Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility.

Intestinal peristalsis is a dynamic physiologic process influenced by dietary and microbial changes. It is tightly regulated by complex cellular interactions; however, our understanding of these controls is incomplete. A distinct population of macrophages is distributed in the intestinal muscularis externa. We demonstrate that, in the steady state, muscularis macrophages regulate peristaltic activity of the colon. They change the pattern of smooth muscle contractions by secreting bone morphogenetic protein 2 (BMP2), which activates BMP receptor (BMPR) expressed by enteric neurons. Enteric neurons, in turn, secrete colony stimulatory factor 1 (CSF1), a growth factor required for macrophage development. Finally, stimuli from microbial commensals regulate BMP2 expression by macrophages and CSF1 expression by enteric neurons. Our findings identify a plastic, microbiota-driven crosstalk between muscularis macrophages and enteric neurons that controls gastrointestinal motility. PAPERFLICK:

Involvement of circRNA Regulators MBNL1 and QKI in the Progression of Esophageal Squamous Cell Carcinoma.

OBJECTIVES: To investigate the role of circRNA regulators MBNL1 and QKI in the progression of esophageal squamous cell carcinoma. BACKGROUND: MBNL1 and QKI are pivotal regulators of pre-mRNA alternative splicing, crucial for controlling circRNA production - an emerging biomarker and functional regulator of tumor progression. Despite their recognized roles, their involvement in ESCC progression remains unexplored. METHODS: The expression levels of MBNL1 and QKI were examined in 28 tissue pairs from ESCC and adjacent normal tissues using data from the GEO database. Additionally, a total of 151 ESCC tissue samples, from stage T1 to T4, consisting of 13, 43, 87, and 8 cases per stage, respectively, were utilized for immunohistochemical (IHC) analysis. RNA sequencing was utilized to examine the expression profiles of circRNAs, lncRNAs, and mRNAs across 3 normal tissues, 3 ESCC tissues, and 3 pairs of KYSE150 cells in both wildtype (WT) and those with MBNL1 or QKI knockouts. Transwell, colony formation, and subcutaneous tumorigenesis assays assessed the impact of MBNL1 or QKI knockout on ESCC cell migration, invasion, and proliferation. RESULTS: ESCC onset significantly altered MBNL1 and QKI expression levels, influencing diverse RNA species. Elevated MBNL1 or QKI expression correlated with patient age or tumor invasion depth, respectively. MBNL1 or QKI knockout markedly enhanced cancer cell migration, invasion, proliferation, and tumor growth. Moreover, the absence of either MBNL1 or QKI modulated the expression profiles of multiple circRNAs, causing extensive downstream alterations in the expression of numerous lncRNAs and mRNAs. While the functions of circRNA and lncRNA among the top 20 differentially expressed genes remain unclear, mRNAs like SLCO4C1, TMPRSS15, and MAGEB2 have reported associations with tumor progression. CONCLUSIONS: This study underscores the tumor-suppressive roles of MBNL1 and QKI in ESCC, proposing them as potential biomarkers and therapeutic targets for ESCC diagnosis and treatment.

Association between serum magnesium levels and risk of acute kidney injury in patients with traumatic brain injury: A retrospective cohort study from the MIMIC-â £ database.

INTRODUCTION: The occurrence of acute kidney injury (AKI) is associated with a higher risk of mortality in patients with traumatic brain injury (TBI). This study aimed to explore the relationship between serum magnesium levels and the risk of AKI in patients with TBI. METHODS: Patients with TBI were identified from the Medical Information Mart Intensive Care Ⅳ (MIMIC-Ⅳ) 2008-2019. The relationship between serum magnesium levels at admission and magnesium coefficient of variation (CV) during hospitalization and the risk of AKI was analyzed using multivariable logistic regression analysis and expressed as odds ratio (OR) and 95% confidence interval (CI). Subgroup analyses were performed according to Glasgow Coma Scale (GCS) score (<14, ≥14), sepsis (no, yes), and estimated glomerular filtration rate (eGFR; <60, ≥60). RESULTS: Of the 991 patients included, 140 (14.13%) developed AKI during hospitalization. Patients with magnesium levels ≤1.7 mg/dL (tertile 1) (OR=1.68, 95%CI: 1.01-2.81) were associated with a higher risk of AKI compared to those with magnesium levels of 1.7-2.0 mg/dL (tertile 2), but no association was found in those with magnesium levels >2.0 mg/dL (tertile 3) (P=0.479). For magnesium CV, patients with magnesium CV >10% (tertile 3) (OR=2.26, 95%CI: 1.16-4.41) were linked to an increased risk of AKI compared to those with magnesium CV ≤4% (tertile 1), but there may be a slight association between magnesium CV of 4%-10% (tertile 2) and AKI risk (OR=1.86, 95%CI: 0.99-3.48; P=0.053). Subgroup analyses showed that lower magnesium levels (≤1.7 mg/dL) or greater magnesium CV (>10%) were associated with a higher risk of AKI only in patients with a GCS score ≥14, non-sepsis, or eGFR ≥60 mL/min/per1.73m2 (P<0.05). CONCLUSION: Lower serum magnesium levels at admission or greater magnesium CV during hospitalization were associated with a higher risk of AKI in patients with TBI.

