Chemotherapy increases CDA expression and sensitizes malignant pleural mesothelioma cells to capecitabine treatment.

The combination of cisplatin and pemetrexed remains the gold standard chemotherapy for malignant pleural mesothelioma (MPM), although resistance and poor response pose a significant challenge. Cytidine deaminase (CDA) is a key enzyme in the nucleotide salvage pathway and is involved in the adaptive stress response to chemotherapy. The cytidine analog capecitabine and its metabolite 5'-deoxy-5-fluorocytidine (5'-DFCR) are converted via CDA to 5-fluorouracil, which affects DNA and RNA metabolism. This study investigated a schedule-dependent treatment strategy, proposing that initial chemotherapy induces CDA expression, sensitizing cells to subsequent capecitabine treatment. Basal CDA protein expression was low in different mesothelioma cell lines but increased in the corresponding xenografts. Standard chemotherapy increased CDA protein levels in MPM cells in vitro and in vivo in a schedule-dependent manner. This was associated with epithelial-to-mesenchymal transition and with HIF-1alpha expression at the transcriptional level. In addition, pretreatment with cisplatin and pemetrexed in combination sensitized MPM xenografts to capecitabine. Analysis of a tissue microarray (TMA) consisting of samples from 98 human MPM patients revealed that most human MPM samples had negative CDA expression. While survival curves based on CDA expression in matched samples clearly separated, significance was not reached due to the limited sample size. In non-matched samples, CDA expression before but not after neoadjuvant therapy was significantly associated with worse overall survival. In conclusion, chemotherapy increases CDA expression in xenografts, which is consistent with our in vitro results in MPM and lung cancer. A subset of matched patient samples showed increased CDA expression after therapy, suggesting that a schedule-dependent treatment strategy based on chemotherapy and capecitabine may benefit a selected MPM patient population.

Effect of Kerosene Dual-Jet Spacing on the Mixing and Combustion Characteristics of a Scramjet Combustor.

As the core of a hypersonic propulsion system, the effective mixing efficiency of fuel and air in a supersonic combustor is crucial for its performance. This study focuses on a cold supersonic flow and employs computational fluid dynamics (CFD) techniques combined with Euler-Lagrange method's discrete-phase model (DPM) for multiphase flows, K-H and R-T (Kelvin-Helmholtz and Rayleigh-Taylor) mixing and atomization models, turbulence models, and surface evaporation models to investigate the injection, atomization, and mixing characteristics of kerosene in supersonic airflow. In order to enhance the mixing efficiency between kerosene and air while reducing flow losses, this study examines a staggered dual-jet injection scheme, with the dual jets arranged at the center of the cavity and having a dual-jet spacing of 10 and 20 mm, respectively. Starting from the interaction mechanism between jets, the impact of different staggered dual-jet spacings on the kerosene jet penetration height, span expansion area, angle of the shock wave, and Sauter mean diameter distribution was analyzed. The results show that a short dual-jet spacing (10 mm) leads to greater penetration height, wider span expansion, and a larger angle of the shock wave. When the dual-jet spacing is shorter, the interaction between the fuel jet and the cavity shear layer is stronger, resulting in an improved fuel mixing efficiency. The achievements of this study are consistent with previous experimental measurements and the literature, demonstrating a strong theoretical foundation for optimizing the design of hypersonic engines by deepening the understanding of the fundamental atomization mechanisms of kerosene jets in cold-state supersonic flows. Moreover, these results hold practical significance in improving the efficiency of kerosene combustion and enhancing the performance of flame stabilization devices.

Evaluation of Influences of Changed Lower Cover Geometry on Kerosene-Air Interaction in a Scramjet Combustor.

