Intratumoral and Peritumoral Edema Radiomics Based on Fat-Suppressed T2- Weighted Imaging for Preoperative Prediction of Triple-Negative Breast Cancer.

AIM: Our aim was to explore the feasibility of using radiomics data derived from intratumoral and peritumoral edema on fat-suppressed T2-weighted imaging (T2 FS) to distinguish triple-negative breast cancer (TNBC) from non-triple-negative breast cancer (non-TNBC). METHODS: This retrospective study enrolled 174 breast cancer patients. According to the MRI examination time, patients before 2021 were divided into training (n = 119) or internal test (n = 30) cohorts at a ratio of 8:2. Patients from 2022 were included in the external test cohort (n = 25). Four regions of interest for each lesion were defined: intratumoral regions, peritumoral edema regions, regions with a combination of intratumoral and peritumoral edema, and regions with a combination of intratumoral and 5-mm peritumoral. Four radiomic signatures were built using the least absolute shrinkage and selection operator (LASSO) method after selecting features. Furthermore, a radio mic-radiological model was constructed using a combination of intratumoral and peritumoral edema regions along with clinical-radiologic features. Area under the receiver operating characteristic curve (AUC) calculations, decision curve analysis, and calibration curve analysis were performed to assess the performance of each model. RESULTS: The radiomic-radiological model showed the highest AUC values of 0.906 (0.788-1.000) and 82.5 (0.622-0.947) in both the internal and external test sets, respectively. The radiology-radiomic model exhibited excellent predictive performance, as evidenced by the calibration curves and decision curve analysis. CONCLUSION: The ensemble model based on T2 FS-based radiomic features of intratumoral and peritumoral edema, along with radiological factors, performed better in distinguishing TNBC from non-TNBC than a single model. We explored the possibility of developing explainable models to support the clinical decision-making process.

Enhancement Effect Induced by the Second Metal to Promote Ozone Catalytic Oxidation of VOCs.

It is a promising research direction to develop catalysts with high stability and ozone utilization for low-temperature ozone catalytic oxidation of VOCs. While bimetallic catalysts exhibit excellent catalytic activity compared with conventional single noble metal catalysts, limited success has been achieved in the influence of the bimetallic effect on the stability and ozone utilization of metal catalysts. Herein, it is necessary to systematically study the enhancement effect in the ozone catalytic reaction induced by the second metal. With a simple continuous impregnation method, a platinum-cerium bimetallic catalyst is prepared. Also highlighted are studies from several aspects of the contribution of the second metal (Ce) to the stability and ozone utilization of the catalysts, including the "electronic effect" and "geometric effect". The synergistic removal rate of toluene and ozone is nearly 100% at 30 °C, and it still shows positive stability after high humidity and a long reaction time. More importantly, the instructive significance, which is the in-depth knowledge of enhanced catalytic mechanism of bimetallic catalysts resulting from a second metal, is provided by this work.

OsMADS6-OsMADS32 and REP1 control palea cellular heterogeneity and morphogenesis in rice.

Precise regulation of cell proliferation and differentiation is vital for organ morphology. Rice palea, serving as sepal, comprises two distinct regions: the marginal region (MRP) and body of palea (BOP), housing heterogeneous cell populations, which makes it an ideal system for studying organ morphogenesis. We report that the transcription factor (TF) REP1 promotes epidermal cell proliferation and differentiation in the BOP, resulting in hard silicified protrusion cells, by regulating the cyclin-dependent kinase gene, OsCDKB1;1. Conversely, TFs OsMADS6 and OsMADS32 are expressed exclusively in the MRP, where they limit cell division rates by inhibiting OsCDKB2;1 expression and promote endoreduplication, yielding elongated epidermal cells. Furthermore, reciprocal inhibition between the OsMADS6-OsMADS32 complex and REP1 fine-tunes the balance between cell division and differentiation during palea morphogenesis. We further show the functional conservation of these organ identity genes in heterogeneous cell growth in Arabidopsis, emphasizing a critical framework for controlling cellular heterogeneity in organ morphogenesis.

Wnt5a deficiency in osteocalcin-expressing cells could not alleviate the osteoarthritic phenotype in a mouse model of post-traumatic osteoarthritis.

