Cucurbitacin IIb Extracted from Hemsleya penxianensis Induces Cell Cycle Arrest and Apoptosis in Bladder Cancer Cells by Regulating Cell Cycle Checkpoints and Mitochondrial Apoptotic Pathway.

Cucurbitacin IIb (CuIIb) extracted from Hemsleya penxianensis has been demonstrated anticancer activity in many malignancies, however, its effect against bladder cancer cells and the molecular mechanism remains unclear. Accordingly, in the present study, we evaluated the effect and further the underlying mechanism of CuIIb on bladder cancer cells. Cell viability and clonogenicity were examined to evaluate growth suppressive effect of CuIIb, alongside mechanism exploration was conducted based on RNA sequencing (RNA-seq). The results showed that CuIIb exposure inhibited the growth of T24 and UM-UC-3 bladder cancer cells as indicated by its obvious suppression on cell viability and clonogenicity. Mechanistic studies by RNA-seq and quantifying analysis of RNA-seq data by TMNP indicated cell cycle modulated by cell cycle checkpoints and apoptosis mediated by PI3K/Akt pathway might account for the anticancer activity of CuIIb. Consistently, results of flow cytometry and AO/EB staining demonstrated that the growth-suppressive effect of CuIIb was mediated by cell cycle arrest in G2/M phase and robust induction of cell apoptosis, which was further confirmed by immunoblotting and mitochondrial membrane potential (ΔΨm) analysis. Collectively, the results presented herein indicated that CuIIb exhibited anticancer activity on bladder cancer which may be a potential candidate for improving bladder cancer outcomes.

Does big data serve policy? Not without context. An experiment with in silico social science.

The DARPA Ground Truth project sought to evaluate social science by constructing four varied simulated social worlds with hidden causality and unleashed teams of scientists to collect data, discover their causal structure, predict their future, and prescribe policies to create desired outcomes. This large-scale, long-term experiment of in silico social science, about which the ground truth of simulated worlds was known, but not by us, reveals the limits of contemporary quantitative social science methodology. First, problem solving without a shared ontology-in which many world characteristics remain existentially uncertain-poses strong limits to quantitative analysis even when scientists share a common task, and suggests how they could become insurmountable without it. Second, data labels biased the associations our analysts made and assumptions they employed, often away from the simulated causal processes those labels signified, suggesting limits on the degree to which analytic concepts developed in one domain may port to others. Third, the current standard for computational social science publication is a demonstration of novel causes, but this limits the relevance of models to solve problems and propose policies that benefit from the simpler and less surprising answers associated with most important causes, or the combination of all causes. Fourth, most singular quantitative methods applied on their own did not help to solve most analytical challenges, and we explored a range of established and emerging methods, including probabilistic programming, deep neural networks, systems of predictive probabilistic finite state machines, and more to achieve plausible solutions. However, despite these limitations common to the current practice of computational social science, we find on the positive side that even imperfect knowledge can be sufficient to identify robust prediction if a more pluralistic approach is applied. Applying competing approaches by distinct subteams, including at one point the vast TopCoder.com global community of problem solvers, enabled discovery of many aspects of the relevant structure underlying worlds that singular methods could not. Together, these lessons suggest how different a policy-oriented computational social science would be than the computational social science we have inherited. Computational social science that serves policy would need to endure more failure, sustain more diversity, maintain more uncertainty, and allow for more complexity than current institutions support.

Enhancement degree of brain metastases: correlation analysis between enhanced T2 FLAIR and vascular permeability parameters of dynamic contrast-enhanced MRI.

