Bioinformatic approaches of liquid-liquid phase separation in human disease.

ABSTRACT: Biomolecular aggregation within cellular environments via liquid-liquid phase separation (LLPS) spontaneously forms droplet-like structures, which play pivotal roles in diverse biological processes. These structures are closely associated with a range of diseases, including neurodegenerative disorders, cancer and infectious diseases, highlighting the significance of understanding LLPS mechanisms for elucidating disease pathogenesis, and exploring potential therapeutic interventions. In this review, we delineate recent advancements in LLPS research, emphasizing its pathological relevance, therapeutic considerations, and the pivotal role of bioinformatic tools and databases in facilitating LLPS investigations. Additionally, we undertook a comprehensive analysis of bioinformatic resources dedicated to LLPS research in order to elucidate their functionality and applicability. By providing comprehensive insights into current LLPS-related bioinformatics resources, this review highlights its implications for human health and disease.

[Cluster Analysis and Ablation Success Rate in Atrial Fibrillation Patients Undergoing Catheter Ablation]. / æˆ¿é¢¤å°„é¢‘æ¶ˆèžæ‚£è€ çš„èšç±»åˆ†æžåŠæ¶ˆèžæˆåŠŸçŽ‡è¯„ä»·.

Objective: Atrial fibrillation (AF) is a disease of high heterogeneity, and the association between AF phenotypes and the outcome of different catheter ablation strategies remains unclear. Conventional classification of AF (e.g. according to duration, atrial size, and thromboembolism risk) fails to provide reference for the optimal stratification of the prognostic risks or to guide individualized treatment plan. In recent years, research on machine learning has found that cluster analysis, an unsupervised data-driven approach, can uncover the intrinsic structure of data and identify clusters of patients with pathophysiological similarity. It has been demonstrated that cluster analysis helps improve the characterization of AF phenotypes and provide valuable prognostic information. In our cohort of AF inpatients undergoing radiofrequency catheter ablation, we used unsupervised cluster analysis to identify patient subgroups, to compare them with previous studies, and to evaluate their association with different suitable ablation patterns and outcomes. Methods: The participants were AF patients undergoing radiofrequency catheter ablation at West China Hospital between October 2015 and December 2017. All participants were aged 18 years or older. They underwent radiofrequency catheter ablation during their hospitalization. They completed the follow-up process under explicit informed consent. Patients with AF of a reversible cause, severe mitral stenosis or prosthetic heart valve, congenital heart disease, new-onset acute coronary syndrome within three months prior to the surgery, or a life expectancy less than 12 months were excluded according to the exclusion criteria. The cohort consisted of 1102 participants with paroxysmal or persistent/long-standing persistent AF. Data on 59 variables representing demographics, AF type, comorbidities, therapeutic history, vital signs, electrocardiographic and echocardiographic findings, and laboratory findings were collected. Overall, data for the variables were rarely missing (<5%), and multiple imputation was used for correction of missing data. Follow-up surveys were conducted through outpatient clinic visits or by telephone. Patients were scheduled for follow-up with 12-lead resting electrocardiography and 24-hours Holter monitoring at 3 months and 6 months after the ablation procedure. Early ablation success was defined as the absence of documented AF, atrial flutter, or atrial tachycardia >30 seconds at 6-month follow-up. Hierarchical clustering was performed on the 59 baseline variables. All characteristic variables were standardized to have a mean of zero and a standard deviation of one. Initially, each patient was regarded as a separate cluster, and the distance between these clusters was calculated. Then, the Ward minimum variance method of clustering was used to merge the pair of clusters with the minimum total variance. This process continued until all patients formed one whole cluster. The "NbClust" package in R software, capable of calculating various statistical indices, including pseudo t2 index, cubic clustering criterion, silhouette index etc, was applied to determine the optimal number of clusters. The most frequently chosen number of clusters by these indices was selected. A heatmap was generated to illustrate the clinical features of clusters, while a tree diagram was used to depict the clustering process and the heterogeneity among clusters. Ablation strategies were compared within each cluster regarding ablation efficacy. Results: Five statistically driven clusters were identified: 1) the younger age cluster (n=404), characterized by the lowest prevalence of cardiovascular and cerebrovascular comorbidities but the highest prevalence of obstructive sleep apnea syndrome (14.4%); 2) a cluster of elderly adults with chronic diseases (n=438), the largest cluster, showing relatively higher rates of hypertension, diabetes, stroke, and chronic obstructive pulmonary disease; 3) a cluster with high prevalence of sinus node dysfunction (n=160), with patients showing the highest prevalence of sick sinus syndrome and pacemaker implantation; 4) the heart failure cluster (n=80), with the highest prevalence of heart failure (58.8%) and persistent/long-standing persistent AF (73.7%); 5) prior coronary artery revascularization cluster (n=20), with patients of the most advanced age (median: 69.0 years old) and predominantly male patients, all of whom had prior myocardial infarction and coronary artery revascularization. Patients in cluster 2 achieved higher early ablation success with pulmonary veins isolation alone compared to extensive ablation strategies (79.6% vs. 66.5%; odds ratio [OR]=1.97, 95% confidence interval [CI]: 1.28-3.03). Although extensive ablation strategies had a slightly higher success rate in the heart failure group, the difference was not statistically significant. Conclusions: This study provided a unique classification of AF patients undergoing catheter ablation by cluster analysis. Age, chronic disease, sinus node dysfunction, heart failure and history of coronary artery revascularization contributed to the formation of the five clinically relevant subtypes. These subtypes showed differences in ablation success rates, highlighting the potential of cluster analysis in guiding individualized risk stratification and treatment decisions for AF patients.

