Blood MALT1 expression could help predict treatment outcomes in psoriasis patients, especially in those receiving biologics.

INTRODUCTION: Mucosa-associated lymphoid tissue 1 (MALT1) modulates T helper cell differentiation, pro-inflammatory cytokine production, and epidermal hyperplasia to participate in the pathology of psoriasis. This study aimed to explore the correlation of blood MALT1 with treatment outcomes in psoriasis patients. METHODS: MALT1 was detected in peripheral blood mononuclear cells by reverse transcription-quantitative polymerase chain reaction in 210 psoriasis patients before starting or converting to a new therapy, 50 disease controls, and 50 healthy controls. The psoriasis area severity index (PASI) score was evaluated at month (M)1, M3, and M6 in psoriasis patients. RESULTS: MALT1 was increased in psoriasis patients versus disease controls and healthy controls (both p < .001); and positively related to body mass index (p = .019) and PASI score (p < .001) in psoriasis patients. PASI75 rate at M1, M3, and M6 was 22.9%, 46.2%, and 71.0%, respectively; while PASI90 rate at M1, M3, and M6 was 3.8%, 29.0%, and 50.5%, respectively, in psoriasis patients. PASI75/90 rates at M1, M3, and M6 were increased in psoriasis patients receiving biologics versus those without (all p < .05). Pretreatment MALT1 was higher in psoriasis patients who achieved PASI75 (p = .001) and PASI90 (p < .001) at M6 compared to those who did not achieve that. Subgroup analyses discovered that pretreatment MALT1 had a stronger ability to predict PASI75 and 90 realizations in psoriasis patients receiving biologics (area under the curve [AUC]: 0.723 and 0.808) versus those without (AUC: 0.594 and 0.675). CONCLUSION: Blood MALT1 measurement may assist in predicting outcomes in psoriasis patients, especially in those receiving biologics.

Deep ultraviolet AlGaN-multiple quantum wells with photoluminescence enhanced by topological corner state.

The AlGaN-based deep ultraviolet light-emitting diode (DUV LED) has advantages of environmentally friendly materials, tunable emission wavelength, and easy miniaturization. However, an increase in Al composition leads to a decline in the lattice quality, thereby reducing the internal quantum efficiency (IQE). In addition, the light extraction efficiency (LEE) is limited due to the strong transverse magnetization polarization emission from the multiple quantum wells. Here, we designed the topological corner structure in AlGaN-MQWs, and the high electric field intensity in a tiny space at the corner results in an extremely high local density of optical states (LDOS), which could shorten the luminescence decay time of the emitter and increase the radiative rate by 26 times. Meanwhile, because the excited topological corner state resonance mode is a transverse-electric mode, enhancing only the transverse-electric luminescence without any gain for transverse-magnetic luminescence, thereby significantly improving the light extraction efficiency. Finally, according to theoretical calculations, the IQE could reach 68.75% at room temperature.

Psychometric assessment of the Adherence to Asthma Medication Questionnaire in asthma patients in China: a validation study.

BACKGROUND: Patients' medication adherence plays a critical role in the treatment and rehabilitation of disease. However, few tools are currently available that can be used to identify the reasons for their nonadherence with their medication regimens. It is possible to evaluate both the level of medication adherence of a patient as well as the reasons for it using the Adherence to Asthma Medication Questionnaire (AAMQ). The purpose of this study was to adapt the AAMQ for use in Chinese patients and a variety of asthma patients. METHODS: A total of 242 asthma patients were recruited from Jinzhou in China. The Adherence to Asthma Medication Questionnaire was translated and back-translated using the Brislin translation model. Test-retest reliability, internal consistency, and stability all play a large role in determining the reliability of a scale. Confirmatory factor analysis was used to examine the scale's construct validity, and expert consultation was used to verify the scale's content validity. Statistics were deemed significant at p < 0.05. RESULTS: The Cronbach's α value of the Chinese version of the AAMQ was 0.866, and the coefficient values for the three domains ranged between 0.702 and 0.798. The split-half reliability and stability values were 0.794 and 0.772, respectively. The content validity index of the scale (S-CVI) was 0.923, and the content validity index of the level of scale entry was 0.857-1.000. According to the confirmatory factor analysis, the chi-square degreed of freedom were 1.484, and the model fitting indices were all within normal limits. CONCLUSIONS: The AAMQ had good reliability and validity for asthmatic patients. The results of the scale's assessment can be used as a criterion for medication adherence among asthmatic patients and to understand the causes. This study provides a reference for solving the problem of medication adherence among asthma patients and implementing targeted nursing measures. PATIENT OR PUBLIC CONTRIBUTION: Gratitude is extended to all individuals collaborating in completing the survey and to the author.

