Intergenerational or intragenerational learning? The relationship between interpersonal neural synchrony and older adult's learning acquisition.

OBJECTIVES: Lifelong learning facilitates active ageing, and intragenerational learning-the process by which older adults learn from their peers-is an effective means of achieving this goal. The present research aims to elucidate the mechanisms and differences between intergenerational and intragenerational learning models for older adults as evidenced by brain-to-brain synchrony. METHODS: Fifty-six instructor-learner dyads completed a study comparing intergenerational and intragenerational learning models, as well as task difficulty. The study utilized a block puzzle task and functional near-infrared spectroscopy (fNIRS) for hyperscanning. RESULTS: The instructor-learner dyads showed greater interpersonal neural synchrony (INS) and learning acquisition in the intragenerational learning model in the difficult task condition (t (54) = 3.49, p < 0.01), whereas the two learning models yielded similar results in the easy condition (t (54) = 1.96, p = 0.06). In addition, INS and self-efficacy mediated the association between learning models and learning acquisition in older adults (b = 0.14, SEM = 0.04, 95 % CI [0.01 0.16]). DISCUSSION: This study is the first to provide evidence of interbrain synchrony in an investigation of the intragenerational learning model in older adults. Our findings suggest that intra-learning is as effective as traditional inter-learning and may be more effective in certain contexts, such as difficult tasks. Encouraging intra-learning in community service or educational activities can effectively mitigate the challenge of limited volunteers and enhance learning acquisition among older adults.

Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

Ozone catalytic oxidation of toluene over triple perovskite-type catalysts modified with KMnO4.

A unique triple perovskite-type catalyst was successfully synthesized using the simple sol-gel approach, and surface acid modification was added to improve the ozone catalytic oxidation (OZCO) process ability to remove toluene more effectively. Our study indicates that La3MnCuNiO9 catalyst treated with KMnO4 shows the best toluene oxidation activity. At 250 °C, the rates of conversion and mineralization were 100% and 83%, respectively, under thermal catalytic system when C7H8 concentration = 500 ppm. During the OZCO system ([C7H8] = 20 ppm, O3/C7H8=8; room temperature), for 6 h, the conversion rate remained at 100%. The high ratios of Mn4+/(Mn4++Mn3+), Cu2+, and abundant surface oxygen species, high specific surface area, and pore volume lead to remarkable catalytic performance of this catalyst. Meanwhile, the catalyst contributes to superior stability and water resistance. The catalytic mechanism of La3MnCuNiO9 after KMnO4 treatment in the context of OZCO was further discussed. Overall, after KMnO4 treatment, the La3MnCuNiO9 catalyst reveals extraordinary catalytic activity and excellent stability combination of this catalyst with ozone exhibits high toluene removal efficiency in the OZCO system and has a good potential for industrial applications.

Preparation of carboxymethylcellulose / ZnO / chitosan composite hydrogel microbeads and its drug release behaviour.

In this study, a novel carboxymethylcellulose / ZnO / chitosan (CMC / ZnO / Cs) hydrogel microbeads loaded with crosslinked porous starch / curcumin (CPS / Cur) were designed and prepared to improve the encapsulation efficiency of curcumin for drug delivery to specific sites. It was found that the total pore volume of crosslinked porous starch (CPS) was increased by 1150 % when compared to the native starch (NS), and the adsorption ratio of curcumin by CPS was enhanced by 27 % when compared to NS. Secondly, the swelling ratio of composite hydrogel microbeads was within 25 % in an acidic environment at pH 1.2, and the swelling ratio of hydrogel microbeads sharply increased to 320 % ~ 370 % at pH 6.8 and 7.4. In addition, the results of in vitro simulated release experiments showed that the released amount of hydrogel microbeads loaded with NS/Cur and CPS/Cur in SGF were within 7 % in simulated gastric fluid (SGF). The highest released amount of curcumin was 65.26 % for hydrogel beads loaded with CPS/Cur, which was 26 % lower than that of hydrogel microbeads loaded with Cur in simulated intestinal fluid (SIF). In simulated colonic fluid (SCF), the released amount of hydrogel microbeads loaded with CPS/Cur and Cur were 73.96 % and 91.69 %, respectively. In conclusion, pH-sensitive drug delivery system with good drug stability and bioavailability were successfully prepared with carboxymethylcellulose / ZnO / chitosan bead, suitable targeting drug delivery to the small intestine.