Objectives: Wnt5a, which regulates the activities of osteoblasts and osteoclasts, is reportedly overexpressed in osteoarthritis (OA) tissues. The purpose of this study was to elucidate its role in the development of OA by deleting Wnt5a in osteocalcin (OCN)-expressing cells. Materials and Methods: Knee OA was induced by anterior cruciate ligament transection (ACLT) in OCN-Cre;Wnt5afl/fl knockout (Wnt5a-cKO) mice and control littermates. Eight weeks after surgery, histological changes, cell apoptosis, and matrix metabolism of cartilage were evaluated by toluidine blue, TUNEL staining, and im-immunohistochemistry analyses, respectively. In addition, the subchondral bone microarchitecture of mice was examined by micro-computed tomography (micro-CT). Results: Histological scores show substantial cartilage degeneration occurred in ACLT knees, coupled with decreased collagen type II expression and enhanced matrix metalloproteinase 13 expression, as well as higher proportions of apoptotic cells. Micro-CT results show that ACLT resulted in decreased bone mineral density, bone volume/trabecular volume, trabecular number, and structure model index of subchondral bones in both Wnt5a-cKO and control littermates; although Wnt5a-cKO mice display lower BMD and BV/TV values, no significant difference was observed between Wnt5a-cKO and control mice for any of these values. Conclusion: Our findings indicate that Wnt5a deficiency in OCN-expressing cells could not prevent an osteoarthritic phenotype in a mouse model of post-traumatic OA.

Illumina and Nanopore sequencing in culture-negative samples from suspected lower respiratory tract infection patients.

Objective: To evaluate the diagnostic value of metagenomic sequencing technology based on Illumina and Nanopore sequencing platforms for patients with suspected lower respiratory tract infection whose pathogen could not be identified by conventional microbiological tests. Methods: Patients admitted to the Respiratory and Critical Care Medicine in Shanghai Ruijin Hospital were retrospectively studied from August 2021 to March 2022. Alveolar lavage or sputum was retained in patients with clinically suspected lower respiratory tract infection who were negative in conventional tests. Bronchoalveolar lavage fluid (BALF) samples were obtained using bronchoscopy. Sputum samples were collected, while BALF samples were not available due to bronchoscopy contraindications. Samples collected from enrolled patients were simultaneously sent for metagenomic sequencing on both platforms. Results: Thirty-eight patients with suspected LRTI were enrolled in this study, consisting of 36 parts of alveolar lavage and 2 parts of sputum. According to the infection diagnosis, 31 patients were confirmed to be infected with pathogens, while 7 patients were diagnosed with non-infectious disease. With regard to the diagnosis of infectious diseases, the sensitivity and specificity of Illumina and Nanopore to diagnose infection in patients were 80.6% vs. 93.5% and 42.9 vs. 28.6%, respectively. In patients diagnosed with bacterial, Mycobacterium, and fungal infections, the positive rates of Illumina and Nanopore sequencer were 71.4% vs. 78.6%, 36.4% vs. 90.9%, and 50% vs. 62.5%, respectively. In terms of pathogen diagnosis, the sensitivity and specificity of pathogens detected by Illumina and Nanopore were 55.6% vs. 77.8% and 42.9% vs. 28.6%, respectively. Among the patients treated with antibiotics in the last 2 weeks, 61.1% (11/18) and 77.8% (14/18) cases of pathogens were accurately detected by Illumina and Nanopore, respectively, among which 8 cases were detected jointly. The consistency between Illumina and diagnosis was 63.9% (23/36), while the consistency between Nanopore and diagnosis was 83.3% (30/36). Between Illumina and Nanopore sequencing methods, the consistency ratio was 55% (22/42) based on pathogen diagnosis. Conclusion: Both platforms play a certain value in infection diagnosis and pathogen diagnosis of CMT-negative suspected LRTI patients, providing a theoretical basis for clinical accurate diagnosis and symptomatic treatment. The Nanopore platform demonstrated potential advantages in the identification of Mycobacterium and could further provide another powerful approach for patients with suspected Mycobacterium infection.

Complete Degradation of Polyolefin Plastic Wastes to High-Value Products.

