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Abstract Background This in vitro study aimed to evaluate the effect of sodium hypochlorite (NaOCl) and ethylene diamine tetraacetic acid (EDTA) as pretreatments on the resin infiltration efficacy and acid resistance of enamel white spot lesions (WSLs). Methods Enamel blocks prepared from the buccal surfaces of sound human premolars were placed in a demineralisation solution for 3 days to establish artificial enamel WSLs. All the blocks with WSLs were randomly divided into four groups (n = 40 per group): RI (Control): resin infiltration only. N/RI: 5.25% NaOCl pretreatment + resin infiltration; E/RI: 17% EDTA pretreatment + resin infiltration; NE/RI: combined pretreatment of 5.25% NaOCl with 17% EDTA + resin infiltration; Enamel pore exposure was measured by using SEM observation and Image J software in each group after pretreatment prior to resin infiltration (n = 8 per group). Resin penetration depth and enamel surface microhardness were assessed after resin infiltration (n = 8 per group for each test) by a confocal laser scanning microscope and a Vickers’ microhardness test respectively. The remaining specimens were subjected 7 days of pH cycling after which surface enamel roughness and microhardness were assessed by an atomic force microscope and a microhardness test respectively. Results Compared to the control group, the enamel surface pore exposure (p = 0.007), resin penetration depth (p = 0.011) and enamel surface microhardness (p

Abstract The dynamic disulfide linkage plays a vital role in various biological processes as well as drugs and biomaterials. The conversion of thiols to their corresponding disulfides is a hallmark of sulfur chemistry, but notoriously difficult to control. Achieving optimal reactivity and selectivity continues to pose significant challenges. Here, we describe a click chemistry for disulfide formation from thiols in both batch and flow-mode using SO2F2, which display exceptional selectivity toward disulfide formation through an effective nucleophilic substitution cascade. This reaction’s unique characteristics satisfy the stringent click-criteria with its high thermodynamic driving force, straightforward conditions, wide scope, quantitative yields, exceptional chemoselectivity, and non-chromatographic purification process. The modular synthesis of symmetrical, unsymmetrical, cyclic and polydisulfides is demonstrated, along with the formation of disulfide cross-linked hydrogels.

Abstract SuFEx click chemistry demonstrates remarkable molecular assembly capabilities. However, the effective utilization of alkyl sulfonyl fluoride hubs in SuFEx chemistry, particularly in reactions with alcohols and primary amines, presents considerable challenges. This study pioneers an intramolecular chalcogen bonding activated SuFEx (S-SuFEx) click chemistry employing alkyl sulfonyl fluorides with γ-S as the activating group. The ChB-activated alkyl sulfonyl fluorides can react smoothly with phenols, alcohols, and amines, exhibiting enhanced reactivity compared to SO2F2. Excellent yields have been achieved with all 75 tested substrates. Pioneering the application of S-SuFEx chemistry, we highlight its immense potential in organic-inorganic linking, considering the critical role of interfacial covalent bonding in material fabrication. The S-SuFEx hub 1c, incorporating a trialkoxy silane group has been specifically designed and synthesized for organic-inorganic linking. In a simple step, 1c efficiently anchors various organic compounds onto surfaces of inorganic materials, forming functionalized surfaces with properties such as antibacterial activity, hydrophobicity, and fluorescence.

Methotrexate (MTX), an anti-metabolite agent, is a widely used chemotherapeutic anticancer drug, but its hepatotoxicity severely limits its clinical application. Nevertheless, the precise mechanisms of MTX-caused liver damage are extremely intricate and still need to be fully clarified. In the current study, we investigated the role of the STING-ERS-ferroptosis axis in MTX-triggered hepatic toxicity in vivo and in vitro models. Male C57BL/6 J mice exposed to a single dose of MTX (0, 2, 5, and 20 mg/kg) for 3 days exhibited severe liver damage and overactivated STING signaling. Moreover, we found that ferroptosis was also involved in MTX-mediated liver damage. Interestingly, STING deficiency alleviated liver damage, inhibited liver inflammation, as well as suppressed hepatic lipid peroxidation and ferroptosis in MTX-treated mice. Consistently, STING inhibitor (C-176) pretreatment also alleviated MTX-induced STING signaling activation, ROS overproduction and ferroptosis in AML12 cells. Finally, we verified that ER stress was responsible for the MTX-induced liver injury and ferroptosis caused by STING activation. Taken together, our study uncovered a novel link between STING signaling and ferroptosis in MTX-triggered hepatic damages, and suggested that targeting the STING-ER stress-ferroptosis axis might be a promising and effective therapeutic approach against MTX-induced liver damage.