A meta-analysis examining the impact of open surgical therapy versus minimally invasive surgery on wound infection in females with cervical cancer.

A meta-analysis study was executed to measure the effect of minimally invasive surgery (MIS) and open surgical management (OSM) on wound infection (WI) in female's cervical cancer (CC). A comprehensive literature study till February 2023 was applied and 1675 interrelated investigations were reviewed. The 41 chosen investigations enclosed 10 204 females with CC and were in the chosen investigations' starting point, 4294 of them were utilizing MIS, and 5910 were utilizing OSM. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were utilized to compute the value of the effect of MIS and OSM on WI in female's CC and by the dichotomous approaches and a fixed or random model. The MIS had significantly lower WI (OR, 0.23; 95% CI, 0.15-0.35, p < 0.001) with no heterogeneity (I2 = 0%) and postoperative aggregate complications (PACs) (OR, 0.49; 95% CI, 0.37-0.64, p < 0.001) in females with CC and compared OSM. However, MIS compared with OSM in females with CC and had no significant difference in pelvic infection and abscess (PIA) (OR, 0.59; 95% CI, 0.31-1.16, p = 0.13). The MIS had significantly lower WI, and PACs, though, had no significant difference in PIA in females with CC and compared with OSM. However, care must be exercised when dealing with its values because of the low sample size of some of the nominated investigations for the meta-analysis.

Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial.

BACKGROUND: Immune checkpoint inhibitors targeting PD-1 or CTLA-4 individually have shown substantial clinical benefits in the treatment of malignancies. We aimed to assess the safety and antitumour activity of cadonilimab monotherapy, a bispecific PD-1/CTLA-4 antibody, in patients with advanced solid tumours. METHODS: This multicentre, open-label, phase 1b/2 trial was conducted across 30 hospitals in China. Patients aged 18 years or older with histologically or cytologically confirmed, unresectable advanced solid tumours, unsuccessful completion of at least one previous systemic therapy, and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible for inclusion. Patients who had previously received anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment were not eligible for inclusion. In the dose escalation phase of phase 1b, patients received intravenous cadonilimab at 6 mg/kg and 10 mg/kg every 2 weeks. In the dose expansion phase of phase 1b, cadonilimab at 6 mg/kg and a fixed dose of 450 mg were given intravenously every 2 weeks. In phase 2, cadonilimab at 6 mg/kg was administered intravenously every 2 weeks in three cohorts: patients with cervical cancer, oesophageal squamous cell carcinoma, and hepatocellular carcinoma. The primary endpoints were the safety of cadonilimab in phase 1b and objective response rate in phase 2, based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The safety analysis was done in all patients who received at least one dose of cadonilimab. Antitumour activity was assessed in the full analysis set for the cervical cancer cohort, and in all patients with measurable disease at baseline and who received at least one dose of cadonilimab in the oesophageal squamous cell carcinoma and hepatocellular carcinoma cohorts. The study is registered on ClinicalTrial.gov, NCT03852251, and closed to new participants; follow-up has been completed. FINDINGS: Between Jan 18, 2019, and Jan 8, 2021, 240 patients (83 [43 male and 40 female] in phase 1b and 157 in phase 2) were enrolled. Phase 2 enrolled 111 female patients with cervical cancer, 22 patients with oesophageal squamous cell carcinoma (15 male and seven female), and 24 patients with hepatocellular carcinoma (17 male and seven female). During dose escalation, no dose-limiting toxicities occurred. Grade 3-4 treatment-related adverse events occurred in 67 (28%) of 240 patients; the most frequent grade 3 or worse treatment-related adverse events were anaemia (seven [3%]), increased lipase (four [2%]), decreased bodyweight (three [1%]), decreased appetite (four [2%]), decreased neutrophil count (three [1%]), and infusion-related reaction (two [1%]). 17 (7%) patients discontinued treatment due to treatment-related adverse events. 54 (23%) of 240 patients reported serious treatment-related adverse events, including five patients who died (one due to myocardial infarction; cause unknown for four). In phase 2, in the cervical cancer cohort, with a median follow-up of 14·6 months (IQR 13·1-17·5), the objective response rate was 32·3% (32 of 99; 95% CI 23·3-42·5). In the oesophageal squamous cell carcinoma cohort, with a median follow-up of 17·9 months (IQR 4·0-15·1), the objective response rate was 18·2% (four of 22; 95% CI 5·2-40·3). In the hepatocellular carcinoma cohort, with a median follow-up of 19·6 months (IQR 8·7-19·8), the objective response rate was 16·7% (four of 24; 95% CI 4·7-37·4). INTERPRETATION: Cadonilimab showed an encouraging tumour response rate, with a manageable safety profile, suggesting the potential of cadonilimab for the treatment of advanced solid tumours. FUNDING: Akeso Biopharma. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

