The application of THz-TDS in the characterization of Bayan Obo magnetite ore composition.

The application of terahertz time-domain spectroscopy (THz-TDS) in the quantitative analysis of major minerals in Bayan Obo magnetite ore was explored. The positive correlation between the optical parameters of the original ore and its iron content is confirmed. The detections of three main iron containing minerals, including magnetite, pyrite, and hematite, were simulated using corresponding reagents. The random forest algorithm is used for quantitative analysis, and FeS2 is detected with precision of R2 = 0.7686 and MAE = 0.6307% in ternary mixtures. The experimental results demonstrate that THz-TDS can distinguish specific iron containing minerals and reveal the potential application value of this testing method in exploration and mineral processing fields.

Establishment of a Mouse Model of Mycoplasma pneumoniae-Induced Plastic Bronchitis.

Plastic bronchitis (PB) constitutes a life-threatening pulmonary disorder, predominantly attributed to Mycoplasma pneumoniae (MP) infection. The pathogenic mechanisms involved remain largely unexplored, leading to the absence of reliable approaches for early diagnosis and clear treatment. Thus, the present investigation aimed to develop an MP-induced mouse model of PB, thereby enhancing our understanding of this complex condition. In the first stage, healthy BALB/c mice were utilized to investigate the optimal methods for establishing PB. This involved the application of nebulization (15-20 min) and intratracheal administration (6-50 µL) with 2-chloroethyl ethyl sulfide (CEES) concentrations ranging from 4.5% to 7.5%. Subsequently, the MP model was induced by administering an MP solution (2 mL/kg/day, 108 CFU/50 µL) via the intranasal route for a duration of five consecutive days. Ultimately, suitable techniques were employed to induce plastic bronchitis in the MP model. Pathological changes in lung tissue were analyzed, and immunohistochemistry was employed to ascertain the expression levels of vascular endothelial growth factor receptor 3 (VEGFR-3) and the PI3K/AKT/mTOR signaling pathway. The administration of 4.5% CEES via a 6 µL trachea was the optimal approach to establishing a PB model. This method primarily induced neutrophilic inflammation and fibrinous exudate. The MP-infected group manifested symptoms indicative of respiratory infection, including erect hair, oral and nasal secretions, and a decrease in body weight. Furthermore, the pathological score of the MP+CEES group surpassed that of the groups treated with MP or CEES independently. Notably, the MP+CEES group demonstrated significant activation of the VEGFR-3 and PI3K/AKT/mTOR signaling pathways, implying a substantial involvement of lymphatic vessel impairment in this pathology. This study successfully established a mouse model of PB induced by MP using a two-step method. Lymphatic vessel impairment is a pivotal element in the pathogenetic mechanisms underlying this disease entity. This accomplishment will aid in further research into treatment methods for patients with PB caused by MP.

Single-Atom Iron Can Steer Atomic Hydrogen toward Selective Reductive Dechlorination: Implications for Remediation of Chlorinated Solvents-Impacted Groundwater.

Atomic hydrogen (H*) is a powerful and versatile reductant and has tremendous potential in the degradation of oxidized pollutants (e.g., chlorinated solvents). However, its application for groundwater remediation is hindered by the scavenging side reaction of H2 evolution. Herein, we report that a composite material (Fe0@Fe-N4-C), consisting of zerovalent iron (Fe0) nanoparticles and nitrogen-coordinated single-atom Fe (Fe-N4), can effectively steer H* toward reductive dechlorination of trichloroethylene (TCE), a common groundwater contaminant and primary risk driver at many hazardous waste sites. The Fe-N4 structure strengthens the bond between surface Fe atoms and H*, inhibiting H2 evolution. Nonetheless, H* is available for dechlorination, as the adsorption of TCE weakens this bond. Interestingly, H* also enhances electron delocalization and transfer between adsorbed TCE and surface Fe atoms, increasing the reactivity of adsorbed TCE with H*. Consequently, Fe0@Fe-N4-C exhibits high electron selectivity (up to 86%) toward dechlorination, as well as a high TCE degradation kinetic constant. This material is resilient against water matrix interferences, achieving long-lasting performance for effective TCE removal. These findings shed light on the utilization of H* for the in situ remediation of groundwater contaminated with chlorinated solvents, by rational design of earth-abundant metal-based single-atom catalysts.