Self-Assembled Acid-Responsive Nanosystem for Synergistic Anti-Angiogenic/Photothermal/Ferroptosis Therapy against Esophageal Cancer.

Esophageal cancer (EC) treatment via anti-angiogenic therapy faces challenges due to non-cytotoxicity and non-specific biodistribution of the anti-angiogenic agents. Hence, the quest for a synergistic treatment modality and a targeted delivery approach to effectively address EC has become imperative. In this study, an acid-responsive release nanosystem (Bev-IR820@FeIII TA) that involves the conjugation of bevacizumab, an anti-angiogenic monoclonal antibody, with TA and Fe3+ to form a metal-phenolic network, followed by loading with the near-infrared photothermal agent (IR820) to achieve combinational therapy, is designed. The construction of Bev-IR820@FeIII TA can be realized through a facile self-assembly process. The Bev-IR820@FeIII TA exhibits tumor-targeting capabilities and synergistic therapeutic effects, encompassing anti-angiogenic therapy, photothermal therapy (PTT), and ferroptosis therapy (FT). Bev-IR820@FeIII TA exhibits remarkable proficiency in delivering drugs to EC tissue through its pH-responsive release properties. Consequently, bevacizumab exerts its therapeutic effects by obstructing tumor angiogenesis, thereby impeding tumor growth. Meanwhile, PTT facilitates localized thermal ablation at the tumor site, directly eradicating EC cells. FT synergistically collaborates with PTT, giving rise to the formation of a reactive oxygen species (ROS) storm, subsequently culminating in the demise of EC cells. In summary, this amalgamated treatment modality carries substantial promise for synergistically impeding EC progression and showcases auspicious prospects for future EC treatment.

Manipulated Fluoro-Ether Derived Nucleophilic Decomposition Products for Mitigating Polarization-Induced Capacity Loss in Li-Rich Layered Cathode.

