The role of botanical triterpenoids and steroids in bile acid metabolism, transport, and signaling: Pharmacological and toxicological implications.

Bile acids (BAs) are synthesized by the host liver from cholesterol and are delivered to the intestine, where they undergo further metabolism by gut microbes and circulate between the liver and intestines through various transporters. They serve to emulsify dietary lipids and act as signaling molecules, regulating the host's metabolism and immune homeostasis through specific receptors. Therefore, disruptions in BA metabolism, transport, and signaling are closely associated with cholestasis, metabolic disorders, autoimmune diseases, and others. Botanical triterpenoids and steroids share structural similarities with BAs, and they have been found to modulate BA metabolism, transport, and signaling, potentially exerting pharmacological or toxicological effects. Here, we have updated the research progress on BA, with a particular emphasis on new-found microbial BAs. Additionally, the latest advancements in targeting BA metabolism and signaling for disease treatment are highlighted. Subsequently, the roles of botanical triterpenoids in BA metabolism, transport, and signaling are examined, analyzing their potential pharmacological, toxicological, or drug interaction effects through these mechanisms. Finally, a research paradigm is proposed that utilizes the gut microbiota as a link to interpret the role of these important natural products in BA signaling.

In situ observations of large-amplitude Alfvén waves heating and accelerating the solar wind.

After leaving the Sun's corona, the solar wind continues to accelerate and cools, but more slowly than expected for a freely expanding adiabatic gas. Alfvén waves are perturbations of the interplanetary magnetic field that transport energy. We use in situ measurements from the Parker Solar Probe and Solar Orbiter spacecraft to investigate a stream of solar wind as it traverses the inner heliosphere. The observations show heating and acceleration of the plasma between the outer edge of the corona and near the orbit of Venus, along with the presence of large-amplitude Alfvén waves. We calculate that the damping and mechanical work performed by the Alfvén waves are sufficient to power the heating and acceleration of the fast solar wind in the inner heliosphere.

Proteomic analysis revealed gender-related differences in the skin mucus proteome of discus fish (Symphysodon haraldi) during the parental and non-parental care periods.

The discus fish, Symphysodon spp., a South American cichlid, has a unique parental care behavior where fry bite on parental skin mucus after hatching. In this study, we used LC-MS/MS technique to compare the skin mucus proteome composition of male or female discus fish during parental and non-parental care periods. By multivariate statistical analysis, we found clear separations between different periods and between different sexes of mucus proteome. Compared with non-parental female fish, parental female fish had 283 up-regulated and 235 down-regulated expressed proteins. Compared with non-parental male fish, parental male fish had 169 up-regulated and 120 down-regulated expressed proteins. The differentially expressed proteins for male fish were enriched in sulfur relay system, mucin type O-glycan biosynthesis and antigen processing and presentation pathways, while those for female fish were enriched in sulfur relay system, steroid biosynthesis and complement and coagulation cascades pathways. During the parental care, both male and female discus showed an enhanced lipid metabolism, producing more phospholipids and cholesterol. The difference is that male discus had increased tricarboxylic acid cycle producing more energy during the parental care, while females produced more nucleotides especially guanylic acid. Our study could provide new insights into the understanding of the unique mucus supply behavior of discus fish based on proteomic change.

A non-enzymatic, isothermal amplification sensor for quantifying the relative abundance of Akkermansia muciniphila.

Herein, we have developed a non-enzymatic, isothermal amplification assay (NIA sensor) based on a catalytic hairpin assembly (CHA) reaction for quantifying the relative abundance of Akkermansia muciniphila. Through detection of the MUC-1437 gene (limit of detection: 8.3 fM) in a dynamic range from 10 fM to 1 nM, the NIA sensor shows high sensitivity and selectivity in preclinical models of mice fed a normal or high-fat diet (HFD), and treated with antibiotics (ATB). The NIA sensor, which operates without the use of any enzymes, leading to simplicity and cost-effectiveness, has great potential for biosensing research and clinical diagnostic applications.

Novel SARS-CoV-2 inhibition properties of the anti-cancer Kang Guan Recipe herbal formula.

