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Bile acids are liver-derived signaling molecules that can be found in the brain, but their role there remains largely unknown. We found increased brain chenodeoxycholic acid (CDCA) in mice with absent 12α-hydroxylase (Cyp8b1), a bile acid synthesis enzyme. In these Cyp8b1−/−, and in Wt mice administered CDCA, stroke infarct area was reduced. Elevated glutamate-induced excitotoxicity mediated by aberrant N-methyl-D-aspartate receptor (NMDAR) overactivation contributes to neuronal death in ischemic stroke. We found reduced glutamate-induced excitotoxicity in neurons from Cyp8b1−/− and CDCA-treated Wt mice. CDCA decreased NMDAR-mediated excitatory post-synaptic currents by reducing over-activation of NMDAR subunit GluN2B in Wt brains. Synaptic NMDAR activity was also decreased in Cyp8b1−/− brains. Expression and synaptic distribution of GluN2B were unaltered in Cyp8b1−/− mice, suggesting CDCA may directly antagonize GluN2B-containing NMDARs. Supporting our findings, in a case-control cohort of acute ischemic stroke patients, we found lower circulatory CDCA. Together, our data suggest that CDCA, acting in the liver-brain axis, decreases GluN2B-containing NMDAR overactivation, contributing to neuroprotection in stroke.

Introduction: EGFR tyrosine kinase inhibitor (TKI) is the standard adjuvant treatment for patients with stages IB to IIIA EGFR-mutated NSCLC. Nevertheless, adapting this approach to include a molecular residual disease (MRD)-guided de-escalation strategy warrants further investigation. Methods: From January 2019 to December 2022, 71 patients with stages I to III NSCLC and EGFR (exon 19 deletion or L858R) mutations were enrolled in this observational study. A total of 375 blood samples were analyzed using the MRD_Navigator assay. Among them, 27 patients suspended EGFR TKI treatment based on undetectable MRD and were thus included in the adaptive, de-escalation group. Results: Overall, the sensitivity of longitudinal MRD was 86.2%. Only four patients (11.8%) recurred with longitudinal undetectable MRD, indicating a negative predictive value of 88.2%. Of the patients who had detectable MRD after surgery, nine subsequently received EGFR TKI treatment, with only one (11.1%) achieving persistent circulating tumor DNA clearance post–EGFR TKI. Furthermore, 22 patients with stages IB to III disease who had previously suspended their TKI treatment based on undetectable MRD were included in the adaptive group, with an average duration of TKI 3.9 (range: 0–35.0) months. The 2-year disease-free survival rate of these 22 patients was 80.2%, and the median was not reached. Five patients (n = 5 of 22, 22.7%) had disease recurrence during the period of drug cessation but were stable under EGFR TKI treatment until the latest follow-up. Two patients remained in complete remission. Conclusions: Our initial findings underscore the potential of an adaptive, de-escalation approach to adjuvant EGFR TKIs based on circulating tumor DNA-MRD monitoring.

The chemical composition of the essential oil from the fruits and leaves of Litsea cubeba (Lour.) Pers. (Lauraceae) growing wild in Baoshan region, Yunnan Province of China was investigated for the first time in 5.36% and 2.16% (w/w) yields, respectively, when analysed by GC and GC/MS. Ten and 25 components were identified in the fruit and leaf oils which constituted 99.15% and 99.4% of the oils. Of the fruit oil, the major components were neral (36.51%), geranial (44.23%), and citronella (8.77%). The major components of the leaf oil were linalool (67.37%), limonene (6.37%), β-bisabolene (6.03%), neral (5.86%), and caryophyllene oxide (3.20%). The analysis of the essential oil obtained from Baoshan revealed a significant abundance of citral and linalool in the fruits and leaves, respectively. This was the first Litsea species to exhibit β-bisabolene as the principal constituent. [ABSTRACT FROM AUTHOR]

