External stakeholder risk response strategies selection in project portfolio.

To improve the effectiveness of external stakeholder risks (ESRs) management in project portfolios (PPs), a portfolio-wide risk response approach is required. However, current research is inadequate to effectively identify response strategies for ESRs, which brings challenges to managing ESRs in PPs. In this context, the purpose of this study is to select an appropriate combination of response strategies for ESRs by considering interactions among ESRs, projects, and response strategies in the PP. A Bayesian influence diagram (BID) coupled with a multi-objective optimization model is deemed suitable for this context. Firstly, a probability-sensitivity matrix is established to determine the key ESRs. Then, a BID is constructed to calculate the expected values of different combinations of response strategies. Finally, integrating stakeholder satisfaction and strategy cost, an optimization model for risk response strategy selection is established to obtain candidate combinations. By combining expected values and candidate combinations, the optimal strategy combination is selected. The proposed model comprehensively considers and evaluates the interactions between risks, projects, and risk responses. This enhances the desirability of expected outcomes and reduces project execution costs.

Photosensitizing metal covalent organic framework with fast charge transfer dynamics for efficient CO2 photoreduction.

Designing artificial photocatalysts for CO2 reduction is challenging, mainly due to the intrinsic difficulty of making multiple functional units cooperate efficiently. Herein, three-dimensional metal covalent organic frameworks (3D MCOFs) were employed as an innovative platform to integrate a strong Ru(ii) light-harvesting unit, an active Re(i) catalytic center, and an efficient charge separation configuration for photocatalysis. The photosensitive moiety was precisely stabilized into the covalent skeleton by using a rational-designed Ru(ii) complex as one of the building units, while the Re(i) center was linked via a shared bridging ligand with an Ru(ii) center, opening an effective pathway for their electronic interaction. Remarkably, the as-synthesized MCOF exhibited impressive CO2 photoreduction activity with a CO generation rate as high as 1840 µmol g-1 h-1 and 97.7% selectivity. The femtosecond transient absorption spectroscopy combined with theoretical calculations uncovered the fast charge-transfer dynamics occurring between the photoactive and catalytic centers, providing a comprehensive understanding of the photocatalytic mechanism. This work offers in-depth insight into the design of MCOF-based photocatalysts for solar energy utilization.

Biomechanism of abnormal stress on promoting osteoarthritis of temporomandibular joint through Piezo1 ion channel.

OBJECTIVE: This study aimed to investigate whether flow fluid shear stress (FFSS)-mediated signal transduction affects the function of Piezo1 ion channel in chondrocyte and to further explore the role of mechanical overloading in development of temporomandibular joint osteoarthritis (TMJ OA). METHODS: Immunohistochemical staining was used to determine the expression of Piezo1 in TMJ OA tissue collected from rat unilateral anterior crossbite (UAC) models. Chondrocytes harvested from normal adult SD rats were treated with FFSS (0, 4, 8, 12 dyn/cm2) in vitro. Immunofluorescent staining, real-time polymerase chain reaction, western blotting, flow cytometry and phalloidin assay were performed to detect the changes of cellular morphology as well as the expression of Piezo1 and certain pro-inflammatory and degradative factors in chondrocyte. RESULTS: Immunohistochemical analysis revealed that significantly increased Piezo1 expression was associated with UAC stimulation (p < .05). As applied FFSS escalated (4, 8 and 12 dyn/cm2), the expression levels of Piezo1, ADAMTS-5, MMP-13 and Col-X gradually increased, compared with the non-FFSS group (p < .05). Administering Piezo1 ion channel inhibitor to chondrocytes beforehand, it was observed that expression of ADAMTS-5, MMP-13 and Col-X was substantially decreased following FFSS treatment (p < .05) and the effect of cytoskeletal thinning was counteracted. The activated Piezo1 ion channel enhanced intracellular Ca2+ excess in chondrocytes during abnormal mechanical stimulation and the increased intracellular Ca2+ thinned the cytoskeleton of F-actin. CONCLUSIONS: Mechanical overloading activates Piezo1 ion channel to promote pro-inflammation and degradation and to increase Ca2+ concentration in chondrocyte, which may eventually result in TMJ OA.

Modulatory effects of gut microbiota on innate and adaptive immune responses following spinal cord injury.

