IL-38 alleviates airway remodeling in chronic asthma via blocking the profibrotic effect of IL-36γ.

Airway remodeling is a major feature of asthma. Interleukin (IL)-36γ is significantly upregulated and promotes airway hyper-responsiveness (AHR) in asthma, but its role in airway remodeling is unknown. Here, we aimed to investigate the role of IL-36γ in airway remodeling, and whether IL-38 can alleviate airway remodeling in chronic asthma by blocking the effects of IL-36γ. IL-36γ was quantified in mice inhaled with house dust mite (HDM). Extracellular matrix (ECM) deposition in lung tissues and AHR were assessed following IL-36γ administration to mice. Airway inflammation, AHR, and remodeling were evaluated after IL-38 or blocking IL-36 receptor (IL-36R) treatment in asthmatic mice. The effects of lung fibroblasts stimulated with IL-36γ and IL-38 were quantified in vitro. Increased expression of IL-36γ was detected in lung tissues of HDM-induced asthmatic mice. The intratracheal instillation of IL-36γ to mice significantly enhanced the ECM deposition, AHR, and the number of activated lung fibroblasts around the airways. IL-38 or blocking IL-36R treated asthmatic mice showed a significant alleviation in the airway inflammation, AHR, airway remodeling, and number of activated fibroblasts around airways as compared with the HDM group. In vitro, IL-36γ promoted the activation and migration of human lung fibroblasts (HFL-1). The administration of IL-38 can counteract these biological processes induced by IL-36γ in HFL-1cells. The results indicated that IL-38 can mitigate airway remodeling by blocking the profibrotic effects of IL-36γ in chronic asthma. IL-36γ may be a new therapeutic target, and IL-38 is a potential candidate agent for inhibiting airway remodeling in asthma.

Clinical and computed tomographic evaluations of periodontal phenotypes in a Chinese population: a cross-sectional study.

OBJECTIVES: To investigate the diagnostic value of probe transparency related to gingival thickness (GT) and keratinized gingival width (KGW) at individual and site levels and explore the relationship of buccal bone plate thickness (BT) with GT and KGW. MATERIALS AND METHODS: A total of 1,606 teeth from 167 patients with periodontally healthy maxillary anterior region were included. GT was measured with probe transparency and transgingival probing. KGW was measured directly. BTs were assessed at the level 1 mm apical to the alveolar crest (BT1) and midpoint of the root (BT2) and evaluated at individual and tooth levels along with their mutual associations. RESULTS: The prevalence of thick gingiva was 53% with probe transparency measurement and 51% with transgingival probing. The cutoff gingival thickness was 0.8 mm, which correlated moderately with a Cohen's kappa of 0.386. The mean GT, KGW, and BTs (BT1 and BT2) in the maxillary anterior region were 0.97 ± 0.46, 5.51 ± 1.62, 0.85 ± 0.31, and 0.79 ± 0.32 mm, respectively. GT and KGW correlated mildly (r = 0.261), and GT and BTs correlated moderately (BT1: r = 0.298; BT2: r = 0.338). GT and BTs differed significantly between men and women and among different tooth sites. CONCLUSIONS: GT and BTs correlated positively in the maxillary anterior region and varied within and among individuals. Sex was a factor influencing the gingival phenotype and bone morphotype. CLINICAL RELEVANCE: GT measured with transgingival probing, with a cutoff of 0.8 mm, could serve as an objective measure to distinguish different gingival phenotypes.

Enhancing Flame Retardancy and Smoke Suppression in Epoxy Resin Composites with Sulfur-Phosphorous Reactive Flame Retardant.

The presence of massive amounts of toxic volatiles and smoke during combustion is a very serious problem facing epoxy resin (EP) composites. Therefore, flame retardants (FRs) can simultaneously enhance flame retardancy and reduce the release of smoke and fatal gases. Herein, a novel sulfur-phosphorous reactive flame retardant (SPMS) was synthesized for epoxy resin. The high efficiency of smoke suppression and flame retardancy of the EP/SPMS-APP hybrid was investigated using a cone calorimeter, a vertical burning test, and limited oxygen index measurements. Compared with those of pure EP, the composite with 20 wt% SPMS-APP reduced the peak heat release rate (pHRR), the peak smoke production rate (SPR), and total smoke production rate (TSR) by 82%, 94%, and 84%, respectively. The results showed a remarkable suppressed effect of alleviating the fire hazard of EP using a sulfur-phosphorus flame retardant.

