MRI quantitative assessment of the effects of low-carbohydrate therapy on Hashimoto's thyroiditis.

Objective: Hashimoto's thyroiditis is an inflammatory disease, and research suggests that a low-carbohydrate diet may have potential anti-inflammatory effects. This study aims to utilize Dixon-T2-weighted imaging (WI) sequence for a semi-quantitative assessment of the impact of a low-carbohydrate diet on the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Methods: Forty patients with Hashimoto's thyroiditis were recruited for this study and randomly divided into two groups: one with a normal diet and the other with a low-carbohydrate diet. Antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) were measured for all participants. Additionally, thyroid water content was semi-quantitatively measured using Dixon-T2WI. The same tests and measurements were repeated for all participants after 6 months. Results: After 6 months of a low-carbohydrate diet, patients with Hashimoto's thyroiditis showed a significant reduction in thyroid water content (94.84 ± 1.57% vs 93.07 ± 2.05%, P < 0.05). Concurrently, a decrease was observed in levels of TPOAb and TgAb (TPOAb: 211.30 (92.63-614.62) vs 89.45 (15.9-215.67); TgAb: 17.05 (1.47-81.64) vs 4.1 (0.51-19.42), P < 0.05). In contrast, there were no significant differences in thyroid water content or TPOAb and TgAb levels for patients with Hashimoto's thyroiditis following a normal diet after 6 months (P < 0.05). Conclusion: Dixon-T2WI can quantitatively assess the degree of thyroid inflammation in patients with Hashimoto's thyroiditis. Following a low-carbohydrate diet intervention, there is a significant reduction in thyroid water content and a decrease in levels of TPOAb and TgAb. These results suggest that a low-carbohydrate diet may help alleviate inflammation in patients with Hashimoto's thyroiditis.

Dynamic Restructuring of Cu7S4/Cu for Efficient CO2 Electro-reduction to Formate.

Optimized catalytic properties and reactant adsorption energy played a crucial role in promoting CO2 electrocatalysis. Herein, Cu7S4/Cu underwent in situ dynamic restructuring to generate S-Cu2O/Cu hybrid catalyst for effective electrochemical CO2 reduction to formate that outperformed Cu2O/Cu and Cu7S4. Thermodynamic and in situ Raman spectra revealed that the optimized adsorption of the HCOO* intermediate on S-Cu2O/Cu was regulated and the H2 pathway (surface H) was suppressed by S-doping. Meanwhile, Cu7S4/Cu nanoflowers created abundant boundaries for ECR and strengthened the CO2 adsorption by inducing Cu. These findings provide a new perspective on synthetic methods for various electrocatalytic reduction processes.

Matrine Targets Intestinal Lactobacillus acidophilus to Inhibit Porcine Circovirus Type 2 Infection in Mice.

Porcine circovirus type 2 (PCV2) has caused huge economic losses to the pig industry across the world. Matrine is a natural compound that has been shown to regulate intestinal flora and has anti-PCV2 activity in mouse models. PCV2 infection can lead to changes in intestinal flora. The intestinal flora has proved to be one of the important pharmacological targets of the active components of Traditional Chinese Medicine. This study aimed to determine whether matrine exerts anti-PCV2 effects by regulating intestinal flora. In this study, fecal microbiota transplantation (FMT) was used to evaluate the effect of matrine on the intestinal flora of PCV2-infected Kunming (KM) mice. The expression of the Cap gene in the liver and the ileum, the relative expression of IL-1ß mRNA, and the Lactobacillus acidophilus (L. acidophilus) gene in the ileum of mice were determined by real-time quantitative polymerase chain reaction (qPCR). ELISA was used to analyze the content of secretory immunoglobulin A (SIgA) in small intestinal fluid. L. acidophilus was isolated and identified from the feces of KM mice in order to study its anti-PCV2 effect in vivo. The expression of the Cap gene in the liver and the ileum and the relative expression of L. acidophilus and IL-1ß mRNA in the ileum were determined by qPCR. The results showed that matrine could reduce the relative expression of IL-1ß mRNA by regulating intestinal flora, and that its pharmacological anti-PCV2 and effect may be related to L. acidophilus. L. acidophilus was successfully isolated and identified from the feces of KM mice. The in vivo experiment revealed that administration of L. acidophilus also reduced the relative expression of IL-1ß mRNA, and that it had anti-PCV2 effects in PCV2-infected mice. It was found that matrine could regulate the abundance of L. acidophilus in the gut of mice to exert an anti-PCV2 effect and inhibit PCV2-induced inflammatory response.

