Open-source large language models in action: A bioinformatics chatbot for PRIDE database.

We here present a chatbot assistant infrastructure (https://www.ebi.ac.uk/pride/chatbot/) that simplifies user interactions with the PRIDE database's documentation and dataset search functionality. The framework utilizes multiple Large Language Models (LLM): llama2, chatglm, mixtral (mistral), and openhermes. It also includes a web service API (Application Programming Interface), web interface, and components for indexing and managing vector databases. An Elo-ranking system-based benchmark component is included in the framework as well, which allows for evaluating the performance of each LLM and for improving PRIDE documentation. The chatbot not only allows users to interact with PRIDE documentation but can also be used to search and find PRIDE datasets using an LLM-based recommendation system, enabling dataset discoverability. Importantly, while our infrastructure is exemplified through its application in the PRIDE database context, the modular and adaptable nature of our approach positions it as a valuable tool for improving user experiences across a spectrum of bioinformatics and proteomics tools and resources, among other domains. The integration of advanced LLMs, innovative vector-based construction, the benchmarking framework, and optimized documentation collectively form a robust and transferable chatbot assistant infrastructure. The framework is open-source (https://github.com/PRIDE-Archive/pride-chatbot).

Primary perineal endometriosis - a case report and literature review.

Endometriosis is a common gynecological disease caused by the implantation of active endometrial cells outside the uterine cavity. In most cases, endometriosis occurs in the pelvic area, such as the ovary, Douglas' pouch, or uterine sacral ligament. Some rare cases of extrapelvic endometriosis can also occur in the perineum, urinary system, gastrointestinal tract, nervous system, chest, subcutaneous tissue, and skin. Endometriosis of the perineum is usually secondary to obstetric trauma, such as perineal laceration or episiotomy. To date, few cases of spontaneous perineal endometriosis have been reported. Herein, we report a rare case of spontaneous deep perineal endometriosis. Notably, the patient had typical symptoms of regular pain during menstruation with no history of delivery or perineal trauma. The patient recovered well after postoperative gonadotropin releasing hormone agonist injection.

Extraction and characterization of polysaccharides from blackcurrant fruits and its inhibitory effects on acetylcholinesterase.

Microwave assisted aqueous two-phase system (MA-ATPS) was used to simultaneously extract two polysaccharides from blackcurrant. Under the suitable ATPS (ethanol/(NH4)2SO4, 26.75 %/18.98 %) combining with the optimal MA conditions (liquid-to-material ratio 58.5 mL/g, time 9.5 min, temperature 60.5 °C, power 587 W) predicted by response surface methodology, the yields of the top/bottom phase polysaccharides were 13.08 ± 0.37 % and 42.65 ± 0.89 %, respectively. After purification through column chromatography, the top phase polysaccharide (PRTP) and bottom phase polysaccharide (PRBP) were obtained. FT-IR, methylation and NMR analyses confirmed that the repeating unit in the backbone of PRTP was →2, 5)-α-L-Araf-(1 â†’ 3)-α-D-Manp-(1 â†’ 6)-ß-D-Galp-(1 â†’ 6)-α-D-Glcp-(1 â†’ 4)-α-L-Rhap-(1 â†’ 4)-α-D-GalAp-(1→, while the possible unit in PRBP was →4)-α-L-Rhap-(1 â†’ 3)-α-D-Manp-(1 â†’ 6)-ß-D-Galp-(1 â†’ 6)-α-D-Glcp-(1 â†’ 2, 5)-α-L-Araf-(1 â†’ 4)-α-D-GalAp-(1→. PRBP with relatively low molecular weight exhibited better stability, rheological property, free radical scavenging and acetylcholinesterase (AChE) inhibitory activities than PRTP. PRTP and PRBP were reversible mixed-type inhibitors for AChE, and the conformation of AChE was changed after binding with the polysaccharides. Molecular docking, fluorescence and isothermal titration calorimetry assays revealed that PRTP and PRBP quenched the fluorescence through static quenching mechanism, and the van der Waals interactions and hydrogen bonding played key roles in the stability of polysaccharide-enzyme complexes. This study provided a theoretical basis for blackcurrant polysaccharides as AChE inhibitors to treat Alzheimer's disease.