Electrolyte engineering is a fascinating choice to improve the performance of Li-rich layered oxide cathodes (LRLO) for high-energy lithium-ion batteries. However, many existing electrolyte designs and adjustment principles tend to overlook the unique challenges posed by LRLO, particularly the nucleophilic attack. Here, we introduce an electrolyte modification by locally replacing carbonate solvents in traditional electrolytes with a fluoro-ether. By benefit of the decomposition of fluoro-ether under nucleophilic O-related attacks, which delivers an excellent passivation layer with LiF and polymers, possessing rigidity and flexibility on the LRLO surface. More importantly, the fluoro-ether acts as "sutures", ensuring the integrity and stability of both interfacial and bulk structures, which contributed to suppressing severe polarization and enhancing the cycling capacity retention from 39 % to 78 % after 300 cycles for the 4.8 V-class LRLO. This key electrolyte strategy with comprehensive analysis, provides new insights into addressing nucleophilic challenge for high-energy anionic redox related cathode systems.

DASES: a database of alternative splicing for esophageal squamous cell carcinoma.

Esophageal carcinoma ranks as the sixth leading cause of cancer-related mortality globally, with esophageal squamous cell carcinoma (ESCC) being particularly prevalent among Asian populations. Alternative splicing (AS) plays a pivotal role in ESCC development and progression by generating diverse transcript isoforms. However, the current landscape lacks a specialized database focusing on alternative splicing events (ASEs) derived from a large number of ESCC cases. Additionally, most existing AS databases overlook the contribution of long non-coding RNAs (lncRNAs) in ESCC molecular mechanisms, predominantly focusing on mRNA-based ASE identification. To address these limitations, we deployed DASES (http://www.hxdsjzx.cn/DASES). Employing a combination of publicly available and in-house ESCC RNA-seq datasets, our extensive analysis of 346 samples, with 93% being paired tumor and adjacent non-tumor tissues, led to the identification of 257 novel lncRNAs in esophageal squamous cell carcinoma. Leveraging a paired comparison of tumor and adjacent normal tissues, DASES identified 59,094 ASEs that may be associated with ESCC. DASES fills a critical gap by providing comprehensive insights into ASEs in ESCC, encompassing lncRNAs and mRNA, thus facilitating a deeper understanding of ESCC molecular mechanisms and serving as a valuable resource for ESCC research communities.

[Role of Liquid-Liquid Phase Separation in Cell Fate Transition and Diseases].

Liquid-liquid phase separation (LLPS), a novel mechanism of the organization and formation of cellular structures, plays a vital role in regulating cell fate transitions and disease pathogenesis and is gaining widespread attention. LLPS may lead to the assemblage of cellular structures with liquid-like fluidity, such as germ granules, stress granules, and nucleoli, which are classic membraneless organelles. These structures are typically formed through the high-concentration liquid aggregation of biomacromolecules driven by weak multivalent interactions. LLPS is involved in regulating various intracellular life activities and its dysregulation may cause the disruption of cellular functions, thereby contributing to the pathogenesis and development of neurodegenerative diseases, infectious diseases, cancers, etc. Herein, we summarized published findings on the LLPS dynamics of membraneless organelles in physiological and pathological cell fate transition, revealing their crucial roles in cell differentiation, development, and various pathogenic processes. This paper provides a fresh theoretical framework and potential therapeutic targets for LLPS-related studies, opening new avenues for future research.

Prevotella copri alleviates sarcopenia via attenuating muscle mass loss and function decline.