Polyether amines are versatile compounds characterized by a flexible structure, consisting of polyoxypropylene and polyoxyethylene as the backbone, with amine groups at each end. They have widespread applications in various industrial processes and daily life. Despite their versatility, the utilization of polyether amines as base catalysts is rare. In this study, one kind of three-arm polyether amine 1 was employed as an environmentally friendly, cost-effective catalyst for the aerobic oxidation of thiophenols, leading to the synthesis of disulfides. The oxidative coupling of thiols serves as a fundamental pathway for the production of disulfides, which are vital in both chemical and biological processes. In contrast to known methods for thiol oxidation, this polyether amine-based catalytic process eliminates the need for expensive stoichiometric oxidants and minimizes the formation of over-oxidized by-products. Using a mere 0.5 mol % of the polyether amine 1 as the catalyst, a remarkable > 96% yield was achieved for all 16 tested substrates, encompassing a diverse range of functional groups, under the catalytic aerobic oxidation conditions. Furthermore, it is noteworthy that over 90% of the polyether amine catalyst can be efficiently recovered for reuse without loss of activity, making this a sustainable and cost-effective catalytic approach.

Background: Anaphase-promoting complex/cyclosome (APC/C) is a multi-subunit E3 ubiquitin ligase that recruits substrates for ubiquitination and subsequent degradation. As one of the two co-activators of APC/C, cell division cycle protein 20 (CDC20) plays a crucial role in cell cycle regulation. The objective of our study was to explore the therapeutic potential of targeting APC/CCDC20 in endometrial carcinoma (EC). Methods: We performed comprehensive bioinformatics analysis to screen novel targets for EC treatment. The expression of CDC20 in normal endometrial and EC tissues was analyzed by immunohistochemistry. We treated EC cells with varying concentrations of APC/C inhibitors and evaluated their effects on cell proliferation and apoptosis using Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis. We performed wound healing and transwell assays to evaluate the migration ability of EC cell lines. Results: CDC20 was identified as a potential therapeutic target for EC. We found that the expression level of CDC20 in EC tissue is significantly higher than in nonmalignant tissue. Treatment with pro-Tosyl-L-Arginine Methyl Ester (TAME) inhibited the proliferation of EC cells in a time- and dose-dependent pattern. High concentrations of pro-TAME induced apoptosis in EC cells. Furthermore, the inhibitory effects of pro-TAME on EC cells were amplified by the co-addition of Apcin at low concentrations. However, treatment with pro-TAME did not affect the migratory ability of EC cells. Conclusions: Our findings suggest that the inhibition of APC/CCDC20 by pro-TAME, in combination with Apcin, may represent a promising approach for the treatment of EC that warrants further investigation.

Abstract Wild‐type sortase A is an important virulence factor displaying a diverse array of proteins on the surface of bacteria. This protein display relies on the transpeptidase activity of sortase A, which is widely engineered to allow protein ligation and protein engineering based on the interaction between sortase A and peptides. Here an unknown interaction is found between sortase A from Staphylococcus aureus and nucleic acids, in which exogenously expressed engineered sortase A binds oligonucleotides in vitro and is independent of its canonical transpeptidase activity. When incubated with mammalian cells, engineered sortase A further mediates oligonucleotide labeling to the cell surface, where sortase A attaches itself and is part of the labeled moiety. The labeling reaction can also be mediated by many classes of wild‐type sortases as well. Cell surface GAG appears involved in sortase‐mediated oligonucleotide cell labeling, as demonstrated by CRISPR screening. This interaction property is utilized to develop a technique called CellID to facilitate sample multiplexing for scRNA‐seq and shows the potential of using sortases to label cells with diverse oligonucleotides. Together, the binding between sortase A and nucleic acids opens a new avenue to understanding the virulence of wild‐type sortases and exploring the application of sortases in biotechnology.

