Poly(Lysine)-Derived Carbon Quantum Dots Conquer Enterococcus faecalis Biofilm-Induced Persistent Endodontic Infections.

Introduction: Persistent endodontic infections (PEIs) mediated by bacterial biofilm mainly cause persistent periapical inflammation, resulting in recurrent periapical abscesses and progressive bone destruction. However, conventional root canal disinfectants are highly damaging to the tooth and periodontal tissue and ineffective in treating persistent root canal infections. Antimicrobial materials that are biocompatible with apical tissues and can eliminate PEIs-associated bacteria are urgently needed. Methods: Here, ε-poly (L-lysine) derived carbon quantum dots (PL-CQDs) are fabricated using pyrolysis to remove PEIs-associated bacterial biofilms. Results: Due to their ultra-small size, high positive charge, and active reactive oxygen species (ROS) generation capacity, PL-CQDs exhibit highly effective antibacterial activity against Enterococcus faecalis (E. faecalis), which is greatly dependent on PL-CQDs concentrations. 100 µg/mL PL-CQDs could kill E. faecalis in 5 min. Importantly, PL-CQDs effectively achieved a reduction of biofilms in the isolated teeth model, disrupting the dense structure of biofilms. PL-CQDs have acceptable cytocompatibility and hemocompatibility in vitro and good biosafety in vivo. Discussion: Thus, PL-CQDs provide a new strategy for treating E. faecalis-associated PEIs.

Exploring the factor structure of a Chinese version of the CORE-OM: insights from network approach and bifactor modeling.

OBJECTIVE: The Clinical Outcomes in Routine Evaluation (CORE-OM) is a measure of clinical outcomes that has been widely used in mental health research. Nevertheless, the exploration of the factor structure of the CORE-OM yields diverse results. This study aims to explore the factor structure with an innovative method known as exploratory graph analysis (EGA) and supplemented with bifactor modeling. METHOD: A Chinese version of the CORE-OM was administrated to a total of 1361 clinical college students. We first examined the factor structure of the CORE-OM using EGA, and then compared the model derived by EGA with other models using CFA to find the most reasonable model. RESULTS: The result of EGA indicated a four-factor model of CORE-OM. The CFA further suggested a bifactor model with a four-factor structure combined with a general factor. The bifactor modeling suggested a significant proportion of shared variance among the variables was attributed to the general factor. The four-factor bifactor model exhibited a satisfactory fit to the data. CONCLUSION: The results confirm the robustness and parsimonious nature of a four-factor bifactor model for the Chinese version of CORE-OM. It is suitable for measuring intrapersonal psychological distress, positive emotions, interpersonal problems, and risk-related issues among the Chinese population.

Sulfated Chitosan-Modified CuS Nanocluster: A Versatile Nanoformulation for Simultaneous Antibacterial and Bone Regenerative Therapy in Periodontitis.

Periodontitis, a prevalent chronic inflammatory disease worldwide, is triggered by periodontopathogenic bacteria, resulting in the progressive destruction of periodontal tissue, particularly the alveolar bone. To effectively address periodontitis, this study proposed a nanoformulation known as CuS@MSN-SCS. This formulation involves coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSNs), followed by surface modification using amino groups and sulfated chitosan (SCS) through electrostatic interactions. The objective of this formulation is to achieve efficient bacteria removal by inducing ROS signaling pathways mediated by Cu2+ ions. Additionally, it aims to promote alveolar bone regeneration through Cu2+-induced pro-angiogenesis and SCS-mediated bone regeneration. As anticipated, by regulating the surface charges, the negatively charged CuS nanoparticles capped with sodium citrate were successfully coated with MSNs, and the subsequent introduction of amine groups using (3-aminopropyl)triethoxysilane was followed by the incorporation of SCS through electrostatic interactions, resulting in the formation of CuS@MSN-SCS. The developed nanoformulation was verified to not only significantly exacerbate the oxidative stress of Fusobacterium nucleatum, thereby suppressing bacteria growth and biofilm formation in vitro, but also effectively alleviate the inflammatory response and promote alveolar bone regeneration without evident biotoxicity in an in vivo rat periodontitis model. These findings contribute to the therapeutic effect on periodontitis. Overall, this study successfully developed a nanoformulation for combating bacteria and facilitating alveolar bone regeneration, demonstrating the promising potential for clinical treatment of periodontitis.

