Unbiasedly decoding the tumor microenvironment with single-cell multiomics analysis in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor prognosis and limited therapeutic options. Research on the tumor microenvironment (TME) of PDAC has propelled the development of immunotherapeutic and targeted therapeutic strategies with a promising future. The emergence of single-cell sequencing and mass spectrometry technologies, coupled with spatial omics, has collectively revealed the heterogeneity of the TME from a multiomics perspective, outlined the development trajectories of cell lineages, and revealed important functions of previously underrated myeloid cells and tumor stroma cells. Concurrently, these findings necessitated more refined annotations of biological functions at the cell cluster or single-cell level. Precise identification of all cell clusters is urgently needed to determine whether they have been investigated adequately and to identify target cell clusters with antitumor potential, design compatible treatment strategies, and determine treatment resistance. Here, we summarize recent research on the PDAC TME at the single-cell multiomics level, with an unbiased focus on the functions and potential classification bases of every cellular component within the TME, and look forward to the prospects of integrating single-cell multiomics data and retrospectively reusing bulk sequencing data, hoping to provide new insights into the PDAC TME.

Prediction errors arising from switches between major and minor modes in music: An fMRI study.

The major and minor modes in Western music have positive and negative connotations, respectively. The present fMRI study examined listeners' neural responses to switches between major and minor modes. We manipulated the final chords of J. S. Bach's keyboard pieces so that each major-mode passage ended with either the major (Major-Major) or minor (Major-Minor) tonic chord, and each minor-mode passage ended with either the minor (Minor-Minor) or major (Minor-Major) tonic chord. If the final major and minor chords have positive and negative reward values respectively, the Major-Minor and Minor-Major stimuli would cause negative and positive reward prediction errors (RPEs) respectively in a listener's brain. We found that activity in a frontoparietal network was significantly higher for Major-Minor than for Major-Major. Based on previous research, these results support the idea that a major-to-minor switch causes negative RPE. The contrast of Minor-Major minus Minor-Minor yielded activation in the ventral insula and visual cortex, speaking against the idea that a minor-to-major switch causes positive RPE. We discuss our results in relation to executive functions and the emotional connotations of major versus minor modes.

Evaluation of postoperative recovery: past, present and future.

Postoperative recovery, as a window to observe perioperative treatment effect and patient prognosis, is a common outcome indicator in clinical research and has attracted more and more attention of surgeons and anaesthesiologists. Postoperative recovery is a subjective, multidimensional, long-term, complex process, so it is unreasonable to only use objective indicators to explain it. Currently, with the widespread use of patient-reported outcomes, various scales become the primary tools for assessing postoperative recovery. Through systematic search, we found 14 universal recovery scales, which have different structures, contents and measurement properties, as well as their own strengths and weaknesses. We also found that it is urgently necessary to perform further researches and develop a scale that can serve as the gold universal standard to evaluate postoperative recovery. In addition, with the rapid development of intelligent equipment, the establishment and validation of electronic scales is also an interesting direction.

Arabinose Plays an Important Role in Regulating the Growth and Sporulation of Bacillus subtilis NCD-2.

A microbial fungicide developed from Bacillus subtilis NCD-2 has been registered for suppressing verticillium wilt in crops in China. Spores are the main ingredient of this fungicide and play a crucial role in suppressing plant disease. Therefore, increasing the number of spores of strain NCD-2 during fermentation is important for reducing the cost of the fungicide. In this study, five kinds of carbon sources were found to promote the metabolism of strain NCD-2 revealed via Biolog Phenotype MicroArray (PM) technology. L-arabinose showed the strongest ability to promote the growth and sporulation of strain NCD-2. L-arabinose increased the bacterial concentration and the sporulation efficiency of strain NCD-2 by 2.04 times and 1.99 times compared with D-glucose, respectively. Moreover, L-arabinose significantly decreased the autolysis of strain NCD-2. Genes associated with arabinose metabolism, sporulation, spore resistance to heat, and spore coat formation were significantly up-regulated, and genes associated with sporulation-delaying protein were significantly down-regulated under L-arabinose treatment. The deletion of msmX, which is involved in arabinose transport in the Bacillus genus, decreased growth and sporulation by 53.71% and 86.46% compared with wild-type strain NCD-2, respectively. Complementing the mutant strain by importing an intact msmX gene restored the strain's growth and sporulation.