Background The alexithymia trait is of high clinical interest. The Perth Alexithymia Questionnaire (PAQ) was recently developed to enable detailed facet-level and valence-specific assessments of alexithymia.Aims In this paper, we introduce the first Chinese version of the PAQ and examine its psychometric properties and clinical applications.Methods In Study 1, the PAQ was administered to 990 Chinese participants. We examined its factor structure, internal consistency, test-retest reliability, as well as convergent, concurrent and discriminant validity. In Study 2, four groups, including a major depressive disorder (MDD) group (n=50), a matched healthy control group for MDD (n=50), a subclinical depression group (n=50) and a matched healthy control group for subclinical depression (n=50), were recruited. Group comparisons were conducted to assess the clinical relevance of the PAQ.Results In Study 1, the intended five-factor structure of the PAQ was found to fit the data well. The PAQ showed good internal consistency and test-retest reliability, as well as good convergent, concurrent and discriminant validity. In Study 2, the PAQ was able to successfully distinguish the MDD group and the subclinical depression group from their matched healthy controls.Conclusions The Chinese version of the PAQ is a valid and reliable instrument for comprehensively assessing alexithymia in the general population and adults with clinical/subclinical depression.

Chinese shrimps are popular among consumers for their delicious taste and high nutritional value, but they are highly susceptible to deterioration due to microbial contamination with degradation of texture, color and flavor. The aim of this study was to evaluate the effects of available chlorine concentration (ACC), processing time and material-liquid ratio on the bacterial inhibition rate of shrimp treated with slightly acidic electrolyzed water (SAEW). The effective parameters were optimized by response surface methodology to the optimal bactericidal conditions: ACC 88 mg/L, processing time 12 min, and material-liquid ratio 1:4. The actual bactericidal inhibition rate of shrimp under these conditions was 37.60 %. On this basis, the quality, color difference and textural changes of shrimp treated with SAEW, sodium hypochlorite and alkaline electrolytic water were compared and investigated during storage at 4 °C. The combined results showed that the SAEW treatment could extend the shelf-life by more than 2 d.

Inspired by the excellent adhesion performances of setae structure from organisms, micro/nano-pillar array has become one of the paradigms for adhesive surfaces. The micropillar arrays are composed of the resin pillars for adhesion and the substrate with different elastic modulus for supporting. The stress singularity at the bi-material corner between the pillars and the substrate can induce the failure of the micropillar-substrate corner and further hinder the fabrication and application of micropillar arrays, yet the design for the stability of the micropillar array lacks systematical and quantitative guides. In this work, we develop a semi-analytical method to provide the full expressions for the stress distribution within the bi-material corner combining analytical derivations and numerical calculations. The predictions for the stress within the singularity field can be obtained based on the full expressions of the stress. The good agreement between the predictions and the FEM results demonstrates the high reliability of our method. By adopting the strain energy density factor approach, the stability of the pillar-substrate corner is assessed by predicting the failure at the corner. For the elastic mismatch between the pillar and substrate given in this paper, the stability can be improved by increasing the ratio of the shear modulus of the substrate to that of the micropillar. Our study provides accurate predictions for the stress distribution at the bi-material corner and can guide the optimization of material combinations of the pillars and the substrate for more stable bioinspired dry adhesives.

Abstract Background This study aimed to investigate the effects of different ferrule heights and crown-to-root ratios on the fracture resistance of endodontically-treated premolars restored with fiber post or cast metal post system. Methods Eighty extracted human mandibular first premolars with single root canal were treated endodontically and cut from 2.0 mm above the buccal cemento-enamel junction, to create horizontal residual roots. The roots were randomly divided into two groups. The roots in group FP were restored with a fiber post-and-core system, while the roots in group MP were restored with a cast metal post-and-core system. Each group was divided into five subgroups with different ferrule heights (0: no ferrule; 1: 1.0 mm ferrule; 2: 2.0 mm ferrule; 3: 3.0 mm ferrule; 4: 4.0 mm ferrule). All specimens were subsequently restored with metal crowns and embedded in acrylic resin blocks. The crown-to-root ratios of the specimens were controlled at approximately 0.6, 0.8, 0.9, 1.1, and 1.3 of the five subgroups, respectively. Fracture strengths and fracture patterns of the specimens were tested and recorded by a universal mechanical machine. Results Mean fracture strengths (mean ± standard deviation (kN)) of FP/0 to FP/4 and MP/0 to MP/4 were: 0.54 ± 0.09, 1.03 ± 0.11, 1.06 ± 0.17, 0.85 ± 0.11; 0.57 ± 0.10, 0.55 ± 0.09, 0.88 ± 0.13, 1.08 ± 0.17, 1.05 ± 0.18 and 0.49 ± 0.09, respectively. Two-way ANOVA revealed significant effects of different ferrule heights and crown-to-root ratios on the fracture resistance (P

Chronic granulomatous disease (CGD) is a rare X-linked recessive primary immunodeficiency disease (PID). Herein, a human induced pluripotent stem cell (iPSC) line was generated from the peripheral blood mononuclear cells (PBMCs) of a CGD patient with a mutation (c.785_786delTT) in the CYBB gene. These iPSCs showed the expression of pluripotency markers, the ability to differentiate into three germ layers. They offer a promising technique for studying the pathogenesis and conducting drug screening for CGD patients.

