mature DCs (sEV-mDCs), respectively. The phenotypes and the phagocytic ability of sEV-iDCs were analyzed by flow cytometry. sEV-mDCs were co-cultured with isolated CD4+ T cells or peripheral blood mononuclear cells (PBMCs) from patients with allergic rhinitis. The levels of Th1 and Th2 cytokines produced by T cells were examined by ELISA and intracellular flow staining. And the following mechanisms were further investigated. We demonstrated that MSC-sEV inhibited the differentiation of human monocytes to iDCs with downregulation of the expression of CD40, CD80, CD86, and HLA-DR, but had no effects on mDCs with these markers. However, MSC-sEV treatment enhanced the phagocytic ability of mDCs. More importantly, using anti-IL-10 monoclonal antibody or IL-10Rα blocking antibody, we identified that sEV-mDCs suppressed the Th2 immune response by reducing the production of IL-4, IL-9, and IL-13 via IL-10. Furthermore, sEV-mDCs increased the level of Treg cells. Our study identified that mDCs treated with MSC-sEV inhibited the Th2 responses, providing novel evidence of the potential cell-free therapy acting on DCs in allergic airway diseases.

Au Nanowires Decorated Ultrathin Co3 O4 Nanosheets toward Light-Enhanced Nitrate Electroreduction.

Nitrate is a reasonable alternative instead of nitrogen for ammonia production due to the low bond energy, large water-solubility, and high chemical polarity for good absorption. Nitrate electroreduction reaction (NO3 RR) is an effective and green strategy for both nitrate treatment and ammonia production. As an electrochemical reaction, the NO3 RR requires an efficient electrocatalyst for achieving high activity and selectivity. Inspired by the enhancement effect of heterostructure on electrocatalysis, Au nanowires decorated ultrathin Co3 O4 nanosheets (Co3 O4 -NS/Au-NWs) nanohybrids are proposed for improving the efficiency of nitrate-to-ammonia electroreduction. Theoretical calculation reveals that Au heteroatoms can effectively adjust the electron structure of Co active centers and reduce the energy barrier of the determining step (*NO → *NOH) during NO3 RR. As the result, the Co3 O4 -NS/Au-NWs nanohybrids achieve an outstanding catalytic performance with high yield rate (2.661 mg h-1 mgcat -1 ) toward nitrate-to-ammonia. Importantly, the Co3 O4 -NS/Au-NWs nanohybrids show an obviously plasmon-promoted activity for NO3 RR due to the localized surface plasmon resonance (LSPR) property of Au-NWs, which can achieve an enhanced NH3 yield rate of 4.045 mg h-1 mgcat -1 . This study reveals the structure-activity relationship of heterostructure and LSPR-promotion effect toward NO3 RR, which provide an efficient nitrate-to-ammonia reduction with high efficiency.

The Src1-PGC1α-AP1 complex-dependent secretion of substance P induces inflammation and apoptosis in encephalomyocarditis virus-infected mice.

Substance P (SP), a neuropeptide consisting of 11 amino acid residues, is involved in the pathogenesis of encephalomyocarditis virus (EMCV)-induced myocarditis by stimulating the production of proinflammatory cytokines. However, the underlying mechanism that regulates SP production is still unknown. In this study, we report the transcriptional regulation of the Tachykinin Precursor 1 (TAC1) gene that encodes SP by a transcriptional complex composed of Steroid Receptor Coactivator 1 (Src1), Peroxisome proliferator-activated receptor-gamma coactivator 1 (PGC1α), and Activator Protein 1 (AP1) transcription factor. Infection of mice with EMCV induced the accumulation of PGC1α and increased TAC1 expression, thereby promoting the secretion of SP, initiating apoptosis, and elevating proinflammatory cytokine levels. In vitro overexpression of the Src1-PGC1α-AP1 members also induced TAC1 expression, increased the SP concentration, initiated apoptosis, and elevated proinflammatory cytokine concentrations. Depletion or inhibition of the Src1-PGC1α-AP1 complex reversed these effects. The administration of gossypol, an Src1 inhibitor, or SR1892, a PGC1α inhibitor, to EMCV-infected mice attenuated myocarditis. Taken together, our results reveal that the upregulation of TAC1 and the secretion of SP in EMCV-induced myocarditis are dependent on the Src1-PGC1α-AP1 complex. Targeting the Src1-PGC1α-AP1 complex may represent a new therapeutic strategy for myocarditis.

