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Supplementary Figure S1: NMR Spectra of HA-Paclitaxel. 1H-NMR spectrum of HA-paclitaxel. Specific groups of HA-paclitaxel are shown with arrows; Supplementary Figure S2: Representative bioluminescent images of animals 24 hrs after intracardiac injection of the 231Br cells; Supplementary Figure S3: Representative image demonstrating that bioluminescence correlates well with histological location and burden of metastatic lesions in brain.

The aim of this study was to investigate the roles of miR-130b-3p and ICAM-1 in gestational diabetes mellitus (GDM) and their potential association.Human placenta mesenchymal stem cells (PlaMSCs) were isolated from GDM patients, and the effects of the PlaMSCs from GDM patients (GDM-MSCs) and the exosomes secreted by GDM-MSCs on human umbilical vein endothelial cell (HUVEC) proliferation, migration, and angiogenesis were detected. Next, GDM-MSCs were transfected with miR-130b-3p antagomir to modify miR-130b-3p expression in GDM-MSCs-derived exosomes, and the exosomes with modified miR-130b-3p expression were cultured with HUVECs to evaluate exosomal miR-130b-3p on HUVEC function. Furthermore, a target gene of miR-130b-3p was predicted and assessed. The miR-130b-3p-modified exosomes were cultured with HUVECs transfected with ICAM-1 shRNA to determine the effect of miR-130b-3p-ICAM-1 crosstalk on HUVEC function. Additionally, a GDM mouse model was conducted to further study the effect of miR-130b-3p in GDM in vivo.GDM-MSCs inhibited HUVEC proliferation and angiogenesis. The elevated expression of miR-130b-3p was found in GDM-MSCs-derived exosomes. GDM-MSCs-derived exosomes repressed the proliferation and angiogenesis of HUVECs and miR-130b-3p inhibition could restrain the inhibition of the exosomes on HUVEC function. Mechanistically, miR-130b-3p downregulated ICAM-1 expression in a targeted manner, and thereby enhanced HUVEC proliferation, migration, and angiogenesis and increased the expression of angiogenesis-related factors. Moreover, miR-130b-3p inhibition promoted placental angiogenesis in GDM mice and upregulated ICAM-1 expression.Conclusively, GDM-MSCs-derived exosomes shuttling miR-130b-3p repressed proliferation, migration, and angiogenesis of HUVECs by regulating ICAM-1 expression.

Understanding the heterogeneous preferences of individuals for disaster insurance attributes is critical for product improvement and policy design. In an era of global environmental change, the Qinghai-Tibet Plateau is a hotspot of natural hazards. Improving the capability of rural housing disaster insurance to foster local residents’ disaster resilience is of great significance but remains under addressed. We used a discrete choice experiment approach to provide the first estimates of rural residents’ preferences for rural housing disaster insurance attributes in central and western Tibet. We estimated residents’ preferences and willingness-to-pay for the sum insured, subsidy rate, insured object, and perils covered. The potential impacts of increasing the sum insured, expanding the insured object, and lowering subsidy rates were evaluated. Our results suggest that residents prefer products with a high sum insured, high subsidy rate, and a complete list of insured objects. Residents who have experienced specific hazards tend to prefer the corresponding perils covered. Females and residents who have a closer social network are more likely to purchase insurance. Product improvement and policy simulation results suggest that, while lowering the subsidy rate, increasing the sum insured and expanding the insured object could promote participation and improve residents’ welfare. Our results could improve the understanding of the preferences of households in remote regions and support policy implementations.

A simpler and more efficient method for preparing sophorolipids (SLs) facilitates the application of SLs. In this study, a new preparation method for SLs named SLs-WpH was designed firstly: the SLs in fermentation broth were separated by sedimentation in a separatory funnel, then dissolved in distilled water by adjusting the pH to 6-7 and centrifuged to remove the yeast brought in the sedimentation process, and the supernatant was vacuum freeze-dried. Secondly, the purity, composition, and antimicrobial activity of SLs-WpH were compared with the other two types SLs purified by ethanol and ethyl acetate (SLs-EtOH, SLs-EAC) in order to evaluate the feasibility of this preparation process. The purity of SLs-WpH was between that of SLs-EtOH and SLs-EAC and there was no difference in the composition, mainly lactonic SLs by TLC and HPLC analysis. SLs-WpH showed broad-spectrum antimicrobial activity against bacteria, fungi and actinomyces. In addition, both the diameter of the inhibition zone (15 to 18 mm) against Staphylococcus aureus and the mycelium inhibition rate (70 to 78%) against Phytophthora infestans were not significantly different among these three types SLs; SLs-WpH had better inhibitory effect against Streptomyces scab and S. bottropensis with MICs of 32 μg mL-1 than the other two types with MICs ≥64 μg mL-1, which is the first reported that SLs had inhibitory activity against actinomyces. The results of this study indicated that the new preparation process of SLs is feasible and SLs have great application potential in the prevention of potato common scabs caused by pathogenic Streptomyces.

