The dual effect of endoplasmic reticulum stress in digestive system tumors and intervention of Chinese botanical drug extracts: a review.

Endoplasmic reticulum (ER) homeostasis is essential for maintaining human health, and once imbalanced, it will trigger endoplasmic reticulum stress (ERS), which participates in the development of digestive system tumors and other diseases. ERS has dual effect on tumor cells, activating adaptive responses to promote survival or inducing apoptotic pathways to accelerate cell death of the tumor. Recent studies have demonstrated that Chinese botanical drug extracts can affect the tumor process of the digestive system by regulating ERS and exert anticancer effects. This article summarizes the dual effect of ERS in the process of digestive system tumors and the intervention of Chinese botanical drug extracts in recent years, as reference for the combined treatment of digestive system tumors with Chinese and modern medicine.

Design, Synthesis, Antitumor Activity Evaluation, and Molecular Dynamics Simulation of Some 2-Aminopyrazine Derivatives.

OBJECTIVE: Cancer poses a great threat to human health, and effective drugs to treat it are always needed. Several compounds containing a 2-aminopyrazine framework have been identified as antitumor agents with SHP2 inhibition activities. This current work aimed to search for more potent novel compounds possessing a 2-aminopyrazine moiety with antitumor activities. METHODS: A series of 12 novel 2-aminopyrazine derivatives was synthesized, and their structures were confirmed by spectroscopic techniques. The inhibitory activities of all the synthesized compounds against MDA-MB-231 and H1975 cancer cell lines were evaluated by an MTT assay. The most potent compound 3e was analyzed by flow cytometry. Subsequently, computational studies were performed to investigate the possible antitumor mechanisms of compound 3e. RESULTS: The results indicated that compound 3e exhibited potent antitumor activities with IC50 values of 11.84±0.83µM against H1975 cells and 5.66±2.39µM against MDA-MB-231 cells, which were more potent than the SHP2 inhibitor GS493 (IC50 = 19.08±1.01 µM against H1975 cells and IC50 = 25.02±1.47 µM against MDA-MB-231 cells). Further analysis by flow cytometry demonstrated that compound 3e induced cell apoptosis in H1975 cells. The results of the molecular docking and MD simulations, including RMSD, RMSF, PCA, DCCM and binding energy and decomposition analyses, revealed that compound 3e probably selectively inhibited SHP2. CONCLUSION: A new compound having a 2-aminopyrazine substructure with potent inhibitory activities against the H1975 and MDA-MB-231 cancer cells was obtained, meriting further investigation as an antitumor drug.

PLAU and GREM1 are prognostic biomarkers for predicting immune response in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a common malignant tumor. Identification of biomarkers and understanding their potential functions will facilitate the treatment and diagnosis in LUAD patients. The yellow module (cor = 0.31, P = 2e-6) was selected as the core module based on weighted gene co-expression network analysis (WGCNA) by integrating RNA-seq data and tumor stage. Two upregulated genes (PLAU and GREM1) in yellow module were identified to be biomarkers. Kaplan-Meier curve analysis displayed that high expression levels of them had a poor overall survival (OS). And, their high expression levels revealed higher tumor stage and relapse possibility in LUAD patients, and could be a prognostic parameter. Both biomarkers showed similar immune cell expression profiles in low- and high-expression groups. Strongly positive correlation between both biomarkers and biomarkers of tumor-infiltrating lymphocytes were also clarified in TCGA-LUAD cohort. Importantly, single gene GSEA showed that transcriptional mis-regulation in cancer and microRNAs in cancer were enriched in LUAD patients. Therefore, a miRNA-mRNA-transcription factors (TFs) co-expression regulatory networks was constructed for each biomarker, various miRNAs and TFs were related to PLAU and GREM1. Among which, 6 downstream TFs were overlapped genes for both biomarkers. Notably, 2 of these TFs (FOXF1 and TFAP2A) exhibited significantly abnormal expression levels. Among which, FOXF1 was downregulated and TFAP2A was upregulated in TCGA-LUAD cohort. Both TFs showed a significantly positive correlation with the expression level of PLAU. In conclusion, we identified 2 biomarkers related to immune response and achieved a good accuracy in predicting OS in patients with LUAD.