Geographical origin of Plasmodium vivax in the Hainan Island, China: insights from mitochondrial genome.

BACKGROUND: Hainan Province, China, has been an endemic region with high transmission of Plasmodium falciparum and Plasmodium vivax. Indigenous malaria caused by P. vivax was eliminated in Hainan in 2011, while imported vivax malaria remains. However, the geographical origin of P. vivax cases in Hainan remains unclear. METHODS: Indigenous and imported P. vivax isolates (n = 45) were collected from Hainan Province, and the 6 kb mitochondrial genome was obtained. Nucleotide (π) and haplotype (h) diversity were estimated using DnaSP. The numbers of synonymous nucleotide substitutions per synonymous site (dS) and nonsynonymous nucleotide substitutions per nonsynonymous site (dN) were calculated using the SNAP program. Arlequin software was used to estimate the genetic diversity index and assess population differentiation. Bayesian phylogenetic analysis of P. vivax was performed using MrBayes. A haplotype network was generated using the NETWORK program. RESULTS: In total, 983 complete mitochondrial genome sequences were collected, including 45 from this study and 938 publicly available from the NCBI. Thirty-three SNPs were identified, and 18 haplotypes were defined. The haplotype (0.834) and nucleotide (0.00061) diversity in the Hainan populations were higher than China's Anhui and Guizhou population, and the majority of pairwise FST values in Hainan exceeded 0.25, suggesting strong differentiation among most populations except in Southeast Asia. Most Hainan haplotypes were connected to South/East Asian and China's others haplotypes, but less connected with populations from China's Anhui and Guizhou provinces. Mitochondrial lineages of Hainan P. vivax belonged to clade 1 of four well-supported clades in a phylogenetic tree, most haplotypes of indigenous cases formed a subclade of clade 1, and the origin of seven imported cases (50%) could be inferred from the phylogenetic tree, but five imported cases (42.8%) could not be traced using the phylogenetic tree alone, necessitating epidemiological investigation. CONCLUSIONS: Indigenous cases in Hainan display high genetic (haplotype and nucleotide) diversity. Haplotype network analysis also revealed most haplotypes in Hainan were connected to the Southeast Asian populations and divergence to a cluster of China's other populations. According to the mtDNA phylogenetic tree, some haplotypes were shared between geographic populations, and some haplotypes have formed lineages. Multiple tests are needed to further explore the origin and expansion of P. vivax populations.

Nongenetic and genetic predictors of haemodynamic instability induced by propofol and opioids: A retrospective clinical study.

AIM: Propofol and opioids are commonly used in anaesthesia, but are highly susceptible to haemodynamic instability, thereby threatening the patient's surgical safety and prognosis. The purpose of this study was to investigate the predictors of haemodynamic instability and establish its predictive model. METHODS: A total of 150 Chinese patients undergoing thyroid or breast surgery participated in the study, with target-controlled infusion concentrations of propofol, opioids dosage, heart rate (HR), mean arterial pressure (MAP) and Narcotrend Index recorded at key points throughout the procedure. The Agena MassARRAY system was used to genotype candidate single nucleotide polymorphisms related to pharmacodynamics and pharmacokinetics of propofol and opioids. RESULTS: Among nongenetic factors, baseline HR (R = -.579, P < .001) and baseline MAP (R = -.725, P < .001) had a significant effect on the haemodynamic instability. Among genetic factors, the CT/CC genotype of GABRB1 rs4694846 (95% confidence interval [CI]: -11.309 to -3.155), AA/AG of OPRM1 rs1799971 (95%CI: 0.773 to 10.290), AA of CES2 rs8192925 (95%CI: 1.842 to 9.090) were associated with higher HR instability; the AA/GG genotype of NR1I2 rs6438550 (95%CI: 0.351 to 7.761), AA of BDNF rs2049046 (95%CI: -9.039 to -0.640) and GG of GABBR2 rs1167768 (95%CI: -10.146 to -1.740) were associated with higher MAP instability. The predictive models of HR and MAP fluctuations were developed, accounting for 45.0 and 59.2% of variations, respectively. CONCLUSION: We found that cardiovascular fundamentals and genetic variants of GABRB1, GABBR2, OPRM1, BDNF, CES2 and NR1I2 are associated with cardiovascular susceptibility, which can provide a reference for haemodynamic management in clinical anaesthesia.