OBJECTIVES: To investigate the correlation between enhancement degrees of brain metastases on contrast-enhanced T2-fluid-attenuated inversion recovery (CE-T2 FLAIR) and vascular permeability parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: Thirty-nine patients with brain metastases were prospectively collected. They underwent non-enhanced T2 FLAIR, DCE-MRI, CE-T2 FLAIR, and contrast-enhanced three-dimensional brain volume imaging (CE-BRAVO). Quantitative parameters of DCE-MRI were evaluated for all lesions, which included volume transfer constant (Ktrans), rate constant (Kep), and fractional volume of the extracellular extravascular space (Ve). Contrast ratio (CR) and percentage increase (PI) values of all lesions on CE-T2 FLAIR were also measured. The tumor enhancement degree on CE-T2 FLAIR in relation to CE-BRAVO was visually classified as higher (group A), equal (group B), and lower (group C). RESULTS: A total of 82 brain metastases were evaluated, including 31 in group A, 19 in group B, and 32 in group C. The Ktrans and Kep were negatively correlated with the CR (ρ = - 0.551, p < 0.001 and ρ = - 0.708, p < 0.001, respectively) and PI (ρ = - 0.511, p < 0.001 and ρ = - 0.621, p < 0.001, respectively). The Ktrans and Kep of group A were significantly lower than those of group C (both p < 0.001). No significant difference was found in Ve among the groups (p = 0.327). CONCLUSIONS: The enhancement degree of brain metastases on CE-T2 FLAIR is negatively correlated with Ktrans and Kep values, which indicate that vascular permeability parameters may play an important role in explaining the difference in enhancement between CE-T2 FLAIR and CE-BRAVO. KEY POINTS: • The enhancement degree on CE-T2 FLAIR was negatively correlated with Ktrans and Kep values. • The vascular permeability of brain metastasis accounted for the difference in enhancement degree between CE-T2 FLAIR and CE-BRAVO. • CE-T2 FLAIR is useful for detecting brain metastases with mild disruption of the blood-brain barrier.

Liangyi Gao extends lifespan and exerts an antiaging effect in Caenorhabditis elegans by modulating DAF-16/FOXO.

Liangyi Gao (LYG), a traditional Chinese medicine, is composed of Ginseng and Radix Rehmanniae Preparata, both of which have been shown to have antiaging properties. In Eastern countries, LYG is used to delay functional declines related to aging and has an obvious antiaging effect in clinical practice. However, little data from evidence-based medicine is available regarding whether LYG is beneficial overall, particularly with respect to lifespan, and how LYG functions. To address these issues, Caenorhabditis elegans, a useful organism for such studies, was employed to explore the antiaging effect and mechanism of LYG in this study. The results showed that LYG could obviously extend lifespan and slow aging-related declines in N2 wild-type C. elegans. To further characterize these antiaging effects and stress resistance, reproductive tests and other aging-related tests were performed. We found that LYG enhanced resistance against oxidative and thermal stress, reproduction, pharynx pumping, motility and growth in N2 wild-type C. elegans. In addition, we analyzed the mechanism for these effects by measuring the activity of superoxide dismutase (SOD) and the expression levels of aging-related genes. We found that LYG enhanced the activities of antioxidant enzymes and upregulated the genes daf-16, sod-3 and sir-2.1, which mediated stress resistance and longevity. In conclusion, LYG had robust and reproducible life-prolonging and antiaging benefits in C. elegans via DAF-16/FOXO regulation.

Antiaging effect of a Jianpi-yangwei formula in Caenorhabditis elegans.

BACKGROUND: Jianpi-yangwei (JPYW), a traditional Chinese medicine (TCM), helps to nourish the stomach and spleen and is primarily used to treat functional declines related to aging. This study aimed to explore the antiaging effects and mechanism of JPYW by employing a Caenorhabditis elegans model. METHODS: Wild-type C. elegans N2 worms were cultured in growth medium with or without JPYW, and lifespan analysis, oxidative and heat stress resistance assays, and other aging-related assays were performed. The effects of JPYW on the levels of superoxide dismutase (SOD) and the expression of specific genes were examined to explore the underlying mechanism of JPYW. RESULTS: Compared to control worms, JPYW-treated wild-type worms showed increased survival times under both normal and stress conditions (P < 0.05). JPYW-treated worms also exhibited enhanced reproduction, movement and growth and decreased intestinal lipofuscin accumulation compared to controls (P < 0.05). Furthermore, increased activity of SOD, downregulated expression levels of the proaging gene clk-2 and upregulated expression levels of the antiaging genes daf-16, skn-1, and sir-2.1 were observed in the JPYW group compared to the control group. CONCLUSION: Our findings suggest that JPYW extends the lifespan of C. elegans and exerts antiaging effects by increasing the activity of an antioxidant enzyme (SOD) and by regulating the expression of aging-related genes. This study not only indicates that this Chinese compound exerts antiaging effects by activating and repressing target genes but also provides a proven methodology for studying the biological mechanisms of TCMs.