The effect of different nerve block strategies on the quality of post-operative recovery in breast cancer patients: A randomized controlled study.

OBJECTIVE: To compare the effects of three types of ultrasound-guided nerve blocks on post-operative recovery quality in patients undergoing modified radical mastectomy for unilateral breast cancer. METHODS: In this randomized double-blinded trial (chictr.org.cn, ChiCTR2200059428), 150 female patients were equally assigned to S group (serratus anterior plane block, SAPB) group, P group (paravertebral block, PVB) or ST group (serratus anterior combined with transverse thoracic muscle plane blocks, SA-TTMPB). The primary outcome was QoR-15 at five time points after surgery. Secondary outcomes were pain scores, time of first rescue analgesic and chronic pain incidence at 3 months. RESULTS: The QoR-15 total score of S group at 24 h, 48 h, 72 h and 7 days post-surgery was significantly lower in groups P and ST, while there was no significant difference between groups P and ST (S vs. P vs. ST, 100.29 ± 6.20 vs. 108.51 ± 7.46 vs. 106.46 ± 6.95; 105.59 ± 6.18 vs. 113.06 ± 7.44 vs. 111.22 ± 6.56; 112.51 ± 6.32 vs. 119.88 ± 6.44 vs. 117.62 ± 6.09; 123.00 ± 5.78 vs. 128.86 ± 5.96 vs. 126.92 ± 5.72, p < 0.05). The dynamic and rest NRS scores at 6 and 12 h post-surgery were significantly higher in group S than in groups P and ST. CONCLUSION: Serratus anterior plane block combined with transverse thoracic muscle plane block and paravertebral block both have better effects than serratus anterior plane block alone in improving patients' early post-operative recovery quality, and also have an advantage in improving early post-operative pain. CLINICAL TRIAL REGISTRATION: chictr.org.cn (ChiCTR2200059428). DATE OF REGISTRATION: 29 April 2022. SIGNIFICANCE: Serratus anterior combined with transverse thoracic muscle plane block may be a safer, easier, and equally effective nerve block strategy than paravertebral block in patients undergoing modified radical mastectomy for unilateral breast cancer.

Improved anaerobic sludge fermentation mediated by a tryptophan-degrading consortium: Effectiveness assessment and mechanism deciphering.

The hydrolysis of extracellular polymeric substances (EPS) represents a critical bottleneck in the anaerobic fermentation of waste activated sludge (WAS), while tryptophan is identified as an underestimated constituent of EPS. Herein, we harnessed a tryptophan-degrading microbial consortium (TDC) to enhance the hydrolysis efficiency of WAS. At TDC dosages of 5%, 10%, and 20%, a notable increase in SCOD was observed by factors of 1.13, 1.39, and 1.88, respectively. The introduction of TDC improved both the yield and quality of short chain fatty acids (SCFAs), the maximum SCFA yield increased from 590.6 to 1820.2, 1957.9 and 2194.9 mg COD/L, whilst the acetate ratio within SCFAs was raised from 34.1% to 61.2-70.9%. Furthermore, as TDC dosage increased, the relative activity of protease exhibited significant increments, reaching 116.3%, 168.0%, and 266.1%, respectively. This enhancement facilitated WAS solubilization and the release of organic substances from bound EPS into soluble EPS. Microbial analysis identified Tetrasphaera and Soehngenia as key participants in WAS solubilization and the breakdown of protein fraction. Metabolic analysis revealed that TDC triggered the secretion of enzymes associated with amino acid metabolism and fatty acid biosynthesis, thereby fostering the decomposition of proteins and production of SCFAs.