BACKGROUND: The gut microbiome and fecal metabolites have been found to influence sarcopenia, but whether there are potential bacteria that can alleviate sarcopenia has been under-investigated, and the molecular mechanism remains unclear. METHODS: To investigate the relationships between the gut microbiome, fecal metabolites and sarcopenia, subjects were selected from observational multi-ethnic study conducted in Western China. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia 2014. The gut microbiome was profiled by shotgun metagenomic sequencing. Untargeted metabolomic analysis was performed to analyse the differences in fecal metabolites. We investigated bacterium with the greatest relative abundance difference between healthy individuals and sarcopenia patients, and the differences in metabolites associated with the bacteria, to verify its effects on muscle mass and function in a mouse model. RESULTS: The study included 283 participants (68.90% females, mean age: 66.66 years old) with and without sarcopenia (141 and 142 participants, respectively) and from the Han (98 participants), Zang (88 participants) and Qiang (97 participants) ethnic groups. This showed an overall reduction (15.03% vs. 20.77%, P = 0.01) of Prevotella copri between the sarcopenia and non-sarcopenia subjects across the three ethnic groups. Functional characterization of the differential bacteria showed enrichment (odds ratio = 15.97, P = 0.0068) in branched chain amino acid (BCAA) metabolism in non-sarcopenia group. A total of 13 BCAA and their derivatives have relatively low levels in sarcopenia. In the in vivo experiment, we found that the blood BCAA level was higher in the mice gavaged with live P. copri (LPC) (P < 0.001). The LPC mice had significantly longer wire and grid hanging time (P < 0.02), longer time on rotor (P = 0.0001) and larger grip strength (P < 0.0001), indicating better muscle function. The weight of gastrocnemius mass and rectus femoris mass (P < 0.05) was higher in LPC mice. The micro-computed tomography showed a larger leg area (P = 0.0031), and a small animal analyser showed a higher lean mass ratio in LPC mice (P = 0.0157), indicating higher muscle mass. CONCLUSIONS: The results indicated that there were lower levels of both P. copri and BCAA in sarcopenia individuals. In vivo experiments, gavage with LPC could attenuate muscle mass and function decline, indicating alleviating sarcopenia. This suggested that P. copri may play a therapeutic potential role in the management of sarcopenia.

Optimization of the Epimedii Folium Mutton-Oil Processing Technology and Testing Its Effect on Zebrafish Embryonic Development.

As a traditional Chinese medicine (TCM), Epimedii folium (EF) has a history in medicine and food that is > 2,000 years old. Clinically, EF processed with mutton oil is often used as a medicine. In recent years, reports of safety risks and adverse reactions of products that use EF as a raw material have gradually increased. Processing can effectively improve the safety of TCM. According to TCM theory, mutton-oil processing can reduce the toxicity of EF and enhance its tonifying effect on the kidneys. However, there is a lack of systematic research and evaluation of EF mutton-oil processing technology. In this study, we used the Box-Behnken experimental design-response surface methodology to optimize the key parameters of the processing technology by assessing the contents of multiple components. The results showed that the optimal mutton-oil processing technology of EF was as follows: heating the mutton oil at 120 °C ± 10 °C, adding the crude EF, stir-frying it gently to 189 °C ± 10 °C until it is evenly shiny, and then removing it and cool. For every 100 kg of EF, 15 kg of mutton oil should be used. The toxicities and teratogenicities of an aqueous extract of crude and mutton-oil processed EF were compared in a zebrafish embryo developmental model. The results showed that the crude herb group was more likely to cause zebrafish deformities, and its half-maximal lethal EF concentration was lower. In conclusion, the optimized mutton-oil processing technology was stable and reliable, with good repeatability. At a certain dose, the aqueous extract of EF was toxic to the development of zebrafish embryos, and the toxicity was stronger for the crude drug than for the processed drug. The results showed that mutton-oil processing reduced the toxicity of crude EF. These findings can be used to improve the quality, uniformity, and clinical safety of mutton oil-processed EF.

Effects of polysaccharides from Gastrodia elata on the immunomodulatory activity and gut microbiota regulation in cyclophosphamide-treated mice.