Belumosudil, ROCK2-specific inhibitor, alleviates cardiac fibrosis by inhibiting cardiac fibroblasts activation.

Cardiac fibrosis is thought to be the hallmark of pathological hypertrophic remodeling, of which the myofibroblast transdifferentiation is the key cell biological event. However, there is still no specific and effective therapeutic agent approved for cardiac fibrosis. To investigate the effects of belumosudil, the first ρ-associated kinase-2 (ROCK2)-specific inhibitor, on cardiac hypertrophy, fibrosis, and dysfunction induced by pressure overload, the transverse aortic constriction (TAC) or sham operation was carried out on wild-type C57BL/6 mice (male, 6-8 wk old) under pentobarbital anesthesia. After that, mice were randomly divided into three groups: sham operation + vehicle, TAC + vehicle, TAC + 50 mg·kg-1·day-1 belumosudil. We found that belumosudil effectively ameliorated cardiac hypertrophy, fibrosis, and dysfunction in TAC mice. To elucidate the underlying mechanism, we inhibited the expression of ROCK2 in vitro by either belumosudil or siRNA. We showed that the inhibition of ROCK2 by either belumosudil or knockdown suppressed cardiac fibroblasts activation and proliferation significantly induced by transforming growth factor-ß1 (TGF-ß1). Furthermore, our study confirmed ROCK2 mediates cardiac fibrosis by interacting with TGF-ß1/mothers against decapentaplegic homolog 2 (Smad2) pathway. Taken together, we demonstrated that belumosudil ameliorates cardiac hypertrophy and fibrosis induced by TAC via inhibiting cardiac fibroblasts activation. In conclusion, belumosudil may be a promising therapeutic drug for cardiac hypertrophy and fibrosis induced by myocardial pressure overload.NEW & NOTEWORTHY Although ρ-associated kinase-2 (ROCK2) is the main isoform of ρ-associated kinases (ROCKs) in the heart and more important in cardiac hypertrophy and fibrosis than ρ-associated kinase-1 (ROCK1), there has not been any pharmacological approach to inhibit ROCK2 selectively. Our study demonstrates for the first time that belumosudil, the first ROCK2-specific inhibitor, effectively ameliorates cardiac hypertrophy, fibrosis, and dysfunction induced by TAC via inhibiting cardiac fibroblasts activation.

IL-37 protects against airway remodeling by reversing bronchial epithelial-mesenchymal transition via IL-24 signaling pathway in chronic asthma.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is one of the mechanisms of airway remodeling in chronic asthma. Interleukin (IL)-24 has been implicated in the promotion of tissue fibrosis, and increased IL-24 levels have been observed in the nasal secretions and sputum of asthmatic patients. However, the role of IL-24 in asthmatic airway remodeling, especially in EMT, remains largely unknown. We aimed to explore the effect and mechanism of IL-24 on EMT and to verify whether IL-37 could alleviate IL-24-induced EMT in chronic asthma. METHODS: BEAS-2B cells were exposed to IL-24, and cell migration was assessed by wound healing and Transwell assays. The expression of EMT-related biomarkers (E-cadherin, vimentin, and α-SMA) was evaluated after the cells were stimulated with IL-24 with or without IL-37. A murine asthma model was established by intranasal administration of house dust mite (HDM) extracts for 5 weeks, and the effects of IL-24 and IL-37 on EMT and airway remodeling were investigated by intranasal administration of si-IL-24 and rhIL-37. RESULTS: We observed that IL-24 significantly enhanced the migration of BEAS-2B cells in vitro. IL-24 promoted the expression of the EMT biomarkers vimentin and α-SMA via the STAT3 and ERK1/2 pathways. In addition, we found that IL-37 partially reversed IL-24-induced EMT in BEAS-2B cells by blocking the ERK1/2 and STAT3 pathways. Similarly, the in vivo results showed that IL-24 was overexpressed in the airway epithelium of an HDM-induced chronic asthma model, and IL-24 silencing or IL-37 treatment could reverse EMT biomarker expression. CONCLUSIONS: Overall, these findings indicated that IL-37 mitigated HDM-induced airway remodeling by inhibiting IL-24-mediated EMT via the ERK1/2 and STAT3 pathways, thereby providing experimental evidence for IL-24 as a novel therapeutic target and IL-37 as a promising agent for treating severe asthma.

