Dysrhythmic saliva microbiota in mobile phone addicts with sleep disorders and restored by acupuncture.

Background: Mobile phone addiction (MPA) greatly affects the biological clock and sleep quality and is emerging as a behavioral disorder. The saliva microbiota has been linked to circadian rhythms, and our previous research revealed dysrhythmic saliva metabolites in MPA subjects with sleep disorders (MPASD). In addition, acupuncture had positive effects. However, the dysbiotic saliva microbiota in MPASD patients and the restorative effects of acupuncture are unclear. Objectives: To probe the circadian dysrhythmic characteristics of the saliva microbiota and acupunctural restoration in MPASD patients. Methods: MPASD patients and healthy volunteers were recruited by the Mobile Phone Addiction Tendency Scale (MPATS) and the Pittsburgh Sleep Quality Index (PSQI). Saliva samples were collected every 4 h for 72 h. After saliva sampling, six MPDSD subjects (group M) were acupuncturally treated (group T), and subsequent saliva sampling was conducted posttreatment. Finally, all the samples were subjected to 16S rRNA gene sequencing and bioinformatic analysis. Results: Significantly increased MPATS and PSQI scores were observed in MPDSD patients (p< 0.01), but these scores decreased (p<0.001) after acupuncture intervention. Compared with those in healthy controls, the diversity and structure of the saliva microbiota in MPASD patients were markedly disrupted. Six genera with circadian rhythms were detected in all groups, including Sulfurovum, Peptostreptococcus, Porphyromonas and Prevotella. There were five genera with circadian rhythmicity in healthy people, of which the rhythmicities of the genera Rothia and Lautropia disappeared in MPASD patients but effectively resumed after acupuncture intervention. Conclusions: This work revealed dysrhythmic salivary microbes in MPASD patients, and acupuncture, as a potential intervention, could be effective in mitigating this ever-rising behavioral epidemic.

Experiment and analysis of physical, mechanical, and viscoelastic properties of the roots and stalks of green leafy vegetables.

Green leafy vegetables are an essential component of Chinese leafy vegetables. Due to their crisp stems and tender leaves, orderly harvester generally causes significant mechanical clamping damage. The physical and mechanical properties of green leafy vegetables are one of the important basis to design the orderly harvester. At the same time, they provide important parameters for the simulation and optimization of harvester. So, this paper measured the physical characteristic parameters of roots and stems of green leafy vegetables. Then, based on the TMS-Pro texture analyzer, the elasticity modulus of the roots and stems of green leafy vegetables were measured. The static friction coefficient, dynamic friction coefficient, and restitution coefficient of green leafy vegetables root-root, stem-stem, root-steel, and stem-steel were measured separately using a combination method of inclined plane and high-speed photography. Uniaxial compression creep experiments were carried out on whole and single leaf of green leafy vegetables using the TA.XT plus C universal testing machine. The constitutive equation of the four-element Burgers model was used to fit the deformation curve of the sample with time during the constant-pressure loading stage. The fitting determination coefficients R2 were all higher than 0.996, which verified the reasonable validity of the selected model. The above experimental results provide a parameter basis and theoretical support for the design and discrete element simulation optimization of orderly harvester critical components of green leafy vegetables.

Clinical characteristics of membranous nephropathy after allogeneic hematopoietic stem cell transplantation: A real-world multicenter study.

Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.

Transcriptome analysis of the degradation process of organic nitrogen by two heterotrophic nitrifying and aerobic denitrifying bacteria.

The heterotrophic nitrification aerobic denitrification bacteria (HNDS) can perform nitrification and denitrification at the same time. Two HNDS strains, Achromobacter sp. HNDS-1 and Enterobacter sp. HNDS-6 which exhibited an amazing ability to solution nitrogen (N) removal have been successfully isolated from paddy soil in our lab. When peptone or ammonium sulfate as sole N source, no significant difference in gene expression related to nitrification and denitrification of the strains was found according to the transcriptome analysis. The expression of phosphomethylpyrimidine synthase (thiC), ABC transporter substrate-binding protein, branched-chain amino acid ABC transporter substrate-binding protein, and RNA polymerase (rpoE) in HNDS-1 were significantly upregulated when used peptone as N source, while the expression of exopolysaccharide production protein (yjbE), RNA polymerase (rpoC), glutamate synthase (gltD) and ABC-type branched-chain amino acid transport systems in HNDS-6 were significantly upregulated. This indicated that these two strains are capable of using organic N and converting it into NH4+-N, then utilizing NH4+-N to synthesize amino acids and proteins for their own growth, and strain HNDS-6 can also remove NH4+-N through nitrification and denitrification.