MIIP downregulation drives colorectal cancer progression through inducing peri-cancerous adipose tissue browning.

BACKGROUND: The enrichment of peri-cancerous adipose tissue is a distinctive feature of colorectal cancer (CRC), accelerating disease progression and worsening prognosis. The communication between tumor cells and adjacent adipocytes plays a crucial role in CRC advancement. However, the precise regulatory mechanisms are largely unknown. This study aims to explore the mechanism of migration and invasion inhibitory protein (MIIP) downregulation in the remodeling of tumor cell-adipocyte communication and its role in promoting CRC. RESULTS: MIIP expression was found to be decreased in CRC tissues and closely associated with adjacent adipocyte browning. In an in vitro co-culture model, adipocytes treated with MIIP-downregulated tumor supernatant exhibited aggravated browning and lipolysis. This finding was further confirmed in subcutaneously allografted mice co-injected with adipocytes and MIIP-downregulated murine CRC cells. Mechanistically, MIIP interacted with the critical lipid mobilization factor AZGP1 and regulated AZGP1's glycosylation status by interfering with its association with STT3A. MIIP downregulation promoted N-glycosylation and over-secretion of AZGP1 in tumor cells. Subsequently, AZGP1 induced adipocyte browning and lipolysis through the cAMP-PKA pathway, releasing free fatty acids (FFAs) into the microenvironment. These FFAs served as the primary energy source, promoting CRC cell proliferation, invasion, and apoptosis resistance, accompanied by metabolic reprogramming. In a tumor-bearing mouse model, inhibition of ß-adrenergic receptor or FFA uptake, combined with oxaliplatin, significantly improved therapeutic efficacy in CRC with abnormal MIIP expression. CONCLUSIONS: Our data demonstrate that MIIP plays a regulatory role in the communication between CRC and neighboring adipose tissue by regulating AZGP1 N-glycosylation and secretion. MIIP reduction leads to AZGP1 oversecretion, resulting in adipose browning-induced CRC rapid progression and poor prognosis. Inhibition of ß-adrenergic receptor or FFA uptake, combined with oxaliplatin, may represent a promising therapeutic strategy for CRC with aberrant MIIP expression.

The integration of multidisciplinary approaches revealed PTGES3 as a novel drug target for breast cancer treatment.

BACKGROUND: The main challenge in personalized treatment of breast cancer (BC) is how to integrate massive amounts of computing resources and data. This study aimed to identify a novel molecular target that might be effective for BC prognosis and for targeted therapy by using network-based multidisciplinary approaches. METHODS: Differentially expressed genes (DEGs) were first identified based on ESTIMATE analysis. A risk model in the TCGA-BRCA cohort was constructed using the risk score of six DEGs and validated in external and clinical in-house cohorts. Subsequently, independent prognostic factors in the internal and external cohorts were evaluated. Cell viability CCK-8 and wound healing assays were performed after PTGES3 siRNA was transiently transfected into the BC cell lines. Drug prediction and molecular docking between PTGES3 and drugs were further analyzed. Cell viability and PTGES3 expression in two BC cell lines after drug treatment were also investigated. RESULTS: A novel six-gene signature (including APOOL, BNIP3, F2RL2, HINT3, PTGES3 and RTN3) was used to establish a prognostic risk stratification model. The risk score was an independent prognostic factor that was more accurate than clinicopathological risk factors alone in predicting overall survival (OS) in BC patients. A high risk score favored tumor stage/grade but not OS. PTGES3 had the highest hazard ratio among the six genes in the signature, and its mRNA and protein levels significantly increased in BC cell lines. PTGES3 knockdown significantly inhibited BC cell proliferation and migration. Three drugs (gedunin, genistein and diethylstilbestrol) were confirmed to target PTGES3, and genistein and diethylstilbestrol demonstrated stronger binding affinities than did gedunin. Genistein and diethylstilbestrol significantly inhibited BC cell proliferation and reduced the protein and mRNA levels of PTGES3. CONCLUSIONS: PTGES3 was found to be a novel drug target in a robust six-gene prognostic signature that may serve as a potential therapeutic strategy for BC.

Aerobic exercise protects MI heart through miR-133a-3p downregulation of connective tissue growth factor.