BACKGROUND: Cyclophosphamide (CTX) is a widely used chemotherapeutic agent for the treatment of malignant tumors and autoimmune diseases. However, it can cause immunosuppression and damage the intestinal mucosa. The development of new agents to counteract these side effects is becoming increasingly important. Previous studies have shown that the polysaccharides from Gastrodia elata (GEPs) have strong immune-enhancing effects; however, their functions regarding the intestines and the underlying mechanism are still unclear. In this study, the effects of GEPs on immunomodulatory activity, intestinal barrier function, and gut microbiota regulation were investigated in a mouse model of CTX-induced immunosuppression. RESULTS: Gastrodia elata polysaccharides attenuated the CTX-induced decrease in organ indices of the thymus and spleen, and promoted the secretion of immune-related cytokines and immunoglobulins in the serum. They also improved the intestinal pathology and restored the intestinal barrier function by elevating the expression of intestinal tight junction proteins, occludin and ZO-1. Moreover, GEPs restored the composition and abundance of the gut microbiota and increased the short-chain fatty acid (SCFA) content in the colon. The abundance of SCFA-producing bacteria (Muribaculaceae, Prevotellaceae, and Bacteroidaceae) also increased. CONCLUSIONS: Gastrodia elata polysaccharides can effectively alleviate immunosuppression and regulate the intestinal barrier integrity and the structure of gut microbiota in CTX-treated mice. They may be used as ingredients to develop functional foods for intestinal health. © 2023 Society of Chemical Industry.

Investigating the Protective Effects of Platycodin D on Non-Alcoholic Fatty Liver Disease in a Palmitic Acid-Induced In Vitro Model.

The occurrence of non-alcoholic fatty liver disease (NAFLD) has been increasing at an alarming rate worldwide. Platycodon grandiflorum is widely used as a traditional ethnomedicine for the treatment of various diseases and is a typical functional food that can be incorporated into the everyday diet. Studies have suggested that platycodin D (PD), one of the main active ingredients in Platycodon grandiflorum, has high bioavailability and significantly mitigates the progress of NAFLD, but the underlying mechanism of this is still unclear. This study aims to investigate the therapeutic effect of PD against NAFLD in vitro. AML-12 cells were pretreated with 300 µM palmitic acid (PA) for 24 h to model NAFLD in vitro. Then, the cells were either treated with PD or received no PD treatment for 24 h. The levels of reactive oxygen species (ROS) were analyzed using 2',7'-dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining, and the mitochondrial membrane potential was determined by the JC-1 staining method. Moreover, the protein expression levels of LC3-II/LC3-I and p62/SQSTM1 in the cell lysates were analyzed by western blotting. PD was found to significantly decrease the ROS and mitochondrial membrane potential levels in the PA-treated group compared to the control group. Meanwhile, PD increased the LC3-II/LC3-I levels and decreased the p62/SQSTM1 levels in the PA-treated group compared to the control group. The results indicated that PD ameliorated NAFLD in vitro by reducing oxidative stress and stimulating autophagy. This in vitro model is a useful tool for studying the role of PD in NAFLD.

Prompt successful response to a COVID-19 outbreak: Performance of community-based rapid screening station.

An outbreak occurred in Wanhua District of Taipei City. It was traced to a cluster infection originating from a teahouse. To prevent further large-scaled community spread, the Taipei City Government established the first community rapid test screening station. This report describes the station's strategy and performance and key factors that contributed to its operation. The project involves collaboration among various departments of Taipei City Government, including the health, environmental, police, transportation, and fire departments. The station provides rapid screening, polymerase chain reaction (PCR) testing, and immediate isolation and follow-up medical services upon the detection of a positive case. These services are accessible to local residents and are intended to ease hospitals' burdens. In 36 days, a total of 8532 people were tested, and 419 confirmed cases were identified. Over the same period, the weekly number of positive cases in Wanhua District decreased from 356 to 40, and the PCR positive rate decreased from 21.7% to 1.2%. The policy of establishing rapid screening station, contact tracing and mask wearing policy are key strategies for interrupting chains of transmission of COVID-19. This intervention has become a model for preventing the spread of the epidemic and establishing community rapid screening stations in Taiwan.

One-year outcome after transcatheter aortic valve replacement for aortic regurgitation: A single-center study.