Serum vitamin C levels and risk of non-alcoholic fatty liver disease: results from a cross-sectional study and Mendelian randomization analysis.

Background and aims: Vitamin C, as an antioxidant, may play a role in the treatment of NAFLD. This research aimed to investigate the association of serum vitamin C levels with the risk of NAFLD and to further examine the causal relationship by Mendelian randomization (MR) method. Methods: The cross-sectional study selected 5,578 participants of the National Health and Nutrition Examination Survey (NHANES), 2005-2006 and 2017-2018. The association of serum vitamin C levels with NAFLD risk was evaluated under a multivariable logistic regression model. A two-sample MR study, using genetic data from large-scale genome-wide association studies (GWAS) of serum vitamin C levels (52,014 individuals) and NAFLD (primary analysis: 1,483 cases /17,781 controls; secondary analysis: 1,908 cases/340,591 controls), was conducted to infer causality between them. The inverse-variance-weighted (IVW) was applied as the main method of MR analysis. A series of sensitivity analyzes were used to evaluate the pleiotropy. Results: In the cross-sectional study, results showed that Tertile 3 group (Tertile 3: ≥1.06 mg/dl) had a significantly lower risk (OR = 0.59, 95% CI: 0.48 ~ 0.74, p < 0.001) of NAFLD than Tertile 1 group (Tertile 1: ≤0.69 mg/dl) after full adjustments. In regard to gender, serum vitamin C was protective against NAFLD in both women (OR = 0.63, 95% CI: 0.49 ~ 0.80, p < 0.001) and men (OR = 0.73, 95% CI: 0.55 ~ 0.97, p = 0.029) but was stronger among women. However, in the IVW of MR analyzes, no causal relationship between serum vitamin C levels and NAFLD risk was observed in the primary analysis (OR = 0.82, 95% CI: 0.47 ~ 1.45, p = 0.502) and secondary analysis (OR = 0.80, 95% CI: 0.53 ~ 1.22, p = 0.308). MR sensitivity analyzes yielded consistent results. Conclusion: Our MR study did not support a causal association between serum vitamin C levels and NAFLD risk. Further studies with greater cases are warranted to confirm our findings.

Effectiveness and safety of traditional Chinese medicine decoction for diabetic gastroparesis: A network meta-analysis.

BACKGROUND: Diabetic gastroparesis (DGP) is a prevalent complication of diabetes that impairs people's quality of life and places a significant financial burden on them. The gastrointestinal symptoms of DGP patients can be improved by several Traditional Chinese Medicine (TCM) decoctions that have been shown to be effective in treating the disease. There are still many unanswered questions regarding the identification of appropriate therapeutic agents for the treatment of DGP in clinical practice. AIM: To analyze the efficacy of several TCM decoctions in the treatment of DGP using Bayesian network meta-analysis for reference. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, China National Kno-wledge Infrastructure, The China Biology Medicine DVD, Wanfang, and CQVIP were searched from inception to September 17, 2022, to collect randomized controlled trials (RCTs) about TCM decoctions for DGP. Clinical effects and symptom scores were the primary outcomes. Additionally, we assessed motilin (MOT), somatostatin (SS), gastrin (GAS), gastric emptying rate, gastric emptying time, and adverse drug events as secondary outcomes. RESULTS: A total of 67 eligible RCTs involving 4790 DGP patients and 7 TCM decoctions were included. The results of network meta-analysis (NMA) and surface under the cumulative ranking curve showed that with western medicine (WM) as a common control, the Banxia Xiexin Decoction (BXXD) + WM was most effective in clinical effects and enhancing early satiety scores; the Simo decoction (SMD) + WM was most effective in improving nausea and vomiting scores and anorexia scores, bloating scores; the Chaishao Liujunzi Decoction (CSLJD) was most effective in MOT, the Zhishi Xiaopi Decoction (ZSXPD) was most effective in SS and upgrading emptying rate; the Jianpi Xiaozhi Decoction was most effective in GAS; the CSLJD + WM was most effective in improving gastric emptying time. CONCLUSION: These NMA results suggest that the BXXD + WM and SMD + WM may be one of the potential optimal treatments. Due to various limitations, further large-sample, double-blind, multi-center randomized RCTs are needed.

