Efficacy and safety of infliximab in the treatment of Kawasaki disease: A systematic review and meta-analysis.

Infliximab is a monoclonal antibody specifically binding tumor necrosis factor-alpha and has been approved for the treatment of several inflammatory disorders. However, the efficacy of infliximab in primary treatment of Kawasaki disease (KD) or retreatment of intravenous immunoglobulin (IVIG)-resistant KD in children is controversial. Therefore, we conducted a meta-analysis to compare the efficacy of infliximab alone or in combination with IVIG to IVIG. Eligible randomized and non-randomized trials were retrieved by searching literature databases prior to May 31, 2023. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated for dichotomous variables, and mean difference (MD) with 95% CI was estimated for continuous variables. A total of 14 eligible studies comprising 1257 participants were included. In refractory KD, infliximab alone was associated with a higher effectiveness rate (OR = 4.48, 95% CI 2.67-7.52) and defervescence rate (OR = 5.01, 95% CI 2.99-8.37) and resulted in a 1.08-day-shorter duration of fever (95% CI 0.61-1.55, P < 0.001) and 1.36-day-shorter length of hospital stay (95% CI 0.65-2.08) compared with IVIG. Incidences of coronary artery lesions (CALs), newly developing CALs, and CAL regression did not differ between both groups. For initial treatment of KD, infliximab in addition to IVIG led to a nominally significant higher effectiveness rate (OR = 2.26, 95% CI 1.02-5.01) and a larger reduction of right coronary artery Z score (MD = -0.24, 95% CI -0.27 to -0.21) but did not show additional efficacy in improving other outcomes. The safety profile was similar between both groups.   Conclusion: The meta-analysis demonstrates that infliximab alone is a well-tolerated and effective treatment for IVIG-resistant KD. The additional efficacy of infliximab to IVIG for initial treatment of KD is limited. More large and high-quality trials are needed to confirm the efficacy of infliximab, especially for intensification of primary treatment for KD. What is Known: • Infliximab is a novel monoclonal antibody specifically blocking tumor necrosis factor-alpha and is approved for treatment of several immune-mediated inflammatory disorders. • The efficacy of infliximab in treating children with Kawasaki disease is controversial. What is New: • Infliximab is an effective and safe treatment for children with refractory Kawasaki disease but adds limited efficacy to intravenous immunoglobulin for initial treatment of Kawasaki disease.

Targeting hypoxia-inducible factor-1, for cancer treatment: Recent advances in developing small-molecule inhibitors from natural compounds.

Rapid progress in molecular cancer biology coupled with the discovery of novel oncology drugs has opened new horizons for cancer target discovery. As one of the crucial signaling pathways related to tumorigenesis, hypoxia-inducible factor-1 (HIF-1) coordinates the activity of many transcription factors and their downstream molecules that impact tumor growth and metastasis. Accumulating evidence suggests that the transcriptional responses to acute hypoxia are mainly attributable to HIF-1α. Moreover, the overexpression of HIF-1α in several solid cancers has been found to be strongly associated with poor prognosis. Thus, pharmacological targeting of the HIF-1 signaling pathways has been considered as a new strategy for cancer therapy in the recent years. Although over the past decade, tremendous efforts have been made in preclinical studies to develop new HIF-1 inhibitors from natural products (reservoirs of novel therapeutic agents), to date, these efforts have not been successfully translated into clinically available treatments. In this review, we provide new insights into the bio-pharmacological considerations for selecting natural compounds as potential HIF-1 inhibitors to accelerate anti-cancer drug development. In addition, we highlighted the importance of assessing the dependency of cancer on HIF1A to shortlist cancer types as suitable disease models. This may subsequently lead to new paradigms for discovering more HIF-1 inhibitors derived from natural products and facilitate the development of potent therapeutic agents targeting specific cancer types.

Age of Acquisition of Mandarin Modulates Cortical Thickness in High-Proficient Cantonese-Mandarin Bidialectals.