Longitudinal change in CDC42 in psoriasis: correlation with disease activity and treatment response.

Objective: To investigate longitudinal CDC42 change and its correlation with disease activity and treatment response in patients with psoriasis. Methods: This prospective study detected serum CDC42 at months (M) 0, M1, M3 and M6 in 150 patients with psoriasis with current initiation of topical therapy/phototherapy/systemic therapy. Results: CDC42 was positively related to systemic biologic treatment history (p = 0.025) but negatively associated with psoriatic area (p = 0.010) and Psoriasis Area Severity Index (PASI; p < 0.001). CDC42 continuously elevated from M0 to M6 (p < 0.001). CDC42 at M1/M3/M6 was enhanced in patients with current systemic biologic therapy and PASI 75 or 90 response at M6 versus those without (all p < 0.050). Conclusion: Increased serum CDC42 level reflects reduced disease severity and better treatment response in patients with psoriasis.

CDC42 is a protein that plays a role in inflammation and immune regulation in autoimmune diseases. CDC42 levels were detected in 150 patients with psoriasis at different time points and 150 healthy people at enrollment. The results showed that patients with psoriasis had lower CDC42 levels versus healthy people. Patients with psoriasis who received previous biologic treatments and those with smaller affected skin areas had higher CDC42 levels. Over time, CDC42 levels increased in patients with psoriasis. Patients who started biologic treatments (versus those who did not) and patients who responded better to treatment had higher CDC42 levels. The increase in CDC42 levels reflects better treatment outcomes in patients with psoriasis.

A systematic genome-wide analysis and screening of the NAC family genes related to wood formation in Cinnamomum camphora.

Many processes, such as growth, aging, and adaptation to abiotic stress, are regulated in plants by NAC transcription factors. In woody plants, NAC transcription factors acts as a primary switch that regulates secondary xylem development by activating various downstream transcription factors and modulating expression levels of genes involved in the synthesis of the secondary cell wall. Our team had previously sequenced the whole genome of the camphor tree (Cinnamomum camphora). Here, we performed a detailed analysis of the NAC gene family of C. camphora and examined its evolutionary history. The genomic sequences of 121 NAC genes of C. camphora were identified and classified into 20 subfamilies in 2 major classes based on the phylogenetic analysis and structural features. Expansion of the CcNAC gene family occurred mainly by fragment replication and was influenced by the purifying selection. By analyzing predicted interactions of the homologous AtNAC proteins, we identified five CcNACs that potentially regulate xylem development in C. camphora. RNA sequencing revealed distinct expression profiles of CcNACs in seven different plant tissues. Subcellular localization prediction revealed that 120, 3, and 2 CcNACs have biological functions in the nucleus, cytoplasm, and chloroplast, respectively. Furthermore, we verified expression patterns of five CcNACs (CcNAC012, CcNAC028, CcNAC055, CcNAC080, and CcNAC119) in various tissue types using qRT-PCR. Our results will facilitate further in-depth studies of the molecular mechanisms by which CcNAC transcription factors regulate wood formation and other processes in C. camphora.

Genome-Wide Characterization and Analysis of bHLH Transcription Factors Related to Anthocyanin Biosynthesis in Cinnamomum camphora ('Gantong 1').