OBJECTIVE: To investigate the effect of aerobic exercise intervention to inhibit cardiomyocyte apoptosis and thus improve cardiac function in myocardial infarction (MI) mice by regulating CTGF expression through miR-133a-3p. METHODS: Male C57/BL6 mice, 7-8 weeks old, were randomly divided into sham-operated group (S group), sham-operated +aerobic exercise group (SE group), myocardial infarction group (MI group) and MI + aerobic exercise group (ME group). The mice were anesthetized the day after training and cardiac function was assessed by cardiac echocardiography. Myocardial collagen volume fraction (CVF%) was analyzed by Masson staining. Myocardial CTGF, Bax and Bcl-2 were detected by Western blotting, and myocardial miR-133a-3p was measured by RT-qPCR. RESULTS: Compared with the S group, miR-133a-3p, Bcl-2 and EF were significantly decreased and CTGF, Bax, Bax/ Bcl-2, Caspase 3, Cleaved Caspase-3, LVIDd, LVIDs and CVF were significantly increased in the MI group. Compared with the MI group, miR-133a-3p, Bcl-2 and EF were significantly increased, cardiac function was significantly improved, and CTGF, Bax, Bax/ Bcl-2, Caspase 3, Cleaved Caspase-3, LVIDd, LVIDs and CVF were significantly decreased in ME group. The miR-133a-3p was significantly lower and CTGF was significantly higher in the H2O2 intervention group compared with the control group of H9C2 rat cardiomyocytes. miR-133a-3p was significantly higher and CTGF was significantly lower in the AICAR intervention group compared to the H2O2 intervention group. Compared with the control group of H9C2 rat cardiomyocytes, CTGF, Bax and Bax/Bcl-2 were significantly increased and Bcl-2 was significantly decreased in the miR-133a-3p inhibitor intervention group; CTGF, Bax and Bax/Bcl-2 were significantly decreased and Bcl-2 was significantly upregulated in the miR-133a-3p mimics intervention group. CONCLUSION: Aerobic exercise down-regulated CTGF expression in MI mouse myocardium through miR-133a-3p, thereby inhibiting cardiomyocyte apoptosis and improving cardiac function.

Diverse functions of myeloid-derived suppressor cells in autoimmune diseases.

Since myeloid-derived suppressor cells (MDSCs) were found suppressing immune responses in cancer and other pathological conditions, subsequent researchers have pinned their hopes on the suppressive function against immune damage in autoimmune diseases. However, recent studies have found key distinctions of MDSC immune effects in cancer and autoimmunity. These include not only suppression and immune tolerance, but MDSCs also possess pro-inflammatory effects and exacerbate immune disorders during autoimmunity, while promoting T cell proliferation, inducing Th17 cell differentiation, releasing pro-inflammatory cytokines, and causing direct tissue damage. Additionally, MDSCs could interact with surrounding cells to directly cause tissue damage or repair, sometimes even as an inflammatory indicator in line with disease severity. These diverse manifestations could be partially attributed to the heterogeneity of MDSCs, but not all. The different disease types, disease states, and cytokine profiles alter the diverse phenotypes and functions of MDSCs, thus leading to the impairment or obversion of MDSC suppression. In this review, we summarize the functions of MDSCs in several autoimmune diseases and attempt to elucidate the mechanisms behind their actions.

A Self-Assembly Pro-Coagulant Powder Capable of Rapid Gelling Transformation and Wet Adhesion for the Efficient Control of Non-Compressible Hemorrhage.

Rapid and effective control of non-compressible massive hemorrhage poses a great challenge in first-aid and clinical settings. Herein, a biopolymer-based powder is developed for the control of non-compressible hemorrhage. The powder is designed to facilitate rapid hemostasis by its excellent hydrophilicity, great specific surface area, and adaptability to the shape of wound, enabling it to rapidly absorb fluid from the wound. Specifically, the powder can undergo sequential cross-linking based on "click" chemistry and Schiff base reaction upon contact with the blood, leading to rapid self-gelling. It also exhibits robust tissue adhesion through covalent/non-covalent interactions with the tissues (adhesive strength: 89.57 ± 6.62 KPa, which is 3.75 times that of fibrin glue). Collectively, this material leverages the fortes of powder and hydrogel. Experiments with animal models for severe bleeding have shown that it can reduce the blood loss by 48.9%. Studies on the hemostatic mechanism also revealed that, apart from its physical sealing effect, the powder can enhance blood cell adhesion, capture fibrinogen, and synergistically induce the formation of fibrin networks. Taken together, this hemostatic powder has the advantages for convenient preparation, sprayable use, and reliable hemostatic effect, conferring it with a great potential for the control of non-compressible hemorrhage.