The fuel in a scramjet combustor must be injected into a high-speed crossflow and mixed with supersonic air in a very short period of time in order for the scramjet jet to operate reliably. More generally, the supersonic air is produced by the lower cover, similar to a Laval type nozzle, of the scramjet combustor. However, significant variation in lower cover geometry is prone to produce unstable vortexes. The unstable vortexes are accompanied by nonuniform stress and strain and are detrimental to the lower cover, even to the combustor. Inspired by mechanical design, this study proposes to change lower cover geometry by decreasing its sizes and then evaluates effects of these changes on kerosene fuel-air interaction in the combustor. The evaluation is based on three-dimensional computational fluid dynamics with couple level set and volume of fluids, which characterizes the penetration height, span expansion area, shock wave angle, and Sauter mean diameter of kerosene jets for three different injection diameters (0.5, 1.0, and 1.5 mm). The simulated air-kerosene interactions reasonably agree with the past numerical findings at identical working conditions. This result demonstrates the effectiveness of the changed lower cover geometry for the scramjet combustor.

BAP1 Deficiency Inflames the Tumor Immune Microenvironment and Is a Candidate Biomarker for Immunotherapy Response in Malignant Pleural Mesothelioma.

Introduction: Malignant pleural mesothelioma (MPM) is a rare and universally lethal malignancy with limited treatment options. Immunotherapy with immune checkpoint inhibitors (ICIs) has recently been approved for unresectable MPM, but response to ICIs is heterogeneous, and reliable biomarkers for prospective selection of appropriate subpopulations likely to benefit from ICIs remain elusive. Methods: We performed multiscale integrative analyses of published primary tumor data set from The Cancer Genome Atlas (TCGA) and the French cohort E-MTAB-1719 to unravel the tumor immune microenvironment of MPM deficient in BAP1, one of the most frequently mutated tumor suppressor genes (TSGs) in the disease. The molecular profiling results were validated in independent cohorts of patients with MPM using immunohistochemistry and multiplex immunohistochemistry. Results: We revealed that BAP1 deficiency enriches immune-associated pathways in MPM, leading to increased mRNA signatures of interferon alfa/gamma response, activating dendritic cells, immune checkpoint receptors, and T-cell inflammation. This finding was confirmed in independent patient cohorts, where MPM tumors with low BAP1 levels are associated with an inflammatory tumor immune microenvironment characterized by increased exhausted precursor T-cells and macrophages but decreased myeloid-derived suppressor cells (MDSCs). In addition, BAP1low MPM cells are in close proximity to T cells and therefore can potentially be targeted with ICIs. Finally, we revealed that BAP1-proficient MPM is associated with a hyperactive mitogen-activated protein kinase (MAPK) pathway and may benefit from treatment with MEK inhibitors (MEKis). Conclusion: Our results suggest that BAP1 plays an immunomodulatory role in MPM and that BAP1-deficient MPM may benefit from immunotherapy, which merits further clinical investigation.

Contrast-enhanced CT in the differential diagnosis of bladder cancer and paraganglioma.

PURPOSE: We sought to summarize the value of contrast-enhanced computed tomography (CECT) in the differential diagnosis of bladder paraganglioma (BPG) and bladder cancer. METHODS: The medical records of 19 patients with BPG (13 males, 6 females) and 56 patients with bladder cancer (49 males, 7 females) between November 2007 and June 2023 were retrospectively reviewed. All patients underwent unenhanced and contrast-enhanced CT scanning. RESULTS: Patient age (46.4 ± 11.1 years vs. 58.6 ± 16.0 years), tumor calcification (1/19 vs. 18/56), stalk (0/19 vs. 10/56), internal vessels (15/19 vs. 19/56) and the enlarged adjacent supplying artery (14/19 vs. 10/56) were significantly different between BPG and bladder cancer (P < 0.05). The CT value in the corticomedullary phase (92.4 ± 16.6 HU vs. 64.0 ± 14.5 HU) and the contrast-enhanced value in the corticomedullary phase (54.5 ± 17.4 HU vs. 28.5 ± 12.8 HU) were significantly greater in BPG patients than in bladder cancer patients (P < 0.001), with corresponding area under the curve values of 0.930 and 0.912, respectively. The optimal cutoff values were 83.2 HU and 38.5 HU, respectively. A CT value > 83.2 HU in the corticomedullary phase and a contrast-enhanced CT value > 38.5 HU in the corticomedullary phase were used to indicate BPG with sensitivities of 78.9% and 89.5%, respectively, and specificities of 94.6% and 75.0%, respectively. CONCLUSION: The corticomedullary phase of CECT plays an important role in the preoperative differential diagnosis of BPG and bladder cancer.