Synergistic Lysosomal Activatable Polymeric Nanoprobe Encapsulating pH Sensitive Imidazole Derivative for Tumor Diagnosis.

Developing optical tumor imaging probes with minimal background noise is very important for its early detection of small lesions and accurate diagnosis of cancer. To overcome the bottleneck of low signal to noise ratio and sensitivity, it needs further improvement in fluorescent probe design and understanding of tumor development process. Recent reports reveal that lysosome's acidity in cancer cells can be below 4.5 with high Na+ /H+ exchange activity, which makes it an ideal target intracellular organelle for cancer diagnosis based on the variation of pH. Herein, a boron 2-(2'-pyridyl) imidazole complex derivative (BOPIM-N) is developed, with the ability to show a pH-activatable "OFF-ON" fluorescent switch by inhibiting twisted intramolecular charge transfer upon protonation at pH 3.8-4.5, which is studied for its selective viable cancer cell imaging ability in both in vitro and in vivo experiments. Interestingly, BOPIM-N can specifically emit green fluorescence in lysosomes of cancer cells, indicating its promising cancer cell specific imaging ability. More importantly, nanoformulated BOPIM-N probes can be specifically light-ON in tumor bearing site of nude mice with resolution up to cellular level, indicating its potential application in tumor diagnosis and precision medicine.

Preoperative education with image illustrations enhances the effect of tetracaine mucilage in alleviating postoperative catheter-related bladder discomfort: a prospective, randomized, controlled study.

BACKGROUND: Catheter-related bladder discomfort (CRBD), secondary to catheterization of urinary bladder is distressing. The aim of this study was to assess the efficacy of preoperative education on CRBD with image illustration for alleviating CRBD. METHODS: Sixty adult male patients, undergoing elective colonal and rectal surgery, were randomized to receive tetracaine mucilage instilled into the urethra and applied to the catheter (tetracain group), or receive tetracaine mucilage in combination with image illustration on CRBD (image group) before urethral catheterization. The incidence and severity of CRBD were assessed at 0.5, 1, 2, and 6 h after patients' extubation. The severity of postoperative pain, incidence of postoperative agitation and other adverse events were also recorded. RESULTS: Patients in image group reported remarkably less CRBD than those in tetracaine group at 0.5,1, 2 and 6 h after extubation (20, 20, 6.7 and 6.7% v.s. 60, 73.3, 53.3 and 53.3%, respectively, P<0.01). Severe CRBD was not reported in either group. However, the incidence of moderate CRBD was significantly lower in image group, with 6.7% at 1 h and thereafter none occurred, compared to 6.7% at 0.5 h, and increasing to 20% at 1 h, 2 h and 6 h in tetracaine group, respectively. Moreover, patients in image group suffered less moderate to severe postoperative pain than that of tetracaine group (13.3% v.s. 40.0% at 1 h, P = 0.039, 33.3% v.s. 60% at 2 h and 6 h, P = 0.038). CONCLUSIONS: Preoperative education on uretheral catheterization via image illustrations could enhance the effect of tetracaine mucilage in reducing both the incidence and severity of CRBD. TRIAL REGISTRATION: The trial was registered at www,clinicaltrials.gov with registration number NCT03199105 (retrospectively registered). Date of trial registration which is "June 26, 2017".

Virtual screening and experimental validation identify novel modulators of nuclear receptor RXRα from Drugbank database.