Protocol of the development of a core outcome set for stroke in multidimensional value assessment of traditional Chinese medicine.

INTRODUCTION: Stroke is the most common cause of death in China. In Chinese clinical practise, traditional Chinese medicine (TCM) and integrative medicine have been widely used as adjuvant therapies for the treatment of stroke. However, their clinical effectiveness, particularly their clinical value, has been inconsistent in the literature mainly because various outcome measures have been used and reported in clinical research. Hence, obtaining a comprehensive list of outcomes for TCM value assessment is crucial for a multidimensional value assessment. Therefore, the main objective of this protocol was to develop an outcome set used in health technology assessment (HTA) decision-making for TCM treatment of stroke. METHODS AND ANALYSIS: The outcome set will be developed in four phases: (1) we will perform a systematic literature review to identify candidate outcomes that have been previously measured in published studies; (2) we will develop a comprehensive list of outcome measures by conducting a multistakeholder semistructured interview; (3) we will conduct two-round Delphi surveys to prioritise outcomes for each HTA domain; and (4) we will finalise the outcome sets by holding a ratification meeting with multiple stakeholder groups. The developed outcome set should be measured and reported as the minimum set of outcomes for HTA assessment for the TCM treatment of acute ischaemic stroke (AIS). ETHICS AND DISSEMINATION: This protocol was reviewed and approved by the Institutional Review Board of the Minhang Hospital of Fudan University. Our findings will be shared at academic conferences and in peer-reviewed publications.

Microwave-assisted aqueous two-phase extraction of polysaccharides from Hippophae rhamnoide L.: Modeling, characterization and hypoglycemic activity.

Natural polysaccharides are concerned for their high biological activity and low toxicity. Two kinds of polysaccharides were extracted from Hippophae rhamnoide L. by microwave-assisted aqueous two-phase system. Under the optimal conditions predicted by RSM model (K2HPO4/ethanol (18.93 %/28.29 %), liquid to material ratio 77 mL/g, power 625 W and temperature 61 °C), the yield of total polysaccharides reached 35.91 ± 0.76 %. Moreover, the polysaccharides extraction was well fitted to the Weibull model. After purification by Sepharose-6B, the polysaccharides from top phase (PHTP, purity of 81.44 ± 1.25 %) and bottom phase (PHBP, purity of 88.85 ± 1.40 %) were obtained. GC, FT-IR, methylation and NMR analyses confirmed the backbone of PHTP was composed of a repeated unit →4)-ß-D-Glcp-(1 â†’ 2)-α-L-Rhap-(1 â†’ 4)-ß-D-Galp-(1 â†’ 4)-α-D-GalAp-(1 â†’ 3)-α-L-Araf-(1 â†’ 3)-α-D-Manp-(1→, while the repeated unit in PHBP was →3)-α-L-Araf-(1 â†’ 2)-α-L-Rhap-(1 â†’ 4)-ß-D-Glcp-(1 â†’ 3)-α-D-Manp-(1 â†’ 4)-ß-D-Galp-(1 â†’ 4)-α-D-GalAp-(1→. Compared with PHTP (6.46 × 106 g/mol), PHBP with relatively low molecular weight (8.2 × 105 g/mol) exhibited the smaller particle size, better water-solubility, thermal and rheological property, stronger anti-glycosylation and α-amylase inhibitory effects. Moreover, PHTP and PHBP displayed a reversible inhibition on α-amylase in a competitive manner. This study provides a high-efficient and eco-friendly method for polysaccharides extraction, and lays a foundation for sea buckthorn polysaccharides as potential therapeutic agents in preventing and ameliorating diabetes.

Ultrasound-assisted extraction of emodin from Rheum officinale Baill and its antibacterial mechanism against Streptococcus suis based on CcpA.