BackgroundAfter 3 years of its zero-COVID policy, China lifted its stringent pandemic control measures with the announcement of the 10 new measures on December 7, 2022. Existing estimates suggest 90%-97% of the total population was infected during December. This change created a massive demand for COVID-19 medications and treatments, either modern medicines or traditional Chinese medicine (TCM). ObjectiveThis study aimed to explore (1) how China’s exit from the zero-COVID policy impacted media and the public’s attention to COVID-19 medications; (2) how social COVID-19 medication discussions were related to existing model estimates of daily cases during that period; (3) what the diversified themes and topics were and how they changed and developed from November 1 to December 31, 2022; and (4) which topics about COVID-19 medications were focused on by mainstream and self-media accounts during the exit. The answers to these questions could help us better understand the consequences of exit strategies and explore the utilities of Sina Weibo data for future infoveillance studies. MethodsUsing a scrapper for data retrieval and the structural topic modeling (STM) algorithm for analysis, this study built 3 topic models (all data, before a policy change, and after a policy change) of relevant discussions on the Chinese social media platform Weibo. We compared topic distributions against existing estimates of daily cases and between models before and after the change. We also compared proportions of weibos published by mainstream versus self-media accounts over time on different topics. ResultsWe found that Weibo discussions shifted sharply from concerns of social risks (case tracking, governmental regulations, etc) to those of personal risks (symptoms, purchases, etc) surrounding COVID-19 infection after the exit from the zero-COVID policy. Weibo topics of “symptom sharing” and “purchase and shortage” of modern medicines correlated more strongly with existing susceptible-exposed-infected-recovered (SEIR) model estimates compared to “TCM formulae” and other topics. During the exit, mainstream accounts showed efforts to specifically engage in topics related to worldwide pandemic control policy comparison and regulations about import and reimbursement of medications. ConclusionsThe exit from the zero-COVID policy in China was accompanied by a sudden increase in social media discussions about COVID-19 medications, the demand for which substantially increased after the exit. A large proportion of Weibo discussions were emotional and expressed increased risk concerns over medication shortage, unavailability, and delay in delivery. Topic keywords showed that self-medication was sometimes practiced alone or with unprofessional help from others, while mainstream accounts also tried to provide certain medication instructions. Of the 16 topics identified in all 3 STM models, only “symptom sharing” and “purchase and shortage” showed a considerable correlation with SEIR model estimates of daily cases. Future studies could consider topic exploration before conducting predictive infoveillance analysis, even with narrowly defined search criteria with Weibo data.

Automatic speech recognition (ASR) has been widely used to realize daily human–machine interactions. Face masks have become everyday wear in our post-pandemic life, and speech through masks may have impaired the ASR. This study explored the effects of different kinds of face masks (e.g., surgical mask, KN95 mask, and cloth mask) on the Mandarin word accuracy of two ASR systems with or without noises. A mouth simulator was used to play speech audio with or without wearing a mask. Acoustic signals were recorded at distances of 0.2 m and 0.6 m. Recordings were mixed with two noises at a signal-to-noise ratio of +3 dB: restaurant noise and speech-shaped noise. Results showed that masks did not affect ASR accuracy without noise. Under noises, masks did not significantly influence ASR accuracy at 0.2 m but had significant effects at 0.6 m. The activated-carbon mask had the most significant impact on ASR accuracy at 0.6 m, reducing the accuracy by 18.5 percentage points compared to that without a mask, whereas the cloth mask had the least effect on ASR accuracy at 0.6 m, reducing the accuracy by 0.9 percentage points. The acoustic attenuation of masks on the high-frequency band at around 3.15 kHz of the speech signal attributed to the effects of masks on ASR accuracy. When training ASR models, it may be important to consider mask robustness.