A novel cell-wall polysaccharide derived from the stipe of Agaricus bisporus inhibits mouse melanoma proliferation and metastasis.

Malignant melanoma is an invasive and highly aggressive skin cancer that-if diagnosed-poses a serious threat to the patient's health and life. In this work, a novel purified cell-wall polysaccharide (termed Abwp) was obtained from the discarded stipe of Agaricus bisporus (A. bisporus) and characterized to be a novel homogeneous polysaccharide consisted of a ß-(1 â†’ 4)- glucosyl backbone with ß-(1 â†’ 2) and (1 â†’ 6)-d-glucosyl side-chains. The anti-melanoma effects of Abwp and its associated mechanisms in mice were then explored using in vitro and in vivo approaches. In vitro results showed that Abwp inhibited B16 melanoma cell proliferation and promoted their apoptosis in both time- and dose-dependent manners. In B16 cells induced with tumor necrosis factor (TNF-α), Abwp significantly decreased the protein expression of inflammatory-related signaling pathway (e.g., p38 MAPK and NF-κB) in time-, concentration-, and dose-dependent manners. Moreover, Abwp blocked nuclear entry of NF-κB-p65. In an in vivo mouse model featuring neoplasm transplantation with B16 melanoma cells, Abwp significantly inhibited the growth and proliferation of mouse melanoma. Hematoxylin staining showed that the invasion of melanoma cells into the lung tissue of the Abwp-treated group was significantly reduced. Immunohistochemical analysis showed that the expression of proliferation cell nuclear antigen (PCNA), N-cadherin, MMP-9, and Snail in the lung of mouse was significantly inhibited. Immunofluorescence showed that Abwp significantly interfered with the nuclear transcription of NF-κB-p65 in a dose-dependent manner. Collectively, these results showed that Abwp mediated p38 MAPK and NF-κB signaling pathways to inhibit the inflammatory response and malignant proliferation and metastasis of melanoma in mice.

Seafood allergy: Allergen, epitope mapping and immunotherapy strategy.

Seafoods are fashionable delicacies with high nutritional values and culinary properties, while seafood belongs to worldwide common food allergens. In recent years, many seafood allergens have been identified, while the diversity of various seafood species give a great challenge in identifying and characterizing seafood allergens, mapping IgE-binding epitopes and allergen immunotherapy development, which are critical for allergy diagnostics and immunotherapy treatments. This paper reviewed the recent progress on seafood (fish, crustacean, and mollusk) allergens, IgE-binding epitopes and allergen immunotherapy for seafood allergy. In recent years, many newly identified seafood allergens were reported, this work concluded the current situation of seafood allergen identification and designation by the World Health Organization (WHO)/International Union of Immunological Societies (IUIS) Allergen Nomenclature Sub-Committee. Moreover, this review represented the recent advances in identifying the IgE-binding epitopes of seafood allergens, which were helpful to the diagnosis, prevention and treatment for seafood allergy. Furthermore, the allergen immunotherapy could alleviate seafood allergy and provide promising approaches for seafood allergy treatment. This review represents the recent advances and future outlook on seafood allergen identification, IgE-binding epitope mapping and allergen immunotherapy strategies for seafood allergy prevention and treatment.

Evolution and functional diversification of catalase genes in the green lineage.