The use of data fusion based with multiple analytical techniques was investigated to provide the accurate geographical origin identification of Atractylodes macrocephala Koidz. (AMK). Inductively coupled plasma - mass spectrometry (ICP-MS), gas chromatography - mass spectrometry (GC-MS) and liquid chromatography - mass spectrometry (LC-MS) were used to characterize Hubei, Zhejiang, and Hunan production regions. After the implementation of data fusion, the ensemble learning method multi-forest joint network (MFJN) and classic machine learning methods were used to identify the AMK production regions. The MFJN based upon high-level data fusion distinguished AMK samples from different regions with the highest accuracy. The classification accurate rate of AMK in the prediction set was 95%, which was significantly better than the results obtained using twenty-five mineral element or nine bioactive component data sets. The results showed that mass spectrometry data fusion in combination with MFJN is suitable for the geographic origin determination of AMK and has potential to ensure this product's fair trade. [ABSTRACT FROM AUTHOR]

Background: Although immunotherapy has achieved great progress in advanced triple-negative breast cancer (TNBC), there are still numerous patients who do not benefit from immunotherapy. Therefore, identification of the key molecule that induces immune escape and clarification of its specific mechanism in TNBC are urgently needed. Methods: In this research, single cell sequencing and bulk sequencing were conducted for biomarker screening. Immunohistochemistry, multiplex immunofluorescence, and orthotopic TNBC tumor model were applied in identifying the key molecule driving immune escape. At the mechanical level, RNA sequencing, in vitro co-culturing system, flow cytometry, Western blotting, ELISA, and real-time qPCR were carried out. Results: Mortality factor 4 like 2 (MORF4L2) expression is significantly up-regulated among patients who developed anti-PD1 resistance. MORF4L2 enhances anti-PD1 resistance by inducing the chemotaxis of macrophage infiltration and promoting their polarization towards the alternative activation phenotype (M2), thus creating an immunosuppressive microenvironment. Mechanistically, MORF4L2 actes as part of NuA4 histone acetyltransferase (HAT) complex, contributes to to histone 4 lysine 12 acetylation (H4K12Ac) and activates the downstream transcription of macrophage colony-stimulating factor (CSF1). CSF1 is secreted by tumor cells and binds to the macrophage-surface CSF1 receptor (CSF1R), which chemotactically converted and polarized macrophages to the M2 phenotype. Furthermore, we revealed that grainyhead like transcription factor 2 (GRHL2) could promote MORF4L2 transcription by binding to the MORF4L2 enhancer region. Notably, BLZ549, an inhibitor of CSF1R, restored the anti-PD1 sensitivity by blocking the GRHL2/MORF4L2/H4K12Ac/CSF1 axis. Conclusions: GRHL2/MORF4L2/H4K12Ac/CSF1 axis plays an important role in anti-PD1 resistance. CSF1R inhibitors can reverse GRHL2/MORF4L2-mediated anti-PD1 resistance. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the clinical application value of the central venous-arterial carbon dioxide partial pressure difference (Pv-aCO2) in postoperative cognitive dysfunction(POCD) in patients with acute aortic dissection. Methods: A retrospective analysis was conducted on the general data of 236 patients. Blood gas samples were collected from the arterial and venous lines at various time points during the surgery, including before and after the initiation of cardiopulmonary bypass (CPB), immediately after CPB initiation, before and after deep hypothermic circulatory arrest, 30 min after rewarming, and 5 min before weaning from CPB. The partial PV-aCO2 was calculated. Based on the average PV-aCO2 value, patients were divided into an observation group (PV-aCO2 > 6 mmHg, n = 112) and a control group (PV-aCO2 < 6 mmHg, n = 124). The perioperative data and Mini-Mental State Examination (MMSE) scores were compared between the two groups to assess the incidence and severity of POCD. Additionally, the expression levels of peripheral serum S100β in the two groups were compared 6 h postoperatively. Results: The incidence of POCD was higher in the observation group compared to the control group, while MMSE scores and serum S100β levels were lower in the observation group. Additionally, the observation group patients with POCD had lower MMSE scores and serum S100β levels compared to the control group patients. In addition, logistic regression analysis revealed that advanced age, serum S100β levels, female gender, CPB time, unilateral brain perfusion time, hyperlipidemia, diabetes, and smoking history were all independent risk factors for postoperative POCD (all P < 0.05). Conclusion: Pv-aCO2 can effectively reflect the intraoperative cerebral metabolic level in patients with acute aortic dissection and can serve as an intraoperative warning indicator for cognitive dysfunction. Its clinical recommendation for use is warranted. [ABSTRACT FROM AUTHOR]