With the rapid development of intelligent sensor technology and the application of scenarios, the video images of moving targets collected by intelligent terminal devices can be obtained in sports teaching scenarios, and then through preprocessing, target tracking and behavior analysis, the analysis report is finally generated to achieve the effect of sports training. However, in the process of processing, the edge information of the video image is damaged, the color deviation exists, and when tracking the moving target, the final result will be affected by the deformation and partial occlusion of the target. In view of the above problems, the original bilateral filtering algorithm is changed to the multi-scale Retinex algorithm in the preprocessing to ensure that the video image is clearer and more complete and can be effectively protected. At the same time, for the target tracking algorithm, the Camshift algorithm which takes the color histogram as the tracking target and records the distribution probability is used. So that the results will not be affected by the deformation and partial occlusion of the target. The final experimental results show that the improved pre-processing algorithm and target tracking algorithm have smaller errors in operation, better protection of the edge information of video images, reduced the time consumption of the target tracking unit to be detected, and also improved its anti-jamming stability. In the future development, the image processing algorithm should have a better operation path, further reduce the running time, improve the value of UCIQE and peak signal to noise ratio, and track multiple targets at the same time with the smallest error, capture the moment to reach the single frame level, and also become better for teaching. In the system design, information security performance is compared with vulnerability identification to evaluate the security level of physical education teaching system.

Abstract The microscopic structures of liquid water at ambient temperatures remain a hot debate, which relates with structural and density fluctuations in the hydrogen bond network. Here, we use molecular dynamics simulations of liquid water to study the properties of three-dimensional cage-like water clusters, which we investigate using extended graph-based hierarchical clustering methods. The water clusters can cover over 95% of hydrogen bond network, among which some clusters maximally encompass thousands of molecules extending beyond 3.0 nm. The clusters imply fractal behaviors forming percolating networks and the morphologies of small and large clusters show different scaling rules. The local favored clusters and the preferred connections between adjacent clusters correspond to lower energy and conformational entropy depending on cluster topologies. Temperature can destroy large clusters into small ones. We show further that the interior of clusters favors high-density patches. The water molecules in the small clusters, inside which are the void regarded as hydrophobic objects, have a preference for being more tetrahedral. Our results highlight the properties and changes of water clusters as the fundamental building blocks of hydrogen bond networks. In addition, the water clusters can elucidate structural and density fluctuations on different length scales in liquid water.

Iodine is a well-known oxidant that is widely used in organic syntheses. Thiol oxidation by stoichiometric iodine is one of the most commonly employed strategies for the synthesis of valuable disulfides. While recent advancements in catalytic aerobic oxidation conditions have eliminated the need for stoichiometric oxidants, concerns persist regarding the use of toxic or expensive catalysts. In this study, we discovered that iodine can be used as a cheap, low-toxicity catalyst in the aerobic oxidation of thiols. In the catalytic cycle, iodine can be regenerated via HI oxidation by O2 at 70 °C in EtOAc. This protocol harnesses sustainable oxygen as the terminal oxidant, enabling the conversion of primary and secondary thiols with remarkable efficiency. Notably, all 26 tested thiols, encompassing various sensitive functional groups, were successfully converted into their corresponding disulfides with yields ranging from >66% to 98% at a catalyst loading of 5 mol%.

Aiming at the problems of high process instantiation cost and difficult version iteration in the current blockchain-based business process management systems, a choreography-driven blockchain business process management framework was proposed.The framework included a general smart contract that could be used to store business process choreography meta-models, model component evolution versions, and instance execution status.The cost of process model instantiation on the blockchain was significantly reduced by delaying model elements instantiation timing and integrating multiple process instances.At the same time, a version control method based on model data reuse and voting mechanism was introduced, so that process instances of different versions of orchestration models could be created in a single smart contract.A real case validates the effectiveness of the framework in distributed business process management.

Abstract Many properties of water, such as turbulent flow, are closely related to water clusters, whereas how water clusters form and transform in bulk water remains unclear. A hierarchical clustering method is introduced to search out water clusters in hydrogen bonded network based on modified Louvain algorithm of graph community. Hydrogen bonds, rings and fragments are considered as 1st-, 2nd-, and 3rd-level structures, respectively. The distribution, dynamics and structural characteristics of 4th- and 5th-level clusters undergoing non-shear- and shear-driven flow are also analyzed at various temperatures. At low temperatures, nearly 50% of water molecules are included in clusters. Over 60% of clusters remain unchanged between neighboring configurations. Obvious collective translational motion of clusters is observed. The topological difference for clusters is elucidated between the inner layer, which favors 6-membered rings, and the external surface layer, which contains more 5-membered rings. Temperature and shearing can not only accelerate the transformation or destruction of clusters at all levels but also change cluster structures. The assembly of large clusters can be used to discretize continuous liquid water to elucidate the properties of liquid water.