3α-Hydroxybufadienolides in Bufo gallbladders: structural insights and biotransformation.

Bufadienolides, naturally occurring steroids primarily found in toads, have garnered attention for their pharmacological properties and ecological significance. In this study, we isolated and identified 21 bufadienolides from the gallbladders of Bufo gargarizans, comprising four new compounds and 17 known ones. Notably, the predominance of 15 bufadienolides with a 3α-OH configuration in toad bile differs significantly from the 3ß-OH bufadienolides found in venom secreted by toad glands. Moreover, our investigation into the biotransformation of 3ß-OH and 3α-OH bufadienolides in the liver and kidney tissues of toads revealed an irreversible conversion from 3ß-OH to 3α-OH bufadienolides, suggesting a crucial role in toad self-detoxification. These findings provide valuable insights into the structural diversity of bufadienolides and advance our understanding of their medical and ecological significance.

Integrated pretreatment diffusion kurtosis imaging and serum squamous cell carcinoma antigen levels: a biomarker strategy for early assessment of radiotherapy outcomes in cervical cancer.

OBJECTIVE: This study aims to explore the utility of pretreatment DKI parameters and serum SCC-Ag in evaluating the early therapeutic response of cervical cancer to radiotherapy. MATERIALS AND METHODS: A total of 33 patients diagnosed with cervical cancer, including 31 cases of cervical squamous cell carcinoma and two cases of adenosquamous carcinoma, participated in the study. All patients underwent conventional MRI and DKI scans on a 3T magnetic resonance scanner before radiotherapy and after ten sessions of radiotherapy. The therapeutic response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients were categorized into a response group (RG), comprising Complete Remission (CR) and Partial Remission (PR), and a non-response group (NRG), comprising Stable Disease (SD) and Progressive Disease (PD). LASSO was employed to select pretreatment DKI parameters, and ROC curves were generated for the selected parameters and serum SCC-Ag. RESULTS: Significant differences were observed in pretreatment MD, Da, Dr, MK, Ka, Kr, and SCC-Ag between the RG and NRG groups (P < 0.01). However, no significant differences were noted for FA and FAK (P = 0.441&0.928). The two selected parameters (MD and MK) demonstrated area under the curve (AUC), sensitivity, and specificity of 0.810, 0.769, 0.850 and 0.827, 0.846, 0.750, respectively. The combination of MD and MK exhibited an improved AUC of 0.901, sensitivity of 0.692, and specificity of 1.000, with a higher Youden index compared to the individual parameters. Conversely, the AUC, sensitivity, and specificity of the combination of MD, MK, and SCC-Ag were 0.852, 0.615, and 1.000, with a Youden index of 0.615. CONCLUSION: Pretreatment MD, MK, and SCC-Ag demonstrate potential clinical utility, with the combined application of MD and MK showing enhanced efficacy in assessing the early therapeutic response of cervical cancer to radiotherapy. The addition of SCC-Ag did not contribute further to the assessment efficacy.

CRISPRing KRAS: A Winding Road with a Bright Future in Basic and Translational Cancer Research.

Once considered "undruggable" due to the strong affinity of RAS proteins for GTP and the structural lack of a hydrophobic "pocket" for drug binding, the development of proprietary therapies for KRAS-mutant tumors has long been a challenging area of research. CRISPR technology, the most successful gene-editing tool to date, is increasingly being utilized in cancer research. Here, we provide a comprehensive review of the application of the CRISPR system in basic and translational research in KRAS-mutant cancer, summarizing recent advances in the mechanistic understanding of KRAS biology and the underlying principles of drug resistance, anti-tumor immunity, epigenetic regulatory networks, and synthetic lethality co-opted by mutant KRAS.