Cinnamomum camphora is one of the most commonly used tree species in landscaping. Improving its ornamental traits, particularly bark and leaf colors, is one of the key breeding goals. The basic helix-loop-helix (bHLH) transcription factors (TFs) are crucial in controlling anthocyanin biosynthesis in many plants. However, their role in C. camphora remains largely unknown. In this study, we identified 150 bHLH TFs (CcbHLHs) using natural mutant C. camphora 'Gantong 1', which has unusual bark and leaf colors. Phylogenetic analysis revealed that 150 CcbHLHs were divided into 26 subfamilies which shared similar gene structures and conserved motifs. According to the protein homology analysis, we identified four candidate CcbHLHs that were highly conserved compared to the TT8 protein in A. thaliana. These TFs are potentially involved in anthocyanin biosynthesis in C. camphora. RNA-seq analysis revealed specific expression patterns of CcbHLHs in different tissue types. Furthermore, we verified expression patterns of seven CcbHLHs (CcbHLH001, CcbHLH015, CcbHLH017, CcbHLH022, CcbHLH101, CcbHLH118, and CcbHLH134) in various tissue types at different growth stages using qRT-PCR. This study opens a new avenue for subsequent research on anthocyanin biosynthesis regulated by CcbHLH TFs in C. camphora.

Optimization of Sintering Conditions to Enhance the Dielectric Performance of Gd3+ and Ho3+ Codoped BaTiO3 Ceramics.

BaTiO3 dielectric capacitors, one of the important energy storage devices, play critical roles in storing electricity from renewable energies of water, wind, solar, etc. The synthesis of BaTiO3 ceramics with weak temperature dependence and a high dielectric constant at room temperature (εRT') is an urgent problem to meet the miniaturization and large capacity of dielectric capacitors. Doping rare earth elements into BaTiO3 can solve this problem, but it is still challenging. In this work, we adopt a synergistic strategy of increasing εRT' and improving the temperature stability by codoping Gd3+ and Ho3+, respectively, to address this challenge. By carefully adjusting the synthesis conditions in the solid-state reaction, codoping 7% Gd3+ and 7% Ho3+ in BaTiO3 (BGTH7) ceramics were synthesized. The temperature-dependent dielectric constant reveals that the obtained optimal BGTH7 ceramic satisfies the X7U specification and displays a stable ε' in the temperature range of -55~125 °C. The optimal BGTH7 ceramic after sintering at 1400 °C for 6 h exhibits a high dielectric constant of 5475 and low dielectric loss (tan δ) of 0.0176, hitherto exhibiting the best performance in X7U ceramics. The findings in this work are conducive to the miniaturization and stabilization of dielectric energy storage devices.

Photoluminescence Properties of Cyan-Emitting Lu3GaxAl5-xO12: Ce3+ Garnet Phosphors Synthesized in Nonreducing Atmosphere and at Different Temperature for High Quality w-LEDs.

The existence of so-called blue-green cavities in the luminescence spectrum has been a hindrance to the improvement in the performance of traditional phosphor-converted white light emitting diodes. The commercial phosphors synthesized in reducing atmospheres can also cause problems such as equipment complexity, increased cost, and environmental pollution. Herein, a series of cyan-emitting Lu3GaxAl5-xO12: Ce3+ (x = 0, 1, 2, 3, 4) garnet phosphors were synthesized by a traditional solid-state reaction in a nonreducing atmosphere at different temperatures. The crystal structure, grain morphology, optical properties, and thermal quenching behavior were used to analyze the optical properties of the as-prepared phosphors. The luminescence intensity of samples is affected by the synthesis temperature and energy gap between the conduction band and the lowest energy of the 5d excited state of the host lattice. With the substitution of Al3+ by Ga3+, the regularity of the excitation and emission band movement is determined by the combined effects of crystal field splitting (CFS) and the nephelauxetic effect (NE). The temperature dependence of luminescence was studied. The thermal quenching mechanism was clarified by the thermal ionization model. Finally, by employing Lu2.94Ga2Al3O12: Ce3+0.06 as a cyan component, a w-LED with a high color rendering index of 93.2 and low correlation color temperature of 3880 K based on a blue chip and commercial red phosphors were fabricated in order to explore its possible application in high quality w-LED.

Ultraviolet Response in Coplanar Silicon Avalanche Photodiodes with CMOS Compatibility.