The ongoing COVID-19 pandemic is a persistent challenge, with continued breakthrough infections despite vaccination efforts. This has spurred interest in alternative preventive measures, including dietary and herbal interventions. Previous research has demonstrated that herbal medicines can not only inhibit cancer progression but also combat viral infections, including COVID-19 by targeting SARS-CoV-2, indicating a multifaceted potential to address both viruses and cancer. Here, we found that the Kang Guan Recipe (KGR), a novel herbal medicine formula, associates with potent inhibition activity against the SARS-CoV-2 viral infection. We demonstrate that KGR exhibits inhibitory activity against several SARS-CoV-2 variants of concern (VOCs). Mechanistically, we found that KGR can block the interaction of the viral spike and human angiotensin-converting enzyme 2 (ACE2). Furthermore, we assessed the inhibitory effect of KGR on SARS-CoV-2 viral entry in vivo, observing that serum samples from healthy human subjects having taken KGR exhibited suppressive activity against SARS-CoV-2 variants. Our investigation provides valuable insights into the potential of KGR as a novel herbal-based preventive and therapeutic strategy against COVID-19.

Liberation from extracorporeal membrane oxygenation in a patient with severe COVID-19-associated acute respiratory distress syndrome using traditional Chinese medicine: A case report.

INTRODUCTION: Due to the continued threat to public health posed by SARS-CoV-2 and the ongoing emergence of novel variants, the integration of traditional Chinese medicine (TCM) with Western medicine provides a novel alternative management for critically ill patients. CASE PRESENTATION: This case report describes a 54-year-old male with severe COVID-19-associated acute respiratory distress syndrome (ARDS) who required extracorporeal membrane oxygenation (ECMO) support. Despite standard treatment, ECMO liberation was unsuccessful, and complications such as pneumothorax and hemothorax ensued. However, upon initiating combined TCM therapy on the 19th day of ECMO support, the patient exhibited gradual improvements in oxygenation and ventilation, leading to successful ECMO liberation on the 31st day. CONCLUSION: This case underscores the potential of integrating TCM with conventional therapies for severe COVID-19 cases, offering a valuable treatment option amidst the evolving landscape of SARS-CoV-2 variants.

Integrated untargeted and targeted lipidomics discovers LPE 16:0 as a protector against respiratory syncytial virus infection.

Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory infections, imposing a substantial burden on healthcare systems globally. While lipid disorders have been observed in the lungs of infants and young children with RSV pneumonia, the specific characterization of these lipids and their roles in the development and progression of RSV pneumonia remain largely unexplored. To address this tissue, we established a non-targeted high-resolution lipidomics platform using UHPLC-Q-Exactive-MS to analyze lipid profiles in bronchoalveolar lavage fluid (BALF) obtained from mice infected with RSV. Through the lipidomics analysis, a total of 72 lipids species were identified, with 40 lipids were significantly changed. Notably, the primary changes were observed in ether phospholipids and lysophospholipids. Furthermore, a targeted lipidomics analysis utilizing UHPLC-QQQ-MS/MS was developed to specifically assess the levels of lysophospholipids, including lysophosphocholine 16:0 (LPC 16:0), lysophosphoethanolamine 16:0 (LPE 16:0) and lysophosphoglycerol 16:0 (LPG 16:0), in RSV-infected mice compared to control mice. Animal experiments revealed that LPE 16:0, rather than LPC 16:0 or LPG 16:0, provided protection against RSV-induced weight loss, reduced lung viral load, regulated immune cells and mitigated lung injury in mice afflicted with RSV pneumonia. In summary, our findings suggested that the host responses to RSV infection pathology are closely with various lipid metabolic. Additionally, our results elucidated novel biological functions of LPE 16:0 and offering new avenues for drug development against RSV pneumonia.

Blocking Gremlin1 inhibits M1 macrophage polarization through Notch1/Hes1 signaling pathway in apical periodontitis.