Overexpression of Wild Soybean Expansin Gene GsEXLB14 Enhanced the Tolerance of Transgenic Soybean Hairy Roots to Salt and Drought Stresses.

As a type of cell-wall-relaxing protein that is widely present in plants, expansins have been shown to actively participate in the regulation of plant growth and responses to environmental stress. Wild soybeans have long existed in the wild environment and possess abundant resistance gene resources, which hold significant value for the improvement of cultivated soybean germplasm. In our previous study, we found that the wild soybean expansin gene GsEXLB14 is specifically transcribed in roots, and its transcription level significantly increases under salt and drought stress. To further identify the function of GsEXLB14, in this study, we cloned the CDS sequence of this gene. The transcription pattern of GsEXLB14 in the roots of wild soybean under salt and drought stress was analyzed by qRT-PCR. Using an Agrobacterium rhizogenes-mediated genetic transformation, we obtained soybean hairy roots overexpressing GsEXLB14. Under 150 mM NaCl- and 100 mM mannitol-simulated drought stress, the relative growth values of the number, length, and weight of transgenic soybean hairy roots were significantly higher than those of the control group. We obtained the transcriptomes of transgenic and wild-type soybean hairy roots under normal growth conditions and under salt and drought stress through RNA sequencing. A transcriptomic analysis showed that the transcription of genes encoding expansins (EXPB family), peroxidase, H+-transporting ATPase, and other genes was significantly upregulated in transgenic hairy roots under salt stress. Under drought stress, the transcription of expansin (EXPB/LB family) genes increased in transgenic hairy roots. In addition, the transcription of genes encoding peroxidases, calcium/calmodulin-dependent protein kinases, and dehydration-responsive proteins increased significantly. The results of qRT-PCR also confirmed that the transcription pattern of the above genes was consistent with the transcriptome. The differences in the transcript levels of the above genes may be the potential reason for the strong tolerance of soybean hairy roots overexpressing the GsEXLB14 gene under salt and drought stress. In conclusion, the expansin GsEXLB14 can be used as a valuable candidate gene for the molecular breeding of soybeans.

[A design of interactive review for computer aided diagnosis of pulmonary nodules based on active learning].

Automatic detection of pulmonary nodule based on computer tomography (CT) images can significantly improve the diagnosis and treatment of lung cancer. However, there is a lack of effective interactive tools to record the marked results of radiologists in real time and feed them back to the algorithm model for iterative optimization. This paper designed and developed an online interactive review system supporting the assisted diagnosis of lung nodules in CT images. Lung nodules were detected by the preset model and presented to doctors, who marked or corrected the lung nodules detected by the system with their professional knowledge, and then iteratively optimized the AI model with active learning strategy according to the marked results of radiologists to continuously improve the accuracy of the model. The subset 5-9 dataset of the lung nodule analysis 2016(LUNA16) was used for iteration experiments. The precision, F1-score and MioU indexes were steadily improved with the increase of the number of iterations, and the precision increased from 0.213 9 to 0.565 6. The results in this paper show that the system not only uses deep segmentation model to assist radiologists, but also optimizes the model by using radiologists' feedback information to the maximum extent, iteratively improving the accuracy of the model and better assisting radiologists.

Association of α-HBDH levels with the severity and recurrence after acute ischemic stroke.

OBJECTIVE: α-HBDH serves as a biomarker of myocardial damage and is implicated in adverse outcomes across various critical illnesses. Our study aimed to assess the correlation between α-HBDH levels, and severity and recurrence of acute ischemic stroke (AIS). METHODS: We enrolled patients with mild-to-moderate AIS within 72 h of onset. Based on the baseline score of the National Institutes of Health Stroke Scale (bNIHSS) at registration, patients were categorized into mild (bNIHSS ≤ 4 points) and moderate AIS groups (4 < bNIHSS ≤ 10 points). Subsequently, based on the normal upper limit of α-HBDH, patients were divided into low-level α-HBDH (≤ 180 U/L) and high-level α-HBDH (> 180 U/L) groups. Multivariate logistic regression analysis and Cox proportional hazard regression analysis were employed to evaluate the relationship between α-HBDH levels and bNIHSS scores as well as the risk of recurrent AIS within 90 days. RESULTS: We observed a significant association between higher baseline levels of α-HBDH and increased bNIHSS scores, indicating a more severe AIS (odds ratio = 24.449; 95% confidence interval [CI], 8.749-68.324; p < 0.01). Additionally, the risk of recurrent AIS within 90 days was 4.666 times higher in the high-level α-HBDH group compared to the low-level group (hazard ratio = 4.666; 95% CI, 2.481-8.777; p < 0.01). CONCLUSIONS: The baseline level of α-HBDH is significantly correlated with the severity of AIS and the risk of recurrent AIS within 90 days.