Schematic graph of PGRFB affecting DSS-induced UC through the AMPK/NF-κB/NLRP3 signaling pathway.

The heteroscorpionate metal hydride complex LZnH 2, LMgH 5 (L = (MePz)2CP(Ph)2NPh, MePz = 3,5-dimethylpyrazolyl), and formate complex 3, were synthesized and utilized for the catalytic hydroboration reaction of CO2.

Binder-free NiFe-based electrocatalyst with aligned pore channels has been prepared by freeze casting and served as a bifunctional catalytic electrode for oxygen and hydrogen evolution reaction (OER and HER). The synergistic effects between Ni and Fe result in the high electrocatalytic performance of porous NiFe electrodes. In 1.0 M KOH, porous Ni7Fe3 attains 100 mA cm−2 at an overpotential of 388 mV with a Tafel slope of 35.8 mV dec−1 for OER, and porous Ni9Fe1 exhibits a low overpotential of 347 mV at 100 mA cm−2 with a Tafel slope of 121.0 mV dec−1 for HER. The Ni9Fe1//Ni9Fe1 requires a low cell voltage of 1.69 V to deliver 10 mA cm−2 current density for overall water splitting. The excellent durability at a high current density of porous NiFe electrodes has been confirmed during OER, HER and overall water splitting. The fine electrocatalytic performances of the porous NiFe-based electrodes owing to the three-dimensionally well-connected scaffolds, aligned pore channels, and bimetallic synergy, offering excellent charge/ion transfer efficiency and sizeable active surface area. Freeze casting can be applied to design and synthesize various three-dimensionally porous non-precious metal-based electrocatalysts with controllable multiphase for energy conversion and storage.

Gut microbiota dysbiosis is already a global problem after antibiotic overuse. This study was to investigate the therapeutic effect of lentinan and the mechanism of recovery of intestinal inflammation on broad-spectrum antibiotic-driven gut microbial dysbiosis in mice. Gut microbiota was elucidated by the Illumina MiSeq platform. Gas chromatography/mass spectrometry was used to investigate short-chain fatty acid content. Colon histology, expression of tight-junction associated proteins and pro-inflammatory cytokines levels were evaluated. The results showed that the gut microbiota of diversity and richness were reduced and various taxonomic levels of the gut microbiota were perturbed after antibiotics gavage. The abundance of Firmicutes and Bacteroidetes shifted to Proteobacteria and increased the relative abundance of harmful microbiota (Parabacteroides and Klebsiella) post-antibiotics, whereas lentinan administration reversed the dysbiosis and increased beneficial microbiota, including S24-7, Lactobacillus, Oscillospira, Ruminococcus and Allobaculum. The concentrations of propionic acid and butyric acid were significantly increased by treatment with lentinan. And lentinan improved colon tissue morphology and reduced pro-inflammatory cytokines via altering NF-κB signaling pathway in antibiotic-driven gut microbial dysbiosis mice. Taken together, the results proved that lentinan can be used as a prebiotic and the result provided a theoretical basis for improving the clinical treatment of broad-spectrum antibiotics side effects.

Near-infrared (NIR)-light-triggered photothermal therapy (PTT) is usually associated with undesirable damage to healthy organs nearby due to the high temperatures (>50 °C) available for tumor ablation. Low-temperature PTT would therefore have tremendous value for clinical application. Here, we construct a hypoxia-responsive gold nanorods (AuNRs)-based nanocomposite of CRISPR-Cas9 for mild-photothermal therapy via tumor-targeted gene editing. AuNRs are modified with azobenzene-4,4'-dicarboxylic acid (p-AZO) to achieve on-demand release of CRISPR-Cas9 using hypoxia-responsive azo bonds. In the hypoxic tumor microenvironment, the azo groups of the hypoxia-activated CRISPR-Cas9 nanosystem based on gold nanorods (APACPs) are selectively reduced by the overexpression of reductases, leading to the release of Cas9 and subsequent gene editing. Owing to the knockout of HSP90α for reducing the thermal resistance of cancer cells, highly effective tumor ablation both in vitro and in vivo was achieved with APACPs under mild PTT.