Physicochemically modulated fluorescence-scattering ratiometric sensor for selective and visual detection of levodopa.

In this study, a facile fluorescence-scattering ratiometric sensor was designed for visual and selective detection of levodopa (LD) via a clever physicochemical modulation scheme. The alkalized products of LD can rapidly react with polyethyleneimine (PEI) to exhibit an intense blue fluorescence and decrease the second-order scattering (SOS) signal of PEI. As the concentration of LD increased, the fluorescence intensity at 420 nm increased and the SOS intensity at 675 nm decreased synchronously. Thus the fluorescence-scattering ratiometric sensor was constructed by virtue of the two simultaneously changed signals. Furthermore, red light-emitting Au nanoclusters (AuNCs) were added into the above mixture solution to enlarge the SOS signal and provide a stable red background fluorescence. The intensity ratio of fluorescence to SOS (F/(S/Sblank)) is linear dependent on CLD in the wide range of 50.0---30000.0 nM, and LD as low as 50.0 nM can be identified with the naked eye via change of fluorescence color. The developed ratiometric sensor is smart, simple and efficient, and has been applied to the convenient assay of LD in real samples. The proposed physicochemical modulation strategy provides a new and facile path for selectively and visually identifying the target from its analogues.

Comparison of Therapeutic Effects Between Tightrope Loop Plate and Endobutton Plate in the Treatment of Acromioclavicular Joint Dislocation / 中国微创外科杂志

Objective To compare the efficacy of TightRope loop plate and Endobutton plate in the treatment of acromioclavicular joint dislocation.Methods A retrospective analysis was conducted on 94 patients with acromioclavicular joint dislocation who were treated at this center from March 2021 to February 2023.They were divided into two groups based on different admission date.The Group E(n =47)received Endobutton plate treatment between March 2021 and February 2022,while the Group T(n =47)received TightRope loop plate treatment between March 2022 and February 2023.At the last follow-up,the perioperative indicators,Visual Analogue Scale(VAS),Constant-Murley shoulder joint function scores,and surgical complications were compared between the two groups.Results The surgical time,intraoperative bleeding,incision length,and VAS scores at 7 days after surgery in the Group T were shorter or lower than those in the Group E(P<0.05).There were no statistical differences in the incidence of perioperative nerve injury,internal fixation displacement,clavicle fracture,vascular injury,and infection between the two groups(P>0.05).The subjective and objective scores of Constant-Murley shoulder joint function in both groups at9 months after surgery showed significant improvement compared to preoperative scores(all P =0.000).There was no significant difference in the subjective and objective scores of Constant-Murley shoulder joint function between the two groups at 9 months after surgery(P>0.05).Conclusions The treatment of acromioclavicular joint dislocation with TightRope loop plate ot or Endobutton plate has a significant effect and can effectively improve shoulder joint function.Compared with Endobutton plate,use of TightRope loop plate has minor surgical trauma,less bleeding,and significantly reduced postoperative pain,being more conducive to early functional exercise for patients.

Clinical application and efficacy analysis of castor stent graft in the treatment of aortic diseases / 中华胸心血管外科杂志

