Stemness related lncRNAs signature for the prognosis and tumor immune microenvironment of ccRCC patients.

Long non-coding RNAs (lncRNAs) and cancer stem cells (CSCs) are crucial for the growth, migration, recurrence, and medication resistance of tumors. However, the impact of lncRNAs related to stemness on the outcome and tumor immune microenvironment (TIME) in clear cell renal cell carcinoma (ccRCC) is still unclear. In this study, we aimed to predict the outcome and TIME of ccRCC by constructing a stem related lncRNAs (SRlncRNAs) signature. We firstly downloaded ccRCC patients' clinical data and RNA sequencing data from UCSC and TCGA databases, and abtained the differentially expressed lncRNAs highly correlated with stem index in ccRCC through gene expression differential analysis and Pearson correlation analysis. Then, we selected suitable SRlncRNAs for constructing a prognostic signature of ccRCC patients by LASSO Cox regression. Further, we used nomogram and Kaplan Meier curves to evaluate the SRlncRNA signature for the prognose in ccRCC. At last, we used ssGSEA and GSVA to evaluate the correlation between the SRlncRNAs signature and TIME in ccRCC. Finally, We obtained a signtaure based on six SRlncRNAs, which are correlated with TIME and can effectively predict the ccRCC patients' prognosis. The SRlncRNAs signature may be a noval prognostic indicator in ccRCC.

Spontaneous-stimulated Raman co-localization dual-modal analysis approach for efficient identification of tumor cells.

The study of highly heterogeneous tumor cells, especially acute myeloid leukemia (AML) cells, usually relies on invasive analytical methods such as morphology, immunology, cytogenetics, and molecular biology classification, which are complex and time-consuming to perform. Mortality is high if patients are not diagnosed in a timely manner, so rapid label-free analysis of gene expression and metabolites within single-cell substructures is extremely important for clinical diagnosis and treatment. As a label-free and non-destructive vibrational detection technique, spontaneous Raman scattering provides molecular information across the full spectrum of the cell but lacks rapid imaging localization capabilities. In contrast, stimulated Raman scattering (SRS) provides a high-speed, high-resolution imaging view that can offer real-time subcellular localization assistance for spontaneous Raman spectroscopic detection. In this paper, we combined multi-color SRS microscopy with spontaneous Raman to develop a co-localized Raman imaging and spectral detection system (CRIS) for high-speed chemical imaging and quantitative spectral analysis of subcellular structures. Combined with multivariate statistical analysis methods, CRIS efficiently differentiated AML from normal leukocytes with an accuracy of 98.1 % and revealed the differences in the composition of nuclei and cytoplasm of AML relative to normal leukocytes. Compared to conventional Raman spectroscopy blind sampling without imaging localization, CRIS increased the efficiency of single-cell detection by at least three times. In addition, using the same approach for further identification of AML subtypes M2 and M3, we demonstrated that intracytoplasmic differential expression of proteins is a marker for their rapid and accurate classifying. CRIS analysis methods are expected to pave the way for clinical translation of rapid tumor cell identification.

Four new species of Russula from the Xizang Autonomous Region and other provinces of China.

Russula is the largest genus in the Russulales and is widespread throughout the world. Almost all Russula species are known to be ectomycorrhizal with high ecological and edible values, and some are lethal poisonous. In this study, four new species belonging to the subgenus Russula crown clade are identified based on morphological and phylogenetic evidence from the Xizang Autonomous Region and other provinces of China. Morphologically, Russula paragraveolens (sect. Polychromae, subsect. Xerampelinae) is mainly characterised by a cherry red to blood red pileus centre, a reddish orange pileus margin; R. pseudograveolens (sect. Polychromae, subsect. Xerampelinae) is characterised by a violet brown to brownish red pileus centre, a pale red to pastel red pileus margin and short basidia; R. shigatseensis (sect. Flavisiccantes, subsect. Lepidinae) is characterised by a brownish orange to madder red pileus centre, pinkish red pileus margin, and having lateral branches or branches of hyphal terminations in pileipellis; R. yadongensis (sect. Tenellae, subsect. Laricinae) is characterised by a dark purplish red pileus centre with brownish purple tints and having isolated to clustered spines of spore ornamentations. Their distinct taxonomic status is confirmed by the positions of the four new species in both the ITS and 4-locus (nucLSU, mtSSU, rpb2, tef1) phylogenetic trees.

