Comprehensive evaluation of freezing tolerance in prickly ash and its correlation with ecological and geographical origin factors.

Low temperatures are a key factor affecting the growth, development, and geographical distribution of prickly ash. This study investigated the impact of ecological and geographical factors on the freezing tolerance of prickly ash germplasm. Thirty-seven germplasm samples from 18 different origins were collected, and their freezing tolerance was comprehensively evaluated. The correlation between freezing tolerance and the ecological and geographical factors of their origins was also analyzed. Significant differences in freezing tolerance were observed among germplasm from different origins. The semi-lethal temperature of the germplasm ranged from - 12.37 to 1.08 °C. As temperatures decreased, the relative conductivity (REC) and catalase (CAT) activity of the germplasm gradually increased, while soluble sugar (SS), soluble protein (SP), free proline (Pro), and Peroxidase (POD) activities decreased and then increased. Superoxide dismutase (SOD) activity initially increased and then decreased. A comprehensive evaluation of freezing tolerance was conducted using a logistic equation, membership function, and cluster analysis. Germplasm from Tongchuan and Hancheng (Shaanxi Province, China), Asakura (Japan), and Yuncheng (Shanxi Province, China) exhibited the highest freezing tolerance, whereas those from Rongchang (Chongqing Municipality, China), Qujing (Yunnan Province, China), and Honghe (Yunnan Province, China) had the lowest. The correlation analysis revealed a significant positive correlation between freezing tolerance and latitude, and a significant negative correlation with the temperature of origin. Germplasm from higher latitudes showed higher SS content, SOD and CAT activities, stronger antioxidant enzyme activity, and better freezing tolerance compared to those from lower latitudes. REC was lower in germplasm originating from low-temperature areas than in those from high-temperature areas. Additionally, SP, Pro content, SOD, and POD activities were higher, indicating effective scavenging of active oxygen free radicals. No significant correlation was found between altitude and longitude of origin and freezing tolerance. However, at similar latitudes, prickly ash from higher altitudes displayed higher antioxidant enzyme activity and stronger freezing tolerance compared to those from lower altitudes. These findings provide a scientific basis for breeding prickly ash cultivars suited to different ecological regions.

Interaction of oat bran and exercise training improved exercise adaptability via alleviating oxidative stress and promoting energy homeostasis.

Skeletal muscle performance is influenced by both diet and the mode of exercise, with diet playing a crucial role in individuals' adaptation to exercise training. Our study investigated the interaction of oat bran (OB) diet and moderate intensity exercise training (MIET) on skeletal muscle function and athletic performance. Studies have reinforced the positive association of high-fat diet (HFD) with chronic systemic inflammation and corresponding peripheral skeletal muscle dysfunction during exercise training. OB could alleviate the inflammation, oxidative stress, and energy homeostasis disorder associated with HFD. We observed improvement in mice limb grip strength and endurance treadmill running distance with OB intake, accompanied by regulation of muscle function-related gene expression. OB intensified exercise training-induced carbohydrate and lipid metabolism, as indicated by changes in lactate, fumarate, malate, pyruvate, succinate, and citrate levels. Additionally, specific probiotic genera producing short-chain fatty acids (SCFAs) were promoted, while inflammation-related circulating metabolites were significantly decreased with oat bran intake. Our findings suggest interactions between OB and MIET improved HFD-induced skeletal muscle dysfunction on both the phenotype and the related mechanisms. This study is an extension of our previous study on the anti-fatigue effect of oat bran, providing a novel prospective by integrating exercise adaptation, gut microbiota, molecular metabolism and skeletal muscle in situ analysis.

Comprehensive transcriptome and scRNA-seq analyses uncover the expression and underlying mechanism of SYNJ2 in papillary thyroid carcinoma.

