Therapeutic potential of Pien Tze Huang in colitis-associated colorectal cancer: mechanistic insights from a mouse model.

BACKGROUND: Pien Tze Huang (PZH), a traditional Chinese medicine formulation, is recognized for its therapeutic effect on colitis and colorectal cancer. However, its protective role and underlying mechanism in colitis-associated colorectal cancer (CAC) remain to be elucidated. METHODS: A CAC mouse model was established using AOM/DSS. Twenty mice were randomly divided into four groups (n = 5/group): Control, PZH, AOM/DSS, and AOM/DSS + PZH groups. Mice in the PZH and AOM/DSS + PZH group were orally administered PZH (250 mg/kg/d) from the first day of experiment, while the control and AOM/DSS group received an equivalent volume of distilled water. Parameters such as body weight, disease activity index (DAI), colon weight, colon length, colon histomorphology, intestinal tumor formation, serum concentrations of pro-inflammatory cytokines, proliferation and apoptosis in colon tissue were assessed. RNA sequencing was employed to identify the differentially expressed transcripts (DETs) in colonic tissues and related signaling pathways. Wnt/ß-Catenin Pathway-Related genes in colon tissue were detected by QPCR and immunohistochemistry (IHC). RESULTS: PZH significantly attenuated AOM/DSS-induced weight loss, DAI elevation, colonic weight gain, colon shortening, histological damage, and intestinal tumor formation in mice. PZH also notably decreased serum concentration of IL-6, IL-1ß, and TNF-α. Furthermore, PZH inhibited cell proliferation and promote apoptosis in tumor tissues. RNA-seq and KEGG analysis revealed key pathways influenced by PZH, including Wnt/ß-catenin signaling pathway. IHC staining confirmed that PZH suppressed the expression of ß-catenin, cyclin D1 and c-Myc in colonic tissues. CONCLUSIONS: PZH ameliorates AOM/DSS-induced CAC in mice by suppressing the activation of Wnt/ß-catenin signaling pathway.

Increased Risk of New-Onset Rheumatoid Arthritis Among Osteoarthritis Patients Received Total Knee Arthroplasty: a global federated health network analysis.

Background: Complications of total knee arthroplasty (TKA) had been widely discussed. However, whether TKA influence risk of rheumatoid arthritis (RA) in osteoarthritis patients remained uncertain. We intend to evaluate the risk of RA in osteoarthritis patients underwent TKA. Methods: In this retrospective cohort study, data was retrieved from the US collaborative networks in TriNetX research network. Within the study period between 2005 and 2017, osteoarthritis patients underwent TKA were enrolled as case cohort whereas osteoarthritis patients never underwent TKA were enrolled as control cohort. Covariates were matched via propensity score matching. Risk of RA in TKA patients were valuated under various follow-up time and sensitivity models. Results: Under 1-year, 3-year and 5-year of follow-up, TKA patients were associated with significantly elevated risk of RA, especially under 1-year follow-up (HR=1.74; 95% CI, 1.39-2.18). Subgroup analysis demonstrated a significant increase in the risk of RA following TKA in the female subgroup (HR=1.42; 95% CI, 1.24-1.63), the subgroup aged 18-64 years (HR=1.48; 95% CI, 1.11-1.97), and the subgroup aged greater than 65 years old (HR=1.38; 95% CI, 1.21-1.58) based on 5-year follow-up. Conclusion: Clinicians should be concerned about uncharted association between TKA and RA reported our current study. Additional prospective studies and in-depth mechanistic inquiries were warranted to determine the causation.

Qing Hua Chang Yin ameliorates chronic colitis in mice by inhibiting PERK-ATF4-CHOP pathway of ER stress and the NF-κB signalling pathway.