As a cultural component of Xi Jinping Thought on Socialism with Chinese Characteristics for a New Era, Xi Jinping Thought on Culture underscores the strategic importance of publicity, and moral and cultural education in the new era. In today' s digital age, the publicity of Xi Jinping Thought on Culture has entered a new arena, where the empowerment of digital technology has become both a necessary requirement and an inevitable choice. This empowerment facilitates targeted dissemination, promotes multi-dimensional presentation, and strengthens international recognition of Xi Jinping Thought on Culture. However, the application of digital technology also presents risks and challenges for its communication. To fully harness the positive potential of digital technology, it is essential to explore optimization pathways for disseminating Xi Jinping Thought on Culture from four key aspects: content, discourse, subjects, and technology of communication. These efforts will help foster a new phase in the construction of socialism with Chinese characteristics and better fulfill the cultural mission of the new era. [ABSTRACT FROM AUTHOR]

A new twofold interpenetrated 3D metal–organic framework (MOF), namely, poly[[μ‐aqua‐diaqua{μ4‐2,2′‐[terephthaloylbis(azanediyl)]diacetato}barium(II)] dihydrate], {[Ba(C12H10N2O6)(H2O)3]·2H2O}n, (I), has been assembled through a combination of the reaction of 2,2′‐[terephthaloylbis(azanediyl)]diacetic acid (TPBA, H2L) with barium hydroxide and crystallization at low temperature. In the crystal structure of (I), the nine‐coordinated BaII ions are bridged by two μ2‐aqua ligands and two carboxylate μ2‐O atoms to form a 1D loop‐like Ba–O chain, which, together with the other two coordinated water molecules and μ2‐carboxylate groups, produces a rod‐like secondary building unit (SBU). The resultant 1D polynuclear SBUs are further extended into a 3D MOF via the terephthalamide moiety of the ligand as a spacer. Two intramolecular dihydrogen bonds (DHBs) between the imine H atoms and the arene H atoms contribute to maintaining the 3D structure. In the crystal, two independent MOFs interpenetrate each other, thereby producing a twofold interpenetrated 3D architecture with a 4‐connected PtS‐X topology. Intermolecular hydrogen bonding and π–π interactions contribute to the stability of the twofold interpenetrated 3D architecture. The noncovalent interactions in the coordination polymer (CP) were further investigated by Hirshfeld surface analysis and the results show that the prominent interactions are H...O (39.6%) and H...H (34.4%), as well as Ba...O (9.8%), contacts. The 3D CP (I) exhibits a fluorescence emission with a quantum yield of 0.134. [ABSTRACT FROM AUTHOR]