Target Discovery of Matrine against PRRSV in Marc-145 Cells via Activity-Based Protein Profiling.

Porcine reproductive and respiratory syndrome (PRRS) seriously endangers the sustainable development of the pig industry. Our previous studies have shown that matrine can resist porcine reproductive and respiratory syndrome virus (PRRSV) infection. This study aimed to explore the anti-PRRSV targets of matrine in Marc-145 cells. Biotin-labeled matrine 1 and 2 were used as probes. MTT assay was used to determine the maximum non-cytotoxic concentration (MNTC) of each probe in Marc-145 cells. The anti-PRRSV activity of each probe was evaluated via MTT, qPCR and Western blot, and its anti-inflammatory activity was evaluated via qPCR and Western blot. The targets of matrine in Marc-145 cells were searched using activity-based protein profiling (ABPP), and compared with the targets predicted via network pharmacology for screening the potential targets of matrine against PRRSV. The protein-protein interaction networks (PPI) of potential targets were constructed using a network database and GO/KEGG enrichment analysis was performed. ACAT1, ALB, HMOX1, HSPA8, HSP90AB1, PARP1 and STAT1 were identified as potential targets of matrine, and their functions were related to antiviral capacity and immunity. Matrine may play an anti-PRRSV role by directly acting on ACAT1, ALB, HMOX1, HSPA8, HSP90AB1, PARP1 and STAT1.

Tailoring a local acid-like microenvironment for efficient neutral hydrogen evolution.

Electrochemical hydrogen evolution reaction in neutral media is listed as the most difficult challenges of energy catalysis due to the sluggish kinetics. Herein, the Ir-HxWO3 catalyst is readily synthesized and exhibits enhanced performance for neutral hydrogen evolution reaction. HxWO3 support is functioned as proton sponge to create a local acid-like microenvironment around Ir metal sites by spontaneous injection of protons to WO3, as evidenced by spectroscopy and electrochemical analysis. Rationalize revitalized lattice-hydrogen species located in the interface are coupled with Had atoms on metallic Ir surfaces via thermodynamically favorable Volmer-Tafel steps, and thereby a fast kinetics. Elaborated Ir-HxWO3 demonstrates acid-like activity with a low overpotential of 20 mV at 10 mA cm-2 and low Tafel slope of 28 mV dec-1, which are even comparable to those in acidic environment. The concept exemplified in this work offer the possibilities for tailoring local reaction microenvironment to regulate catalytic activity and pathway.

Kynurenine monooxygenase regulates inflammation during critical illness and recovery in experimental acute pancreatitis.

Kynurenine monooxygenase (KMO) blockade protects against multiple organ failure caused by acute pancreatitis (AP), but the link between KMO and systemic inflammation has eluded discovery until now. Here, we show that the KMO product 3-hydroxykynurenine primes innate immune signaling to exacerbate systemic inflammation during experimental AP. We find a tissue-specific role for KMO, where mice lacking Kmo solely in hepatocytes have elevated plasma 3-hydroxykynurenine levels that prime inflammatory gene transcription. 3-Hydroxykynurenine synergizes with interleukin-1ß to cause cellular apoptosis. Critically, mice with elevated 3-hydroxykynurenine succumb fatally earlier and more readily to experimental AP. Therapeutically, blockade with the highly selective KMO inhibitor GSK898 rescues the phenotype, reducing 3-hydroxykynurenine and protecting against critical illness and death. Together, our findings establish KMO and 3-hydroxykynurenine as regulators of inflammation and the innate immune response to sterile inflammation. During critical illness, excess morbidity and death from multiple organ failure can be rescued by systemic KMO blockade.