Current development of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies (Review).

The coronavirus disease 2019 pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) seriously affected global public health security. Studies on vaccines, neutralizing antibodies (NAbs) and small molecule antiviral drugs are currently ongoing. In particular, NAbs have emerged as promising therapeutic agents due to their well­defined mechanism, high specificity, superior safety profile, ease of large­scale production and simultaneous application for both prevention and treatment of viral infection. Numerous NAb therapeutics have entered the clinical research stages, demonstrating promising therapeutic and preventive effects. These agents have been used for outbreak prevention and control under urgent authorization processes. The present review summarizes the molecular targets of SARS­CoV­2­associated NAbs and screening and identification techniques for NAb development. Moreover, the current shortcomings and challenges that persist with the use of NAbs are discussed. The aim of the present review is to offer a reference for the development of NAbs for any future emergent infectious diseases, including SARS­CoV­2.

Platinum-ruthenium-iron embedded in nitrogen-doped ordered mesoporous carbon for adrenaline electrochemical sensing study.

A novel nitrogen-doped ordered mesoporous carbon (OMC) pore-embedded growth Pt-Ru-Fe nanoparticles (Pt1-Ru7.5-Fex@N-OMCs) composite was designed and synthesized for the first time. SBA-15 was used as a template, and dopamine was used as a carbon and nitrogen source and metal linking reagent. The oxidative self-polymerization reaction of dopamine was utilized to polymerize dopamine into two-dimensional ordered SBA-15 template pores. Iron porphyrin was introduced as an iron source at the same time as polymerization of dopamine, which was introduced inside and outside the pores using dopamine-metal linkage. Carbonization of polydopamine, nitrogen doping and iron nanoparticle formation were achieved by one-step calcination. Then the templates were etched to form Fex@N-OMCs, and finally the Pt1-Ru7.5-Fex@N-OMCs composites were stabilized by the successful introduction of platinum-ruthenium nanoparticles through the substitution reaction. The composite uniformly embeds the transition metal nanoparticles inside the OMC pores with high specific surface area, which limits the size of the metal nanoparticles inside the pores. At the same time, the metal nanoparticles are also loaded onto the surface of the OMCs, realizing the uniform loading of metal nanoparticles both inside and outside the pores. This enhances the active sites of the composite, promotes the mass transfer process inside and outside the pores, and greatly enhances the electrocatalytic performance of the catalyst. The material shows high electrocatalytic performance for adrenaline, which is characterized by a wide linear range, high sensitivity and low detection limit, and can realize the detection of actual samples.

Ultrasensitive Hierarchical AuNRs@SiO2@Ag SERS Probes for Enrichment and Detection of Insulin and C-Peptide in Serum.

Introduction: Insulin and C-peptide played crucial roles as clinical indicators for diabetes and certain liver diseases. However, there has been limited research on the simultaneous detection of insulin and C-peptide in trace serum. It is necessary to develop a novel method with high sensitivity and specificity for detecting insulin and C-peptide simultaneously. Methods: A core-shell-satellites hierarchical structured nanocomposite was fabricated as SERS biosensor using a simple wet-chemical method, employing 4-MBA and DTNB for recognition and antibodies for specific capture. Gold nanorods (Au NRs) were modified with Raman reporter molecules and silver nanoparticles (Ag NPs), creating SERS tags with high sensitivity for detecting insulin and C-peptide. Antibody-modified commercial carboxylated magnetic bead@antibody served as the capture probes. Target materials were captured by probes and combined with SERS tags, forming a "sandwich" composite structure for subsequent detection. Results: Under optimized conditions, the nanocomposite fabricated could be used to detect simultaneously for insulin and C-peptide with the detection limit of 4.29 × 10-5 pM and 1.76 × 10-10 nM in serum. The insulin concentration (4.29 × 10-5-4.29 pM) showed a strong linear correlation with the SERS intensity at 1075 cm-1, with high recoveries (96.4-105.3%) and low RSD (0.8%-10.0%) in detecting human serum samples. Meanwhile, the C-peptide concentration (1.76 × 10-10-1.76 × 10-3 nM) also showed a specific linear correlation with the SERS intensity at 1333 cm-1, with recoveries 85.4%-105.0% and RSD 1.7%-10.8%. Conclusion: This breakthrough provided a novel, sensitive, convenient and stable approach for clinical diagnosis of diabetes and certain liver diseases. Overall, our findings presented a significant contribution to the field of biomedical research, opening up new possibilities for improved diagnosis and monitoring of diabetes and liver diseases.