High moisture extrusion is a widely used technology for producing fibrous meat analogues in an efficient and scalable manner. Extrusion of soy, wheat gluten, and pea is well-documented and related products are already available in the market. There has been growing interest to diversify the protein sources used for meat analogues due to concerns over food waste, monocropping and allergenicity. Optimizing the extrusion process for plant proteins (e.g., hemp, mung bean, fava bean) tends to be time consuming and relies on the operators' intuition and experience to control the process well. Simulating the extrusion process has been challenging so far due to the diverse inputs and configurations involved during extrusion. This review details the mechanism for fibrous structure formation and provides an overview of the extrusion parameters used for texturizing a broad range of plant protein sources. Referring to these data reduces the resources needed for optimizing the extrusion process for novel proteins and may be useful for future extrusion modeling efforts. The review also highlights potential challenges and opportunities for extruding plant proteins, which may help to accelerate the development and commercialization of related products. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between sarcopenia, short-term efficacy, and long-term survival in patients with extensive small-cell lung cancer (SCLC) treated with standard first-line immunochemotherapy. Methods: A total of 63 patients initially diagnosed with extensive-stage small cell lung cancer were enrolled in the prospective study from December 1, 2020 to December 31, 2022. The clinical characteristics, body composition, blood test results, and image data were obtained before treatment. Patients were divided into sarcopenia and non-sarcopenia groups according to the diagnostic criteria of the Asian Sarcopenia Working Group 2019. The primary outcome was overall survival (OS) and comprehensive survival analyses were performed. Secondary outcomes included short-term efficacy and adverse events associated with first-line immunochemotherapy. Results: The median age of the 63 patients enrolled in our study was 63.0 years (40–80 years). The incidence of sarcopenia was 19.0% (12/63) in patients with extensive SCLC. Compared with non-sarcopenia patients, extensive-stage SCLC patients with sarcopenia were significantly older (69.0 vs. 62.0, P = 0.017), and had lower body mass index (BMI) (20.29 vs. 24.27, P < 0.001), hand grip strength (HGS) (20.42 vs. 30.75, P < 0.001), and albumin (35.9 vs. 41.40, P < 0.001). The objective response rate after two cycles of standard first-line immunochemotherapy in the sarcopenia group was lower than in the non-sarcopenia group (30.0 vs. 78.9%, P = 0.012). There was no significant difference in chemotherapy-related hematological toxicity between the two groups. During a median follow-up of 15 months (3–33 months), patients with extensive SCLC had a median OS of 24 months, with 1-year survival of 75% and 2-year survival of 52%, respectively. Compared to non-sarcopenia patients, the median OS in the sarcopenia group was significantly shorter (9 vs. 24 months, P = 0.0014). Multivariate Cox analysis showed that sarcopenia was an independent risk factor for OS in patients with extensive SCLC (HR = 4.993, 95%CI = 1.106–22.538, P = 0.037). Conclusions: Patients with Extensive SCLC and sarcopenia had worse clinical outcomes and shorter OS. Sarcopenia is a prognostic factor affecting first-line treatment efficacy and long-term survival of patients with SCLC in the era of immunotherapy. [ABSTRACT FROM AUTHOR]

This study aimed to prepare Gardenia fructus carbon dots (GF-CDs) and examine their efficacy in mitigating oxidative stress and apoptosis in intestinal porcine epithelial cells from the jejunum (IPEC-J2 cells) induced by lipopolysaccharide (LPS). The GF-CDs were synthesized using a one-step hydrothermal method. The oxidative damage model of IPEC-J2 cells was induced through LPS treatment. The potential mechanism by which GF-CDs affect cellular oxidative damage was examined through the perspectives of apoptosis, reactive oxygen species level, antioxidant-related enzyme index, mRNA transcription of antioxidant-related genes, and the expression of antioxidant proteins. The results revealed that GF-CDs, characterized by particle sizes<7 nm, abundant functional groups, and good water solubility, were synthesized using a one-step hydrothermal method. The carbon spots of Gardenia fructus at concentrations of 50, 100, and 200 μg/mL exhibited protective effects, as evidenced by their ability to enhance viability (P <0.01) and restore cellular morphology after oxidative damage. The GF-CDs decreased oxidative damage and reduced the apoptosis rate of cells by upregulating AKT1 expression and downregulating the expression of Caspase 3, STAT3, TNF-α, and JNK. These results indicate that GF-CDs have the characteristic physicochemical properties of CDs, exhibit biological activities related to antioxidation and cellular damage mitigation, and may serve as a potential healthcare product in swine raising. [ABSTRACT FROM AUTHOR]