Methodology for Good Machine Learning with Multi-Omics Data.

In 2020, Novartis Pharmaceuticals Corporation and the U.S. Food and Drug Administration (FDA) started a 4-year scientific collaboration to approach complex new data modalities and advanced analytics. The scientific question was to find novel radio-genomics-based prognostic and predictive factors for HR+/HER- metastatic breast cancer under a Research Collaboration Agreement. This collaboration has been providing valuable insights to help successfully implement future scientific projects, particularly using artificial intelligence and machine learning. This tutorial aims to provide tangible guidelines for a multi-omics project that includes multidisciplinary expert teams, spanning across different institutions. We cover key ideas, such as "maintaining effective communication" and "following good data science practices," followed by the four steps of exploratory projects, namely (1) plan, (2) design, (3) develop, and (4) disseminate. We break each step into smaller concepts with strategies for implementation and provide illustrations from our collaboration to further give the readers actionable guidance.

Quantitative relationship between soil pH and electrical conductivity values and cadmium phytoavailability for Chinese cabbage under simulated conditions.

Pot experiments were conducted to investigate the impacts of continuous addition of different concentrations of calcium chloride (CaCl2) and/or low-molecular-weight organic acids (LMWOAs) on soil pH, electrical conductivity (EC), and cadmium (Cd) transformation. These factors subsequently affected Cd phytoavailability in a system consisting of Cd-contaminated soil and Chinese cabbage (Brassica chinensis L.). The results indicate that CaCl2 addition had a greater impact on reducing soil pH value, increasing soil EC value, and enhancing Cd phytoaccumulation in Chinese cabbage compared to LMWOAs. When soil pH dropped by 0.3 unit and the soil EC increased by 500 µS cm-1, the Cd concentration in the Chinese cabbage shoots was 3 times higher than that in the control group. Throughout two planting terms of Chinese cabbage, the addition of CaCl2 (1.6-3.2 g kg-1) and LMWOAs (≤ 1.0 g kg-1) led to phytoextracted Cd concentration exceeding exchangeable Cd concentration in soil samples before the pot experiment. Regarding phytoextracted Cd, desorption from carbonate-bound Cd contributes more than desorption from bound to organic matter Cd and adsorption to Fe/Mn oxide Cd. This study underscores the influence of soil pH and EC value variations and Cd transformation on Cd phytoavailability. Special attention should be given to leafy vegetables grown in Cd-contaminated soil, as the phytoavailable Cd concentration reaches approximately 2.0 µg kg-1, which may lead to Cd levels surpassing acceptable limits for Chinese cabbage.

Regionalization and optimization strategy of ecological management in Xinjiang, China based on supply-demand relationship and spatial flow of ecosystem services.

As an important basis for the optimization of territorial space, ecological management zoning is of great significance for maintaining regional ecological security and promoting the construction of ecological civilization. With 10 ecosystem services, such as wind break and sand fixation, water conservation, and forest and grass supply, we built a supply index system for Xinjiang. Modelling and ecological economics methods were used to quantify ecosystem service supply. Ecosystem service demand of Xinjiang in 2020 was quantitatively assessed by combining land use intensity, population, and economic status. Based on the ecosystem service supply-demand ratio model and quadrant matching method, we explored the matching relationship and spatial differentiation of ecosystem ser-vice supply and demands on the 1 km grid scale. The breaking point formula and field intensity formula were used to evaluate the flow range and intensity of ecosystem services, and then ecological management zones were divided and corresponding control measures were proposed. The results showed obvious spatial differences in the supply and demand of ecosystem services in Xinjiang in 2020. The high-supply areas were mainly distributed in river valleys and along river systems, while the demand was concentrated in oasis-central cities. The overall supply of ecosystem services was less than the demand. The spatial distribution was dominated by low supply-low demand areas and high supply-high demand areas. There were seven output zones of ecosystem services in Xinjiang, namely Fuyun County, Fuhai County, Yizhou District, Shanshan County, Alashankou City, Keping County and Qira County. The rests were input zones. According to the comprehensive analysis, Xinjiang could be divided into five ecological management areas, i.e., mountain ecological barrier area, oasis ecological restoration area, desert ecological improvement area, desert-oasis ecological protection area, and patch ecological transport area.