Systematic analysis for clinical characteristics and outcomes of IgG4-related disease patients during the COVID-19 pandemic.

BACKGROUND: To systematically describe clinical characteristics and investigate factors associated with COVID-19-related infection, hospital admission, and IgG4-related disease relapse in IgG4-RD patients. METHODS: Physician-reported IgG4-RD patients were included in this retrospective study. Using multivariable logistic regression analysis to determine factors for primary outcome (COVID-19-related IgG4-RD relapse) and secondary outcome (COVID-19-related infection and hospital admission). Covariates included age, sex, body mass index, smoking status, comorbidities, IgG4-RD clinical features, and treatment strategies. RESULTS: Among 649 patients, 530 had a diagnosis of COVID-19, 25 had COVID-19-related hospital admission, and 69 had COVID-19-related IgG4-RD relapse. Independent factors associated with COVID-19 infection were age (OR, 0.98; 95% CI, 0.96-1.00), body mass index (1.10, 1.03-1.18), and tofacitinib (0.34, 0.14-0.79). Further analysis indicated that age (1.10, 1.03-1.16), coronary heart disease (24.38, 3.33-178.33), COVID-19-related dyspnea (7.11, 1.85-27.34), pulmonary infection (73.63, 16.22-4615.34), and methotrexate (17.15, 1.93-157.79) were associated with a higher risk of COVID-19-related hospital admission. Importantly, age (0.93, 0.89-0.98), male sex (0.16, 0.03-0.80), ever/current smoking (19.23, 3.78-97.80), COVID-19-related headache (2.98, 1.09-8.17) and psychiatric symptoms (3.12, 1.07-9.10), disease activity before COVID-19 (1.89, 1.02-3.51), number of involved organs (1.38, 1.08-1.76), glucocorticoid dosage (1.08, 1.03-1.13), and methotrexate (5.56, 1.40-22.08) were strong factors for COVID-19-related IgG4-RD relapse. CONCLUSIONS: Our data add to evidence that smoking and disease-specific factors (disease activity, number of involved organs, and specific medications) were risk factors of COVID-19-related IgG4-RD relapse. The results highlight the importance of adequate disease control with b/tsDMARDs, preferably without using methotrexate and increasing glucocorticoid dosages in the COVID-19 era. Key Points • COVID-19-related infection or hospital admission were associated with known general factors (age, body mass index, specific comorbidities and methotrexate) among IgG4-RD patients. • Smoking and disease-specific factors (disease activity, number of involved organs and specific medications) were associated with higher odds of COVID-19-related IgG4-RD relapse. • The results highlight the importance of adequate disease control with b/tsDMARDs, preferably without using methotrexate or increasing glucocorticoid dosages.

Deciphering the key factors affecting pesticide residue risk in vegetable ecosystem.

Soil contamination, particularly from pesticide residues, presents a significant challenge to the sustainable development of agricultural ecosystems. Identifying the key factors influencing soil pesticide residue risk and implementing effective measures to mitigate their risks at the source are essential. Here, we collected soil samples and conducted a comprehensive survey among local farmers in the Three Gorges Reserve Area, a major agricultural production region in Southwest China. Subsequently, employing a dual analytical approach combining structural equation modeling (SEM) and random forest modeling (RFM), we examined the effects of various factors on pesticide residue accumulation in vegetable ecosystems. Our SEM analysis revealed that soil characteristics (path coefficient 0.85) and cultivation factor (path coefficient 0.84) had the most significant effect on pesticide residue risk, while the farmer factors indirectly influenced pesticide residues by impacting both cultivation factors and soil characteristics. Further exploration using RFM identified the three most influential factors contributing to pesticide residue risk as cation exchange capacity (CEC) (account for 18.84%), cultivation area (account for 14.12%), and clay content (account for 13.01%). Based on these findings, we carried out experimental trials utilizing Integrated Pest Management (IPM) technology, resulting in a significant reduction in soil pesticide residues and notable improvements in crop yields. Therefore, it is recommended that governmental efforts should prioritize enhanced training for vegetable farmers, promotion of eco-friendly plant protection methods, and regulation of agricultural environments to ensure sustainable development.

