Progress of uric acid in cardiovascular disease.

Due to the global prevalence of hyperuricemia (HUA), there is growing interest in research on uric acid (UA). HUA is a common condition that has various adverse consequences, including gout and kidney disease. However, recent studies have also implicated UA in the development of cardiovascular diseases (CVD) such as atrial fibrillation (AF) and coronary heart disease (CHD). Experimental and clinical research has extensively demonstrated the detrimental effects of elevated serum UA levels on cardiovascular health. Furthermore, serum UA levels have been identified as predictors of CVD outcomes following percutaneous coronary intervention (PCI) and catheter ablation. Additionally, the use of UA-lowering therapy holds important implications for the management of CVD. This review aims to consolidate the current evidence on the relationship between serum UA and CVD.

Rotating Sonotrode Design for Ultrasonic-Assisted Arc Welding of Metal Materials.

In the process of the ultrasonic-assisted arc welding of metal materials, traditional ultrasonic application methods, such as the low-frequency impact of ultrasonic horns on a base material, can easily cause the non-fusion defect. In order to solve this problem, a rotating sonotrode with a groove and double thin ends was designed in this study. The ultrasonic vibration is transmitted into the weld pool by the rolling of the sonotrode on both sides of the weld. The resonant frequency was set at 50 kHz. Firstly, based on the Mindlin theory, a rotating sonotrode without a groove was designed by solving the frequency equation and by conducting a finite element simulation. Secondly, the effects of the groove, perforation, and transition mode on the resonant frequency, stress distribution, and amplification factor were investigated by finite element simulation. Finally, the optimum rotating sonotrode with a groove was obtained. The results show that the size of a rotating sonotrode that has a small frequency error can be obtained by using the discrete interval solver method combined with finite element simulation. The groove can significantly reduce the resonant frequency. The stress concentration can be effectively reduced by using the elliptical transition mode. The resonant frequency and amplification factor of a rotating sonotrode with a groove could be effectively adjusted by a method of double-position joint perforation. The final resonant frequency was 49.721 kHz and the amplification factor was 3.02. This study provides an effective design method for a sonotrode with double thin ends and a groove structure.

Circulating Immune Landscape Profiling in Psoriasis Vulgaris and Psoriatic Arthritis by Mass Cytometry.

Background: Psoriasis, a systemic disorder mediated by the immune system, can appear on the skin, joints, or both. Individuals with cutaneous psoriasis (PsC) have an elevated risk of developing psoriatic arthritis (PsA) during their lifetime. Despite this known association, the cellular and molecular mechanisms underlying this progression remain unclear. Methods: We performed high-dimensional, in-depth immunophenotyping of peripheral blood mononuclear cells (PBMCs) in patients with PsA and psoriasis vulgaris (PsV) by mass cytometry. Blood samples were collected before and after therapy for a longitudinal study. Then three sets of comparisons were made here: active PsA vs. active PsV, untreated PsV vs. treated PsV, and untreated PsA vs. treated PsA. Results: Marked differences were observed in multiple lymphocyte subsets of PsA related to PsV, with expansion of CD4+ T cells, CD16- NK cells, and B cells. Notably, two critical markers, CD28 and CD127, specifically differentiated PsA from PsV. The expression levels of CD28 and CD127 on both Naïve T cells (TN) and central memory CD4+ T cells (TCM) were considerably higher in PsA than PsV. Meanwhile, after treatment, patients with PsV had higher levels of CD28hi CD127hi CD4+ TCM cells, CD28hi CD127hi CD4+ TN cells, and CD16- NK cells. Conclusion: In the circulation of PsA patients, the TN and CD4+ TCM are characterized with more abundant CD28 and CD127, which effectively distinguished PsA from PsV. This may indicate that individuals undergoing PsV could be stratified at high risk of developing PsA based on the circulating levels of CD28 and CD127 on specific cell subsets.

A peptide selectively recognizes Gram-negative bacteria and forms a bacterial extracellular trap (BET) through interfacial self-assembly.