BACKGROUND: Gremlin1 is a multifunctional protein whose expression is demonstrated to be involved in a series of physiology and pathological processes. The association between Gremlin1 and apcial periodontitis (AP) has been established. M1-polarized macrophages are crucial immune cells that exacerbate the progression of apical periodontal inflammatory response, but the function of Gremlin1 during macrophages activation in periapical lesions is still unclear. This study attempts to explore the regulatory effects of Gremlin1 on macrophage polarization on apical periodontitis microenviroment. METHODS: Clinical specimens were used to determine the expression of Gremlin1 in periapical tissues by immunohistochemical (IHC) staining. Then, the disease models of periapical inflammation in rats were established, and adenovirus- associated virus (AAVs) was used to blockade Gremlin1 expression. Lentivirus carrying sh-Gremlin1 particles were used to transfect THP-1 induced M1-subtype macrophages. To assess the expression of associated molecules, Western blot, immunofluorescence staining were performed. RESULTS: Gremlin1 was significantly up-regulated in the periapical tissues of subjects with AP as identified by IHC staining, and positively correlated with levels of M1 macrophage-associated genes. Rats AP model with inhibition of Gremlin1 in periapical lesions exhibited limited infiltration of macrophages and decreased expression of M1 macrophage-related genes in periapical lesions. Furthermore, Gremlin1 blockade substantially decreased the Notch1/Hes1 signaling pathway activation level. The in vitro experiments confirmed the above results. CONCLUSION: Taken together, current study illustrated that the Gremlin1 suppression in periapical lesions inhibited M1 macrophage polarization through Notch1/Hes1 axis. Moreover, Gremlin1 may act as a potential candidate in the treatment of AP.

Characterising polycyclic aromatic hydrocarbons in road dusts and stormwater in urban environments.

The presence of polycyclic aromatic hydrocarbons (PAHs) pollution on urban road surfaces is one of the major environmental concerns. However, knowledge on the distribution variability of PAHs in road dusts (RDS) and stormwater is limited, which would restrict the further risk evaluation and mitigation implementation of PAHs in road stormwater runoff. This study collected RDS samples and stormwater samples on fourteen urban roads in Shenzhen, China. This study investigated the variation of sixteen PAHs species in RDS and stormwater, and further evaluated the intrinsic and extrinsic factors which influence PAHs accumulation on urban road surfaces. The research outcomes showed significant differences on spatial distribution of PAHs in RDS and in stormwater. The land use types, industrial, commercial and port areas and vehicular volume have a positive relationship with PAHs abundance while dust particle size showed a negative correlation with PAHs abundance. For two phases in stormwater, fluctuation of PAHs with the rainfall duration in total dissolved solid (TDS) was more intensive than in dissolved liquid phase (DLP). This indicated when PAHs attached to RDS enter stormwater, most of PAHs still tend to be on solid particles than in liquid. The study outcomes are expected to contribute to efficient designs of PAHs polluted stormwater mitigation.

High sensitivity fiber SPR sensor based on a spiral coarse cone structure.

A fiber SPR sensor can achieve rapid and portable detection of trivalent arsenic ions (As3+) in drinking water or food, but their sensitivity and detection limit need to be further improved and developed toward specific detection. This article proposed the implementation of the SPR sensor using a biased core fiber spiral coarse cone structure. The fine core of the biased core fiber was used to reduce the mode of transmitted light. By controlling the pitch of the spiral core to control the SPR incidence angle, a significant increase in the sensitivity of the fiber SPR sensor was achieved. Meanwhile, the harmless glutathione (GSH) was modified on the surface of the sensing gold film to achieve the specific detection of As3+. The experimental results indicate that the spiral coarse cone fiber SPR sensor proposed in this article has a detection sensitivity of 32.48 nm/ppb for As3+, with a detection limit as low as 0.011 ppb, meeting the detection requirements of the World Health Organization for As3+ in water, which provides a new feasible solution for fast, portable, and highly sensitive detection of metal ions in water and food.

Synthesizing LiFePO4 by phosphate & iron recovered from sludge-incinerated ash and Li extracted from concentrated brines.