Isolation and structure determination of a new bisabolane-type sesquiterpenoid with cytotoxicity from Penicillium oxalicum MZY-202312-521.

Endophytic fungi can produce attractive secondary metabolites with various biological activities that have contributed significantly to pharmacotherapy. In this study, three bisabolane-type sesquiterpenoids, including a new one, namely, inonotic acid C (1), together with previously reported compounds (S)-(+)-11-dehydrosydonic acid (2) and sydonic acid (3), were isolated from a marine algal-derived endophytic fungus Penicillium oxalicum MZY-202312-521. Their structures were determined by means of extensive spectroscopic analyses. The absolute configurations of inonotic acid C (1) were established by single-crystal X-ray diffraction method. In vitro cytotoxic experiments on human A549, MCF-7, HeLa, and HepG2 carcinoma cell lines were carried out. The new compound inonotic acid C (1) was found to possess strong inhibitory activity against the MCF-7 cell line, with an IC50 value of 7.7 µM.

To Investigate the Mechanism of Qinpi Tongfeng Formula in Treating Acute Gouty Arthritis by UHPLC-Q-Orbitrap-MS, Network Pharmacology and Experimental Validation.

Background: Acute gouty arthritis (AGA) is characterized by the accumulation of monosodium urate crystals within the joints, leading to inflammation and severe pain. Western medicine treatments have limitations in addressing this condition. Previous studies have shown the efficacy of Qinpi Tongfeng formula (QPTFF) in treating AGA, but further investigation is needed to understand its mechanism of action. Methods: We used ultra-high-performance liquid chromatography tandem Q-Exactive Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-MS) to identify compounds in QPTFF. Target proteins regulated by these compounds were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Chemistry Database, and Swiss Target Prediction Database. AGA-related targets were searched and screened from various databases, including Genecards, PharmGKB, Drugbank, etc. Intersection targets of QPTFF and AGA were analyzed for protein-protein interaction networks, GO function enrichment, and KEGG pathway enrichment. We then verified QPTFF's mechanism of action using an AGA rat model, assessing pathological changes via H&E staining and target expression via ELISA, RT-qPCR, and Western blot. Results: UHPLC-Q-Orbitrap-MS identified 207 compounds in QPTFF, with 55 selected through network pharmacology. Of 589 compound-regulated targets and 1204 AGA-related targets, 183 potential targets were implicated in QPTFF's treatment of AGA. Main target proteins included IL-1ß, NFKBIA, IL-6, TNF, CXCL8, and MMP9, with the IL-17 signaling pathway primarily regulated by QPTFF. Experimental results showed that medium and high doses of QPTFF significantly reduced serum inflammatory factors and MMP-9 expression, and inhibited IL-17A, IL-6, IKK-ß, and NF-κB p65 mRNA and protein expression in AGA rats compared to the model group. Conclusion: Key targets of QPTFF include IL-1ß, NFKBIA, IL-6, TNF-α, CXCL8, and MMP9. QPTFF effectively alleviates joint inflammation in AGA rats, with high doses demonstrating no liver or kidney toxicity. Its anti-inflammatory mechanism in treating AGA involves the IL-17A/NF-κB p65 signaling pathway.

The changes of intestinal microbiota and metabolomics during the inhibition of bladder cancer by liquiritigenin.