Microbial Contamination Characteristics on Touch Surfaces in Outpatient Self-Service Facilities.

BACKGROUND: With the development of science and technology, self-service facilities have been widely used in hospitals. This study aimed to assess the microbial contamination characteristics on touch surfaces in outpatient, self-service facilities from Monday to Friday. METHODS: Touch surfaces in outpatient facilities were swabbed and surveyed for total microbial growth before and after work every morning. Selected bacteria were identified to screen for pathogenic organisms. RESULTS: There were 360 samples collected, 87 samples (24.2%) were culture-positive. Staphylococcus species were the main microbial contamination. The three most common bacteria were S. hominis, S. epidermidis and S. hemolyticus. After work, more microbial contamination was found on Monday (p = 0.029). There was no difference in sample positive rates between self-service facilities and manual service area. Although, the antibiotic resistance patterns of different staphylococcus species were different, the overall drug resistance rate is low. Only one S. aureus was methicillin-Sensitive S. aureus. CONCLUSIONS: The self-service facilities' touch surfaces microbial contamination were similar to manual service area, but the more used, the more microbial contamination was found. Hospitals should enhance cleaning times of self-service facilities to keep them clean, especially on Mondays.

Three-dimensional quantitative measurement of buccal augmented tissue with modified coronally advanced tunnel technique and de-epithelialized gingival graft: a prospective case series.

BACKGROUND: The aim of this study is to investigate three-dimensional quantitative analysis of buccal augmented tissue alterations after surgery using a modified coronally advanced tunnel (MCAT) technique combined with a de-epithelialized gingival graft (DGG) within 1 year post-op, based on intraoral scanning. METHODS: 25 Cairo class I gingival recession defects were treated using an MCAT technique with DGG. Digital impressions were taken using an intraoral scanner at baseline, 2 weeks, 6 weeks, 3 months, and 1 year after the surgery. Three-dimensional quantitative measurements within 1 year were analyzed for buccal augmented tissue after surgery, including postoperative gingival height gain (GHG), area gain (GAG), volume gain (GVG) and mean thickness (GMT) of region of interest, as well as the tissue thickness change at 1, 2, and 3 mm (TTC1, TTC2, and TTC3) apical to the cemento-enamel junction. RESULTS: Postoperative GHG, GAG, GVG, and GMT were distinctly encountered at 2 weeks post-op, then gradually decreased. At 1 year, GHG, GAG, GVG, and GMT were 2.211 ± 0.717 mm, 7.614 ± 2.511 mm2, 7.690 ± 4.335 mm3 and 0.965 ± 0.372 mm, respectively. Significant decreases were recorded between 6 weeks and 1 year in terms of GHG, GAG, and GVG. The GMT was sustained after 6 weeks with an increase of nearly 1 mm at 1 year. TTC1 and TTC2 yielded thicker tissue change than TTC3. CONCLUSIONS: Three-dimensional quantitative measurements taken via intraoral scanning showed that buccal augmented tissue acquired via MCAT with DGG tends to be stable after 3 months post-op. Digital measurement can be applied in periodontal plastic surgery as a clinically feasible and non-invasive evaluation method for achieving volumetric outcomes. TRIAL REGISTRATION: This study was retrospectively registered in the Chinese Clinical Trial Registry: ChiCTR1900026768. Date of registration: 21/10/2019.

Evaluation of salivary biomarkers for the diagnosis of periodontitis.