Emodin was extracted from Rheum officinale Baill by ultrasound-assisted extraction (UAE), and ethanol was chosen as the suitable solvent through SEM and molecular dynamic simulation. Under the optimum conditions (power 541 W, time 23 min, liquid to material ratio 13:1 mL/g, ethanol concentration 83 %) predicted by RSM, the yield of emodin was 2.18 ± 0.11 mg/g. Moreover, ultrasound power and time displayed the significant effects on the extraction process. Extracting dynamics analysis indicated that the extraction process of emodin by UAE conformed to Fick's second diffusion law. The results of antibacterial experiments suggested that emodin can damage cell membrane and inhibit the expression of cps2A, sao, mrp, epf, neu and the hemolytic activity of S. suis. Biolayer interferometry and FT-IR multi-peak fitting assays demonstrated that emodin induced a secondary conformational shift in CcpA. Molecular docking and molecular dynamics confirmed that emodin bound to CcpA through hydrogen bonding (ALA248, GLU249, GLY129 and ASN196) and π-π T-shaped interaction (TYR225 and TYR130), and the mutation of amino acid residues affected the affinity of CcpA to emodin. Therefore, emodin inhibited the sugar utilization of S. suis through binding to CcpA, and CcpA may be a potential target to inhibit the growth of S. suis.

Notch3 restricts metastasis of breast cancers through regulation of the JAK/STAT5A signaling pathway.

PURPOSE: To explore the potential role of signal transducer and activator of transcription 5A (STAT5A) in the metastasis of breast cancer, and its mechanism of regulation underlying. METHODS AND RESULTS: TCGA datasets were used to evaluate the expression of STAT5A in normal and different cancerous tissues through TIMER2.0, indicating that STAT5A level was decreased in breast cancer tissues compared with normal ones. Gene Set Enrichment Analysis predicted that STAT5A was associated with the activation of immune cells and cell cycle process. We further demonstrated that the infiltration of immune cells was positively associated with STAT5A level. Influorescence staining revealed the expression and distribution of F-actin was regulated by STAT5A, while colony formation assay, wound healing and transwell assays predicted the inhibitory role of STAT5A in the colony formation, migratory and invasive abilities in breast cancer cells. In addition, overexpression of the Notch3 intracellular domain (N3ICD), the active form of Notch3, resulted in the increased expression of STAT5A. Conversely, silencing of Notch3 expression by siNotch3 decreased STAT5A expression, supporting that STAT5A expression is positively associated with Notch3 in human breast cancer cell lines and breast cancer tissues. Mechanistically, chromatin immunoprecipitation showed that Notch3 was directly bound to the STAT5A promoter and induced the expression of STAT5A. Moreover, overexpressing STAT5A partially reversed the enhanced mobility of breast cancer cells following Notch3 silencing. Low expression of Notch3 and STAT5A predicted poorer prognosis of patients with breast cancer. CONCLUSION: The present study demonstrates that Notch3 inhibits metastasis in breast cancer through inducing transcriptionally STAT5A, which was associated with tumor-infiltrating immune cells, providing a novel strategy to treat breast cancer.

Methylation of ESR1 promoter induced by SNAI2-DNMT3B complex promotes epithelial-mesenchymal transition and correlates with poor prognosis in ERα-positive breast cancers.

Estrogen receptor α (ERα) serves as an essential therapeutic predictor for breast cancer (BC) patients and is regulated by epigenetic modification. Abnormal methylation of cytosine phosphoric acid guanine islands in the estrogen receptor 1 (ESR1) gene promoter could silence or decrease ERα expression. In ERα-negative BC, we previously found snail family transcriptional repressor 2 (SNAI2), a zinc-finger transcriptional factor, recruited lysine-specific demethylase 1 to the promoter to transcriptionally suppress ERα expression by demethylating histone H3 lysine 4 dimethylation (H3K4me2). However, the role of SNAI2 in ERα-positive BC remains elusive. In this study, we observed a positive correlation between SNAI2 and ESR1 methylation, and SNAI2 promoted ESR1 methylation by recruiting DNA methyltransferase 3 beta (DNMT3B) rather than DNA methyltransferase 1 (DNMT1) in ERα-positive BC cells. Subsequent enrichment analysis illustrated that ESR1 methylation is strongly correlated with cell adhesion and junction. Knocking down DNMT3B could partially reverse SNAI2 overexpression-induced cell proliferation, migration, and invasion. Moreover, high DNMT3B expression predicted poor relapse-free survival and overall survival in ERα-positive BC patients. In conclusion, this study demonstrated the novel mechanisms of the ESR1 methylation mediated with the SNAI2/DNMT3B complex and enhanced awareness of ESR1 methylation's role in promoting epithelial-mesenchymal transition in BC.