Fatty acid export protein BnFAX6 functions in lipid synthesis and axillary bud growth in Brassica napus.

Sugar is considered as the primary regulator of plant apical dominance, whereby the outgrowth of axillary buds is inhibited by the shoot tip. However, there are some deficiencies in this theory. Here, we reveal that Fatty Acid Export 6 (BnFAX6) functions in FA transport, and linoleic acid or its derivatives acts as a signaling molecule in regulating apical dominance of Brassica napus. BnFAX6 is responsible for mediating FA export from plastids. Overexpression of BnFAX6 in B. napus heightened the expression of genes involved in glycolysis and lipid biosynthesis, promoting the flow of photosynthetic products to the biosynthesis of FAs (including linoleic acid and its derivatives). Enhancing expression of BnFAX6 increased oil content in seeds and leaves and resulted in semi-dwarf and increased branching phenotypes with more siliques, contributing to increased yield per plant relative to wild-type. Furthermore, decapitation led to the rapid flow of the carbon from photosynthetic products to FA biosynthesis in axillary buds, consistent with the overexpression of BnFAX6 in B. napus. In addition, free FAs, especially linoleic acid, were rapidly transported from leaves to axillary buds. Increasing linoleic acid in axillary buds repressed expression of a key transcriptional regulator responsible for maintaining bud dormancy, resulting in bud outgrowth. Taken together, we uncovered that BnFAX6 mediating FA export from plastids functions in lipid biosynthesis and in axillary bud dormancy release, possibly through enhancing linoleic acid level in axillary buds of B. napus.

Polyesterified Sesquiterpenoids from the Seeds of Celastrus paniculatus as Lifespan-Extending Agents for the Nematode Caenorhabditis elegans.

Eighteen new polyesterified dihydro-ß-agarofurans, celaspaculins A-R, as well as 11 known ones, were purified from the seeds of Celastrus paniculatus. The structures of new isolates were identified by extensive spectroscopic analysis and X-ray diffraction studies. The lifespan-extending activity of the dihydro-ß-agarofuran-enriched fraction and 10 abundant polyesterified dihydro-ß-agarofurans was evaluated on the nematode Caenorhabditis elegans model. Consequently, the dihydro-ß-agarofuran-enriched fraction and compounds 5, 14, and 21 notably increased the average survival time of C. elegans by 23%, 16%, 18%, and 17%, respectively, compared with the blank control group (p < 0.0001).

Diterpenoids from the Root Bark of Pinus massoniana and Evaluation of Their Phosphodiesterase Type 4D Inhibitory Activity.

Thirty-two diterpenoids were obtained from the root bark of Pinus massoniana, and, among them, five compounds (pinmassins A-E) were identified as undescribed analogues. Spectroscopic methods, X-ray single-crystal diffraction analysis, and ECD calculations were applied to establish the structure of the new isolates. Pinmassin D (4) and abieta-8,11,13,15-tetraen-18-oic acid (23) showed moderate phosphodiesterase type 4D (PDE4D) inhibitory effects with IC50 values of 2.8 ± 0.18 and 3.3 ± 0.50 µM, respectively, and their binding modes were investigated by a molecular docking study.

Neuroprotective Dihydro-ß-agarofuran-Type Sesquiterpenes from the Seeds of Euonymus maackii.