Identification of cadmium phytoavailability in response to cadmium transformation and changes in soil pH and electrical conductivity.

Owing to complex changes in the soil environment, determining cadmium (Cd) phytoavailability is challenging. We devised a soil-wheat system to monitor alterations in soil pH, electrical conductivity (EC), and Cd transformation under various rates of calcium chloride and/or low-molecular-weight organic acids (LMWOAs) addition. The findings indicate that decreasing soil pH value, increasing soil EC value, and Cd transformation affect the phytoextraction of Cd. The exchangeable Cd and transformation of Cd under shifts in soil pH and EC contribute differentially to the phytoextracted Cd. The level of potentially phytoavailable Cd was identified through complete wheat cultivation in which the soil pH decreased by 0.47 unit and soil EC increased by 600-1000 µS cm-1, resembling the concentration of 0.01 M LMWOAs extractable Cd, when transitioning from paddy to dryland soil. Based on considering the phytoextracted Cd as the phytoavailable Cd throughout a complete wheat growth term, the threshold for phytoavailable Cd in soil, ensuring the safety of wheat grain (limit: 0.1 mg kg-1), is determined to be 2.90 µg kg-1. Maintaining control over Cd phytoavailability in soil emerges as the key factor in ensuring the safety of wheat grain cultivation.

Immune-related biomarkers predict the prognosis and immune response of breast cancer based on bioinformatic analysis and machine learning.

Breast cancer (BC) is the malignancy with the highest mortality rate among women, identification of immune-related biomarkers facilitates precise diagnosis and improvement of the survival rate in early-stage BC patients. 38 hub genes significantly positively correlated with tumor grade were identified based on weighted gene coexpression network analysis (WGCNA) by integrating the clinical traits and transcriptome analysis. Six candidate genes were screened from 38 hub genes basing on least absolute shrinkage and selection operator (LASSO)-Cox and random forest. Four upregulated genes (CDC20, CDCA5, TTK and UBE2C) were identified as biomarkers with the log-rank p < 0.05, in which high expression levels of them showed a poor overall survival (OS) and recurrence-free survival (RFS). A risk model was finally constructed using LASSO-Cox regression coefficients and it possessed superior capability to identify high risk patients and predict OS (p < 0.0001, AUC at 1-, 3- and 5-years are 0.81, 0.73 and 0.79, respectively). Decision curve analysis demonstrated risk score was the best prognostic predictor, and low risk represented a longer survival time and lower tumor grade. Importantly, multiple immune cell types and immunotherapy targets were observed increase in expression levels in high-risk group, most of which were significantly correlated with four genes. In summary, the immune-related biomarkers could accurately predict the prognosis and character the immune responses in BC patients. In addition, the risk model is conducive to the tiered diagnosis and treatment of BC patients.

Multifunctional two-component in-situ hydrogel for esophageal submucosal dissection for mucosa uplift, postoperative wound closure and rapid healing.

Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.

Identification of GnRH-like peptide and its potential signaling pathway involved in the oocyte meiotic maturation in the Chinese mitten crab, Eriocheir sinensis.