Potential Targets and Mechanisms of Jiedu Quyu Ziyin Decoction for Treating SLE-GIOP: Based on Network Pharmacology and Molecular Docking.

Background: Systemic lupus erythematosus (SLE) is characterized by poor regulation of the immune response leading to chronic inflammation and multiple organ dysfunction. Glucocorticoid (GC) is currently one of the main treatments. However, a high dose or prolonged use of GC may result in glucocorticoid-induced osteoporosis (GIOP). Jiedu Quyu Ziyin decoction (JP) is effective in treating SLE and previous clinical studies have proved that JP can prevent and treat SLE steroid osteoporosis (SLE-GIOP). We aim to examine JPs main mechanism on SLE-GIOP through network pharmacology and molecular docking. Methods: TCMSP and TCMID databases were used to screen potential active compounds and targets of JP. The SLE-GIOP targets are collected from GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases. R software was used to obtain the cross-targets of JP and SLE-GIOP and to perform GO and KEGG enrichment analysis. Cytoscape software was used to make the Chinese Medicines-Active Ingredient-Intersection Targets network diagram. STRING database construct protein-protein interaction network and obtain the core targets. Auto Dock Tools and Pymol software were used for docking. Results: Fifty eight targets overlapped between JP and SLE-GIOP were suggested as potential targets of JP in the treatment of SLE-GIOP. Network topology analysis identified five core targets. GO enrichment analysis was obtained 1,968 items, and the top 10 biological process, closeness centrality, and molecular function were displayed. A total of 154 signaling pathways were obtained by KEGG enrichment analysis, and the top 30 signaling pathways were displayed. JP was well bound by MAPK1, TP53, and MYC according to the molecular docking results. Conclusion: We investigated the potential targets and signaling pathways of JP against SLE-GIOP in this study. It shows that JP is most likely to achieve the purpose of treating SLE-GIOP by promoting the proliferation and differentiation of osteoblasts. A solid theoretical foundation will be provided for the future study of clinical and experimental topics.

Ozone catalytic oxidation of low-concentration formaldehyde over ternary Mn-Ce-Ni oxide catalysts modified with FeOx.

Manganese oxide-based catalysts have attracted extensive attention due to their relatively low cost and remarkable performance for removing VOCs. In this research, we used the Pechini method to synthesize manganese-cerium-nickel ternary oxide catalysts (MCN) and evaluated the effectiveness of catalytic destruction of formaldehyde (HCHO) and ozone at room temperature. FeOx prepared by the impregnation method was applied to modify the catalyst. After FeOx treatment, the catalyst represented the best performance on both HCHO destruction and ozone decomposition under dry conditions and exhibited excellent water vapor resistance. The as-prepared catalysts were next characterized via H2-temperature programmed reduction (H2-TPR), temperature programmed desorption of O2 (O2-TPD), and X-ray photoelectron spectroscopy (XPS), and the results demonstrated that addition of FeOx increased Mn3+ and Ce3+ concentrations, oxygen vacancies and surface lattice oxygen species, facilitated adsorption, and redox properties. Based on the results of in situ diffuse reflectance infrared Fourier transform spectrometry (DRIFTS), possible mechanisms of ozone catalytic oxidation of HCHO were proposed. Overall, the ternary mixed-oxide catalyst developed in this study holds great promise for HCHO and ozone decomposition in the indoor environment.