Assessment of pulmonary physiological changes caused by aging, cigarette smoking, and COPD with hyperpolarized 129Xe magnetic resonance.

OBJECTIVE: To comprehensively assess the impact of aging, cigarette smoking, and chronic obstructive pulmonary disease (COPD) on pulmonary physiology using 129Xe MR. METHODS: A total of 90 subjects were categorized into four groups, including healthy young (HY, n = 20), age-matched control (AMC, n = 20), asymptomatic smokers (AS, n = 28), and COPD patients (n = 22). 129Xe MR was utilized to obtain pulmonary physiological parameters, including ventilation defect percent (VDP), alveolar sleeve depth (h), apparent diffusion coefficient (ADC), total septal wall thickness (d), and ratio of xenon signal from red blood cells and interstitial tissue/plasma (RBC/TP). RESULTS: Significant differences were found in the measured VDP (p = 0.035), h (p = 0.003), and RBC/TP (p = 0.003) between the HY and AMC groups. Compared with the AMC group, higher VDP (p = 0.020) and d (p = 0.048) were found in the AS group; higher VDP (p < 0.001), d (p < 0.001) and ADC (p < 0.001), and lower h (p < 0.001) and RBC/TP (p < 0.001) were found in the COPD group. Moreover, significant differences were also found in the measured VDP (p < 0.001), h (p < 0.001), ADC (p < 0.001), d (p = 0.008), and RBC/TP (p = 0.032) between the AS and COPD groups. CONCLUSION: Our findings indicate that pulmonary structure and functional changes caused by aging, cigarette smoking, and COPD are various, and show a progressive deterioration with the accumulation of these risk factors, including cigarette smoking and COPD. CLINICAL RELEVANCE STATEMENT: Pathophysiological changes can be difficult to comprehensively understand due to limitations in common techniques and multifactorial etiologies. 129Xe MRI can demonstrate structural and functional changes caused by several common factors and can be used to better understand patients' underlying pathology. KEY POINTS: Standard techniques for assessing pathophysiological lung function changes, spirometry, and chest CT come with limitations. 129Xe MR demonstrated progressive deterioration with accumulation of the investigated risk factors, without these limitations. 129Xe MR can assess lung changes related to these risk factors to stage and evaluate the etiology of the disease.

Natural products for the treatment of age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a chronic retinal disease that significantly influences the vision of the elderly. PURPOSE: There is no effective treatment and prevention method. The pathogenic process behind AMD is complex, including oxidative stress, inflammation, and neovascularization. It has been demonstrated that several natural products can be used to manage AMD, but systematic summaries are lacking. STUDY DESIGN AND METHODS: PubMed, Web of Science, and ClinicalTrials.gov were searched using the keywords "Biological Products" AND "Macular Degeneration" for studies published within the last decade until May 2023 to summarize the latest findings on the prevention and treatment of age-related macular degeneration through the herbal medicines and functional foods. RESULTS: The eligible studies were screened, and the relevant information about the therapeutic action and mechanism of natural products used to treat AMD was extracted. Our findings demonstrate that natural substances, including retinol, phenols, and other natural products, prevent the development of new blood vessels and protect the retina from oxidative stress in cells and animal models. However, they have barely been examined in clinical studies. CONCLUSION: Natural products could be highly prospective candidate drugs used to treat AMD, and further preclinical and clinical research is required to validate it to control the disease.

Structural modification and biomechanical analysis of lumbar disc prosthesis: A finite element study.