Retinoid X receptor alpha (RXRα), an important ligand-dependent transcription factor, plays a critical role in the development of various cancers and metabolic and neurodegenerative diseases. Therefore, RXRα represents one of the most important targets in modern drug discovery. In this study, Drugbank 2.0 with 1280 old drugs were virtually screened by Glide according to the crystal structure of ligand-binding domain (LBP) of RXRα. 15 compounds selected were tested for their binding and transcriptional activity toward RXRα by Biacore and reporter gene assay, respectively. The identified new scafford ligand of RXRα, Pitavastatin (1), was chemically optimized. Our results demonstrated that statin compounds Pitavastatin (1) and Fluvastatin (4) could bind to the LBP of RXRα (KD=13.30µM and 11.04µM, respectively) and serve as transcriptional antagonists of RXRα. On the contrary, compound (12) (domperidone) and (13) (rosiglitazone maleate) could bind to the LBP of RXRα (KD=8.80µM and 15.01µM, respectively) but serve as transcriptional agonists of RXRα.

AlCl3·6H2O-Catalyzed Friedel-Crafts Alkylation of Indoles by the para-Quinone Methide Moiety of Celastrol.

A classical Friedel-Crafts alkylation of different indoles catalyzed by AlCl3·6H2O has been developed for a well-known important natural product, celastrol, resulting in a series of derivatives for further biological evaluation. The catalyst loading was reduced to 5 mol %, the reaction proceeds at ambient temperature and reaction time is only 3 h. The product yields range from 20% to 99%. A reaction mechanism is also proposed, based on our experiment results.

Binding characterization, synthesis and biological evaluation of RXRα antagonists targeting the coactivator binding site.

Previously we identified the first retinoid X receptor-alpha (RXRα) modulators that regulate the RXRα biological function via binding to the coregulator-binding site. Here we report the characterization of the interactions between the hit molecule and RXRα through computational modeling, mutagenesis, SAR and biological evaluation. In addition, we reported studies of additional new compounds and identified a molecule that mediated the NF-κB pathway by inhibiting the TNFα-induced IκBα degradation and p65 nuclear translocation.

Fenton-like degradation of Methylene Blue using paper mill sludge-derived magnetically separable heterogeneous catalyst: Characterization and mechanism.

For the paper industry, the disposal and management of the yielded sludge are a considerable challenge. In our work, the paper mill sludge-derived magnetically separable heterogeneous catalyst (PMS-Fe-380) was prepared easily through a facile synthesis method. The morphology and structure of PMS-Fe-380 were fully characterized by means of X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and Brunauer-Emmet-Teller analysis. The catalytic activity of PMS-Fe-380 was evaluated by degradation of Methylene Blue (MB). The reusability and stability of PMS-Fe-380 were evaluated in five repeated runs, which suggested that PMS-Fe-380 manifested excellent stability of catalytic activity. Moreover, leaching tests indicated that the leached iron is negligible (<0.5mg/L). This study provides an alternative environmentally friendly reuse method for paper mill sludge and a novel catalyst PMS-Fe-380 that can be considered as a promising heterogeneous Fenton-like catalyst.

LINC00839 in Human Disorders: Insights into its Regulatory Roles and Clinical Impact, with a Special Focus on Cancer.

LINC00839 has captured significant attention within a spectrum of human disorders, including acute lung injury, osteoarthritis, and childhood obesity. Notably, aberrant expression patterns of LINC00839 have been observed across diverse cancer tissues and cell lines. LINC00839 emerges as an oncogenic factor in tumorigenesis and exerts a positive influence on tumor-associated behaviors. Its therapeutic potential for various cancers is underscored by its modulatory impact on pivotal signaling pathways, such as PI3K/AKT, OXPHOS, and Wnt/ß-catenin. Additionally, LINC00839's role in reducing sensitivity to drug and radiotherapy interventions presents opportunities for targeted intervention. Furthermore, elevated LINC00839 expression indicates advanced clinicopathological features and foretells unfavorable prognoses, as validated by publications and comprehensive analyses of tumor types using TCGA datasets. This review elucidates the multiple regulatory mechanisms and functional implications of LINC00839 in various diseases, especially malignancies, emphasizing its potential as a predictive biomarker and therapeutic target across multiple disease domains in humans.