Spinal cord injury (SCI) represents a highly debilitating trauma to the central nervous system, currently lacking effective therapeutic strategies. The cascade of inflammatory responses induced by secondary damage following SCI disrupts the local immune environment at the injury site, ultimately exacerbating functional impairments post-injury. With advancing research on the gut-brain axis, evidence suggests that dysbiosis of the gut microbiota post-SCI amplifies inflammatory responses and plays a pivotal role in modulating post-injury immune-inflammatory responses. In this review article, we will explore the significant role of the gut microbiota and its metabolic products in modulating the responses of central and peripheral immune cells post-SCI, as well as their potential as therapeutic interventions for SCI treatment.

Carrimycin inhibits coronavirus replication by decreasing the efficiency of programmed -1 ribosomal frameshifting through directly binding to the RNA pseudoknot of viral frameshift-stimulatory element.

The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity. Here, we show that carrimycin, a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials, decreases the efficiency of programmed -1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion. Carrimycin binds directly to the coronaviral frameshift-stimulatory element (FSE) RNA pseudoknot, interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes. Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses. Because the FSE mechanism is essential in all coronaviruses, carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA. This finding may open a new direction in antiviral drug discovery for coronavirus variants.

Apigenin suppresses the low oxaliplatin-induced epithelial-mesenchymal transition in oral squamous cell carcinoma cells via LINC00857.

Background: Apigenin is a natural flavonoid compound with proven antitumor activity. However, its precise underlying pharmacological mechanism remains unclear. Oxaliplatin (OXA) is commonly utilized for cancer treatment as a platinum-based chemotherapy drug. However, the utilization of low-dose OXA carries the risk of inducing epithelial-mesenchymal transition (EMT) in cancer cells and promoting tumor metastasis, thereby giving rise to potential side effects. The purpose of this study is to investigate the synergistic inhibitory effect of apigenin and OXA and its potential mechanism. Methods: HSC-3 cells of oral squamous carcinoma cells (OSCCs) were divided into control, apigenin-treated and co-treated groups. A wound healing assay was conducted to assess alterations in cellular motility and migration, an invasion assay was performed to assess invasiveness, and a three-dimensional culture assay was employed to evaluate angiogenic capacity. Cultured cells were utilized for total DNA extraction, followed by reverse transcription. Relative RNA levels were obtained, and quantitative polymerase chain reaction (qPCR) analysis was conducted to assess the efficiency of LINC00857 expression. Results: The administration of a low dose of OXA promoted the migratory, invasive, and angiogenic capabilities of HSC-3 cells, while also regulating EMT-associated molecular markers to facilitate the process of EMT. The inhibitory impact on OSCC proliferation was enhanced by the synergistic effect of apigenin and OXA. Furthermore, the tumor-promoting effects induced by low-dose OXA were notably suppressed through LINC00857. Conclusions: Evidence from this study indicates that apigenin can effectively suppress the metastasis of OSCC cancer cells induced by low-dose OXA through inhibiting the level of LINC00857, suggesting a promising therapeutic strategy.

High-level reverse intersystem crossing of charge transfer compounds: to fluoresce or not to fluoresce?

Thermally activated delayed fluorescence (TADF) has been widely applied to electroluminescent materials to take the best advantage of triplet excitons. For some materials, the TADF originates from high-level reverse intersystem crossing (hRISC), and has attracted much attention due to its high efficiency for utilizing the triplet excitons. However, reports concerning the mechanistic studies on the hRISC-TADF process and structure-property correlation are sparse. In this study, we prepared three compounds containing triphenylamine and benzophenone with different substitution positions, o-TPA-BP, m-TPA-BP, and p-TPA-BP, in which only p-TPA-BP displays strong luminescence and hRISC-TADF features. To investigate the mechanism of the substituent-position-dependent hRISC-TADF, ultrafast time-resolved spectroscopy was utilized to observe the deactivation pathways with the assistance of theoretical calculations. The results show that o-TPA-BP will not generate triplet species, and the triplet species for m-TPA-BP will rapidly deactivate. Only p-TPA-BP can transition back to the singlet state from the T2 state effectively and exhibit a large gap between T1 and T2 to favor the hRISC route. These results illustrate how the substitution position affects the ISC and further influences the luminescence properties, which can provide new insights for developing new high-efficiency luminescent materials.

Characteristics of PM2.5 bounded carbonaceous aerosols, carbon dioxide and its stable carbon isotopes (δ13C) in rural households in northwest China: Effect of different fuel combustion.