A hydrogel-based first-aid tissue adhesive with effective hemostasis and anti-bacteria for trauma emergency management.

BACKGROUND: Clinical tissue adhesives remain some critical drawbacks for managing emergency injuries, such as inadequate adhesive strength and insufficient anti-infection ability. Herein, a novel, self-healing, and antibacterial carboxymethyl chitosan/polyaldehyde dextran (CMCS/PD) hydrogel is designed as the first-aid tissue adhesive for effective trauma emergency management. METHODS: We examined the gel-forming time, porosity, self-healing, antibacterial properties, cytotoxicity, adhesive strength, and hemocompatibility. Liver hemorrhage, tail severance, and skin wound infection models of rats are constructed in vivo, respectively. RESULTS: Results demonstrate that the CMCS/PD hydrogel has the rapid gel-forming (~ 5 s), good self-healing, and effective antibacterial abilities, and could adhere to tissue firmly (adhesive strength of ~ 10 kPa and burst pressure of 327.5 mmHg) with excellent hemocompatibility and cytocompatibility. This suggests the great prospect of CMCS/PD hydrogel in acting as a first-aid tissue adhesive for trauma emergency management. The CMCS/PD hydrogel is observed to not only achieve rapid hemostasis for curing liver hemorrhage and tail severance in comparison to commercial hemostatic gel (Surgiflo ®) but also exhibit superior anti-infection for treating acute skin trauma compared with clinical disinfectant gel (Prontosan ®). CONCLUSIONS: Overall, the CMCS/PD hydrogel offers a promising candidate for first-aid tissue adhesives to manage the trauma emergency. Because of the rapid gel-forming time, it could also be applied as a liquid first-aid bandage for mini-invasive surgical treatment.

Probiotic-loaded calcium alginate/fucoidan hydrogels for promoting oral ulcer healing.

Probiotics are beneficial bacteria located in the oral cavity which exhibit antimicrobial properties and contribute to the regulation of immune function and the modulation of tissue repair. Fucoidan (FD), a marine prebiotic, may further enhance the ability of probiotics to promote ulcer healing. However, neither FD nor probiotics are attached to the oral cavity and neither are well-suited for oral ulcer healing owing to the wet and highly dynamic environment. In this study, probiotic-loaded calcium alginate/fucoidan composite hydrogels were developed for use as bioactive oral ulcer patches. The well-shaped hydrogels exhibited remarkable wet-tissue adhesion, suitable swelling and mechanical properties, sustained probiotic release, and excellent storage durability. Moreover, in vitro biological assays demonstrated that the composite hydrogel exhibited excellent cyto/hemocompatibility and antimicrobial effects. Importantly, compared to commercial oral ulcer patches, bioactive hydrogels show superior therapeutic capability for promoting ulcer healing in vivo by enhancing cell migration, inducing epithelial formation and orderly collagen fiber deposition, as well as facilitating neovascularization. These results demonstrate that this novel composite hydrogel patch demonstrates great potential for the treatment of oral ulcerations.

Differences in central symptoms of anxiety and depression between college students with different academic performance: A network analysis.

Objective: The prevalence of anxiety and depressive symptoms for Chinese college students are high. Academic pressure is one of the prominent risk factors of psychological well-beings for Chinese college students. The application of network analysis provides researchers a more comprehensive understanding of symptom-symptom interaction in mental disorders. This study aims to find out whether there is a difference in central symptoms between students with different academic performance. Method: A total sample of 1,291 college students was included in our study. Anxiety and depressive symptoms were measured by PHQ-9 and GAD-7. Central symptoms were identified through centrality indices. Network stability was examined using the case-dropping method. Results: For the poor academic group, the most central symptom is PHQ-2 (feeling depressed). The most central symptom of the good academic group is GAD-2 (uncontrolled worry). The least central symptom for both groups is PHQ-9 (suicidal thought). Network structure is statistically different between two groups, global strength is not statistically different between two groups. Conclusion: The pertinent symptom is feeling depressed, followed by uncontrolled worry and poor appetite, and for the good academic group, the pertinent symptom is an uncontrolled worry, theoretical explanation and clinical implications is discussed.