Transcription factors (TFs) can manage the coordinated expression of genes clusters or multiple genes. TF was used to improve bacterial denitrification ability in this study. During denitrification, the ntrY of R. azotoformans, which encodes the sensor of NtrX/Y system, was significantly upregulated in transcription. Denitrification of the mutant △ntrY was significantly inhibited, and it was recovered after replenishing this gene to the mutant, which indicates the NtrX/Y system plays an important role in regulating bacterial denitrification. According to additional research, the NtrX/Y system regulates bacterial denitrification by directly promoting the expression of the nitrite reductase. ntrY overexpression appears to accelerate bacterial denitrification, and the introduction of a strong promoter tac in conjunction with iron supply optimization increases the rate by 72% further. This study realizes bacterial denitrification enhancement from the perspective of global transcription regulation, which provides a novel strategy for improving microbial ability to degrade pollutants.

Background: Indiolethylamine-N-methyltransferase (INMT) is a methyltransferase responsible for transferring methyl groups from methyl donor SAM to its substrate. S-adenosyl-l-methionine (SAM), obtained from the methionine cycle, is a naturally occurring sulfonium compound that is vital to cellular metabolism. The expression of INMT is down-regulated in many tumorous tissues, and it may contribute to tumor invasion and metastasis. Nevertheless, the expression of INMT and its relationship to methylation and immune infiltrates in head and neck squamous cell carcinoma (HNSC) remains a mystery. Thus, we evaluated expression, clinicopathological features, prognosis, several critical pathways, DNA methylation, and immune cell infiltration for the first time.Methods: Analysis of the clinicopathological characteristics of INMT expression, several tumor-related bioinformatics databases were utilized. In addition, the role of INMT expression was analyzed for prognosis. Several INMT-related pathways were enriched on the LinkedOmics website. In addition, we have analyzed the methylation of INMT in HNSC in detail by using several methylation databases. Lastly, the relationship between INMT gene expression and immune infiltration was analyzed with ssGSEA, Timer, and TISIDB.Results: In HNSC, mRNA and protein levels were significantly lower than in normal tissues. The low expression of INMT was statistically associated with T stage, histological grade, gender, smoking history, and alcohol consumption. HNSC patients with low INMT expression have a poorer OS (overall survival) compared to those with high levels of expression. In addition, the multivariate analysis revealed INMT expression to be a remarkable independent predictor of prognosis in HNSC patients. An analysis of gene enrichment showed that several pathways were enriched in INMT, including the Ras signaling pathway, the cGMP-PKG signaling pathway, and others. Moreover, methylation patterns of INMT detected in a variety of methylation databases are closely associated with mRNA expression and prognosis. Finally, INMT was significantly correlated with immune infiltration levels.Conclusion: HNSC with low levels of INMT exhibits poor survival, hypomethylation, and immune infiltration. For HNSC, this study presented evidence that INMT is both a biomarker of poor prognosis and a target of immunotherapy.

Xylanases have the potential to be used as bio-deinking and bio-bleaching materials and their application will decrease the consumption of the chlorine-based chemicals currently used for this purpose. However, xylanases with specific properties could act effectively, such as having significant thermostability and alkali resistance, etc. In this study, we found that TfXyl10A, a xylanase from Thermobifida fusca, was greatly induced to transcript by microcrystalline cellulose (MCC) substrate. Biochemical characterization showed that TfXyl10A is optimally effective at temperature of 80 °C and pH of 9.0. After removing the carbohydrate-binding module (CBM) and linker regions, the optimum temperature of TfXyl10A-CD was reduced by 10°C (to 70°C), at which the enzyme’s temperature tolerance was also weakened. While truncating only the CBM domain (TfXyl10AdC) had no significant effect on its thermostability. Importantly, polysaccharide-binding experiment showed that the auxiliary domain CBM2 could specifically bind to cellulose substrates, which endowed xylanase TfXyl10A with the ability to degrade xylan surrounding cellulose. These results indicated that TfXyl10A might be an excellent candidate in bio-bleaching processes of paper industry. In addition, the features of active-site architecture of TfXyl10A in GH10 family were further analyzed. By mutating each residue at the -2 and -1 subsites to alanine, the binding force and enzyme activity of mutants were observably decreased. Interestingly, the mutant E51A, locating at the distal -3 subsite, exhibited 90% increase in relative activity compared with wild-type (WT) enzyme TfXyl10A-CD (the catalytic domain of TfXyl110A). This study explored the function of a GH10 xylanase containing a CBM2 domain and the contribution of amino acids in active-site architecture to catalytic activity. The results obtained provide guidance for the rational design of xylanases for industrial applications under high heat and alkali-based operating conditions, such as paper bleaching.