BACKGROUND: Most ball-in-socket artificial lumbar disc implanted in the spine result in increased hypermobility of the operative level and overloading of the facet joint. METHODS: A finite element model was established and validated for the lumbar spine (L1-L5). The structure of the Mobidisc prosthesis was modified, resulting in the development of two new intervertebral disc prostheses, Movcore and Mcopro. The prostheses were implanted into the L3/L4 level to simulate total disc replacement, and the biomechanical properties of the lumbar spine model were analyzed after the operation. FINDINGS: Following the implantation of the prostheses, the mobility of operative level, peak stress of lumbar spine models, and peak stress of facet joint increased. The performance of mobility was found to be more similar between Movcore and Mobidisc. The mobility and facet joint peak stress of the Mcopro model decreased progressively with an increase in the Young's modulus of the artificial annulus during flexion, extension, and lateral bending. Among all the models, the Mcopro50 model had the mobility closest to the intact model. It showed a 3% decrease in flexion, equal range of motion in extension, a 9% increase in left lateral bending, a 7% increase in right lateral bending, and a 3% decrease in axial rotation. INTERPRETATION: The feasibility of the new intervertebral disc prostheses, Movcore and Mcopro, has been established. The Mcopro prosthesis, which features an artificial annular structure, offers significant advantages in terms of reduced mobility of the operative level and peak stress of facet joint.

Chemical Structures, Biological Activities, and Biosynthetic Analysis of Secondary Metabolites from Agaricus Mushrooms: A Review.

Agaricus mushrooms are an important genus in the Agaricaceae family, belonging to the order Agaricales of the class Basidiomycota. Among them, Agaricus bisporus is a common mushroom for mass consumption, which is not only nutritious but also possesses significant medicinal properties such as anticancer, antibacterial, antioxidant, and immunomodulatory properties. The rare edible mushroom, Agaricus blazei, contains unique agaricol compounds with significant anticancer activity against liver cancer. Agaricus blazei is believed to expel wind and cold, i.e., the pathogenic factors of wind and cold from the body, and is an important formula in traditional Chinese medicine. Despite its nutritional richness and outstanding medicinal value, Agaricus mushrooms have not been systematically compiled and summarized. Therefore, the present review compiles and classifies 70 natural products extracted from Agaricus mushrooms over the past six decades. These compounds exhibit diverse biological and pharmacological activities, with particular emphasis on antitumor and antioxidant properties. While A. blazei and A. bisporus are the primary producers of these compounds, studies on secondary metabolites from other Agaricus species remain limited. Further research is needed to explore and understand the anticancer and nutritional properties of Agaricus mushrooms. This review contributes to the understanding of the structure, bioactivity, and biosynthetic pathways of Agaricus compounds and provides insights for the development of functional foods using these mushrooms.

Approaching Temporal Dynamics in the Dimension-Level Associations Between Career Adaptability/Ambivalence and Internalizing Symptoms Among Chinese Adolescents Throughout Their High Middle School Years.

Despite the well-established associations between adolescents' internalizing symptoms and career development, it still remains unclear whether adolescents' internalizing symptoms are precursors or consequences of their career adaptability/ambivalence. Subtler nuance inherent within such association also await to be revealed, because internalizing symptoms and career development have been primarily treated as broad constructs, despite the multifaceted nature of both. To narrow such gaps, this study examined the potentially dynamic associations among career adaptability, career ambivalence, and internalizing symptoms using three-wave longitudinal data. The study collected data from 3196 Chinese adolescents (52.72% girls, mean age = 15.56 years, SD = 0.58) at Wave 1, with 2820 (attrition rate = 11.76%) participating in Wave 2 and 2568 (attrition rate = 8.93%) in Wave 3. The measurement invariance suggested that there were no significant differences across both waves and genders. This study approached associations at both broader construct levels and subtler dimension levels. Results of cross-lagged path models at broader construct levels demonstrated a unidirectional association between internalizing symptoms and career adaptability. Results of models at subtler dimension levels indicated a series of transactional links over time between career adaptability dimensions/ambivalence and depressive symptoms in particular. Career adaptability dimensions and career ambivalence predicted later anxiety symptoms rather than the reverse. Group model comparisons showed no difference across waves and genders. These findings shed light on the dynamic nature of the associations during adolescence between career adaptability/ambivalence and internalizing symptoms, particularly at subtler dimensional levels, which should be considered in relevant clinical and educational practices.

Berberine attenuates obesity-induced insulin resistance by inhibiting miR-27a secretion.