Modulation of T Cell Responses by Fucoidan to Inhibit Osteogenesis.

Fucoidan has sparked considerable interest in biomedical applications because of its inherent (bio)physicochemical characteristics, particularly immunomodulatory effects on macrophages, neutrophils, and natural killer cells. However, the effect of fucoidan on T cells and the following regulatory interaction on cellular function has not been reported. In this work, the effect of sterile fucoidan on the T-cell response and the subsequent modulation of osteogenesis is investigated. The physicochemical features of fucoidan treated by high-temperature autoclave sterilization are characterized by UV-visible spectroscopy, X-ray diffraction, Fourier transform infrared and nuclear magnetic resonance analysis. It is demonstrated that high-temperature autoclave treatment resulted in fucoidan depolymerization, with no change in its key bioactive groups. Further, sterile fucoidan promotes T cells proliferation and the proportion of differentiated T cells decreases with increasing concentration of fucoidan. In addition, the supernatant of T cells co-cultured with fucoidan greatly suppresses the osteogenic differentiation of MC3T3-E1 by downregulating the formation of alkaline phosphatase and calcium nodule compared with fucoidan. Therefore, our work offers new insight into the fucoidan-mediated T cell and osteoblast interplay.

The Application of Human Figure Drawing as a Supplementary Tool for Depression Screening.

Objective: Depression is one of the most prevalent mental disorder in college students. The traditional screening method for is psychological measurements or scales, but social desirability can cause students to mask their thoughts, and an auxiliary projective test may be needed. This study was designed to measure the validity of applying human figure drawing (HFD) test as an auxiliary tool for depression screening in this population. Methods: The HFD test was administered to 113 clinical participants diagnosed with major depressive disorder and 97 healthy college students with self-rating depression scale scores <50. Correlation analysis, chi-square tests, and logistic regression were conducted to identify specific drawing features that associated with depression and could differentiate between the clinical and control subjects. ROC curve was also implemented to evaluate the diagnostic accuracy. Results: Eleven drawing features were significantly related to depression based on the chi-square test results and seven drawing features were associated with depression based on correlation analysis. After logistic regression by controlling gender and age, three drawing features were associated with depression: shaded eyes, drawing clothes in detail, and drawing other personal belongings. Further, drawing clothes in detail and drawing other personal belongings were two significant variables in ROC curve analysis. Conclusion: Logistic regression showed that shaded eyes, drawing clothes in detail and drawing other personal belongings were significant drawing features. Individuals with depression will have less energy to put extra effort into drawing and are less likely to have detailed drawings. And the shading of eyes may represent that depressive individuals have a low willingness to communicate and tend to isolate themselves. The results indicated that Human Figure Drawing could be used as an auxiliary tool in college students' depression screening. Further, the ROC curve analysis showed low discrimination of single drawing features, suggesting that the application of Human Figure Drawing should be considered as a whole instead of focusing on the single drawing feature.

Regulation of T Cell Responses by Nano-Hydroxyapatite to Mediate the Osteogenesis.

Nano-hydroxyapatite (nHA) has been widely applied as a tissue-engineering biomaterial and interacted with osteoblasts/stem cells to repair bone defects. In addition, T cells that coexist with osteoblasts/stem cells in the bone modulate the regulation of osteoimmunology by cytokine formation. However, the effects of nHA on T cells and the following regulatory interplay on osteogenic differentiation have been rarely examined. In this work, the physicochemical properties of needle-like nHA are characterized by field emission scanning electron microscopy, zeta potential, Fourier transform-infrared and X-ray diffraction. It is found that as the concentration of nHA increases, the proliferation of T cells gradually increases, and the proportion of apoptotic T cells decreases. The percentage of CD4+ T cells is higher than that of CD8+ T cells under the regulation of needle-like nHA. Furthermore, the supernatant of T cells co-cultured with nHA significantly inhibits the osteogenic differentiation of MC3T3-E1 by downregulating the formation of alkaline phosphatase and calcium nodule compared with the supernatant of nHA. Thus, our findings provide new insight into the nHA-mediated T cell and osteoblast interactions.