BACKGROUND: Presently, there are limited reports in the literature on the postoperative (midterm) clinical outcome for pure aortic regurgitation (AR) following transcatheter aortic valve replacement (TAVR). METHODS: Between March 2014 and June 2019, a total of 134 high-risk patients with pure, symptomatic severe AR patients were enrolled in the current study. The outcome was assessed according to the Valve Academic Research Consortium-2 criteria. Procedural results, clinical outcomes, and the patients' hemodynamics for a period of 1 year were analyzed. RESULTS: The patient mean was 73.1 ± 6.4 years and 25.4% were female. The average Society of Thoracic Surgeons score was 9.8 ± 5.3%. Procedural success was 97.1% (130/134), and the device success rate was 96.3% (129/134). Five cases were converted to open surgery, while two patients underwent valvular reinterventions (surgical aortic valve replacement for thrombosis and increasing paravalvular regurgitation). The mean aortic valve gradient was 10.2 ± 4.1 mmHg, while the moderate and severe AR was 1.6% at 1 year. Paravalvular regurgitation was none/trivial in 79.8% and mild in 18.5%. The 1-year all-cause mortality rate was 7.4%. At 1 year, the stroke incidence rate was 2.2%, and a pacemaker was implanted in 8.9% of the enrolled patients. CONCLUSIONS: In high-risk patients undergoing transapical TAVR for AR, the use of the J-Valve is safe, and effective TAVR should be considered as a reasonable option for high-risk patients with pure AR.

Management and outcomes of surgical patients with intestinal Behçet's disease and Crohn's disease in southwest China.

BACKGROUND: Gastrointestinal involvement in Behçet's disease (GIBD) and Crohn's disease (CD) are inflammatory diseases sharing a considerable number of similarities. However, different from CD, the operative and postoperative management of GIBD remains largely empirical because of the lack of comprehensive treatment guidelines. AIM: To compare surgical patients with GIBD and those with CD in a medical center and identify notable clinical features and effective postoperative treatment for surgical patients with GIBD. METHODS: We searched patients diagnosed with CD and GIBD who underwent operations for gastrointestinal complications from 2009 to 2015 at West China Hospital of Sichuan University. A total of 10 surgical patients with GIBD and 106 surgical patients with CD were recruited. Information including demographic data, medication, and operative and postoperative parameters were collected and analyzed. As the incidence of surgical GIBD is low, their detailed medical records were reviewed and compared to previous studies. Moreover, the prognoses of CD and GIBD were evaluated respectively between groups treated with biological and non-biological agents. RESULTS: Indication for first surgery was often acute intestinal perforation for GIBD patients (7/10 vs 0/106, P < 0.001), whereas intestinal fistulae (0/10 vs 44/106, P = 0.013) and ileus (0/10 vs 40/106, P = 0.015) were the indications for surgical CD patients. Approximately 40% of patients with GIBD and 23.6% of patients with CD developed postoperative complications, 50% of patients with GIBD and 38.7% of patients with CD had recurrence postoperatively, and 40% (4/10) of patients with GIBD and 26.4% (28/106) of patients with CD underwent reoperations. The average period of postoperative recurrence was 7.87 mo in patients with Behçet's disease (BD) and 10.43 mo in patients with CD, whereas the mean duration from first surgery to reoperation was 5.75 mo in BD patients and 18.04 mo in CD patients. Surgical patients with GIBD more often used corticosteroids (6/10 vs 7/106, P < 0.001) and thalidomide (7/10 vs 9/106, P < 0.001) postoperatively, whereas surgical patients with CD often used infliximab (27/106), azathioprine, or 6-mercaptopurine (74/106) for maintenance therapy. CONCLUSION: Patients suffering GIBD require surgery mostly under emergency situations, which may be more susceptible to recurrence and reoperation and need more aggressive postoperative treatment than patients with CD.

Channel-Unet: A Spatial Channel-Wise Convolutional Neural Network for Liver and Tumors Segmentation.