Previous studies showed that the onset age of second language acquisition (AoA-L2) can modulate brain structure of bilinguals. However, the underlying mechanism of anatomical plasticity induced by AoA-L2 is still a question in debate. In order to explore the issue, we recruited two groups of native Cantonese-Mandarin speakers, the early group began to speak in Mandarin at about 3.5 and the late group at about 6.5 years old. In addition, the early group had earlier experience in reading Chinese characters than the late group did. Through estimating the cortical thickness (CT), we found that (1) compared with the late group, the early group had thicker CT in the lateral occipital region, left middle temporal gyrus, and left parahippocampal region, which are all involved in visuospatial processing, probably reflecting the effect induced by the earlier or later experiences in processing the characters of Chinese for the two groups; and (2) compared with the late group, the early group had thicker CT in left superior parietal region, which is believed to be involved in language switching, maybe for the early group had the earlier experience in switching back and forth between Cantonese and Mandarin and therefore recruited the executive control network earlier. Our findings revealed the effects of the AoA-L2 in oral language acquisition as well as in written language acquisition as the main determinants of bilingual language structural representation in human brain.

Colorimetric determination of lead(II) or mercury(II) based on target induced switching of the enzyme-like activity of metallothionein-stabilized copper nanoclusters.

It is shown that metallothionein-stabilized copper nanoclusters (MT-CuNCs) display catalase-like activity. In the presence of either lead(II) or mercury(II), the catalase-like activity is converted to a peroxidase-like activity. On addition of Pb(II) or Hg(II), the inhibitory effect of MT-CuNCs on the chromogenic reaction of 3,3',5,5'-tetramethylbenzidine (TMB) with H2O2 is weakened. On the other hand, the catalytic effect of the nanoclusters on the chromogenic reaction is increased. The system MT-CuNCs-Pb(II)/Hg(II) exhibits high affinity for the substrates TMB and H2O2. Their catalytic behavior follows Michaelis-Menten kinetics. Based on these findings, a method was developed for visual detection (via the blue coloration formed) and spectrophotometric determination (at 450 nm) of Pb(II) and Hg(II). The linear range for Pb(II) extends from 0.7 to 96 µM, and the linear ranges for Hg(II) from 97 nM to 2.3 µM and from 3.1 µM to 15.6 µM. The detection limits are 142 nM for Pb(II) and 43.8 nM for Hg(II). Graphical abstract Metallothionein-stabilized copper nanoclusters (MT-CuNCs) display catalase-like activity. On addition of Pb(II) or Hg(II), the catalase-like activity is converted to a peroxidase-like activity. The latter catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2.

Novel and label-free colorimetric detection of radon using AuNPs and lead(II)-induced GR5 DNAzyme-based amplification strategy.

Radioactive radon decays into a stable daughter product, 210Pb, which was used as the detection target to determine the radon radiation dose in a new technique. Pb2+ triggers DNAzyme to cleave a molecular beacon (MB), resulting in the stem-loop structure opening and forming two single DNA strands (ssDNA). The ssDNA binds to unmodified gold nanoparticles and effectively prevents their aggregation in a salt solution. The detached enzyme strands continue to complement the remaining MB to amplify the response signal. The method proposed in this study exhibited a good linear relationship for Pb2+ and radon concentrations in the range of 6.22 × 102-1.02 × 105 Bq h/m3 with a detection limit of 186.48 Bq h/m3 using an ultraviolet-visible spectrometer. In practical applications, this sensitive method can avoid radioactive damage in field testing, and the detection limit meets the national standard in China. Importantly, this simple, highly sensitive strategy uses simple equipment and has a strong anti-interference ability. Graphical abstract.

Bimetallic tandem catalysis-enabled enantioselective cycloisomerization/carbonyl-ene reaction for construction of 5-oxazoylmethyl α-silyl alcohol.

A bimetallic tandem catalysis-enabled enantioselective cycloisomerization/carbonyl-ene reaction was developed. The reaction proceeded well with a broad range of N-propargylamides and acylsilanes, affording the target chiral 5-oxazoylmethyl α-silyl alcohols in up to 95% yield and 99% ee under mild conditions. Importantly, this facile protocol was available for the late-stage modification of several bioactive molecules. Based on the mechanistic study and control experiments, a possible catalytic cycle and transition state are proposed to elucidate the reaction process and enantioinduction.

Comprehensive analysis and experimental validation reveal elevated CLCN4 is a promising biomarker in endometrial cancer.