BackgroundUlcerative colitis (UC) is an inflammatory lesion of the colon from various causes. As current therapeutic drugs have adverse effects on patients with UC, there is a growing demand for alternative medicines from natural and functional foods. Locust bean gum, as a dietary fiber, has a variety of physiological effects.MethodsIn the present study, locust bean gum hydrolysate (LBGH) was obtained from the acid hydrolysis of locust bean gum. The structure of LBGH was characterized by thin-layer chromatography and high performance liquid chromatography (HPLC)-electrospray ionization (ESI)-mass spectrometry (MS)/MS analysis. And we investigated the therapeutic effect of LBGH on a mouse model of dextran sulfate sodium (DSS)-induced colitis.ResultsIt was observed that the LBGH consisted of a mixture of monosaccharides and oligosaccharides with a degree of polymerization (DP) 2–7. LBGH treatment dramatically alleviated colonic pathological damage, suppressed the overproduction of pro-inflammatory factors and the activation of nuclear factor κB (NF-κB), increased the mRNA expression of tight junction proteins, and increased the abundance of probiotics such as Lactobacillus and Bifidobacterium in the gut.ConclusionThere is a correlation between these mitigating effects on inflammation and the treatment of LBGH. Therefore, LBGH has tremendous potential in the treatment of colitis.

Dysregulation of the ubiquitin-proteasome system (UPS) pathway greatly affects uncontrolled proliferation, genomic instability, and carcinogenesis, particularly in those with renal papillary cell carcinoma (PRCC). However, there is little information at the molecular level about the full link between changes in the genes involved in ubiquitin-mediated proteolysis and PRCC.The Cancer Genome Atlas (TCGA) and GeneCards databases were utilized to find the clinical data and gene expression patterns of patients with PRCC. Univariate Cox regression analysis and absolute shrinkage and selection operator (LASSO) analyses identified a risk signature formed by ten optimal UPS genes. The predictive value of the risk signature in TCGA-PRCC cohorts was evaluated using Kaplan-Meier analysis and receiver operating characteristic (ROC) curves. By utilizing GO enrichment and the KEGG pathway, the interactions of differentially expressed genes connected to ubiquitin-mediated proteolysis were functionally examined. The protein expression of the hub genes was affirmed using the Human Protein Atlas (HPA) database. The effectiveness of particular CDC20 and UBE2CTen of the best ubiquitin-mediated proteolysis genes (UBE2C, DDB2, CBLC, BIRC3, PRKN, UBE2O, SIAH1, SKP2, UBC, and CDC20) were detected to create a risk signature. The high-risk score group stratified was associated with advanced tumor status and poor survival of PRCC patients. 10 genes were also found to be associated with the cell cycle pathway and ubiquitin-mediated proteolysis to GO and KEGG analysis. Of these 10 genes, CDC20 and UBE2C are highly expressed in tumor tissue and correlated with cancer immunity founded on the analyses of the expression of human protein atlas and TISIDB. The downregulation of UBE2C facilitated tumor inhibition and the anti-immune effect was confirmed byOur results indicate that the risk model created from the ubiquitin-mediated proteolysis genes can be reliably and accurately predict the prognosis of PRCC patients, highlighting its targeted value for PRCC treatment. Particularly, the expression of UBE2C may be crucial for the prognosis and immunological treatment of renal cancer.

The aim of this work was to study the effect and mechanism of β-carotene on insulin resistance and glucose transport in gestational diabetes mellitus (GDM). Placental tissue and venous blood of 26 GDM patients and 18 normal women were collected. Mice fed a high-fat diet were established as GDM models and treated with β-carotene, from which peripheral blood and placenta tissue were collected. HTR-8/SVneo cells were treated with 10

Immunization programs against SARS-CoV-2 with commercial intramuscular (IM) vaccines prevent disease but not infections. The continued evolution of variants of concern (VOC) like Delta and Omicron has increased infections even in countries with high vaccination coverage. This is due to commercial vaccines being unable to prevent viral infection in the upper airways and exclusively targeting the spike (S) protein that is subject to continuous evolution facilitating immune escape. Here we report a multi-antigen, intranasal vaccine, NanoSTING-NS that yields sterilizing immunity and leads to the rapid and complete elimination of viral loads in both the lungs and the nostrils upon viral challenge with SARS-CoV-2 VOC. We formulated vaccines with the S and nucleocapsid (N) proteins individually to demonstrate that immune responses against S are sufficient to prevent disease whereas combination immune responses against both proteins prevents viral replication in the nasal compartment. Studies with the highly infectious Omicron VOC showed that even in vaccine-naïve animals, a single dose of NanoSTING-NS significantly reduced transmission. These observations have two implications: (1) mucosal multi-antigen vaccines present a pathway to preventing transmission and ending the pandemic, and (2) an explanation for why hybrid immunity in humans is superior to vaccine-mediated immunity by current IM vaccines.