Synaptojanin 2 (SYNJ2) has crucial role in various tumors, but its role in papillary thyroid carcinoma (PTC) remains unexplored. This study first detected SYNJ2 protein expression in PTC using immunohistochemistry method and further assessed SYNJ2 mRNA expression through mRNA chip and RNA sequencing data and its association with clinical characteristics. Additionally, KEGG, GSVA, and GSEA analyses were conducted to investigate potential biological functions, while single-cell RNA sequencing data were used to explore SYNJ2's underlying mechanisms in PTC. Meanwhile, immune infiltration status in different SYNJ2 expression groups were analyzed. Besides, we investigated the immune checkpoint gene expression and implemented drug sensitivity analysis. Results indicated that SYNJ2 is highly expressed in PTC (SMD = 0.66 [95% CI: 0.17-1.15]) and could distinguish between PTC and non-PTC tissues (AUC = 0.74 [0.70-0.78]). Furthermore, the study identified 134 intersecting genes of DEGs and CEGs, mainly enriched in the angiogenesis and epithelial-mesenchymal transition (EMT) pathways. Subsequent analysis showed the above pathways were activated in PTC epithelial cells. PTC patients with high SYNJ2 expression showed higher sensitivity to the six common drugs. Summarily, SYNJ2 may promote PTC progression through angiogenesis and EMT pathways. High SYNJ2 expression is associated with better response to immunotherapy and chemotherapy.

Acupuncture's Emergence as A Promising Non-Pharmacological Therapy for Appetite Management in Cancer Chemotherapy.

OBJECTIVE: The primary objective of this investigation was to assess the impact of acupuncture intervention and explore the intricacies of acupoint selection as a therapeutic strategy for chemotherapy-induced Anorexia (CIA). METHOD: Eight electronic databases were searched to identify relevant studies on the use of acupuncture for the treatment of CIA to conduct a comprehensive meta-analysis. Following this, the Apriori algorithm, correlation analysis, and cluster analysis were performed to identify correlations between the selection of acupoints. RESULTS: Acupuncture significantly reduced the incidence of anorexia (RR = 0.76, 95%CI: 0.65, 0.90; I2=63%; p = 0.001; n = 503) and anorexia score (SMD=-0.33, 95%CI: -0.53, -0.14; I2=22%; p = 0.0008; n = 419), as well as preserved body mass (MD = 2.70, 95%CI: 1.08, 4.32; I2=0%; p = 0.001; n = 187) and enhanced physical strength (MD = 4.23, 95%CI: 1.90, 6.55; I2=58%; p = 0.0004; n = 377). Moreover, subgroup analysis highlighted its efficacy in managing anorexia associated with non-gastrointestinal tumors and mitigating the severity of cisplatin-induced anorexia. Meanwhile, Zusanli (ST36), Neiguan (PC6), Tianshu (ST25), Zhongwan (RN12), and Qihai (RN6) were identified as crucial acupoints in CIA management. CONCLUSION: Acupuncture holds promise as a potential non-pharmacological approach for managing anorexia during cancer chemotherapy. To provide robust evidence of its effectiveness, well-designed Randomized Controlled Trials (RCTs) with larger participant cohorts, and consistent core outcome measures are essential.

LC-MS coupled with diagnostic ion strategy facilitated the discovery of 5-methylcoumarin meroterpenoids from Gerbera piloselloides.

Plant-derived natural products remain crucial in drug development. However, the identification of undescribed natural products is becoming increasingly challenging. A comprehensive strategy combining LC-MS with diagnostic ions was proposed for the discovery of undescribed 5-methylcoumarin meroterpenoids. Thirteen undescribed 5-methylcoumarin meroterpenoids, including five pairs of enantiomers (1a/1b and 5a/5b-8a/8b), were isolated from the whole plant of Gerbera piloselloides. Their structures and absolute configurations were unambiguously determined based on their spectroscopic data, calculated and experimental ECD data and X-ray diffraction analysis. Bioassays conducted on scopolamine-induced injury PC12 cells revealed that compounds 5a/5b, 7a/7b and 8a/8b possessed mild protective effects. Additionally, compounds 2 and 8 showed notable IL-6 inhibition in lipopolysaccharide-induced BEAS-2B cells.