Plastic wastes continuously accumulate, causing critical environmental issues. It is urgent to develop efficient strategies to convert them to valuable products. Very recently, two novel approaches for plastic recycling were reported by Huber et al. (Science, 2023, 381, 660-666) and Liu et al. (Science, 2023, 381, 666-671) , where polyethylene (PE) and polypropylene (PP) plastics were converted into potentially valuable products, such as alcohols, aldehydes, surfactants, and detergents. The two processes achieved complete degradation, high selectivity of target products, as well as high values of products, showing economic feasibility for industrial scale-up. These breakthroughs for plastic recycling are highlighted in this article.

Shrimp Cultured in Low-Salt Saline-Alkali Water has a Better Amino Acid Nutrition and Umami─Comparison of Flavors between Saline-Alkali Water- and Seawater-Cultured Litopenaeus vannamei.

The advantages of Litopenaeus vannamei farming in saline-alkali water have gradually attracted attention, but few studies have focused on its flavor. In this study, L. vannamei cultured in saline-alkali water (SS) and ordinary seawater (CS) (both have a breeding time of 120 days) were selected for analysis (n = 5). High-performance liquid chromatography (HPLC) was used to measure free amino acids and flavoring nucleotides in the muscles of L. vannamei, while the taste activity value (TAV) and equivalent umami concentration (EUC) were used to analyze the degree of umami. The total essential amino acids (TEAA) in the SS group were 238.41 ± 46.24 mg/mL, significantly higher than that in the CS group (107.06 ± 15.65 mg/mL). The total amount of flavor nucleotides in the SS group was 2948.51 ± 233.66 µg/mL, significantly higher than those in the CS group (2530.37 ± 114.67 µg/mL). The content and TAV of some free amino acids (Glu, Cys-s) in the SS group were significantly higher. Meanwhile, due to the significant increase in IMP, the synergistic effect of free amino acids and flavored nucleotides leads to higher EUC. The significant separation of SS and CS samples in principal component analysis (PCA) indicates a significant difference between the two groups. Our results indicate that shrimp cultured in saline-alkali water has a stronger umami. This study enriches the basic theories related to the flavor of salt-alkali water crustaceans.

Gradient Functional Layer Anode for Carbonate-Superstructured Solid Fuel Cells with Ethane Fuel.

Carbonate-superstructured solid fuel cells (CSSFCs) are an emerging type of fuel cells with high flexibility of fuels. However, using ethane fuel for solid fuel cells is a great challenge due to serious degradation of their anodes. Herein, this critical issue is solved by creating a novel gradient functional layer anode for CSSFCs. First, a finer-scale anode with a larger surface area is demonstrated to provide more active sites for the internal reforming reaction of ethane, achieving a 60% higher ethane conversion rate and 40% lower polarization resistance than conventional anodes. Second, incorporating a gradient functional layer into the anode results in an additional 50% enhancement in the peak power density of CSSFCs to a record high value (up to 241 mW cm-2) with dry ethane fuel at a low temperature of 550 °C, which is even comparable to the power density of conventional solid oxide fuel cells above 700 °C. Furthermore, the CSSFC with the gradient anode exhibits excellent durability for over 200 h. This finding provides a new strategy to develop efficient anodes for hydrocarbon fuels.

Research progress on the biological regulatory mechanisms of selenium on skeletal muscle in broilers.

As one of the indispensable trace elements for both humans and animals, selenium widely participates in multiple physiological processes and facilitates strong anti-inflammatory, antioxidant, and immune enhancing abilities. The biological functions of selenium are primarily driven by its presence in selenoproteins as a form of selenocysteine. Broilers are highly sensitive to selenium intake. Recent reports have demonstrated that selenium deficiency can adversely affect the quality of skeletal muscles and the economic value of broilers; the regulatory roles of several key selenoproteins (e.g., GPX1, GPX4, TXNRD1, TXNRD3, SelK, SelT, and SelW) have been identified. Starting from the selenium metabolism and its biological utilization in the skeletal muscle, the effect of the selenium antioxidant function on broiler meat quality is discussed in detail. The progress of research into the prevention of skeletal muscle injury by selenium and selenoproteins is also summarized. The findings emphasize the necessity of in vivo and in vitro research, and certain mechanism problems are identified, which aids their further examination. This mini-review will be helpful to provide a theoretical basis for the further study of regulatory mechanisms of selenium nutrition in edible poultry.