An innate immune system intricately leverages unique mechanisms to inhibit colonization of external invasive Bacteria, for example human defensin-6, through responsive encapsulation of bacteria. Infection and accompanying antibiotic resistance stemming from Gram-negative bacteria aggregation represent an emerging public health crisis, which calls for research into novel anti-bacterial therapeutics. Herein, inspired by naturally found host-defense peptides, we design a defensin-like peptide ligand, bacteria extracellular trap (BET) peptide, with modular design composed of targeting, assembly, and hydrophobic motifs with an aggregation-induced emission feature. The ligand specifically recognizes Gram-negative bacteria via targeting cell wall conserved lipopolysaccharides (LPS) and transforms from nanoparticles to nanofibrous networks in situ to trap bacteria and induce aggregation. Importantly, treatment of the BET peptide was found to have an antibacterial effect on the Pseudomonas aeruginosa strain, which is comparable to neomycin. Animal studies further demonstrate its ability to trigger aggregation of bacteria in vivo. This biomimetic self-assembling BET peptide provides a novel approach to fight against pathogenic Gram-negative bacteria.

Can green funds improve corporate environmental, social, and governance performance? Evidence from Chinese-listed companies.

Green funds play pivotal roles in driving corporate sustainable development. Utilizing data from Chinese publicly listed companies from 2010 to 2021, we examine the impact of green funds on corporate environmental, social, and governance (ESG) performance and the underlying mechanisms. The research findings claim that green funds positively affect corporate ESG performance. Mechanism analysis systematically demonstrates that green funds contribute to elevated corporate ESG performance by alleviating financial constraints, enhancing managerial efficiency, and fostering green innovation. Heterogeneity analysis further underscores that the effect of green funds is particularly potent in companies with high external attention. Furthermore, green funds also play significant roles in production capabilities and economic value. This research enriches the micro-level evidence on the development of green funds and furnishes substantial implications for sustainable development.

Canagliflozin regulates metabolic reprogramming in diabetic kidney disease by inducing fasting-like and aestivation-like metabolic patterns.

AIMS/HYPOTHESIS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2i) are antihyperglycaemic drugs that protect the kidneys of individuals with type 2 diabetes mellitus. However, the underlying mechanisms mediating the renal benefits of SGLT2i are not fully understood. Considering the fuel switches that occur during therapeutic SGLT2 inhibition, we hypothesised that SGLT2i induce fasting-like and aestivation-like metabolic patterns, both of which contribute to the regulation of metabolic reprogramming in diabetic kidney disease (DKD). METHODS: Untargeted and targeted metabolomics assays were performed on plasma samples from participants with type 2 diabetes and kidney disease (n=35, 11 women) receiving canagliflozin (CANA) 100 mg/day at baseline and 12 week follow-up. Next, a systematic snapshot of the effect of CANA on key metabolites and pathways in the kidney was obtained using db/db mice. Moreover, the effects of glycine supplementation in db/db mice and human proximal tubular epithelial cells (human kidney-2 [HK-2]) cells were studied. RESULTS: Treatment of DKD patients with CANA for 12 weeks significantly reduced HbA1c from a median (interquartile range 25-75%) of 49.0 (44.0-57.0) mmol/mol (7.9%, [7.10-9.20%]) to 42.2 (39.7-47.7) mmol/mol (6.8%, [6.40-7.70%]), and reduced urinary albumin/creatinine ratio from 67.8 (45.9-159.0) mg/mmol to 47.0 (26.0-93.6) mg/mmol. The untargeted metabolomics assay showed downregulated glycolysis and upregulated fatty acid oxidation. The targeted metabolomics assay revealed significant upregulation of glycine. The kidneys of db/db mice undergo significant metabolic reprogramming, with changes in sugar, lipid and amino acid metabolism; CANA regulated the metabolic reprogramming in the kidneys of db/db mice. In particular, the pathways for glycine, serine and threonine metabolism, as well as the metabolite of glycine, were significantly upregulated in CANA-treated kidneys. Glycine supplementation ameliorated renal lesions in db/db mice by inhibiting food intake, improving insulin sensitivity and reducing blood glucose levels. Glycine supplementation improved apoptosis of human proximal tubule cells via the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. CONCLUSIONS/INTERPRETATION: In conclusion, our study shows that CANA ameliorates DKD by inducing fasting-like and aestivation-like metabolic patterns. Furthermore, DKD was ameliorated by glycine supplementation, and the beneficial effects of glycine were probably due to the activation of the AMPK/mTOR pathway.

Immune-like sandwich multiple hotspots SERS biosensor for ultrasensitive detection of NDKA biomarker in serum.