BACKGROUND: Salivary interleukin (IL)-1ß, matrix metalloproteinase (MMP)-8, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and Porphyromonas gingivalis (Pg) are related to periodontitis. This study aimed to investigate the diagnostic potential of these biomarkers and to build a prediction panel for diagnosing periodontal disease. METHODS: A total of 80 participants were enrolled in a cross-sectional study and divided into healthy (n = 25), gingivitis (n = 24), and periodontitis (n = 31) groups based on their periodontal exam results. A full mouth periodontal examination was performed and unstimulated saliva was collected. Salivary IL-1ß, MMP-8, ICTP, and Pg were assessed using enzyme-linked immunosorbent assay (ELISA) and quantitative real time PCR (qPCR). Their potentials for diagnosing periodontal disease were analyzed and combined prediction panels of periodontal disease were evaluated. RESULTS: As a single marker, IL-1ß showed the best diagnostic value of the four markers evaluated and exhibited an area under the curve (AUC) value of 0.88 with 90% sensitivity and 76% specificity for discriminating periodontitis subjects from healthy subjects, an AUC value of 0.80 with 83% sensitivity and 76% specificity for discriminating gingivitis subjects from healthy subjects and an AUC value of 0.66 with 68% sensitivity and 64% specificity for differentiating periodontitis subjects from gingivitis subjects. The combination of IL-1ß, ICTP, and Pg exhibited the highest efficacy for discriminating periodontitis subjects from healthy subjects (AUC = 0.94) and gingivitis subjects (AUC = 0.77). The combination of IL-1ß and MMP-8 exhibited the best ability to discriminate gingivitis from healthy subjects (AUC = 0.84). CONCLUSIONS: Salivary IL-1ß, MMP-8, ICTP, and Pg showed significant effectiveness for diagnosing periodontal disease. The combination of IL-1ß, ICTP, and Pg can be used to discriminate periodontitis subjects from healthy subjects and gingivitis subjects, and the combination of IL-1ß and MMP-8 can be used to discriminate gingivitis subjects from healthy subjects.

Manganese(II)-doped zinc/germanium oxide nanoparticles as a viable fluorescent probe for visual and time-resolved fluorometric determination of ascorbic acid and its oxidase.

A method is described for the determination of ascorbic acid (AA) in complex biological fluids. It based on maganese(II)-doped zinc/germanium oxide nanoparticles (Mn@ZnGe NPs) with appealing time-resolved phosphorescence (TRP). TRP can provide a background-free reporter signal in analytical methods. The absorption of AA overlaps the excitation band of Mn@ZnGe NPs at 254 nm. This reduces the intensity of fluorescence via an inner filter effect (IFE) with increasing concentration of AA. Typical experimental conditions include an emission peak at 536 nm, a delay time of 50 µs and a counting time of 2 ms. This method can detect AA in a range of 5-500 µM with a 0.13 µM limit of detection. If AA is oxidized by the enzyme AA oxidase (AAOx), dehydroascorbic acid will be formed which doesn't absorb at 254 nm. Hence, the IFE cannot occur and fluorescence is not reduced. The strategy can be used to quantify AAOx in the activity range of 1-4 U·mL-1. By using a handheld UV lamp and a smart phone with a color-scanning feature, the feasibility for visual detection and real-time/onsite quantitative scanometric monitoring of AA and AAOx is demonstrated. Graphical abstract Schematic presentation of a fluorometric method for determination of ascorbic acid (AA) and ascorbic oxidase and a scanometric visual assay. It based on the use of maganese(II)-doped zinc/germanium oxide nanoparticles (Mn@ZnGe NPs) with appealing time-resolved phosphorescence (TRP) and the inner-filter effect (IFE) between AA and Mn@ZnGe NPs.

DACT1 is involved in human placenta development by promoting Wnt signaling.

OBJECTIVE: The aim of this study was to evaluate the expression of DACT1 in human placenta tissue and the relationship between DACT1 and target genes of the Wnt signaling pathway. METHOD: Real-time PCR and western blotting were used to detect the expression of DACT1 and the target genes of Wnt signaling pathway in human placenta tissue. And the relationship between them was analyzed using SPSS 19. RESULTS: Real-time PCR results showed that DACT1 expression was significantly higher in 49- to 71-day placenta tissues (mean value = 0.020) than that in 39- to 48-day (the mean value = 0.009). The mRNA expressions of the Wnt signaling pathway target genes, CCND1, CCND2, FOSL1, DAB2 and JUN, were also increased expressed in human placenta tissues. Significant positive associations between DACT1 and CCND1, CCND2, FOSL1, DAB2 and JUN were observed. Western blotting analysis showed that the protein expression of DACT1, CCND1, CCND2, FOSL1, DAB2 and JUN displayed the increasing trend in 43-, 49- and 71-day placenta samples. CONCLUSION: DACT1 might play an important role in human placenta development via promoting Wnt signaling.

