Control of large amplitude limit cycle of a multi-dimensional nonlinear dynamic system of a composite cantilever beam.

For the first time, a control strategy based on Fuzzy Sliding Mode Control is implemented in the control of a large amplitude limit cycle of a composite cantilever beam in a multi-dimensional nonlinear form. In the dynamic model establishment of the investigated structure, the higher-order shearing effect is applied, as well as the second-order discretization. Numerical simulation demonstrates that a multi-dimensional nonlinear dynamic system of the investigated structure is demanded for accurate estimation of large amplitude limit cycle responses. Therefore, a control strategy is employed to effectively suppress such responses of the beam in multi-dimensional nonlinear form.

Unlocking the potential of biochar: an iron-phosphorus-based composite modified adsorbent for adsorption of Pb(II) and Cd(II) in aqueous environments and response surface optimization of adsorption conditions.

In this work, iron-phosphorus based composite biochar (FPBC) was prepared by modification with potassium phosphate and iron oxides for the removal of heavy metal ions from single and mixed heavy metal (Pb and Cd) solutions. FTIR and XPS characterization experiments showed that the novel modified biochar had a greater number of surface functional groups compared to the pristine biochar. The maximum adsorption capacities of FPBC for Pb(II) and Cd(II) were 211.66 mg·g-1 and 94.08 mg·g-1 at 293 K. The adsorption of Pb(II) and Cd(II) by FPBC followed the proposed two-step adsorption kinetic model and the Freundlich isothermal adsorption model, suggesting that the mechanism of adsorption of Pb(II) and Cd(II) by FPBC involved chemical adsorption of multiple layers. Mechanistic studies showed that the introduction of -PO4 and -PO3 chemisorbed with Pb(II) and Cd(II), and the introduction of -Fe-O increased the ion exchange with Pb(II) and Cd(II) during the adsorption process and produced precipitates such as Pb3Fe(PO4)3 and Cd5Fe2(P2O7)4. Additionally, the abundant -OH and -COOH groups also participated in the removal of Pb(II) and Cd(II). In addition, FPBC demonstrated strong selective adsorption of Pb(II) in mixed heavy metal solutions. The Response Surface Methodology(RSM) analysis determined the optimal adsorption conditions for FPBC as pH 5.31, temperature 26.01 °C, and Pb(II) concentration 306.30 mg·L-1 for Pb(II). Similarly, the optimal adsorption conditions for Cd(II) were found to be pH 5.66, temperature 39.34 °C, and Cd(II) concentration 267.68 mg·L-1. Therefore, FPBC has the potential for application as a composite-modified adsorbent for the adsorption of multiple heavy metal ions.

Differences between resident self-assessments and faculty- assessments on Anesthesiology Milestones and associated factors: a cross-sectional study.

BACKGROUND: Accurate self-assessment is crucial for the professional development of physicians. There has been sparse data on the accuracy of self-assessments on Anesthesiology Milestones. The aim of this study was to investigate the differences between resident self-assessments and faculty-assessments on Anesthesiology Milestones and the associated factors. METHODS: This was a cross-sectional study conducted in a general tertiary university-affiliated hospital. We included anesthesia residents who were enrolled in the standardized residency training program in postgraduate year two and three at the time of the Milestone evaluation. We requested evaluations of competencies from both the Clinical Competency Committee faculty and the anesthesia residents themselves, utilizing the Chinese version of Anesthesiology Milestones in January 2023 and January 2024. The primary outcome was the differences between self- and faculty-assessments, calculated by subtracting the faculty-rated score from the self-rated score on each subcompetency. RESULTS: A total of 46 and 42 residents were evaluated in year 2023 and 2024, respectively. The self-rated sum score was significantly higher than that rated by faculty [mean (standardized deviation): 120.39 (32.41) vs. 114.44 (23.71), P = 0.008 in paired t test] with an intraclass correlation coefficient of 0.55 [95% confidence interval (CI): 0.31 to 0.70]. The Bland-Altman plots revealed significant overestimation in patient care (bias 0.32, 95% CI: 0.05 to 0.60), practice-based learning and improvement (bias 0.45, 95% CI: 0.07 to 0.84), and professionalism (bias 0.37, 95% CI: 0.02 to 0.72). Ratings from residents with master's degrees (mean difference: -1.06, 95% CI: -1.80 to -0.32, P = 0.005) and doctorate degrees (mean difference: -1.14, 95% CI: -1.91 to -0.38, P = 0.003) were closer to the faculty-assessments than residents with bachelor's degrees. Compared with patient care, the differences between self- and faculty- rated scores were smaller in medical knowledge (mean difference: -0.18, 95% CI: -0.35 to -0.02, P = 0.031) and interpersonal and communication skills (mean difference: -0.41, 95% CI: -0.64 to -0.19, P < 0.001) in the generalized estimating equation logistic regression model. CONCLUSIONS: This study revealed that residents tended to overestimate themselves, emphasizing the need to improve the accuracy of Milestones self-assessment. The differences between self- and faculty-assessments were associated with residents' degrees and domains of competency.