Bioinspired Hydrophobicity for Enhancing Electrochemical CO2 Reduction.

Electrochemical carbon dioxide reduction (CO2 R) is a promising pathway for converting greenhouse gasses into valuable fuels and chemicals using intermittent renewable energy. Enormous efforts have been invested in developing and designing CO2 R electrocatalysts suitable for industrial applications at accelerated reaction rates. The microenvironment, specifically the local CO2 concentration (local [CO2 ]) as well as the water and ion transport at the CO2 -electrolyte-catalyst interface, also significantly impacts the current density, Faradaic efficiency (FE), and operation stability. In nature, hydrophobic surfaces of aquatic arachnids trap appreciable amounts of gases due to the "plastron effect", which could inspire the reliable design of CO2 R catalysts and devices to enrich gaseous CO2 . In this review, starting from the wettability modulation, we summarize CO2 enrichment strategies to enhance CO2 R. To begin, superwettability systems in nature and their inspiration for concentrating CO2 in CO2 R are described and discussed. Moreover, other CO2 enrichment strategies, compatible with the hydrophobicity modulation, are explored from the perspectives of catalysts, electrolytes, and electrolyzers, respectively. Finally, a perspective on the future development of CO2 enrichment strategies is provided. We envision that this review could provide new guidance for further developments of CO2 R toward practical applications.

Preparation of Ribes nigrum L. polysaccharides-stabilized selenium nanoparticles for enhancement of the anti-glycation and α-glucosidase inhibitory activities.

Seven kinds of selenium nanoparticles (RP-SeNPs) were prepared by using the polysaccharides extracted from Ribes nigrum L. (RP) as the stabilizer and dispersant. Among them, RP-SeNPs-1 (94.2 nm), RP-SeNPs-2 (101.2 nm) and RP-SeNPs-3 (107.6 nm) with relatively smaller mean particle size exhibited stronger α-glucosidase inhibitory activity than other RP-SeNPs (115.3-164.2 nm) and SeNPs (288.9 nm). Ultraviolet-visible spectrophotometry, Fourier transform-infrared, X-ray diffraction, energy dispersive X-ray and X-ray photoelectron spectroscopy analyses confirmed that SeNPs were ligated with RP to form nanocomposites and displayed amorphous form. Electron microscopy images revealed that RP-SeNPs-1 - RP-SeNPs-3 were regular shape spherical nanocomposites with much better dispersion than SeNPs. Compared with SeNPs, RP-SeNPs displayed relatively high thermal, storage, pH and salt ion stability. Moreover, RP-SeNPs-1-RP-SeNPs-3 showed significantly better anti-glycation and α-glucosidase inhibitory activity than SeNPs, especially RP-SeNPs-1 with the smallest particle size. Inhibitory kinetics analysis indicated that SeNPs and RP-SeNPs inhibited α-glucosidase with competitive type and reversible mechanism. In addition, the conformation of the α-glucosidase was changed after binding with the SeNPs and RP-SeNPs-1. Fluorescence quenching and isothermal titration calorimetry assays revealed that these two nanoparticles could interact with α-glucosidase to form non-fluorescent complexes through hydrogen bonding, and the formation was spontaneously driven by enthalpy.

