Single-cell RNA sequencing integrated with bulk RNA sequencing analysis identifies a tumor immune microenvironment-related lncRNA signature in lung adenocarcinoma.

BACKGROUND: Recently, long non-coding RNAs (lncRNAs) have been demonstrated as essential roles in tumor immune microenvironments (TIME). Nevertheless, researches on the clinical significance of TIME-related lncRNAs are limited in lung adenocarcinoma (LUAD). METHODS: Single-cell RNA sequencing and bulk RNA sequencing data are integrated to identify TIME-related lncRNAs. A total of 1368 LUAD patients are enrolled from 6 independent datasets. An integrative machine learning framework is introduced to develop a TIME-related lncRNA signature (TRLS). RESULTS: This study identified TIME-related lncRNAs from integrated analysis of single­cell and bulk RNA sequencing data. According to these lncRNAs, a TIME-related lncRNA signature was developed and validated from an integrative procedure in six independent cohorts. TRLS exhibited a robust and reliable performance in predicting overall survival. Superior prediction performance barged TRLS to the forefront from comparison with general clinical features, molecular characters, and published signatures. Moreover, patients with low TRLS displayed abundant immune cell infiltration and active lipid metabolism, while patients with high TRLS harbored significant genomic alterations, high PD-L1 expression, and elevated DNA damage repair (DDR) relevance. Notably, subclass mapping analysis of nine immunotherapeutic cohorts demonstrated that patients with high TRLS were more sensitive to immunotherapy. CONCLUSIONS: This study developed a promising tool based on TIME-related lncRNAs, which might contribute to tailored treatment and prognosis management of LUAD patients.

Integrated Exploration of Epigenetic Dysregulation Reveals a Stemness/EMT Subtype and MMP12 Linked to the Progression and Prognosis in Hepatocellular Carcinoma.

Epigenetic dysregulation drives aberrant transcriptional programs playing a critical role in hepatocellular carcinoma (HCC), which may provide novel insights into the heterogeneity of HCC. This study performed an integrated exploration on the epigenetic dysregulation of miRNA and methylation. We discovered and validated three patterns endowed with gene-related transcriptional traits and clinical outcomes. Specially, a stemness/epithelial-mesenchymal transition (EMT) subtype was featured by immune exhaustion and the worst prognosis. Besides, MMP12, a characteristic gene, was highly expressed in the stemness/EMT subtype, which was verified as a pivotal regulator linked to the unfavorable prognosis and further proven to promote tumor proliferation, invasion, and metastasis in vitro experiments. Proteomic analysis by mass spectrometry sequencing also indicated that the overexpression of MMP12 was significantly associated with cell proliferation and adhesion. Taken together, this study unveils innovative insights into epigenetic dysregulation and identifies a stemness/EMT subtype-specific gene, MMP12, correlated with the progression and prognosis of HCC.

Cellular Ligand-Receptor Perturbations Unravel MEIS2 as a Key Factor for the Aggressive Progression and Prognosis in Stage II/III Colorectal Cancer.

Approximately 10-15% of stage II and 25-30% of stage III colorectal cancer (CRC) patients experience recurrence within 5 years after surgery, and existing taxonomies are insufficient to meet the needs of clinical precision treatment. Thus, robust biomarkers and precise management were urgently required to stratify stage II and III CRC and identify potential patients who will benefit from postoperative adjuvant therapy. Alongside, interactions of ligand-receptor pairs point to an emerging direction in tumor signaling with far-reaching implications for CRC, while their impact on tumor subtyping has not been elucidated. Herein, based on multiple large-sample multicenter cohorts and perturbations of the ligand-receptor interaction network, four well-characterized ligand-receptor-driven subtypes (LRDS) were established and further validated. These molecular taxonomies perform with unique heterogeneity in terms of molecular characteristics, immune and mutational landscapes, and clinical features. Specifically, MEIS2, a key LRDS4 factor, performs significant associations with proliferation, invasion, migration, and dismal prognosis of stage II/III CRC, revealing promising directions for prognostic assessment and individualized treatment of CRC patients. Overall, our study sheds novel insights into the implications of intercellular communication on stage II/III CRC from a ligand-receptor interactome perspective and revealed MEIS2 as a key factor in the aggressive progression and prognosis for stage II/III CRC.