Surgical treatment of urachal adenocarcinoma with lung metastasis: A case report and literature review.

Arising from the urachal epithelial lining, the urachal carcinoma is a rare tumor, which accounts for 0.35%-0.7% of all bladder cancers. Urachal carcinoma has a higher predilection in men with median age around 50-60 years old. The most common clinical symptom is intermittent painless gross hematuria, and less-reported presentations include suprapubic mass, dysuria, lower abdominal pain, and frequent urination. The pathological study reveals that most cases (90%) are categorized as an intestinal adenocarcinoma subtype, while other morphological variants, including mucinous, enteric, signet ring cell subtype, not otherwise specified (NOS), squamous cell carcinoma, urothelial carcinoma, sarcoma, small cell carcinoma, and undifferentiated carcinoma, totally account for about 10%. The urachal carcinoma occurs mostly in the lower segment of urachal tube and bladder dome or anterior wall. However, due to the classically silent nature of the early lesions and high malignancy, urachal carcinoma patients are commonly diagnosed in advanced stage. Treatment modalities for local recurrence or metastatic urachal cancer include surgery and chemotherapy (cisplatin and 5-FU based-chemotherapy). Meanwhile, the EGFR-, PD-L1-, and MEK-targeted therapies in the metastatic urachal carcinoma cases showed satisfactory response. We presented a rare case of Sheldon stage IVB urachal adenocarcinoma with pulmonary metastasis, and the patient had no progression of disease 6 months following surgical treament without chemoradiotherapy.

Advance in the pathogenesis of otitis media with effusion induced by platelet-activating factor.

A non-suppurative inflammatory disease of the middle ear with middle ear effusion and conductive hearing loss is called otitis media with effusion. Poor eustachian tube function, immunological factors, viral factors, and other factors are primarily involved in its pathophysiology, which has not yet been completely understood. Several researcher scholars have recently studied platelet-activating factor and they found that platelet-activating factor is closely associated to the occurrence, development, and outcome of otitis media with effusion. Platelet-activating factor is a significant element contributing to the extension of otitis media with effusion. In order to give a reference for further investigation into the mechanism and clinical management of this illness, the research status of platelet-activating factor and otitis media with effusion during the past two decades is reviewed in this study, along with the mechanisms of otitis media with effusion leading to otitis media with effusion.

[Characteristics of intestinal microbiota in the acute phase of Kawasaki disease in infants and children]. / å©´å¹¼å„¿å·å´Žç— æ€¥æ€§æœŸè‚ é“èŒç¾¤çš„ç‰¹å¾åˆ†æž.

OBJECTIVES: To study the composition, abundance, and functional profiles of the intestinal microbiota in infants and young children with Kawasaki disease (KD) during the acute phase, and to explore the potential role of intestinal microbiota in the pathogenesis of KD. METHODS: Six children aged 0-3 years with acute KD admitted to the Department of Cardiology, Children's Hospital Affiliated to Capital Institute of Pediatrics from July to October 2021 were prospectively included as the KD group. Six age- and sex-matched healthy children who underwent physical examinations at the hospital during the same period were selected as the healthy control group. Metagenomics sequencing was used to detect and compare the differences in the microflora structure and functional profiles of fecal samples between the two groups. RESULTS: There were significant differences in the structural composition and diversity of intestinal microbiota between the two groups (P<0.05). Compared with the healthy control group, the abundance of Listeria_monocytogenes (family Listeriaceae and genus Listeria), Bifidobacterium_rousetti, Enterococcus_avium, and Enterococcus_hirae was significantly higher in the intestinal microbiota in the KD group (|LDA|>2.0, P<0.05). The steroid degradation and apoptosis pathways were significantly upregulated in the KD group compared with the healthy control group, while the Bacterial_secretion_system, Sulfur_metabolism, Butanoate_metabolism, Benzoate_degradation, ß-alanine metabolism, and α-linolenic acid pathways were significantly downregulated (|LDA|>2, P<0.05). CONCLUSIONS: There are significant differences in the structure and diversity of intestinal microbiota between children aged 0-3 years with acute KD and healthy children, suggesting that disturbances in intestinal microbiota occur during the acute phase of KD. In particular, Listeria_monocytogenes, Enterococcus_avium, and Enterococcus_hirae may be involved in the pathogenesis of KD through steroid degradation and apoptosis pathways.