A water-stable dual-responsive Cd-CP for fluorometric recognition of hypochlorite and acetylacetone in aqueous media.

One novel cadmium(II)-coordination polymer [Cd3L2(datrz)(H2O)3] (CP 1) is controllably synthesized by surmising the astute combination of semi-rigid tricarboxylate acid 4-(2',3'-dicarboxylphenoxy) benzoic acid (H3L) and auxiliary ligand 3,5-diamino-1,2,4-triazole (datrz). Structure analysis shows that CP 1 has a two-dimensional (2D) layer structure with a 5-nodal (43) (44·62) (45·64·8) (45·6) (47·66·82) topology. Further investigations reveal that CP 1 shows superordinary water stability and good thermal stability. The fluorescent explorations suggest that the as-synthesized CP 1 could emit blue light centered at 485 nm, attributing to ligand-based emission. In terms of sensing investigations, CP 1 could act as a fluorescent sensor for detecting hypochlorite (ClO-) and acetylacetone (acac) through fluorescence turn-off process in aqueous solution, and the detection limit could reach 0.18 µM and 0.056 µM, respectively. Further research reveals that it is more likely the N-H···O-Cl hydrogen bonds between -NH2 groups of the triazole ligands and O atoms of ClO- plays the key role in the system, which may serve as a bridge for the energy transfer, leading to fluorescence quenching of the chemosensor. While the photoinduced electron transfer (PET) combined with inner filter effect (IFT) should be responsible for the turn-off fluorescence of CP 1 triggered by acac.

[Responses of plant C:N:P stoichiometry to soil properties on unstable slopes of dry-hot valley]. / 干热河谷失稳性坡面植物碳氮磷化学计量特征对土壤性质的响应.

In this study, we examined plant C:N:P stoichiometry of herbaceous plants in different sections (stable area, unstable area and deposition area) of the unstable slope on both shade and sunny aspects of dry-hot valley with different soil properties. The results showed that C concentration (320.59 g·kg-1), N concentration (12.15 g·kg-1), and N:P ratio (25.37) of shoot on the unstable slope were significantly higher than those of root, with 254.01 g·kg-1, 6.12 g·kg-1 and 13.43, respectively. The average value of the C:N ratio was significantly higher in root (43.09) than shoot (31.90). The C content and N:P ratio of shoot and root in stable and unstable areas were significantly higher than in deposition area, whereas the N content in unstable area was significantly higher than that in deposition area on the sunny slope. In addition, the N and P contents of shoot and the root P content in deposition area were significantly higher than in stable and unstable areas, whereas the C content of root in stable and unstable areas were significantly higher than in deposition area on the shade slope. Moreover, the shoot growth of plants was mainly limited by P, whereas root growth was mainly limited by N and the limitation gradually increased as the section goes down. Soil water content (SWC) was an important factor controlling the C, N, and P contents change of shoot with the relative influence ratios of 28.8%, 20.8%, and 19.9%, respectively. Soil organic carbon (SOC) had a significant impact on the C and P contents of root with the relative influence ratios of 49.5% and 22.1%. The change of root N content was mainly affected by soil pH (24.3%). Our results revealed that nutrient allocation of plant was significantly affected by slope aspects, sections and soil factors, which were mainly constituted by SWC, SOC, and soil pH.

Dinuclear osmium complexes as mitochondrion-targeting antitumor photothermal agents in vivo.

Four dinuclear osmium complexes have been constructed for antitumor phototherapy. The most potent Os4 has extremely high photothermal conversion capability under irradiation of an 808 nm low-power laser, targets mitochondria in human melanoma cells without nucleus affinity, and acts as an antitumor photothermal therapy agent in vitro and in vivo.