INTRODUCTION: Berberine (BBR) is an alkaloid found in plants. It has neuroprotective, anti-inflammatory and lipid-lowering activity. However, the efficacy of treatment with BBR and the mechanisms through which it acts need further study. AIMS: This study investigated the therapeutic effects and the mechanism of action of BBR on obesity-induced insulin resistance in peripheral tissues. METHODS: High-fat-fed C57BL/6J mice and low-fat-fed C57BL/6J mice with miR-27a overexpression were given BBR intervention (100 mg/kg, po), and the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed. Palmitic acid-stimulated hypertrophic adipocyte models were treated with BBR (10 µM). Related indicators and protein expression levels were examined. RESULTS: The AUCs of the OGTT and the ITT in the BBR intervention group were reduced significantly (p < 0.01) (p < 0.05), and the serum biochemical parameters, including FBG, TC, TG and LDL-C were significantly reduced after BBR intervention. In the in vitro experiments, the triglyceride level and volume of lipid droplets decreased significantly after BBR intervention (p < 0.01) (p < 0.05). Likewise, BBR ameliorates skeletal muscle and pancreas insulin signalling pathways in vivo and in vitro. DISCUSSION: The results showed that BBR significantly ameliorated insulin resistance, reduced body weight and percent body fat and improved serum biochemical parameters in mice. Likewise, BBR reduced triglyceride level and lipid droplet volume in hypertrophic adipocytes, BBR improved obesity effectively. Meanwhile, BBR ameliorated the histomorphology of the pancreas, and skeletal muscle and pancreas insulin related signalling pathways of islets in in vitro and in vivo experiments. The results further demonstrated that BBR inhibited miR-27a levels in serum from obese mice and supernatant of hypertrophic adipocytes. miR-27a overexpression in low-fat fed mice indicated that miR-27a caused insulin resistance, and BBR intervention significantly improved the miR-27a induced insulin resistance status. CONCLUSION: This study demonstrates the important role of BBR in obesity-induced peripheral insulin resistance and suggest that the mechanism of its effect may be inhibition of miR-27a secretion.

Label-Free Identification of AML1-ETO Positive Acute Myeloid Leukemia Using Single-Cell Raman Spectroscopy.

Acute myeloid leukemia (AML) is a malignant hematological tumor disease. Chromosomal abnormality is an independent prognostic factor in AML. AML with t(8:21) (q22; q22)/AML1-ETO (AE) is an independent disease group. In this research, a new method based on Raman spectroscopy is reported for label-free single-cell identification and analysis of AE fusion genes in clinical AML patients. Raman spectroscopy reflects the intrinsic vibration information of molecules in a label-free and non-destructive manner, and the fingerprint Raman spectrum of cells characterizes intracellular molecular types and relative concentration information, so as to realize the identification and molecular metabolism analysis of different kinds of cells. We collected the Raman spectra of bone marrow cells from clinically diagnosed AML M2 patients with and without the AE fusion gene. Through comparison of the average spectra and identification analysis based on multivariate statistical methods such as principal component analysis and linear discriminant analysis, the distinction between AE positive and negative sample cells in M2 AML patients was successfully achieved, and the single-cell identification accuracy was more than 90%. At the same time, the Raman spectra of the two types of cells were analyzed by the multivariate curve resolution alternating least squares decomposition method. It was found that the presence of the AE fusion gene may lead to the metabolic changes of lipid and nucleic acid in AML cells, which was consistent with the results of genomic and metabolomic multi-omics studies. The above results indicate that single-cell Raman spectroscopy has the potential for early identification of AE-positive AML.

Effect of Public Fillers on Cement-Stabilized Recycled Mixes of Road Performance: Mechanical Properties, Microstructure, and Durability.

In order to address the challenges of resource utilization posed by construction waste, the substitution of natural aggregate (NA) with public fill (PF) contents was investigated for load reclamation and road grassroots applications. A comprehensive assessment of road performance for the recycled mixture was conducted, focusing on parameters such as unconfined compressive strength, splitting strength, compressive resilience modulus, dry shrinkage, and frost resistance. Additionally, the impact of incorporating PF at various types and replacement ratios on the microstructure of cement-stabilized aggregate (CSA) was analyzed. The results indicated that the unconfined compressive strength of cement-stabilized recycled mixture with varying PF contents meets the base strength requirements for heavy, medium, and light traffic pavement on secondary and sub-secondary roads in China. Notably, the unconfined compressive strength and resilience modulus follow a similar pattern, reaching their peak at a 25% PF content. Microscopic examination reveals that an appropriate PF content leads to the predominant formation of C(N)-A-S-H, hydrotalcite, Ca(OH)2, and CaCO3 as paste reaction products. As the replacement of public fill increases from 0% to 25%, there is a gradual stacking of gel products, which enhances the compactness of the microstructure by cementing together unreacted particles. Consequently, this process reduces dry shrinkage strain and effectively mitigates the formation of reflection cracks. Applying large quantities of public fill to road construction can effectively deal with various waste accumulation problems and produce a novel road material with significant social, economic, and environmental benefits.