Phosphorus (P) recovered from sludge-incinerated ash (SIA) could be applied to synthesize highly added-value products (FePO4 and LiFePO4) with in situ Fe in SIA. Indeed, LiFePO4 is a future of rechargeable batteries, which makes lithium (Li) highly needed. Alternatively, Li could also be extracted from concentrated brines to face a potential crisis of Li depletion on lands. Based on H3PO4 and Fe3+ co-extracted from the acidic leachate of SIA by tributyl phosphate (TBP), FePO4 (31.2 wt% Fe, 17.6 wt% P and the molar ratio of Fe/P = 0.98) was easily formed only adjusting pH of the stripping solution to 1.6. Interestingly, the organic phase from the first-stage co-extraction process of Fe3+ and H3PO4 could be utilized for Li-extraction from salt-lake brine, based on the TBP-FeCl3-kerosene system, and a good performance (78.7%) of Li-extraction and separation factors (ß) (186.0-217.4) were obtained. Furthermore, the compounds with Li-extraction are complex, possibly LiFeCl4∙2TBP, in which Li+ could be stripped to form Li2CO3 by 4.0 M HCl (with a stripping rate up to 83%). Besides, Li2CO3 could also be obtained from desalinated brine by adsorption with manganese oxide ion sieve (HMO) and desorption with HCl. In the two cases, almost pure Li2CO3 products were obtained, up to 99.7 and 99.5 wt% Li2CO3 respectively, after further purification and concentration. Finally, recovered FePO4 and extracted Li2CO3 were synthesized for producing LiFePO4 that had a similar electrochemical property (69.5 and 77.8 mAh/g of the initial discharge capacity) to those synthesized from commercial raw materials.

Distribution characteristics of sulfonamide antibiotics between water and extracellular polymeric substances in municipal sludge.

The interaction between extracellular polymeric substances (EPS) in municipal sludge and antibiotics in wastewater is critical in wastewater treatment, resource recovery, and sludge management. Therefore, it is increasingly urgent to investigate the distribution coefficient (Log K) of sulfonamide antibiotics (SAs) in EPS, particularly in sludge-derived dissolved organic carbon (DOC) and aqueous phase systems. Herein, through balance experiments, the concentrations of SAs were determined using alkaline extraction EPS (AEPS) and alginate-like extracellular polymer (ALE) systems, and the Log KDOC values were determined. The results showed that the Log KDOC of AEPS was higher than that of ALE, which exhibited a negative KDOC value, indicating an inhibitory effect on dissolution. For the three SAs studied, the Log KDOC values were in the following order: sulfamethoxazole > sulfapyridine > sulfadiazine. This order can be attributed to the differing physicochemical properties, such as polarity, of the SAs. Three-dimensional excitation-emission matrix fluorescence spectra and fitting results indicated a lack of aromatic proteins dominated by tryptophan and humus-like substances in ALE. Meanwhile, the hydrophobic interaction of aromatic proteins dominated by tryptophan was the main driving force in the binding process between AEPS and SAs.

Pituitary apoplexy after surgery for cervical stump adenocarcinoma: A case report and literature review.

Pituitary apoplexy (PA) is an emergency condition caused by sudden hemorrhage or infarction and characterized by sudden sella turcica compression, intracranial hypertension and meningeal stimulation. PA usually occurs secondary to pituitary adenomas and can serve as the initial manifestation of an undiagnosed pituitary adenoma in an individual. In the present study, a case of PA following surgery for cervical stump adenocarcinoma was reported. The patient experienced an abrupt onset of headache and drowsiness on postoperative day 1 (POD1), and developed blurred vision and blepharoptosis of the left eye on POD4. Pituitary MRI confirmed the diagnosis of PA, prompting the initial administration of hydrocortisone to supplement endogenous hormones, followed by trans-sphenoidal resection. At the six-week follow-up, the patient had fully recovered, with only mild residual blurring of vision. Diagnosing PA post-surgery can be a challenging task due to its symptomatic overlap with postoperative complications. The existing literature on PA after surgery was also reviewed, including the symptoms, time of onset, imageological examination, management, potential risk factors and outcome to improve on early detection and individualized treatment in the future.