Polyphyllin I alleviates neuroinflammation after cerebral ischemia-reperfusion injury via facilitating autophagy-mediated M2 microglial polarization.

Microglial activation and polarization play a central role in poststroke inflammation and neuronal damage. Modulating microglial polarization from pro-inflammatory to anti-inflammatory phenotype is a promising therapeutic strategy for the treatment of cerebral ischemia. Polyphyllin I (PPI), a steroidal saponin, shows multiple bioactivities in various diseases, but the potential function of PPI in cerebral ischemia is not elucidated yet. In our study, the influence of PPI on cerebral ischemia-reperfusion injury was evaluated. Mouse middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation and reoxygenation (OGD/R) model were constructed to mimic cerebral ischemia-reperfusion injury in vivo and in vitro. TTC staining, TUNEL staining, RT-qPCR, ELISA, flow cytometry, western blot, immunofluorescence, hanging wire test, rotarod test and foot-fault test, open-field test and Morris water maze test were performed in our study. We found that PPI alleviated cerebral ischemia-reperfusion injury and neuroinflammation, and improved functional recovery of mice after MCAO. PPI modulated microglial polarization towards anti-inflammatory M2 phenotype in MCAO mice in vivo and post OGD/R in vitro. Besides, PPI promoted autophagy via suppressing Akt/mTOR signaling in microglia, while inhibition of autophagy abrogated the effect of PPI on M2 microglial polarization after OGD/R. Furthermore, PPI facilitated autophagy-mediated ROS clearance to inhibit NLRP3 inflammasome activation in microglia, and NLRP3 inflammasome reactivation by nigericin abolished the effect of PPI on M2 microglia polarization. In conclusion, PPI alleviated post-stroke neuroinflammation and tissue damage via increasing autophagy-mediated M2 microglial polarization. Our data suggested that PPI had potential for ischemic stroke treatment.

Molecular basis underlying default mode network functional abnormalities in postpartum depression with and without anxiety.

Although Postpartum depression (PPD) and PPD with anxiety (PPD-A) have been well characterized as functional disruptions within or between multiple brain systems, however, how to quantitatively delineate brain functional system irregularity and the molecular basis of functional abnormalities in PPD and PPD-A remains unclear. Here, brain sample entropy (SampEn), resting-state functional connectivity (RSFC), transcriptomic and neurotransmitter density data were used to investigate brain functional system irregularity, functional connectivity abnormalities and associated molecular basis for PPD and PPD-A. PPD-A exhibited higher SampEn in medial prefrontal cortex (MPFC) and posterior cingulate cortex (PPC) than healthy postnatal women (HPW) and PPD while PPD showed lower SampEn in PPC compared to HPW and PPD-A. The functional connectivity analysis with MPFC and PPC as seed areas revealed decreased functional couplings between PCC and paracentral lobule and between MPFC and angular gyrus in PPD compared to both PPD-A and HPW. Moreover, abnormal SampEn and functional connectivity were associated with estrogenic level and clinical symptoms load. Importantly, spatial association analyses between functional changes and transcriptome and neurotransmitter density maps revealed that these functional changes were primarily associated with synaptic signaling, neuron projection, neurotransmitter level regulation, amino acid metabolism, cyclic adenosine monophosphate (cAMP) signaling pathways, and neurotransmitters of 5-hydroxytryptamine (5-HT), norepinephrine, glutamate, dopamine and so on. These results reveal abnormal brain entropy and functional connectivities primarily in default mode network (DMN) and link these changes to transcriptome and neurotransmitters to establish the molecular basis for PPD and PPD-A for the first time. Our findings highlight the important role of DMN in neuropathology of PPD and PPD-A.