A Synthetic Strategy toward S-, N-, and O-Heterocyclooctynes Facilitates Bioconjugation Using Multifunctional Handles.

Over the past two decades, the introduction of bioorthogonal reactions has transformed the ways in which chemoselective labeling, isolation, imaging, and drug delivery are carried out in a complex biological milieu. A key feature of a good bioorthogonal probe is the ease with which it can be attached to a target compound through bioconjugation. This paper describes the expansion of the utility of a class of unique S-, N-, and O-containing heterocyclooctynes (SNO-OCTs), which show chemoselective reactivity with type I and type II dipoles and divergent reactivities in response to electronic tuning of the alkyne. Currently, bioconjugation of SNO-OCTs to a desired target is achieved through an inconvenient aryl or amide linker at the sulfamate nitrogen. Herein, a new synthetic approach toward general SNO-OCT scaffolds is demonstrated that enables the installation of functional handles at both propargylic carbons of the heterocycloalkyne. This capability increases the utility of SNO-OCTs as labeling reagents through the design of bifunctional bioorthogonal probes with expanded capabilities. NMR kinetics also revealed up to sixfold improvement in cycloaddition rates of new analogues compared to first-generation SNO-OCTs.

Enhancement of Nutrient Composition and Non-Volatile Flavor Substances in Muscle Tissue of Red Drum (Sciaenops ocellatus) Through Inland Low Salinity Saline-Alkaline Water Culture.

The red drum (Sciaenops ocellatus), a globally significant marine aquaculture species, boasts formidable osmoregulatory capabilities and remarkable adaptability to low salinity, making it an ideal candidate for commercial cultivation in inland low salinity saline-alkaline waters. However, studies on the fundamental nutritional composition and flavor quality of S. ocellatus in these inland low salinity saline-alkaline waters remain unreported. This study delves into the impact of inland low salinity saline-alkaline environments on the basic nutritional components and nonvolatile flavor substances (including free amino acids and free nucleotides) in the muscle tissue of S. ocellatus. The findings reveal that redfish cultivated in these conditions exhibit a significant increase in the crude fat, ash, and protein content in their dorsal muscle tissue, coupled with a decrease in moisture content (p < 0.05), indicating an enhancement in the nutritional value of the dorsal muscle tissue. Furthermore, this cultivation environment significantly elevates the content of free amino acids in the muscle tissue (p < 0.05), particularly those contributing to umami and sweet tastes, while reducing the relative content of bitter amino acids. Although the total content of free nucleotides decreased, the equivalent umami concentration (EUC) in the muscle tissue markedly increased (p < 0.05) due to the synergistic effect of umami amino acids and flavor nucleotides, enhancing the umami taste characteristics. Therefore, inland low salinity saline-alkaline aquaculture not only elevates the nutritional value of S. ocellatus muscle tissue but also improves its umami flavor characteristics. This discovery opens new perspectives for further research into the impact of inland low salinity saline-alkaline environments on the flavor properties of marine animals.

Comprehensive HRMS Screening and Risk Assessments of Aristolochic Acid Analogues in Asari Radix et Rhizoma and Related Commercial Health Products.

Aristolochic acid analogues (AAAs) are well-known toxins. We performed the first comprehensive screening on AAAs in Asari Radix et Rhizoma (underground part of Asarum heterotropoides Schmidt), the only Aristolochiaceae plant widely used in clinical practice. LC-HRMS revealed 70 trace AAAs using polygonal mass defect filtering and precursor ion list strategies, 38 of which were newly discovered in A. heterotropoides. UHPLC-QTrap-MS/MS was then utilized for quantitative/semiquantitative analysis of 26 abundant compounds. Seventeen AAAs were detected from 91 batches of A. heterotropoides and 20 AAAs from 166 consumable products. For 141 Asari-containing proprietary products, aristolactam I and aristolactam II-glucoside exhibited the widest distribution, present in 98% products. AA IVa was the most abundant, detected in 91%. Notably, 60% of the products contained AA I (0.03-0.79 ppm). The safety was assessed using linear extrapolation, permitted daily exposure, cumulative amount, and the margin of exposure. It is recommended that AA I content be limited to 3 ppm.

Exploring functional genes' correlation with (S)-equol concentration and new daidzein racemase identification.