Low-level viremia episodes appear to affect the provirus composition of the circulating cellular HIV reservoir during antiretroviral therapy.

Low-level viremia (LLV) ranging from 50 to 1,000 copies/ml is common in most HIV-1-infected patients receiving antiretroviral therapy (ART). However, the source of LLV and the impact of LLV on the HIV-1 reservoir during ART remain uncertain. We hypothesized that LLV may arise from the HIV reservoir and its occurrence affect the composition of the reservoir after LLV episodes. Accordingly, we investigated the genetic linkage of sequences obtained from plasma at LLV and pre-ART time points and from peripheral blood mononuclear cells (PBMCs) at pre-ART, pre-LLV, LLV, and post-LLV time points. We found that LLV sequences were populated with a predominant viral quasispecies that accounted for 67.29%∼100% of all sequences. Two episodes of LLV in subject 1, spaced 6 months apart, appeared to have originated from the stochastic reactivation of latently HIV-1-infected cells. Moreover, 3.77% of pre-ART plasma sequences were identical to 67.29% of LLV-3 plasma sequences in subject 1, suggesting that LLV may have arisen from a subset of cells that were infected before ART was initiated. No direct evidence of sequence linkage was found between LLV viruses and circulating cellular reservoirs in all subjects. The reservoir size, diversity, and divergence of the PBMC DNA did not differ significantly between the pre- and post-LLV sampling points (P > 0.05), but the composition of viral reservoir quasispecies shifted markedly before and after LLV episodes. Indeed, subjects with LLV had a higher total PBMC DNA level, greater viral diversity, a lower proportion of variants with identical sequences detected at two or more time points, and a shorter variant duration during ART compared with subjects without LLV. Overall, our findings suggested that LLV viruses may stem from an unidentified source other than circulating cellular reservoirs. LLV episodes may introduce great complexity into the HIV reservoir, which brings challenges to the development of treatment strategies.

Identification of Prolactinoma in Pituitary Neuroendocrine Tumors Using Radiomics Analysis Based on Multiparameter MRI.

This study aims to investigate the feasibility of preoperatively predicting histological subtypes of pituitary neuroendocrine tumors (PitNETs) using machine learning and radiomics based on multiparameter MRI. Patients with PitNETs from January 2016 to May 2022 were retrospectively enrolled from four medical centers. A cfVB-Net network was used to automatically segment PitNET multiparameter MRI. Radiomics features were extracted from the MRI, and the radiomics score (Radscore) of each patient was calculated. To predict histological subtypes, the Gaussian process (GP) machine learning classifier based on radiomics features was performed. Multi-classification (six-class histological subtype) and binary classification (PRL vs. non-PRL) GP model was constructed. Then, a clinical-radiomics nomogram combining clinical factors and Radscores was constructed using the multivariate logistic regression analysis. The performance of the models was evaluated using receiver operating characteristic (ROC) curves. The PitNET auto-segmentation model eventually achieved the mean Dice similarity coefficient of 0.888 in 1206 patients (mean age 49.3 ± SD years, 52% female). In the multi-classification model, the GP of T2WI got the best area under the ROC curve (AUC), with 0.791, 0.801, and 0.711 in the training, validation, and external testing set, respectively. In the binary classification model, the GP of T2WI combined with CE T1WI demonstrated good performance, with AUC of 0.936, 0.882, and 0.791 in training, validation, and external testing sets, respectively. In the clinical-radiomics nomogram, Radscores and Hardy' grade were identified as predictors for PRL expression. Machine learning and radiomics analysis based on multiparameter MRI exhibited high efficiency and clinical application value in predicting the PitNET histological subtypes.

Different High-Intensity Interval Training Programs versus Moderate Intensity Continuous Training for Heart Failure Patients: a systematic review and meta-analysis.