Isomalto-Oligosaccharide Potentiates Alleviating Effects of Intermittent Fasting on Obesity-Related Cognitive Impairment during Weight Loss and the Rebound Weight Gain.

Obesity-related cognitive dysfunction poses a significant threat to public health. The present study demonstrated mitigating effects of intermittent fasting (IF) and its combination with isomalto-oligosaccharides and IF (IF + IMO) on cognitive impairments induced by a high-fat-high-fructose (HFHF) diet in mice, with IF + IMO exhibiting superior effects. Transcriptomic analysis of the hippocampus revealed that the protective effects on cognition might be attributed to the suppression of toll-like receptor 4 (TLR4)/NFκB signaling, oxidative phosphorylation, and neuroinflammation. Moreover, both IF and IF + IMO modulated the gut microbiome and promoted the production of short-chain fatty acids, with IF + IMO displaying more pronounced effects. IF + IMO-modulated gut microbiota, metabolites, and molecular targets associated with cognitive impairments were further corroborated using human data from public databases Gmrepo and gutMgene. Furthermore, the fecal microbiome transplantation confirmed the direct impacts of IF + IMO-derived microbiota on improving cognition functions by suppressing TLR4/NFκB signaling and increasing BDNF levels. Notably, prior exposure to IF + IMO prevented weight-regain-induced cognitive decline, suppressed TLR4/NFκB signaling and inflammatory cytokines in the hippocampus, and mitigated weight regain-caused gut dysbacteriosis without altering body weight. Our study underscores that IMO-augmented alleviating effects of IF on obesity-related cognitive impairment particularly during weight-loss and weight-regain periods, presenting a novel nutritional strategy to tackle obesity-related neurodegenerative disorders.

Structural-informed functional MRI analysis of patients with empathy impairment following stroke.

BACKGROUND: The underlying functional alterations of brain structural changes among patients with empathy impairment following stroke remain unclear. We sought to investigate functional connectivity changes informed by brain structural abnormalities in multimodal magnetic resonance imaging (MRI) among patients with empathy impairment following stroke. METHODS: We enrolled people who had experienced their first ischemic stroke, along with healthy controls. We assessed empathy 3 months after stroke using the Chinese version of the Empathy Quotient (EQ). During the acute phase, all patients underwent basic magnetic resonance imaging (MRI), followed by multimodal MRI during follow-up. Our MRI analyses encompassed acute infarction segmentation, volumetric brain measurements, regional quantification of diffusion parameters, and both region-of-interest-based and seed-based functional connectivity assessments. We grouped patients based on the severity of their empathy impairment for comparative analysis. RESULTS: We included 84 patients who had stroke and 22 healthy controls. Patients had lower EQ scores than controls. Patients with low empathy had larger left cortical infarcts (odds ratio [OR] 4.082, 95% confidence interval [CI] 1.183-14.088), more pronounced atrophy in the right cingulate cortex (OR 1.248, 95% CI 1.038-1.502), and lower scores on the Montreal Cognitive Assessment (OR 0.873, 95% CI 0.74-0.947). In addition, the cingulate cortex served as the seed in the seed-based analysis, which showed heightened functional connectivity between the anterior cingulate gyrus and the right superior parietal lobule, specifically in the low-empathy group. LIMITATIONS: We did not evaluate the relationship between specific network involvement and empathy impairment among patients following stroke. CONCLUSION: Among patients with subacute ischemic stroke, reduced empathy was strongly associated with a more severe cognitive profile and atrophy of the right cingulate cortex. Our subsequent structural-informed functional MRI analysis suggests that the enhanced connectivity between the anterior cingulate gyrus and the superior parietal lobule may function as a compensatory mechanism for this atrophy.