In order to fully understand the carbon emission from different fuels in rural villages of China, especially in the typical atmospheric pollution areas. The characteristics of carbonaceous aerosols and carbon dioxide (CO2) with its stable carbon isotope (δ13C) were investigated in six households, which two households used coal, two households used wood as well as two households used biogas and liquefied petroleum gas (LPG), from two rural villages in Fenwei Plain from March to April 2021. It showed that the fine particulate matter (PM2.5) emitted from biogas and LPG couldn't be as lower as expected in this area. However, the clean fuels could relatively reduce the emissions of organic carbon (OC) and element carbon (EC) in PM2.5 compare to the solid fuels. The pyrolyzed carbon (OP) accounted more total carbon (TC) in coal than the other fuels use households, indicating that more water-soluble OC existed, and it still had the highest secondary organic carbon (SOC) than the other fuels. Meantime, the coal combustions in the two villages had the highest CO2 concentration of 527.6 ppm and 1120.6 ppm, respectively, while the clean fuels could effectively reduce it. The average δ13C values (-26.9‰) was much lighter than almost all the outdoor monitoring and similar to the δ13C values for coal combustion and vehicle emission, showing that they might be the main contributors of the regional atmospheric aerosol in this area. During the sandstorm, the indoor PM2.5 mass and CO2 were increasing obviously. The indoor cancer risk of PAHs for adults and children were greater than 1 × 10-6, exert a potential carcinogenic risk to human of solid fuels combustion in rural northern China. It is important to continue concern the solid fuel combustion and its health impact in rural areas.

Dose-Response Relationship Between Alcohol Consumption and Gout Risk: Do Subtypes of Alcoholic Beverages Make a Difference?

OBJECTIVE: Although previous studies have explored the association of drinking with gout risk, we sought to explore the dose-response relationship and the evidence between subtypes of alcoholic beverages and gout risk. METHODS: The weekly alcoholic beverage consumption of patients in the UK Biobank was collected and calculated. The Cox regression model was applied to assess the effects of drinking alcohol in general and its subtypes on gout risk by calculating the hazard ratio (HR) and 95% CIs. Additionally, the restricted cubic splines were used to estimate the dose-response relationship between alcohol consumption and gout risk. To evaluate the robustness, we performed subgroup analysis across various demographic characteristics. RESULTS: During a mean follow-up period of 11.7 years, a total of 5728 new incident gout cases were diagnosed among 331,865 participants. We found that light alcohol consumption was linked to a slight decrease in gout incidence among female individuals (HR 0.78, 95% CI 0.65-0.94, P = 0.01), whereas there was no significant association in male individuals. Moreover, the dose-response relationship showed that drinking light red wine and fortified wine could reduce the gout risk, whereas beer or cider, champagne or white wine, and spirits increased the gout risk at any dose. CONCLUSION: Our study suggested a J-shaped dose-response relationship between drinking and gout risk in female individuals, but not in male individuals. For specific alcoholic beverages, light consumption of red wine and fortified wine was associated with reduced gout risk. These findings offer new insights into the roles of alcoholic beverages in gout incidence risk, although further validation is warranted.

Clinical Characteristics and Fatality Risk Factors for Patients with Listeria monocytogenes Infection: A 12-Year Hospital-Based Study in Xi'an, China.

INTRODUCTION: Listeriosis is a severe food-borne disease caused by Listeria monocytogenes infection. The data of listeriosis in Xi'an population are limited. The aim of this study is to evaluate the clinical features and fatality risk factors for listeriosis in three tertiary-care hospitals in Xi'an, China METHODS: The characteristics of demographic data, underlying diseases, clinical manifestations, laboratory indicators, cranial imaging examination, antibiotics therapeutic schemes, and clinical outcomes were collected between 2011 and 2023. Logistic regression analysis was performed. RESULTS: Seventy-one etiologically confirmed listeriosis patients were enrolled, including 12 neonatal and 59 non-neonatal cases. The majority of neonatal listeriosis presented as preterm (50%) and fetal distress (75%). The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%). The fatality rate in neonatal cases was higher than in non-neonatal listeriosis (42 vs. 17%). Although no deaths were reported in maternal listeriosis, only two of 23 patients had an uneventful obstetrical outcome. Five maternal listeriosis delivered culture-positive neonates, three of whom decreased within 1 week post-gestation due to severe complications. Twenty-eight cases were neurolisteriosis and 43 cases were bacteremia. Neurolisteriosis had a higher fatality rate compared with bacteremia listeriosis (36 vs. 12%). The main neuroradiological images were cerebral edema/hydrocephalus, intracranial infection, and cerebral hernia. Listeria monocytogenes showed extremely low resistance to ampicillin (two isolates) and penicillin (one isolate). The fatality risk factors were the involvement of the central nervous system, hyperbilirubinemia, and hyponatremia for all enrolled subjects. Hyperuricemia contributed to the elevation of fatality risk in non-neonatal listeriosis. CONCLUSIONS: When the patients suffered with symptoms of fever and central nervous system infection, they should be alert to the possibility of listeriosis. Early administration of ampicillin- or penicillin-based therapy might be beneficial for recovery of listeriosis.