It is a challenge to automatically and accurately segment the liver and tumors in computed tomography (CT) images, as the problem of over-segmentation or under-segmentation often appears when the Hounsfield unit (Hu) of liver and tumors is close to the Hu of other tissues or background. In this paper, we propose the spatial channel-wise convolution, a convolutional operation along the direction of the channel of feature maps, to extract mapping relationship of spatial information between pixels, which facilitates learning the mapping relationship between pixels in the feature maps and distinguishing the tumors from the liver tissue. In addition, we put forward an iterative extending learning strategy, which optimizes the mapping relationship of spatial information between pixels at different scales and enables spatial channel-wise convolution to map the spatial information between pixels in high-level feature maps. Finally, we propose an end-to-end convolutional neural network called Channel-UNet, which takes UNet as the main structure of the network and adds spatial channel-wise convolution in each up-sampling and down-sampling module. The network can converge the optimized mapping relationship of spatial information between pixels extracted by spatial channel-wise convolution and information extracted by feature maps and realizes multi-scale information fusion. The proposed ChannelUNet is validated by the segmentation task on the 3Dircadb dataset. The Dice values of liver and tumors segmentation were 0.984 and 0.940, which is slightly superior to current best performance. Besides, compared with the current best method, the number of parameters of our method reduces by 25.7%, and the training time of our method reduces by 33.3%. The experimental results demonstrate the efficiency and high accuracy of Channel-UNet in liver and tumors segmentation in CT images.

Traceability of Geographical Origin in Gentiana straminea by UPLC-Q Exactive Mass and Multivariate Analyses.

The root of Gentiana straminea Maxim. (Gentianaceae), is officially listed as "Qin-Jiao" in the Chinese Pharmacopoeia for the treatment of rheumatic arthritis, icteric hepatitis, constipation, pain, and hypertension. To establish the geographical origin traceability in G. straminea, its chemical profiles were determined by a UPLC-Q exactive mass spectrometer, from which 43 compounds were identified by comparing retention times and mass spectrometry. Meanwhile, a pair of isomers (loganin and secologanol) was identified by mass spectrometry based on their fragmentation pathway. A total of 42 samples from difference habitats were determined by an UPLC-Q exactive mass spectrometer and the data were assayed with multivariate statistical analysis. Eight characteristic compounds were identified to determine the geographical origin of the herb. To estimate the key characteristic markers associated with pharmacological function, the inhibiting activities of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced macrophages were examined. This finding is crucial in realizing the determination of botanical origin and evaluating the quality of G. straminea.

Comparison of treatment response, survival and safety between drug-eluting bead transarterial chemoembolization with CalliSpheres® microspheres versus conventional transarterial chemoembolization in treating hepatocellular carcinoma.

PURPOSE: To compare the efficacy and safety between drug-eluting bead (DEB) transarterial chemoembolization (TACE) with CalliSpheres® microspheres (CSM) and conventional TACE (cTACE) in hepatocellular carcinoma (HCC) patients, and to explore the predictive factors for treatment response and survival. METHODS: 89 HCC patients receiving DEB-TACE with CSM or cTACE were consecutively recruited in this cohort study. Treatment response was assessed at month 1 (M1)/M3/M6. Progression free survival (PFS) and overall survival (OS) were calculated. Liver function indexes were measured at M1 and adverse events occurred during operation and hospitalization were recorded. RESULTS: Higher complete response (CR) rate and objective response rate (ORR) at M1/M3 in DEB-TACE group were found compared to cTACE group, and no difference of PFS and OS was noted between the two groups. Multivariate analysis of ORR, DFS and OS disclosed that multifocal disease, ALT≥1upper limit of normal (ULN) and ALP≥1ULN independently predicted lower ORR, while bilobar tumor location and abnormal CA19.9 level were independent predictive factors for unfavorable PFS. As for liver function, there was no difference of all liver function indexes changes (M1-M0) between the two groups. Moreover, DEB-TACE group displayed more frequent pain during treatment, and more frequent pain and fever during hospitalization compared to cTACE group. CONCLUSIONS: The short-term CR and ORR of DEB-TACE treatment with CSM are better, while OS, DFS and safety were equivalent compared to cTACE in treating HCC patients.

Amphiphilic Tetraphenylethene-Based Pyridinium Salt for Selective Cell-Membrane Imaging and Room-Light-Induced Special Reactive Oxygen Species Generation.