Liquiritigenin is a natural medicine. However, its inhibitory effect and its potential mechanism on bladder cancer (BCa) remain to be explored. It was found that it could be visualized that the transplanted tumours in the low-dose liquiritigenin -treated group and the high-dose liquiritigenin -treated group were smaller than those in the model group. Liquiritigenin treatment led to alterations in Lachnoclostridium, Escherichia-Shigella, Alistipes and Akkermansia. Non-targeted metabolomics analysis showed that a total of multiple differential metabolites were identified between the model group and the high-dose liquiritigenin-treated group. This provides a new direction and rationale for the antitumour effects of liquiritigenin.

High intraoperative fluid load associated with prolonged length of hospital stay and complications after non-cardiac surgery in neonates.

Inappropriate perioperative fluid load can lead to postoperative complications and death. This retrospective study was designed to investigate the association between intraoperative fluid load and outcomes in neonates undergoing non-cardiac surgery. From April 2020 to September 2022, 940 neonates who underwent non-cardiac surgery were retrospectively enrolled and their perioperative data were harvested for further analysis. According to recorded intraoperative fluid volumes defined as ml.kg-1 h-1, patients were mandatorily divided into quintile with fluid load as restrictive (quintile 1, Q1), moderately restrictive (Q2), moderate (Q3), moderately liberal (Q4), and liberal (Q5). The primary outcomes were defined as prolonged length of hospital stay (LOS) (postoperative LOS ≥ 14 days), complications beyond prolonged LOS, and 30-day mortality. Secondary outcomes included postoperative complications within 14 days of hospital stay. The intraoperative fluid load was in Q1 of 6.5 (5.3-7.3) (median and IQR); Q2: 9.2 (8.7-9.9); Q3: 12.2 (11.4-13.2); Q4: 16.5 (15.4-18.0); and Q5: 26.5 (22.3-32.2) ml.kg-1 h-1. The odd of prolonged LOS was positively correlated with an increase fluid volume (Q5 quintile: OR 2.602 [95% CI 1.444-4.690], P = 0.001), as well as complications beyond prolonged LOS (Q5: OR 3.322 [95% CI 1.656-6.275], P = 0.001). The overall 30-day mortality rate was increased with high intraoperative fluid load but did not reach to a statistical significance after adjusted with confounders. Furthermore, the highest quintile of fluid load (26.5 ml.kg-1 h-1, IQR [22.3-32.2]) (Q5 quintile) was significantly associated with longer postoperative mechanical ventilation time compared with Q1 (Q5: OR 2.212 [95% CI 1.101-4.445], P = 0.026).    Conclusion: Restrictive intraoperative fluid load had overall better outcomes, whilst high fluid load was significantly associated with prolonged LOS and complications after non-cardiac surgery in neonates.    Trial registration:  Chictr.org.cn Identifier: ChiCTR2200066823 (December 19, 2022). What is Known: • Inappropriate perioperative fluid load can lead to postoperative complications and even death. What is New: • High perioperative fluid load was significantly associated with an increased length of stay after non-cardiac surgery in neonates, whilst low fluid load was consistently related to better postoperative outcomes.

A new cassane diterpenoid from the seed of Caesalpinia sappan.

In this study, a previously undescribed cassane diterpenoid, named caesalpinin JF (1), along with two known cassane diterpenoids caesanine C (2) and tomocinol B (3), was isolated from 95% EtOH extract of the seeds of Caesalpinia sappan Linn. Additionally, three known compounds including pulcherrin R (4), syringaresinol-4'-O-ß-D-glucopyranoside (5) and kaempferol (6) were also identified. The structures of the isolated compounds were elucidated by comprehensive 1D and 2D NMR spectroscopic analyses. Additionally, electronic circular dichroism (ECD) calculation was used to identify the absolute structure of compound 1. Among the isolated compounds, compound 1 displayed a potent anti-neuroinflammation with an IC50 value of 9.87 ± 1.71 µM.

Modified traditional TNM staging of pyriform sinus and hypopharyngeal and laryngeal cancer based on lymph node ratio and its clinical significance: a population-based study combined with external validation.