Objective:To summarize the use of Castor stent graft in aortic diseases and to analyze their efficacy.Methods:The clinical data of patients with aortic diseases treated with Castor stent graft from November 2017 to August 2022 in Fujian Provincial Hospital were collected and divided into branched stent group and branched stent co-operative group according to the operation method, and the clinical data of both groups were summarized.Results:A total of 75 cases of aortic disease were treated with Castor stents, and finally 53 cases were classified as branched stent group and 22 cases as branched stent co-operative group. The operations in both groups were successful. The median operative time in the branched stent group was 120(100, 160)min, and the median postoperative hospital stay was 7.0(5.5, 10.5)days.There was no postoperative ischemic stroke, no spinal cord ischemia. One case of new aortic dissection occurred. During follow-up, there was one lost case and two deaths, and the rest did not have endoleak, branch stent stenosis, ischemic stroke or re-intervention. In the branched stent co-operative group, there was one postoperative ischemic stroke, one case of slight stenosis of the left subclavian artery stent during follow-up, the remaining cases had satisfactory postoperative outcomes.Conclusion:Castor stent graft is a safe and effective procedure in the treatment of aortic diseases. And Castor stent graft can be used in combination with other endovascular repair techniques in the treatment of complex aortic diseases, with safe and reliable postoperative outcomes.

Implementation of Individualized Low-Dose Computed Tomography-Guided Hook Wire Localization of Pulmonary Nodules: Feasibility and Safety in the Clinical Setting.

Background: CT-guided hook-wire localization is an essential step in the management of small pulmonary nodules. Few studies, however, have focused on reducing radiation exposure during the procedure. Purpose: This study aims to explore the feasibility of implementing a low-dose computed tomography (CT)-guided hook wire localization using tailored kVp based on patients' body size. Materials and Methods: A total of 151 patients with small pulmonary nodules were prospectively enrolled for CT-guided hook wire localization using individualized low-dose CT (LDCT) vs. standard-dose CT (SDCT) protocols. Radiation dose, image quality, characteristics of target nodules and procedure-related variables were compared. All variables were analyzed using Chi-Square and Student's t-test. Results: The mean CTDIvol was significantly reduced for LDCT (for BMI ≤ 21 kg/m2, 0.56 ± 0.00 mGy and for BMI > 21 kg/m2, 1.48 ± 0.00 mGy) when compared with SDCT (for BMI ≤ 21 kg/m2, 5.24 ± 0.95 mGy and for BMI > 21 kg/m2, 6.69 ± 1.47 mGy). Accordingly, the DLP of LDCT was significantly reduced as compared with that of SDCT (for BMI ≤ 21 kg/m2, 56.86 ± 4.73 vs. 533.58 ± 122.06 mGy.cm, and for BMI > 21 kg/m2, 167.02 ± 38.76 vs. 746.01 ± 230.91 mGy.cm). In comparison with SDCT, the effective dose (ED) of LDCT decreased by an average of 89.42% (for BMI ≤ 21 kg/m2) and 77.68% (for BMI > 21 kg/m2), respectively. Although the images acquired with the LDCT protocol yielded inferior quality to those acquired with the SDCT protocol, they were clinically acceptable for hook wire localization. Conclusions: LDCT-guided localization can provide safety and nodule detection performance comparable to SDCT-guided localization, benefiting radiation dose reduction dramatically, especially for patients with small body mass indexes.

An optimized protocol for the generation and monitoring of conditional orthotopic lung cancer in the KP mouse model using an adeno-associated virus vector compatible with biosafety level 1.

BACKGROUND: The inducible Kras/p53 lung adenocarcinoma mouse model, which faithfully recapitulates human disease, is routinely initiated by the intratracheal instillation of a virus-based Cre recombinase delivery system. Handling virus-based delivery systems requires elevated biosafety levels, e.g., biosafety level 2 (BSL-2). However, in experimental animal research facilities, following exposure to viral vectors in a BSL-2 environment, rodents may not be reclassified to BSL-1 according to standard practice, preventing access to small animal micro-computed tomography (micro-CT) scanners that are typically housed in general access areas such as BSL-1 rooms. Therefore, our goal was to adapt the protocol so that the Cre-induced KP mouse model could be handled under BSL-1 conditions during the entire procedure. RESULTS: The Kras-Lox-STOP-Lox-G12D/p53 flox/flox (KP)-based lung adenocarcinoma mouse model was activated by intratracheal instillation of either an adenoviral-based or a gutless, adeno-associated viral-based Cre delivery system. Tumor growth was monitored over time by micro-CT. We have successfully substituted the virus-based Cre delivery system with a commercially available, gutless, adeno-associated, Cre-expressing vector that allows the KP mouse model to be handled and imaged in a BSL-1 facility. By optimizing the anesthesia protocol and switching to a microscope-guided vector instillation procedure, productivity was increased and procedure-related complications were significantly reduced. In addition, repeated micro-CT analysis of individual animals allowed us to monitor tumor growth longitudinally, dramatically reducing the number of animals required per experiment. Finally, we documented the evolution of tumor volume for different doses, which revealed that individual tumor nodules induced by low-titer AAV-Cre transductions can be monitored over time by micro-CT. CONCLUSION: Modifications to the anesthesia and instillation protocols increased the productivity of the original KP protocol. In addition, the switch to a gutless, adeno-associated, Cre-expressing vector allowed longitudinal monitoring of tumor growth under BSL-1 conditions, significantly reducing the number of animals required for an experiment, in line with the 3R principles.