A diagnostic scoring model of ENKTCL in the nose-Waldeyer's ring based on logistic regression: Differential diagnosis from DLBCL.

Objective: To establish a logistic regression model based on CT and MRI imaging features and Epstein-Barr (EB) virus nucleic acid to develop a diagnostic score model to differentiate extranodal NK/T nasal type (ENKTCL) from diffuse large B cell lymphoma (DLBCL). Methods: This study population was obtained from two independent hospitals. A total of 89 patients with ENKTCL (n = 36) or DLBCL (n = 53) from January 2013 to May 2021 were analyzed retrospectively as the training cohort, and 61 patients (ENKTCL=27; DLBCL=34) from Jun 2021 to Dec 2022 were enrolled as the validation cohort. All patients underwent CT/MR enhanced examination and EB virus nucleic acid test within 2 weeks before surgery. Clinical features, imaging features and EB virus nucleic acid results were analyzed. Univariate analyses and multivariate logistic regression analyses were performed to identify independent predictors of ENKTCL and establish a predictive model. Independent predictors were weighted with scores based on regression coefficients. A receiver operating characteristic (ROC) curve was created to determine the diagnostic ability of the predictive model and score model. Results: We searched for significant clinical characteristics, imaging characteristics and EB virus nucleic acid and constructed the scoring system via multivariate logistic regression and converted regression coefficients to weighted scores. The independent predictors for ENKTCL diagnosis in multivariate logistic regression analysis, including site of disease (nose), edge of lesion (blurred), T2WI (high signal), gyrus like changes, EB virus nucleic acid (positive), and the weighted score of regression coefficient was 2, 3, 4, 3, 4 points. The ROC curves, AUCs and calibration tests were carried out to evaluate the scoring models in both the training cohort and the validation cohort. The AUC of the scoring model in the training cohort were 0.925 (95% CI, 0.906-0.990) and the cutoff point was 5 points. In the validation cohort, the AUC was 0.959 (95% CI, 0.915-1.000) and the cutoff value was 6 points. Four score ranges were as follows: 0-6 points for very low probability of ENKTCL, 7-9 points for low probability; 10-11 points for middle probability; 12-16 points for very high probability. Conclusion: The diagnostic score model of ENKTCL based on Logistic regression model which combined with imaging features and EB virus nucleic acid. The scoring system was convenient, practical and could significantly improve the diagnostic accuracy of ENKTCL and the differential diagnosis of ENKTCL from DLBCL.

Baicalin ameliorates high fat diet-induced nonalcoholic fatty liver disease in mice via adenosine monophosphate-activated protein kinase-mediated regulation of SREBP1/Nrf2/NF-κB signaling pathways.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease around the world, imposing severe threats on human health. Unfortunately, no clinically approved drugs are available for use as yet. Baicalin (BA) is reported to have hepatoprotective effects, and it is not clear whether BA can treat NAFLD and how. Here, a high-fat diet (HFD)-induced NAFLD mouse model was established to explore the protective roles and mechanisms of BA against HFD-induced NAFLD. Physiochemical results showed that BA exhibited significantly protective effects against HFD-induced NAFLD in mice. Liver transcriptomic analysis revealed that BA attenuated HFD-induced NAFLD via activating AMPK pathway, which was confirmed by the AMPK inhibitor Compound C. Additionally, the expression changes of AMPK downstream genes demonstrated that BA exerted ameliorative effects against NAFLD through AMPK-mediated inhibition of SREBP1 and NF-κB pathways, and activation of Nrf2 pathway. Taken together, our study reveals the protective roles of BA against HFD-caused NAFLD through AMPK-mediated modulation of SREBP1/Nrf2/NF-κB pathways, suggesting that BA has potential drug development implications. Most importantly, our study creates a paradigm through the combination of molecular biology and bioinformatics for further studies of action mechanisms of biomolecules combating diseases.

Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model.

BACKGROUND: Porcine circovirus type 2 (PCV2) is one of the major pathogens commonly found in pigs, which causes immunosuppression and apoptosis. Vaccination and a single drug cannot totally prevent and treat PCV2 infection. Our previous in vitro study reported that the synergistic anti-PCV2 effect of Matrine and Osthole was better than that of Matrine or Osthole alone, This study was aimed to evaluate the synergistic anti-PCV2 effect as well as the underline molecular mechanism of Matrine and Osthole in Kunming (KM) mice model infected with PCV2. KM mice were randomly divided into 8 groups namely control group, PCV2 infected, Matrine combined with Osthole high dose treatment (40 mg/kg + 12 mg/kg), medium dose treatment (20 mg/kg + 6 mg/kg), low dose treatment (10 mg/kg + 3 mg/kg), Matrine treatment (40 mg/kg), Osthole treatment (12 mg/kg) and Ribavirin positive control (40 mg/kg) groups. PCV2 was intraperitoneally (i.p.) injected in all mice except the control group. 5 days of post-infection (dpi), mice in different treatment groups were injected i.p. with various doses of Matrine, Osthole and Ribavirin once daily for the next 5 consecutive days. RESULTS: The synergistic inhibitory effect of Matrine and Osthole on PCV2 replication in mouse liver was significantly heigher than that of Matrine and Osthole alone. The expression of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, cleaved caspase-3 and Bax proteins were significantly reduced, while that of Bcl-2 was significantly increased in Matrine combined with Osthole groups, which alleviated the pathological changes caused by PCV2, such as interstitial pneumonia, loss of spleen lymphocytes, infiltration of macrophages and eosinophils. CONCLUSIONS: The synergistic anti-apoptotic effect of Matrine and Osthole was better than their alone effect, Both Matrine and Osthole had directly inhibited the expression of PCV2 Cap and the apoptosis of spleen cells induced by PCV2 Cap through the PERK pathway activated by endoplasmic reticulum (ER) GRP78. These results provided a new insight to control PCV2 infection and provide good component prescription candidate for the development of novel anti-PCV2 drugs.

Curcumol inhibits EMCV replication by activating CH25H and inhibiting the formation of ROs.

BACKGROUND: Zedoary turmeric oil extracted from the roots of curcuma (Curcuma aeruginosa Roxb.) is used for the treatment of myocarditis in China. EMCV infection causes abortion in pregnant sows and myocarditis in piglets. Our previous studies demonstrated that curcumol significantly increased the expression of IFN-ß in EMCV infected HEK-293T cells. The present results showed that curcumol inhibits EMCV replication by interfering the host cell cholesterol homeostasis and reducing ROs production through activation of the JAK/STAT signaling pathway. METHOD: This study was designed to explore whether curcumol can inhibit the replication of encephalomyocarditis viruses (EMCV) in cell culture. The expression level of JAK1, IRF9, STAT2, P-STAT2, CH25H, PI4KA and OSBP in EMCV-infected HEK-293T cells treated with curcumol, ribavirin or hydroxypropyl-ß-CD (HPCD) were determined by Western blotting (WB). The cholesterol level in EMCV infected HEK-293T cells treated with curcumol and HPCD were detected using Amplex™ Red Cholesterol Assay Kit. The antiviral effects of curcumol and HPCD on EMCV were also quantitatively detected by real-time fluorescence quantitative PCR (q-PCR). The amount and morphology of ROs were observed by transmission electron microscopy (TEM). RESULTS: The results demonstrated that curcumol significantly (P < 0.05) increased the expression of JAK1, IRF9, P-STAT2 and CH25H proteins, while that of STAT2, PI4KA and OSBP were remained unchanged. Compared with virus group (0.134 µg.µg-1 proteins), the total cholesterol level was significantly (P < 0.05) reduced by curcumol (0.108 µg.µg-1 proteins) and HPCD (0.089 µg.µg-1 proteins). Compared with virus group (88237 copies), curcumol (41802 copies) and HPCD (53 copies) significantly (P < 0.05) reduced EMCV load. Curcumol significantly reduced the production of ROs in EMCV-infected HEK-293T cells and activated CH25H through the JAK/STAT signaling pathway. CONCLUSION: Curcumol inhibited EMCV replication by affecting the cholesterol homeostasis and the production of ROs in HEK-293T cell.