Inflammatory corpuscle AIM2 facilitates macrophage foam cell formation by inhibiting cholesterol efflux protein ABCA1.

The inflammatory corpuscle recombinant absents in melanoma 2 (AIM2) and cholesterol efflux protein ATP binding cassette transporter A1(ABCA1) have been reported to play opposing roles in atherosclerosis (AS) plaques. However, the relationship between AIM2 and ABCA1 remains unclear. In this study, we explored the potential connection between AIM2 and ABCA1 in the modulation of AS by bioinformatic analysis combined with in vitro experiments. The GEO database was used to obtain AS transcriptional profiling data; screen differentially expressed genes (DEGs) and construct a weighted gene co-expression network analysis (WGCNA) to obtain AS-related modules. Phorbol myristate acetate (PMA) was used to induce macrophage modelling in THP-1 cells, and ox-LDL was used to induce macrophage foam cell formation. The experiment was divided into Negative Control (NC) group, Model Control (MC) group, AIM2 overexpression + ox-LDL (OE AIM2 + ox-LDL) group, and AIM2 short hairpin RNA + ox-LDL (sh AIM2 + ox-LDL) group. The intracellular cholesterol efflux rate was detected by scintillation counting; high-performance liquid chromatography (HPLC) was used to detect intracellular cholesterol levels; apoptosis levels were detected by TUNEL kit; levels of inflammatory markers (IL-1ß, IL-18, ROS, and GSH) were detected by ELISA kits; and levels of AIM2 and ABCA1 proteins were detected by Western blot. Bioinformatic analysis revealed that the turquoise module correlated most strongly with AS, and AIM2 and ABCA1 were co-expressed in the turquoise module with a trend towards negative correlation. In vitro experiments demonstrated that AIM2 inhibited macrophage cholesterol efflux, resulting in increased intracellular cholesterol levels and foam cell formation. Moreover, AIM2 had a synergistic effect with ox-LDL, exacerbating macrophage oxidative stress and inflammatory response. Silencing AIM2 ameliorated the above conditions. Furthermore, the protein expression levels of AIM2 and ABCA1 were consistent with the bioinformatic analysis, showing a negative correlation. AIM2 inhibits ABCA1 expression, causing abnormal cholesterol metabolism in macrophages and ultimately leading to foam cell formation. Inhibiting AIM2 may reverse this process. Overall, our study suggests that AIM2 is a reliable anti-inflammatory therapeutic target for AS. Inhibiting AIM2 expression may reduce foam cell formation and, consequently, inhibit the progression of AS plaques.

Rapid pulmonary 129Xe ventilation MRI of discharged COVID-19 patients with zigzag sampling.

PURPOSE: To demonstrate the feasibility of zigzag sampling for 3D rapid hyperpolarized 129Xe ventilation MRI in human. METHODS: Zigzag sampling in one direction was combined with gradient-recalled echo sequence (GRE-zigzag-Y) to acquire hyperpolarized 129Xe ventilation images. Image quality was compared with a balanced SSFP (bSSFP) sequence with the same spatial resolution for 12 healthy volunteers (HVs). For another 8 HVs and 9 discharged coronavirus disease 2019 subjects, isotropic resolution 129Xe ventilation images were acquired using zigzag sampling in two directions through GRE-zigzag-YZ. 129Xe ventilation defect percent (VDP) was quantified for GRE-zigzag-YZ and bSSFP acquisitions. Relationships and agreement between these VDP measurements were evaluated using Pearson correlation coefficient (r) and Bland-Altman analysis. RESULTS: For 12 HVs, GRE-zigzag-Y and bSSFP required 2.2 s and 10.5 s, respectively, to acquire 129Xe images with a spatial resolution of 3.96 × 3.96 × 10.5 mm3. Structural similarity index, mean absolute error, and Dice similarity coefficient between the two sets of images and ventilated lung regions were 0.85 ± 0.03, 0.0015 ± 0.0001, and 0.91 ± 0.02, respectively. For another 8 HVs and 9 coronavirus disease 2019 subjects, 129Xe images with a nominal spatial resolution of 2.5 × 2.5 × 2.5 mm3 were acquired within 5.5 s per subject using GRE-zigzag-YZ. VDP provided by GRE-zigzag-YZ was strongly correlated (R2 = 0.93, p < 0.0001) with that generated by bSSFP with minimal biases (bias = -0.005%, 95% limit-of-agreement = [-0.414%, 0.424%]). CONCLUSION: Zigzag sampling combined with GRE sequence provides a way for rapid 129Xe ventilation imaging.