The activity of hyaD contributed to the virulence of avian Pasteurella multocida.

Fowl cholera is an infectious disease that affects both poultry and wild birds, characterized by hemorrhagic and septicemic symptoms, caused by Pasteurella multocida (P. multocida), and leading to substantial economic losses in the poultry sector. The development of genetic engineering vaccines against avian P. multocida encountered early-stage challenges due to the limited availability of effective gene editing tools. Presently, NgAgoDM-enhanced homologous recombination stands as a potent technique for achieving efficient gene knockout in avian P. multocida. Hence, this study employed NgAgoDM-enhanced homologous recombination to target and knockout hyaE (239-359aa), hyaD, hexABC, and hexD, denoted as ΔhyaE (239-359aa), ΔhyaD, ΔhexABC, and ΔhexD, respectively. Additionally, we generated a hyaD recovery strain with two point mutations, designated as mhyaD. Thus, this study systematically examined the impact of capsular synthetic gene clusters on the pathogenicity of P. multocida. Moreover, the study demonstrated the critical role of hyaD activity in the virulence of avian P. multocida. This study offers novel insights for enhancing attenuated vaccines further.

Facile preparation of MoO3@Mo2CTxnanocomposite with high lithium storage performance byin situoxidation.

In this work, a new MoO3@Mo2CTxnanocomposite was prepared from two-dimensional (2D) Mo2CTxMXene byin situoxidization in air, which exhibited wonderful lithium-storage performance as anodes of lithium-ion batteries (LIBs). The precursor Mo2CTxwas synthesized from Mo2Ga2C by selective etching of NH4F at 180 °C for 24 h. Thereafter, the Mo2CTxwas oxidized in air at 450 °C for 30 min to obtain MoO3@Mo2CTxnanocomposite. In the composite,in situgenerated MoO3nanocrystals pillar the layer structure of Mo2CTxMXene, which increases the interlayer space of Mo2CTxfor Li storage and enhances the structure stability of the composite. Mo2CTx2D sheets provide a conductive substrate for MoO3nanocrystals to enhance the Li+accessibility. As anodes of LIBs, the final discharge specific capacity of the MoO3@Mo2CTxcomposite was 511.1 mAh g-1at a current density of 500 mA g-1after 100 cycles, which is about 36.7 times that of pure Mo2CTxMXene (13.9 mAh g-1) and 3.2 times that of pure MoO3(159.9 mAh g-1). In the composites, both Mo2CTxand MoO3provide high lithium storage capacity and can enhance the performance of each other. Moreover, this composite can be made by a facile method ofin situoxidation. Therefore, the MoO3@Mo2CTxMXene nanocomposite is a promising anode of LIB with high performance.

MIRAGE Syndrome Due to a de novo SAMD9 c.2944C > T (p.Arg982Cys) Variant: a Case Report and Relevant Literature Review.

BACKGROUND: MIRAGE syndrome is a rare autosomal dominant genetic disorder. METHODS: We studied a 15-month-old girl with growth retardation and refractory respiratory infections. RESULTS: The patient had thrombocytopenia and was positive for Epstein-Barr virus, cytomegalovirus IgM and IgG, and herpes simplex virus type I and II IgG. The genomic analysis reported a heterozygous de novo SAMD9 c.2944C > T (p.Arg982Cys) pathogenic variant. She improved after antibiotic treatments, but finally died due to severe recurrent infection. CONCLUSIONS: Patients with MIRAGE syndrome could have various clinical presentations. Infections from mixed pathogens are common, which require adequate coverage for bacteria, viruses, and fungi.

Chemical Constituents from the Heartwood of Solanum Verbascifolium L. And Their Anti-Inflammatory Activities Combined Network Pharmacology.