Family resilience and vulnerability of patients at diagnosis of lung cancer: A qualitative study.

AIM: To explore and analyse the adaptation process of patients and their families at the point of lung cancer diagnosis. METHODS: Totally 23 operable lung cancer patients were included in this study. Colaizzi's method of phenomenology was employed for data analysis. RESULTS: This study found two different aspects of family adaptation at the diagnosis of lung cancer. For family resilience, three themes emerged: (1) Positive family belief systems (giving meaning to a cancer diagnosis and maintaining a positive/optimistic attitude), (2) Flexible family organizational patterns (maintaining the stability of family structure and function, adjusting the relationship between patients and family members and receiving external support and help) and (3) Good communication and problem-solving strategies (open communication on an equal basis, positive and open expression of emotions and collaborative problem-solving). For family vulnerability, three themes were as follows: (1) Negative family belief systems (negative attitudes and concealment and self-isolation due to stigma), (2) Rigid family organizational patterns (adaptation lost, conflicts between family support and patients' willingness and pressure upon social support) and (3) Unhealthy communication and problem-solving (poor communication, emotional asymmetry of family members and tendency to solve problems alone). CONCLUSION: The study highlights the existence of the family resilience and family vulnerability at the point of lung cancer diagnosis and provides patient's perspective for understanding family resilience in specific cultural contexts. PATIENT CONTRIBUTION: The data were collected through face-to-face interviews. TRAIL REGISTRATION NUMBER: ChiCTR2300074801.

Enterotoxin-related genes PPFIA4 and SCN3B promote colorectal cancer development and progression.

To identify the role of enterotoxin-related genes in colorectal cancer (CRC) development and progression. Upregulated differentially expressed genes shared by three out of five Gene Expression Omnibus (GEO) data sets were included to screen the key enterotoxin-induced oncogenes (EIOGs) according to criteria oncogene definition, enrichment, and protein-protein interaction (PPI) network analysis, followed by prognosis survival, immune infiltration, and protential drugs analyses was performed via integration of RNA-sequencing data and The Cancer Genome Atlas-derived clinical profiles. We screened nine common key EIOGs from at least three GEO data sets. A Cox proportional hazards regression models verified that more alive cases, decreased overall survival, and highest 4-year survival prediction in CRC patients with high-risk score. Protein tyrosine phosphatase receptor type F polypeptide-interacting protein alpha-4 (PPFIA4), STY11, SCN3B, and SPTBN5 were shared in the same PPI network. Immune infiltration results showed that SCN3B and synaptotagmin 11 expression were obviously associated with B cell, macrophage, myeloid dendritic cell, neutrophils, and T cell CD4+ and CD8+ in both colon adenocarcinoma and rectal adenocarcinoma. CHIR-99021, MLN4924, and YK4-279 were identified as the potential drugs for treatment. Finally, upregulated EIOGs genes PPFIA4 and SCN3B were found in colon adenocarcinoma and PPFIA4 and SCN3B were proved to promote cell proliferation and migration in vitro. We demonstrated here that EIOGs promoting a malignancy phenotype was related with poor survival and prognosis in CRC, which might be served as novel therapeutic targets in CRC management.

The coupling of sulfide and Fe-Mn mineral promotes the migration of lead and zinc in the redox cycle of high pH floodplain soils.