OBJECTIVE: To explore the effect sizes of different HIIT protocols on cardiorespiratory parameters when compared with the MICT in different HF subtypes. DATA SOURCES: Electronic databases were searched from their inception date until January 23rd, 2023. STUDY SELECTION: Randomized controlled trials (RCTs) were included if they compared HIIT to MICT in HF patients. The primary outcomes was peak oxygen consumption (VO2peak). Two reviewers independently evaluated 99 initially identified studies, resulting in the selection of 15 RCTs that met the eligibility criteria. DATA EXTRACTION: Data was extracted independently by two observers using data extraction form drafted based on the CONSORT statement and the TIDieR; and the The methodological quality of the studies was analyzed individually based on the TESTEX scale. DATA SYNTHESIS: Fifteen RCTs with 553 HF patients were included in the systematic review. The studies included had moderate to good overall methodological quality. The results showed that HIIT was generally more effective than MICT at improving VO2peak in HF patients (n=541, 15 RCT; MD: 1.49 mL/kg/min, I2=66%, p<0.001). However, the effect size varied depending on the HF subtype and HIIT protocol used. For HFrEF patients, the long-interval (high-intensity interval lasting≥ 4 min) and high-volume HIIT (high-intensity efforts in total ≥ 15 min) showed the largest benefits over the MICT (n=261, 6 RCT; MD: 2.11 mL/kg/min, p<0.001); followed by the short-interval (≤ 1 min) and high-volume HIIT (≥ 15 min; n=71, 3 RCT; MD: 0.91 mL/kg/min, p=0.12); and the short-interval and low-volume HIIT showed the least superiority over MICT (n=68, 3 RCT; MD: 0.54 mL/kg/min; p=0.05). For HFpEF patients, there was a modest beneficial effect from HIIT over MICT (n=141, 3 RCT; MD: 0.55 mL/kg/min; p=0.32). CONCLUSIONS: The long-interval and high-volume HIIT protocol may produce greater benefits than MICT for improving cardiopulmonary fitness in HFrEF patients. Further research is needed to determine the optimal HIIT protocol for different HF subtypes and to provide definitive recommendations for clinical practice.

Effect of crystal-water on the optical and dielectric characteristics of calcium sulfate in the THz band.

The effect of crystal-water contents on the optical properties and dielectric characteristics of calcium sulfate in the THz band is investigated. The complex dielectric constant and conductivity are analyzed using the Drude-Smith model. The refractive index and absorption coefficient are linearly increased with the content of crystal-water, and the corresponding linear fitting lines of R2 over 0.97 are obtained. The dielectric properties of calcium sulfate are significantly affected by the crystal-water content. These results indicate that a new method to quantitative measurement of the crystal-water content in hydrous minerals is provided.

High-sensitivity fiber-tip acoustic sensor with ultrathin gold diaphragm.

Miniature acoustic sensors with high sensitivity are highly desired for applications in medical photoacoustic imaging, acoustic communications and industrial nondestructive testing. However, conventional acoustic sensors based on piezoelectric, piezoresistive and capacitive detectors usually require a large element size on a millimeter to centimeter scale to achieve a high sensitivity, greatly limiting their spatial resolution and the application in space-confined sensing scenarios. Herein, by using single-crystal two-dimensional gold flakes (2DGFs) as the sensing diaphragm of an extrinsic Fabry-Perot interferometer on a fiber tip, we demonstrate a miniature optical acoustic sensor with high sensitivity. Benefiting from the ultrathin thickness (∼8 nm) and high reflectivity of the 2DGF, the fiber-tip acoustic sensor gives an acoustic pressure sensitivity of ∼300 mV/Pa in the frequency range from 100 Hz to 20 kHz. The noise-equivalent pressure of the fiber-tip acoustic sensor at the frequency of 13 kHz is as low as 62.8 µPa/Hz1/2, which is one or two orders of magnitude lower than that of reported optical acoustic sensors with the same size.

Rare oxoisoaporphine alkaloids from Menispermum dauricum with potential anti-inflammatory activity.