A high-quality chromosome-level genome assembly of the endangered tree Kmeria septentrionalis.

Kmeria septentrionalis is a critically endangered tree endemic to Guangxi, China, and is listed on the International Union for Conservation of Nature's Red List. The lack of genetic information and high-quality genome data has hindered conservation efforts and studies on this species. In this study, we present a chromosome-level genome assembly of K. septentrionalis. The genome was initially assembled to be 2.57 Gb, with a contig N50 of 11.93 Mb. Hi-C guided genome assembly allowed us to anchor 98.83% of the total length of the initial contigs onto 19 pseudochromosomes, resulting in a scaffold N50 of 135.08 Mb. The final chromosome-level genome, spaning 2.54 Gb, achieved a BUSCO completeness of 98.9% and contained 1.67 Gb repetitive elements and 35,927 coding genes. This high-quality genome assembly provides a valuable resource for understanding the genetic basis of conservation-related traits and biological properties of this endangered tree species. Furthermore, it lays a critical foundation for evolutionary studies within the Magnoliaceae family.

[Correlation between parameters of suppression head impulse paradigm and changesin DHI score in acute vestibular neuritis].

Objective:To explore the correlation between the parameters of suppression head impulse paradigm（SHIMP） and changes in dizziness handicap inventory（DHI） scores. Additionally, to evaluate the degree of vertigo and prognosis of patients with acute vestibular neuritis through SHIMP parameters. Methods:Thirty-three patients with acute vestibular neuritis were enrolled for DHI evaluation, vHIT and SHIMP. A secondary DHI score were evaluated after after two weeks, once patients no longer exhibited spontaneous nystagmus. The decrease in the second DHI score was used as the efficacy index（EI）. All patients were divided into significantly effective group, effective group and ineffective group based on EI. Differences of the VOR gain values of SHIMP and the anti-compensatory saccade were compared among the three groups. Results:There were 13 cases in the significant effective group, 11 cases in the effective group, and 9 cases in the ineffective group. ①The mean gain of the horizontal semicircular canal in the significant effective group, the effective group, and the ineffective group was（0.50±0.11）, （0.44±0.12）, and（0.34±0.08）, respectively. The difference between the significant effective group and the ineffective group was statistically significant（P<0.01）. The gain of horizontal semicircular canal was positively correlated with EI（r=0.538 5, P<0.01） 。②The occurrence rate of the anti-compensatory saccade in the significant effective group, the effective group, and the ineffective group was（51.23±19.59）, （33.64±17.68）, and（13.78±11.81）, respectively. Pairwise comparisons between each group showed statistical significance（P<0.05）. The occurrence rate of anti-compensatory saccade was positively correlated with EI（r=0.658 2, P<0.01）. Conclusion:The horizontal semicircular canal gain and the occurrence rate of the anti-compensatory saccade in SHIMP for patients with acute vestibular neuritis were closely correlated with decrease in DHI score.

Hi-C-guided many-polymer model to decipher 3D genome organization.

We propose a high-throughput chromosome conformation capture data-based many-polymer model that allows us to generate an ensemble of multi-scale genome structures. We demonstrate the efficacy of our model by validating the generated structures against experimental measurements and employ them to address key questions regarding genome organization. Our model first confirms a significant correlation between chromosome size and nuclear positioning. Specifically, smaller chromosomes are distributed at the core region, whereas larger chromosomes are at the periphery, interacting with the nuclear envelope. The spatial distribution of A- and B-type compartments, which is nontrivial to infer from the corresponding high-throughput chromosome conformation capture maps alone, can also be elucidated using our model, accounting for an issue such as the effect of chromatin-lamina interaction on the compartmentalization of conventional and inverted nuclei. In accordance with imaging data, the overall shape of the 3D genome structures generated from our model displays significant variation. As a case study, we apply our method to the yellow fever mosquito genome, finding that the predicted morphology displays, on average, a more globular shape than the previously suggested spindle-like organization and that our prediction better aligns with the fluorescence in situ hybridization data. Our model has great potential to be extended to investigate many outstanding issues concerning 3D genome organization.