In this study, we investigated the impact of fluctuating water levels on the distribution of lead (Pb) and zinc (Zn) in soil and sediments at a historical Pb-Zn smelting site along the Xiangjiang River. Despite the high pH levels (7 to 11) in the study area, which generally inhibits heavy metal solubility, we found that regular changes in water levels still affect Pb-Zn movement. Soil analysis revealed distinct redox zones within the unconfined aquifer, as shown by the variable Fe/Mn and Ce/Ce* ratios. Advanced techniques such as Mn K-edge XAFS, Mössbauer spectroscopy, and TOF-SIMS indicated persistent Fe-Mn redox cycling and highlighted the presence of Pb and Zn-rich manganese oxides near sulfur-bearing minerals. These findings suggest that acidic microzones produced by the oxidation of sulfur-bearing minerals become "refuges" for microbial and heavy metal activity. Considering that sulfur-containing minerals are widespread waste types in nonferrous metal smelting sites, these findings are instructive for a better understanding of the transformation mechanisms of heavy metal ions in nonferrous metal smelting-polluted environments and for guiding pollution remediation strategies.

Ionic-physical-chemical triple cross-linked all-biomass-based aerogel for thermal insulation applications.

Aerogels, as a unique porous material, are expected to be used as insulation materials to solve the global environmental and energy crisis. Using chitosan, citric acid, pectin and phytic acid as raw materials, an all-biomass-based aerogel with high modulus was prepared by the triple strategy of ionic, physical and chemical cross-linking through directional freezing technique. Based on this three-dimensional network, the aerogel exhibited excellent compressive modulus (24.89 ± 1.76 MPa) over a wide temperature range and thermal insulation properties. In the presence of chitosan, citric acid and phytic acid, the aerogel obtained excellent fire safety (LOI value up to 31.2%) and antibacterial properties (antibacterial activity against Staphylococcus aureus and Escherichia coli reached 81.98% and 67.43%). In addition, the modified aerogel exhibited excellent hydrophobicity (hydrophobic angle of 146°) and oil-water separation properties. More importantly, the aerogel exhibited a biodegradation rate of up to 40.31% for 35 days due to its all-biomass nature. This work provides a green and sustainable strategy for the production of highly environmentally friendly thermal insulation materials with high strength, flame retardant, antibacterial and hydrophobic properties.

Efficacy of bougie first approach for endotracheal intubation with video laryngoscopy during continuous chest compression: a randomized crossover manikin trial.

BACKGROUND: Endotracheal intubation is challenging during cardiopulmonary resuscitation, and video laryngoscopy has showed benefits for this procedure. The aim of this study was to compare the effectiveness of various intubation approaches, including the bougie first, preloaded bougie, endotracheal tube (ETT) with stylet, and ETT without stylet, on first-attempt success using video laryngoscopy during chest compression. METHODS: This was a randomized crossover trial conducted in a general tertiary teaching hospital. We included anesthesia residents in postgraduate year one to three who passed the screening test. Each resident performed intubation with video laryngoscopy using the four approaches in a randomized sequence on an adult manikin during continuous chest compression. The primary outcome was the first-attempt success defined as starting ventilation within a one minute. RESULTS: A total of 260 endotracheal intubations conducted by 65 residents were randomized and analyzed with 65 procedures in each group. First-attempt success occurred in 64 (98.5%), 57 (87.7%), 56 (86.2%), and 46 (70.8%) intubations in the bougie-first, preloaded bougie, ETT with stylet, and ETT without stylet approaches, respectively. The bougie-first approach had a significantly higher possibility of first-attempt success than the preloaded bougie approach [risk ratio (RR) 8.00, 95% confidence interval (CI) 1.03 to 62.16, P = 0.047], the ETT with stylet approach (RR 9.00, 95% CI 1.17 to 69.02, P = 0.035), and the ETT without stylet approach (RR 19.00, 95% CI 2.62 to 137.79, P = 0.004) in the generalized estimating equation logistic model accounting for clustering of intubations operated by the same resident. In addition, the bougie first approach did not result in prolonged intubation or increased self-reported difficulty among the study participants. CONCLUSIONS: The bougie first approach with video laryngoscopy had the highest possibility of first-attempt success during chest compression. These results helped inform the intubation approach during CPR. However, further studies in an actual clinical environment are warranted to validate these findings. TRIAL REGISTRATION: Clinicaltrials.gov; identifier: NCT05689125; date: January 18, 2023.