The cell membrane is the protecting frontier of cells, which is crucial for maintaining cell integrity, and has a close relationship with cell growth and death. There is a growing need for cell membrane imaging and monitoring in both living and dying cells. Herein, we report a new amphiphilic tetraphenylethene-based pyridinium salt (TPE-MEM) with aggregation-induced emission features for discriminatory cell membrane imaging. The fluorogenic probe with high yield was synthesized following asymmetric McMurry reaction, Williamson ether synthesis reaction, Suzuki coupling, and aldol condensation between a double-charged pyridinium salt and hexyloxytetraphenylethene benzaldehyde. TPE-MEM shows good water solubility, biocompatibility, and cell membrane specificity. Interestingly, a reactive oxygen species (ROS) is produced by the molecule (TPE-MEM) under room-light irradiation, which could destroy the integrity of the plasma membrane and cause cell necrosis. This enables a visible observation of cell necrosis and the phototherapeutic effect under a mild condition. Preliminary animal investigations also demonstrated the photodynamic therapy (PDT) effectiveness of TPE-MEM in tumor growth inhibition. We conclude that TPE-MEM is potentially a cell membrane-selective photosensitizer for PDT and it is worthy of further exploration of the phototherapeutic effect on animals systematically.

Light-enhanced bacterial killing and wash-free imaging based on AIE fluorogen.

The rapid acquisition of antibiotic resistance poses difficulties in the development of effective methods to eliminate pathogenic bacteria. New bactericides, especially those do not induce the emergence of resistance, are thus in great demand. In this work, we report an aggregation-induced emission fluorogen, TPE-Bac, for bacterial imaging and elimination. TPE-Bac can be readily dissolved in aqueous solution with weak emission. The presence of bacteria can turn on its emission, and thus no washing step is required in the imaging process. Meanwhile, TPE-Bac can be applied as a bactericide for elimination of bacteria. The amphiphilic TPE-Bac bearing two long alkyl chains and two positively charged amines can intercalate into the membrane of bacteria, increase membrane permeability and lead to dark toxicity. The efficiency of bacteria killing is greatly enhanced under light irradiation. TPE-Bac can serve as a photosensitizer to induce reactive oxygen species (ROS) generation, which ensures the efficient killing of bacteria. The TPE-Bac-containing agar plates can be continuously used for bacteria killing by applying light to induce ROS generation.

Biomechanical study of expandable pedicle screw fixation in severe osteoporotic bone comparing with conventional and cement-augmented pedicle screws.

Pedicle screws are widely utilized to treat the unstable thoracolumbar spine. The superior biomechanical strength of pedicle screws could increase fusion rates and provide accurate corrections of complex deformities. However, osteoporosis and revision cases of pedicle screw substantially reduce screw holding strength and cause loosening. Pedicle screw fixation becomes a challenge for spine surgeons in those scenarios. The purpose of this study was to determine if an expandable pedicle screw design could be used to improve biomechanical fixation in osteoporotic bone. Axial mechanical pull-out test was performed on the expandable, conventional and augmented pedicle screws placed in a commercial synthetic bone block which mimicked a human bone with severe osteoporosis. Results revealed that the pull-out strength and failure energy of expandable pedicle screws were similar with conventional pedicle screws augmented with bone cement by 2 ml. The pull-out strength was 5-fold greater than conventional pedicle screws and the failure energy was about 2-fold greater. Besides, the pull-out strength of expandable screw was reinforced by the expandable mechanism without cement augmentation, indicated that the risks of cement leakage from vertebral body would potentially be avoided. Comparing with the biomechanical performances of conventional screw with or without cement augmentation, the expandable screws are recommended to be applied for the osteoporotic vertebrae.

A targeted theranostic platinum(IV) prodrug containing a luminogen with aggregation-induced emission (AIE) characteristics for in situ monitoring of drug activation.

A targeted theranostic platinum(IV) prodrug based on a luminogen with aggregation-induced emission (AIE) characteristics was developed for selective and real-time monitoring of drug activation in situ.