Study on the mechanism of scutellarin's protective effect against ZEA-induced mouse ovarian granulosa cells injury.

Zearalenone (ZEA), a mycotoxin produced by Fusarium, can cause reproductive disorders by targeting ovarian granulosa cells (GCs). We previous showed that scutellarin (Scu) rescues ZEA-induced GCs damage in mice. In this study, we employed iTRAQ-based proteomics to investigate the mechanism underlying the restorative effects of Scu in this model. Compared to the model group, we identified 415 differentially expressed proteins (DEPs) in both the control and Scu-treated groups, and found that these were enriched mainly in the biosynthesis and metabolism, drug metabolism, and pentose phosphate pathway. Moreover, the MAPK and heat shock protein-necroptosis pathway were implicated in regulating ZEA toxicity and the protective effect of Scu. Receptor-interacting serine threonine-protein kinase 1 (RIPK1) showed the highest fold-change in expression in the Scu-treated group. Small-interfering RNA-mediated RIPK1 knockdown further promoted the increase in cleaved-caspase-3 expression induced by ZEA, but not in the cells treated with Scu. These data indicated the involvement of multiple targets and pathways in the protective effect of Scu against ZEA-induced damage. Our findings also indicated that RIPK1 may be involved in the inhibition of GCs apoptosis induced by ZEA.

MRI Extraprostatic Extension Grade: Accuracy and Clinical Incremental Value in the Assessment of Extraprostatic Cancer.

Objective: The purpose was to compare the accuracy of extraprostatic extension (EPE) grade on MRI predicting EPE with Partin tables, Memorial Sloan Kettering Cancer Center nomogram (MSKCCn), and combined models and to analyze the clinical incremental value of EPE grade. Materials and Methods: 105 prostate cancer patients confirmed by pathology after radical prostatectomy in our hospital from 2017 to 2021 were selected. The clinical stage, PSA, Gleason score, number of positive biopsy cores, and percentage of positive biopsy cores were recorded. Evaluate EPE grade according to EPE grade criteria, and calculate the probability of predicting EPE with Partin tables and MSKCCn. EPE grade is combined with Partin tables and MSKCCn to construct EPE grade+Partin tables and EPE grade+MSKCCn models. Calculate the area under the curve (AUC), sensitivity, and specificity of EPE grade, Partin tables, MSKCCn, EPE grade+Partin tables, and EPE grade+MSKCCn and compare their diagnostic efficacy. The clinical decision curve was used to analyze the clinical net income of each prediction scheme. Results: The AUC of EPE grade was 0.79, Partin tables was 0.50, MSKCCn was 0.78, the EPE grade+Partin table model was 0.79, and the EPE grade+MSKCCn model was 0.83. After EPE grade was combined with Partin tables and MSKCCn, the diagnostic efficiency of clinical model was significantly improved (P < 0.05). There was no significant difference in the diagnostic efficacy of the combined model compared with the single EPE grade (P > 0.05). The calibration curve of the combined model shows that it has a good calibration degree for EPE. In the analysis of the decision curve, the net income of the EPE grade is higher than that of Partin tables and MSKCCn and is equal to the EPE grade+Partin tables and is slightly lower than that of EPE grade+MSKCCn. The clinical net income of the combined model is obviously higher than that of individual clinical models. Conclusion: The accuracy of EPE classification in predicting prostate cancer EPE is high, and combined with the clinical model, it can significantly improve the diagnostic efficiency of the clinical model and increase the clinical benefit.