Developing the rapid, specific, and sensitive tumor marker NDKA biosensor has become an urgent need in the field of early diagnosis of colorectal cancer (CRC). Surface-enhanced Raman spectroscopy (SERS) with the advantages of high sensitivity, high resolution as well as providing sample fingerprint, enables rapid and sensitive detection of tumor markers. However, many SERS biosensors rely on boosting the quantity of Raman reporter molecules on individual nanoparticle surfaces, which can result in nanoparticle agglomeration, diminishing the stability and sensitivity of NDKA detection. Here, we proposed an immune-like sandwich multiple hotspots SERS biosensor for highly sensitive and stable analysis of NDKA in serum based on molecularly imprinted polymers and NDKA antibody. The SERS biosensor employs an array of gold nanoparticles, which are coated with a biocompatible polydopamine molecularly imprinted polymer as a substrate to specifically capture NDKA. Then the biosensor detects NDKA through Raman signals as a result of the specific binding of NDKA to the SERS nanotag affixed to the capture substrate along with the formation of multiple hotspots. This SERS biosensor not only avoids the aggregation of nanoparticles but also presents a solution to the obstacles encountered in immune strategies for certain proteins lacking multiple antibody or aptamer binding sites. Furthermore, the practical application of the SERS biosensor is validated by the detection of NDKA in serum with the lower limit of detection (LOD) of 0.25 pg/mL, meanwhile can detect NDKA of 10 ng/mL in mixed proteins solution, illustrating high sensitivity and specificity. This immune-like sandwich multiple hotspots biosensor makes it quite useful for the early detection of CRC and also provides new ideas for cancer biomarker sensing strategy in the future.

Correlation between carcinoembryonic antigen (CEA) expression and EGFR mutations in non-small-cell lung cancer: a meta-analysis.

OBJECTIVES: The purpose of this meta-analysis was to investigate the relationship between serum carcinoembryonic antigen (CEA) expression and epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC). METHODS: Databases such as PubMed, Cochrane, EMBASE and Google Scholar were systematically searched to identify studies assessing the association of serum CEA expression with EGFR mutations. Across 19 studies, 4168 patients were included between CEA expression and EGFR mutations odds ratio (OR) conjoint analysis of correlations. RESULTS: Compared with CEA-negative NSCLC, CEA-positive tumors had an increased EGFR mutation rate (OR = 1.85, 95% confidence interval: 1.48-2.32, P < 0.00001). This association was observed in both stage IIIB/IV patients (OR = 1.60, 95% CI: 1.18-2.15, P = 0.002) and stage I-IIIA (OR = 1.67, 95% CI: 1.01-2.77, P = 0.05) patients. In addition, CEA expression was associated with exon 19 (OR = 1.97, 95% CI: 1.25-3.11, P = 0.003) and exon 21 (OR = 1.51, 95% CI: 1.07-2.12, P = 0.02) EGFR mutations. In ADC pathological type had also showed the correlation (OR = 1.84, 95% CI: 1.31-2.57, P = 0.0004). CONCLUSIONS: This meta-analysis indicated that serum CEA expression was associated with EGFR mutations in NSCLC patients. The results of this study suggest that CEA level may play a predictive role in the EGFR mutation status of NSCLC patients. Detecting serum CEA expression levels can give a good suggestion to those patients who are confused about whether to undergo EGFR mutation tests. Moreover, it may help better plan of the follow-up treatment.

Canagliflozin improves fatty acid oxidation and ferroptosis of renal tubular epithelial cells via FOXA1-CPT1A axis in diabetic kidney disease.