Improving the Shape Memory Effect of a Fe-Mn-Si-Cr-Ni Alloy through Shot Peening.

To improve the shape memory effect, the solutionized Fe-24Mn-6Si-9Cr-6Ni alloy was shot peened and subsequently annealed. The phase constituent was examined using the X-ray diffraction method. Microstructure evolution was characterized using an optical microscope and the electronic backscatter diffraction method, and the shape memory effect was evaluated using a bending test. The results show that α'-martensite and ε-martensite were introduced into the shot-peened surface layer. The α'-martensite remained after annealing even at 850 °C. Microstructure of the surface layer was refined through shot peening and subsequent annealing. Compared with those of the solutionized specimen, the shape recovery ratio and recovery strain of the specimens that are shot peened and subsequently annealed are significantly improved at different prestrains.

Synthesis and bioactivities evaluation of oleanolic acid oxime ester derivatives as α-glucosidase and α-amylase inhibitors.

Different oleanolic acid (OA) oxime ester derivatives (3a-3t) were designed and synthesised to develop inhibitors against α-glucosidase and α-amylase. All the synthesised OA derivatives were evaluated against α-glucosidase and α-amylase in vitro. Among them, compound 3a showed the highest α-glucosidase inhibition with an IC50 of 0.35 µM, which was ∼1900 times stronger than that of acarbose, meanwhile compound 3f exhibited the highest α-amylase inhibitory with an IC50 of 3.80 µM that was ∼26 times higher than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compounds 3a and 3f were reversible and mixed types towards α-glucosidase and α-amylase, respectively. Molecular docking studies analysed the interaction between compound and two enzymes, respectively. Furthermore, cytotoxicity evaluation assay demonstrated a high level of safety profile of compounds 3a and 3f against 3T3-L1 and HepG2 cells.HighlightsOleanolic acid oxime ester derivatives (3a-3t) were synthesised and screened against α-glucosidase and α-amylase.Compound 3a showed the highest α-glucosidase inhibitory with IC50 of 0.35 µM.Compound 3f presented the highest α-amylase inhibitory with IC50 of 3.80 µM.Kinetic studies and in silico studies analysed the binding between compounds and α-glucosidase or α-amylase.

Antibacterial quaternary ammonium chitosan/carboxymethyl starch/alginate sponges with enhanced hemostatic property for the prevention of dry socket.

Tooth extraction commonly leads to postoperative wound bleeding, bacterial infection, and even the occurrence of dry socket. Therefore, developing a biomedical material with favorable antibacterial and excellent hemostatic properties to prevent the post-extraction dry socket is necessary. Herein, quaternary ammonium chitosan/ carboxymethyl starch/alginate (ACQ) sponges are developed via Ca2+ cross-linking, electrostatic interaction, and lyophilization methods. The results show that the bio-multifunctional sponges exhibit interconnected porous structures with significant fluid absorption rates and suitable water vapor transmission rates. In vitro cellular and hemolysis experiments indicate that the developed sponges have acceptable biocompatibility. Notably, the constructed sponges effectively inhibit the growth of E. coli, S. aureus, and C. albicans, as well as achieve rapid hemostasis in the mouse liver injury and mini-pig tooth extraction models by absorbing blood and promoting red blood cell adhesion. Thus, the created bio-multifunctional sponges show tremendous promise as a hemostatic material for wound management after tooth extraction.