Dynamic structural evolution of MgO-supported palladium catalysts: from metal to metal oxide nanoparticles to surface then subsurface atomically dispersed cations.

Supported noble metal catalysts, ubiquitous in chemical technology, often undergo dynamic transformations between reduced and oxidized states-which influence the metal nuclearities, oxidation states, and catalytic properties. In this investigation, we report the results of in situ X-ray absorption spectroscopy, scanning transmission electron microscopy, and other physical characterization techniques, bolstered by density functional theory, to elucidate the structural transformations of a set of MgO-supported palladium catalysts under oxidative treatment conditions. As the calcination temperature increased, the as-synthesized supported metallic palladium nanoparticles underwent oxidation to form palladium oxides (at approximately 400 °C), which, at approximately 500 °C, were oxidatively fragmented to form mixtures of atomically dispersed palladium cations. The data indicate two distinct types of atomically dispersed species: palladium cations located at MgO steps and those embedded in the first subsurface layer of MgO. The former exhibit significantly higher (>500 times) catalytic activity for ethylene hydrogenation than the latter. The results pave the way for designing highly active and stable supported palladium hydrogenation catalysts with optimized metal utilization.

Central venous-to-arterial carbon dioxide partial pressure difference as a guiding parameter for cardiotonic drug administration in patients with early-stage septic shock.

OBJECTIVE: This study aimed to investigate the effect of the central venous-to-arterial carbon dioxide partial pressure difference (Pcv-aCO2) on the administration of cardiotonic drugs in patients with early-stage septic shock. METHODS: A retrospective study was conducted on 120 patients suffering from septic shock. At admission, the left ventricular ejection fraction (LVEF) and Pcv-aCO2 of the patients were obtained. On the premise of mean arterial pressure (MAP) ≥ 65 mmHg, the patients were divided into two groups according to the treatment approaches adopted by different doctors-Control group: LVEF ≤50%; Observation group: Pcv-aCO2 ≥ 6. Both groups received cardiotonic therapy. RESULTS: The two groups of patients had similar general conditions and pre-resuscitation conditions (P > 0.05). Compared to the Control group, the Observation group had a higher MAP, Lac clearance rate, and urine output after six hours of resuscitation (P < 0.05), but a lower absolute value of Lac, total fluid intake in 24 hours, and a lower number of patients receiving renal replacement therapy during hospitalization (P < 0.05). After six hours of resuscitation, the percentages of patients meeting central venous oxygen saturation and central venous pressure targets were not significantly different between the Control and Observation groups (P > 0.05). There was no difference in the 28-day mortality rate between the two groups (P > 0.05). CONCLUSION: Pcv-aCO2 is more effective than LVEF in guiding the administration of cardiotonic drugs in the treatment of patients with septic shock.

Wettability behavior of DTMS modified SiO2: Experimental and molecular dynamics study.

In this research, the wetting behavior of SiO2 modified with dodecyltrimethoxysilane (DTMS) was explored using both experimental and molecular dynamics (MD) simulation approaches. The experimental results reveal that DTMS can chemically bond to the SiO2 surface, and the contact angle (CA) reaches the maximum value of 157.7° when the mass of DTMS is twice that of SiO2. The different wetting behaviors caused by DTMS grafting were analyzed by CA fitting, ionic pairs, concentration distribution, molecule orientation, and interfacial interaction energy. The results demonstrate that a 25 % DTMS grafting rate resulted in a maximum CA of 158.2°, which is ascribed to the disruption of interfacial hydrogen bonding and changes in the hydration structure caused by DTMS grafting. Moreover, the above hydrophobic SiO2 model shows a slight decrease in CA as the water temperature increases, which is consistent with the experimental findings. In contrast, an opposite change was observed for the pristine SiO2 model. Although the higher water temperature enhances the diffusion capacity of water molecules in both models, the difference in interfacial interactions is responsible for the change in CA. We hope this finding will contribute to a deeper understanding of the wetting adjustment of SiO2.