Impaired fatty acid oxidation (FAO) is a metabolic hallmark of renal tubular epithelial cells (RTECs) under diabetic conditions. Disturbed FAO may promote cellular oxidative stress and insufficient energy production, leading to ferroptosis subsequently. Canagliflozin, an effective anti-hyperglycemic drug, may exert potential reno-protective effects by upregulating FAO and inhibiting ferroptosis in RTECs. However, the mechanisms involved remain unclear. The present study is aimed to characterize the detailed mechanisms underlying the impact of canagliflozin on FAO and ferroptosis. Type 2 diabetic db/db mice were administrated daily by gavage with canagliflozin (20 mg/kg/day, 40 mg/kg/day) or positive control drug pioglitazone (10 mg/kg/day) for 12 weeks. The results showed canagliflozin effectively improved renal function and structure, reduced lipid droplet accumulation, enhanced FAO with increased ATP contents and CPT1A expression, a rate-limiting enzyme of FAO, and relieved ferroptosis in diabetic mice. Moreover, overexpression of FOXA1, a transcription factor related with lipid metabolism, was observed to upregulate the level of CPT1A, and further alleviated ferroptosis in high glucose cultured HK-2 cells. Whereas FOXA1 knockdown had the opposite effect. Mechanistically, chromatin immunoprecipitation assay and dual-luciferase reporter gene assay results demonstrated that FOXA1 transcriptionally promoted the expression of CPT1A through a sis-inducible element located in the promoter region of the protein. In conclusion, these data suggest that canagliflozin improves FAO and attenuates ferroptosis of RTECs via FOXA1-CPT1A axis in diabetic kidney disease.

A Homochiral Fulgide Organic Ferroelectric Crystal with Photoinduced Molecular Orbital Breaking.

Thermally triggered spatial symmetry breaking in traditional ferroelectrics has been extensively studied for manipulation of the ferroelectricity. However, photoinduced molecular orbital breaking, which is promising for optical control of ferroelectric polarization, has been rarely explored. Herein, for the first time, we synthesized a homochiral fulgide organic ferroelectric crystal (E)-(R)-3-methyl-3-cyclohexylidene-4-(diphenylmethylene)dihydro-2,5-furandione (1), which exhibits both ferroelectricity and photoisomerization. Significantly, 1 shows a photoinduced reversible change in its molecular orbitals from the 3 π molecular orbitals in the open-ring isomer to 2 π and 1 σ molecular orbitals in the closed-ring isomer, which enables reversible ferroelectric domain switching by optical manipulation. To our knowledge, this is the first report revealing the manipulation of ferroelectric polarization in homochiral ferroelectric crystal by photoinduced breaking of molecular orbitals. This finding sheds light on the exploration of molecular orbital breaking in ferroelectrics for optical manipulation of ferroelectricity.

Large Phase-Transition Temperature Enhancement Achieved in a Layered Lead Iodide Hybrid Crystal by H/F Substitution.

Organic-inorganic hybrid metal halides with structural flexibility and solution processability have been widely investigated for different application scenarios. However, the effective construction of phase-transition materials with a high phase-transition temperature (Ttr) for potential practical applications remains a great challenge, and reports on the regulation of Ttr with significant enhancement have been rare. In this manuscript, we have realized a large Ttr increase of 148 K in a layered hybrid lead iodide crystal (4-FTMBA)4Pb3I10 (4-FTMBA = 4-fluoro-N,N,N-trimethylbenzenaminium) by the H/F substitution strategy. Compared to the parent (TMBA)4Pb3I10 (TMBA = N,N,N-trimethylbenzenaminium), H/F substitution preserves the structural framework and crystal symmetry in (4-FTMBA)4Pb3I10. The introduction of heavier fluorine will significantly increase the motion barrier for the order-disorder transition, resulting in the remarkably improved Ttr. Temperature-dependent crystal structures, Raman spectra, and dielectric analyses well support the phase-transition behavior. In addition, evident thermochromism with a tunable direct band gap in (4-FTMBA)4Pb3I10 has been observed using UV-vis spectra. To the best of our knowledge, the achieved Ttr enhancement of 148 K by H/F substitution is the highest among the organic-inorganic hybrid lead halide phase-transition materials. This finding would greatly inspire the rational design of functional materials with high performance.

In-silico annotation of the chemical composition of Tibetan tea and its mechanism on antioxidant and lipid-lowering in mice.