Grey matter abnormalities in major depressive disorder patients with suicide attempts: A systematic review of age-specific differences.

Background: Previous studies have reported alterations in brain structure in major depressive disorder (MDD) patients with suicide attempts. However, age-related changes in suicidal MDD patients remain unclear. Methods: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Embase, PubMed, and Web of Science were searched to identify relevant studies from inception to January 2023. All voxel-based and surface-based morphometry studies comparing suicidal MDD patients to MDD or healthy controls were included. Studies were then grouped by age range (old, middle-age, adolescent) and the commonalities and age-related structural brain alterations were summarized. The included studies were evaluated using the Newcastle-Ottawa Scale (NOS). Results: A total of 17 studies met the inclusion criteria, including 3 of late-life depression (LLD) patients, 11 of middle-aged depression (MAD) patients, and 3 of adolescent depression (AOD) patients. The majority of studies had moderate to high NOS scores, indicating good quality. Patients in all three age groups exhibited extensive alterations in the lateral, medial, and orbital regions of the frontal lobes. Furthermore, suicidal MAD patients showed a specific decrease in the gray matter volume of the dorsolateral prefrontal cortex compared to suicidal LLD patients. Cortical thickness and left angular gyrus volume were decreased in suicidal MAD and suicidal LLD patients, but increased in suicidal AOD patients. Conclusion: This systematic review summarizes structural brain changes in suicidal MDD patients at three age groups: elderly, middle-aged, and adolescent. These findings help elucidate the common circuitry of MDD related to suicide over the lifespan and highlight unique circuitry associated with different ages. These findings may help predict the risk of suicide in MDD patients at different ages.

Immediate efficacy of acupuncture combined with active exercise as 10 min rapid therapy for pain and movement disorders in patients suffering from acute stiff neck: protocol for a randomised controlled trial.

INTRODUCTION: Stiff neck is a condition mainly characterised by persistent pain and limited neck movement, which can substantially impact patients' daily lives during acute episodes. Accordingly, rapid pain relief and restoration of normal activities are the main needs of patients during doctor visits. This study aims to assess the immediate efficacy of acupuncture combined with active exercises in rapidly relieving pain and improving movement disorders within 10 min in patients with acute stiff neck (ASN). METHODS AND ANALYSIS: This randomised controlled clinical trial is being conducted at a single centre in China. 120 participants diagnosed with ASN will randomly be assigned in a 1:1:1 ratio to one of three groups: the acupuncture combined with active exercise group (group A), sham acupuncture combined with active exercise group (group B) and active exercise only group (group C). Each participant will undergo a single 10 min session. The primary outcome is the effective rate at 10 min of treatment. Secondary outcomes include the effective rate at other time points (0-1, 2, 4, 6 and 8 min), Visual Analogue Scale score and cervical range of motion. The intention-to-treat analysis will include all randomised participants. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of the Second Affiliated Hospital of Yunnan University of Chinese Medicine (2022-009). Written informed consent will be obtained from all participants before randomisation. The findings of this study will be disseminated through publication in a peer-reviewed journal and presentation at conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200066997.

Immediate Efficacy of Contralateral Acupuncture on SI3 Combined with Active Exercise for Acute Lumbar Sprains: Protocol for a Randomized Controlled Trial.