Quantification of the renal sinus fat and exploration of its relationship with ectopic fat deposition in normal subjects using MRI fat fraction mapping.

Purpose: To determine the renal sinus fat (RSF) volume and fat fraction (FF) in normal Chinese subjects using MRI fat fraction mapping and to explore their associations with age, gender, body mass index (BMI) and ectopic fat deposition. Methods: A total of 126 subjects were included in the analysis. RSF volume and FF, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area, and hepatic and pancreatic FFs were measured for each subject. The comparisons in gender were determined using two-tailed t-tests or the nonparametric Mann-Whitney U-test for normally or non-normally distributed data for continuous variables and the chi-square test for categorical variables. Comparisons of RFS volume and FF between right and left kidneys were determined using paired sample t-tests. Multivariable logistic models were performed to confirm whether RSF differences between men and women are independent of VAT or SAT area. When parameters were normally distributed, the Pearson correlation coefficient was used; otherwise, the Spearman correlation coefficient was applied. Results: The RSF volumes (cm3) of both kidneys in men (26.86 ± 8.81 for right and 31.62 ± 10.32 for left kidneys) were significantly bigger than those of women (21.47 ± 6.90 for right and 26.03 ± 8.55 for left kidneys) (P < 0.05). The RSF FFs (%) of both kidneys in men (28.33 ± 6.73 for right and 31.21 ± 6.29 for left kidneys) were significantly higher than those of the women (23.82 ± 7.74 for right and 27.92 ± 8.15 for left kidneys) (P < 0.05). The RSF differences between men and women are independent of SAT area and dependent of VAT area (except for right RSF volume). In addition, the RSF volumes and FFs in both kidneys in the overall subjects show significant correlations with age, BMI, VAT area, hepatic fat fraction and pancreatic fat fraction (P < 0.05). However, the patterns of these correlations varied by gender. The RSF volume and FF of left kidney were significantly larger than those of the right kidney (P < 0.05). Conclusion: The association between renal sinus fat and ectopic fat deposition explored in this study may help establish a consensus on the normal values of RSF volume and FF for the Chinese population. This will facilitate the identification of clinicopathological changes and aid in the investigation of whether RSF volume and FF can serve as early biomarkers for metabolic diseases and renal dysfunction in future studies.

Exploring the Catalytic Flexibility and Reversibility of Plant Glycosyltransferase HtUGT72AS1 for Glycodiversification of Phenolic Compounds.