With its estrogenic activity, (S)-equol plays an important role in maintaining host health and preventing estrogen-related diseases. Exclusive production occurs through the transformation of soy isoflavones by intestinal bacteria, but the reasons for variations in (S)-equol production among different individuals and species remain unclear. Here, fecal samples from humans, pigs, chickens, mice, and rats were used as research objects. The concentrations of (S)-equol, along with the genetic homology and evolutionary relationships of (S)-equol production-related genes [daidzein reductase (DZNR), daidzein racemase (DDRC), dihydrodaidzein reductase (DHDR), tetrahydrodaidzein reductase (THDR)], were analyzed. Additionally, in vitro functional verification of the newly identified DDRC gene was conducted. It was found that approximately 40% of human samples contained (S)-equol, whereas 100% of samples from other species contained (S)-equol. However, there were significant variations in (S)-equol content among the different species: rats > pigs > chickens > mice > humans. The distributions of the four genes displayed species-specific patterns. High detection rates across various species were exhibited by DHDR, THDR, and DDRC. In contrast, substantial variations in detection rates among different species and individuals were observed with respect to DZNR. It appears that various types of DZNR may be associated with different concentrations of (S)-equol, which potentially correspond to the regulatory role during (S)-equol synthesis. This enhances our understanding of individual variations in (S)-equol production and their connection with functional genes in vitro. Moreover, the newly identified DDRC exhibits higher potential for (S)-equol synthesis compared to the known DDRC, providing valuable resources for advancing in vitro (S)-equol production. IMPORTANCE: (S)-equol ((S)-EQ) plays a crucial role in maintaining human health, along with its known capacity to prevent and treat various diseases, including cardiovascular diseases, metabolic syndromes, osteoporosis, diabetes, brain-related diseases, high blood pressure, hyperlipidemia, obesity, and inflammation. However, factors affecting individual variations in (S)-EQ production and the underlying regulatory mechanisms remain elusive. This study examines the association between functional genes and (S)-EQ production, highlighting a potential correlation between the DZNR gene and (S)-EQ content. Various types of DZNR may be linked to the regulation of (S)-EQ synthesis. Furthermore, the identification of a new DDRC gene offers promising prospects for enhancing in vitro (S)-EQ production.

Inhibition of MER proto-oncogene tyrosine kinase by an antisense oligonucleotide enhances treatment efficacy of immunoradiotherapy.

BACKGROUND: The combination of radiotherapy and immunotherapy (immunoradiotherapy) has been increasingly used for treating a wide range of cancers. However, some tumors are resistant to immunoradiotherapy. We have previously shown that MER proto-oncogene tyrosine kinase (MerTK) expressed on macrophages mediates resistance to immunoradiotherapy. We therefore sought to develop therapeutics that can mitigate the negative impact of MerTK. We designed and developed a MerTK specific antisense oligonucleotide (ASO) and characterized its effects on eliciting an anti-tumor immune response in mice. METHODS: 344SQR cells were injected into the right legs on day 0 and the left legs on day 4 of 8-12 weeks old female 129sv/ev mice to establish primary and secondary tumors, respectively. Radiation at a dose of 12 Gy was given to the primary tumors on days 8, 9, and 10. Mice received either anti-PD-1, anti-CTLA-4 or/and MerTK ASO starting from day 1 post tumor implantation. The composition of the tumor microenvironment and the level of MerTK on macrophages in the tumor were evaluted by flow cytometry. The expression of immune-related genes was investigated with NanoString. Lastly, the impact of MerTK ASO on the structure of the eye was histologically evaluated. RESULTS: Remarkably, the addition of MerTK ASO to XRT+anti-PD1 and XRT+anti-CTLA4 profoundly slowed the growth of both primary and secondary tumors and significantly extended survival. The ASO significantly reduced the expression of MerTK in tumor-associated macrophages (TAMs), reprograming their phenotype from M2 to M1. In addition, MerTK ASO increased the percentage of Granzyme B+ CD8+ T cells in the secondary tumors when combined with XRT+anti-CTLA4. NanoString results demonstrated that the MerTK ASO favorably modulated immune-related genes for promoting antitumor immune response in secondary tumors. Importantly, histological analysis of eye tissues demonstrated that unlike small molecules, the MerTK ASO did not produce any detectable pathology in the eyes. CONCLUSIONS: The MerTK ASO can significantly downregulate the expression of MerTK on TAMs, thereby promoting antitumor immune response. The combination of MerTK ASO with immunoradiotherapy can safely and significantly slow tumor growth and improve survival.