Phytochemical studies on 95 % ethanol extract of the heartwood of Solanum verbascifolium L. resulted in the isolation of one new amide derivative (1), and 21 known phenylpropanoids compounds. The structures were characterized by spectral analysis and high-resolution mass spectrometric analysis. The anti-inflammatory activity of amide compounds 1-4 and 6-9 by investigating their impact on the release of nitric oxide (NO) in MH-S cells. Our findings unveiled significant inhibitory effects on NO secretion. Compound 1 exhibited robust dose-dependent suppression, with pronounced inhibition observed at both 20 µM (P<0.01) and 40 µM (P<0.01). Furthermore, compound 9 demonstrated noteworthy inhibitory effects at 40 µM (P<0.01). Similarly, compounds 3 and 4 displayed substantial inhibition of NO secretion at the same concentration, although the significance level was slightly lower (P<0.05). It is expected that there is a substantial association between the anti-inflammatory activities of amides and their targets, specifically PTGS2, by combining network pharmacology and molecular docking techniques. This discovery emphasizes amides' potential as an interesting subject for additional study in the realm of anti-inflammatory medications.

Innovative hybrid strategy for quality improvement of Goji tea: ultrasonic-ethyl oleate pretreatment combined with heat pump drying.

BACKGROUND: Goji berries, renowned for their nutritional benefits, are traditionally dried to extend shelf life and preserve quality. However, conventional drying methods often result in uneven drying, color loss and reduced rehydration capacity. This study investigates an innovative hybrid strategy combining ultrasonic-ethyl oleate (US+AEEO) pretreatment with heat pump drying (HPD) to enhance the drying process of Goji berries. RESULTS: Fresh Goji berries underwent US+AEEO pretreatment, which significantly disrupted the waxy layer, enhancing drying efficiency and water infiltration during rehydration. Compared to freeze drying (FD), HPD combined with US+AEEO pretreatment resulted in higher retention of total polyphenol content (TPC) and total flavonoid content (TFC) in the Goji soaking soup. Specifically, the HPD-US+AEEO samples exhibited the highest TPC and TFC levels, significantly outperforming FD samples. Additionally, the DPPH and ABTS antioxidant assays demonstrated higher scavenging activities in HPD-US+AEEO samples. The rehydration kinetics revealed that HPD samples had a superior rehydration rate and final moisture content compared to FD samples. Low-field nuclear magnetic resonance and magnetic resonance imaging analyses confirmed enhanced water distribution and higher mobility in HPD-US+AEEO samples. Scanning electron microscopy indicated a more porous structure in US+AEEO-treated samples, facilitating better water absorption and functional component retention. CONCLUSION: The combination of US+AEEO pretreatment with HPD significantly improves the drying process of Goji berries, enhancing nutrient retention, color preservation and rehydration properties. This innovative drying method offers a promising solution for producing high-quality dried Goji berries, benefiting both the food industry and health-conscious consumers. © 2024 Society of Chemical Industry.

Machine learning algorithm-generated and multi-center validated melanoma prognostic signature with inspiration for treatment management.

BACKGROUND: Although immunotherapy and targeted treatments have dramatically improved the survival of melanoma patients, the intra- or intertumoral heterogeneity and drug resistance have hindered the further expansion of clinical benefits. METHODS: The 96 combination frames constructed by ten machine learning algorithms identified a prognostic consensus signature based on 1002 melanoma samples from nine independent cohorts. Clinical features and 26 published signatures were employed to compare the predictive performance of our model. RESULTS: A machine learning-based prognostic signature (MLPS) with the highest average C-index was developed via 96 algorithm combinations. The MLPS has a stable and excellent predictive performance for overall survival, superior to common clinical traits and 26 collected signatures. The low MLPS group with a better prognosis had significantly enriched immune-related pathways, tending to be an immune-hot phenotype and possessing potential immunotherapeutic responses to anti-PD-1, anti-CTLA-4, and MAGE-A3. On the contrary, the high MLPS group with more complex genomic alterations and poorer prognoses is more sensitive to the BRAF inhibitor dabrafenib, confirmed in patients with BRAF mutations. CONCLUSION: MLPS could independently and stably predict the prognosis of melanoma, considered a promising biomarker to identify patients suitable for immunotherapy and those with BRAF mutations who would benefit from dabrafenib.