Increased plasma expression of a disintegrin and metalloproteinase with thrombospondin motifs like 4 in patients with idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) can result in right heart failure. We aimed to evaluate the plasma protein levels of a disintegrin and metalloproteinase with thrombospondin motifs like 4 (ADAMTSL4) and its relationship with IPAH and CTEPH. Plasma ADAMTSL4 protein levels were measured using proteomics analysis in eight patients with IPAH and nine healthy controls. ADAMTSL4 levels in pulmonary tissues were assessed using bioinformatics tools. Protein expression of ADAMTSL4 in platelet-derived growth factor (PDGF)-BB-treated primary rat pulmonary arterial smooth muscle cells (PASMCs) was detected by Western blot. Plasma ADAMTSL4 concentrations were measured in 45 patients (15 with IPAH and 30 with CTEPH) using enzyme-linked immunosorbent assay (ELISA). Correlation between ADAMTSL4 levels and clinical parameters was evaluated. In patients with IPAH, the plasma levels of ADAMTSL4 protein were significantly higher than those in healthy controls (flod change [FC] 1.85, p < 0.05), and mRNA expression levels were significantly elevated (log FC 0.66, p < 0.05). The protein expression of ADAMTSL4 was significantly increased in PDGF-BB-treated PASMCs compared to that in the control grAoup (p < 0.05). Plasma ADAMTSL4 protein levels in patients with IPAH (4.71 ± 0.73 ng/mL, p < 0.01) and CTEPH (4.22 ± 0.66 ng/mL, p < 0.01) were higher than in healthy controls (3.01 ± 0.46 ng/mL). Plasma ADAMATL4 protein levels had a cutoff value of 3.55 ng/mL based on the receiver operator characteristic curve and were positively correlated with mean pulmonary artery pressure (mPAP) (r = 0.305, p < 0.05). In patients with IPAH and CTEPH, elevated plasma ADAMTSL4 levels were positively associated with mPAP.

Dual-targeting lanthanide-ICG-MOF nanoplatform for cancer Theranostics: NIR II luminescence imaging guided sentinel lymph nodes surgical navigation.

Sentinel lymph node imaging is important for breast tumor staging and prediction of postoperative metastasis. However, clinical sentinel lymph node imaging has limitations such as low specificity, low contrast, and short retention time. The combination of bio-conjugates chemistry and luminescence technology may achieve the specific targeting effect. In this research, we designed a dual-targeting composite nanoprobe (∼50 nm) using a metal-organic framework (MOF) as carrier, loaded with lanthanide and ICG, and combined with hyaluronic acid and folic acid to detect metastatic lymph nodes. The coupled hyaluronic acid and folic acid can target to the tumor cells and dentritic cells with a dual-targeting effect. The FA-HA/ZIF-8@ICG nanoprobes can accumulate rapidly in sentinel lymph node with a stronger luminescence intensity (1.6 times) than that of normal popliteal lymph nodes in vivo, thus distinguish metastatic sentinel lymph node from normal effectively. Furthermore, due to the MOF carrier, the integrated lanthanide and near-infrared dye by transferring the absorbed excitation energy from ICG to Nd3+ can enhance the signal-to-background ratio of NIR II imaging and have long retention time in vivo imaging. Finally, the FA-HA/ICG@Ln@ZIF-8 nanoplatform increased the penetration depth and contrast of imaging, prolonged the retention time, and achieved the sentinel lymph nodes surgical resection. This study has important implications for lymph node imaging and surgical navigation.

Glutathione-Exhausting Nanoprobes for NIR-II Fluorescence Imaging-Guided Surgery and Boosting Radiation Therapy Efficacy via Ferroptosis in Breast Cancer.