[Preparation and optimum process of walnut peel activated carbon by zinc chloride as activating agent].

Walnut peel as raw material, zinc chloride was used as activating agent for preparation walnut peel activated carbon in the muffle furnace in this experiment, using orthogonal design. Yield, the specific surface area and iodine number of walnut peel activated carbon were determined at all designed experimental conditions and the optimum technological condition of preparation was obtained. By analysis of aperture, infrared spectra and the content of acidic group in surface with Boehm, walnut peel activated carbon of prepared at the optimum condition was characterized. The results showed the optimum technological parameters of preparation: activation temperature (600 °C), activation time (1 h), the concentration of zinc chloride (50%), the particle size (60 mesh). The specific surface area of walnut peel activated carbon obtained at optimum condition was mounting to 1258.05 m2 · g(-1), the ratio of medium porous 32.18%. Therefore, walnut peel can be used in the preparation of the high-quality activated carbon of large surface area. Agricultural wastes, as walnut peel, not only were implemented recycle, but also didn't make any pollution. Meanwhile, a cheap adsorbent was provided and it was of great significance to open a new source of activated carbon.

Inhibition of lysyl oxidase by pharmacological intervention and genetic manipulation alleviates epilepsy-associated cognitive disorder.

Epilepsy-associated cognitive disorder (ECD), a prevalent comorbidity in epilepsy patients, has so far uncharacterized etiological origins. Our prior work revealed that lysyl oxidase (Lox) acted as a novel contributor of ferroptosis, a recently discovered cell death mode in the regulation of brain function. However, the role of Lox-mediated ferroptosis in ECD remains unknown. ECD mouse model was established 2 months later following a single injection of kainic acid (KA) for. After chronic treatment with KA, mice were treated with different doses (30 mg/kg, 100 mg/kg and 300 mg/kg) of Lox inhibitor BAPN. Additionally, hippocampal-specific Lox knockout mice was also constructed and employed to validate the role of Lox in ECD. Cognitive functions were assessed using novel object recognition test (NOR) and Morris water maze test (MWM). Protein expression of phosphorylated cAMP-response element binding (CREB), a well-known molecular marker for evaluation of cognitive performance, was also detected by Western blot. The protein distribution of Lox was analyzed by immunofluorescence. In KA-induced ECD mouse model, ferroptosis process was activated according to upregulation of 4-HNE protein and a previously discovered ferroptosis in our group, namely, Lox was remarkably increased. Pharmacological inhibition of Lox by BAPN at the dose of 100 mg/kg significantly increased the discrimination index following NOR test and decreased escape latency as well as augmented passing times within 60 s following MWM test in ECD mouse model. Additionally, deficiency of Lox in hippocampus also led to pronounced improvement of deficits in ECD model. These findings indicate that the ferroptosis regulatory factor, Lox, is activated in ECD. Ablation of Lox by either pharmacological intervention or genetic manipulation ameliorates the impairment in ECD mouse model, which suggest that Lox serves as a promising therapeutic target for treating ECD in clinic.

Survival of nonsurgically splinted mandibular anterior teeth during supportive maintenance care in periodontitis patients.