Iron indices mediate but not modify association of parathyroid hormone with erythropoietin resistance in hemodialysis patients.

INTRODUCTION: Disordered iron balance and abnormal parathyroid hormone (PTH) concentrations, both prevalent in hemodialysis patients, are risk factors of erythropoietin (EPO) resistance. Few studies have evaluated the correlation between iron indices and PTH and the potential role of iron markers on the association of PTH with EPO resistance in hemodialysis population. METHODS: In this cross-sectional study of 71 maintenance hemodialysis patients, iron indices including hepcidin, ferritin, reticulocyte hemoglobin content (CHr) and transferrin saturation (TSAT) were examined. EPO responsiveness was measured as EPO resistance index (ERI). Lowess regression curves were performed to explore the cor-relations of iron indices, PTH and ERI. The association between PTH and ERI was modeled using linear regressions. Potential role of iron indices on this association was examined using stratified analyses and mediation analyses. RESULTS: The average ERI value of 10.3 ± 5.3 IU w-1 kg-1 (g/dL) -1. ERI was linked to PTH, hepcidin, CHr and TSAT (all P<0.05). PTH was associated with ERI levels (ß=0.007, 95%CI: 0.002-0.012, P=0.007). Hepcidin and PTH were closely correlated with each other (r = 0.28, P = 0.020). No clinically significant interaction between iron indexes and PTH was identified. Hepcidin appeared to mediate about one-fourth of the total association between PTH and ERI in hemodialysis population (25.71%, P=0.020). CONCLUSION: Iron indices and PTH levels were related to ERI values. Hepcidin ap-peared to be closely correlated to PTH and partly mediate the association between PTH and ERI in he-modialysis population.

The influence of social feedback on reward learning in the Iowa gambling task.

Learning, an important activity for both human and animals, has long been a focal point of research. During the learning process, subjects assimilate not only their own information but also information from others, a phenomenon known as social learning. While numerous studies have explored the impact of social feedback as a reward/punishment during learning, few studies have investigated whether social feedback facilitates or inhibits the learning of environmental rewards/punishments. This study aims to test the effects of social feedback on economic feedback and its cognitive processes by using the Iowa Gambling Task (IGT). One hundred ninety-two participants were recruited and categorized into one non-social feedback group and four social feedback groups. Participants in the social feedback groups were informed that after the outcome of each choice, they would also receive feedback from an online peer. This peer was a fictitious entity, with variations in identity (novice or expert) and feedback type (random or effective). The Outcome-Representation Learning model (ORL model) was used to quantify the cognitive components of learning. Behavioral results showed that both the identity of the peer and the type of feedback provided significantly influenced the deck selection, with effective social feedback increasing the ratio of chosen good decks. Results in the ORL model showed that the four social feedback groups exhibited lower learning rates for gain and loss compared to the nonsocial feedback group, which suggested, in the social feedback groups, the impact of the recent outcome on the update of value decreased. Parameters such as forgetfulness, win frequency, and deck perseverance in the expert-effective feedback group were significantly higher than those in the non-social feedback and expert-random feedback groups. These findings suggest that individuals proactively evaluate feedback providers and selectively adopt effective feedback to enhance learning.

Chirality-Dependent Valley Polarization in Magnetic van der Waals Heterostructures via Spin-Selective Charge Transfer.

Magnetic proximity interaction provides a promising route to manipulate the spin and valley degrees of freedom in van der Waals heterostructures. Here, we report a control of valley pseudospin in the WS2/MoSe2 heterostructure by utilizing the magnetic proximity effect of few-layered CrBr3 and, for the first time, observe a substantial difference in valley polarization of intra/interlayer excitons under different circularly polarized laser excitations, referred to as chirality-dependent valley polarization. Theoretical and experimental results reveal that the spin-selective charge transfer between MoSe2 and CrBr3, as well as between MoSe2 and WS2, is mostly responsible for the chiral feature of valley polarization in comparison with the proximity exchange field. This means that a long-distance manipulation of exciton behaviors in multilayer heterostructures can be achieved through spin-selective charge transfer. This work marks a significant advancement in the control of spin and valley pseudospin in multilayer structures.