Breast-conserving surgery (BCS) is the standard of care for early breast cancer patients, while the high ratio of reoperation is still a challenge due to inaccurate margin assessments. In patients with locally advanced or advanced breast cancer, radiotherapy is an important treatment for local control or improvement of quality of life. However, enhancing sensitization to radiotherapy is an unmet medical need. To solve the above clinical predicaments, a glutathione (GSH) exhausting virus-like silicon dioxide nanoprobe with Gd coating and folic acid (FA) modification is designed. After loading ICG in the mesopores, the VGd@ICG-FA probe efficiently targets tumor cells with high resolution, due to its virus-like morphology and folate acid anchoring. Especially, the fabricated nanoprobe enables the identification of tiny cancers and navigates precise surgery under NIR-II fluorescence imaging. Moreover, after the nanoprobes enter into the cytoplasm of cancer cells, tetrasulfide linkages in the silica framework are broken under the triggering of high GSH concentrations. In turn, the broken framework exhausts GSH to disrupt intracellular reactive oxygen species (ROS) homeostasis, and Gd produces more ROS under radiotherapy, further activating ferroptosis, and resulting in the enhancement of radiotherapy in breast cancer. Therefore, our nanoprobe exhibits tremendous potential as a NIR-II fluorescence imaging agent with no systematic side effects for precise cancer surgery and nanotherapeutics for boosting radiation sensitivity in future clinical translation of breast cancer.

PD-L1 aptamer-functionalized degradable hafnium oxide nanoparticles for near infrared-II diagnostic imaging and radiosensitization.

Immune checkpoint blockade is now recognized as a paradigm-shifting cancer therapeutic strategy, whereas there remains difficulty in accurately predicting immunotherapy efficacy by PD-L1 expression. In addition, radiotherapy for cancer patients faces the problem of insufficient dose of radiotherapy at the tumor site while which have been not tolerated by normal tissues. In this study, we created PD-L1 aptamer-anchored spherical nucleic acids (SNAs) with a shell made of PD-L1 aptamer and indocyanine green (ICG) embedded in a mesoporous hafnium oxide nanoparticle core (Hf@ICG-Apt). Upon low pH irradiation in the tumor sites, the nano-system enabled the release of ICG in the high PD-L1 expression tumor to develop a high tumor-to-background ratio of 7.97 ± 0.76 and enhanced the ICG tumor retention to more than 48 h. Moreover, Hf@ICG-Apt improved radiation therapy (RT) when combined with radiation. Notably, Hf@ICG-Apt showed scarcely any systemic toxicity in vivo. Overall, this research offered a novel approach for applying reliable monitoring of PD-L1 expression and localization and robust RT sensitization against cancer with good biosafety.

The activity and mechanism of vidofludimus as a potent enzyme inhibitor against NDM-1-positive E. coli.

New Delhi metallo-ß-lactamase-1 (NDM-1) is the most important and prevalent enzyme among all metallo-ß-lactamases. NDM-1 can hydrolyze almost all-available ß-lactam antibiotics including carbapenems, resulting in multidrug resistance, which poses an increasing clinical threat. However, there is no NDM-1 inhibitor approved for clinical treatment. Therefore, identifying a novel and potential enzyme inhibitor against NDM-1-mediated infections is an urgent need. In this study, vidofludimus was identified as a potential NDM-1 inhibitor by structure-based virtual screening and an enzyme activity inhibition assay. Vidofludimus significantly inhibited NDM-1 hydrolysis activity with a significant dose-dependent effect. When the vidofludimus concentration was 10 µg/ml, the inhibition rate and 50% inhibitory concentration were 93.3% and 13.8 ± 0.5 µM, respectively. In vitro, vidofludimus effectively restored the antibacterial activity of meropenem against NDM-1-positive Escherichia coli (E. coli), and the minimum inhibitory concentration of meropenem was decreased from 64 µg/ml to 4 µg/ml, a 16-fold reduction. The combination of vidofludimus and meropenem showed a significant synergistic effect with a fractional inhibitory concentration index of 0.125 and almost all the NDM-1-positive E. coli were killed within 12 h. Furthermore, the synergistic therapeutic effect of vidofludimus and meropenem in vivo was evaluated in mice infected with NDM-1 positive E. coli. Compared with the control treatment, vidofludimus combined with meropenem significantly improved the survival rate of mice infected with NDM-1-positive E. coli (P < 0.05), decreased the white blood cell count, the bacterial burden and inflammatory response induced by NDM-1-positive E. coli (P < 0.05), and alleviated histopathological damage in infected mice. It was demonstrated by molecular dynamic simulation, site-directed mutagenesis and biomolecular interaction that vidofludimus could interact directly with the key amino acids (Met67, His120, His122 and His250) and Zn2+ in the active site of NDM-1, thereby competitively inhibiting the hydrolysis activity of NDM-1 on meropenem. In summary, vidofludimus holds promise as anNDM-1 inhibitor, and the combination of vidofludimus and meropenem has potential as a therapeutic strategy for NDM-1-mediated infections.