Purpose: Acute lumbar sprain (ALS) is a common clinical disease characterized by persistent intolerable low back pain and limitation of movement, and quick pain relief and restoration of mobility in a short time are the main needs of patients when they visit the clinic. This study aims to evaluate the immediate efficacy of contralateral acupuncture (CAT) on SI3 combined with active exercise in treating ALS. Methods and Analysis: This study is a randomized controlled trial which will recruit 118 eligible participants aged 18 to 55 years with ALS at the Second Affiliated Hospital of Yunnan University of Chinese Medicine between March 2024 and December 2026. Participants will be randomly assigned to the acupuncture group or the sham-acupuncture group in a 1:1 ratio. The acupuncture group will receive a 10-minute acupuncture treatment combined with active exercise, while the sham-acupuncture group will receive a 10-minute sham acupuncture treatment combined with active exercise. Randomization will use a computer-generated sequence with allocation concealed in opaque envelopes. The primary outcome will be the pain visual analogue scale (VAS) scores after 10 minutes of treatment. Secondary outcomes will include the pain VAS scores at other time points (2, 4, 6, and 8 minutes post-treatment), the lumbar range of motion (ROM) scores at various time points, blinded assessment, the treatment effect expectancy scale, and the rescue analgesia rate. The analysis will follow the intention-to-treat principle. The primary outcome will be analyzed using ANCOVA, and secondary outcomes with repeated measures ANOVA. The rescue analgesia rate will be assessed using either the χ2 test or Fisher's exact test. Discussion: This study is the first randomized controlled trial to assess the immediate efficacy of CAT in combination with active exercise for ALS. This study will provide a simple, rapid, and effective treatment for the clinical management of ALS.

Implications of Liquid-Liquid Phase Separation and Ferroptosis in Alzheimer's Disease.

Neuronal cell demise represents a prevalent occurrence throughout the advancement of Alzheimer's disease (AD). However, the mechanism of triggering the death of neuronal cells remains unclear. Its potential mechanisms include aggregation of soluble amyloid-beta (Aß) to form insoluble amyloid plaques, abnormal phosphorylation of tau protein and formation of intracellular neurofibrillary tangles (NFTs), neuroinflammation, ferroptosis, oxidative stress, liquid-liquid phase separation (LLPS) and metal ion disorders. Among them, ferroptosis is an iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. The sensitivity to ferroptosis is tightly linked to numerous biological processes. Moreover, emerging evidences indicate that LLPS has great impacts on regulating human health and diseases, especially AD. Soluble Aß can undergo LLPS to form liquid-like droplets, which can lead to the formation of insoluble amyloid plaques. Meanwhile, tau has a high propensity to condensate via the mechanism of LLPS, which can lead to the formation of NFTs. In this review, we summarize the most recent advancements pertaining to LLPS and ferroptosis in AD. Our primary focus is on expounding the influence of Aß, tau protein, iron ions, and lipid oxidation on the intricate mechanisms underlying ferroptosis and LLPS within the domain of AD pathology. Additionally, we delve into the intricate cross-interactions that occur between LLPS and ferroptosis in the context of AD. Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for AD.

Contralateral acupuncture for migraine without aura: a randomized trial protocol with multimodal MRI.

Introduction: Migraine is a common clinical disorder, ranks as the second most disabling disease worldwide, and often manifests with unilateral onset. Contralateral acupuncture (CAT), as a classical acupuncture method, has been proven to be effective in the treatment of migraine without aura (MWoA). However, its neural mechanisms have not been investigated using multimodal magnetic resonance imaging (MRI). Methods and analysis: In this multimodal neuroimaging randomized trial, a total of 96 female MWoA participants and 30 female healthy controls (HCs) will be recruited. The 96 female MWoA participants will be randomized into three groups: Group A (CAT group), Group B [ipsilateral acupuncture (IAT) group], and Group C (sham CAT group) in a 1:1:1 allocation ratio. Each group will receive 30 min of treatment every other day, three times a week, for 8 weeks, followed by an 8-week follow-up period. The primary outcome is the intensity of the migraine attack. Data will be collected at baseline (week 0), at the end of the 8-week treatment period (weeks 1-8), and during the 8-week follow-up (weeks 9-16). Adverse events will be recorded. Multimodal MRI scans will be conducted at baseline and after 8-week treatment. Discussion: This study hypothesized that CAT may treat MWoA by restoring pathological alterations in brain neural activity, particularly by restoring cross-integrated functional connectivity with periaqueductal gray (PAG) as the core pathological brain region. The findings will provide scientific evidence for CAT in the treatment of MWoA. Ethics and dissemination: The Medical Ethics Committee of the Second Affiliated Hospital of Yunnan University of Chinese Medicine has given study approval (approval no. 2022-006). This trial has been registered with the Chinese Clinical Trials Registry (registration no. ChiCTR2300069456). Peer-reviewed papers will be used to publicize the trial's findings. Clinical trial registration: https://clinicaltrials.gov/, identifier ChiCTR2300069456.