BACKGROUND: To evaluate the application value of a new TLNRM staging prediction model based on lymph node ratio (LNR) in patients with Pyriform Sinus and Hypopharyngeal and Laryngeal cancer (PHLC). METHODS: A total of 2,257 patients with pathologically diagnosed PHLC from 2004 through 2019 were collected from the SEE database for analysis. The N staging of AJCC was replaced by LNR, and we compared the differences in patient prognosis and judgment ability between the new TLNRM staging and the 8th edition TNM staging. At the same time, data from 1,094 people in our hospital were included for external verification and validation. RESULTS: We selected four cutoff points based on LNR and reclassified N staging into five groups (LNR1-5). Compared to the traditional TNM staging (8th edition), the new TLNRM staging showed a statistically significant 5-year OS difference. The decision curve showed that the new TLNRM staging had a higher net benefit for different decision thresholds than the traditional TNM staging system's prediction line. The smaller AIC and BIC suggested that the new staging system had a higher sensitivity to prognosis evaluation compared to the traditional staging system. TLNRM stage III patients can benefit from radiotherapy, while TLNRM IVA and IVB patients can benefit from chemoradiotherapy. The same conclusion has been drawn from external validation data from our center. CONCLUSIONS: Compared with the traditional 8th edition AJCC staging system, the new TLNRM staging system has advantages in predicting the staging and prognosis of PHLC patients, and can independently guide postoperative chemoradiotherapy in patients.

Unveiling Collagen's Role in Breast Cancer: Insights into Expression Patterns, Functions and Clinical Implications.

Collagen, the predominant protein constituent of the mammalian extracellular matrix (ECM), comprises a diverse family of 28 members (I-XXVIII). Beyond its structural significance, collagen is implicated in various diseases or cancers, notably breast cancer, where it influences crucial cellular processes including proliferation, metastasis, apoptosis, and drug resistance, intricately shaping cancer progression and prognosis. In breast cancer, distinct collagens exhibit differential expression profiles, with some showing heightened or diminished levels in cancerous tissues or cells compared to normal counterparts, suggesting specific and pivotal biological functions. In this review, we meticulously analyze the expression of individual collagen members in breast cancer, utilizing Transcripts Per Million (TPM) data sourced from the GEPIA2 database. Through this analysis, we identify collagens that deviate from normal expression patterns in breast cancer, providing a comprehensive overview of their expression dynamics, functional roles, and underlying mechanisms. Our findings shed light on recent advancements in understanding the intricate interplay between these aberrantly expressed collagens and breast cancer. This exploration aims to offer valuable insights for the identification of potential biomarkers and therapeutic targets, thereby advancing the prospects of more effective interventions in breast cancer treatment.

Punicalagin attenuates hyperuricemia via restoring hyperuricemia-induced renal and intestinal dysfunctions.

INTRODUCTION: It is estimated that 90% of hyperuricemia cases are attributed to the inability to excrete uric acid (UA). The two main organs in charge of excreting UA are the kidney (70%) and intestine (30%). Previous studies have reported that punicalagin (PU) could protect against kidney and intestinal damages, which makes it a potential candidate for alleviating hyperuricemia. However, the effects and deeper action mechanisms of PU for managing hyperuricemia are still unknown. OBJECTIVE: To investigate the effect and action mechanisms of PU for ameliorating hyperuricemia. METHODS: The effects and action mechanisms of PU on hyperuricemia were assessed using a hyperuricemia mice model. Phenotypic parameters, metabolomics analysis, and 16S rRNA sequencing were applied to explore the effect and fundamental action mechanisms inside the kidney and intestine of PU for improving hyperuricemia. RESULTS: PU administration significantly decreased elevated serum uric acid (SUA) levels in hyperuricemia mice, and effectively alleviated the kidney and intestinal damage caused by hyperuricemia. In the kidney, PU down-regulated the expression of UA resorption protein URAT1 and GLUT9, while up-regulating the expression of UA excretion protein ABCG2 and OAT1 as mediated via the activation of MAKP/NF-κB in hyperuricemia mice. Additionally, PU attenuated renal glycometabolism disorder, which contributed to improving kidney dysfunction and inflammation. Similarly, PU increased UA excretion protein expression via inhibiting MAKP/NF-κB activation in the intestine of hyperuricemia mice. Furthermore, PU restored gut microbiota dysbiosis in hyperuricemia mice. CONCLUSION: This research revealed the ameliorating impacts of PU on hyperuricemia by restoring kidney and intestine damage in hyperuricemia mice, and to be considered for the development of nutraceuticals used as UA-lowering agent.