Several studies have reported the role of CLCN4 in tumor progression. However, its mechanism remains to be thoroughly studied. The objective of this study was to explore the potential pathogenic role of CLCN4 in endometrial carcinoma (UCEC) with a better understanding of the pathological mechanisms involved. The potential roles of CLCN4 in different tumors were explored based on The Cancer Genome Atlas (TCGA), the expression difference, mutation, survival, pathological stage, Immunity subtypes, Immune infiltration, tumor microenvironment (TME), tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR) related to CLCN4 were analyzed. Then, the expression, prognosis, mutation, and functional enrichment of CLCN4 in UCEC were analyzed. Immunohistochemical experiment was used to verify the expression of CLCN4 in endometrial cancer tissues and normal tissues. In vitro, we knocked down of CLCN4 in HEC-1-A cells and performed CCK8, WB, RT-PCR, wound-healing, transwell assays to further validation of the molecular function. Results revealed that high expression of CLCN4 was observed in 20 cancer types of TCGA. CLCN4 expression correlates with poor survival in MESO, BLCA, THCA, especially UCEC tumors. CLCN4 expression was significantly associated with CD4+ T-cell infiltration, especially CD4+ Th1-cell. Immunohistochemical experiment reveals that CLCN4 is high expressed in endometrial tumors, in vitro experiment reveals that knockdown of CLCN4 inhibits the cells proliferation, migration and invasion. Our study is the first to offer a comprehensive understanding of the oncogenic roles of CLCN4 on different tumors. CLCN4 may become a potential biomarker in UCEC.

Multifunctional acetylated distarch phosphate based conducting hydrogel with high stretchability, ultralow hysteresis and fast response for wearable strain sensors.

The rapid development of flexible sensors has greatly increased the demand for high-performance hydrogels. However, it remains a challenge to fabricate flexible hydrogel sensors with high stretching, low hysteresis, excellent adhesion, good conductivity, sensing characteristics and bacteriostatic function in a simple way. Herein, a highly conducting double network hydrogel is presented by incorporating lithium chloride (LiCl) into the hydrogel consisting of poly (2-acrylamide-2-methylpropanesulfonic acid/acrylamide/acrylic acid) (3A) network and acetylated distarch phosphate (ADSP). The addition of ADSP not only formed hydrogen bonds with 3A to improve the toughness of the hydrogel but also plays the role of "physical cross-linking" in 3A by "anchoring" the polymer molecular chains together. Tuning the composition of the hydrogel allows the attainment of the best functions, such as high stretchability (∼770 %), ultralow hysteresis (2.2 %, ε = 100 %), excellent electrical conductivity (2.9 S/m), strain sensitivity (GF = 3.0 at 200-500 % strain) and fast response (96 ms). Based on the above performance, the 3A/ADSP/LiCl hydrogel strain sensor can repeatedly and stably detect and monitor large-scale human movements and subtle sensing signals. In addition, the 3A/ADSP/LiCl hydrogel shows a good biocompatibility and bacteriostatic ability. This work provides an effective strategy for constructing the conductive hydrogels for wearable devices and flexible sensors.

The effect of habitat and human disturbance on the spatiotemporal activity of two urban carnivores: The results of an intensive camera trap study.

With rising urbanization, the presence of urban wildlife is becoming more common, increasing the need for wildlife-friendly spaces in urban planning. Despite this, understanding is limited to how wildlife exploits urban environments and interacts with human populations, and this is vital to our ability to manage and conserve wildlife in urban habitats. Here, we investigate how two urban mammal species, the red fox (Vulpes vulpes) and the European badger (Meles meles), exploit urban environments. Using intensive camera trap surveys, we assessed how habitat and human disturbance influenced the spatiotemporal activity of these species across south-west London. Firstly, we found elevated activity levels of both species at boundaries and within built-up areas, suggesting movement paths follow anthropogenic features. However, badgers were most active in woodland, indicating the importance of high cover habitats suitable for setts and foraging. Secondly, we found badger activity levels were negatively affected by human activity, whilst foxes were unaffected. Further investigation suggested foxes may adapt their activity patterns to avoid human disturbance, with badger activity patterns less plastic. Whilst the results of this study are useful for both the conservation and management of urban wildlife populations, these results also show potential factors which either facilitate or limit wildlife from fully exploiting urban environments.

Toward Mass Customization Through Additive Manufacturing: An Automated Design Pipeline for Respiratory Protective Equipment Validated Against 205 Faces.

Respiratory protective equipment (RPE) is traditionally designed through anthropometric sizing to enable mass production. However, this can lead to long-standing problems of low-compliance, severe skin trauma, and higher fit test failure rates among certain demographic groups, particularly females and non-white ethnic groups. Additive manufacturing could be a viable solution to produce custom-fitted RPE, but the manual design process is time-consuming, cost-prohibitive and unscalable for mass customization. This paper proposes an automated design pipeline which generates the computer-aided design models of custom-fit RPE from unprocessed three-dimensional (3D) facial scans. The pipeline successfully processed 197 of 205 facial scans with <2 min/scan. The average and maximum geometric error of the mask were 0.62 mm and 2.03 mm, respectively. No statistically significant differences in mask fit were found between male and female, Asian and White, White and Others, Healthy and Overweight, Overweight and Obese, Middle age, and Senior groups.