Transcriptomic analyses of treatment-naïve pediatric ulcerative colitis patients and exploration of underlying disease pathogenesis.

BACKGROUND: Ulcerative colitis (UC) is a form of chronic inflammatory bowel disease of nonspecific origin. This study used an RNA-Sequencing (RNA-Seq) approach to evaluate the transcriptomic landscape of a well-stratified treatment-naïve pediatric UC patient population by comparing them with healthy control children. The data were analyzed to evaluate the mechanisms driving UC-related intestinal inflammation and fibrosis. METHODS: Intestinal mucosal samples from five pediatric UC patients and five healthy controls were analyzed by RNA-Seq, and results were verified by qPCR. A CRISPR/Cas9 approach was used to knock out the expression of HLA-DRB5, and molecular biology techniques were used for additional mechanistic studies. RESULTS: In these analyses, 2290 genes were found to be differentially expressed between the UC and control samples, of which 1258 and 1032 were upregulated and downregulated, respectively. Gene Ontology analysis showed that these genes were enriched in extracellular matrix (ECM)-related processes and that 7 of 8 differentially expressed genes of interest (PIK3CD, IL1ß, IL1α, TIMP1, MMP1, MMP12, COL6A3, and HLADRB5) were upregulated and involved in ECM-receptor interaction and inflammatory bowel disease-related pathways. Increased HLA-DRB5 expression driven by intestinal bacteria was found to promote IL-1α secretion, leading to intestinal inflammation and fibrosis, suggesting a possible target for the treatment of UC. CONCLUSION: These data suggest that intestinal inflammation is present in pediatric UC patients for extended periods before the onset of symptoms, and intestinal fibrosis begins even during the early stages of UC. Intestinal bacteria were also found to trigger intestinal inflammation and fibrosis, with HLA-DRB5 playing a central role in this process.

Emulsifying properties of plant-derived polypeptide and their conjugates: a self-consistent-field calculation study of the impact of hydrolysis.

By considering the hydrolysates of soy protein produced by trypsin as an example, the emulsion stabilizing properties of plant-based protein fragments have been investigated theoretically. We apply Self-Consistent-Field (SCF) calculations to determine the colloidal interactions induced between a pair of droplets stabilized by adsorbed layers of various soy protein fragments. The study is extended to conjugates of such polypeptides, formed by covalent bonding with a suitable hydrophilic sidechain (e.g. a polysaccharide). Our results show that the relatively longer fragments, with a greater number of hydrophobic amino acids, will display a stronger degree of adsorption affinity compared to the smaller hydrolysates, even where the latter may have a higher overall ratio of hydrophobic residues. This suggested that the degree of protein hydrolysis should be carefully controlled and limited to modest values to avoid the generation of a large number of short polypeptides, while still sufficient to improve solubility. While the emulsion stabilizing performance of a protein fragment type is strongly dependent on the conformation it adopts on the interface, we find this to be less critical for the conjugated polypeptides. However, we argue that with increasing degree of hydrolysis, many small fragments will not have the chance to form bonds with polysaccharides. It is demonstrated that the abundance of these unreacted polypeptides in the system severely reduces the efficiency of the conjugated longer protein fragments, preventing their presence on the surface of the droplets through competitive adsorption process.

Construction of Co3O4 nanopolyhedra with rich oxygen vacancies from ZIF-67 for efficient photocatalytic nitrogen fixation.