BACKGROUND: Catalases (CATs) break down hydrogen peroxide into water and oxygen to prevent cellular oxidative damage, and play key roles in the development, biotic and abiotic stresses of plants. However, the evolutionary relationships of the plant CAT gene family have not been systematically reported. RESULTS: Here, we conducted genome-wide comparative, phylogenetic, and structural analyses of CAT orthologs from 29 out of 31 representative green lineage species to characterize the evolution and functional diversity of CATs. We found that CAT genes in land plants were derived from core chlorophytes and detected a lineage-specific loss of CAT genes in Fabaceae, suggesting that the CAT genes in this group possess divergent functions. All CAT genes were split into three major groups (group α, ß1, and ß2) based on the phylogeny. CAT genes were transferred from bacteria to core chlorophytes and charophytes by lateral gene transfer, and this led to the independent evolution of two types of CAT genes: α and ß types. Ten common motifs were detected in both α and ß groups, and ß CAT genes had five unique motifs, respectively. The findings of our study are inconsistent with two previous hypotheses proposing that (i) new CAT genes are acquired through intron loss and that (ii) the Cys-343 residue is highly conserved in plants. We found that new CAT genes in most higher plants were produced through intron acquisition and that the Cys-343 residue was only present in monocots, Brassicaceae and Pp_CatX7 in P. patens, which indicates the functional specificity of the CATs in these three lineages. Finally, our finding that CAT genes show high overall sequence identity but that individual CAT genes showed developmental stage and organ-specific expression patterns suggests that CAT genes have functionally diverged independently. CONCLUSIONS: Overall, our analyses of the CAT gene family provide new insights into their evolution and functional diversification in green lineage species.

Anti-IgE effect of small-molecule-compound arctigenin on food allergy in association with a distinct transcriptome profile.

BACKGROUND: Excessive production of IgE plays a major role in the pathology of food allergy. In an attempt to identify anti-IgE natural products, Arctium Lappa was one of the most effective herbs among approximately 300 screened medicinal herbs. However, little is known about its anti-IgE compounds. OBJECTIVE: To identify compounds from Arctium Lappa for targeted therapy on IgE production and explore their underlying mechanisms. METHODS: Liquid-liquid extraction and column chromatographic methods were used to purify the compounds. IgE inhibitory effects were determined on IgE-producing human myeloma U266 cells, peanut-allergic murine model and PBMCs from food-allergic patients. Genes involved in IgE inhibition in PBMCs were studied by RNA sequencing. RESULTS: The main compounds isolated were identified as arctiin and arctigenin. Both compounds significantly inhibited IgE production in U266 cells, with arctigenin the most potent (IC50=5.09µg/mL). Arctigenin (at a dose of 13 mg/kg) markedly reduced peanut-specific IgE levels, blocked hypothermia and histamine release in a peanut-allergic mouse model. Arctigenin also significantly reduced IgE production and Th2 cytokines (IL-5, IL-13) by PBMCs. We found 479 differentially expressed genes in PBMCs with arctigenin treatment (p < .001 and fold-change ≥1.5), involving 24 gene ontology terms (p < .001, FDR <0.05); cell division was the most significant. Eleven genes including UBE2C and BCL6 were validated by qPCR. CONCLUSION: Arctigenin markedly inhibited IgE production in U266 cells, peanut-allergic murine model and PBMCs from allergic patients by down-regulating cell division, cell cycle-related genes and up-regulating anti-inflammatory factors.

A small molecule compound berberine as an orally active therapeutic candidate against COVID-19 and SARS: A computational and mechanistic study.

The novel coronavirus disease, COVID-19, has grown into a global pandemic and a major public health threat since its breakout in December 2019. To date, no specific therapeutic drug or vaccine for treating COVID-19 and SARS has been FDA approved. Previous studies suggest that berberine, an isoquinoline alkaloid, has shown various biological activities that may help against COVID-19 and SARS, including antiviral, anti-allergy and inflammation, hepatoprotection against drug- and infection-induced liver injury, as well as reducing oxidative stress. In particular, berberine has a wide range of antiviral activities such as anti-influenza, anti-hepatitis C, anti-cytomegalovirus, and anti-alphavirus. As an ingredient recommended in guidelines issued by the China National Health Commission for COVID-19 to be combined with other therapy, berberine is a promising orally administered therapeutic candidate against SARS-CoV and SARS-CoV-2. The current study comprehensively evaluates the potential therapeutic mechanisms of berberine in preventing and treating COVID-19 and SARS using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analysis, and in silico molecular docking. An orally available immunotherapeutic-berberine nanomedicine, named NIT-X, has been developed by our group and has shown significantly increased oral bioavailability of berberine, increased IFN-γ production by CD8+ T cells, and inhibition of mast cell histamine release in vivo, suggesting a protective immune response. We further validated the inhibition of replication of SARS-CoV-2 in lung epithelial cells line in vitro (Calu3 cells) by berberine. Moreover, the expression of targets including ACE2, TMPRSS2, IL-1α, IL-8, IL-6, and CCL-2 in SARS-CoV-2 infected Calu3 cells were significantly suppressed by NIT-X. By supporting protective immunity while inhibiting pro-inflammatory cytokines; inhibiting viral infection and replication; inducing apoptosis; and protecting against tissue damage, berberine is a promising candidate in preventing and treating COVID-19 and SARS. Given the high oral bioavailability and safety of berberine nanomedicine, the current study may lead to the development of berberine as an orally, active therapeutic against COVID-19 and SARS.