In Vivo Assessment of Astrocyte Reactivity in Patients with Progressive Supranuclear Palsy.

OBJECTIVE: Although astrocytic pathology is a pathological hallmark of progressive supranuclear palsy (PSP), its pathophysiological role remains unclear. This study aimed to assess astrocyte reactivity in vivo in patients with PSP. Furthermore, we investigated alterations in brain lactate levels and their relationship with astrocyte reactivity. METHODS: We included 30 patients with PSP-Richardson syndrome and 30 healthy controls; in patients, tau deposition was confirmed through 18F-florzolotau positron emission tomography. Myo-inositol, an astroglial marker, and lactate were quantified in the anterior cingulate cortex through magnetic resonance spectroscopy. We measured plasma biomarkers, including glial fibrillary acidic protein as another astrocytic marker. The anterior cingulate cortex was histologically assessed in postmortem samples of another 3 patients with PSP with comparable disease durations. RESULTS: The levels of myo-inositol and plasma glial fibrillary acidic protein were significantly higher in patients than those in healthy controls (p < 0.05); these increases were significantly associated with PSP rating scale and cognitive function scores (p < 0.05). The lactate level was high in patients, and correlated significantly with high myo-inositol levels. Histological analysis of the anterior cingulate cortex in patients revealed reactive astrocytes, despite mild tau deposition, and no marked synaptic loss. INTERPRETATION: We discovered high levels of astrocyte biomarkers in patients with PSP, suggesting astrocyte reactivity. The association between myo-inositol and lactate levels suggests a link between reactive astrocytes and brain energy metabolism changes. Our results indicate that astrocyte reactivity in the anterior cingulate cortex precedes pronounced tau pathology and neurodegenerative processes in that region, and affects brain function in PSP. ANN NEUROL 2024.

The effect of liver metastases on clinical efficacy of first-line programmed death-1 inhibitor plus chemotherapy in esophageal squamous cell carcinoma: A post hoc analysis of ASTRUM-007 and meta-analysis.

OBJECTIVE: To explore the efficacy of serplulimab plus chemotherapy in esophageal squamous cell carcinoma (ESCC) patients with liver metastases. METHODS: A post hoc exploratory analysis of ASTRUM-007 study was performed, focusing on the association between the liver metastases status and the clinical outcomes. A systematic literature search of electronic databases was conducted to identify eligible randomized controlled trials for the meta-analysis. Study-level pooled analyses of hazard ratios (HRs) for PFS according to liver metastases were performed. RESULTS: The post hoc analysis of ASTRUM-007 showed that although patients with liver metastases had a worse prognosis comparing with the non-liver metastases patients in both treatment arms (serplulimab plus chemotherapy arm: median PFS, 5.7 vs. 6.6 months, HR 1.57 [95% CI, 1.15-2.13]; median OS, 13.7 vs. 15.3 months, HR 1.48 [95% CI, 1.09-1.98]; placebo plus chemotherapy arm: median PFS, 4.3 vs. 5.5 months, HR 1.58 [95% CI, 1.01-2.39]; median OS, 10.3 vs. 11.2 months, HR 1.32 [95% CI, 0.84-2.00]), OS and PFS benefits derived from serplulimab plus chemotherapy versus placebo plus chemotherapy in this study were observed in both patients with liver metastases (HR of PFS: 0.60; 95% CI, 0.37-0.97; HR of OS: 0.68; 95% CI, 0.43-1.11) and the non-liver metastases patients (HR of PFS: 0.62; 95% CI, 0.49-0.80; HR of OS: 0.69; 95% CI, 0.55-0.87) with similar magnitude. Three randomized controlled trials were included in the meta-analysis. Pooled HRs demonstrated that the addition of anti-PD-1 antibodies significantly improved PFS compared to chemotherapy alone regardless of liver metastases status. CONCLUSIONS: This study reveals that the presence of liver metastases is a poor prognostic factor but does not affect the improvements in both PFS and OS brought by adding PD-1 blockade to chemotherapy in ESCC patients. Predictive biomarkers for survival in these patients warrant further investigation.