Traditional herbal medicine: Therapeutic potential in acute gouty arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute gouty arthritis (AGA) is characterized by a rapid inflammatory reaction caused by the build-up of monosodium urate (MSU) crystals in the tissues surrounding the joints. This condition often associated with hyperuricemia (HUA), is distinguished by its symptoms of intense pain, active inflammation, and swelling of the joints. Traditional approaches in AGA management often fall short of desired outcomes in clinical settings. However, recent ethnopharmacological investigations have been focusing on the potential of Traditional Herbal Medicine (THM) in various forms, exploring their therapeutic impact and targets in AGA treatment. AIM OF THE REVIEW: This review briefly summarizes the current potential pharmacological mechanisms of THMs - including active ingredients, extracts, and prescriptions -in the treatment of AGA, and discusses the relevant potential mechanisms and molecular targets in depth. The objective of this study is to offer extensive information and a reference point for the exploration of targeted AGA treatment using THMs. MATERIALS AND METHODS: This review obtained scientific publications focused on in vitro and in vivo studies of anti-AGA THMs conducted between 2013 and 2023. The literature was collected from various journals and electronic databases, including PubMed, Elsevier, ScienceDirect, Web of Science, and Google Scholar. The retrieval and analysis of relevant articles were guided by keywords such as "acute gouty arthritis and Chinese herbal medicine," "acute gouty arthritis herbal prescription," "acute gouty arthritis and immune cells," "acute gouty arthritis and inflammation," "acute gouty arthritis and NOD-like receptor thermoprotein domain associated protein 3 (NLRP3)," "acute gouty arthritis and miRNA," and "acute gouty arthritis and oxidative stress." RESULTS: We found that AGA has a large number of therapeutic targets, highlighting the effectiveness the potential of THMs in AGA treatment through in vitro and in vivo studies. THMs and their active ingredients can mitigate AGA symptoms through a variety of therapeutic targets, such as influencing macrophage polarization, neutrophils, T cells, natural killer (NK) cells, and addressing factors like inflammation, NLRP3 inflammasome, signaling pathways, oxidative stress, and miRNA multi-target interactions. The anti-AGA properties of THMs, including their active components and prescriptions, were systematically summarized and categorized based on their respective therapeutic targets. CONCLUSION: phenolic, flavonoid, terpenoid and alkaloid compounds in THMs are considered the key ingredients to improve AGA. THMs and their active ingredients achieve enhanced efficacy through interactions with multiple targets, of which NLRP3 is a main therapeutic target. Nonetheless, given the intricate composition of traditional Chinese medicine (TCM), additional research is required to unravel the underlying mechanisms and molecular targets through which THMs alleviate AGA.

Human immunoglobulin in combination with antimicrobial agents enhances the treatment efficacy and reduces inflammatory response in children with severe pneumonia.

OBJECTIVE: To investigate the efficacy of human immunoglobulin combined with antibiotics in treating severe pediatric pneumonia. METHODS: A retrospective analysis was performed on 210 pediatric patients with severe pneumonia admitted to the Department of Neonatology of Cangzhou Central Hospital from April 2019 to October 2022. Patients were divided into two groups (the observation group and the control group) based on the administration of human immunoglobulin. Clinical indexes of both groups before and after treatment were analyzed to determine the therapeutic effect of different treatment methods on pediatric severe pneumonia. RESULTS: The durations of cough, fever, pulmonary rales, and lung shadow, and hospitalization time in the observation group were significantly shorter than those in the control group (all P<0.05). The total clinical effective rate in the observation group was significantly higher than that in the control group (P<0.05). Levels of inflammatory factors (IL-6, IL-8 and hsCRP) were decreased in both groups after treatment (all P<0.05), and were lower in the observation group compared with the control group after treatment (all P<0.05). The serum levels of IgA, IgG and IgM after five days of intervention were obviously higher than those before intervention in the observation group (all P<0.05), but the serum levels of IL-4, INF-γ and INF-γ/IL-4 were obviously lower (all P<0.05). The total incidence of adverse reactions between two groups after intervention was not statistically different (P<0.05). CONCLUSION: The combination of human immunoglobulin and antibiotics for the treatment of pediatric severe pneumonia is beneficial, because it improves efficacy, boosts the immune system, and reduces inflammation.