Background/purpose: Splinting mobile teeth is a choice to improve the patient's oral comfort. The purpose of this study was to assess the survival and stability of mobile anterior mandibular teeth after splinting in patients with periodontitis undergoing supportive periodontal therapy (SPT). Materials and methods: Patients with splinted mobile anterior mandibular teeth were assessed retrospectively. Periodontal statuses were recorded at baseline and follow-up visits. Tooth and splint survival as well as splint repairs were recorded. Multilevel Cox regression analyses were performed to evaluate patient- and tooth-related factors that might have influenced the survival rates of splints. Results: Sixty-one patients, collectively having 161 splints, were followed for an average of 5.44 years. On average, probing depth (PD) of splinted teeth decreased from 4.31 mm to 2.93 mm and clinical attachment loss (CAL) decreased from 5.02 mm to 4.58 mm. Alveolar bone was stable in the follow-up period. None of the splinted teeth were extracted, The overall survival rate of the splints was 65.2%. Splints made of composite resin alone were associated with a higher risk of breakage when compared to splints composed of composite resin with mesh grid strips. Conclusion: Splinting showed long-term survival and splinting combined with periodontal supportive treatment is a feasible option to maintain mobile mandibular anterior teeth.

Rich Organic Nitrogen Impacts Clavulanic Acid Biosynthesis through the Arginine Metabolic Pathway in Streptomyces clavuligerus F613-1.

Clavulanic acid (CA) is the preferred clinical drug for the treatment of infections by ß-lactam antibiotic-resistant bacteria. CA is produced by Streptomyces clavuligerus, and although there have been many reports on the effects of carbon and nitrogen sources on CA production, the mechanisms involved remain unclear. In this study, we found that CA accumulation in S. clavuligerus F613-1 was increased significantly in MH medium, which is rich in organic nitrogen, compared with that in ML medium, which contains half the amount of organic nitrogen present in MH medium. Transcriptome analysis revealed that genes involved in CA biosynthesis, such as ceas1, ceas2, bls1, bls2, cas2, pah2, gcaS, and cad, and arginine biosynthesis, such as argB, argC, argD, argG, argH, argJ, and argR, were upregulated under rich organic nitrogen. Metabolome data revealed notable differences between cultures of F613-1 grown in MH and ML media with regard to levels of key intracellular metabolites, most of which are involved in arginine metabolic pathways, including arginine, glutamine, and glutamic acid. Additionally, supplementation of ML medium with arginine, glutamine, or glutamic acid resulted in increased CA production by S. clavuligerus F613-1. Our results indicate that rich organic nitrogen mainly affects CA biosynthesis by increasing the levels of amino acids associated with the arginine metabolic pathway and activating the expression of the CA biosynthetic gene cluster. These findings provide important insights for improving medium optimization and engineering of S. clavuligerus F613-1 for high-yield production of CA. IMPORTANCE The bacterium Streptomyces clavuligerus is used for the industrial production of the broad-spectrum ß-lactamase inhibitor clavulanic acid (CA). However, much remains unknown about the factors which affect CA yields. We investigated the effects of different levels of organic nitrogen on CA production. Our analyses indicate that higher organic nitrogen levels were associated with increased CA yields and increased levels of arginine biosynthesis. Further analyses supported the relationship between arginine metabolism and CA production and demonstrated that increasing the levels of arginine or associated amino acids could boost CA yields. These findings suggest approaches for improving the production of this clinically important antibiotic.

[Preparation of porous organic cage and its use as chiral stationary phase for capillary electrochromatography].