Multivalent Phthalocyanine-Based Cationic Polymers with Enhanced Photodynamic Activity for the Bacterial Capture and Bacteria-Infected Wound Healing.

The solubility and photosensitive activity of phthalocyanine are crucial to photodynamic antibacterial performance. However, highly conjugated phthalocyanine with high singlet oxygen generation efficiency tends to aggregate in aqueous environments, leading to poor solubility and photodynamic antibacterial activity. Herein, we propose a novel photodynamic antibacterial therapeutic platform by a phthalocyanine-based polymeric photosensitizer for the efficient healing of a bacteria-infected wound. A prepared phthalocyanine-based chain-transfer agent and a tertiary amino group-containing monomer are applied in the reversible addition-fragmentation chain-transfer polymerization for the preparation of the polymeric photosensitizer, which is subsequently quaternized to obtain a positively charged surface. This water-soluble phthalocyanine-based polymer can strongly concentrate on bacterial membranes via electrostatic interaction. The formed singlet oxygen by the phthalocyanine-based polymer after 680 nm light irradiation plays an essential role in killing the Gram-positive and Gram-negative bacteria. The study of antibacterial action indicates that this nanocomposite can cause irreversible damage to the bacterial membranes, which can cause cytoplasm leakage and bacterial death. Moreover, this therapeutic platform has excellent biocompatibility and the capacity to heal the wounds of bacterial infections. Experimental results indicate that the design strategy of this phthalocyanine-based polymer can extend the application of the hydrophobic photosensitizer in the biomedical field.

Successful management of chronic urticaria and food allergies in a pediatric population using integrative traditional Chinese medicine therapy: a case series.

BACKGROUND: Food allergy is becoming increasingly common among the pediatric population. Despite strict avoidance of food allergens, a subgroup of sensitive individuals still develops frequent, persistent, and difficult to treat hives (FPDTH) for which there is no curative therapy. Although these cases are rare, these patients are in most need of therapy. CASE PRESENTATIONS: This is a retrospective review of 3 pediatric patients with highly sensitive food allergies who initially presented with hives daily or every other day, or multiple times a day, but achieved marked remission after traditional Chinese medicine (TCM) therapies. Patient 1 (P1) is a 5-year-old who has experienced 140 reactions in his lifetime. Reactions were mostly hives with 4 episodes of anaphylaxis. P1 had used Prednisone 20 times, had an Epinephrine injection 4 times, and had 3 emergency room (ER) visits. Patient 2 (P2) is a 12-year-old who had experienced hives since age 3. Despite daily antihistamine use, P2 had > 730 reactions in his lifetime at the time of presentation including 2 episodes of anaphylaxis. He had been prescribed prednisone 4 times, an Epinephrine injection 2 times, and had 1 ER visit. Patient 3 (P3) is a 20-month-old girl who had experienced > 120 reactions including 1 episode of anaphylaxis. She was on daily desonide and frequently used an antihistamine, yet still had required a course of prednisone once, an Epinephrine injection once, and had 1 ER visit to manage her reaction. After presenting to our clinic, patients received internal and external TCM treatments, including herbal baths and creams (Remedy A-D) as basic remedies to reduce food reactions, including but not limited to frequent hives. Within 7-9 months of TCM treatment, remarkably all patients had complete remission of atopic symptoms. All three patients also experienced an improvement in other conditions including food intolerance, diarrhea, anxiety, eczema, and environmental allergies. After 1 year of treatment, all three patients had reductions in food-specific IgE levels that had been previously elevated, and additionally, P1 and P3, who initially had high total IgE levels, experienced a marked decrease in total IgE levels as well. All three patients continued to introduce foods into their diet that they previously had reactions to, and all 3 patients remain symptom-free. CONCLUSIONS: Three pediatric patients with a known history of multiple food sensitivities and physician-diagnosed food allergies that presented with FPDTH underwent a TCM regimen and experienced dramatic improvement in symptoms and reduction in their IgE levels. This regimen appears to be effective in FPDTH population although a further study in a controlled clinical setting is required.