CONTEXT: Ulcerative colitis has been clinically treated with Qing Hua Chang Yin (QHCY), a traditional Chinese medicine formula. However, its precise mechanisms in mitigating chronic colitis are largely uncharted. OBJECTIVE: To elucidate the therapeutic efficiency of QHCY on chronic colitis and explore its underlying molecular mechanisms. MATERIALS AND METHODS: A total ion chromatogram fingerprint of QHCY was analysed. Chronic colitis was induced in male C57BL/6 mice using 2% dextran sodium sulphate (DSS) over 49 days. Mice were divided into control, DSS, DSS + QHCY (0.8, 1.6 and 3.2 g/kg/d dose, respectively) and DSS + mesalazine (0.2 g/kg/d) groups (n = 6). Mice were intragastrically administered QHCY or mesalazine for 49 days. The changes of disease activity index (DAI), colon length, colon histomorphology and serum pro-inflammatory factors in mice were observed. RNA sequencing was utilized to identify the differentially expressed transcripts (DETs) in colonic tissues and the associated signalling pathways. The expression of endoplasmic reticulum (ER) stress-related protein and NF-κB signalling pathway-related proteins in colonic tissues was detected by immunohistochemistry staining. RESULTS: Forty-seven compounds were identified in QHCY. Compared with the DSS group, QHCY significantly improved symptoms of chronic colitis like DAI increase, weight loss, colon shortening and histological damage. It notably reduced serum levels of IL-6, IL-1ß and TNF-α. QHCY suppressed the activation of PERK-ATF4-CHOP pathway of ER stress and NF-κB signalling pathways in colonic tissues. DISCUSSION AND CONCLUSIONS: The findings in this study provide novel insights into the potential of QHCY in treating chronic colitis patients.

Comparison of tandem pumping and direct pumping on high-power linearly polarized fiber laser.

In this article, a thorough model of linearly polarized fiber laser considering polarization coupling, mode coupling, SBS, and SRS effects is established. The output results of direct pumping and tandem pumping linearly polarized fiber laser under different SBS and SRS intensity settings are simulated. The results show that direct pumping is a better pumping scheme at present, and if the doping concentration of gain fiber can be further increased and the mode field quality of corresponding passive fiber can be optimized, the disadvantages of tandem pumping can be suppressed. To explore the potential of tandem pumping, a backward tandem pumped linearly polarized fiber amplifier is built and 875 W over 13 dB linearly polarized laser output is obtained.

Transcriptome sequencing identifies prognostic genes involved in gastric adenocarcinoma.

Gastric adenocarcinoma (GAC) is one of the world's most lethal malignant tumors. It has been established that the occurrence and progression of GAC are linked to molecular changes. However, the pathogenesis mechanism of GAC remains unclear. In this study, we sequenced 6 pairs of GAC tumor tissues and adjacent normal tissues and collected GAC gene expression profile data from the TCGA database. Analysis of this data revealed 465 differentially expressed genes (DEGs), of which 246 were upregulated and 219 were downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that DEGs were observably enriched in ECM-receptor interaction, protein digestion and absorption, and gastric acid secretion pathways. Six key genes (MATN3, COL1A1, COL5A2, P4HA3, SERPINE1 and VCAN) associated with poor GAC prognosis were screened from the protein‒protein interaction (PPI) network by survival analysis, and P4HA3 and MATN3 have rarely been reported to be associated with GAC. We further analyzed the function of P4HA3 in the GAC cell line SGC-7901 by RT‒qPCR, MTT, flow cytometry, colony formation, wound healing, Transwell and western blot assays. We found that P4HA3 was upregulated in the SGC-7901 cell line versus normal control cells. The outcomes of the loss-of-function assay illustrated that P4HA3 significantly enhanced the ability of GAC cells to proliferate and migrate. This study provides a new basis for the selection of prognostic markers and therapeutic targets for GAC.

Controllable Preparation of Gold Nanocrystals with Different Porous Structures for SERS Sensing.