Photocatalytic nitrogen fixation has attracted much attention due to the fact that it is a way of using solar energy to achieve clean and sustainable conversion of nitrogen to ammonia under mild conditions. In this paper, different proportions of Zn-doped Co3O4 nanopolyhedrons were synthesized using bimetallic ZIFs containing Co2+ and Zn2+ as precursors for the construction of photocatalytic nitrogen fixation semiconductor materials for the first time. The synthesized Co3O4 nano-polyhedron still retains the rhombic dodecahedron shape of ZIF-67 and exhibits a large specific surface area. Moreover, Zn doping results in abundant oxygen vacancies on the surface of Co3O4 polyhedron. These oxygen vacancies not only provide active sites for nitrogen adsorption and activation, but also enhance the separation ability of photocarriers, which can significantly improve the efficiency of photocatalytic nitrogen fixation of the material. When Zn-Co3O4-30 is utilized as the catalyst for photocatalytic nitrogen fixation, the nitrogen fixation rate is 96.8 µmol g-1 h-1, which is much higher than that of pure-Co3O4. In this study, heteroatom-doped Co3O4 polyhedron with rich oxygen vacancy was synthesized by low-temperature oxidation method, which provides a new idea for the design and synthesis of skeleton-based photocatalytic nitrogen fixation materials.

Lithium storage performance enhanced by lithiation-induced structural phase transitions of fluorinated MXenes.

Structural phase transitions in electrode materials of Li-ion batteries (LIBs) often occur along with Li-ion extraction/intercalation during charge and discharge processes. Lithiation-induced phase transition behaviors of two-dimensional fluorinated MXenes were investigated systematically by first-principles density functional calculations. The calculated results show that fluorine atoms in the nine MXenes studied moved from the FCC site (or HCP site for Ta2CF2) to the TOP site during Li adsorption. Further all the predicted phase transitions were confirmed by ab initio molecular dynamic simulations. The band structure, density of state, diffusion energy barrier, average voltage and storage capacity were calculated to evaluate the lithium storage properties of fluorinated MXenes, which revealed that V2CF2 and Ti2CF2 are the optimal candidates for LIB electrode materials. The structural phase transition led to improvements in the cycle stability, storage capacity, average voltage, and other lithium storage properties of the fluorinated MXenes.

A systematic computational investigation of lithiation-induced structural phase transitions of O-functionalized MXenes.

Along with Li-ion extraction/intercalation during charge and discharge processes, structural phase transitions often occur in the electrode materials of Li-ion batteries (LIBs). By determining atomic positions before and after Li adsorptions, structural phase transitions of two-dimensional MXenes were investigated systematically using first-principles density functional calculations. The lithiation-induced phase transitions of ten M2C MXenes with oxygen groups can be divided into three types. No phase transitions occur for Ti-type MXenes including Ti2CO2, Zr2CO2 and Hf2CO2. The oxygens in Ta-type MXenes (Sc2CO2, Y2CO2, Nb2CO2 and Ta2CO2) move from one type of octahedral void to another type of octahedral void. However, for Mo-type MXenes including V2CO2, Cr2CO2 and Mo2CO2, the oxygens move from octahedral voids to tetrahedral voids. The mechanisms whether phase transitions happen or not are dependent on the sizes of M ions. Furthermore, all the predicted phase transitions were confirmed by ab initio molecular dynamics simulations. The calculated results of electron localization functions and Bader charge illustrate that there exist strong Coulomb interactions (ionic bonds) between Li and MXene surfaces. The band structure, diffusion energy barrier, open circuit voltage and storage capacity were calculated to evaluate the lithium storage properties of different MXenes, which reveals that V2CO2 and Cr2CO2 should be optimal candidates as electrode materials for LIBs.

Characteristics of the oropharyngeal microbiota among infants with pneumonia and their effects on immune response and subsequent respiratory morbidity.