Porous organic cages (POCs) are a unique type of microporous materials composed of discrete molecules with internal cavities that are accessible to various compounds. In this study, a prismatic chiral POC with good thermochemical stability was synthesized by condensing (1R,2R)-diaminocyclohexane and 3,3',5,5'-teturonic-4,4'-biphenediol via the Schiff base reaction and characterized by proton nuclear magnetic resonance spectroscopy, infrared (IR) spectroscopy, thermogravimetric analysis (TGA), and scanning electron microscopy. The IR spectrum of the POC revealed a strong characteristic absorption peak at 1635 cm-1, indicating that it formed imine bonds (C=N). The absorption peak at 3425 cm-1 was attributed to the stretching vibrations of -OH, the absorption peaks at 2925 and 2858 cm-1 were attributed to the stretching vibrations of N=C-H and C-H, and the absorption peaks at 1446 and 1383 cm-1 were attributed to the stretching vibrations of C=C-H and C=C in the benzene ring. High-resolution mass spectral analysis of the POC showed a molecular ion peak at m/z 1363.7228, indicating its successful synthesis. TGA was performed from 25 to 800 ℃ at a rate of 10 ℃/min, and the results of this analysis showed that the POC was stable up to approximately 300 ℃. The POC was dissolved in dichloromethane and uniformly coated on the inner wall of a quartz capillary via the dynamic coating method to prepare a capillary electrochromatographic column. The experimental results revealed that the chiral electrochromatographic column could not only resolve ofloxacin, Troger's base, 2-amino-1-butanol, and 1-phenyl-1-amyl alcohol but also separate the isomers of o-, m-, and p-toluidine and o-, m-, and p-chloroaniline, indicating its good chiral separation ability. Investigation of the optimal separation conditions for ofloxacin, Troger's base, 2-amino-1-butanol, and 1-phenyl-1-amyl alcohol revealed that the voltage, buffer solution concentration, and pH significantly affected their separation degree. In particular, the optimal separation voltage for ofloxacin, Troger's base, and 2-amino-1-butanol was 15 kV, while that for 1-phenyl-1-amyl alcohol was 17 kV. The optimal buffer concentration and pH for ofloxacin, Troger's base, 2-amino-1-butanol, and 1-phenyl-1-amyl alcohol were 0.100 mol/L and 7.5. Under optimal chromatographic conditions, the resolution values for ofloxacin, Troger's base, 2-amino-1-butanol, and 1-phenyl-1-pentanol were 1.80, 3.33, 1.69, and 1.18, respectively. The results collectively demonstrate that the prepared POC may serve as a good chiral stationary phase for capillary electrochromatography with a certain chiral resolution ability and has good application prospects in chromatographic separation.

Mitophagy-related gene signature predicts prognosis, immune infiltration and chemotherapy sensitivity in colorectal cancer.

BACKGROUND: Mitophagy plays essential role in the development and progression of colorectal cancer (CRC). However, the effect of mitophagy-related genes in CRC remains largely unknown. AIM: To develop a mitophagy-related gene signature to predict the survival, immune infiltration and chemotherapy response of CRC patients. METHODS: Non-negative matrix factorization was used to cluster CRC patients from Gene Expression Omnibus database (GSE39582, GSE17536, and GSE37892) based on mitophagy-related gene expression. The CIBERSORT method was applied for the evaluation of the relative infiltration levels of immune cell types. The performance signature in predicting chemotherapeutic sensitivity was generated using data from the Genomics of Drug Sensitivity in Cancer database. RESULTS: Three clusters with different clinicopathological features and prognosis were identified. Higher enrichment of activated B cells and CD4+ T cells were observed in cluster III patients with the most favorable prognosis. Next, a risk model based on mitophagy-related genes was developed. Patients in training and validation sets were categorized into low-risk and high-risk subgroups. Low risk patients showed significantly better prognosis, higher enrichment of immune activating cells and greater response to chemotherapy (oxaliplatin, irinotecan, and 5-fluorouracil) compared to high-risk patients. Further experiments identified CXCL3 as novel regulator of cell proliferation and mitophagy. CONCLUSION: We revealed the biological roles of mitophagy-related genes in the immune infiltration, and its ability to predict patients' prognosis and response to chemotherapy in CRC. These interesting findings would provide new insight into the therapeutic management of CRC patients.

Automatic mechanisms for measuring subjective unit of discomfort.

Current practice in Virtual Reality Exposure Therapy (VRET) is that therapists ask patients about their anxiety level by means of the Subjective Unit of Discomfort (SUD) scale. With an aim of developing a home-based VRET system, this measurement ideally should be done using speech technology. In a VRET system for social phobia with scripted avatar-patient dialogues, the timing of asking patients to give their SUD score becomes relevant. This study examined three timing mechanisms: (1) dialogue dependent (i.e. naturally in the flow of the dialogue); (2) speech dependent (i.e. when both patient and avatar are silent); and (3) context independent (i.e. randomly). Results of an experiment with non-patients (n = 24) showed a significant effect for the timing mechanisms on the perceived dialogue flow, user preference, reported presence and user dialog replies. Overall, dialogue dependent timing mechanism seems superior followed by the speech dependent and context independent timing mechanism.