Twenty-one dihydro-ß-agarofuran derivatives were purified from the seeds of Euonymus maackii, and eight compounds (1-8) were identified as new natural products. Their structures were deduced by extensive spectroscopic analysis, X-ray diffraction studies, and comparison of observed and reported NMR data. Compounds 10, 12, 17, and 18 significantly increased the cell viability of Aß25-35-treated SH-SY5Y cells with effects similar to that of epigallocatechin gallate (EGCG). In addition, the abundant compound 9 reduced the seizure-like locomotor activity of zebrafish at 10 µM compared with a pentylenetetrazol-treated group.

TOC1: a valuable tool in assessing disease progression in the rTg4510 mouse model of tauopathy.

All tauopathies result in various forms of cognitive decline and neuronal loss. Although in some diseases, tau mutations appear to cause neurodegeneration, the toxic "form" of tau remains elusive. Tau is the major protein found within neurofibrillary tangles (NFTs) and therefore it seemed rational to assume that aggregation of tau monomers into NFTs was causal to the disease process. However, the appearance of oligomers rather than NFTs coincides much better with the voluminous neuronal loss in many of these diseases. In this study, we utilized the bigenic mouse line (rTg4510) which conditionally expresses P301L human tau. A novel tau antibody, termed Tau Oligomer Complex 1 (TOC1) was employed to probe mouse brains and assess disease progression. TOC1 selectively recognizes dimers/oligomers and appears to constitute an early stage marker of tau pathology. Its peak reactivity is coincident with other well-known early stage pathological markers such as MC1 and the early-stage phospho-marker CP13. TOC1's reactivity depends on the conformation of the tau species since it does not react with monomer under native conditions, although it does react with monomers under SDS-denaturation. This indicates a conformational change must occur within the tau aggregate to expose its epitope. Tau oligomers preferentially form under oxidizing conditions and within this mouse model, we observe tau oligomers forming at an increased rate and persisting much longer, most likely due to the aggressive P301L mutation. With the help of other novel antibodies, the use of this antibody will aid in providing a better understanding of tau toxicity within Alzheimer's disease and other tauopathies.

Ventilation failure after endotracheal intubation in an infant with abdominal compartment syndrome: A case report.

Intra-abdominal hypertension and abdominal compartment syndrome (ACS) are distinct clinical stages of pathology caused by increased intra-abdominal pressure, which may lead to respiratory and circulatory dysfunction in children and is associated with high pediatric mortality. An emergency exploratory laparotomy was planned for an infant with ACS. After induction of anesthesia and endotracheal intubation, the patient developed ventilation failure and any management was ineffective. Ventilation was resumed after a race against time abdominal decompression by the surgical team. Abdominal decompression is the primary treatment to relieve respiratory and circulatory failure in children with ACS.

Two new limonoid glycosides from the seeds of Citrus Limon and their PDE4D inhibitory activities.

Two new limonoid glycosides, named limonosides A (1) and B (2), along with four known limonoids (3-6) were obtained from the seeds of Citrus limon. Their structures were deduced based on extensive spectroscopic analysis. Limonoside A (1) and nomilin (4) were found to possess moderate phosphodiesterase type 4D (PDE4D) inhibitory effect with values of 89.8 ± 2.4% and 98.9 ± 3.0% at 10 µM, respectively.

Fabrication of a novel polyvinylpyrrolidone/chitosan-Schiff base/Fe2O3 nanocomposite for efficient adsorption of Pb(II) and Hg(II) ions from aqueous solution.

A novel magnetic polyvinylpyrrolidone/chitosan-Schiff base/Fe2O3 (PVP/CS-SB/Fe2O3) adsorbent was prepared by one-pot facile co-precipitation route for adsorption of Pb(II) and Hg(II) ions from aqueous solution. Fourier transform infrared-spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscope (SEM), vibrating sample magnetometer (VSM) and Brunauer-Emmett-Teller (BET) were used to characterize the synthesized PVP/CS-SB/Fe2O3. The results predicted that the successfully synthesis of magnetic CSSB-PVP@Fe2O3. The effects of important factors such as pH solution, contact time, concentration of metal ions, adsorbent dose and co-existing ions on Pb(II) and Hg(II) adsorption were investigated. The maximum adsorption capacities of Pb(II) and Hg(II) ions at optimal conditions were 120 mg/g and 102.5 mg/g, respectively. The kinetic studies predicted that the adsorption followed the pseudo-second-order (PSO) model as chemisorption using the coordination of active sites of PVP/CS-SB/Fe2O3 with the metal ions and also n-π interactions. Reproducibility results predicted that the excellent regeneration ability after 6 adsorption cycles. According to the results of this work, the PVP/CS-SB/Fe2O3 nanocomposite is promising for Pb(II) and Hg(II) ions adsorption and can be potential as a simple, low-cost, high-efficient adsorbent for decontamination of other heavy metal ions from aqueous solution.