Establishment of a Jaw Fibrosarcoma Patient-Derived Xenograft and Evaluation of the Tumor Suppression Efficacy of Plumbagin Against Jaw Fibrosarcoma.

Background: Head and neck fibrosarcoma is a rare malignant tumor, accounting for about 1% of all head and neck tumors. It can also occur in the jaw bone, for which surgical resection is the main treatment but the recurrence rate is high and the prognosis is usually poor. Due to the lack of models mimicking the biological characteristics of the tumor, there is little progress in the research of the pathogenesis and treatment of fibrosarcoma. Therefore, there is an urgent need to explore a high-fidelity model that can reflect the biological characteristics of fibrosarcoma for the sake of improving the therapeutic outcome and prognosis, and preventing recurrence. Patient-derived xenografts (PDX) may more accurately reflect the human disease, and is an attractive platform to study disease biology and develop treatments and biomarkers. In this study we describe the establishment of jaw fibrosarcoma PDX models and compare PDX tumors to those of human origin. Methods: Tumor biopsies from a patient with jaw fibrosarcoma were implanted in immunodeficient mice. Primary and PDX tumors were characterized extensively by histology, immunohistochemistry and humanized identification. Based on the finding of our previous preliminary research that plumbagin had an anti-tumor effect against head and neck cancer, we used this model in the present study to evaluate the anti-tumor effect of plumbagin on jaw fibrosarcoma. Results: The established PDX model maintained the histological and immunohistochemical characteristics of the primary tumor. Plumbagin significantly inhibited the tumor growth in the jaw fibrosarcoma PDX model. Conclusion: We successfully established a PDX model of jaw fibrosarcoma and demonstrated that this PDX model preserved the important molecular characteristics of the human primary tumor, thus providing a powerful tool for treatment research and new drug development of jaw fibrosarcoma. In addition, plumbagin was found to have an inhibitory effect on the growth of PDX modeled jaw fibrosarcoma, which provides a preliminary research basis for its clinical application.

Initial chest CT findings in COVID-19: correlation with clinical features.

In December 2019, coronavirus disease 2019 (COVID-19), a new de novo infectious disease, was first identified in Wuhan, China and quickly spread across China and around the world. The etiology was a novel betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Lu et al., 2020). On Mar. 11, 2020, World Health Organization (WHO) characterized COVID-19 as a global pandemic. As of Mar. 22, 2020, over 292 000 confirmed COVID-19 cases have been reported globally. To date, COVID-19, with its high infectivity, has killed more people than severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) combined (Wu and McGoogan, 2020).

The penetration and distribution of topical atropine in animal ocular tissues.

PURPOSE: To conduct a multi-tissue investigation on the penetration and distribution of topical atropine in myopia treatment, and determine if atropine is detectable in the untreated contralateral eye after uniocular instillation. METHODS: Nine mature New Zealand white rabbits were evenly divided into three groups. Each group was killed at 5, 24 and 72 hr, respectively, following uniocular instillation of 0.05 ml of 1% atropine. Tissues were sampled after enucleation: conjunctiva, sclera, cornea, iris, ciliary body, lens, retina, aqueous, and vitreous humors. The assay for atropine was performed using liquid chromatography-mass spectrometry (LC-MS), and molecular tissue distribution was illustrated using matrix-assisted laser desorption ionization-imaging mass spectrometry (MALDI-IMS) via an independent experiment on murine eyes. RESULTS: At 5 hr, the highest (mean ± SEM) concentration of atropine was detected in the conjunctiva (19.05 ± 5.57 ng/mg, p < 0.05) with a concentration gradient established anteriorly to posteriorly, as supported by MALDI-IMS. At 24 hr, preferential binding of atropine to posterior ocular tissues occurred, demonstrating a reversal of the initial concentration gradient. Atropine has good ocular bioavailability with concentrations of two magnitudes higher than its binding affinity in most tissues at 3 days. Crossing-over of atropine to the untreated eye occurred within 5 hr post-administration. CONCLUSION: Both transcorneal and transconjunctival-scleral routes are key in atropine absorption. Posterior ocular tissues could be important sites of action by atropine in myopic reduction. In uniocular atropine trials, cross-over effects on the placebo eye should be adjusted to enhance results reliability. Combining the use of LC-MS and MALDI-IMS can be a viable approach in the study of the ocular pharmacokinetics of atropine.