Changes in airway microbiota among infants with pneumonia and their impact on subsequent respiratory health are largely unknown. The present study aimed to analyze the oropharyngeal microbiota of infants with pneumonia and to explore the impact of disturbances of the microbiota on disease severity and long-term respiratory morbidities. The oropharyngeal microbiome was characterized using 16S ribosomal RNA-based sequencing, while serum immune mediators were assessed using cytometric bead array, and invariant natural killer T (iNKT) cells were detected using flow cytometry in infants with pneumonia < 6 months of age. Patients were followed up to 3 years of age, and clinical and respiratory morbidity data were collected. A total of 106 infants with pneumonia were enrolled in this study. Diversity of the respiratory microbiota was inversely correlated with the severity of pneumonia and length of hospitalization. Patients who experienced wheezing during pneumonia exhibited lower percentages of total iNKT cells, CD8-positive ( +), and CD4-CD8- subsets, and higher CD4 + subsets than those without. The relative abundances of Prevotella and Veillonella species were lower in patients with severe pneumonia. The abundance of Veillonella was higher in patients who experienced wheezing during pneumonia and in those with subsequent recurrent wheezing than in those without wheezing. The relative abundance and total counts of Bifidobacterium, Lactobacillus, and Neisseria were higher in patients who did not experience subsequent recurrent wheezing. CONCLUSIONS: Diversity of the respiratory microbiota was inversely associated with pneumonia severity, and the percentage of iNKT cells was associated with wheezing during pneumonia. Several species may be associated with subsequent respiratory morbidities and warrant further investigation. WHAT IS KNOWN: • Early life airway microbiota symbiosis affects the severity of respiratory infection and the risk for the development of asthma. • Changes in airway microbiota among infants with pneumonia and their impact on subsequent respiratory health are largely unknown. WHAT IS NEW: • The diversity of the airway microbiome was inversely associated with the severity of pneumonia and length of hospitalization. • The abundance of Veillonella was higher in patients who experienced wheezing during pneumonia and in those with subsequent recurrent wheezing.

PI3K pathway mutation predicts an activated immune microenvironment and better immunotherapeutic efficacy in head and neck squamous cell carcinoma.

BACKGROUND: PI3K pathway is the most frequently mutated pathway in head and neck squamous cell carcinoma (HNSC), which plays a crucial role in tumorigenesis and progression. In the present study, we aimed to investigate the role of PI3K pathway mutation in clinical prognosis prediction and the relationship with immune microenvironment and response rate to immunotherapy. METHODS: We collected 129 samples with immunotherapy information from MSKCC-2019 cohort as well as 501 and 40 samples from TCGA-HNSC and MD-Anderson non-immunotherapy cohorts, respectively. Somatic mutation data was utilized to characterize the mutational status of the PI3K pathway. Subsequently, we further analyzed the differences in prognosis, immunotherapy response, genomic alterations, functional characteristics, and immune microenvironment between the mutation and wild groups. RESULTS: The Kaplan-Meier survival curves displayed that PI3K pathway mutation predicted observably prolonged overall survival (OS) in the immunotherapy cohort MSKCC-2019 (p = 0.012) but did not reach statistical significance in the non-immunotherapy cohorts TCGA-HNSC (p = 0.68) and MD-Anderson (p = 0.68). After incorporating several clinicopathologic features such as age, gender, and tumor mutation burden (TMB), the results of multivariate Cox regression analysis also demonstrated that the PI3K pathway mutation could indicate better immunotherapy outcomes in HNSC patients with a hazard ratio (HR) of 0.533 (95% CI: 0.313-0.910; p = 0.021) in the immunotherapy cohort MSKCC-2019, compared with 0.888 (95% CI: 0.636-1.241; p = 0.487) and 1.939 (95% CI: 0.483-7.781; p = 0.351) in the non-immunotherapy cohorts TCGA-HNSC and MD-Anderson. In addition, the results of the subclass mapping (SubMap) and the tumor immune dysfunction and exclusion (TIDE) also consistently suggested that patients in the mutation group are more likely to benefit from immunotherapy. And further studies showed that the mutation group owned significantly higher TMB, activated immune-related pathways, richer abundance of immune cells, and higher expression levels of immunomodulators. To improve the prognosis of the wild group, we identified five relatively sensitive potential drugs for the wild group, including "BMS-536924," "linsitinib," "NVP-TAE684," "PLX-4720," and "clonazepam." CONCLUSIONS: The PI3K pathway mutation status could be considered as a potential biomarker to predict better immunotherapeutic efficacy and clinical outcomes after immunotherapy in HNSC patients.