Highly sensitive ultraviolet (UV) photodetectors are highly desired for industrial and scientific applications. However, the responsivity of silicon photodiodes in the UV wavelength band is relatively low due to high-density Si/SiO2 interface states. In this paper, a coplanar avalanche photodiode (APD) was developed with a virtual guard ring design. When working in Geiger mode, it exhibited a strong UV response. The responsivity of 4 × 103 A/W (corresponding to a gain of 8 × 106) at 261 nm is measured under the incident power of 0.6 µW with an excess bias of 1.5 V. To the best of our knowledge, the maximum 3-dB bandwidth of 1.4 GHz is the first report ever for a Si APD when working in the Geiger mode in spite of the absence of an integrated CMOS read-out circuit.

Dynamic Changes of Ocular Surface in First-Time Contact Lens Wearers and the Effective Factors of Contact Lens Discomfort.

Purpose: The purpose of the study is to investigate the dynamic changes in ocular surface indicators in first-time contact lens (CL) wearers and identify the most influential factors in CL discomfort (CLD). Methods: A total of 26 healthy non-CL wearers (26 eyes) were recruited and fitted monthly with disposable hydrogel CLs. Each participant underwent a full ocular surface evaluation, which include Efron grading, tear film breakup time, Schirmer's I test, corneal dendritic cell (DCs) imaging by in vivo confocal microscopy (IVCM), and conjunctival microvasculature evaluation by functional slit-lamp biomicroscopy. CLD was assessed using the Ocular Surface Disease Index questionnaire at baseline, 1 week, 1, 3, and 6 months after wearing it and another 6 months after discontinuing it. Results: Clinical signs and CLD were significantly increased in the first week (p < 0.05). The microvascular response and DC activation peaked at the 1-month interval (p < 0.05). During CL wear, CLD is positively correlated with corneal staining (B = 0.238, p = 0.002), papillary conjunctivitis (B = 0.245, p < 0.001), and microvascular blood flow velocity (B = 0.353, p < 0.001). After discontinuation, only DC activation remained elevated at 6 months, whereas the other signs recovered. Conclusions: The first week of CL wear was the main period for the appearance of ocular surface clinical signs, and the first month was the main period for the activation of subclinical inflammation. Corneal staining and conjunctival microvascular response are the main factors affecting CLD. Even if the clinical signs recover after discontinuing wear, subclinical inflammation may persist.

Different Surface Appearances Caused by Unbalanced Mn2+ Accumulation in Gallstones Consisting of Cholesterol and CaCO3 Obtained from a Patient After Cholecystectomy.

Gallstones were examined for 58 patients in Jilin, Jilin. It was found that gallstones from only one who suffered from cholecystectomy were composed of 20 spheroidal stones and they rarely exhibited three different types of surface appearances. Six representative powder samples were analyzed for gallstones compositions and Mn2+ using X-ray diffraction (XRD)/Infrared (IR) and electron spin resonance (ESR), respectively. The results suggested that all gallstones from this patient were identified by XRD to be gallstones consisting mainly of cholesterol and CaCO3 (GCCC). They rarely exhibited three different kinds of surface appearances corresponding to different concentration of trace Mn2+ in calcite (CMn2+/CCal): 18 dark/light brown spheres with smooth surfaces and CMn2+/CCal = 0-6 µg/g/%, a yellowish-brown huge sphere with a rougher surface and CMn2+/CCal = 30 µg/g/%, and an ashy sphere composed of tens of microspheres with the roughest surface and CMn2+/CCal = 60 µg/g/%. The difference in surface appearance showed significant association with CMn2+/CCal, and its increase made the gallstone's surface change from smooth to rough and to fade in color. The unbalanced and competitive Mn2+ accumulation could occur occasionally in individual stones owing to different affinities to Mn2+, resulting in the formation of a huge stone and an ashy sphere. These two aberrations caused by higher CMn2+/CCal played an important role in suppressing the crystalline growth of the majority of dark/light brown spheres. GCCC from a patient might have a prominent Mn2+ partitioning feature corresponding to different surface appearances.

Toward an Orthogonal Protein Lysine Acylation and Deacylation System.