Signs or symptoms of suspected preeclampsia - A retrospective national database study of prevalence, costs, and outcomes.

BACKGROUND: Most patients with signs or symptoms (s/s) of suspected preeclampsia are not diagnosed with preeclampsia. We sought to determine and compare the prevalence of s/s, pregnancy outcomes, and costs between patients with and without diagnosed preeclampsia. METHODS: This retrospective cohort study analyzed a large insurance research database. Pregnancies with s/s of preeclampsia versus a confirmed preeclampsia diagnosis were identified using International Classification of Diseases codes. S/s include hypertension, proteinuria, headache, visual symptoms, edema, abdominal pain, and nausea/vomiting. Pregnancies were classed as 1) s/s of preeclampsia without a confirmed preeclampsia diagnosis (suspicion only), 2) s/s with a confirmed diagnosis (preeclampsia with suspicion), 3) diagnosed preeclampsia without s/s recorded (preeclampsia only), and 4) no s/s, nor preeclampsia diagnosis (control). RESULTS: Of 1,324,424 pregnancies, 29.2 % had ≥1 documented s/s of suspected preeclampsia, and 14.2 % received a preeclampsia diagnosis. Hypertension and headache were the most common s/s, leading 20.2 % and 9.2 % pregnancies developed to preeclampsia diagnosis, respectively. Preeclampsia, with or without suspicion, had the highest rates of hypertension-related severe maternal morbidity (HR [95 % CI]: 3.0 [2.7, 3.2] and 3.6 [3.3, 4.0], respectively) versus controls. A similar trend was seen in neonatal outcomes such as preterm delivery and low birth weight. Cases in which preeclampsia was suspected but not confirmed had the highest average total maternal care costs ($6096 [95 % CI: 602, 6170] over control). CONCLUSION: There is a high prevalence but poor selectivity of traditional s/s of preeclampsia, highlighting a clinical need for improved screening method and cost-effectiveness disease management.

Ginsenoside Rg3 decreases breast cancer stem-like phenotypes through impairing MYC mRNA stability.

Breast cancer stem cells (BCSCs) are responsible for breast cancer metastasis, recurrence and treatment resistance, all of which make BCSCs potential drivers of breast cancer aggression. Ginsenoside Rg3, a traditional Chinese herbal medicine, was reported to have multiple antitumor functions. Here, we revealed a novel effect of Rg3 on BCSCs. Rg3 inhibits breast cancer cell viability in a dose- and time-dependent manner. Importantly, Rg3 suppressed mammosphere formation, reduced the expression of stemness-related transcription factors, including c-Myc, Oct4, Sox2 and Lin28, and diminished ALDH(+) populations. Moreover, tumor-bearing mice treated with Rg3 exhibited robust delay of tumor growth and a decrease in tumor-initiating frequency. In addition, we found that Rg3 suppressed breast cancer stem-like properties mainly through inhibiting MYC expression. Mechanistically, Rg3 accelerated the degradation of MYC mRNA by enhancing the expression of the let-7 family, which was demonstrated to bind to the MYC 3' untranslated region (UTR). In conclusion, our findings reveal the remarkable suppressive effect of Rg3 on BCSCs, suggesting that Rg3 is a promising therapeutic treatment for breast cancer.

Discovery of potential components characteristic by conjugated enone from the branches and leaves of Croton lauioides with anti-neuroinflammatory activity via regulating the NF-κB pathway.