Effects of selenoprotein extracts from Cardamine hupingshanensis on growth, selenium metabolism, antioxidant capacity, immunity and intestinal health in largemouth bass Micropterus salmoides.

This study aimed to assess the impact of dietary selenoprotein extracts from Cardamine hupingshanensis (SePCH) on the growth, hematological parameters, selenium metabolism, immune responses, antioxidant capacities, inflammatory reactions and intestinal barrier functions in juvenile largemouth bass (Micropterus salmoides). The base diet was supplemented with four different concentrations of SePCH: 0.00, 0.30, 0.60 and 1.20 g/Kg (actual selenium contents: 0.37, 0.59, 0.84 and 1.30 mg/kg). These concentrations were used to formulate four isonitrogenous and isoenergetic diets for juvenile largemouth bass during a 60-day culture period. Adequate dietary SePCH (0.60 and 1.20 g/Kg) significantly increased weight gain and daily growth rate compared to the control groups (0.00 g/Kg). Furthermore, 0.60 and 1.20 g/Kg SePCH significantly enhanced amounts of white blood cells, red blood cells, platelets, lymphocytes and monocytes, and levels of hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin in the hemocytes. In addition, 0.60 and 1.20 g/Kg SePCH increased the mRNA expression levels of selenocysteine lyase, selenophosphate synthase 1, 15 kDa selenoprotein, selenoprotein T2, selenoprotein H, selenoprotein P and selenoprotein K in the fish liver and intestine compared to the controls. Adequate SePCH not only significantly elevated the activities of antioxidant enzymes (Total superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase), the levels of total antioxidant capacity and glutathione, while increased mRNA transcription levels of NF-E2-related factor 2, Cu/Zn-superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase. However, adequate SePCH significantly decreased levels of malondialdehyde and H2O2 and the mRNA expression levels of kelch-like ECH-associated protein 1a and kelch-like ECH-associated protein 1b in the fish liver and intestine compared to the controls. Meanwhile, adequate SePCH markedly enhanced the levels of immune factors (alkaline phosphatase, acid phosphatase, lysozyme, complement component 3, complement component 4 and immunoglobulin M) and innate immune-related genes (lysozyme, hepcidin, liver-expressed antimicrobial peptide 2, complement component 3 and complement component 4) in the fish liver and intestine compared to the controls. Adequate SePCH reduced the levels of pro-inflammatory cytokines (tumour necrosis factor-α, interleukin 8, interleukin 1ß and interferon γ), while increasing transforming growth factor ß1 levels at both transcriptional and protein levels in the liver and intestine. The mRNA expression levels of mitogen-activated protein kinase 13 (MAPK 13), MAPK14 and nuclear factor kappa B p65 were significantly reduced in the liver and intestine of fish fed with 0.60 and 1.20 g/Kg SePCH compared to the controls. Histological sections also demonstrated that 0.60 and 1.20 g/Kg SePCH significantly increased intestinal villus height and villus width compared to the controls. Furthermore, the mRNA expression levels of tight junction proteins (zonula occludens-1, zonula occludens-3, Claudin-1, Claudin-3, Claudin-5, Claudin-11, Claudin-23 and Claudin-34) and Mucin-17 were significantly upregulated in the intestinal epithelial cells of 0.60 and 1.20 g/Kg SePCH groups compared to the controls. In conclusion, these results found that 0.60 and 1.20 g/Kg dietary SePCH can not only improve growth, hematological parameters, selenium metabolism, antioxidant capacities, enhance immune responses and intestinal functions, but also alleviate inflammatory responses. This information can serve as a useful reference for formulating feeds for largemouth bass.