Plant bioactive metabolites such as flavonoids are usually present in glycosylated forms by the attachment of various sugar groups. In this study, a catalytically flexible and reversible glycosyltransferase (HtUGT72AS1) was cloned and characterized from Helleborus thibetanus. HtUGT72AS1 could directly accept six sugar donors (UDP-glucose/-arabinose/-galactose/-xylose/-N-acetylglucosamine/-rhamnose) to catalyze the 3-OH glycosylation of flavonols. It also catalyzed the 4' and 7-OH glycosylation of other types of flavonoids, which lacked the 3-OH group. Additionally, the HtUGT72AS1-catalyzed reaction was highly reversible when using 2-chloro-4-nitrophenyl glycosides as substrates, which could be used for one-pot or coupled production of bioactive glycosides. It is the first reported UGT for the synthesis of arabinosides and galactosides using a transglycosylation platform. Based on structural modeling and mutagenetic analysis, the mutation of Tyr377 to Ara enhanced the catalytic efficiency of HtUGT72AS1 toward UDP-N-acetylglucosamine, and the V146S mutant gained an improvement in the regioselectivity toward 7-OH of flavonoids.

Discovery of anti-allergic components in Guomingkang Formula using sensitive HEMT biochips coupled with in vitro and in vivo validation.

BACKGROUND: Allergic rhinitis (AR) is a prevalent allergic disease, which seriously affects the sufferers' life quality and increases the socioeconomic burden. Guominkang (GMK), a well-known prescription for AR treatment, showed satisfactory effects; while its anti-allergic components remain to be disclosed. AlGaN/GaN HEMT biochip is more sensitive and cost-effective than other binding equipments, indicating its great potential for screening of active ingredients from herbal medicines. METHODS: AR mouse models were first established to test the anti-allergic effect of GMK and discover the ingredients absorbed into blood by ultra-high performance liquid chromatography-mass spectra (UHPLC-MS). Then, novel Syk/Lyn/Fyn-functionalized high electron mobility transistor (HEMT) biochips with high sensitivity and specificity were constructed and applied to screen the active components. Finally, the results from HEMT biochips screening were validated via in silico (molecular docking and molecular dynamics simulation), in vitro (RBL-2H3 cells), and in vivo (PCA mice model) assays. RESULTS: GMK showed a potent therapeutic effect on AR mice, and fifteen components were identified from the medicated plasma. Furthermore, hamaudol was firstly found to selectively inhibit the Syk and Lyn, and emodin was to selectively inhibit Lyn, which were further confirmed by isothermal titration calorimetry, molecular docking, and molecular dynamics simulation analyses. Suppression of the activation of FcεRI-MAPK signals might be the possible mechanism of the anti-allergic effect of hamaudol. CONCLUSIONS: The targets of emodin and hamaudol were discovered by HEMT biochips for the first time. This study provided a novel and effective strategy to discover active components in a complex herbal formula by using AlGaN/GaN HEMT biochips.

HVCMM: A Hybrid-View Abstractive Model of Automatic Summary Generation for Teaching.

With the continuous development of educational informatization, more and more emerging technologies are applied in teaching activities. These technologies provide massive and multidimensional information for teaching research, but at the same time, the information obtained by teachers and students presents an explosive increase. Extracting the core content of the class record text through text summarization technology to generate concise class minutes can significantly improve the efficiency of teachers and students to obtain information. This article proposes a hybrid-view class minutes automatic generation model (HVCMM). The HVCMM model uses a multilevel encoding strategy to encode the long text of the input class records to avoid memory overflow in the calculation after the long text is input into the single-level encoder. The HVCMM model uses the method of coreference resolution and adds role vectors to solve the problem that the excessive number of participants in the class may lead to confusion about the referential logic. Machine learning algorithms are used to analyze the topic and section of the sentence to capture structural information. We test the HVCMM model on the Chinese class minutes dataset (CCM) and the augmented multiparty interaction (AMI) dataset, and the results show that the HVCMM model outperforms other baseline models on the ROUGE metric. With the help of the HVCMM model, teachers can improve the efficiency of reflection after class and improve the teaching level. Students can review the key content to strengthen their understanding of what they have learned with the help of the class minutes automatically generated by the model.

The Preventive Effects of Probiotic Prevotella histicola on the Bone Loss of Mice with Ovariectomy-Mediated Osteoporosis.