The novel function of an orphan pheromone receptor reveals the sensory specializations of two potential distinct types of sex pheromones in noctuid moth.

Sex pheromones play crucial role in mating behavior of moths, involving intricate recognition mechanisms. While insect chemical biology has extensively studied type I pheromones, type II pheromones remain largely unexplored. This study focused on Helicoverpa armigera, a representative species of noctuid moth, aiming to reassess its sex pheromone composition. Our research unveiled two previously unidentified candidate type II sex pheromones-3Z,6Z,9Z-21:H and 3Z,6Z,9Z-23:H-in H. armigera. Furthermore, we identified HarmOR11 as an orphan pheromone receptor of 3Z,6Z,9Z-21:H. Through AlphaFold2 structural prediction, molecular docking, and molecular dynamics simulations, we elucidated the structural basis and key residues governing the sensory nuances of both type I and type II pheromone receptors, particularly HarmOR11 and HarmOR13. This study not only reveals the presence and recognition of candidate type II pheromones in a noctuid moth, but also establishes a comprehensive structural framework for PRs, contributing to the understanding of connections between evolutionary adaptations and the emergence of new pheromone types.

Wave type fiber SPR sensor for rapid and highly sensitive detection of hyperoside.

The fiber surface plasmon resonance (SPR) sensor used for the detection of active ingredients in traditional Chinese medicine has the problems of low sensitivity and difficult specific recognition. This paper proposed a wave type fiber SPR sensor, which reduced the mode of transmitted light through a periodic wave structure and caused concentrated and total reflection of the transmitted beam at the interface between the bent peak cladding and the air. A 50 nm gold film was coated on the surface of the cladding in the wave structure area to form the SPR sensing area. By controlling the width and height of the wave structure to control the total reflection angle of the transmitted light, i.e., the SPR incidence angle, the sensitivity of the fiber SPR sensor was effectively improved to 4972 nm/RIU. Furthermore, HSP90AA protein was modified on the gold film of the sensor to achieve specific detection of hyperoside. The longest single detection time was only 3 minutes, and the detection sensitivity was 0.53 nm/(µg/ml), with a detection limit as low as 0.68µg/ml, which is comparable to liquid chromatography. The proposed wave type fiber SPR sensor is fast in production and has high structural mechanical strength, providing a new approach for the rapid, highly sensitive, and specific detection of active ingredients in traditional Chinese medicine.

Opioid Nonadherence Risk Prediction of Patients with Cancer-Related Pain Based on Five Machine Learning Algorithms.

Objectives: Opioid nonadherence represents a significant barrier to cancer pain treatment efficacy. However, there is currently no effective prediction method for opioid adherence in patients with cancer pain. We aimed to develop and validate a machine learning (ML) model and evaluate its feasibility to predict opioid nonadherence in patients with cancer pain. Methods: This was a secondary analysis from a cross-sectional study that included 1195 patients from March 1, 2018, to October 31, 2019. Five ML algorithms, such as logistic regression (LR), random forest, eXtreme Gradient Boosting, multilayer perceptron, and support vector machine, were used to predict opioid nonadherence in patients with cancer pain using 43 demographic and clinical factors as predictors. The predictive effects of the models were compared by the area under the receiver operating characteristic curve (AUC_ROC), accuracy, precision, sensitivity, specificity, and F1 scores. The value of the best model for clinical application was assessed using decision curve analysis (DCA). Results: The best model obtained in this study, the LR model, had an AUC_ROC of 0.82, accuracy of 0.82, and specificity of 0.71. The DCA showed that clinical interventions for patients at high risk of opioid nonadherence based on the LR model can benefit patients. The strongest predictors for adherence were, in order of importance, beliefs about medicines questionnaire (BMQ)-harm, time since the start of opioid, and BMQ-necessity. Discussion. ML algorithms can be used as an effective means of predicting adherence to opioids in patients with cancer pain, which allows for proactive clinical intervention to optimize cancer pain management. This trial is registered with ChiCTR2000033576.