Streptomyces albulus is a kind of safety bacteria that is used to produce a natural food preservative named ε-poly-l-lysine (ε-PL). Environmental autoacidification (the pH declined from 6.8 to approximately 3.0) inevitably occurred in ε-PL biosynthesis by S. albulus. In this study, the dynamic responses of S. albulus QLU58 and its acid-tolerant mutants to autoacidification were investigated at the physiological and transcriptional levels. The results showed that cell growth, ε-PL production, cell respiratory activity, and intracellular pH (pHi) homeostasis were disturbed by autoacidification. In the initial autoacidification stage (before 24 h), the acid tolerance of S. albulus was effectively improved by increasing the intracellular ATP and related amino acids contents and the H+-ATPase activity, regulating the membrane fatty acids composition, and maintaining the pHi at about 7.7. However, as the autoacidification degree deepened (after 24 h), the metabolic activities decreased and negative cell growth appeared, which weakened the acid tolerance and caused the pHi to decline to about 6.5. Additionally, the acid-tolerant mutants exhibited better performances during autoacidification, which was also confirmed by the related genes’ improved transcription levels. These results provide references for the analysis of progressive environmental modification in ε-PL production.

Objectives. Antinuclear antibody (ANA) positivity is a key finding in JIA-associated uveitis (JIAU), but there are quite a few patients with negative ANA. There is no relevant report on the difference of their clinical manifestations. Previous animal model studies have found that the occurrence of uveitis is related to macrophage activation. In this article, our goal is to investigate changes in the morphology and cytokines of peripheral blood mononuclear cells (PBMCs) in uveitis patients testing positive or negative for ANAs after lipopolysaccharide (LPS) stimulation. Methods. A total of 30 patients were included in this study (10 in each group). They were divided into three groups (the ANA-positive [ANA+] group, ANA-negative [ANA-] group, and control group). There were ten patients (6 females and 4 males) in each group. Peripheral venous blood was collected into a heparinized tube, and PBMCs were isolated as soon as possible by the Ficoll-Hypaque density gradient separation method. Isolated cells were mixed with RPMI-1640 medium, and the cell concentration was adjusted to ensure that each patient had the same number of cells entering the study. After putting the extracted PBMC into the culture plate, LPS was added carefully to the plate. The cell culture supernatants were collected at 0 h, 3 h, 6 h, 12 h, and 24 h after LPS stimulation to detect the concentrations of IL-6, IL-1, TNF-α, and IL-10. Immunofluorescence was used to discover the deformation of macrophages after LPS stimulation. Results. The newly isolated cells were approximately round. 6 h after LPS stimulation, the ratio of noncircular cells/circular cells was the highest in the ANA+ group. Unlike IL-10 that has been rising during the observation period, IL-6, IL-1, and TNF-α peaked at 6 h after LPS stimulation. Conclusion. With LPS motivation, cytokines in the ANA+ group increased the most violently.

Purpose: To evaluate averaged, repeat Spot Vision Screener (Welch Allyn) refractive screening with and without maximal atropine cycloplegia in preschool Chinese children. Methods: Refractive errors of 450 preschool children aged 3 to 6 years were measured by cycloplegic retinoscopy as the gold standard. The Spot Vision Screener was used to examine the refractive errors of these children before and after cycloplegia. The differences between the two methods were assessed using the Wilcoxon test and Bland-Altman plot. The accuracy of the Spot Vision Screener in detecting refractive errors was evaluated by receiver operating characteristic curve analysis. Results: Before cycloplegia, the Spot Vision Screener provided statistically significantly lower values of sphere (median difference: 1.50 diopters [D], 95% CI: 1.38 to 1.63 D) and spherical equivalent (median difference: 1.56 D, 95% CI: 1.50 to 1.69 D). For hyperopia of greater than 3.00 D spherical value (n = 118), the median difference between the Spot Vision Screener and cycloplegic retinoscopy was 2.63 D (95% CI: 2.50 to 2.88 D). The Bland-Altman plot showed that the difference between the results of the two examination methods was large. The sensitivity of the Spot Vision Screener for detecting refractive errors increased after the screening criteria were optimized. Conclusions: The Spot Vision Screener was efficient in detecting anisometropia in Chinese preschool children. The Spot Vision Screener without cycloplegia underestimated the spherical value of hyperopia and the difference was larger when the cycloplegic hyperopia increased. The performance of the Spot Vision Screener without cycloplegia in detecting cycloplegic hyperopia was not complete. The instrument referral criteria of the Spot Vision Screener should be adjusted according to clinical practice, but it is not simple and users should do it with expert assistance. [ J Pediatr Ophthalmol Strabismus . 2021;58(3):146–153.]