Time-dependent dual beneficial modulation of interferon-γ, interleukin 5, and Treg cytokines in asthma patient peripheral blood mononuclear cells by ganoderic acid B.

Th2 cytokines play a dominant role in the pathogenesis of allergic asthma. Interferon gamma (IFN-γ), a Th1 cytokine, links to therapeutic mechanisms of allergic asthma. Interleukin (IL)-10, a regulatory cytokine, is involved in the induction of immune tolerance. We previously demonstrated that Anti-Asthma Simplified Herbal Medicine Intervention (ASHMI) suppressed Th2 and increased IFN-γ in patients with asthma and in animal models, but its bioactive compound is unknown. Ganoderic acid beta (GAB) was isolated from Ganoderma lucidum (one herb in ASHMI). Human peripheral blood mononuclear cells (PBMCs) from adult patients with asthma were cultured with GAB or dexamethasone (Dex) in the presence of environmental allergens. The cytokine levels of IL-10, IFN-γ, IL-5, transcription factors T-bet, Foxp-3, and GATA3 were measured. Following 3-day culture, GAB, but not Dex, significantly increased IL-10 and IFN-γ levels by allergic patients' PBMCs. Following 6-day treatment, GAB inhibited IL-5 production, but IL-10 and IFN-γ remained high. Dex suppressed production of all three cytokines. GAB suppressed GATA3 and maintained Foxp-3 and T-bet gene expression, while Dex significantly suppressed GATA3 and T-bet expression. GAB simultaneously increased IL-10, IFN-γ associated with induction of T-bet and Foxp3, while suppressing IL-5, which was associated with suppression of GATA3, demonstrating unique beneficial cytokine modulatory effect, which distinguishes from Dex's overall suppression.

SnO2 quantum dots-functionalized Ti3C2 MXene nanosheets for electrochemical determination of dopamine in body fluids.

A novel SnO2 quantum dots (SnO2QDs)-functionalized Ti3C2 MXene nanocomposite was prepared via in situ synthesis method, resulting in well-regulated the nucleation and growth of SnO2QDs to evenly distribute onto MXene nanosheets. Ultra-small size SnO2QDs decorated on the surface of Ti3C2 MXene nanosheets can effectively prevent the restacking of MXene and remarkably increase the electroactive surface area of the electrode, which can further increase electrocatalytic activity toward dopamine. Then, an ultrasensitive electroanalytical method based on SnO2QDs-functionalized Ti3C2 MXene nanocomposite for dopamine monitoring was developed, and the effects of experimental condition were investigated systematically. Under optimized conditions, the prepared sensor presented a linear dependence for dopamine in the concentration range from 0.004 to 8.0 µM with the detection limit of 2.0 nM (S/N = 3). Moreover, it selectively perceived dopamine in presence of physiological interferents in urine and serum samples with excellent linearities (correlation coefficients higher than 0.9920). The relative recoveries were in the range 97.67-105.3% and 103.0-106.8%, while the limits of quantitation were 10.12 nM and 9.62 nM in urine and serum sample, respectively, demonstrating the method suitability for dopamine sensing and being envisioned as a promising candidate for neurotransmitter monitoring in biological diagnosis.

Mechanistic insight into cost-effective dedicated oxidation of alkanes by inactivating soil organic matter with FeOOH formed in situ.

Modified Fenton technique has been widely used to remediate soils contaminated with crude oil but significantly limited to soil organic matter (SOM) consuming oxidants. In this study, soils with developed SOM inactivation by FeOOH formed in situ were created and spiked with crude oil (total petroleum hydrocarbons (TPH): 19453 mg/kg), then treated by modified Fenton reagents. The reaction activity of hydroxyl radicals (•OH) relative to TPH (K) notably increased to 0.65 when the degree of developed inactivation of the SOM (ß) was 100% (DIS-100), which was 1.45, 2.03 and 2.83-fold than that of DIS-50, DIS-15 and control (CK), respectively. Meanwhile, the higher the K, the more •OH transferred, which realized the efficient oriented oxidation of TPH. Moreover, improving the transfer of •OH from SOM to TPH was more important than increasing •OH production in soil remediation. With the ß increasing to 100%, the ratio of invalid H2O2 decomposition to produce O2 decreased to 22%, equal to 25% reduction compared to CK. Therefore, when ß was 100%, the utilization efficiency of H2O2 was improved to 1.48 mg/mmol, which was approximately 1.39, 3.35 and 5.43-fold higher than the efficiency got by DIS-50, DIS-15 and CK, respectively, achieving the cost-effective dedicated oxidation of TPH. In addition, the FeOOH cross-linked with SOM via Fe-O-C and Fe-N bonds to develop inactivation of SOM. In general, this study highlighted a new insight into the effect of developed inactivation of SOM on soil remediation.