Abstract CRISPR-based genome perturbation provides a new avenue to conveniently change DNA sequences, transcription, and epigenetic modifications in genetic screens. However, it remains challenging to assay the complex molecular readouts after perturbation at high resolution and at scale. By introducing an A/G mixed capture sequence into the gRNA scaffold, we demonstrate that gRNA transcripts could be directly reverse transcribed by poly (dT) primer together with the endogenous mRNA, followed by high-content molecular phenotyping in scRNA-seq (Direct-seq). With this method, the CRISPR perturbation and its transcriptional readouts can be profiled together in a streamlined workflow.

Abstract Background In mammals, specification of primordial germ cells (PGCs) is established in the early post­implantation embryo. The bone morphogenetic protein (BMP)-SMAD and WNT3-β-catenin signaling initiate the gene regulatory network for PGC specification. The activation of SOX17-BLIMP1 axis is critical for human PGC program. Moreover, EpCAM and INTEGRINα6 were identified as surface markers of human PGC-like cells (PGCLCs) recently. However, the signaling mechanism for PGC specification in non­rodent mammals remains to be clarified. Methods We differentiated human induced pluripotent stem cells (hiPSCs) into PGCLCs in vitro in response to Activin A and BMP4. The percentage of EpCAM/INTEGRINα6 double-positive cells (PGCLCs) was analyzed by flow cytometry. The expression of PGC genes was evaluated by qRT-PCR and immunofluorescence. The expression dynamic of multi-lineage genes during the differentiation process was evaluated by qRT-PCR. Results Under the stimulation for PGCLC induction, the embryoids derived from hiPSCs initiated significant upregulation of the early PGC genes (BLIMP1, TFAP2C, and NANOS3), but maintained low or no levels of DPPA3 and late PGC genes (DAZL and DDX4). The percentage of EpCAM/INTEGRINα6 double-positive PGCLCs reached the highest at day 6 of induction. After pre-induction, the incipient mesoderm-like cells (iMeLCs) upregulated most of the mesoderm genes (EOMES, T, MSXI, RUNX2, and MIXL1). The differentiating embryoids showed high levels of key pluripotency genes, OCT4 and NANOG, but became negative for SOX2. In contrast to iMeLCs, the differentiating embryoids downregulated mesoderm genes RUNX2 and EOMES, and ectoderm gene PAX6, but increased the expression of endoderm gene SOX17. Conclusions During PGCLC induction process in vitro, the differentiating embryoids not only activated the PGC-related genes, but also displayed complex regulation of pluripotency genes and multi-lineage genes. These results would be meaningful for future research investigating the regulation of human early germ line development.

In this paper, we study the optimal photoinitiator (camphorquinone, CQ) concentration for light-cured dental resins by combining such properties as the degree of conversion, mechanical properties, and curing depth (the depth at which the hardness is 80% of the surface hardness). The material properties of the light-cured dental resins (Bis-GMA/TEGDMA in a mass ratio of 70:30) are characterized by in-situ near-infrared (NIR) spectroscopy and nanoindentation tests. Experimental results indicate that the degree of conversion (DC) and mechanical properties such as elastic modulus and hardness increase, while the curing depth decreases with the increase of CQ concentration. However, above a certain concentration (~0.5 wt%), these properties do not benefit from the further increasing CQ concentration because of potential self-annihilation between free radicals. The presented study offers a method to determine the optimal photoinitiator concentration for light-cured resins and establishes the correlations between the photoinitiators, polymerization kinetics, and mechanical properties of the light-cured resins.