Social anxiety and associated factors among graduate students under the normalization of epidemic prevention and control / 中国学校卫生

Objective@#To understand social anxiety and relevant factors among graduate students under the normalization stage of COVID-19 epidemic prevention and control.@*Methods@#Using convenience sampling method, an online questionnaire survey on graduate students from 5 universities in Jiangsu Province was conducted. Measurements used in the survey includes General Self Efficacy Scale (GSES), General Alienation Scale (GAS), Interaction Anxiousness Scale (IAS) and self made survey for basic information and household living conditions.@*Results@#The overall score of graduate students self efficacy was (2.58±0.50). Average score was (30.68±6.22) for alienation, and (47.55±8.77) for interaction anxiety, with detection rate of social anxiety being 43.96%. Increased dependence on smartphones and electronic devices ( OR=1.86, 95%CI =1.32-2.61) and high alienation score (medium level: OR=2.06, 95%CI =1.45-2.92; high level: OR=5.19, 95%CI =1.00-27.00) were positively correlated with social anxiety. Increased communication with friends ( OR=0.65, 95%CI =0.47-0.90 and high self efficacy (medium level: OR= 0.37 , 95%CI =0.21-0.66; high level: OR=0.15, 95%CI =0.08-0.30) were negatively correlated with social anxiety.@*Conclusion@#At the normalization stage of COVID-19 epidemic prevention and control, social anxiety of graduate students is one of the mental health issues which need further attention. Participation in peer support helps prevent social anxiety through developing self efficacy, alleviating individual alienation, and reducing dependence on electronic devices among graduate students.

MMS22L Expression as a Predictive Biomarker for the Efficacy of Neoadjuvant Chemoradiotherapy in Oesophageal Squamous Cell Carcinoma.

Long-term survival in oesophageal squamous cell carcinoma (ESCC) is related with pathological response after neoadjuvant chemoradiotherapy (NCRT) followed by surgery. However, effective biomarkers to predict the pathologic response are still lacking. Therefore, a systematic analysis focusing on genes associated with the efficacy of chemoradiotherapy in ESCC will provide valuable insights into the regulation of molecular processes. By screening publications deposited in PubMed, we collected genes associated with the efficacy of chemoradiotherapy. A specific subnetwork was constructed using the Steiner minimum tree algorithm. Survival analysis in Kaplan-Meier Plotter online resources was performed to explore the relationship between gene mRNA expression and the prognosis of patients with ESCC. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemical staining (IHC) were used to evaluate the expression of key genes in cell lines and human samples. The areas under the receiver operating characteristic (ROC) curves (AUCs) were used to describe performance and accuracy. Transwell assays assessed cell migration, and cell viability was detected using the Cytotoxicity Assay. Finally, we identified 101 genes associated with efficacy of chemoradiotherapy. Additionally, specific molecular networks included some potential related genes, such as CUL3, MUC13, MMS22L, MME, UBC, VAPA, CYP1B1, and UGDH. The MMS22L mRNA expression level showed the most significant association with the ESCC patient outcome (p < 0.01). Furthermore, MMS22L was downregulated at both the mRNA (p < 0.001) and protein levels in tumour tissues compared with that in normal tissues. Lymph node metastasis was significantly associated with low MMS22L expression (p < 0.01). MMS22L levels were inversely correlated with the NCRT response in ESCC (p < 0.01). The resulting area under the ROC curve was 0.847 (95% CI: 0.7232 to 0.9703; p < 0.01). In conclusion, low expression of MMS22L is associated with poor response to NCRT, worse survival, lymph node metastasis, and enhanced migration of tumour cells in ESCC.

The impact of adjuvant therapy on survival for node-negative esophageal squamous cell carcinoma: a propensity score-matched analysis.