Engineering of a Baeyer-Villiger monooxygenase to improve substrate scope, stereoselectivity and regioselectivity.

Baeyer-Villiger monooxygenases belong to a family of flavin-binding proteins that catalyze the Baeyer-Villiger (BV) oxidation of ketones to produce lactones or esters, which are important intermediates in pharmaceuticals or sustainable materials. Phenylacetone monooxygenase (PAMO) from Thermobifida fusca with moderate thermostability catalyzes the oxidation of aryl ketone substrates, but is limited by high specificity and narrow substrate scope. In the present study, we applied loop optimization by loop swapping followed by focused saturation mutagenesis in order to evolve PAMO mutants capable of catalyzing the regioselective BV oxidation of cyclohexanone and cyclobutanone derivatives with formation of either normal or abnormal esters or lactones. We further modulated PAMO to increase enantioselectivity. Crystal structure studies indicate that rotation occurs in the NADP-binding domain and that the high B-factor region is predominantly distributed in the catalytic pocket residues. Computational analyses further revealed dynamic character in the catalytic pocket and reshaped hydrogen bond interaction networks, which is more favorable for substrate binding. Our study provides useful insights for studying enzyme-substrate adaptations.

Association between childhood obesity and gut microbiota: 16S rRNA gene sequencing-based cohort study.

BACKGROUND: This study aimed to identify characteristic gut genera in obese and normal-weight children (8-12 years old) using 16S rDNA sequencing. The research aimed to provide insights for mechanistic studies and prevention strategies for childhood obesity. Thirty normal-weight and thirty age- and sex-matched obese children were included. Questionnaires and body measurements were collected, and fecal samples underwent 16S rDNA sequencing. Significant differences in body mass index (BMI) and body-fat percentage were observed between the groups. Analysis of gut microbiota diversity revealed lower α-diversity in obese children. Di-fferences in gut microbiota composition were found between the two groups. Prevotella and Firmicutes were more abundant in the obese group, while Bacteroides and Sanguibacteroides were more prevalent in the control group. AIM: To identify the characteristic gut genera in obese and normal-weight children (8-12-year-old) using 16S rDNA sequencing, and provide a basis for subsequent mechanistic studies and prevention strategies for childhood obesity. METHODS: Thirty each normal-weight, 1:1 matched for age and sex, and obese children, with an obese status from 2020 to 2022, were included in the control and obese groups, respectively. Basic information was collected through questionnaires and body measurements were obtained from both obese and normal-weight children. Fecal samples were collected from both groups and subjected to 16S rDNA sequencing using an Illumina MiSeq sequencing platform for gut microbiota diversity analysis. RESULTS: Significant differences in BMI and body-fat percentage were observed between the two groups. The Ace and Chao1 indices were significantly lower in the obese group than those in the control group, whereas differences were not significant in the Shannon and Simpson indices. Kruskal-Wallis tests indicated significant differences in unweighted and weighted UniFrac distances between the gut microbiota of normal-weight and obese children (P < 0.01), suggesting substantial disparities in both the species and quantity of gut microbiota between the two groups. Prevotella, Firmicutes, Bacteroides, and Sanguibacteroides were more abundant in the obese and control groups, respectively. Heatmap results demonstrated significant differences in the gut microbiota composition between obese and normal-weight children. CONCLUSION: Obese children exhibited lower α-diversity in their gut microbiota than did the normal-weight children. Significant differences were observed in the composition of gut microbiota between obese and normal-weight children.

Intermittent melena and refractory anemia due to jejunal cavernous lymphangioma: A case report.