The suppression of OTUD7B by miR-491-5p enhances the ubiquitination of VEGFA to suppress vascular mimicry in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the main type of lung cancer with high morbidity and mortality. Vascular mimicry (VM), a distinct microcirculation model in tumors that differs from classical angiogenesis, is strongly associated with poor clinical outcomes in cancer patients. miR-491-5p has been reported to prevent NSCLC progression, including proliferation, metastasis, and angiogenesis. However, the effect and mechanism of miR-491-5p on VM have not been studied in NSCLC. METHODS: The expression of miR-491-5p was detected by quantitative reverse transcription PCR (qPCR) and fluorescence in situ hybridization (FISH). Cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining assays were used to examine cell growth. Tube formation assay was used to assess VM in NSCLC cells. Immunohistochemistry (IHC) and western blot were performed to detect protein expression. Immunoprecipitation was used to confirm the interaction between OTU deubiquitinase 7B (OTUD7B) and vascular endothelial growth factor A (VEGFA), and the level of ubiquitinated VEGFA. A nude mouse tumorigenesis model was used to evaluate the carcinogenic capacity of NSCLC cells in vivo. Luciferase reporter assay was used to identify the potential target of miR-491-5p. RESULTS: MiR-491-5p was found downregulated in NSCLC tissues, and miR-491-5p deficiency was strongly associated with angiogenesis. miR-491-5p mimics suppressed cell viability, migration, and VM. Conversely, an inhibitor of miR-491-5p had the opposite effect. OTUD7B, a deubiquitinase, was identified as a downstream target of miR-491-5p. A luciferase reporter assay indicated that miR-491-5p directly binds to the 3'UTR of OTUD7B. Moreover, mimics of miR-491-5p caused a significant reduction in the OTUD7B protein in NSCLC cells, and an inhibitor of miR-491-5p stabilized the OTUD7B protein. In addition, overexpression of OTUD7B promoted cell proliferation, migration, and VM, similar to the effects of an inhibitor of miR-491-5p. Further exploration revealed that OTUD7B interacts with VEGFA and that the miR-491-5p-OTUD7B axis modulates the ubiquitination of VEGFA. The rescue experiment indicated that OTUD7B compromised the inhibitory effects of miR-491-5p on the cellular function of NSCLC cells. CONCLUSIONS: Overall, our study first proved that miR-491-5p impedes VM by suppressing OUTD7B and promoting the ubiquitination of VEGFA. The miR-491-5p/OTUD7B axis may be a novel target for antiangiogenic therapy in NSCLC.

DDAH1 deficiency exacerbates cerebral vascular endothelial dysfunction by aggravating BBB disruption and oxidative stress in thoracic blast-induced brain injury.

As terrorist incidents and underground explosion events have become more frequent around the world, brain injury caused by thoracic blast exposure has been more highlighted due to its injured organ, subsequent social and economic burden. It has been reported dimethylarginine dimethylaminohydrolase 1 (DDAH1) plays important roles in regulating vascular endothelial injury repair and angiogenesis, but its role in thoracic blast-induced brain injury remains to be explained. This study seeks to investigate the mechanism of DDAH1 on thoracic blast-induced brain injury. 40 C57BL/6 wild type mice and 40 DDAH1 knockout mice were randomly and equally divided into control group and blast group, respectively. The integrity of blood-brain barrier (BBB) was detected by Evans blue test. The serum inflammatory factors, nitric oxide (NO) contents, and asymmetric dimethylarginine (ADMA) levels were determined through ELISA. HE staining and reactive oxygen species (ROS) detection were performed for histopathological changes. Western blot was used to detect the proteins related to oxidative stress, tight junction, focal adhesion, vascular endothelial injury, and the DDAH1/ADMA/eNOS signaling pathway. DDAH1 deficiency aggravated thoracic blast-induced BBB leakage, inflammatory response, and the increased levels of inflammatory-related factors. Additionally, DDAH1 deficiency also increased ROS generation, MDA and IRE-α expression. Regarding cerebral vascular endothelial dysfunction, DDAH1 deficiency increased the expression of MCAM, FN1, LIMK1, VEGF, MMP9, Vimentin and N-cadherin, while lowering the expression of FMR1, Occludin, claudin-3, claudin-5, Lyn, LIMA1, Glrb, Sez6, Dystrophin, and phosphorylation of VASP. Also, DDAH1 deficiency exacerbated explosion-induced increase of ADMA and decrease of eNOS activity and NO contents. Thus, we conclude that DDAH1 could prevent cerebral vascular endothelial dysfunction and related injury by inhibiting ADMA signaling and increasing eNOS activity in thoracic blast induced brain injury.