BACKGROUND/OBJECTIVES: Tibetan tea is a kind of dark tea, due to the inherent complexity of natural products, the chemical composition and beneficial effects of Tibetan tea are not fully understood. The objective of this study was to unravel the composition of Tibetan tea using knowledge-guided multilayer network (KGMN) techniques and explore its potential antioxidant and hypolipidemic mechanisms in mice. MATERIALS/METHODS: The C57BL/6J mice were continuously gavaged with Tibetan tea extract (T group), green tea extract (G group) and ddH2O (H group) for 15 days. The activity of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in mice was detected. Transcriptome sequencing technology was used to investigate the molecular mechanisms underlying the antioxidant and lipid-lowering effects of Tibetan tea in mice. Furthermore, the expression levels of liver antioxidant and lipid metabolism related genes in various groups were detected by the real-time quantitative polymerase chain reaction (qPCR) method. RESULTS: The results showed that a total of 42 flavonoids are provisionally annotated in Tibetan tea using KGMN strategies. Tibetan tea significantly reduced body weight gain and increased T-AOC and SOD activities in mice compared with the H group. Based on the results of transcriptome and qPCR, it was confirmed that Tibetan tea could play a key role in antioxidant and lipid lowering by regulating oxidative stress and lipid metabolism related pathways such as insulin resistance, P53 signaling pathway, insulin signaling pathway, fatty acid elongation and fatty acid metabolism. CONCLUSIONS: This study was the first to use computational tools to deeply explore the composition of Tibetan tea and revealed its potential antioxidant and hypolipidemic mechanisms, and it provides new insights into the composition and bioactivity of Tibetan tea.

Establishment of RNA Interference Genetic Transformation System and Functional Analysis of FlbA Gene in Leptographium qinlingensis.

Leptographium qinlingensis is a pathogenic fungus of Pinus armandii that is epidemic in the Qinling Mountains. However, an effective gene interference strategy is needed to characterize the pathogenic genes in this fungus on a functional level. Using the RNA silencing vector pSilent-1 as a template, we established an RNA interference genetic transformation system mediated by Agrobacterium tumefaciens GV3101, which is suitable for the gene study for Leptographium qinlingensis by homologous recombination and strain interference system screening. The LqFlbA gene was silenced using the RNA interference approach described above, and the resulting transformants displayed various levels of silencing with a gene silencing effectiveness ranging from 41.8% to 91.4%. The LqFlbA-RNAi mutant displayed altered colony morphology, sluggish mycelium growth, and diminished pathogenicity toward the host P. armandii in comparison to the wild type. The results indicate that this method provides a useful reverse genetic system for studying the gene function of L. qinlingensis, and that LqFlbA plays a crucial role in the growth, development, and pathogenicity of L. qinlingensis.

LncRNA GAS5 Attenuates Cardiac Electrical Remodeling Induced by Rapid Pacing via the miR-27a-3p/HOXa10 Pathway.

Previous studies indicated long non-coding RNAs (lncRNAs) participated in the pathogenesis of atrial fibrillation (AF). However, little is known about the role of lncRNAs in AF-induced electrical remodeling. This study aimed to investigate the regulatory effect of lncRNA GAS5 (GAS5) on the electrical remodeling of neonatal rat cardiomyocytes (NRCMs) induced by rapid pacing (RP). RNA microarray analysis yielded reduced GAS5 level in NRCMs after RP. RT-qPCR, western blot, and immunofluorescence yielded downregulated levels of Nav1.5, Kv4.2, and Cav1.2 after RP, and whole-cell patch-clamp yielded decreased sodium, potassium, and calcium current. Overexpression of GAS5 attenuated electrical remodeling. Bioinformatics tool prediction analysis and dual luciferase reporter assay confirmed a direct negative regulatory effect for miR-27a-3p on lncRNA-GAS5 and HOXa10. Further analysis demonstrated that either miR-27a-3p overexpression or the knockdown of HOXa10 further downregulated Nav1.5, Kv4.2, and Cav1.2 expression. GAS5 overexpression antagonized such effects in Nav1.5 and Kv4.2 but not in Cav1.2. These results indicate that, in RP-treated NRCMs, GAS5 could restore Nav1.5 and Kv4.2 expression via the miR-27a-3p/HOXa10 pathway. However, the mechanism of GAS5 restoring Cav1.2 level remains unclear. Our study suggested that GAS5 regulated cardiac ion channels via the GAS5/miR-27a-3p/HOXa10 pathway and might be a potential therapeutic target for AF.

Echocardiographic parameters predicting spontaneous closure of ductus arteriosus in preterm infants.