Porous Au nanocrystals (Au NCs) have been widely used in catalysis, sensing, and biomedicine due to their excellent localized surface plasma resonance effect and a large number of active sites exposed by three-dimensional internal channels. Here, we developed a ligand-induced one-step method for the controllable preparation of mesoporous, microporous, and hierarchical porous Au NCs with internal 3D connecting channels. At 25 °C, using glutathione (GTH) as both a ligand and reducing agent combined with the Au precursor to form GTH-Au(I), and under the action of the reducing agent ascorbic acid, the Au precursor is reduced in situ to form a dandelion-like microporous structure assembled by Au rods. When cetyltrimethylammonium bromide (C16TAB) and GTH are used as ligands, mesoporous Au NCs formed. When increasing the reaction temperature to 80 °C, hierarchical porous Au NCs with both microporous and mesoporous structures will be synthesized. We systematically explored the effect of reaction parameters on porous Au NCs and proposed possible reaction mechanisms. Furthermore, we compared the SERS-enhancing effect of Au NCs with three different pore structures. With hierarchical porous Au NCs as the SERS base, the detection limit for rhodamine 6G (R6G) reached 10-10 M.

Synthesis of a Porous [14]Annulene Graphene Nanoribbon and a Porous [30]Annulene Graphene Nanosheet on Metal Surfaces.

The electrical and mechanical properties of graphene-based materials can be tuned by the introduction of nanopores, which are sensitively related to the size, morphology, density, and location of nanopores. The synthesis of low-dimensional graphene nanostructures containing well-defined nonplanar nanopores has been challenging due to the intrinsic steric hindrance. Herein, we report the selective synthesis of one-dimensional (1D) graphene nanoribbons (GNRs) containing periodic nonplanar [14]annulene pores on Ag(111) and two-dimensional (2D) porous graphene nanosheet containing periodic nonplanar [30]annulene pores on Au(111), starting from a same precursor. The formation of distinct products on the two substrates originates from the different thermodynamics and kinetics of coupling reactions. The reaction mechanisms were confirmed by a series of control experiments, and the appropriate thermodynamic and kinetic parameters for optimizing the reaction pathways were proposed. In addition, the combined scanning tunneling spectroscopy (STS) and density functional theory (DFT) calculations revealed the electronic structures of porous graphene structures, demonstrating the impact of nonplanar pores on the π-conjugation of molecules.

Efficient UV-visible emission enabled by 532†nm CW excitation in an Ho3+-doped ZBLAN fiber.

Rare-earth-doped ZBLAN (ZrF4-BaF2-LaF3-AlF3-NaF) fibers have evolved to become promising candidates for efficient UV-visible emission because of their low phonon energy and low optical losses, as well as their well-defined absorption bands. We investigate the efficient emission of UV-visible light in a low-concentration (0.1 mol%) Ho3+-doped ZBLAN fiber excited by a 532 nm CW laser. In addition to the direct populating of the thermalized 5F4+5S2 levels by ground-state absorption, the upconversion processes responsible for UV-visible emission from the higher emitting levels, 3P1+3D3, 3K7+5G4, 5G5, and 5F3, of the Ho3+ ions are examined using excited-state absorption. The dependence of UV-visible fluorescence intensity on launched green pump power is experimentally determined, confirming the one-photon and two-photon characters of the observed processes. We theoretically investigate the excitation power dependence of the population density for nine Ho3+ levels based on a rate equation model. This qualitative model has shown a good agreement with the measured power dependence of UV-visible emission. Moreover, the emission cross-sections for blue, green, red, and deep-red light in the visible region are measured using the Füchtbauer-Ladenburg method and corroborated by McCumber theory, and the corresponding gain coefficients are derived. We propose an alternative approach to achieve efficient UV-visible emission in an Ho3+-doped ZBLAN fiber using a cost-effective, high-brightness 532 nm laser.

High-power and high-brightness Er:Yb codoped fiber MOPA operating at 1535 nm.

In this paper, we study the emerging 1535 nm Er: Yb codoped fiber MOPA with high power and high brightness. To characterize the interstage influence of this ASE-sensitive system, we conduct an interstage numerical model based on steady energy transfer model, where the seed and amplifier converge together. We analyze the amplifier setup, the seed pumping scheme, and feedback from inner reflection based on the model. Afterwards, we experimentally demonstrate a 1535 nm all fiber large mode area Er: Yb codoped fiber MOPA with the output power of 174.5 W, the brightness of 13.97 W/µm2sr, and ASE suppression ratio of 45 dB. To the best of our knowledge, this is the highest power and brightness of 1535 nm fiber lasers to date.