Lysine acetylation is one of the most basic molecular mechanisms to mediate protein functions in living organisms, and its abnormal regulation has been linked to many diseases. The drug development associated to this process is of great significance but severely hindered by the complex interplay of lysine acetylation and deacetylation in thousands of proteins, and we reasoned that targeting a specific protein acetylation or deacetylation event instead of the related enzymes should be a feasible solution to this issue. Toward this goal, we devised an orthogonal lysine acylation and deacylation (OKAD) system, which potentially could precisely dissect the biological consequence of an individual acetylation or deacetylation event in living cells. The system includes a genetically encoded acylated lysine (PhOAcK) that is not a substrate of endogenous deacetylases, and an evolved sirtuin (CobB2/CobB3) that displays PhOAcK deacylase activities as well as reduced deacetylase activities. We believe the strategy introduced here holds potential for future in-depth biological applications.

Limited value of serum neutrophil-to-lymphocyte ratio in the diagnosis of chronic periprosthetic joint infection.

BACKGROUND: Diagnosing chronic periprosthetic joint infection (PJI) is challenging. No single biomarker can accurately recognize PJI preoperatively in a timely manner. Therefore, the aim of the present study was to investigate the usefulness of the serum neutrophil-to-lymphocyte ratio (NLR) in aiding the diagnosis of chronic PJI. MATERIALS AND METHODS: We retrospectively evaluated the medical records of 158 patients who had undergone revision arthroplasty (104 with aseptic mechanic failure and 54 with chronic PJI) from July 2011 to July 2020. Univariate analysis followed by multivariate logistic regression was applied to compare NLR, C-reactive protein (CRP), and erythrocyte sedimentation ratio (ESR) between the two groups. The receiver operating characteristic (ROC) curve was used to assess the diagnostic performance of NLR alone and in combination with CRP and ESR. RESULTS: NLR, CRP, and ESR were significantly higher in patients with chronic PJI than in the aseptic revision group (p < 0.05). ROC curve analysis revealed that NLR had a sensitivity of 57.41% and a specificity of 77.88% with an optimal threshold of 2.56. The optimal threshold for CRP and ESR was 7.00 mg/L (sensitivity 62.50% and specificity 83.12%) and 43 mm/h (sensitivity 59.38% and specificity 80.52%), respectively. The combined diagnostic value of NLR with CRP and ESR was shown to have no additional diagnostic value in predicting chronic PJI. CONCLUSION: Compared with traditional inflammatory biomarkers (ESR and CRP), the value of serum NLR alone or combined with CRP and ESR for diagnosing chronic PJI is limited. LEVEL OF EVIDENCE: Level 3.

Corneal Vertical and Horizontal Thickness Profiles Generated by UHR-OCT for Suspected and Subclinical Keratoconus Diagnosis.

PURPOSE: To verify the diagnostic power of vertical and horizontal thickness profiles of the corneal sublayers generated by ultra-high resolution optical coherence tomography (UHROCT) in subclinical and suspected keratoconus. METHODS: In this cross-sectional study, 25 eyes with confirmed keratoconus, 63 eyes with suspected keratoconus, 15 eyes with subclinical keratoconus, and 42 normal eyes were investigated. Vertical and horizontal thickness profiles of the corneal epithelium, Bowman's layer, and stroma were measured by UHR-OCT. Diagnostic indices included ratios of thickness distribution and multimeric discriminant functions calculated by multiple logistic regression based on them. Receiver operating characteristic curves were used to verify the predictive accuracy by the area under the curve (AUC). RESULTS: Function consisting of two indices (vertical maximum ectasia index of epithelium and horizontal maximum ectasia index of Bowman's layer) performed well to discriminate subclinical keratoconus (AUC = 0.967) and suspected keratoconus (AUC = 0.932) from normal. In addition, when four indices were combined, the diagnostic power for subclinical keratoconus (AUC = 0.984) and suspected keratoconus (AUC = 0.971) was further increased. However, both binary and quaternary functions could not adequately discriminate suspected from subclinical keratoconus. CONCLUSIONS: UHR-OCT-generated thickness indices from the vertical and horizontal thickness profiles of the corneal epithelium and Bowman's layer showed an evident diagnostic efficacy in discriminating suspected and subclinical keratoconus from normal eyes. The early changes in keratoconus might prefer thickness distribution in corneal sublayers rather than corneal thickness or topography. [J Refract Surg. 2021;37(7):438-445.].