P2X7 receptor involved in antitumor activity of atractylenolide I in human cervical cancer cells.

Atractylenolide I (Atr-I) was found to sensitize a variety of human cancer cells in previous studies. Purinergic P2X7R plays important role in different cancers. However, whether Atr-I could generate antitumor activity in human cervical cancer cells and P2X7R get involved in this effect remain unclear. In this study, Hela (HPV 18 +) and SiHa (HPV 16 +) cells were treated with different doses of Atr-I. The results indicated that agonist and antagonist of P2X7 receptors, BzATP and JNJ-47965567 (JNJ), could suppress the proliferation of Hela and SiHa cells. Atr-I demonstrated a considerable antitumor effect in both human cervical cancer cells in vitro. Atr-I combined with P2X7R agonist, BzATP, restored Atr-I-induced growth inhibition in Hela cells but not in SiHa cells. However, the combinatorial treatment of P2X7R antagonist JNJ and Atr-I has an additive effect on cell growth inhibition in SiHa cells rather than in Hela cells. It implied that P2X7R would get involved in the anti-human cervical cancer cells effect of Atr-I.

1D Chiral Enantiomer Lead-Free Perovskites Induced Chiralopical Activity and Photoelectric Response.

Chirality is a fascinating geometrical concept with widespread applications in biology, chemistry, and materials. Incorporating chirality into hybrid perovskite materials can induce novel physical properties (chiral optical activity, nonlinear optics, etc.). Hybrid lead-free or lead-substituted perovskite materials, as representatives of perovskites, have been widely used in fields such as photovoltaics, sensors, catalysis, and detectors. However, the successful introduction of chirality into hybrid lead-free perovskites, which can enable their potential applications in areas such as circularly polarized light photodetectors, memories, and spin transistors, remains a challenging research topic. Here, we synthesized two new chiral lead-free perovskites, [(R)-2-methylpiperazine][BiI5] and [(S)-2-methylpiperazine][BiI5]. The material possesses a perovskite structure with a one-dimensional (1D) arrangement, denoted as ABX5. This structure is composed of chiral cations, specifically methylpiperazine, and endless chains of [BiI3] along the a-axis. These chains are assembled from distorted coplanar [BiI5]2- octahedra. The testing results revealed that (R)-1 and (S)-1 have narrow band gaps (Eg-R = 2.016 eV, Eg-S = 1.964 eV), high photoelectric response, and long carrier lifetime [R = 4.94 µs (τ), S = 7.85 µs (τ)]. It is worth noting that 1D chiral lead-free perovskites (R)-1 and (S)-1, which are synthesized in this study with narrow band gaps, high photoelectric response, and long carrier lifetime, have the potential to serve as alternative materials for the perovskite layer in future iterations of lead-free perovskite solar cells. Moreover, this research will inspire the preparation of multifunctional, lead-free perovskites.

Saliva - a new opportunity for fluid biopsy.

Saliva is a complex biological fluid with a variety of biomolecules, such as DNA, RNA, proteins, metabolites and microbiota, which can be used for the screening and diagnosis of many diseases. In addition, saliva has the characteristics of simple collection, non-invasive and convenient storage, which gives it the potential to replace blood as a new main body of fluid biopsy, and it is an excellent biological diagnostic fluid. This review integrates recent studies and summarizes the research contents of salivaomics and the research progress of saliva in early diagnosis of oral and systemic diseases. This review aims to explore the value and prospect of saliva diagnosis in clinical application.

Nanocomposite Hydrogels in Regenerative Medicine: Applications and Challenges.