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Background: Microglia-associated neuroinflammation plays a crucial role in the initiation and development of neuropathic pain (NeuP). AdipoRon is an analog of adiponectin, which can activate the adiponectin receptors and exhibit anti-inflammatory property in various diseases. Adenosine monophosphate-activated protein kinase (AMPK) is the main downstream target of adiponectin receptor 1 (AdipoR1). Activation of AdipoR1 promotes the conversion of AMPK to phosphorylated AMPK (p-AMPK). The AdipoR1/AMPK pathway is involved in the regulation of inflammation. And therapies targeting this pathway are beneficial for a variety of diseases. This study aimed to investigate whether AdipoRon could alleviate NeuP by inhibiting the expression of microglia-derived tumor necrosis factor-alpha (TNF-α) through the AdipoR1/AMPK pathway.Methods: In vivo, the spared nerve injury (SNI) model was established in mice to simulate NeuP. Using the Von Frey test to detect the effect of AdipoRon on mechanical paw withdrawal threshold. Western Blot was performed to detected the effects of AdipoRon on the expression of AdipoR1, AMPK, p-AMPK and TNF-α. Immunofluorescence was performed to observed the effects of AdipoRon on spinal microglia. In vitro, using lipopolysaccharide (LPS) to induce inflammatory responses in BV2 cells. The effect of AdipoRon on cell proliferation was detected by CCK-8. Using qPCR to examined the effects of AdipoRon on the expression of TNF-α and polarization markers in LPS-treated BV2 cells. And the effect of AdipoRon on the AdipoR1/AMPK pathway was confirmed by Western Blot.Results: Intraperitoneal injection of AdipoRon alleviated mechanical pain in SNI mice. Moreover, the application of AdipoRon reduced expression of TNF-α and the number of activated microglia in the ipsilateral spinal cord. Then, AdipoRon decreased the protein level of AdipoR1 and increased the protein level of p-AMPK in the ipsilateral spinal cord. In vitro, AdipoRon inhibited BV2 cell proliferation and reversed LPS-induced TNF-α expression and polarization imbalance. Furthermore, AdipoRon abrogated the LPS-induced increase in AdipoR1 expression and decrease in p-AMPK expression in BV2 cells.Conclusions: Our results suggest that AdipoRon alleviates NeuP by inhibiting the expression of microglia-derived TNF-α through the AdipoR1/AMPK pathway.

A simple aptazyme-induced cascade signal amplification (denoted as ACSA) was integrated with a triple-channel volumetric bar-chart chip (TV-Chip) to visually quantitate aflatoxin B1 (AFB1) and adenosine triphosphate (ATP). Bifunctional aptazymes consisting of aptamers and G-quadruplex-forming sequences were modified on magnetic silica nanoparticles (MSNPs) to construct sensing probes. The recognition of aptamers and targets leads to the formation of hemin/G-quadruplex (hGQ) DNAzymes, which can mimic the horseradish peroxidase (HRP)-accelerated signal enhancement reaction, enabling the polymerization of dopamine and subsequent deposition of polydopamine (PDA) on the MSNP probes, thereby providing abundant anchor sites to covalently immobilize numerous 4-mercaptophenylboric acid (4-MPBA)-modified platinum nanoparticles (PtNPs) (MPt). As a result, this strategy possesses high sensitivity by introducing a large number of PtNPs into the TV-Chip. The detection limits of AFB1 and ATP with 0.075 pM and 0.818 pM, respectively, were easily achieved without any additional instruments. In addition, the detection results of AFB1-spiked food samples were in good agreement with the commercial AFB1 ELISA kit, which verified the accuracy and reliability of this method. The ACSA-based TV-Chip would show great promise for on-site and real-time visual quantitation of trace targets.

Xylanases have the potential to be used as bio-deinking and bio-bleaching materials and their application will decrease the consumption of the chlorine-based chemicals currently used for this purpose. However, xylanases with specific properties could act effectively, such as having significant thermostability and alkali resistance, etc. In this study, we found that

The target of EGR1 protein 1 (TOE1) is evolutionarily conserved from Caenorhabditis elegans to mammals, which plays a critical role in the maturation of a variety of small nuclear RNAs. Mutation in human TOE1 has been reported to cause pontocerebellar hypoplasia type 7, a severe neurodegenerative syndrome. However, the role of TOE1 in early embryonic development remains unclear. Herein, we found that Toe1 mRNA and protein were expressed in mouse preimplantation embryos. Silencing Toe1 by siRNA led to morula-to-blastocyst transition failure. This developmental arrest can be rescued by Toe1 mRNA microinjection. EdU incorporation assay showed a defect in blastomere proliferation within developmentally arrested embryos. Further studies revealed that Toe1 knockdown caused increased signals for γH2AX and micronuclei, indicative of sustained DNA damage. Moreover, mRNA levels of cell cycle inhibitor p21 were significantly upregulated in Toe1 knockdown embryos before developmental arrest. Together, these results suggest that TOE1 is indispensable for mouse early embryo development potentially through maintaining genomic integrity. Our findings provide further insight into the role of TOE1 in mouse preimplantation embryonic development.