High Starch Induces Hematological Variations, Metabolic Changes, Oxidative Stress, Inflammatory Responses, and Histopathological Lesions in Largemouth Bass (Micropterus salmoides).

This study evaluated effects of high starch (20%) on hematological variations, glucose and lipid metabolism, antioxidant ability, inflammatory responses, and histopathological lesions in largemouth bass. Results showed hepatic crude lipid and triacylglycerol (TAG) contents were notably increased in fish fed high starch. High starch could increase counts of neutrophils, lymphocytes, monocytes, eosinophils, and basophils and serum contents of TAG, TBA, BUN, and LEP (p < 0.05). There were increasing trends in levels of GLUT2, glycolysis, gluconeogenesis, and LDH in fish fed high starch through the AKT/PI3K signal pathway. Meanwhile, high starch not only triggered TAG and cholesterol synthesis, but mediated cholesterol accumulation by reducing ABCG5, ABCG8, and NPC1L1. Significant increases in lipid droplets and vacuolization were also shown in hepatocytes of D3-D7 groups fed high starch. In addition, high starch could decrease levels of mitochondrial Trx2, TrxR2, and Prx3, while increasing ROS contents. Moreover, high starch could notably increase amounts of inflammatory factors (IL-1ß, TNF-α, etc.) by activating NLRP3 inflammasome key molecules (GSDME, caspase 1, etc.). In conclusion, high starch could not only induce metabolic disorders via gluconeogenesis and accumulation of glycogen, TAG, and cholesterol, but could disturb redox homeostasis and cause inflammatory responses by activating the NLRP3 inflammasome in largemouth bass.

Multiomics integration reveals NETosis heterogeneity and TLR2 as a prognostic biomarker in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant neoplasm characterized by a poor prognosis and limited therapeutic strategy. The PDAC tumor microenvironment presents a complex heterogeneity, where neutrophils emerge as the predominant constituents of the innate immune cell population. Leveraging the power of single-cell RNA-seq, spatial RNA-seq, and multi-omics approaches, we included both published datasets and our in-house patient cohorts, elucidating the inherent heterogeneity in the formation of neutrophil extracellular traps (NETs) and revealed the correlation between NETs and immune suppression. Meanwhile, we constructed a multi-omics prognostic model that suggested the patients exhibiting downregulated expression of NETs may have an unfavorable outcome. We also confirmed TLR2 as a potent prognosis factor and patients with low TLR2 expression had more effective T cells and an overall survival extension for 6 months. Targeting TLR2 might be a promising strategy to reverse immunosuppression and control tumor progression for an improved prognosis.

Prenatal LPS leads to increases in RAS expression within the PVN and overactivation of sympathetic outflow in offspring rats.

The renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) are two major blood pressure-regulating systems. The link between the renal and cerebral RAS axes was provided by reflex activation of renal afferents and efferent sympathetic nerves. There is a self-sustaining enhancement of the brain and the intrarenal RAS. In this study, prenatal exposure to lipopolysaccharide (LPS) led to increased RAS activity in the paraventricular nucleus (PVN) and overactivation of sympathetic outflow, accompanied by increased production of reactive oxygen species (ROS) and disturbances between inhibitory and excitatory neurons in PVN. The AT1 receptor blocker losartan and α2 adrenergic receptor agonist clonidine in the PVN significantly decreased renal sympathetic nerve activity (RSNA) and synchronously reduced systolic blood pressure. Prenatal LPS stimulation caused H3 acetylation at H3K9 and H3K14 in the PVN, which suggested that epigenetic changes are involved in transmitting the prenatal adverse stimulative information to the next generation. Additionally, melatonin treatment during pregnancy reduced RAS activity and ROS levels in the PVN; balanced the activity of inhibitory and excitatory neurons in the PVN; increased urine sodium secretion; reduced RSNA and blood pressure. In conclusion, prenatal LPS leads to increased RAS expression within the PVN and overactivation of the sympathetic outflow, thereby contributing to hypertension in offspring rats. Melatonin is expected to be a promising agent for preventing prenatal LPS exposure-induced hypertension.