Eleven alkaloids including four previously undescribed oxoisoaporphine alkaloids, menisoxoisoaporphines A-D (1-4), four known analogues (5-8), and three aporphine alkaloids (9-11), were isolated and identified from the rhizomes of Menispermum dauricum. Their structures were elucidated by extensive spectroscopic data and single-crystal X-ray diffraction analyses. Among them, compounds 1 and 4 were the first samples of oxoisoaporphine with C-6 isopentylamino moiety, and 2 was a rare C-4 methylation product of oxoisoaporphine alkaloid. The in vitro anti-inflammatory activity of compounds 1-11 was performed by evaluating the inhibition of NO level in LPS-induced RAW264.7 macrophages. Among them, compound 4 exhibited the most potent NO inhibition activity with an IC50 value of 1.95 ± 0.33 µM. The key structure-activity relationships of those oxoisoaporphine alkaloids for anti-inflammatory effects have been summarized.

YAP promotes the early development of temporomandibular joint bony ankylosis by regulating mesenchymal stem cell function.

To explore the role of YAP, a key effector of the Hippo pathway, in temporomandibular joint (TMJ) ankylosis. The temporal and spatial expression of YAP was detected via immunohistochemistry and multiplex immunohistochemistry on postoperative Days 1, 4, 7, 9, 11, 14 and 28 in a sheep model. Isolated mesenchymal stem cells (MSCs) from samples of the Day 14. The relative mRNA expression of YAP was examined before and after the osteogenic induction of MSCs. A YAP-silenced MSC model was constructed, and the effect of YAP knockdown on MSC function was examined. YAP is expressed in the nucleus of the key sites that determine the ankylosis formation, indicating that YAP is activated in a physiological state. The expression of YAP increased gradually over time. Moreover, the number of cells coexpressing of RUNX2 and YAP-with the osteogenic active zone labelled by RUNX2-tended to increase after Day 9. After the osteogenic induction of MSCs, the expression of YAP increased. After silencing YAP, the osteogenic, proliferative and migratory abilities of the MSCs were inhibited. YAP is involved in the early development of TMJ bony ankylosis. Inhibition of YAP using shRNA might be a promising way to prevent or treat TMJ ankylosis.

Homotypic cell membrane-camouflaged biomimetic PLGA nanoparticle loading triptolide for the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Beside early detection, early diagnosis, and early surgery, it is urgent to try new strategies for the treatment of HCC. Triptolide (TPL) has been employed to treat HCC. However, its clinical applications were restricted by the narrow therapeutic window, severe toxicity, and poor water-solubility. In this study, we developed cancer cell membrane-camouflaged biomimetic PLGA nanoparticles loading TPL (TPL@mPLGA) with the homologous targeting property for the treatment of HCC. The TPL@mPLGA was successfully prepared with particle size of 195.5 ± 7.5 nm and zeta potential at -21.5 ± 0.2 mV with good stability. The drug loading (DL) of TPL@mPLGA was 2.94%. After Huh-7 cell membrane coating, the natural Huh-7 cell membrane proteins were found to be retained on TPL@mPLGA, thus endowing the TPL@mPLGA with enhanced accumulation at tumor site, and better anti-tumor activity in vitro and in vivo when compared with TPL or TPL@PLGA. The TPL@mPLGA showed enhanced anti-tumor effects and reduced toxicity of TPL, which could be adopted for the treatment of HCC.

Hybrid nano-stimulator for specific amplification of oxidative stress and precise tumor treatment.

The use of reactive oxygen species (ROS) to target cancer cells has become a hot topic in tumor therapy. Although ROS has strong cytotoxicity against tumor cells, the key issue currently is how to generate a large amount of ROS within tumor cells. Organic/inorganic hybrid nanoreactor materials combine the advantages of organic and inorganic components and can amplify cancer treatment by increasing targeting and material self-action. The multifunctional organic/inorganic hybrid nanoreactor is helpful to overcome the shortcomings of current reactive oxygen species in cancer treatment. It can realize the combination of in situ dynamic therapy and immunotherapy strategies, and has a synergistic anti-tumor effect. This paper reviews the research progress of organic/inorganic hybrid nanoreactor materials using tumor components to amplify reactive oxygen species for cancer treatment.The article reviews the tumor treatment strategies of nanohybrids from the perspectives of cancer cells, immune cells, tumor microenvironment, as well as 3D printing and electrospinning techniques, which are different from traditional nanomaterial technologies, and will arouse interest among scientists in tumor therapy and nanomedicine.