Effects of the Fungicide Prothioconazole on Lipid Metabolism in Mice: Whitening Alterations of Brown Adipose Tissue.

With considerable concerns about the associations between metabolic disorders and agricultural biocides, there are scattered data suggesting that the triazole fungicide prothioconazole (PTC) at lower doses than the no observed adverse effect level of 5000 µg/kg/d possibly has the potential to disrupt glycolipid metabolism in mammals. Here, we investigated the effects of 50, 500, and 5000 µg/kg/d of PTC on glycolipid metabolism in mice following 8 weeks of administration via drinking water, with specific attention on brown adipose tissue (BAT) and white adipose tissue (WAT) in addition to the liver. We found that along with the increased serum triglyceride level in the 5000 µg/kg/d group, small fatty vacuoles occurred in livers in all treatment groups, indicating lipid accumulation. No change in WAT was observed, but PTC caused BAT whitening, characterized by adipocyte hypertrophy, more unilocular adipocytes with enlarged lipid droplets, reduced UCP1 levels, and down-regulated Doi2 expression, and even the dose of 50 µg/kg/d was effective. Transcriptomic analysis revealed immune inhibition and circadian rhythm disturbance in BAT from the 5000 µg/kg/d group, which are in agreement with BAT whitening and inactivation. On employing the C3H10T1/2 cells in vitro, we found that PTC treatment concentration-dependently promoted lipid accumulation in brown adipocytes, along with altered expression of thermogenesis-related and circadian genes. Taken together, our study shows that low doses of PTC caused BAT whitening, calling for much attention to the new target by pollutants.

Complex pectin metabolism by Lactobacillus and Streptococcus suggests an effective control approach for Maillard harmful products in brown fermented milk.

Harmful Maillard reaction products (HMRPs) derived from brown fermented milk pose a potential threat to human health, but the conversion mechanism during the manufacturing process remains elusive and urgently needs to be controlled. Acrylamide (FC 2.14, adjusted p-value = 0.041), 5-hydroxymethylfurfural (FC 2.61, adjusted p-value = 0.026) and methylglyoxal (FC 2.07, adjusted p-value = 0.019) were identified as the significantly increased HMRPs after browning in this study and the analysis of proteomics integrated with untargeted metabolomics demonstrated that the degradation of HMRPs was jointly accomplished by Streptococcus thermophilus and Lactobacillus bulgaricus. The galactose oligosaccharide metabolism in Streptococcus thermophilus was identified as a key biochemical reaction for HMRPs degradation, and the hydrolysates of pectin could be utilized as prebiotics for Streptococcus thermophilus. Eighteen classes of enzymes of L. bulgaricus and Streptococcus thermophilus related to energy metabolism were upregulated in the pectin-added group, indicating that the entry of acrylamide and methylglyoxal into the tricarboxylic acid cycle was accelerated. NAD-aldehyde dehydrogenase and alanine dehydrogenase are enzymes belonging to Streptococcus thermophilus, and their downregulation accelerated the efflux of acetate, which was beneficial for the proliferation of L. bulgaricus and prevented the conversion of pyruvate to l-alanine, thus facilitating the energy metabolism. The recoveries and relative standard deviations of the intraday and interday precision experiments were 89.1%-112.5%, 1.3%-8.4% and 2.1%-9.4%, respectively, indicating that the developed approach was credible. Sensory evaluation results revealed that the brown fermented milk added with pectin had a better flavor, which was due to the fact that the supplement of polysaccharide promoted the fatty acid metabolism of lactic acid bacteria and increased the aroma substances including octoic acid and valeric acid. This study provided an insight into the formation and degradation mechanism of HMRPs in brown fermented milk, aiming to reduce the intake of advanced glycation end products in the diet.