Gonadotropin-releasing hormone (GnRH) plays a pivotal role in reproductive regulation in vertebrates. However, GnRH was rarely isolated and its function remains poorly characterized in invertebrates. The existence of GnRH in ecdysozoa has been controversial for a long. Here, we isolated and identified two GnRH-like peptides from brain tissues in Eriocheir sinensis. Immunolocalization showed that the presence of EsGnRH-like peptide in brain, ovary and hepatopancreas. Synthetic EsGnRH-like peptides can induce germinal vesicle breakdown (GVBD) of oocyte. Similar to vertebrates, ovarian transcriptomic analysis revealed a GnRH signaling pathway in the crab, in which most genes exhibited dramatically high expression at GVBD. RNAi knockdown of EsGnRHR suppressed the expression of most genes in the pathway. Co-transfection of the expression plasmid for EsGnRHR with reporter plasmid bearing CRE-luc or SRE-luc response element into 293T cells showed that EsGnRHR transduces its signal via cAMP and Ca2+ signaling transduction pathways. In vitro incubation of the crab oocyte with EsGnRH-like peptide confirmed the cAMP-PKA cascade and Ca2+ mobilization signaling cascade but lack of a PKC cascade. Our data present the first direct evidence of the existence of GnRH-like peptides in the crab and demonstrated its conserved role in the oocyte meiotic maturation as a primitive neurohormone.

Selective leaching process for efficient and rapid recycling of spent lithium iron phosphate batteries.

With the continuous development of new energy vehicles, the number of decommissioned lithium iron phosphate (LiFePO4) batteries has been constantly increasing. Therefore, it is necessary to recover metal from spent LiFePO4 batteries due to the high potential for environmental protection and high resource value. In this study, sodium persulfate (Na2S2O8) was selected as the oxidant to regulate and control the oxidation state and proton activity of the leaching solution through its high oxidizing ability. Selective recovery of lithium from LiFePO4 batteries was achieved by oxidizing LiFePO4 to iron phosphate (FePO4) during the leaching process. This paper reports an extensive investigation of the effects of various factors, including the acid concentration, initial volume fraction of the oxidant, reaction temperature, solid-liquid ratio, and reaction time, on lithium leaching. Li+ reached a high leaching rate of 93.3% within 5 minutes even at a low concentration of sulphuric acid (H2SO4), and high-purity lithium carbonate (Li2CO3) was obtained through impurity removal and precipitation reactions. In addition, the leaching mechanism was analysed by both X-ray diffraction and X-ray photoelectron spectroscopy characterization. The results show that the obtained high lithium-ion (Li+) leaching efficiency and fast Li+ leaching time can be ascribed to the superior oxidizing properties of Na2S2O8 and the stability of the crystal structure of LiFePO4 during the oxidative leaching process. The adopted method has significant advantages in terms of safety, efficiency and environmental protection, which are conducive to the sustainable development of lithium batteries.

Revealing the effects of ligands of silver nanoclusters on the interactions between them and ctDNA: Abstraction to visualization.

Silver nanoclusters (AgNCs) have been widely applied in the field of biology, drug therapy and cell imaging in the last decade. In order to study the biosafety of AgNCs, GSH-AgNCs and DHLA-AgNCs were synthesized using glutathione (GSH) and dihydrolipoic acid (DHLA) as ligands, and their interactions with calf thymus DNA (ctDNA) from abstraction to visualization were studied. The results of spectroscopy, viscometry and molecular docking demonstrated that GSH-AgNCs mainly bound to ctDNA in a groove mode, while DHLA-AgNCs were both groove and intercalation binding. Fluorescence experiments suggested that the quenching mechanism of both AgNCs to the emission of ctDNA-probe were both in static mode, and thermodynamic parameters demonstrated that the main forces between GSH-AgNCs and ctDNA were hydrogen bonds and van der Waals forces, while hydrogen bonds and hydrophobic forces contributed to the binding of DHLA-AgNCs to ctDNA. The binding strength demonstrated that DHLA-AgNCs bound to ctDNA more strongly than that of GSH-AgNCs. The results of circular dichroism (CD) spectroscopy reflected small effects of both AgNCs on the structure of ctDNA. This study will support the theoretical foundation for the biosafety of AgNCs and have a guiding significance for the preparation and application of AgNCs.

Alterations of nasal microbiome in eosinophilic chronic rhinosinusitis.