Dietary Zn Deficiency Inhibits Cell Proliferation via the GPR39-Mediated Suppression of the PI3K/AKT/mTOR Signaling Pathway in the Jejunum of Broilers.

A prior investigation revealed that a lack of Zinc (Zn) could hinder intestinal cell proliferation in broiler chickens; however, the mechanisms responsible for this effect remain unclear. We aimed to investigate the possible mechanisms of dietary Zn deficiency in inhibiting the jejunal cell proliferation of broilers. For this study, a total of 112 chickens (21 days old) were randomly divided into two treatments (seven replicate cages per treatment, eight chickens per replicate cage): the control group (CON) and the Zn deficiency group. The duration of feeding was 21 d. Chickens in the control group were provided with a basal diet containing an extra addition of 40 mg Zn/kg in the form of Zn sulfate, whereas chickens in the Zn deficiency group were given the basal diet with no Zn supplementation. The results indicated that, in comparison to the CON, Zn deficiency increased (p < 0.05) the duodenal and jejunal crypt depth (CD) of broilers on d 28 and jejunal and ileal CD on d 35, and decreased (p < 0.05) the duodenal, jejunal, and ileal villus height/crypt depth (VH/CD) on d 28 and the jejunal VH, jejunal and ileal villus surface area, and VH/CD on d 35. Furthermore, Zn deficiency decreased (p < 0.0001) the number of proliferating cell nuclear antigen-positive cells and downregulated (p < 0.01) the mRNA or protein expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated PI3K, phosphorylated serine-threonine kinase (AKT), phosphorylated mechanistic target of rapamycin (mTOR), G protein-coupled receptor 39 (GPR39), and extracellular-regulated protein kinase, but upregulated (p < 0.05) the mRNA or protein expression levels of P38 mitogen-activated protein kinase, c-jun N-terminal kinase (JNK) 1 and JNK2, and phosphorylated protein kinase C in the jejunum of the broilers on d 42. It was concluded that dietary Zn deficiency inhibited cell proliferation possibly via the GPR39-mediated suppression of the PI3K/AKT/mTOR signaling pathway in the jejunum of broilers.

Development of on-DNA Formation of Benzofuran for DNA-Encoded Library Synthesis.

Using a novel homologation-heterocyclization cascade, the on-DNA synthesis of benzofurans from aldehydes has been developed. The methodology, based on an innovative use of the Seyferth-Gilbert homologation, followed by a high yielding Sonogashira coupling in situ intramolecular cyclization one-pot, two-step reaction, provides a powerful and unique pathway for DNA-encoded library (DEL) synthesis of a wide array of pharmaceutically relevant benzofuran-based scaffolds.

Dietary copper requirement of broilers fed a corn-soybean meal diet during 22-42 d of age.

This research was to assess the dietary copper (Cu) requirement of broiler chickens fed a practical corn-soybean meal diet during 22-42 d of age. A total of 288 numbered Arbor Acres male broilers at 22 d of age were randomly allotted 6 treatments with 8 replicate cages (6 broilers per cage) per treatment. Broilers were fed a Cu-unsupplemented corn-soybean meal basal diet (control, containing 7.36 mg Cu/kg) or the basal diet added with 3, 6, 9, 12, or 15 mg Cu/kg from CuSO4·5H2O for 21 d. Quadratic, asymptotic and broken-line models were fitted and the best fitted models were selected to determine dietary Cu requirements. The results revealed that the contents of Cu in serum and liver, mRNA expression levels of Cu- and zinc-containing superoxide dismutase (CuZnSOD) in liver and monoamine oxidase b (MAO B) in heart, as well as protein expression level of CuZnSOD in liver were affected (P < 0.05) by supplemental Cu levels, and the above indices varied linearly and quadratically (P < 0.05) with increasing Cu levels. Dietary Cu requirements assessed according to the best fitted broken-line models (P < 0.05) of the above indexes were 10.45-13.81 mg/kg. It was concluded that mRNA expression levels of CuZnSOD in liver and MAO B in heart, as well as liver CuZnSOD protein expression level were new specific sensitive biomarkers for estimating dietary Cu requirements, and the dietary Cu requirement was recommended to be 14 mg/kg to support Cu metabolic needs related to key Cu-containing enzymes in broilers fed the corn-soybean meal diet during 22-42 d of age, which was higher than the dietary Cu requirement (8 mg/kg) for broilers at the corresponding stage suggested by the Chinese Feeding Standard of Chicken.