Fluorescence and colorimetric rapid dual-signal "on-off-on" switching detection of ascorbic acid based on TSPP/DCIP.

A fluorescence and colorimetric dual-signal sensing system for the determination of ascorbic acid (AA) in complex media was developed by using 5,10,15, 20-tetrakis(4-sulfonyl) porphyrin (TSPP) as a sensing probe and sodium 2,6-dichloroindophenol (DCIP) as a bridge. A fluorescence resonance energy transfer (FRET) effect occurred when DCIP was added to the TSPP solution, resulting in the quenching of the fluorescence signal of TSPP and a change in the color of the solution from pink to blue. The DCIP in the system reacted with AA in a redox reaction to produce colorless phenol imine, the color of the solution changed from blue to green causing an obvious colorimetric response, and the TSPP/DCIP sensing system's fluorescence signal restored owing to AA introduced. The fluorescence method for AA showed good linearity in the ranges 0.08 mM ~ 1 mM and 1 mM ~ 43.6 mM with a detection limit of 6.4 µM. And the colorimetric method for AA showed excellent linearity in the range 0.46 mM ~ 40.2 mM with a detection limit of 76.0 µM. The constructed "dual-signal" probe in the study has been successfully applied to the detection of AA in practical samples. The method proposed has great potential for practical applications and provides new ideas for the visual inspection of portable measurements.

Multi-scale transcriptomics reveals that specific tumor cells promote lung adenocarcinoma metastasis through crosstalk with the microenvironment.

Most advanced lung adenocarcinoma (LUAD) patient deaths are attributed to metastasis. However, the complete understanding of the metastatic mechanism in LUAD remains elusive. Single-cell RNA-seq (scRNA-seq), spatial RNA-seq (stRNA-seq) and bulk RNA-seq of primary LUAD were integrated to investigate metastatic driver genes, cell-cell interactions, and spatial colocalization of cells and ligand-receptor pairs. A lung adenocarcinoma metastasis risk scoring model (LMRS) was established to estimate the risk of metastasis in LUAD. Forty-two metastasis driver genes were identified and tumor epithelial cells were classified into two subtypes. Epithelial cell subclass characterized by susceptibility to metastasis are referred to as Epithelial_LM, and the remaining as Epithelial_LL. Epithelial_LM subtype has intimate ligand-receptor interactions with inflammatory endothelial cells (iendo), inflammatory cancer-associated fibroblasts (iCAF), and NKT cells. Epithelial_LM cells have a spatial colocalization relationship with these three types of cells. The LMRS was established and its efficacy was verified in bulk RNA-seq. We identified a subclass of epithelial cells prone to metastasis and demonstrated the contribution of inflammatory stromal cells and NKT cells in facilitating tumor metastasis.

Etiological stratification and prognostic assessment of haemophagocytic lymphohistiocytosis by machine learning on onco-mNGS data and clinical data.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare, complicated and life threatening hyperinflammatory syndrome that maybe triggered by various infectious agents, malignancies and rheumatologic disorders. Early diagnosis and identification of the cause is essential to initiate appropriate treatment and improve the quality of life and survival of patients. The recently developed Onco-mNGS technology can be successfully used for simultaneous detection of infections and tumors. Methods: In the present study, 92 patients with clinically confirmed HLH were etiologically subtyped for infection, tumor and autoimmunity based on CNV and microbial data generated by Onco-mNGS technology, and a predictive model was developed and validated for the differential diagnosis of the underlying disease leading to secondary HLH. Furthermore, the treatment outcomes of patients with HLH triggered by EBV infection and non-EBV infection were evaluated, respectively. Results: The current study demonstrated that the novel Onco-mNGS can identify the infection and malignancy- related triggers among patients with secondary HLH. A random forest classification model based on CNV profile, infectious pathogen spectrum and blood microbial community was developed to better identify the different HLH subtypes and determine the underlying triggers. The prognosis for treatment of HLH patients is not only associated with CNV, but also with the presence of pathogens and non- pathogens in peripheral blood. Higher CNV burden along with frequent deletions on chromosome 19, higher pathogen burden and lower non-pathogenic microbes were prognosis factors that significantly related with unfavorable treatment outcomes. Discussion: Our study provided comprehensive knowledge in the triggers and prognostic predictors of patients with secondary HLH, which may help early diagnosis and appropriate targeted therapy, thus improving the survival and prognosis of the patients.