Abstract Background Human adenovirus type 3 (HAdV-3) and 7 (HAdV-7) cause significant morbidity and develop severe complications and long-term pulmonary sequelae in children. However, epidemiologic reports have suggested that nearly all highly severe or fatal adenoviral diseases in children are associated with HAdV-7 rather than HAdV-3. Here, we conduct in-depth investigations to confirm and extend these findings through a comprehensive series of assays in vitro and in vivo as well as clinical correlates. Methods A total of 8248 nasopharyngeal aspirate (NPA) samples were collected from hospitalized children with acute respiratory infections in Children’s Hospital of Chongqing Medical University from June 2009 to May 2015. Among 289 samples that tested positive for HAdVs, clinical data of 258 cases of HAdV-3 (127) and HAdV-7 (131) infections were analyzed. All HAdV-positive samples were classified by sequencing the hexon and fiber genes, and compared with clinical data and virological assays. We also performed in vitro assays of virus quantification, viral growth kinetics, competitive fitness, cytotoxicity and C3a assay of the two strains. Mouse adenovirus model was used to evaluate acute inflammatory responses. Results Clinical characteristics revealed that HAdV-7 infection caused more severe pneumonia, toxic encephalopathy, respiratory failure, longer mean hospitalization, significantly lower white blood cell (WBC) and platelet counts, compared to those of HAdV-3. In cell culture, HAdV-7 replicated at a higher level than HAdV-3, and viral fitness showed significant differences as well. HAdV-7 also exhibited higher C3a production and cytotoxic effects, and HAdV-7-infected mice showed aggravated pathology and higher pulmonary virus loads, compared to HAdV-3-infected mice. Macrophages in BALF remained markedly high during infection, with concomitant increase in pro-inflammatory cytokines (TNF-α, IL-1β, IFN-γ, and IL-6), compared HAdV-3 infection. Conclusions These results document that HAdV-7 replicates more robustly than HAdV-3, and promotes an exacerbated cytokine response, causing a more severe airway inflammation. The findings merit further mechanistic studies that offer the pediatricians an informed decision to proceed with early diagnosis and treatment of HAdV-7 infection.

International students are underrepresented in Australian health literature, and this population is especially vulnerable to the well-documented negative impacts associated with racial microaggressions in their adjustment to settling in the new society, as well as to the many challenges they already face as international students. This study investigated the prevalence of racial microaggressions among international students and its impact on stress and psychological well-being. This research was conducted during the COVID-19 pandemic which has been documented to contribute to anti-Asian racism. Participants included 54 international students, of which 72% were Asian. The Racial and Ethnic Microaggressions Scale (REMS), Perceived Stress Scale (PSS) and the Perceived General Wellbeing Indicator (PGWBI) were used to measure the participants' responses. All participants reported experiencing racial microaggression in the last six months, and significant correlations and regression models were found between REMS, certain elements of the PSS scale and time in Australia. Despite the small sample size, this research corroborated outcomes from recent studies and provided insight into the prevalence and impact of racial microaggressions among such populations, highlighting the need for further exploration.

BackgroundX-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by Bruton’s tyrosine kinase (BTK) mutation. Patients are susceptible to severe enterovirus infections. The underlying mechanism remains unknown. BTK is involved in toll-like receptors pathway, which initiates antiviral responses including interferon (IFN) productions.ObjectiveTo demonstrate type I and III IFN productions in dendritic cells of XLA patients is decreased in response to oral poliovirus vaccine (OPV) but not H1N1 virus.MethodsMonocyte-derived dendritic cells (MoDCs) were derived from nine XLA patients aged 22–32 years old and 23 buffy coats from Hong Kong Red Cross blood donors. LFM-A13 was used to inhibit BTK. OPV Sabin type 1 and H1N1 influenza virus were used to stimulate MoDCs with RPMI as mock stimulation. The antiviral cytokine productions and phenotypic maturation of MoDCs were determined 24 h post-stimulation. OPV RNA was determined at 0, 6, 12, and 24 h post-stimulation.ResultsUpon OPV stimulation, IFN-α2, IFN-β, and IFN-λ1 productions in MoDCs from XLA patients and BTK-inhibited MoDCs of healthy controls were significantly lower than that from healthy controls. Whereas upon H1N1 stimulation, the IFN-α2, IFN-β, and IFN-λ1 productions were similar in MoDCs from XLA patients, BTK-inhibited MoDCs of healthy controls and healthy controls. The mean fluorescent intensities (MFI) of CD83, CD86, and MHC-II in MoDCs from XLA patients in response to OPV was similar to that in response to mock stimulation, while the MFI of CD83, CD86, and MHC-II were significantly higher in response to H1N1 stimulation than that in response to mock stimulation. Whereas, the MFI of CD83, CD86, and MHC-II in MoDCs of healthy controls were significantly higher in response to both OPV and H1N1 stimulation compared to that in response to mock stimulation.ConclusionProduction of type I and III IFN in response to OPV was deficient in MoDCs from XLA patients, but was normal in response to H1N1 due to deficient BTK function. Moreover, phenotypic maturation of MoDCs from XLA patients was impaired in response to OPV but not to H1N1. These selective impairments may account for the unique susceptibility of XLA patients toward severe enterovirus infections.