BACKGROUND: At present, the primary treatment of esophageal cancer is surgery-based comprehensive treatment, including adjuvant therapy such as chemotherapy and/or radiotherapy. However, the role of adjuvant therapy for esophageal squamous cell carcinoma (ESCC) with pathologically node-negative (pN0) disease is controversial. This study aimed to evaluate the impact of postoperative adjuvant therapy on survival in patients with pN0 ESCC. METHODS: Patients with ESCC who underwent R0 esophagectomy in the Department of Thoracic Surgery of Sichuan Cancer Hospital from January 2008 to December 2013 were enrolled. Patients were divided into two groups: a surgery alone (Group S) group or a surgery + adjuvant therapy (Group S + A) group. The primary outcomes were overall survival (OS) and disease-free survival (DFS), and every consecutive case was followed up until death or the last follow-up. RESULTS: A total of 387 patients with ESCC patients who had pN0 were enrolled in the study. After propensity score matching (PSM), each group consisted of 150 patients. In the overall cohort, the 5-year OS (75.6% vs. 69.7%; P=0.004) and 5-year DFS (64.9% vs. 48.2%; P=0.003) rates were higher in Group S + A than in Group S. In the matched samples, the same outcomes were observed (5-year OS: 75.6% vs. 69.7%, P=0.026; 5-year DFS: 67.6% vs. 69.6%, P=0.036). Multivariate regression analysis indicated that postoperative chemotherapy was associated with longer OS [hazard ratio (HR): 0.622, 95% confidence interval (CI): 0.416-0.928; P=0.02] and DFS (HR: 0.571, 95% CI: 0.390-0.836; P=0.004); in contrast, T3 stage tumors (HR: 1.953, 95% CI: 1.238-3.082; P=0.004) and <15 lymph node dissections (HR: 1.81; 95% CI: 1.238-2.648; P = 0.002) were found to be independent risk factors for pN0 ESCC. CONCLUSIONS: Adjuvant therapy, especially chemotherapy, prolonged OS and DFS for patients with ESCC who had pN0 disease. Fewer lymph node dissections and T3 stage tumors were independent risk factors for OS and DFS.

Moderately differentiated esophageal squamous cell carcinoma has a poor prognosis after neoadjuvant chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) plus surgery is the standard treatment for esophageal squamous cell carcinoma (ESCC); however, further analysis is needed to detail the histopathological characteristics of ESCC and their clinical significance after NCRT. This study aimed to present the pathological characteristics of ESCC and their association with prognosis after NCRT. METHODS: All patients with ESCC who underwent NCRT followed by surgical resection at Sichuan Cancer Hospital (China) from January 2018 to December 2019 were included. Resection specimens of both the primary disease and lymph nodes were re-evaluated by an experienced pathologist. After NCRT, the pathological characteristics of the residual tumor were evaluated based on the Japanese residual tumor pattern, Mandard tumor regression grade (Mandard-TRG), local inflammatory infiltration classification, and lymph node status. RESULTS: Among the 103 patients with ESCC included in this study, the pathological complete response (pCR) rate was 34% (35/103). The pCR rate of patients with poorly differentiated tumors (31/72) was higher (43.1%) than that of patients with well or moderately differentiated tumors (P<0.05). The residual tumor rate was 66% (68/103). A positive correlation was noted between the Japanese residual tumor pattern and Mandard-TRG (Kendall's tau-b =0.857, P<0.001). Tumor infiltration depth, lymph node positivity, moderate differentiation, and tumor recurrence were associated with poor oncological outcomes (P<0.05). CONCLUSIONS: Patients with poorly differentiated tumors can obtain an excellent short-term response; however, they have extremely poor long-term survival. For patients with moderately differentiated tumors, both the short- and long-term outcomes are poor. Lymph node status after NCRT is a prognostic factor for ESCC treated with NCRT.

Synthesis and biological evaluation of coumarin derivatives as α-glucosidase inhibitors.

In this study, two series of coumarin derivatives 5a∼i and 6a∼i were synthesized, and their inhibitory activity against α-glucosidase was determined. The results indicated that most of the synthesized derivatives exhibited prominent inhibitory activities against α-glucosidase. Among them, compounds 5a and 5b showed the strongest inhibition with the IC50 values of 19.64 µM and 12.98 µM, respectively. Enzyme kinetic studies of compounds 5a and 5b proved that their inhibition was reversible and a mixed type. The KI and KIS values of compound 5a were calculated to be 27.39 µM and 13.02 µM, respectively, and the corresponding values for compound 5b being 27.02 µM and 13.65 µM, respectively. The docking studies showed that compound 5b could be inserted into the active pocket of α-glucosidase and form hydrogen bonds with LYS293 to enhance the binding affinity.