Fast biodegradation of long-alkanes by enhancing bacteria performance rate by per-oxidation.

The long-alkanes biodegradation rate was generally found slow during widely used pre-oxidation combined with biodegradation for oil contamination treatment, resulting in long and unsustainable removal. In this study, different chitosan content was used to produce iron catalysts for pre-oxidation, and nutrients were added for the long-alkanes biodegradation experiment. Mechanism of Fenton pre-oxidation and improvement in the biodegradation rate of long-alkanes were studied by analyzing the change in organic matter and bacterial community structure, the amount and activity of bacteria in the biological stage, and the degradation amount long-alkanes hydrocarbon before and after pre-oxidation. Results showed that the destruction of bacteria greatly reduced when hydroxyl radical intensity decreased to 4.40 a.u.. Also, the proportion of humic acid-like was high (40.88%), and the community structure was slightly changed with the pre-oxidation for the fast biodegradation (FB) group. In the subsequent biodegradation, it was found that the degradation rate of each long-alkanes in the FB group increased significantly (C30: 4.18-8.32 mg/(kg·d)) with the increase of the degradation of long-alkanes (10-50%). Further studies showed that the high nutrient dynamics (6.05 mg/(kg·d)) of the FB group resulted in high bacteria performance rate (0.53 mol CO2 × log CFU/(104 g2 d)), which further accelerated the substrate transformation(41%). Therefore, the biodegradation rate of long-alkanes was increased (43.8 mg/(kg·d)) with the removal rate of long-alkanes of 76%. The half-life of long-alkanes for the FB group (64 d) was 33 d shorter than the slow biodegradation group (99 d). These results exhibited that pre-oxidation regulation can shorten the bioremediation cycle by improving the biodegradation rate of long-alkanes. This research has good engineering application value.

Traditional Chinese medicine for food allergy and eczema.

OBJECTIVE: To summarize the recent evidence of traditional Chinese medicine (TCM) for food allergy and eczema. DATA SOURCES: Published literature from PubMed database and abstract conference presentations. STUDY SELECTIONS: Studies relevant to TCM for food allergy and eczema were included. RESULTS: TCM is the main component of complementary and alternative medicine in the United States. Food Allergy Herbal Formula 2 (FAHF-2) (derived from the classical formula Wu Mei Wan) prevented systemic anaphylaxis in murine models and was found to have safety and preliminary immunomodulatory effects on T cells and basophils. The phase II trial of combined TCM with oral immunotherapy and omalizumab for multiple food allergy is ongoing. Retrospective practice-based evidence study revealed that comprehensive TCM therapy effectively prevented frequent and severe food anaphylaxis triggered by skin contact or protein inhalation. The traditional Japanese herbal medicine Kakkonto suppressed allergic diarrhea and decreased mast cells in intestinal mucosa in a murine model. The active compounds from TCM were found to have potent inhibition of immunoglobulin (Ig) E, mast cell activation, and proinflammatory cytokine or signaling pathway (tumor necrosis factor alpha, interleukin 8, NF-κB) suggesting value for both IgE and non-IgE-mediated food allergy. Triple TCM therapy including ingestion, bath, and cream markedly improved skin lesion, itching, and sleep loss in patients with corticosteroid dependent, recalcitrant, or topical steroid withdrawal. Xiao Feng San and Japanese and Korean formulas were found to have effectiveness in eczema. Furthermore, acupuncture reduced wheal size, skin itching, and basophil activation in atopic dermatitis. Moreover, TCM is generally safe. CONCLUSION: TCM has potential as safe and effective therapy for food allergy and eczema. Further research is needed for botanical drug development and to further define the mechanisms of actions. TRIAL REGISTRATION: FAHF-2: https://ichgcp.net/clinical-trials-registry/NCT00602160; ethyl acetate and butanol purified FAHF-2: https://clinicaltrials.gov/ct2/show/NCT02879006.

Disruption of Cell-Cell Communication in Anaplastic Thyroid Cancer as an Immunotherapeutic Opportunity.