In this study, the chemical composition and pharmacological activity of Croton lauioides were investigated for the first time. The bioactive and HPLC-UV guided isolation led to the discovery of twenty-three conjugated enone-type components (1-23), including nine previously unknown sesquiterpenoid derivatives (1-4, 9-10, 12-14). Notably, compounds 1 and 12 are epoxides containing an endoperoxide bridge (1) or a unique dioxaspiro core (12), respectively. Compounds 2-7 are non-benzenoid aromatics featuring a tropone function, while 9-11 possess a rare rearranged scaffold with tropone shift into benzene. Extensive characterization was performed using NMR spectra, HRESIMS data, and electronic circular dichroism (ECD) calculations. Furthermore, we evaluated the bioactivities of all isolated compounds against neuroinflammation in LPS-stimulated BV-2 microglial cells. Remarkably, most sesquiterpenoid derivatives exhibited significant NO inhibit activities, and compound 5 showed the most potent effect with an IC50 value of 0.14 ± 0.04 µM. Structure-activity relationship (SAR) analysis revealed that sesquiterpenoids modified with endocyclic enone conjugation may serve as a key pharmacophore for NO inhibition, particularly involving aromatic tropone moiety. The qPCR and Western blot results demonstrated that 5 exerted an inhibitory effect on the mRNA levels of iNOS, TNF-α and COX-2 in a time-dependent manner, as well as suppressed the protein expression of iNOS, TNF-α, COX-2. In mechanism, 5 could prevented activation of NF-κB pathway by suppressing phosphorylation of p65 and IκB-α. These findings revealed C. lauioides might be a promising resource for drug candidate development targeting neuroinflammation.

Berberine promotes the degradation of phenylacetic acid to prevent thrombosis by modulating gut microbiota.

BACKGROUND: Berberine is the main bioactive constituent of Coptis chinensis, a quaternary ammonium alkaloid. While berberine's cardiovascular benefits are well-documented, its impact on thrombosis remains not fully understood. PURPOSE: This study investigates the potential of intestinal microbiota as a novel target for preventing thrombosis, with a focus on berberine, a natural compound known for its effectiveness in managing cardiovascular conditions. METHODS: Intraperitoneal injection of carrageenan induces the secretion of chemical mediators such as histamine and serotonin from mast cells to promote thrombosis. This model can directly and visually observe the progression of thrombosis in a time-dependent manner. Thrombosis was induced by intravenous injection of 1 % carrageenan solution (20 mg/kg) to all mice except the vehicle control group. Quantitative analysis of gut microbiota metabolites through LC/MS. Then, the gut microbiota of mice was analyzed using 16S rRNA sequencing to assess the changes. Finally, the effects of gut microbiota on thrombosis were explored by fecal microbiota transplantation. RESULTS: Our research shows that berberine inhibits thrombosis by altering intestinal microbiota composition and related metabolites. Notably, berberine curtails the biosynthesis of phenylacetylglycine, a thrombosis-promoting coproduct of the host-intestinal microbiota, by promoting phenylacetic acid degradation. This research underscores the significance of phenylacetylglycine as a thrombosis-promoting risk factor, as evidenced by the ability of intraperitoneal phenylacetylglycine injection to reverse berberine's efficacy. Fecal microbiota transplantation experiment confirms the crucial role of intestinal microbiota in thrombus formation. CONCLUSION: Initiating our investigation from the perspective of the gut microbiota, we have, for the first time, unveiled that berberine inhibits thrombus formation by promoting the degradation of phenylacetic acid, consequently suppressing the biosynthesis of PAG. This discovery further substantiates the intricate interplay between the gut microbiota and thrombosis. Our study advances the understanding that intestinal microbiota plays a crucial role in thrombosis development and highlights berberine-mediated intestinal microbiota modulation as a promising therapeutic approach for thrombosis prevention.

Factors influencing the length of stay (LOS) undergoing robot-assisted thoracoscopic lung surgery in the setting of enhanced recovery after surgery (ERAS) protocol for pediatric patients: a retrospective study.