Because of the increased incidence and prevalence, ulcerative colitis (UC) has become a global health issue in the world. Current therapies for UC are not totally effective which result in persistent and recurrent symptom of many patients. Lactobacillus with anti-inflammatory effects might be beneficial to the prevention or treatment for UC. Here, we examined the ameliorative effects of the metabolites of Lactobacillus fermentum F-B9-1 (MLF) in Caco-2 cells and dextran sodium sulfate (DSS)-induced UC model mice. MLF displayed intestinal barrier-protective activities in Caco-2 cells by increasing the expression of Occludin and ZO-1. They also showed anti-inflammatory potential in interleukin (IL)-1β and IL-6. In order to further examine the in vivo anti-inflammatory effect of MLF, the MLF was gavaged in the DSS-induced UC model mice. The intragastric administration of MLF effectively alleviated colitis symptoms of weight loss, diarrhea, colon shortening, and histopathological scores, protected intestinal barrier function by increasing Occludin and ZO-1, and attenuated colonic and systemic inflammation by suppressing production of IL-1β and IL-6. Finally, the use of MLF remodeled the diversity of the gut microbiota and increased the number of beneficial microorganisms. Overall, the results demonstrated that MLF relieved DSS-induced UC in mice. And MLF might be an effective therapy method to UC in the clinic in the future.

Respiratory viral infections, especially Influenza (endemic) or SARS-CoV-2 (pandemic since 2020), cause morbidity and mortality worldwide. Despite remarkable progress in the development and deployment of vaccines, they are clearly impacted by the rapid emergence of viral variants. The development of an off-the-shelf, effective, safe, and low-cost drug for prophylaxis against respiratory viral infections is a major unmet medical need. Here, we developed NanoSTING, a liposomally encapsulated formulation of the endogenous STING agonist, 2’-3’ cGAMP, to function as an immunoantiviral. NanoSTING rapidly activates the body’s innate immune system to facilitate a broad-spectrum antiviral response against SARS-CoV-2 and influenza variants in hamsters and mice. We demonstrate that a single intranasal dose of NanoSTING can: (1) treat infections throughout the respiratory system and minimize clinical symptoms, (2) protect against highly pathogenic strains of SARS-CoV-2 (alpha and delta), (3) provide durable protection against reinfection from the same strains without the need for retreatment, (4) prevent transmission of the highly infectious SARS-CoV-2 Omicron strain, and (5) provide protection against both oseltamivir-sensitive and resistant strains of influenza. Mechanistically, administration of NanoSTING rapidly upregulated interferon-stimulated and antiviral pathways in both the nasal turbinates and lung. Our results support using NanoSTING as a thermostable, immunoantiviral with broad-spectrum antiviral properties making it appealing as a therapeutic for prophylactic or early post-exposure treatment.

α-l-Arabinofuranosidase (Abf), a debranching enzyme that can remove arabinose substituents from arabinoxylan, promotes the hydrolysis of hemicellulose in plant biomass. However, the functional specificity of Abfs from different glycoside hydrolase (GH) families on the digestion of arabinoxylan and their synergistic interaction with xylanase have not been systematically studied. In this work, we characterized three Abfs (AxhA, AbfB, and AbfC) from GH62, GH54, and GH51 families in

Triple-negative breast cancer (TNBC) is a rapidly recurring and highly metastatic malignancy with high heterogeneity and chemoradiotherapy resistance. Chronic unpredictable mild stress (CUMS) can induce the occurrence of tumors and enhance lymphatic infiltration and distant metastasis through direct interaction with the sympathetic nervous system; however, its relevance in TNBC is yet to be clarified. In this study, DARS-AS1, a newly reported CUMS-responsive lncRNA, was found to be enriched in TNBC clinical tumors and cells and positively correlated with late clinical stage in patients with TNBC. DARS-AS1 overexpression significantly enhanced the migration and invasion of TNBC tumors by inhibiting miR-129-2-3p and upregulated CDK1 to activate the NF-κB/STAT3 signaling pathway both in vitro and in vivo. Treatment with DARS-AS1 siRNA-loaded exosomes (EXOs) substantially slowed CUMS-induced TNBC cell growth and liver metastasis. Therefore, DARS-AS1 represents a potential therapeutic target for metastatic TNBC, and EXOs may serve as siRNA delivery carriers in clinical therapy.