Synthesis, Structure and Antibacterial Activity of Two Novel Coordination Polymers Based on N,N'-bis(4-carbozvlbenzvl)-4-aminotoluene and Heterocyclic Ligand against S. aureus.

As the use of antibiotics increases, the increasing resistance of bacteria is the main reason for the reduced efficiency of antibacterial drugs, making the research of new antibacterial materials become new hot spot. In this article, two novel coordination polymers (CPs), namely, [Cd2(L)2(bibp)2]n (1) and [Ni(L)(bib)]n (2), where H2L = N,N'-bis(4-carbozvlbenzvl)-4-aminotoluene, bibp = 4,4'-bis(imidazol-1-yl)biphenyl, and bib = 1,3-bis(1-imidazoly)benzene, have been synthesized under solvothermal and hydrothermal condition. Structural clarification was performed through infrared spectrum and single-crystal X-ray diffraction analysis, while thermal analysis and XRD technology were used for the performance assessment of compounds 1 and 2. In addition, antibacterial performance experiments showed that compounds 1 and 2 have certain selectivity in their antibacterial properties and have good antibacterial properties against S. aureus. As the concentration of the compound increases, the inhibitory effect gradually strengthens, and when the concentration of the compound reaches 500 µg/mL and 400 µg/mL, the concentration of the S. aureus solution no longer increases and has been completely inhibited.

Longitudinal effects of sexual minority stigma on depressive symptoms among young men who have sex with men: Distinguish between and within person effects.

BACKGROUND: Young men who have sex with men (YMSM) may experience high levels of sexual minority stigma (SMS) and depressive symptoms (DS) over the world and in China. However, there is a lack of studies investigating the longitudinal effects of SMS on DS of YMSM, especially focusing on YMSM and separating the between-person and within-person effects. This study aimed to fill the said gaps. METHODS: Study data were derived from a prospective cohort of 349 YMSM from central China (Wuhan, Changsha, Nanchang), the baseline survey was started in 2017 with one follow-up visit every year. SMS and DS were measured three times using valid and reliable instruments. The cross-lagged panel model (CLPM) and the random intercept CLPM (RI-CLPM) were used to examine the between-person and within-person concurrent and lagged effects, respectively. RESULTS: Findings of CLPM revealed bidirectional associations between SMS and DS over time. RI-CLPM suggested that at the between-person level, SMS was significantly associated with DS, echoing the results of CLPM. However, this reciprocal relationship has not been found at the within-person level. CONCLUSION: The associations between SMS and DS among YMSM at the population level is more significant than that at the individual level. We suggest that interventions should be against the adverse effects of cultural marginalization and systemic change the social concepts to reduce the amount of SMS in society.

Transcriptome Analysis Reveals POD as an Important Indicator for Assessing Low-Temperature Tolerance in Maize Radicles during Germination.

Low-temperature stress (TS) limits maize (Zea mays L.) seed germination and agricultural production. Exposure to TS during germination inhibits radicle growth, triggering seedling emergence disorders. Here, we aimed to analyse the changes in gene expression in the radicles of maize seeds under TS by comparing Demeiya1 (DMY1) and Zhengdan958 (ZD958) (the main Northeast China cultivars) and exposing them to two temperatures: 15 °C (control) and 5 °C (TS). TS markedly decreased radicle growth as well as fresh and dry weights while increasing proline and malondialdehyde contents in both test varieties. Under TS treatment, the expression levels of 5301 and 4894 genes were significantly different in the radicles of DMY1 and ZD958, respectively, and 3005 differentially expressed genes coexisted in the radicles of both varieties. The phenylpropanoid biosynthesis pathway was implicated within the response to TS in maize radicles, and peroxidase may be an important indicator for assessing low-temperature tolerance during maize germination. Peroxidase-encoding genes could be important candidate genes for promoting low-temperature resistance in maize germinating radicles. We believe that this study enhances the knowledge of mechanisms of response and adaptation of the maize seed germination process to TS and provides a theoretical basis for efficiently assessing maize seed low-temperature tolerance and improving maize adversity germination performance.