It has been demonstrated that the disturbance of gut microbiota (GM) is closely related to the reduction of bone mass and incidence of osteoporosis (OP). The aim of this study is to investigate whether the supplementation of Prevotella histicola (Ph) can prevent the bone loss in mice with ovariectomy (OVX)-mediated OP, and further explore relevant mechanisms. Regular (once a day for 8 consecutive weeks) and quantitative (200 µL/d) perfusion of Ph (the bacteria that orally gavaged) was conducted starting from 1 week after the construction of mice models. Bone mass and bone microstructure were detected by Micro-computed tomography (Micro-CT). Expressions of intestinal permeability, pro-inflammatory cytokines, and osteogenic and osteoclastic activities of mice were analyzed by histological staining and immunohistochemistry (IHC). 16S rRNA high throughput sequencing technique was applied to analyze the alterations of composition, abundance, and diversity of collected feces. Regular and quantitative perfusion of Ph mitigated the bone loss in mice with OVX-mediated OP. Compared with OVX + PBS group, perfusion of Ph repressed osteoclastogenesis and promoted osteogenesis, reduced release of pro-inflammatory cytokine cytokines (interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α)), and reversed expressions of tight junction proteins (zonula occludens protein 1 (ZO-1) and Occludin). Besides, the perfusion of Ph improved the composition, abundance, and diversity of GM. Collectively, this study revealed that regular and quantitative perfusion of Ph can improve the bone loss in mice with OVX-mediated OP by repairing intestinal mucosal barrier damage, optimizing intestinal permeability, inhibiting release of pro-osteoclastogenic cytokines, and improving disturbance of GM.

Monoterpenoid indole alkaloid adducts and dimers from Melodinus fusiformis.

Eight unprecedented monoterpenoid indole alkaloid (MIA) adducts and dimers, melofusinines A-H (1-8), and three undescribed melodinus-type MIA monomers, melofusinines I-K (9-11), together with six putative biogenetic precursors were isolated from the twigs and leaves of Melodinus fusiformis Champ. ex Benth. Compounds 1 and 2 are unusual hybrid indole alkaloids incorporating an aspidospermatan-type MIA with a monoterpenoid alkaloid unit via C-C coupling. Compounds 3-8 feature the first MIA dimers constructed through an aspidospermatan-type monomer and a rearranged melodinus-type monomer with two different types of couplings. Their structures were elucidated by spectroscopic data, single crystal X-ray diffraction, and calculated electric circular dichroism spectra analysis. In addition, dimers 5 and 8 showed significant neuroprotection effects on MPP +-injured primary cortical neurons.

General Anesthesia Versus Regional Anesthesia in the Elderly Patients Undergoing Hip Fracture Surgeries: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Surgery is the preferred treatment option for the elderly patients with hip fractures. However, the choice of general anesthesia (GA) or regional anesthesia (RA) remains controversial. The quality of evidence has further improved with the advent of several high-quality randomized clinical trials (RCTs) in the last two years. The purpose of this study was to compare the clinical outcomes of two anesthetic techniques in elderly patients undergoing hip fracture surgeries. METHODS: Eligible studies were identified from PubMed/MEDLINE, Web of Science, Scopus, EMBASE and reference lists from January 2000 to June 2022 in this current systematic review and meta-analysis. The outcomes included the surgery-related outcomes (duration of surgery, duration of anesthesia, intraoperative blood loss and number of transfusions) and postoperative outcomes (30-day mortality, postoperative delirium,cardiovascular events and other complications). RESULTS: A total of 10 RCTs were included, and a total of 3594 patients were analyzed. RA was associated with shorter duration of surgery, shorter length of hospital stays and less intraoperative blood loss compared to GA. There were no significant differences between the two groups in the number of blood transfusions, duration of anesthesia, 30-day mortality or postoperative delirium. CONCLUSIONS: Our pooled analysis identified no significant differences in terms of the safety between RA and GA, while RA reduces intraoperative blood loss, length of hospital stays and duration of surgery. These results suggest that RA appears to be preferable for the elderly patients with hip fractures.