Deoxynivalenol damages the intestinal barrier and biota of the broiler chickens.

BACKGROUND: In the livestock feed industry, feed and feed raw materials are extremely susceptible to mycotoxin contamination. Deoxynivalenol (DON) is one of the main risk factors for mycotoxin contamination in broiler feed and feedstuff, however, there is still little knowledge about this. Hence, the purpose of this study was to explore the toxicity effect of DON on the intestinal barrier and the microecological balance of the biota in broiler chickens. RESULTS: In our present study, we compared the pathological scores of the small intestines of broilers on the 5th, 7th, and 10th day, and chose the 7th day to analyze the small intestine histomorphology, tight junctions, and cecal biota of the broilers. The results showed the damage to the small intestine worsened over time, the small intestinal villi of broilers were breakage, the tight junctions of the small intestine were destroyed, the cecal biota was unbalanced, and the growth performance of broilers was reduced on the 7th day. CONCLUSIONS: DON could damage the functional and structural completeness of the intestinal tract, disorder the Intestinal biota, and finally lead to declined broiler performance. Our study provided a basis for the prevention and treatment of DON in broiler production.

A Trifunctional Ni-P/Fe-P Collaborated Electrocatalyst Enables Self-Powered Energy Systems.

Recently, extensive research efforts have been devoted to drive electrocatalytic water-splitting for hydrogen generation by electricity or solar cells. However, electricity from power grid and the intermittent property of sunlight inevitably brings about environmental pollution and energy loss. Thus, a novelty energy system for simultaneous generating H2 from solar energy and overcoming the intermittence of sunlight is highly desirable. Herein, a self-powered energy system with solar energy as the sole input energy is successfully assembled by integrated Zn-air batteries with stable output voltage, solar cells, and water splitting electrolyzer to efficient H2 production. Specially, the Zn-air batteries are charged by the solar cell to store intermitted solar energy as electricity during light reaction. Under unassisted light reaction, the batteries could release electric energy to drive H2 production. Therefore, the aim for simultaneous generating H2 and eliminating the restrictions of intermittent sunlight are realized. The solar-to-hydrogen efficiency and solar-to-water splitting device efficiency of the self-powered energy system are up to 4.6% and 5.9%, respectively. This work provides the novel design systems for H2 production and the usage of renewable energy.

Fe2 Dimers for Non-Polar Diatomic O2 Electroreduction.

Non-polar diatomic molecule activation is of great significance for catalysis. Despite the high atomic efficiency, the catalytic performance of single-atom catalysts is limited by insufficient receiving sites for diatomic molecule adsorption. Here, Fe2 dimers were successfully synthesized through precisely regulating the metal loading on metal-organic frameworks. The unique role of metal dimers in activating diatomic O2 molecules was explored. In alkaline electrolytes, the specific oxygen reduction reaction activity of Fe2 dimers was 7 times higher than that of Fe1 counterparts. The hydrogen atom transfer probes indicated a different activation mode for O2 on Fe1 and Fe2 dimers, respectively. Theoretical calculation results revealed that Fe2 dimers opened up a new reaction pathway by promoting the direct breaking of O=O bonds, thus avoiding the usual formation of *OOH intermediates, which helped explain the lower H2 O2 yield and higher specific activity.

Strong Oxide-Support Interaction over IrO2 /V2 O5 for Efficient pH-Universal Water Splitting.