Risk of drug-induced delirium in older patients- a pharmacovigilance study of FDA adverse event reporting system database.

BACKGROUND: Drug-induced delirium is known risk factors associated with increased morbidity and mortality in older patients. The objective was to evaluate the risk of drug-related delirium in older patients based on the FDA Adverse Event Reporting System (FAERS). RESEARCH DESIGN AND METHODS: Delirium reports in older patients (age ≥65) extracted from the FAERS database using Open Vigil 2.1. The reported odds ratio and the proportional reported ratio were calculated to detect the adverse reaction signal of delirium. Combined with published evidence, suspected drugs were categorized as known, possible, or new potential delirium-risk-increasing drugs. RESULTS: Of the 130,885 reports (including 28,850 delirium events and 1,857 drugs) analyzed for this study, 314 positive signal drugs were detected. Positive signal drugs are mainly concentrated on the drug of nervous system, cardiovascular system , alimentary tract and metabolism and anti-infectives for systemic use. Of the positive signal drugs, 26.11% (82/314) were known delirium-risk increasing drugs, 44.90% (141/314) were possible and 28.98% (91/314) were new potential. CONCLUSION: Drug-induced delirium risk is prevalent in older patients, according to the FAERS. The risk level of drug-induced delirium should be taken into account to optimize drug therapy in clinical practice.

Upregulation of Hepatic Glutathione S-Transferase Alpha 1 Ameliorates Metabolic Dysfunction-Associated Steatosis by Degrading Fatty Acid Binding Protein 1.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common metabolic disease of the liver, characterized by hepatic steatosis in more than 5% of hepatocytes. However, despite the recent approval of the first drug, resmetirom, for the management of metabolic dysfunction-associated steatohepatitis, decades of target exploration and hundreds of clinical trials have failed, highlighting the urgent need to find new druggable targets for the discovery of innovative drug candidates against MASLD. Here, we found that glutathione S-transferase alpha 1 (GSTA1) expression was negatively associated with lipid droplet accumulation in vitro and in vivo. Overexpression of GSTA1 significantly attenuated oleic acid-induced steatosis in hepatocytes or high-fat diet-induced steatosis in the mouse liver. The hepatoprotective and anti-inflammatory drug bicyclol also attenuated steatosis by upregulating GSTA1 expression. A detailed mechanism showed that GSTA1 directly interacts with fatty acid binding protein 1 (FABP1) and facilitates the degradation of FABP1, thereby inhibiting intracellular triglyceride synthesis by impeding the uptake and transportation of free fatty acids. Conclusion: GSTA1 may be a good target for the discovery of innovative drug candidates as GSTA1 stabilizers or enhancers against MASLD.

Association of vulnerable plaques with white matter hyperintensities on high-resolution magnetic resonance imaging.