Spectral pedestal during the kilowatt-level amplification of a random fiber laser operating near the lasing threshold.

The amplification of random fiber lasers (RFLs) attracts much attention due to their unique characteristics such as wavelength flexibility and low coherence. We present that, in the kilowatt-level amplification of RFL operating near its lasing threshold, a broad and flat spectral pedestal can co-exist with the narrow spectral peak of RFL. This phenomenon is different from the case in the amplification of fixed-cavity laser seeds. Time-domain measurements show that the broad and flat spectral pedestal, which extends to long wavelengths, is composed of temporal pulses, while few temporal pulses exist in the narrow spectral peak. We attribute the spectral pedestal to intensity fluctuations from the random seed laser and modulation instability in the amplification stage. Control experiments reveal that the working status of the random seed laser and the effective length of the amplifier can influence the spectral bandwidth. By taking advantage of this phenomenon, we propose a novel approach to achieve a high-power broadband light source through the amplification of RFLs operating near the lasing threshold.

Spatiotemporal analysis of an all-fiber multimode interference-based saturable absorber via a mode-resolved nonlinear Schrodinger equation.

This paper presents an approach that combines the generalized multimode nonlinear Schrodinger equation with a transmission model to analyze spatiotemporal characteristics of multimode interference in single mode/large mode area fiber-graded-index multimode fiber-single mode fiber (SMF/LMA-GIMF-SMF) structures for the first time. Approximated self-imaging (ASIM) behavior in GIMF and the study of the latter structure used in spatiotemporal mode-locked fiber lasers are first demonstrated. Simulations show that these structures can work as saturable absorbers enabling high-energy pulse output due to nonlinear intermodal interactions and intensity-dependent multimode interference. Otherwise, underlying ASIM is proven that it can perturb the transmission of SMF/LMA-GIMF-SMF, causing instability of their saturable-absorption characteristics. This paper provides a theoretical guide for many applications, such as beam shaping, mode conversion, and high-energy ultrafast fiber laser.

3D APT and NOE CEST-MRI of healthy volunteers and patients with non-enhancing glioma at 3 T.

OBJECTIVE: Clinical application of chemical exchange saturation transfer (CEST) can be performed with investigation of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) effects. Here, we investigated APT- and NOE-weighted imaging based on advanced CEST metrics to map tumor heterogeneity of non-enhancing glioma at 3 T. MATERIALS AND METHODS: APT- and NOE-weighted maps based on Lorentzian difference (LD) and inverse magnetization transfer ratio (MTRREX) were acquired with a 3D snapshot CEST acquisition at 3 T. Saturation power was investigated first by varying B1 (0.5-2 µT) in 5 healthy volunteers then by applying B1 of 0.5 and 1.5 µT in 10 patients with non-enhancing glioma. Tissue contrast (TC) and contrast-to-noise ratios (CNR) were calculated between glioma and normal appearing white matter (NAWM) and grey matter, in APT- and NOE-weighted images. Volume percentages of the tumor showing hypo/hyperintensity (VPhypo/hyper,CEST) in APT/NOE-weighted images were calculated for each patient. RESULTS: LD APT resulting from using a B1 of 1.5 µT was found to provide significant positive TCtumor,NAWM and MTRREX NOE (B1 of 1.5 µT) provided significant negative TCtumor,NAWM in tissue differentiation. MTRREX-based NOE imaging under 1.5 µT provided significantly larger VPhypo,CEST than MTRREX APT under 1.5 µT. CONCLUSION: This work showed that with a rapid CEST acquisition using a B1 saturation power of 1.5 µT and covering the whole tumor, analysis of both LD APT and MTRREX NOE allows for observing tumor heterogeneity, which will be beneficial in future studies using CEST-MRI to improve imaging diagnostics for non-enhancing glioma.

Cerebrospinal fluid predictors of shunt-dependent hydrocephalus after hemorrhagic stroke: a systematic review and meta-analysis.