BACKGROUND: Lymphangiomas in the gastrointestinal tract are extremely rare in adults. As a benign lesion, small intestine lymphangiomas often remain asymptomatic and pose challenges for definitive diagnosis. However, lymphangiomas can give rise to complications such as abdominal pain, bleeding, volvulus, and intussusception. Here, we report a case of jejunal cavernous lymphangioma that presented with intermittent melena and refractory anemia in a male adult. CASE SUMMARY: A 66-year-old man presented with intermittent melena, fatigue and refractory anemia nine months prior. Esophagogastroduodenoscopy and colonoscopy were performed many times and revealed no apparent bleeding. Conservative management, including transfusion, hemostasis, gastric acid secretion inhibition and symptomatic treatment, was performed, but the lesions tended to recur shortly after surgery. Ultimately, the patient underwent capsule endoscopy, which revealed a more than 10 cm lesion accompanied by active bleeding. After single-balloon enteroscopy and biopsy, a diagnosis of jejunal cavernous lymphangioma was confirmed, and the patient underwent surgical resection. No complications or recurrences were observed postoperatively. CONCLUSION: Jejunal cavernous lymphangioma should be considered a cause of obscure gastrointestinal bleeding. Capsule endoscopy and single-balloon enteroscopy can facilitate diagnosis. Surgical resection is an effective management method.

Anti-HBV Activities of Cembranoids from the South China Sea Soft Coral Sinularia pedunculata and Their Structure Activity Relationship.

Hepatitis B Virus (HBV) infection is a global public health challenge that seriously endangers human health. Soft coral, as a major source of terpenoids, contains many structurally novel and highly bioactive compounds. In previous studies, it has been demonstrated that cembranoid-type diterpenoids showed significant anti-inflammatory and anti-colorectal cancer activities. In this study, cembranoids isolated from Sinularia pedunculata was found with anti-HBV activity for the first time. Among them, compound 6 showed significant anti-HBV activity with an IC50 value of 5.57 µM without cytotoxicity. We analysed the preliminary structure-activity relationship (SAR). Furthermore, it is demonstrated that compound 6 can accelerate the formation of capsid, inhibit HBeAg, HBV core particle DNA, HBV total RNA and pregenomic RNA in a dose dependent manner. We also confirmed the anti-HBV activity in HepG2-NTCP infection system. Finally, we find the anti-HBV mechanism of these compounds by inhibiting the ENI/Xp enhancer/promoter.

Combination of omics, bioinformatics, molecular docking, and experimental validation to elucidate the hepatoprotective effects, mechanisms, and active compounds of Shandougen.

Omics, bioinformatics, molecular docking, and experimental validation were used to elucidate the hepatoprotective effects, mechanisms, and active compounds of Shandougen (SDG) based on the biolabel-led research pattern. Integrated omics were used to explore the biolabels of SDG intervention in liver tissue. Subsequently, bioinformatics and molecular docking were applied to topologically analyze its therapeutic effects, mechanisms, and active compounds based on biolabels. Finally, an animal model was used to verify the biolabel analysis results. Omics, bioinformatics, and molecular docking revealed that SDG may exert therapeutic effects on liver diseases in the multicompound and multitarget synergistic modes, especially liver cirrhosis. In the validation experiment, SDG and its active compounds (betulinic acid and gallic acid) significantly improved the liver histopathological damage in the CCl4-induced liver cirrhosis model. Meanwhile, they also produced significant inhibitory effects on the focal adhesion pathway (integrin alpha-1, myosin regulatory light chain 2, laminin subunit gamma-1, etc.) and alleviated the associated pathological processes: focal adhesion (focal adhesion kinase 1)-extracellular matrix (collagen alpha-1(IV) chain, collagen alpha-1(VI) chain, and collagen alpha-2(VI) chain) dysfunction, carcinogenesis (alpha-fetoprotein, NH3, and acetylcholinesterase), inflammation (tumor necrosis factor alpha, interleukin-1 [IL-1], IL-6, and IL-10), and oxidative stress (reactive oxygen species, malonaldehyde, and superoxide dismutase). This study provides new evidence and insights for the hepatoprotective effects, mechanisms, and active compounds of SDG.

The role of fungi in the diagnosis of colorectal cancer.

Colorectal cancer (CRC) is a prevalent tumour with high morbidity rates worldwide, and its incidence among younger populations is rising. Early diagnosis of CRC can help control the associated mortality. Fungi are common microorganisms in nature. Recent studies have shown that fungi may have a similar association with tumours as bacteria do. As an increasing number of tumour-associated fungi are discovered, this provides new ideas for the diagnosis and prognosis of tumours. The relationship between fungi and colorectal tumours has also been recently identified by scientists. Therefore, this paper describes the limitations and prospects of the application of fungi in diagnosing CRC and predicting CRC prognosis.