Constructing strong oxide-support interaction (SOSI) is compelling for modulating the atomic configurations and electronic structures of supported catalysts. Herein, ultrafine iridium oxide nanoclusters (≈1 nm) are anchored on vanadium oxide support (IrO2 /V2 O5 ) via SOSI. The as made catalyst, with a unique distorted IrO2 structure, is discovered to significantly boost the performance for pH-universal oxygen evolution reaction (OER). Based on experimental results and theoretical calculations, the distorted IrO2 active sites with flexible redox states in IrO2 /V2 O5 server as electrophilic centers balance the adsorption of oxo-intermediates and effectively facilitate the process of OO coupling, eventually propelling the fast turnover of water oxidation. As a result, IrO2 /V2 O5 demonstrates not only ultralow overpotentials at 10 mA cm-2 (266 mV, pH = 0; 329 mV, pH = 7; 283 mV, pH = 14) for OER, but also high-performance overall water electrolysis over a broad pH range, with a potential of mere 1.50 V (pH = 0), 1.65 V (pH = 7) or 1.49 V (pH = 14) at 10 mA cm-2 . In addition, SOSI can simultaneously secure the distorted active sites and thus remarkably improving the catalytic stability, making it a promising strategy to develop high-performance catalytic systems.

Molecular Patterns in Acute Pancreatitis Reflect Generalizable Endotypes of the Host Response to Systemic Injury in Humans.

OBJECTIVE: Acute Pancreatitis (AP) is sudden onset pancreas inflammation that causes systemic injury with a wide and markedly heterogeneous range of clinical consequences. Here, we hypothesized that this observed clinical diversity corresponds to diversity in molecular subtypes that can be identified in clinical and multiomics data. SUMMARY BACKGROUND DATA: Observational cohort study. n = 57 for the discovery cohort (clinical, transcriptomics, proteomics, and metabolomics data) and n = 312 for the validation cohort (clinical and metabolomics data). METHODS: We integrated coincident transcriptomics, proteomics, and metabolomics data at serial time points between admission to hospital and up to 48 hours after recruitment from a cohort of patients presenting with acute pancreatitis. We systematically evaluated 4 different metrics for patient similarity using unbiased mathematical, biological, and clinical measures of internal and external validity.We next compared the AP molecular endotypes with previous descriptions of endotypes in a critically ill population with acute respiratory distress syndrome (ARDS). RESULTS: Our results identify 4 distinct and stable AP molecular endotypes. We validated our findings in a second independent cohort of patients with AP.We observed that 2 endotypes in AP recapitulate disease endotypes previously reported in ARDS. CONCLUSIONS: Our results show that molecular endotypes exist in AP and reflect biological patterns that are also present in ARDS, suggesting that generalizable patterns exist in diverse presentations of critical illness.

Interfacial Assembly of Nanowire Arrays toward Carbonaceous Mesoporous Nanorods and Superstructures.

Synthesis of anisotropic carbonaceous nano- and micro-materials with well-ordered mesoporous structures has attracted increasing attention for a broad scope of applications. Although hard-templating method has been widely employed, overcoming the viscous forces to prepare anisotropic mesoporous materials is particularly challenging via the universal soft-templating method, especially from sustainable biomass as a carbon resource. Herein, the synthesis of biomass-derived nanowire-arrays based mesoporous nanorods and teeth-like superstructures is reported, through a simple and straightforward polyelectrolyte assisted soft-templating hydrothermal carbonization (HTC) approach. A surface energy induced interfacial assembly mechanism with the synergetic interactions between micelles, nanowire, nanorods, and polyelectrolyte is proposed. The polyelectrolyte acts not only as a stabilizer to decrease the surface energy of cylindrical micelles, nanowires and nanorods, but also as a structure-directing agent to regulate the oriented attachment and anisotropic assembly of micelles, nanowires, and nanorods. After a calcination treatment, the carbon nanorod and teeth-like superstructure are successfully coupled with Ru to directly produce supported catalysts for the hydrogen evolution reaction, exhibiting much better performance than the isotropic nanospheres based catalyst. This HTC approach will open up new avenues for the synthesis of anisotropic materials with various morphologies and dimensions, expanding the palette of materials selection for many applications.