Hydrocephalus is a common complication of hemorrhagic stroke and has been reported to contribute to poor neurological outcomes. Herein, we aimed to investigate the validity of cerebrospinal fluid (CSF) data in predicting shunt-dependent hydrocephalus (SDHC) in patients with hemorrhagic stroke. PubMed, CENTRAL, and Embase databases were searched for relevant studies published through July 31, 2021. The 16 studies with 1505 patient included those in which CSF data predicted risk for SDHC and reports on CSF parameters in patients in whom SDHC or hydrocephalus that was not shunt-dependent developed following hemorrhagic stroke. We appraised the study quality using Newcastle-Ottawa Scale and conducted a meta-analysis of the pooled estimates of the CSF predictors. The meta-analysis revealed three significant CSF predictors for shunt dependency, i.e., higher protein levels (mean difference [MD] = 32.09 mg/dL, 95% confidence interval [CI] = 25.48-38.70, I2 = 0%), higher levels of transforming growth factor ß1 (TGF-ß1; MD = 0.52 ng/mL, 95% CI = 0.42-0.62, I2 = 0%), and higher ferritin levels (MD = 108.87 µg/dL, 95% CI = 56.68-161.16, I2 = 36%). The red blood cell count, lactate level, and glucose level in CSF were not significant in predicting SDHC in patients with hemorrhagic stroke. Therefore, higher protein, TGF-ß1, and ferritin levels in CSF are significant predictors for SDHC in patients with hemorrhagic stroke. Measuring these CSF parameters would help in the early recognition of SDHC risk in clinical care.

Platelet Distribution Width: A Significant Predictor of Poor Outcome After Mechanical Thrombectomy.

OBJECTIVES: Elevated platelet distribution width (PDW) is a recognized marker of platelet activity. Herein, we investigated the association between admission PDW values and clinical outcome at 3 months in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy (MT). MATERIALS AND METHODS: We retrospectively collected consecutive patients diagnosed with AIS following MT from two stroke centers. PDW was measured on admission. Subjects were divided into two groups according to the clinical outcome using the modified Rankin Scale at 3 months. Multiple regression analyses and receiver operating characteristic (ROC) curves were performed to determine the associations between admission PDW values, clinical parameters, and functional outcome. RESULTS: A total of 162 subjects were enrolled. Patients in the poor outcome group had a significantly higher percentage of PDW >16.0 fL compared with the good outcome group (57.3% vs. 26.9%, P < 0.001). After adjusting for a range of confounding factors, multiple regression analysis showed that PDW >16.0 fL was an independent predictor of poor outcome at 3 months (odds ratio 4.572, 95% confidence interval 1.896-11.026, P = 0.001). ROC curve analysis revealed that PDW >16.0 fL predicted poor outcome with 57.3% sensitivity and 73.1% specificity (the area under the ROC curve 0.637, 95% confidence interval 0.558-0.711, P = 0.004). CONCLUSIONS: Elevated PDW is an independent predictor of poor functional outcome in patients with anterior circulation AIS undergoing MT at 3 months.

Quantitative proteomics reveals the effect of Yigu decoction (YGD) on protein expression in bone tissue.

BACKGROUND: Osteoporosis (OP) is a systemic bone disease characterized by decreased bone mass, destruction of the bone tissue microstructure, increased bone brittleness and an increased risk of fracture. OP has a high incidence rate and long disease course and is associated with serious complications. Yigu decoction (YGD) is a compound prescription in traditional Chinese medicine that is used to treat OP. However, its mechanism in OP is not clear. This study used a tandem mass tag (TMT)quantitative proteomics method to explore the potential bone-protective mechanism of YGD in an osteoporotic rat model. MATERIALS AND METHODS: A rat model of OP was established by ovariectomy. Eighteen 12-week-old specific-pathogen-free female Wistar rats weighing 220 ± 10 g were selected. The eighteen rats were randomly divided into 3 groups (n = 6 in each group): the normal, model and YGD groups. The right femurs from each group were subjected to quantitative biological analysis. TMT quantitative proteomics was used to analyze the proteins extracted from the bone tissue of rats in the model and YGD groups, and the differentially expressed proteins after intervention with YGD were identified as biologically relevant proteins of interest. Functional annotation correlation analysis was also performed to explore the biological function and mechanism of YGD. RESULT: Compared with the model group, the YGD group showed significant upregulation of 26 proteins (FC > 1.2, P < 0.05) and significant downregulation of 39 proteins (FC < 0.833, P < 0.05). Four important targets involved in OP and 5 important signaling pathways involved in bone metabolism were identified. CONCLUSIONS: YGD can significantly increase the bone mineral density (BMD) of osteoporotic rats and may play a therapeutic role by regulating target proteins involved in multiple signaling pathways. Therefore, these results improve the understanding of the OP mechanism and provide an experimental basis for the clinical application of YGD in OP treatment.