Objective: To evaluate the value of echocardiographic parameters in predicting early spontaneous closure of ductus arteriosus in premature infants. Methods: 222 premature infants admitted to the neonatal ward of our hospital were selected, and patent ductus arteriosus was detected by echocardiography 48 h after birth. On the 7th day, whether the ductus arteriosus was closed naturally in this cohort was observed. The infants whose ductus arteriosus were not closed were identified as the PDA group (n = 109), and the other infants were included in the control group (n = 113). The echocardiographic parameters of the two groups of premature infants at 48 h after birth were single-factor statistically and Pearson correlation analyzed, and the parameters with statistically significant differences in single-factor analyzed were selected for multivariate logistic stepwise regression analysis. Results: The ductus arteriosus shunt velocity and the pressure difference between the descending aorta and the pulmonary artery (ΔPs) in the PDA group were lower than those in the control group (P < 0.05). The pulmonary artery pressure (PASP) in the PDA group was higher than that in the control group (P < 0.05). According to the multivariate logistic stepwise regression analysis, only the maximum shunt velocity of ductus arteriosus was correlated with early spontaneous closure of ductus arteriosus in 48 h first echocardiographic parameters (P = 0.049). The receiver operating characteristic (ROC) curve indicates the optimal critical point of echocardiographic ductus arteriosus shunt velocity in premature infants 48 h after birth was 1.165 m/s. Conclusion: Echocardiographic parameters are of great value in predicting the early spontaneous closure of ductus arteriosus in premature infants. In particular, the ductus arteriosus shunt velocity is correlated with the early spontaneous closure of ductus arteriosus.

Construction and validation of a nomogram of risk factors for new-onset atrial fibrillation in advanced lung cancer patients after non-surgical therapy.

Objective: Risk factors of new-onset atrial fibrillation (NOAF) in advanced lung cancer patients are not well defined. We aim to construct and validate a nomogram model between NOAF and advanced lung cancer. Methods: We retrospectively enrolled 19484 patients with Stage III-IV lung cancer undergoing first-line antitumor therapy in Shanghai Chest Hospital between January 2016 and December 2020 (15837 in training set, and 3647 in testing set). Patients with pre-existing AF, valvular heart disease, cardiomyopathy were excluded. Logistic regression analysis and propensity score matching (PSM) were performed to identify predictors of NOAF, and nomogram model was constructed and validated. Results: A total of 1089 patients were included in this study (807 in the training set, and 282 in the testing set). Multivariate logistic regression analysis showed that age, c-reactive protein, centric pulmonary carcinoma, and pericardial effusion were independent risk factors, the last two of which were important independent risk factors as confirmed by PSM analysis. Nomogram included independent risk factors of age, c-reactive protein, centric pulmonary carcinoma, and pericardial effusion. The AUC was 0.716 (95% CI 0.661-0.770) and further evaluation of this model showed that the C-index was 0.716, while the bias-corrected C-index after internal validation was 0.748 in the training set. The calibration curves presented good concordance between the predicted and actual outcomes. Conclusion: Centric pulmonary carcinoma and pericardial effusion were important independent risk factors for NOAF besides common ones in advanced lung cancer patients. Furthermore, the new nomogram model contributed to the prediction of NOAF.

LIPUS-S/B@NPs regulates the release of SDF-1 and BMP-2 to promote stem cell recruitment-osteogenesis for periodontal bone regeneration.

Purpose: Poly (lactic-co-glycolic acid)-based nanoparticles (PLGA NPs) have been widely used as the carrier for sustainable drug delivery. However, the drug release from the NPs was usually incomplete and uncontrollable. Herein, a low intensity pulsed ultrasound (LIPUS) assisted SDF-1/BMP-2@nanoparticles (S/B@NPs) system was fabricated to facilitate stem cell recruitment-osteogenesis for periodontal bone regeneration. Methods: In this work, S/B@NPs were prepared with double-emulsion synthesis method. Then the S/B release profile from NPs was evaluated with or without low intensity pulsed ultrasound treatment. Afterwards, the stem cell recruiting and osteoinductive capacities of LIPUS-S/B@NPs were detected with human periodontal ligament cells (hPDLCs) in vitro and in a rat periodontal bone defect model. Results: The results indicated that S/B@NPs were successfully prepared and LIPUS could effectively regulate the release of S/B and increase their final releasing amount. Moreover, LIPUS-S/B@NPs system significantly promoted hPDLCs migrating and osteogenesis in vitro and recruiting rBMSCs to the rat periodontal defect and facilitated bone regeneration in vivo. Conclusion: Our LIPUS assisted S/B@NPs system can effectively facilitate stem cell recruitment and periodontal bone regeneration. Considering its reliable safety and therapeutic effect on bone fracture, LIPUS, as an adjuvant therapy, holds great potential in the regulation of drug delivery systems for bone healing.

miRNA, lncRNA and circRNA: targeted molecules with therapeutic promises in Mycoplasma pneumoniae infection.