BACKGROUND: Exposure to microbes may be important in the development of chronic rhinosinusitis (CRS). Dysbiosis of the nasal microbiome is considered to be related to CRS with nasal polyps (CRSwNP). The link between the nasal microbiota and eosinophilic CRSwNP (eCRSwNP) has rarely been studied. OBJECTIVE: The aim of this study was to rigorously characterize nasal dysbiosis in a cohort of patients with eCRSwNP and compare the nasal microbiomes of these patients with those of healthy controls (HCs). METHODS: We performed a cross-sectional study of 34 patients with eCRSwNP, 10 patients without CRSwNP, and 44 HCs by using 16S rRNA gene sequencing. An independent cohort of 14 patients with eCRSwNP, 9 patients without CRSwNP, and 11 HCs was used to validate the results. RESULTS: Compared with the nasal microbiome of healthy controls, the nasal microbiome of patients with eCRSwNP was characterized by higher α-diversity (Shannon and Chao1 index) and a distinct composition of microbes. Notably, the distinct differences in microbial composition between patients with eCRSwNP and HCs were significantly correlated with eCRSwNP disease status. Furthermore, in a diagnostic model generated by using these differences, a combination of 15 genera could be used to distinguish patients with eCRSwNP from HCs, with an area under the curve of approximately 0.8 in both the exploration and validation cohorts. CONCLUSION: Our study establishes the compositional alterations in the nasal microbiome in eCRSwNP and suggests the potential for using the nasal microbiota as a noninvasive predictive classifier for the diagnosis of eCRSwNP.

Sensitive Small Molecule Aptasensing based on Hybridization Chain Reaction and CRISPR/Cas12a Using a Portable 3D-Printed Visualizer.

Next-generation biosensing tools based on CRISPR/Cas have revolutionized the molecular detection. A number of CRISPR/Cas-based biosensors have been reported for the detection of nucleic acid targets. The establishment of efficient methods for non-nucleic acid target detection would further broaden the scope of this technique, but up to now, the concerning research is limited. In the current study, we reported a versatile biosensing platform for non-nucleic acid small-molecule detection called SMART-Cas12a (small-molecule aptamer regulated test using CRISPR/Cas12a). Simply, hybridization chain reaction cascade signal amplification was first trigged by functional nucleic acid (aptamer) through target binding. Then, the CRISPR/Cas system was integrated to recognize the amplified products followed by activation of the trans-cleavage. As such, the target can be ingeniously converted to nucleic acid signals and then fluorescent signals that can be readily visualized and analyzed by a customized 3D-printed visualizer with the help of a home-made App-enabled smartphone. Adenosine triphosphate was selected as a model target, and under the optimized conditions, we achieved fine analytical performance with a linear range from 0.1 to 750 µM and a detection limit of 1.0 nM. The satisfactory selectivity and recoveries that we have obtained further demonstrated this method to be suitable for a complex sample environment. The sample-to-answer time was less than 100 min. Our work not only expanded the reach of the CRISPR-Cas system in biosensing but also provided a prototype method that can be generalized for detecting a wider range of analytes with desirable adaptability, sensitivity, specificity, and on-site capability.

Emission factors and source profiles of volatile organic compounds from typical industrial sources in Guangzhou, China.

Volatile organic compounds (VOCs) are important precursors of ozone (O3) and fine particulate matter (PM2.5). An accurate depiction of the emission characteristics of VOCs is the key to formulating VOC control strategies. In this study, the VOC emission factors and source profiles in five industrial sectors were developed using large-scale field measurements conducted in Guangzhou, China (100 samples for the emission factors and 434 samples for the source profile measurements). The emission factors based on the actual measurement method and the material balance method were 1.6-152.4 kg of VOCs per ton of raw materials (kg/t) and 3.1-242.2 kg/t, respectively. The similarities between the emission factors obtained using these two methods were examined, which showed a coefficient of divergence (CD) of 0.34-0.72. Among the 33 subdivided VOC source profiles developed in this study, sources including light guide plate (LGP), photoresist mask, and plastic products were the first time developed in China. Due to regional diversities in terms of production technologies, materials, and products, the emission characteristics of the VOCs varied, even in the same sector, thereby demonstrating the importance of developing localized source profiles of VOCs. The ozone formation potential (OFP) of the shipbuilding and repair sector from fugitive emissions was the highest value among all the industrial sectors. Controlling the emissions of aromatics and OVOCs was critical to reducing the O3 growth momentum in industrial sectors. In addition, 1,2-dibromoethane showed high carcinogenic risk potentials (CRPs) during most of the industrial sectors and should be prioritized for controlling.