Individualized intensive insulin therapy of diabetes: Not only the goal, but also the time.

Intensive insulin therapy has been extensively used to control blood glucose levels because of its ability to reduce the risk of chronic complications of diabetes. According to current guidelines, intensive glycemic control requires individualized glucose goals rather than as low as possible. During intensive therapy, rapid blood glucose reduction can aggravate microvascular and macrovascular complications, and prolonged overuse of insulin can lead to treatment-induced neuropathy and retinopathy, hypoglycemia, obesity, lipodystrophy, and insulin antibody syndrome. Therefore, we need to develop individualized hypoglycemic plans for patients with diabetes, including the time required for blood glucose normalization and the duration of intensive insulin therapy, which deserves further study.

Xuanfu Daizhe Tang alleviates reflux esophagitis in rats by inhibiting the STAT1/TREM-1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Reflux esophagitis (RE) is a common chronic inflammatory disease of the esophageal mucosa with a high prevalence and recurrence rate, for which a satisfactory therapeutic strategy is still lacking. Chinese medicine has its characteristics and advantages in treating RE, and the clinical application of Xuanfu Daizhe Tang (XDT) in treating RE has achieved sound therapeutic effects. However, there needs to be more research on its mechanism of action. AIM OF THE STUDY: The present work aimed to investigate the mechanism of XDT action in RE through the Signal Transducer and Activator of Transcription 1 (STAT1)/Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) pathway. MATERIALS AND METHODS: The main active components of XDT were analyzed by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS). The effect of XDT on RE was evaluated in a rat model of RE induced by "Cardioplasty + pyloric ligation + Roux-en-Y esophagojejunostomy". Each administration group was treated by gavage. The degree of damage to the esophageal mucosa was evaluated by visual observation, and the Potential of Hydrogen (PH) method and Hematoxylin-eosin staining (HE) staining were performed. Serum levels of Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), Tumor Necrosis Factor alpha (TNF-α), and Inducible Nitric Oxide Synthase (iNOS) were measured by ELISA. Quantitative Real-time PCR (qPCR), Western Blot (WB), and Immunofluorescence (IF) methods were used to detect Claudin-4, Claudin-5, TREM-1, and p-STAT1 in esophageal tissues for studying the mechanism of action and signaling pathway of XDT. Immunohistochemistry (IHC) analysis was used to detect the expression of TREM-1 and CD68 in esophageal tissues. Flow Cytometry (FC) was used to detect the polarization of macrophages in the blood. After conducting preliminary experiments to verify our hypothesis, we performed molecular docking between the active component of XDT and STAT1 derived from rats and parallel experiments with STAT1 inhibitor. The selective increaser of STAT1 transcription (2-NP) group was used to validate the mechanism by which XDT acts. RESULTS: XDT alleviated esophageal injury and attenuated histopathological changes in RE rats. XDT also inhibited the inflammatory response and decreased serum IL-1ß, IL-6, TNF-α, and iNOS levels in RE rats. qPCR and WB results revealed that XDT inhibited the expression of Claudin-4, Claudin-5, TREM-1, and STAT1 in the esophageal mucosa of RE rats. IHC and FC results showed that XDT reduced TREM-1 levels in esophageal tissues and polarized macrophages toward M2. The molecular docking results showed that rat-derived STAT1 can strongly bind to Isochronogenic acid A in XDT. The parallel experimental results of STAT1 inhibitor showed that XDT has anti-inflammatory effects similar to STAT1 inhibitors. The 2-NP group confirmed that XDT exerts its therapeutic effect on reflux esophagitis through the STAT1/TREM-1 pathway, with STAT1 as the upstream protein. CONCLUSIONS: This study suggests that XDT may treat reflux esophagitis by modulating the STAT1/TREM-1 pathway.