China is one of the countries affected most by natural hazards. With the rapid urbanization process, the susceptibility of Chinese cities to natural disasters increases. In this paper, we propose an integrated natural disaster urban resilience evaluation framework for Chinese cities. We aggregate city-level economic, social, infrastructural, and environmental indicators of 39 major Chinese cities from 2002 to 2017 and convert them to a multi-dimensional resilience index using factor analysis. We validate our measure by showing that cities with larger resilience indices have lower natural disaster losses. We further investigate the regional characteristics of our urban resilience index and find that Chinese cities improved their resilience to natural hazards across the years. Although cities in the eastern coastal area tend to be more resilient than cities in other regions, the gap has been narrowed. Our paper provides some insights into how cities may measure and improve their urban resilience system.

Reduction of carbonyl derivatives by using Earth-abundant, cheap, and environmentally benign metal-based catalysts through an atom-efficient method is a challenging task. Herein, we report the synthesis and characterization of dinuclear magnesium complexes 1–3 chelated by a phosphinimino amide skeleton. In combination with pinacolborane (HBpin) as a reducing agent, complex 1 bearing an ortho-methyl substituent on the phenyl ring of the ligand showed excellent reduction capability for a broad range of carbonyl derivatives under mild reaction conditions. Aldehydes, ketones, and acrolein substrates were efficiently reduced to the corresponding alkoxy-borane products with a record high TOF. Besides, acrolein derivatives were exclusively reduced to 1,2-regioselective products. Using two equiv. of HBpin, ester substrates were reduced to two kinds of alkoxy-borane products. Carbonate reduction accomplished by using complex 1 and three equiv. of HBpin afforded diols and a methanol precursor, respectively. When chiral substrates such as (S)-1,2-propanediol carbonate and L-lactide or polymeric P(L-LA) were employed, the chirality was almost retained in their reductive products.

Multiple endocrine neoplasia type 1 (MEN 1) is a rare hereditary disease which transmitted as autosomal dominant disorder with high penetrance. MEN1 includes vary combinations of more than 20 endocrine and non-endocrine tumors. Clinically, MEN1 is characterized by tumor or hyperplasia in two or more endocrine tissues (parathyroid, pituitary, pancreas, adrenal glands). Since it is a rare condition, there are no guidelines with respect to the follow-up of pregnant women with MEN 1, here we the first Asian case of a 32-year-old primigravida with a confirmed diagnosis of MEN1 and primary hypertension prior to conception, cesarean section was performed at 34+2 weeks for severe preeclampsia and potential risks, both the patient and fetus recovered well.

ObjectiveTo assess the incidence, risk factors, and clinical characteristics of perinatal stroke in Beijing.MethodsThis multicenter prospective study included all the live births from 17 representative maternal delivery hospitals in Beijing from March 1, 2019 to February 29, 2020. Neonates with a stroke were assigned to the study group. Clinical data, including general information, clinical manifestations, and risk factors, were collected. Up until 18 months after birth, neonates were routinely assessed according to the Ages and Stages Questionnaire (ASQ) and/or the Bayley scale. Statistical analysis was done using the chi-squared, t-tests, and logistic regression analysis using SPSS version 26.0.OutcomesIn total, 27 cases were identified and the incidence of perinatal stroke in Beijing was 1/2,660 live births, including 1/5,985 for ischemic stroke and 1/4,788 for hemorrhagic stroke. Seventeen cases (62.96%) of acute symptomatic stroke and convulsions within 72 h (10 cases, 37.04%) were the most common presentations. Ten patients showed no neurological symptoms and were found to have had a stroke through routine cranial ultrasonography after being hospitalized for non-neurological diseases. The risk factors include primiparity, placental or uterine abruption/acute chorioamnionitis, intrauterine distress, asphyxia, and severe infection. In the study group, 11.1% (3/27) of patients had adverse neurodevelopmental outcomes. The patients in the study group had lower scores for the ASQ than those in the control group in the communication, gross, and fine motor dimensions.ConclusionThe incidence of perinatal stroke in Beijing was consistent with that in other countries. Routine neuroimaging of infants with risk factors may enable identification of asymptomatic strokes in more patients. Patients who have suffered from a stroke may have neurological sequelae; therefore, early detection, treatment, and regular follow-ups are beneficial for improving their recovery outcomes.

The heteroscorpionate zinc hydride complex LZnH 2, (L = (MePz)