Human Vγ9Vδ2-T cells recognize nonpeptidic antigens and exert effector functions against microorganisms and tumors, but little is known about their roles in humoral immune response against influenza virus infection. Herein, in the coculture of autologous human B cells, dendritic cells and/or naïve CD4 T cells, and Vγ9Vδ2-T cells, we demonstrated that Vγ9Vδ2-T cells could facilitate H9N2 influenza virus-specific IgG and IgM productions in a CD4 T cell-dependent manner. Vγ9Vδ2-T cells promoted the differentiation of CXCR5+PD1+CD4+ T follicular helper (Tfh) cells, CD19+IgD−CD38++ plasma cells (PCs), and drove B cell proliferation as well as immunoglobulin class switching. Interestingly, Vγ9Vδ2-T cells acquired Tfh-associated molecules such as CXCR5, PD1, CD40L, and ICOS during influenza virus stimulation, especially in the presence of CD4 T cells. Moreover, Vγ9Vδ2-T cells promoted CD4 T cells to secrete IL-13 and IL-21, and neutralizing IL-13 and IL-21 significantly reduced the number of CD19+IgD−CD38++ PCs. Using humanized mice, we further demonstrated that Vγ9Vδ2-T cells could synergize CD4 T cells to produce influenza virus-specific antibody. Our findings provide a greater scope for Vγ9Vδ2-T cells in adaptive immunity, especially for the Tfh development and humoral immune responses against influenza virus infection.

BACKGROUND: Regulatory T cells (Treg cells), which are essential for regulation of immune response to respiratory syncytial virus (RSV) infection, are promoted by pharyngeal commensal pneumococcus. The effects of pharyngeal microflora disruption by antibiotics on airway responsiveness and relative immune responses after RSV infection have not been clarified. METHODS: Female BALB/c mice (aged 3 weeks) were infected with RSV and then treated with either oral antibiotics or oral double distilled water (ddH(2)O) from 1 d post infection (pi). Changes in pharyngeal microflora were analyzed after antibiotic treatment for 7 d and 14 d. At 8 d pi and 15 d pi, the inflammatory cells in bronchoalveolar lavage fluid (BALF) were investigated in combination with tests of pulmonary histopathology, airway hyperresponsiveness (AHR), pulmonary and splenic Treg cells responses. Pulmonary Foxp3 mRNA expression, IL-10 and TGF-β1 in BALF and lung homogenate were investigated at 15 d pi. Ovalbumin (OVA) challenge was used to induce AHR after RSV infection. RESULTS: The predominant pharyngeal commensal, Streptococcus, was cleared by antibiotic treatment for 7 d. Same change also existed after antibiotic treatment for 14 d. After RSV infection, AHR was promoted by antibiotic treatment at 15 d pi. Synchronous decreases of pulmonary Treg cells, Foxp3 mRNA and TGF-β1 were detected. Similar results were observed under OVA challenge. CONCLUSIONS: After RSV infection, antibiotic treatment cleared pharyngeal commensal bacteria such as Streptococcus, which consequently, might induce AHR and decrease pulmonary Treg cells.

Concealed information test (CIT) has been utilized for long to perform single measurements. The combination of multiple measures outperforms single measures because of the diverse cognitive processes they reflect and the reduction in random errors facilitated by multiple measures. To further explore the performance of the CIT with multiple measurements, 57 participants were recruited and randomly assigned into guilty and innocent groups. Subsequently, simultaneously recorded reaction time (RT), skin conductance responses (SCRs), heart rate (HR), and neuroimaging data were collected from functional near‐infrared spectroscopy (fNIRS) to detect participants' concealed information in a standard CIT. The results demonstrated that all indicators including RT (area under the curve (AUC) = 0.87), SCRs (AUC = 0.79), HR (AUC = 0.78), and fNIRS (channel 8, AUC = 0.85) could differentiate guilty and innocent groups. Importantly, the use of multiple indicators achieved higher detection efficiency (AUC = 0.96) compared to the use of any single indicator. These results illustrate the effectiveness and feasibility of integrating multiple indicators for concealed information detection in CIT. The present study confirms the validity of the concealed information test (CIT) using multiple indicators in a mock crime scenario. It provides robust evidence that integrating multiple indicators in detecting concealed information (AUC = 0.96) could surpass any single traditional measures, including behavioral measures (reaction time, AUC = 0.87), autonomic measures (skin conductance response, AUC = 0.79; heart rate, AUC = 0.78), and neuroimaging measures (functional near‐infrared spectroscopy, channel 8, AUC = 0.85). Our research provides both interesting and substantial insights into the discrete theoretical foundations of various measurements in CIT and has a positive impact on practical applications. [ABSTRACT FROM AUTHOR]