Novel Dual-Emission Emitters Featuring Phenothiazine-S-Oxide and Phenothiazine-S,S-Dioxide Motifs.

In this study, we have successfully designed and synthesized two novel dual-emission emitters featuring phenothiazine-5-oxide and phenothiazine-5,5-dioxide motifs, characterized by highly lopsided and asymmetric conformational states. Through rigorous spectral examinations and DFT calculations, the compounds exhibit distinctive ICT phenomena, coupled with efficient emission in solid states and AIEE characteristics under high water fractions in DMF/H2O mixtures. These non-planar luminogens exhibit vibrant green and blue solid-state luminescence, with fluorescence quantum yields of 24.1% and 15.21%, respectively. Additionally, they both emit green fluorescence in THF solution, with notable emission quantum yields 36.4% and 30.4%. Comprehensive theoretical investigations unveil well-defined electron cloud density separation between the energies of HOMO/LUMO levels within the two luminogens. Notably, the targeted molecule harboring the phenothiazine-S,S-dioxide motif also demonstrates remarkable reversible mechanofluorochromic properties. Moreover, we testify their potential in applications such as solid-state rewritable information storage and live-cell imaging in solution states. Through theoretical calculations and comparative studies, we have explored the intrinsic relationship between molecular structure and performance, effectively screening and identifying new fluorescent molecules exhibiting outstanding luminescent attributes. These discoveries establish robust theoretical and technical foundation for the synthesis and application of efficient DSE-based MFC materials, opening new avenues in the realm of advanced luminescent materials.

Negative life events and suicidality among adolescents in Western China: the mediating effect of depressive symptoms and the moderating effect of self-esteem.

OBJECTIVE: To investigate the mediating role of depressive symptoms in the relationship between negative life events (NLEs) and suicidality, as well as to test the moderating effect of self-esteem in the mediation model. METHODS: A total of 3,003 adolescents from Han, Tibetan, and Yi ethnic groups living in Western China were included in this study. Utilizing the structural equation model, a mediation model and a moderated mediation model were constructed. RESULTS: The presence of NLEs was positively associated with suicidality (ß = 0.17, p < 0.001). Depressive symptoms partially mediated the relationship between NLEs and suicidality (indirect effect ß = 0.19, p < 0.001). Self-esteem moderated both the antecedent and subsequent segments of the mediating paths of "NLEs → depressive symptoms → suicidality" and the direct relationship between NLEs and suicidality. Among adolescents with a low level of self-esteem, the mediating effect coefficient of depressive symptoms was higher at 0.18 (95% confidence interval (CI): 0.14-0.23), in contrast to adolescents with a high level of self-esteem, where the mediating effect coefficient of depressive symptoms was 0.04 (95% CI: 0.02-0.07). CONCLUSION: NLEs are directly associated with an increased risk of suicidality and indirectly related to suicidality by increasing the risk of depressive symptoms among adolescents. Self-esteem can moderate the mediating effect of depressive symptoms and the relationship between NLEs and suicidality. The intervention strategy for preventing suicidality among adolescents who have experienced NLEs should focus on reducing depressive symptoms and improving self-esteem.

Edaravone dexborneol regulates γ-aminobutyric acid transaminase in rats with acute intracerebral hemorrhage.