Use of Urban Residential Community Parks for Stress Management During the COVID-19 Lockdown Period in China.

During the pandemic lockdown period, residents had to stay at home and increased stress and other mental health problems have been associated with the lockdown period. Since most public parks were closed, community parks within gated residential areas became the most important green space in Chinese cities, and the use of such space might help to reduce the residents' stress levels. This study aimed to investigate to what extent urban residents in China used community parks, engaged in outdoor activity during the lockdown period (23 January-8 April 2020) and if the use of such spaces helped to reduce their stress levels. An online questionnaire survey (n = 1342) was carried out from 23 March to 23 April 2020. Ordinary Least Squares regression was used to analyse the association between community park use, outdoor activity, willingness to engage in outdoor activity, and stress level. All results have been further analysed by two-sampled t-test to explore the difference between young and old age groups. We found that the overall self-reported stress level of the respondents was relatively moderate during the lockdown period. Respondents had generally reduced their use of community parks and engagement in outdoor activity. There was no significant association between stress level and the use of community parks or the engagement in outdoor activities. However, we found that older people showed much lower stress levels, used community parks more frequently, and engaged in more outdoor activities than younger adults. The findings suggest that outdoor activities and spatial characteristics in urban China differ from Western studies and advance the need to integrate the stress management role of community parks with urban green space policy to optimise the use of community parks blended in with everyday life, particularly during the lockdown period.

Periodontitis induced by Porphyromonas gingivalis drives impaired glucose metabolism in mice.

Periodontitis has been demonstrated to be bidirectionally associated with diabetes and has been recognized as a complication of diabetes. As a periodontal pathogen, Porphyromonas gingivalis is a possible pathogen linking periodontal disease and systemic diseases. It has also been found to be involved in the occurrence and development of diabetes. In this study, 6-week-old male C57BL/6 mice were orally administered the P. gingivalis strain ATCC381 for 22 weeks. Histological analysis of the gingival tissue and quantified analysis of alveolar bone loss were performed to evaluate periodontal destruction. Body weight, fasting glucose, glucose tolerance test (GTT), and insulin tolerance test (ITT) were used to evaluate glucose metabolism disorder. We then analyzed the expression profiles of inflammatory cytokines and chemokines in gingival tissue, the liver, and adipose tissue, as well as in serum. The results showed that mice in the P. gingivalis-administered group developed apparent gingival inflammation and more alveolar bone loss compared to the control group. After 22 weeks of P. gingivalis infection, significant differences were observed at 30 and 60 min for the GTT and at 15 min for the ITT. P. gingivalis-administered mice showed an increase in the mRNA expression levels of the pro-inflammatory cytokines (TNF-α, IL-6, IL-17, and IL-23) and chemokines (CCL2, CCL8, and CXCL10) in the gingiva and serum. The expression levels of the glucose metabolism-related genes were also changed in the liver and adipose tissue. Our results indicate that oral administration of P. gingivalis can induce changes in the inflammatory cytokines and chemokines in the gingiva and blood, can lead to alveolar bone loss and to inflammatory changes in the liver and adipose tissues, and can promote glucose metabolism disorder in mice.

Rare cause of voice muffling: pyogenic vallecular cyst.

A vallecular cyst is a benign laryngeal cyst that rarely causes symptoms in adults. We report a rare case of an infected vallecular cyst in a man who is in his 60s with diabetes mellitus. The patient presented to us with acute onset of voice muffling and respiratory distress. He showed signs of sepsis and upper airway obstruction. He had spikes of high-grade fever with an elevated total white cell count (predominantly neutrophil count) and C reactive protein level. Plain cervical X-ray revealed a large, smooth, lobulated mass in the vallecular area. Direct laryngoscopic findings supported the diagnosis of an infected vallecular cyst with suppuration, which originated from the vallecula fossa. The cyst was drained and excised completely, and the pus culture revealed the presence of Klebsiella pneumoniae The patient responded well to the administration of intravenous cefuroxime for 2 weeks according to the sensitivity and culture test. He was discharged after the completion of the course of antibiotics, having recovered fully. This case illustrates the versatility of a plain cervical X-ray in giving clues about this rare, unexpected pathology.