Accuracy of Ultrasound Jugular Venous Pressure Height in Predicting Central Venous Congestion.

BACKGROUND: Assessment of volume status through the estimation of central venous pressure (CVP) is integral in the care of heart failure (HF). Bedside assessment is limited by obesity, variation in physical examination skills, and expertise in ultrasonography. OBJECTIVE: To validate the accuracy of quantitative and qualitative point-of-care ultrasonography assessment of jugular venous pressure (JVP) in predicting elevated CVP. DESIGN: Prospective observational study using convenience sampling. SETTING: 2 U.S. academic hospitals. PATIENTS: Adult patients undergoing right heart catheterization between 5 February 2019 and 1 March 2021. MEASUREMENTS: Estimation of the JVP height by handheld ultrasound device (uJVP), JVP by traditional physical examination, and qualitative presence of a distended uJVP in the upright position (upright-uJVP) was done before invasive measurements. Receiver-operating characteristic analysis of the uJVP was compared with invasive hemodynamics. RESULTS: In 100 participants undergoing right heart catheterization for HF indications (mean age, 59.6 years; 44% with preserved ejection fraction), the uJVP in a reclined position accurately predicted elevated right atrial pressure (RAP) (>10 mm Hg), with an area under the curve of 0.84. A positive uJVP in the upright position was 94.6% specific for predicting elevated RAP. LIMITATION: Limited examiners, only 2 centers, and convenience sampling. CONCLUSION: Point-of-care ultrasonography assessment of the uJVP is feasible, reproducible, and accurately predictive of elevated CVPs in patients undergoing right heart catheterization. Further investigation of clinical application of ultrasound-measured JVP seems warranted. PRIMARY FUNDING SOURCE: None.

Dendrocandin U from Dendrobium officinale Kimura et Migo Inhibits M1 Polarization in Alveolar Macrophage by Suppressing NF-κB Signaling Pathway.

Dendrobium officinale Kimura et Migo is a valuable and homologous medicine and food traditional Chinese medicine. Currently there are few studies on the anti-inflammatory activity of lipophilic components. The aim of this study was to explore the anti-inflammatory effect and mechanism of the lipophilic compounds in Dendrobium officinale. Six compounds were isolated and identified, including three bibenzyl compounds, dendrocandin U, dendronbibisline B, erianin, and three lignans, (-)-syringaresinol, (+)-syringaresinol-O-ß-D-glucopyranoside, 5-methoxy-(+)-isolariciresinol. Among them, dendronbibisline B and 5-methoxy-(+)-isolariciresinol were isolated from Dendrobium officinale for the first time. Besides, we found dendrocandin U, dendronbibisline B and (-)-syringaresinol exhibited the anti-inflammation to inhibit nitric oxide secretion induced by lipopolysaccharide (LPS)/interferon (IFN-γ) in MH-S cells. Furthermore, dendrocandin U could inhibit the expression of tumor necrosis factor-α (TNF-α), Cluster of Differentiation 86 (CD86), and reduce inflammatory morphological changes of macrophages. Meanwhile, we confirmed that the anti-inflammation mechanism of dendrocandin U was to inhibit M1 polarization by suppressing toll-like receptor 4 (TLR4)/recombinant myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway. In this paper, dendrocandin U with significant anti-inflammatory activity was found from Dendrobium officinale, which could provide a basis for the study of its anti-inflammatory drugs.