In Situ Regeneration of Phenol-Saturated Activated Carbon Fiber by an Electro-peroxymonosulfate Process.

Regeneration is required to restore the adsorption performance of activated carbon used as an adsorbent in water purification. Conventional thermal and electrochemical regenerations have high energy consumption and poor mineralization of pollutants, respectively. In this study, phenol-saturated activated carbon fiber was regenerated in situ using an electro-peroxymonosulfate (E-PMS) process, which mineralized the desorbed contaminants with relatively low energy consumption. The initial adsorbed phenol (81.90%) was mineralized, and only 4.07% of the initial concentration remained in the solution after 6 h of E-PMS regeneration. The phenol degradation was dominated by hydroxyl radical oxidation. Adding the PMS in three doses at 2 h intervals improves the regeneration performance from 75% to more than 82%. Regeneration retained 60% of its initial effectiveness even in the 10th cycle with 4.40% of the initial concentration of phenol remaining in the solution. These results confirm the E-PMS regeneration process as effective, sustainable, and environmentally friendly for regenerating activated carbon.

Particulates and particulates-bound mercury (Hg(p)) sizes (PM18, PM10, PM2.5, PM1, PM<1) distributions study by using MOUDI sampler at a complex sampling site.

The objectives of this study were to measure ambient air particles concentrations of different particulates sizes ranges (PM18, PM10, PM2.5, PM1, PM<1) at a complex (traffic, residential and commercial) site. Besides, particulates-bound mercury (Hg(p)) concentrations for various particulates sizes (PM18, PM10, PM2.5, PM1, PM<1) at mixed site were also studied. Finally, ambient air particulates and Hg(p) size distributions were also described at this complex sampling site. The results showed that the average PM18, PM10, PM2.5, PM1, PM<1 concentrations were 48.83, 41.78, 35.41, 19.89, and 11.86 µg/m3, respectively. And the average ambient air particulates-bound mercury (Hg(p)) which attached on PM18, PM10, PM2.5, PM1, PM<1 particles concentrations were 0.0838, 0.0867, 0.0790, 0.0546, and 0.0373 ng/m3, respectively, in the summer season. In addition, the average ambient air Hg(p) which attached on PM18, PM10, PM2.5, PM1, PM<1 particles concentrations were 0.0175, 0.0144, 0.0120, 0.0092, and 0.0057 ng/m3, respectively, in the autumn season. Finally, the average ambient air Hg(p) which attached on PM18, PM10, PM2.5, PM1, PM<1 particles concentrations were 0.0070, 0.0053, 0.0038, 0.0026, and 0.0014 ng/m3, respectively, in the winter season. And July has the average highest PM18 and PM10 concentrations. As for PM2.5, PM1 and PM<1 particulates, the average highest particulates concentrations all occurred in November. In addition, the highest average Hg(p) in PM18, PM10, PM2.5, PM1, and PM<1 concentrations all occurred in July. Moreover, the average particles and particulates-bound mercury m.m.d. values were ranged from 1.0 to 1.8 and 0.7 to 2.0 µm from July to December of 2018, respectively, at this mixed sampling site. As for monthly ambient air particles sizes distributions, the results further showed that the main peaks for July, September, and December all occurred in the sizes of 10-18 µm. The main peaks for October and November all occurred in the sizes of 2.5-10 µm. As for monthly Hg(p) sizes distributions, the results further showed that the main peaks for July occurred in the size of 0.3-1 µm. The main peak for September occurred in the size of 1-2.5 µm. The main peaks for October to December all occurred in the size of 10-18 µm. The above finding further concluded that the particulates-bound mercury (Hg(p)) was tended to be associated with the large particles sizes mode during the winter season. Finally, this study further shows that the Taichung Thermal Power Plant was responsible for the main emission source of Hg(p) especially in summer season of Central Taiwan.