A nomogram diagnostic prediction model of pancreatic metastases of small cell lung carcinoma based on clinical characteristics, radiological features and biomarkers.

Objective: To investigate clinical characteristics, radiological features and biomarkers of pancreatic metastases of small cell lung carcinoma (PM-SCLC), and establish a convenient nomogram diagnostic predictive model to differentiate PM-SCLC from pancreatic ductal adenocarcinomas (PDAC) preoperatively. Methods: A total of 299 patients with meeting the criteria (PM-SCLC n=93; PDAC n=206) from January 2016 to March 2022 were retrospectively analyzed, including 249 patients from hospital 1 (training/internal validation cohort) and 50 patients from hospital 2 (external validation cohort). We searched for meaningful clinical characteristics, radiological features and biomarkers and determined the predictors through multivariable logistic regression analysis. Three models: clinical model, CT imaging model, and combined model, were developed for the diagnosis and prediction of PM-SCLC. Nomogram was constructed based on independent predictors. The receiver operating curve was undertaken to estimate the discrimination. Results: Six independent predictors for PM-SCLC diagnosis in multivariate logistic regression analysis, including clinical symptoms, CA199, tumor size, parenchymal atrophy, vascular involvement and enhancement type. The nomogram diagnostic predictive model based on these six independent predictors showed the best performance, achieved the AUCs of the training cohort (n = 174), internal validation cohort (n = 75) and external validation cohort (n = 50) were 0.950 (95%CI, 0.917-0.976), 0.928 (95%CI, 0.873-0.971) and 0.976 (95%CI, 0.944-1.00) respectively. The model achieved 94.50% sensitivity, 83.20% specificity, 86.80% accuracy in the training cohort and 100.00% sensitivity, 80.40% specificity, 86.70% accuracy in the internal validation cohort and 100.00% sensitivity, 88.90% specificity, 87.50% accuracy in the external validation cohort. Conclusion: We proposed a noninvasive and convenient nomogram diagnostic predictive model based on clinical characteristics, radiological features and biomarkers to preoperatively differentiate PM-SCLC from PDAC.

Network pharmacology-based study on the mechanism of scutellarin against zearalenone-induced ovarian granulosa cell injury.

Zearalenone(ZEA) is a kind of mycotoxin widely existing in nature, its toxic effects can lead to the reproductive disorders in humans and animals. The aim of this study was to investigate the mechanism of scutellarin against ovarian granulosa cell(GCs) injury induced by ZEA based on network pharmacology, molecular docking method. The results show that 293 drug targets of scutellarin were found from PhamMapper database, and 583 disease targets were selected from Genecards database. Finally, 57 scutellarin targets were obtained for the repair of GCs injury with gene intersection. The protein-protein interaction(PPI), gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) analysis indicated that MAPK signaling pathway was most likely activated by scutellarin. Scutellarin with JNK or Caspase-3 had minimal and negative free binding energy in molecular docking analysis, indicating that they might be the acting targets of scutellarin. Cell viability was significantly decreased in ZEA treated cells. However, GCs viability, the level of estradiol(E2) and progesterone(P4) were significantly increased with addition of scutellarin to ZEA treated cells. Western blot analysis showed that scutellarin significantly reduced the expression of JNK, c-jun and Cleaved-caspasee-3 in GCs compared with ZEA treatment. In conclusion, scutellarin could alleviate the ovarian GCs injury by down-regulating the expression of JNK, c-jun and Cleaved-caspase-3 through the activation of MAPK/JNK signaling pathway. Our results will provide a theoretical foundation for the treatment of reproductive disorders with scutellarin.