E3 ubiquitin ligase TRIM24 deficiency promotes NLRP3/caspase-1/IL-1ß-mediated pyroptosis in endometriosis.

Endometriosis is an inflammation-dependent disease that shares similarities with malignant tumors including attachment and infiltration. Tripartite motif-containing 24 (TRIM24) has been illustrated in inflammatory responses and gynecological tumors, and Nod-like receptor protein 3 (NLRP3) inflammasome has been implicated in endometriosis. However, the involvement of TRIM24 and the role of NLRP3/caspase-1/interleukin-1ß (IL-1ß)-mediated pyroptosis in endometriosis remain obscure. In this study, we originally detected the decreased expression of TRIM24 in the ectopic endometrium of endometriosis compared with the normal endometrium. Then we measured the promoted protein expression of pyroptotic biomarkers (NLRP3, procaspase-1, caspase-1, pro-IL-1ß, and IL-1ß) using Western blot analysis and the stimulated secretion of IL-1ß and IL-18 by enzyme-linked immunosorbent assay in ectopic human endometrial stromal cells (hESC) compared with normal hESC. TRIM24-small-interfering RNA (siTRIM24) was used to silence TRIM24, whereas TRIM24-pcDNA3.1 was used for overexpressing TRIM24. The migration of hESC was determined by a Transwell migration assay. Coimmunoprecipitation and ubiquitination analyses were conducted to explore the interaction between TRIM24 and NLRP3. Subsequently, we found that TRIM24 negatively regulated NLRP3/caspase-1/IL-1ß-mediated pyroptosis and cell migration of hESC, and CY-09, the specific inhibitor of NLRP3, could reverse the promoted pyroptosis and cell migration induced by siTRIM24. Furthermore, TRIM24 interacted with NLRP3 and the upregulation of TRIM24 facilitated the ubiquitination of NLRP3 in ectopic hESC. Our findings suggest that TRIM24 may participate in the progression of endometriosis through the NLRP3/caspase-1/IL-1ß-mediated pyroptotic pathway via ubiquitination of NLRP3, which reveals the significant molecular mechanism underlying endometriosis.

Relationship between corneal biomechanical parameters and corneal sublayer thickness measured by Corvis ST and UHR-OCT in keratoconus and normal eyes.

BACKGROUND: To explore the relationship between corneal biomechanical parameters and corneal sublayer thickness using corneal visualization Scheimpflug technology (Corvis ST) and ultrahigh-resolution optical coherence tomography (UHR-OCT) in clinical and suspected keratoconus and normal eyes. METHODS: Cross-sectional prospective study. A total of 94 eyes of 70 participants were recruited. Twenty five eyes of 19 keratoconus patients, 52 eyes of 34 patients showing high risk of developing keratoconus according to the Belin/Ambrosio Enhanced Ectasia Display, and each eye of 17 normal subjects were enrolled. All participants underwent Corvis ST, Pentacam, and UHR-OCT examinations at the same time. Stiffness parameter A1 (SP-A1), deformation amplitude ratio (DA ratio), and other biomechanical parameters were recorded using Corvis ST. The vertical and horizontal thickness profiles of central 3 mm corneal epithelium, Bowman's layer, and stroma as measured by the perpendicular distance between the neighboring interfaces were generated using UHR-OCT. The flat keratometry and steep keratometry were obtained using Pentacam. Analysis of correlation was applied to explore the association between variables. RESULTS: Most of the biomechanical parameters and corneal sublayer thickness profiles showed statistical differences among three groups. A statistically significant linear relationship was noted between SP-A1 and DA ratio in all three groups. SP-A1 was found to be positively correlated with epithelial and Bowman's layer thickness in the keratoconus (KC) group, and with stromal thickness in all three groups. In the normal and suspected keratoconus (SKC) groups, only stromal thickness was included in the stepwise linear regression to predict SP-A1, whereas in the KC group, steep keratometry and Bowman's layer thickness were included. CONCLUSIONS: Significant and different correlations were noted between corneal stiffness and corneal sublayer thickness in different groups, indicating that corneal sublayers may play different roles in maintaining corneal biomechanical stability between keratoconus and normal eyes.