Evidence and Potential Mechanisms of Traditional Chinese Medicine for the Adjuvant Treatment of Coronary Heart Disease in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

Traditional Chinese medicine (TCM) has long been used to treat diabetes mellitus and angina. It has also gained widespread clinical applications in China as a common adjuvant treatment. Although there is high-quality evidence that TCM is effective in regulating glucose and lipid metabolism, the cardiovascular protective effect of TCM in the treatment of diabetes mellitus has not been fully elucidated, especially in patients with both diabetes mellitus and coronary heart disease (CHD). We systematically assessed the efficacy and safety of TCM for the adjuvant treatment of patients with CHD and diabetes mellitus and examined the pharmacological effects and potential mechanisms of TCM medication/herbs on diabetes mellitus with CHD. We found that TCM could improve the control effect of conventional treatment on cardiac function, hemorheology, blood glucose, blood lipid, and inflammation, thus reducing the frequency of angina and the incidence of cardiovascular events and all-cause mortality. These findings indicate that TCM may be used as a complementary approach for patients with diabetes mellitus and CHD. Nevertheless, more rigorously designed randomized controlled trials and long-term evaluations are needed to support these findings.

Dilated left ventricle with multiple outpouchings - a severe congenital ventricular diverticulum or left-dominant arrhythmogenic cardiomyopathy: A case report.

BACKGROUND: Left-dominant arrhythmogenic cardiomyopathy (LDAC) is a relatively rare disease characterized by poor prognosis that exacerbates the incidence of sudden cardiac death and ventricular arrhythmias. Clinically, LDAC is constantly overlooked or misdiagnosed as myocardial infarction, myocarditis, and dilated cardiomyopathy, owing to atypical and nonspecific clinical manifestations at an early stage. CASE SUMMARY: A 57-year-old woman was diagnosed with sinus bradycardia and chronic bifascicular block during a health check. She occasionally experienced mild chest pain and paroxysmal palpitation during activity in the past 2 years. Comprehensive auxiliary examinations, including electrocardiogram, echocardiography, coronary computerized tomography angiography, and magnetic resonance imaging, revealed that she had LDAC instead of congenital ventricular diverticulum. The physicians prescribed standard oral therapy for heart failure and implantable cardioverter-defibrillator. Consequently, her left ventricular systolic function and symptoms remained stable at the 2-year follow-up after discharge. CONCLUSION: Based on this case, clinicians need to be aware of LDAC in patients with localized left ventricular lesions and multiple electrocardiographic abnormalities. Multimodality cardiovascular imaging is effective in identification of multiple types of cardiomyopathy and cardiac inner structures.

Induction of Broadly Cross-Reactive Antibody Responses to SARS-CoV-2 Variants by S1 Nanoparticle Vaccines.

Despite the rapid deployment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, the emergence of SARS-CoV-2 variants and reports of their immune evasion characteristics have led to an urgent need for novel vaccines that confer potent cross-protective immunity. In this study, we constructed three different SARS-CoV-2 spike S1-conjugated nanoparticle vaccine candidates that exhibited high structural homogeneity and stability. Notably, these vaccines elicited up to 50-times-higher neutralizing antibody titers than the S1 monomer in mice. Crucially, it was found that the S1-conjugated nanoparticle vaccine could elicit comparable levels of neutralizing antibodies against wild-type or emerging variant SARS-CoV-2, with cross-reactivity to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), the effect of which could be further enhanced using our designed nanoparticles. Our results indicate that the S1-conjugated nanoparticles are promising vaccine candidates with the potential to elicit potent and cross-reactive immunity against not only wild-type SARS-CoV-2, but also its variants of concern, variants of interest, and even other pathogenic betacoronaviruses. IMPORTANCE The emergence of SARS-CoV-2 variants led to an urgent demand for a broadly effective vaccine against the threat of variant infection. The spike protein S1-based nanoparticle designed in our study could elicit a comprehensive humoral response toward different SARS-CoV-2 variants of concern and variants of interest and will be helpful to combat COVID-19 globally.