Mycoplasma pneumoniae (MP) is primarily recognized as a respiratory pathogen that causes community-acquired pneumonia, which can lead to acute upper and lower airway inflammation and extrapulmonary syndrome. Refractory pneumonia caused by MP can cause severe complications and even be life-threatening, particularly in infants and the elderly. It is well-known that non-coding RNAs (ncRNAs) represented by miRNAs, lncRNAs and circRNAs have been manifested to be widely involved in the regulation of gene expression. Growing evidence indicates that these ncRNAs have distinct differentiated expression in MP infection and affect multiple biological processes, playing an indispensable role in the initiation and promotion of MP infection. However, the epigenetic mechanisms involved in the development of MP infection remain unclear. This article reviews the mechanisms by which miRNAs, lncRNAs, and circRNAs mediate MP infection, such as inflammatory responses, apoptosis and pulmonary fibrosis. Focusing on miRNAs, lncRNAs and circRNAs associated with MP infection could provide new insights into this disease's early diagnosis and therapeutic approaches.

Promoter engineering for efficient production of sucrose phosphorylase in Bacillus subtilis and its application in enzymatic synthesis of 2-O-α-D-glucopyranosyl-L-ascorbic acid.

2-O-α-D-glucopyranosyl-L-ascorbic acid (AA-2G), a stable glucoside derivative of L-ascorbic acid (L-AA), can be one-step synthesized by sucrose phosphorylase (SPase). In this study, we attempted to produce extracellular SPase in Bacillus subtilis WB800 for the food-grade production of AA-2G. The results showed that the secretion of SPases did not require signal peptide. Promoter and its compatibility to target SPase gene were proved to be the key factors for high-level secretion. The strong promoter P43 and synthetic SPase gene derived from Bifidobacterium longum (BloSPase) were selected due to generate a relatively high extracellular activity (0.94 U/mL) for L-AA glycosylation. A highly active dual-promoter system PsigH-100-P43 was further constructed, which produced the highest extracellular and intracellular activity were 5.53 U/mL and 6.85 U/mL in fed-batch fermentation, respectively. Up to 113.58 g/L of AA-2G could be achieved by the supernatant of fermentation broth and a higher yield of 146.42 g/L was obtained by whole-cells biotransformation. Therefore, the optimal dual-promoter system in B. subtilis is suitable for the food-grade scale-up production of AA-2G.

Psoriasis and Leprosy: An Arcane Relationship.

Purpose: Psoriasis (Ps) and leprosy are chronic inflammatory skin disorders, characterised by enhanced innate and adaptive immunity. Ps and leprosy rarely coexist. The molecular immune mechanism of the Ps and leprosy rarely coexistence is unclear. Patients and Methods: RNA-sequencing (RNA-seq) was performed on 20 patients with Ps, 5 adults with lepromatous leprosy (L-lep), and 5 patients with tuberculoid leprosy (T-lep) to analyse the differentially expressed genes (DEGs) between them. Moreover, the biological mechanism of Ps and leprosy was explored by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Gene Ontology (GO) analysis, Gene Set Enrichment Analysis analysis, and protein-protein interaction (PPI) analyses. Finally, 13 DEGs of 10 skin biopsies of Ps patients, 6 samples of L-lep patients, 6 samples of T-lep patients and 5 healthy controls were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The PPI network was constructed and primarily associated with immune response, IL-17 signalling, and Toll-like receptor pathway between Ps and leprosy. Th17 markers (interleukin (IL)-19, IL-20, IL-36A, IL-36G, IL-22, IL-17A, and lipocalin-2 (LCN2) had higher expression in Ps than in L-lep and T-lep, whereas macrophage biomarkers (CLEC4E and TREM2), SPP1, and dendritic cell (DC)-related hallmarks (ITGAX) and TNF-a had significantly lower expression across Ps and T-lep than in L-lep. Conclusion: To put it simply, Ps patients with IL-17A, IL-19, IL-20, IL-36A, IL-36G, and IL-22 in conjunction with LCN2 with up-graduated expression might be not susceptible to L-lep. However, high levels of CLEC4E, TREM2, and SPP1 in L-lep patients indicated that they unlikely suffered from Ps.