Ursolic Acid Protects Against Proliferation and Inflammatory Response in LPS-Treated Gastric Tumour Model and Cells by Inhibiting NLRP3 Inflammasome Activation.

BACKGROUND: Inflammation is considered as one of the hallmarks of cancer development and progression. Ursolic acid (UA) showed strong effects as an anti-inflammatory and antioxidant. However, the anti-cancer effects of ursolic acid require further study. METHODS: This study aimed to investigate the role of ursolic acid in a lipopolysaccharide (LPS)-treated gastric tumour mouse model and in a human gastric carcinoma cell line (BGC-823 cells). This study also aimed to confirm whether ursolic acid can protect against proliferation and the inflammatory response induced by LPS, by inhibiting the activation of the NLRP3 inflammasome via the NF-κB pathway. RESULTS: The present study demonstrated that ursolic acid significantly attenuated LPS-treated proliferation in a gastric tumour mouse model and the human gastric carcinoma BGC-823 cell line, reduced the expression of the NLRP3 inflammasome and suppressed the release of pro-inflammatory cytokines. In addition, ursolic acid inhibited the LPS-induced activation of NF-κB. Furthermore, the NF-κB pathway regulated the activation of the NLRP3 inflammasome. CONCLUSION: In conclusion, these results demonstrated that ursolic acid could suppress proliferation and the inflammatory response in an LPS-induced mouse gastric tumour model and human BGC-823 cells by inhibiting the activation of the NLRP3 inflammasome via the NF-κB pathway. This indicates that ursolic acid can be a potential therapeutic agent for the treatment of gastric cancer.

Cinobufacini Inhibits Colon Cancer Invasion and Metastasis via Suppressing Wnt/ß-Catenin Signaling Pathway and EMT.

Cinobufacini is a well-known Chinese medicine extracted from Venenum Bufonis, also called Chan Su. It has been used clinically for various cancers, including colon cancer. However, the function of Cinobufacini on colon cancer invasion and metastasis, and its underlying molecular mechanism, is still not clear. In this study, we investigated the function and mechanism of Cinobufacini on colon cancer invasion and metastasis both in vitro and in vivo studies. Human colon cancer cells were cultured. CCK assay was used to detect the effect of Cinobufacini on colon cancer cells proliferation. The invasion and migration abilities were observed by transwell assays, and the expression of invasion and migration related genes MMP2, MMP9, and epithelial-to-mesenchymal transition (EMT) relate genes were observed by Western blot assays. An orthotopic xenograft model in nude mice was established using colon cancer HCT116 cells, and the function of Cinobufacini on colon cancer invasion and metastasis were observed in vivo. We found Cinobufacini significantly inhibited colon cancer cell proliferation in a dose/time-dependent manner; the invasion and migration abilities of colon cancer were decreased after treated with Cinobufacini. The metastasis and EMT related genes MMP9, MMP2, N-cadherin and Snail were obviously down-regulated, while the expression of E-cadherin was up-regulated after treatment with Cinobufacini. The Wnt/ß-catenin signaling pathway related genes were observed using WB,and results show that the expression of ß-catenin, wnt3a, c-myc, cyclin D1, and MMP7 were all down-regulated after being treated with cinobufacini, while the expression of APC was up-regulated. In vivo studies of the volume and weight of orthotopic xenograft tumors showed significantly shrinkage in the Cinobufacini group compared to the control group. The enterocoelia and liver metastasis tumors were significantly decreased, and the expression of MMP9, MMP2, and ß-catenin were also down-regulated, while E-cadherin was up-regulated in vivo after the treatment with Cinobufacini. Our data proves that Cinobufacini can inhibit colon cancer invasion and metastasis both in vitro and in vivo; the mechanism is related by suppressing the Wnt/ß-catenin signaling pathway and then inhibiting the EMT of CRC.