Design, synthesis and biological evaluation of glucose-containing scutellarein derivatives as neuroprotective agents based on metabolic mechanism of scutellarin in vivo.

Based on metabolic mechanism of scutellarin in vivo that scutellarin could be hydrolyzed into scutellarein by ß-glucuronide enzyme, some glucose-containing scutellarein derivatives were designed and synthesized through the introduction of glucose moiety at C-7 position of scutellarein via a glucosidic bond. Biological activity evaluation showed that these glucose-containing scutellarein derivatives exhibited potent DPPH radical scavenging activities. Furthermore, the improvement of physicochemical properties such as anticoagulant and neuroprotective activities alongside with the water solubility was achieved by introducing glucose. These findings suggest that the introduction of the glucose moiety to scutellarein wattants further development of this kind of compounds as neuroprotective agents.

Comparative analysis of the efficacy and safety of electromagnetic navigation bronchoscopy combined with x-ray or radial endobronchial ultrasound biopsy in the diagnosis of small peripheral pulmonary nodules.

OBJECTIVE: To compare the clinical value and safety of electromagnetic navigation bronchoscopy (ENB) combined with radial endobronchial ultrasound (R-EBUS) or x-ray in the diagnosis of small peripheral pulmonary nodules that cannot be diagnosed by conventional bronchoscopy. METHODS: Fifty-six patients with peripheral pulmonary nodules of <3 cm in diameter who underwent bronchoscopy at the First Affiliated Hospital of Soochow University and Dushu Lake Hospital of Soochow University from February 2019 to January 2022 were selected as the study subjects, including 24 patients who underwent ENB combined with x-ray and 32 patients who underwent ENB combined with R-EBUS. ENB was used as the guiding method in both groups, and x-ray group and R-EBUS group were combined with x-ray and R-EBUS, respectively, to determine whether the lesion was reached. In x-ray group, biopsy and brushing were performed under fluoroscopic guidance. Using the results of surgery, puncture pathology, or clinical follow-up 1 year as the gold standard, the diagnostic sensitivity, specificity, negative predictive value (NPV), diagnostic yield, negative likelihood ratio (LR-), Youden index, missed diagnosis rate, success rate, and κ value were compared between the two groups, and the occurrence of postoperative complications was also compared between the two groups. RESULTS: The negative predictive value of the R-EBUS group was significantly better than that of the x-ray group (p = 0.006). CONCLUSION: Even with smaller nodule diameters, the negative predictive value of ENB combined with R-EBUS were still higher than that of the x-ray group.

Novel flexible sensing technology for nondestructive detection on live fish health/quality during waterless and low-temperature transportation.

Fish health/quality issues are increasingly attracting attention during waterless and low-temperature transportation. Nondestructive detection has become a great need for an effective method to improve fish health/quality. Currently, emerging Internet of Things, novel flexible electronics and data fusion technology have received great interest for nondestructive detection on live fish health/quality. This paper analysized nondestructive detection mechanisms using novel flexible sensing technology to achieve high-precision sensing of key parameters, and machine learning based data fusion modeling to achieve live fish health/quality nondestructive evaluation during waterless and low-temperature transportation. Recent studies on novel flexible electrochemical and physiological biosensors development and application for solving key ambient and physiological parameter sensing were summarized. The ML based data fusion modeling framework and application for live fish health/quality nondestructive evaluation was also highlighted. The future perspective is also proposed to provide promising solutions for accurate sensing of multi-parameter and real applications of live fish health/quality nondestructive detection during waterless and low-temperature transportation.