Detection of radon with biosensors based on the lead(II)-induced conformational change of aptamer HTG and malachite green fluorescence probe.

The aim of this paper is to assemble a new biosensor for detecting the accumulated radon dose in the environment to achieve rapid monitor of radon. Based on the correlation between radon and its stable decay daughter 210Pb, a biosensor using the lead-induced specific aptamer HTG conformational changes, and the organic dye malachite green (MG) as a fluorescent probe was assembled. In these studies, we explored a novel, sensitive, label-free, fluorescence biosensing method for the detection of both radon and lead. The fluorescence intensity difference has a linear relationship with Pb2+ and the accumulated radon concentration from 6.87 × 103 Bq·h/m3 to 3.49 × 105 Bq·h/m3. The lead and radon detection limits of this method are 6.7 nmol/L and 2.06 × 103 Bq·h/m3, respectively. The student's t-test results indicated that the new method was reliable and stable. The detection method is sensitive, accurate, easy to operate, has a wide linear range and is highly selective. In the sampling and determination processes of radon, the radiation harm to human health can be effectively avoided.

Amplified colorimetric sensor for detecting radon by its daughter lead based on the free-fixed auto-assembly structure of Duplex-hemin/G-quadruplex.

A novel signal amplification strategy based on a Pb2+-dependent DNAzyme is proposed for detecting Pb2+ and radon through Pb2+-induced DNAzyme cleavage and the auto-assembly of a duplex-hemin/G-quadruplex with two loop-stem structures and enzyme-mimicking catalytic activity. First, the Pb2+-specific DNAzyme cleaves a primer sequence, which induces assembly of the hairpin probe Hp1/Hp2 into a double helix structure. Subsequently, a G-quadruplex forms after the insertion of hemin into the free G-rich sequences; this G-quadruplex possesses the catalytic activity of horseradish peroxidase and changes colorless TMB to its deeply colored oxidized state. lead-dependent DNAzymes were constantly sheared by Pb2+, and the free primer strands were continuously assembled into double chains by hybridization with hairpin probes, providing amplification for the detection of lead (II) and radon. Under the optimum conditions, there was a good linear relationship between ΔA and the lead concentration for Pb2+ concentrations ranging from 2.58 to 18 nM, and the detection limit was 0.77 nM. Analysis of actual samples indicated that when the radon concentration was in the range of 5.41 × 103- 1.65 × 105 Bq·h/m3, the radon concentration and the absorbance were linearly correlated with a detection limit of 1.62 × 103 Bq·h/m3. During the process of radon sampling and detection, radiation damage from the radioactive gas radon can be avoided. In this study, the primer dissociated by the DNAzyme was in a free state. Compared with the fixed-state primer chain, this system will be more convenient for the biological analysis of ultratrace metal ions. Therefore, this strategy has good application prospects for biosensors and is expected to become a novel platform for the amplification and detection of metal ion signals.

Highly stretchable hydrogels for UV curing based high-resolution multimaterial 3D printing.

We report a method to prepare highly stretchable and UV curable hydrogels for high resolution DLP based 3D printing. Hydrogel solutions were prepared by mixing self-developed high-efficiency water-soluble TPO nanoparticles as the photoinitiator with an acrylamide-PEGDA (AP) based hydrogel precursor. The TPO nanoparticles make AP hydrogels UV curable, and thus compatible with the DLP based 3D printing technology for the fabrication of complex hydrogel 3D structures with high-resolution and high-fidelity (up to 7 µm). The AP hydrogel system ensures high stretchability, and the printed hydrogel sample can be stretched by more than 1300%, which is the most stretchable 3D printed hydrogel. The printed stretchable hydrogels show an excellent biocompatibility, which allows us to directly 3D print biostructures and tissues. The great optical clarity of the AP hydrogels offers the possibility of 3D printing contact lenses. More importantly, the AP hydrogels are capable of forming strong interfacial bonding with commercial 3D printing elastomers, which allows us to directly 3D print hydrogel-elastomer hybrid structures such as a flexible electronic board with a conductive hydrogel circuit printed on an elastomer matrix.