Background: One of the widespread manifestations of cerebral small vessel disease (CSVD) of the brain parenchyma is white matter lesion, which appears as white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI). Previous studies have illustrated that large artery atherosclerosis is related to CSVD, but the precise progress of pathogenesis remains unknown. High-resolution MRI (HR-MRI) has the ability to delineate intracranial vascular walls, enabling a thorough exploration of the structure and composition of unstable plaques. This study aimed to apply HR-MRI to characterize the wall changes and plaque characteristics of middle cerebral arteries in patients with WMHs and to investigate the correlation between plaque vulnerability parameters and different degrees of WMHs. Methods: In this study, 138 patients with acute ischemic stroke at Harbin Medical University's First Clinical Hospital (May 2021 to October 2023) were cross-sectionally reviewed and underwent conventional brain and HR-MRI using T1-weighted 3D volumetric isotropic turbo spin echo acquisition (T1W-3D-VISTA) of the unilateral middle cerebral artery (MCA). According to Fazekas grade (0-6), the patients were divided into two groups: Fazekas score 0-2, no-or-mild WMHs; and Fazekas 3-6, moderate-to-severe WMHs. The intraplaque hemorrhage, plaque distribution, plaque enhancement, plaque load, remodeling pattern, and stenosis of the two groups were measured. Binary logistic regression analysis was conducted to evaluate the relationship between vulnerable plaques and WMHs. Results: Of the participants who were initially considered for inclusion, 71 were deemed eligible, among whom 34 were placed in the no-or-mild WMH group and 37 in the moderate-to-severe WMH group. Between the two groups, there were significant differences in intraplaque hemorrhage (P=0.01), a wide distribution (P=0.02), and plaque enhancement (P=0.02). Univariate analysis showed that WMHs were associated with age [odds ratio (OR) =1.080; 95% confidence interval (CI): 1.020-1.144; P=0.008], hypertension (OR =3.500; 95% CI: 1.276-9.597; P=0.01), intraplaque hemorrhage (OR =3.955; 95% CI: 1.247-12.538; P=0.02), a wide distribution (OR =3.067; 95% CI: 1.159-8.115; P=0.02), and significant plaque enhancement (OR =4.372; 95% CI: 1.101-17.358; P=0.03); however, the multivariate results showed that the only independent factors associated with WMHs were age (OR =1.095; 95% CI: 1.019-1.176; P=0.01) and intraplaque hemorrhage (OR =5.88; 95% CI: 1.466-23.592; P=0.01). Conclusions: Our findings suggest that age and intraplaque hemorrhage may be associated with more severe WMHs in patients with acute ischemic stroke, which may be helpful for further clinical examination and intervention treatment.

Identification of CFH and FHL2 as biomarkers for idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown etiology with a poor prognosis, characterized by a lack of effective diagnostic and therapeutic interventions. The role of immunity in the pathogenesis of IPF is significant, yet remains inadequately understood. This study aimed to identify potential key genes in IPF and their relationship with immune cells by integrated bioinformatics analysis and verify by in vivo and in vitro experiments. Methods: Gene microarray data were obtained from the Gene Expression Omnibus (GEO) for differential expression analysis. The differentially expressed genes (DEGs) were identified and subjected to functional enrichment analysis. By utilizing a combination of three machine learning algorithms, specific genes associated with idiopathic pulmonary fibrosis (IPF) were pinpointed. Then their diagnostic significance and potential co-regulators were elucidated. We further analyzed the correlation between key genes and immune infiltrating cells via single-sample gene set enrichment analysis (ssGSEA). Subsequently, a single-cell RNA sequencing data (scRNA-seq) was used to explore which cell types expressed key genes in IPF samples. Finally, a series of in vivo and in vitro experiments were conducted to validate the expression of candidate genes by western blot (WB), quantitative real-time PCR (qRT-PCR), and immunohistochemistry (IHC) analysis. Results: A total of 647 DEGs of IPF were identified based on two datasets, including 225 downregulated genes and 422 upregulated genes. They are closely related to biological functions such as cell migration, structural organization, immune cell chemotaxis, and extracellular matrix. CFH and FHL2 were identified as key genes with diagnostic accuracy for IPF by three machine learning algorithms. Analysis using ssGSEA revealed a significant association of both CFH and FHL2 with diverse immune cells, such as B cells and NK cells. Further scRNA-seq analysis indicated CFH and FHL2 were specifically upregulated in human IPF tissues, which was confirmed by in vitro and in vivo experiments. Conclusion: In this study, CFH and FHL2 have been identified as novel potential biomarkers for IPF, with potential diagnostic utility in future clinical applications. Subsequent investigations into the functions of these genes in IPF and their interactions with immune cells may enhance comprehension of the disease's pathogenesis and facilitate the identification of therapeutic targets.

The intramolecular self-assembly of bidesmosidic kalopanaxsaponins.

The phenomena of intramolecular self-assembly of bidesmosidic kalopanaxsaponins was identified for the first time in this paper. NMR (1H-NMR, NOESY), transmission electron microscopy (TEM), and molecular dynamics (MD) simulation techniques were used to compare the spatial structures of bidesmosidic kalopanaxsaponins and monodesmosidic kalopanaxsaponins. The results showed that the bidesmosidic kalopanaxsaponins formed a clustered and twisted structure in space, whereas the monodesmosidic kalopanaxsaponins were in an extended state. This discovery confirmed the presence of intramolecular self-assembly in bidesmosidic kalopanaxsaponins.