Background: A prolonged length of stay (LOS) after surgery may result in higher hospital costs and hospital-acquired complications. This study aims to identify the risk factors associated with a prolonged hospital stay after robot-assisted thoracoscopic lung surgery for pediatric patients in the context of enhanced recovery after surgery. Methods: The data for this retrospective study were collected from pediatric patients undergoing robot-assisted thoracoscopic lung surgery. Patients were divided into two subgroups based on median postoperative LOS (Group I: LOS > median 5 days and Group II: LOS ≤ median 5 days). Logistic regression analysis was used to identify the potential factors associated with increased LOS. Results: This study included 241 patients, 71 (29.46%) with an LOS of >5 days. The proportion of older children was significantly higher in Group I than that in Group II (P=0.004). Patients in Group I were more likely to experience a longer duration of anesthesia and surgery (P<0.001). They also had significantly higher rates of pneumonia, pleural effusion, and liver function damage (P<0.05). Several factors were identified to be associated with an increased LOS after robot-assisted thoracoscopic lung surgery: age >6 years [odds ratio (OR) =3.214, 95% confidence interval (CI): 1.464-7.502, P=0.004], surgery duration >100 min (OR =2.138, 95% CI: 1.296-4.387, P=0.005), intra-albumin (OR =13.778, 95% CI: 1.470-129.116, P=0.022), and blood loss >5 mL (OR =2.184, 95% CI: 1.082-4.409, P=0.029). Conclusions: The results revealed that older age, longer surgery duration, use of intra-albumin, and more blood loss predict longer postoperative hospital stay in pediatric patients with congenital lung lesions after robot-assisted thoracoscopic lung surgery.

The molecular mechanism of action for the potent antitumor component extracted using supercritical fluid extraction from Croton crassifolius root.

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Croton crassifolius has been used as a traditional Chinese medicine (TCM), called Radix Croton Crassifolius, and commonly known as "Ji Gu Xiang" in Chinese. Its medicinal value has been recorded in several medical books or handbooks, such as "Sheng Cao Yao Xing Bei Yao", "Ben Cao Qiu Yuan" and "Zhong Hua Ben Cao". It has been traditional employed for treating sore throat, stomach-ache, rheumatism and cancer. AIM OF THE STUDY: At present, there are limited studies on the evaluation of low-polarity extracts of roots in C. crassifolius. Consequently, the aim of this study was to evaluate the antitumor effect of the low-polarity extract of C. crassifolius root. MATERIALS AND METHODS: Extracts were obtained by supercritical fluid extraction. The extracts were tested for antitumor effects in vitro on several cancer cell lines. A CCK-8 kit was used for further analysis of cell viability. A flow cytometer and propidium iodide staining were used to evaluate the cell cycle and apoptosis. Hoechst staining, JC-1 staining and the fluorescence probe DCFH-DA were used to evaluate apoptotic cells. Molecular mechanisms of action were analyzed by quantitative RT‒PCR and Western blotting. Immunohistochemistry was used for the evaluation of xenograft tumors in male BALB/c mice. Finally, molecular docking was employed to predict the bond between the desired bioactive compound and molecular targets. RESULTS: Eleven diterpenoids were isolated from low-polarity C. crassifolius root extracts. Among the compounds, chettaphanin II showed the strongest activity (IC50 = 8.58 µM) against A549 cells. Evaluation of cell viability and the cell cycle showed that Chettaphanin II reduced A549 cell proliferation and induced G2/M-phase arrest. Chttaphanin II significantly induced apoptosis in A549 cells, which was related to the level of apoptosis-related proteins. The growth of tumor tissue was significantly inhibited by chettaphanin II in experiments performed on naked mice. The antitumor mechanism of chettaphanin II is that it can obstruct the mTOR/PI3K/Akt signaling pathway in A549 cells. Molecular docking established that chettaphanin II could bind to the active sites of Bcl-2 and Bax. CONCLUSIONS: Taken together, the natural diterpenoid chettaphanin II was identified as the major antitumor active component, and its potential for developing anticancer therapies was demonstrated for the first time by antiproliferation evaluation in vitro and in vivo.