The causal relationship between immune cells and ankylosing spondylitis: a bidirectional Mendelian randomization study.

BACKGROUND: Ankylosing spondylitis (AS) is one of several disorders known as seronegative spinal arthritis (SpA), the origin of which is unknown. Existing epidemiological data show that inflammatory and immunological factors are important in the development of AS. Previous research on the connection between immunological inflammation and AS, however, has shown inconclusive results. METHODS: To evaluate the causal association between immunological characteristics and AS, a bidirectional, two-sample Mendelian randomization (MR) approach was performed in this study. We investigated the causal connection between 731 immunological feature characteristic cells and AS risk using large, publically available genome-wide association studies. RESULTS: After FDR correction, two immunophenotypes were found to be significantly associated with AS risk: CD14 - CD16 + monocyte (OR, 0.669; 95% CI, 0.544 ~ 0.823; P = 1.46 × 10-4; PFDR = 0.043), CD33dim HLA DR + CD11b + (OR, 0.589; 95% CI = 0.446 ~ 0.780; P = 2.12 × 10-4; PFDR = 0.043). AS had statistically significant effects on six immune traits: CD8 on HLA DR + CD8 + T cell (OR, 1.029; 95% CI, 1.015 ~ 1.043; P = 4.46 × 10-5; PFDR = 0.014), IgD on IgD + CD24 + B cell (OR, 0.973; 95% CI, 0.960 ~ 0.987; P = 1.2 × 10-4; PFDR = 0.021), IgD on IgD + CD38 - unswitched memory B cell (OR, 0.962; 95% CI, 0.945 ~ 0.980; P = 3.02 × 10-5; PFDR = 0.014), CD8 + natural killer T %lymphocyte (OR, 0.973; 95% CI, 0.959 ~ 0.987; P = 1.92 × 10-4; PFDR = 0.021), CD8 + natural killer T %T cell (OR, 0.973; 95% CI, 0.959 ~ 0.987; P = 1.65 × 10-4; PFDR = 0.021). CONCLUSION: Our findings extend genetic research into the intimate link between immune cells and AS, which can help guide future clinical and basic research.

Inhibitory effect of Lonicera japonica flos on Streptococcus mutans biofilm and mechanism exploration through metabolomic and transcriptomic analyses.

Introduction: Streptococcus mutans was the primary pathogenic organism responsible for dental caries. Lonicera japonica flos (LJF) is a traditional herb in Asia and Europe and consumed as a tea beverage for thousands of years. Methods: The inhibitory effect and mechanism of LJF on biofilm formation by S. mutans was investigated. The active extracts of LJF were validated for their inhibitory activity by examining changes in surface properties such as adherence, hydrophobicity, auto-aggregation abilities, and exopolysaccharides (EPS) production, including water-soluble glucan and water-insoluble glucan. Results and discussion: LJF primarily inhibited biofilm formation through the reduction of EPS production, resulting in alterations in cell surface characteristics and growth retardation in biofilm formation cycles. Integrated transcriptomic and untargeted metabolomics analyses revealed that EPS production was modulated through two-component systems (TCS), quorum sensing (QS), and phosphotransferase system (PTS) pathways under LJF stress conditions. The sensing histidine kinase VicK was identified as an important target protein, as LJF caused its dysregulated expression and blocked the sensing of autoinducer II (AI-2). This led to the inhibition of response regulator transcriptional factors, down-regulated glycosyltransferase (Gtf) activity, and decreased production of water-insoluble glucans (WIG) and water-soluble glucans (WSG). This is the first exploration of the inhibitory effect and mechanism of LJF on S. mutans, providing a theoretical basis for the application of LJF in functional food, oral health care, and related areas.