Small airway inflammation in atypical asthma.

Background: Less attention has been paid to the pathophysiological changes in atypical asthma such as cough variant asthma (CVA) and chest tightness variant asthma (CTVA). The obstruction of large and small airways is the important component in the development of asthma. We investigated whether small airway inflammation (SAI) induced small airway dysfunction (SAD) in these atypical asthmatics. Methods: Six hundred and eighty-six patients were enrolled and analyzed in the study. The partitioned airway inflammation was assessed by fractional exhaled nitric oxide (FeNO), such as FnNO, FeNO50, FeNO200, and calculated alveolar fraction of exhaled NO (CaNOdual). Correlations between exhaled NOs and SAD-related variables were assessed, whereas cell classification was evaluated by Spearman's rank tests. Classic asthma, CVA, and CTVA about potential risk were conducted using binary logistic regression models. Results: The whole airway inflammation increased in classic and atypical asthma than controls, whereas the central and peripheral airway inflammation in the CVA and CTVA groups increased compared with the classic asthma group. Smoking exposure was found to increase the central and peripheral airway inflammation in patients with asthma. The exhaled NO of FeNO50 and FeNO200 was associated with SAD in classic asthma, but not in CVA and CTVA. FeNO200 was the main risk (adjusted odds ratio [OR], 1.591; 95 % CI, 1.121-2.259; P = .009) in classic asthma and (adjusted OR, 1.456; 95 % CI, 1.247-1.700; P = .000) in CVA. The blood eosinophil levels were correlated with FeNO50 and FeNO200 in classic asthma and atypical asthma. Conclusion: More severe inflammatory process was present in central and peripheral airways in CVA and CTVA, which might reflect a pre-asthmatic state. SAI was the predominant risk factor in the development of asthma before SAD.

Analysis of the CPZ/Wnt4 osteogenic pathway for high-bonding-strength composite-coated magnesium scaffolds through transcriptomics.

Magnesium (Mg)-based scaffolds are garnering increasing attention as bone repair materials owing to their biodegradability and mechanical resemblance to natural bone. Their effectiveness can be augmented by incorporating surface coatings to meet clinical needs. However, the limited bonding strength and unclear mechanisms of these coatings have impeded the clinical utility of scaffolds. To address these issues, this study introduces a composite coating of high-bonding-strength polydopamine-microarc oxidation (PDA-MHA) on Mg-based scaffolds. The results showed that the PDA-MHA coating achieved a bonding strength of 40.56 ± 1.426 MPa with the Mg scaffold surface, effectively enhancing hydrophilicity and controlling degradation rates. Furthermore, the scaffold facilitated bone regeneration by influencing osteogenic markers such as RUNX-2, OPN, OCN, and VEGF. Transcriptomic analyses further demonstrated that the PDA-MHA/Mg scaffold upregulated carboxypeptidase Z expression and activated the Wnt-4/ß-catenin signaling pathway, thereby promoting bone regeneration. Overall, this study demonstrated that PDA can synergistically enhance bone repair with Mg scaffold, broadening the application scenarios of Mg and PDA in the field of biomaterials. Moreover, this study provides a theoretical underpinning for the application and clinical translation of Mg-based scaffolds in bone tissue engineering endeavors.