Introduction: Inflammatory bowel disease (IBD), including ulcerative colitis, is marked by intestinal barrier disruptions, immune system dysregulation, and an imbalance in the gut microbiota. The golden chanterelle mushroom, Cantharellus cibarius Fr., a popular edible mushroom, has shown potential therapeutic benefits. This study examines the therapeutic potential of a crude polysaccharide extract obtained from C. cibarius Fr. (CCP) on intestinal barrier integrity, inflammatory cytokine levels, and gut microbiota composition in a murine model of colitis induced by dextran sulfate sodium (DSS). Methods: To induce colitis BALB/c mice were provided to consume autoclaved water with 3% DSS for 7 days, followed by 14 days of CCP supplementation. To assess the effects of CCP, histological analysis of colon tissue was performed, gene expression, inflammatory responses, tight junction proteins expression, gut barrier integrity, and cytokines levels were measured and analyzed and 16S rRNA sequencing were evaluated. Results and Discussion: CCP treatment alleviates colitis symptoms by improving body weight, and enhancing intestinal integrity through increased mucin-2 and tight junction protein expression. Additionally, CCP administration regulates the altered immune response by mitigating the expression of pro-inflammatory cytokines and upregulating anti-inflammatory cytokines. Furthermore, CCP supplementation effectively modulates DSS-induced dysbiosis as demonstrated by 16S rRNA sequencing results. These findings suggest that crude polysaccharides from the golden chanterelle mushroom, C. cibarius Fr., hold promise for treating colitis, via strengthening the intestinal barrier, regulating inflammatory responses, and reshaping the gut dysbiosis in a DSS-induced colitis model. CCP offers a novel approach for managing colitis, as a chronic inflammatory condition. [ABSTRACT FROM AUTHOR]

In 2018, the State Council issued the Three-year Action Plan for Winning the Blue Sky Defense War （Blue Sky Defense War）. To study the characteristics and sources of PM 2.5 pollution in the early stage （first stage）, middle stage （second stage）, and late stage （third stage） of the Blue Sky Defense War in Handan City in autumn and winter, PM 2.5 samples were collected in the autumn and winter from 2016 to 2021. Based on the concentration data of eight water-soluble ions, EC, and OC the source analysis was performed using the positive definite matrix factorization model, backward trajectory, and potential source contribution factor （PSCF） analysis. The results showed that in recent years, the annual and autumn-winter concentrations of PM 2.5 showed an overall decreasing trend, and the concentrations of water-soluble ions and total carbon decreased stage by stage during the three stages of sampling. The concentration in the third stage （52.70 μg·m -3 and 17.17 μg·m -3 ） decreased by 34.31% and 63.38% compared with that in the first stage （80.23 μg·m -3 and 46.89 μg·m -3 ）, respectively. The concentration of SNA in the three stages accounted for 46.79%, 48.86%, and 43.22% of the total concentration of PM 2.5 , respectively. The proportion of SOC in PM 2.5 was 12.43%, 14.05%, and 6.81%, all of which first increased and then decreased. The mean of SOR in the three stages was 0.34, 0.37, and 0.36, respectively, and NOR was 0.23, 0.28, and 0.28, indicating that the secondary transformation degree was the highest during the Blue Sky Defense War. From the perspective of pollutant sources, the main sources of PM 2.5 in Handan City were secondary, combustion sources, industrial sources, traffic sources, and dust sources. During the Blue Sky Defense War, the primary emissions decreased （mainly combustion sources and industrial sources）； afterward, the end of the primary emissions increased, of which the contribution rate of industrial sources increased from 12.17% to 20.20%. Moreover, the backward trajectory clustering analysis showed that the contribution rate of secondary sources in the second stage was significantly higher than that in other stages, especially the airflow from Shandong and Shanxi. The analysis of potential sources showed that the regions with high WPSCF values in the three stages were mainly concentrated in the south of Hebei and the north of Henan. The difference was that the potential source areas in the third stage shifted from the central part of Shanxi to the south compared with the first stage. This work confirms that the environmental benefits of the Blue Sky Defense War are obvious. With the development of the Blue Sky Defense War, the contribution of secondary components is prominent. After the Blue Sky Defense War, the proportion of secondary components decreased, the influence of primary components increased, and the control of direct emissions should be strengthened.