Physiological and Full-Length Transcriptome Analyses Reveal the Dwarfing Regulation in Trifoliate Orange (Poncirus trifoliata L.).

Dwarfing rootstocks are capable of high-density planting and are therefore urgently needed in the modern citrus cultivation system. However, little is known about the physiological relevance and molecular basis underlying citrus height. This study aimed to comprehensively analyze phytohormone, carbohydrate, and associated transcriptome changes in the stem of two weak growth rootstocks ('TO' and 'FD') relative to the vigorous 'CC' rootstock. The phenotypic observation revealed that the plant height, plant weight, and internode length were reduced in dwarfing rootstocks. Moreover, the contents of indole-3-acetic acid (IAA), trans-zeatin (tZ), and abscisic acid (ABA), were higher in TO and FD rootstocks, whereas the gibberellin 3 (GA3) content was higher in the CC rootstocks. The carbohydrate contents, including sucrose, fructose, glucose, starch, and lignin significantly decreased in both the TO and FD rootstocks. The full-length transcriptome analysis revealed a potential mechanism regulating dwarfing phenotype that was mainly related to the phytohormone signaling transduction, sugar and starch degradation, lignin synthesis, and cellulose and hemicellulose degradation processes. In addition, many transcription factors (TFs), long non-coding RNAs (lncRNAs), and alternative splicing (AS) events were identified, which might act as important contributors to control the stem elongation and development in the weak growth rootstocks. These findings might deepen the understanding of the complex mechanisms of the stem development responsible for citrus dwarfing and provide a series of candidate genes for the application in breeding new rootstocks with intensive dwarfing.

The value of a risk model combining specific risk factors for predicting postoperative severe morbidity in biliary tract cancer.

Purpose: Several surgical risk models are widely utilized in general surgery to predict postoperative morbidity. However, no studies have been undertaken to examine the predictive efficacy of these models in biliary tract cancer patients, and other perioperative variables can also influence morbidity. As a result, the study's goal was to examine these models alone, as well as risk models combined with disease-specific factors, in predicting severe complications. Methods: A retrospective study of 129 patients was carried out. Data on demographics, surgery, and outcomes were gathered. These model equations were used to determine the morbidity risks. Severe morbidity was defined as the complication comprehensive index ≥ 40. Results: Severe morbidity was observed in 25% (32/129) patients. Multivariate analysis demonstrated that four parameters [comprehensive risk score ≥1, T stage, albumin decrease value, and international normalized ratio (INR)] had a significant influence on the probability of major complications. The area under the curve (AUC) of combining the four parameters was assessed as having strong predictive value and was superior to the Estimation of Physiologic Ability and Surgical Stress System (E-PASS) alone (the AUC value was 0.858 vs. 0.724, p = 0.0375). The AUC for the modified E-PASS (mE-PASS) and Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) in patients over the age of 70 was classified as no predictive value (p = 0.217 and p = 0.063, respectively). Conclusion: The mE-PASS and POSSUM models are ineffective in predicting postoperative morbidity in patients above the age of 70. In biliary tract cancer (BTC) patients undergoing radical operation, a combination of E-PASS and perioperative parameters generates a reasonable prediction value for severe complications.

[Current status and our consideration on clinical transformation of acupuncture research].

It has become one of the major strategic directions to develop translational medicine and realize the stride leap from basic research to clinical application in the national biomedical field. In recent years, both basic and clinical researches of acupuncture and moxibustion have made landmark progress. However, the transformation of acupuncture and moxibustion techniques still faced with many difficulties, such as low conversion rate and high difficulty of transformation. In this article, we mainly made a preliminary discussion on the current situations of acupuncture and moxibustion transformation from the aspects of basic research content, evidence-based medicine and clinical trials, evaluation criteria for the conclusion of scientific research projects and transformation mode, put forward some existing problems in the transformation process, and proposed some corresponding countermeasures to the problems.