OBJECTIVES: Edaravone dexborneol is neuroprotective against ischemic stroke, with free radical-scavenging and anti-inflammatory effects, but its effects in hemorrhagic stroke remain unclear. We evaluated whether edaravone dexborneol has a neuroprotective effect in intracerebral hemorrhage, and its underlying mechanisms. MATERIALS AND METHODS: Bioinformatics were used to predict the pathway of action of edaravone dexborneol. An intracerebral hemorrhage model was established using type IV collagenase in edaravone dexborneol, intracerebral hemorrhage, Sham, adeno-associated virus + edaravone dexborneol, and adeno-associated virus + intracerebral hemorrhage groups. The modified Neurological Severity Score was used to evaluate neurological function in rats. Brain water content was measured using the dry-wet weight method. Tumor necrosis factor-α, interleukin-1ß, inducible nitric oxide synthase, and γ-aminobutyric acid levels were determined by enzyme-linked immunosorbent assay. The expression levels of neurofilament light chain and γ-aminobutyric acid transaminase were determined by western blot. Nissl staining was used to examine neuronal morphology. Cognitive behavior was evaluated using a small-animal treadmill. RESULTS: Edaravone dexborneol alleviated neurological defects, improved cognitive function, and reduced cerebral edema, neuronal degeneration, and necrosis in rats with cerebral hemorrhage. The expression levels of neurofilament light chain, tumor necrosis factor-α, interleukin-1ß, inducible nitric oxide synthase, and γ-aminobutyric acid were decreased, while γ-aminobutyric acid transaminase expression was up-regulated. CONCLUSIONS: Edaravone dexborneol regulates γ-aminobutyric acid content by acting on the γ-aminobutyric acid transaminase signaling pathway, thus alleviating oxidative stress, neuroinflammation, neuronal degeneration, and death caused by excitatory toxic injury of neurons after intracerebral hemorrhage.

Effects of different extrusion temperatures on the physicochemical properties, edible quality and digestive attributes of multigrain reconstituted rice.

Multigrain reconstituted rice, as a nutritious and convenient staple, holds considerable promise for the food industry. Furthermore, highland barley, corn, and other coarse cereals are distinguished by their low glycemic index (GI), rendering them effective in mitigating postprandial blood glucose levels, thereby underscoring their beneficial physiological impact. This study investigated the impact of extrusion temperature on the physicochemical properties, edible quality, and digestibility of multigrain reconstituted rice. The morphology revealed that starch particles that are not fully gelatinized in multigrain reconstituted rice are observed at an extrusion temperature range of 60 °C-90 °C. As the extrusion temperature increased, the degree of gelatinization (DG) increased, while the contents of water, protein, total starch, and amylopectin decreased substantially. Concurrently, the relative crystallinity, orderliness of starch, and heat absorption enthalpy (ΔH) decreased significantly, and water absorption (WAI) and water solubility (WSI) increased markedly. Regarding edible quality, sensory evaluation displayed an initial increase followed by a decrease. In terms of digestibility, the estimated glycemic index (eGI) increased from 61.10 to 70.81, and the GI increased from 60.41 to 75.33. In addition, the DG was significantly correlated with both eGI (r = 0.886**) and GI (r = 0.947**). The results indicated that the ideal extrusion temperature for multigrain reconstituted rice was 90 °C. The findings underscored the pivotal role of optimal extrusion temperatures in the production of multigrain reconstituted rice, which features low GI and high nutritional quality.

The role of Pleistocene dispersal in shaping species richness of sky island wintergreens from the Himalaya-Hengduan Mountains.

In addition to topography and climate, biogeographic dispersal has been considered to influence plant diversity in the Himalaya-Hengduan Mountains (HHM), yet, the mode and tempo of sky island dispersal and its influence on species richness has been little explored. Through phylogenetic analysis of Gaultheria ser. Trichophyllae, a sky island alpine clade within the HHM, we test the hypothesis that dispersal has affected current local species richness. We inferred the dynamics of biogeographic dispersal with correlation tests on direction, distance, occurrence time, and regional species richness. We found that G. ser. Trichophyllae originated at the end of the Miocene and mostly dispersed toward higher longitudes (eastward). In particular, shorter intra-regional eastward dispersals and longer inter-regional westward dispersals were most frequently observed. We detected a prevalence of eastward intra-region dispersals in both glacial periods and interglacials. These dispersals may have been facilitated by the reorganization of paleo-drainages and monsoon intensification through time. We suggest that the timing of dispersal corresponding to glacial periods and the prevalence of intra-region dispersal, rather than dispersal frequency, most influenced the pattern of species richness of G. ser. Trichophyllae. This study facilitates a more comprehensive understanding of biodiversity in the sky islands within the HHM.