Regenerative medicine is a highly regarded multidisciplinary field that aims to transform the future of clinical medicine through curative strategies rather than palliative therapies. As an emerging field, the development of regenerative medicine cannot be achieved without multifunctional biomaterials. Among the various bioscaffold materials, hydrogels are one of the materials of interest in bioengineering and medical research because of their similarity to the natural extracellular matrix and good biocompatibility. However, conventional hydrogels have simple internal structures and single cross-linking modes, which require improvement in a single function and structural stability. Introducing multifunctional nanomaterials into 3D hydrogel networks physically or chemically avoids their disadvantages. Nanomaterials (NMs) are materials in the size range of 1-100 nm with distinct physical and chemical properties that differ from that of the macroscopic size and enable hydrogels to exhibit multifunctionality. Although regenerative medicine and hydrogels have been well researched in their respective fields, the connection between nanocomposite hydrogels (NCHs) and regenerative medicine has not been elaborated. Therefore, this review briefly describes the preparation and design requirements of NCHs and discusses their applications and challenges in regenerative medicine, hoping to clarify the relationship between the two.

MicroRNA-19b-3p dysfunction of mesenchymal stem cell-derived exosomes from patients with abdominal aortic aneurysm impairs therapeutic efficacy.

Senescence of vascular smooth muscle cells (VSMCs) contributes to the formation of abdominal aortic aneurysm (AAA). Although mesenchymal stem cell exosomes (MSC-EXO) have been confirmed to restrict the development of AAA, their biological activity depends largely on the physiological state of the MSCs. This study aimed to compare the effects of adipose-derived MSC-EXO from healthy donors (HMEXO) and AAA patients (AMEXO) on senescence of VSMCs in AAA and explore the underlying mechanisms. An ApoE-/- mouse model of AAA was used to investigate the therapeutic effects of HMEXO, AMEXO or miR-19b-3p-AMEXO on AAA development. This in vitro model of AAA was established by treating VSMCs with Ang II (Angiotensin II). The senescence of VSMCs was determined by senescence-associated ß-galactosidase (SA-ß-gal) staining. The morphology of mitochondria in VSMCs was examined by MitoTracker staining. HMEXO exhibited superior capacity compared with AMEXO to inhibit VSMC senescence and attenuate AAA formation in Ang II-treated ApoE-/- mice. In vitro, both AMEXO and HMEXO inhibited Ang II-induced VSMC senescence via downregulation of mitochondrial fission. Notably, compared with HMEXO, the ability of AMEXO to inhibit VSMC senescence was significantly decreased. miRNA sequencing and the expression of miR-19b-3p was significantly decreased in AMEXO compared with HMEXO. Luciferase assay suggested that MST4 (Mammalian sterile-20-like kinase 4) is a potential target of miR-19b-3p. Mechanistically, miR-19b-3p in HMEXO ameliorated VSMC senescence by inhibiting mitochondrial fission via regulation of the MST4/ERK/Drp1 signaling pathway. Overexpression of miR-19b-3p in AMEXO improved their beneficial effect on AAA formation. Our study reveals that MSC-exosomal miR-19b-3p exerts protective effects against Ang II-induced AAA and VSMC senescence via regulation of the MST4/ERK/Drp1 pathway. The pathological state of AAA patients alters the miRNA components of AMEXO and impairs their therapeutic benefits.

Impact of ultraviolet radiation on cardiovascular and metabolic disorders: The role of nitric oxide and vitamin D.

BACKGROUND/PURPOSE: Ultraviolet (UV) radiation has both harmful and beneficial effects on human skin and health. It causes skin damage, aging, and cancer; however, it is also a primary source of vitamin D. Additionally, UV radiation can impact energy metabolism and has protective effects on several cardiovascular and metabolic disorders in mice and humans. However, the mechanisms of UV protection against these diseases have not been clearly identified. METHODS: This review summarizes the systemic effects of UV radiation on hypertension and several metabolic diseases such as obesity, diabetes, and nonalcoholic fatty liver disease (NAFLD) in mice, and we also consider the mechanisms of action of the related regulators nitric oxide (NO) and vitamin D. RESULTS: UV exposure can lower blood pressure and prevent the development of cardiovascular diseases and metabolic disorders, such as metabolic syndrome, obesity, and type 2 diabetes, primarily through mechanisms that depend on UV-induced NO. UV radiation may also effectively delay the onset of type 1 diabetes through mechanisms that rely on UV-induced vitamin D. UV-induced NO and vitamin D play roles in preventing and slowing the progression of NAFLD. CONCLUSION: UV exposure is a promising nonpharmacological intervention for cardiovascular and metabolic disorders. NO and vitamin D may play a crucial role in mediating these effects. However, further investigations are required to elucidate the exact mechanisms and determine the optimal dosage and exposure duration of UV radiation.