Thyroid cancer incidence is increasing at an alarming rate, almost tripling every decade. About 44,280 new cases of thyroid cancer (12,150 in men and 32,130 in women) are estimated to be diagnosed in 2021, with an estimated death toll of around 2200. Although most thyroid tumors are treatable and associated with a favorable outcome, anaplastic thyroid cancer (ATC) is extremely aggressive with a grim prognosis of 6-9 months post-diagnosis. A large contributing factor to this aggressive nature is that ATC is completely refractory to mainstream therapies. Analysis of the tumor microenvironment (TME) associated with ATC can relay insight to the pathological realm that encompasses tumors and aids in cancer progression and proliferation. The TME is defined as a complex niche that surrounds a tumor and involves a plethora of cellular components whose secretions can modulate the environment in order to favor tumor progression. The cellular heterogeneity of the TME contributes to its dynamic function due to the presence of both immune and nonimmune resident, infiltrating, and interacting cell types. Associated immune cells discussed in this chapter include macrophages, dendritic cells (DCs), natural killer (NK) cells, and tumor-infiltrating lymphocytes (TILs). Nonimmune cells also play a role in the establishment and proliferation of the TME, including neuroendocrine (NE) cells, adipocytes, endothelial cells (ECs), mesenchymal stem cells (MSCs), and fibroblasts. The dynamic nature of the TME contributes greatly to cancer progression.Recent work has found ATC tissues to be defined by a T cell-inflamed "hot" tumor immune microenvironment (TIME) as evidenced by presence of CD3+ and CD8+ T cells. These tumor types are amenable to immune checkpoint blockade (ICB) therapy. This therapeutic avenue, as of 2021, has remained unexplored in ATC. New studies should seek to explore the therapeutic feasibility of a combination therapy, through the use of a small molecule inhibitor with ICB in ATC. Screening of in vitro model systems representative of papillary, anaplastic, and follicular thyroid cancer explored the expression of 29 immune checkpoint molecules. There are higher expressions of HVEM, BTLA, and CD160 in ATC cell lines when compared to the other TC subtypes. The expression level of HVEM was more than 30-fold higher in ATC compared to the others, on average. HVEM is a member of tumor necrosis factor (TNF) receptor superfamily, which acts as a bidirectional switch through interaction with BTLA, CD160, and LIGHT, in a cis or trans manner. Given the T cell-inflamed hot TIME in ATC, expression of HVEM on tumor cells was suggestive of a possibility for complex crosstalk of HVEM with inflammatory cytokines. Altogether, there is emerging evidence of a T cell-inflamed TIME in ATC along with the expression of immune checkpoint proteins HVEM, BTLA, and CD160 in ATC. This can open doors for combination therapies using small molecule inhibitors targeting downstream effectors of MAPK pathway and antagonistic antibodies targeting the HVEM/BTLA axis as a potentially viable therapeutic avenue for ATC patients. With this being stated, the development of adaptive resistance to targeted therapies is inevitable; therefore, using a combination therapy that targets the TIME can serve as a preemptive tactic against the characteristic therapeutic resistance that is seen in ATC. The dynamic nature of the TME, including the immune cells, nonimmune cells, and acellular components, can serve as viable targets for combination therapy in ATC. Understanding the complex interactions of these associated cells and the paradigm in which their secretions and components can serve as immunomodulators are critical points of understanding when trying to develop therapeutics specifically tailored for the anaplastic thyroid carcinoma microenvironment.

[Analysis of animal models of chronic skin ulcers based on characteristics of clinical symptoms of traditional Chinese and Western medicine].

Based on the characteristics of clinical symptoms of chronic skin ulcers in traditional Chinese and Western medicine, the current animal models of skin ulcers are summarized. This article analyzes the advantages and disadvantages of animal models according to the etiology and pathogenesis of chronic skin ulcers, traditional Chinese and Western medicine diagnostic criteria and observation indicators, and eva-luates the agreement between the existing animal models and the characteristics of clinical syndromes of traditional Chinese and Western medicine for chronic skin ulcers. Through analysis and comparison, it is found that most of the existing modeling methods are single-factor animal models, and there are certain gaps in the physiological and pathological characteristics of chronic skin ulcers caused by clinical multi-factors and interactions. Most of the modeling methods are guided by Western medicine. The lack of pathogenic factors of traditional Chinese medicine(TCM) in the process of modeling. Therefore, this article proposes to establish a reasonable quantification standard for chronic skin ulcer animal models, and to establish a combination model of chronic skin ulcer disease with traditional Chinese and Western medicine as the focus of future animal model research.