Quadrivalent mosaic HexaPro-bearing nanoparticle vaccine protects against infection of SARS-CoV-2 variants.

Emerging SARS-CoV-2 variants of concern (VOCs) harboring multiple mutations in the spike protein raise concerns on effectiveness of current vaccines that rely on the ancestral spike protein. Here, we design a quadrivalent mosaic nanoparticle vaccine displaying spike proteins from the SARS-CoV-2 prototype and 3 different VOCs. The mosaic nanoparticle elicits equivalent or superior neutralizing antibodies against variant strains in mice and non-human primates with only small reduction in neutralization titers against the ancestral strain. Notably, it provides protection against infection with prototype and B.1.351 strains in mice. These results provide a proof of principle for the development of multivalent vaccines against pandemic and potential pre-emergent SARS-CoV-2 variants.

Correlation of mismatch repair deficiency with clinicopathological features and programmed death-ligand 1 expression in thyroid carcinoma.

BACKGROUND: Mutations in DNA mismatch repair (MMR) genes associated with thyroid carcinoma (TC) have rarely been reported, especially in East Asian populations. METHODS: We examined tumor tissue from a cohort of 241 patients diagnosed with TC between 2008 and 2020. MMR proteins were detected using tissue microarray-based immunohistochemistry in order to identify MMR-protein-deficient (MMR-D) and MMR-protein-intact (MMR-I) tumors. We retrospectively summarized the clinicopathologic characteristics of patients with MMR-D TC, measured the expression of PD-L1, and recorded overall survival (OS) and other clinical outcomes. RESULTS: In our cohort, there were 18 (7.5%) MMR-D (MLH1, MSH2, MSH6, and PMS2) patients, including 12 with papillary TC (PTC) (6.7%), 2 with poorly differentiated TC (PDTC) (4.7%), and 4 with anaplastic TC (ATC) (22.2%). Half of them (9/18) showed a specific deletion in MSH6, and 6 of them also carried variants in the MSH6 and PMS2 gene. Survival was significantly better in patients with MMR-D ATC than in those with MMR-I tumors (p = 0.033). Four of the 18 MMR-D patients (22%) were found to be PD-L1 positive. Their OS was much shorter than that of PD-L1-negative patients. CONCLUSIONS: MMR-D and PD-L1 positivity appear to be associated with clinicopathological characteristics and prognosis in TC. The results indicate that MMR status may have important prognostic significance in TC. Therefore, immune checkpoint inhibitors that target the PD-1/PD-L1 pathway may be a treatment option for TCs.

Design of a mutation-integrated trimeric RBD with broad protection against SARS-CoV-2.

The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.

Treatment and prognosis analysis of perineural invasion on sinonasal adenoid cystic carcinoma / 中华肿瘤杂志

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.

Bacteriological and molecular typing of Clostridium perfringens strains isolated in retail beef in Beijing, China.

Clostridium perfringens is an important zoonotic pathogen. This study was designed to explore the prevalence and toxin types of C. perfringens in retail beef collected from Beijing, China. Among 221 beef samples collected, 53 samples were positive for C. perfringens, resulting in the average prevalence as 23.98%. By toxin gene-based typing, the most C. perfringens strains belong to type A (96.23%, 51/53), only 2 strains were identified as type D. By a multi-locus sequence typing (MLST)-based analysis, a total of 36 sequence types (STs) were detected, and the most STs (n=30) represented just a single strain. These finding suggested that the prevalence of C. perfringens in retail beef in Beijing was considerably high and these bacteria displayed extreme diversity in genetics.

Structure and computation-guided design of a mutation-integrated trimeric RBD candidate vaccine with broad neutralization against SARS-CoV-2

The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the "immune-escape" Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.