Molecular and functional imaging in cancer-targeted therapy: current applications and future directions.

Targeted anticancer drugs block cancer cell growth by interfering with specific signaling pathways vital to carcinogenesis and tumor growth rather than harming all rapidly dividing cells as in cytotoxic chemotherapy. The Response Evaluation Criteria in Solid Tumor (RECIST) system has been used to assess tumor response to therapy via changes in the size of target lesions as measured by calipers, conventional anatomically based imaging modalities such as computed tomography (CT), and magnetic resonance imaging (MRI), and other imaging methods. However, RECIST is sometimes inaccurate in assessing the efficacy of targeted therapy drugs because of the poor correlation between tumor size and treatment-induced tumor necrosis or shrinkage. This approach might also result in delayed identification of response when the therapy does confer a reduction in tumor size. Innovative molecular imaging techniques have rapidly gained importance in the dawning era of targeted therapy as they can visualize, characterize, and quantify biological processes at the cellular, subcellular, or even molecular level rather than at the anatomical level. This review summarizes different targeted cell signaling pathways, various molecular imaging techniques, and developed probes. Moreover, the application of molecular imaging for evaluating treatment response and related clinical outcome is also systematically outlined. In the future, more attention should be paid to promoting the clinical translation of molecular imaging in evaluating the sensitivity to targeted therapy with biocompatible probes. In particular, multimodal imaging technologies incorporating advanced artificial intelligence should be developed to comprehensively and accurately assess cancer-targeted therapy, in addition to RECIST-based methods.

Clinical applications of deep learning in breast MRI.

Deep learning (DL) is one of the most powerful data-driven machine-learning techniques in artificial intelligence (AI). It can automatically learn from raw data without manual feature selection. DL models have led to remarkable advances in data extraction and analysis for medical imaging. Magnetic resonance imaging (MRI) has proven useful in delineating the characteristics and extent of breast lesions and tumors. This review summarizes the current state-of-the-art applications of DL models in breast MRI. Many recent DL models were examined in this field, along with several advanced learning approaches and methods for data normalization and breast and lesion segmentation. For clinical applications, DL-based breast MRI models were proven useful in five aspects: diagnosis of breast cancer, classification of molecular types, classification of histopathological types, prediction of neoadjuvant chemotherapy response, and prediction of lymph node metastasis. For subsequent studies, further improvement in data acquisition and preprocessing is necessary, additional DL techniques in breast MRI should be investigated, and wider clinical applications need to be explored.

Physical and Rehabilitation Therapy for Overactive Bladder in Women: A Systematic Review and Meta-Analysis.

Objective: To compare the effects of different physical and rehabilitation therapies on women with overactive bladder (OAB). Design: Network meta-analysis. Data source: The Embase, Scopus, and PubMed databases were systematically searched from their inception to June 22, 2022. We included only RCTs, with no language restrictions. Articles in the reference lists and related studies were thoroughly reviewed. Review Methods. This network meta-analysis included related studies on different physical and rehabilitation therapies for OAB. Data were extracted independently from the included randomized controlled trials by two authors, and they used the Cochrane Collaboration's tool to evaluate the risk of bias. We used RevMan to assess the risk assessment of research bias. This network meta-analysis was performed using the Stata software. We completed the review in accordance with the PRISMA items for systematic reviews and meta-analyses statement. Results: Twelve randomized controlled trials involving 637 patients were included in this meta-analysis. All physical and rehabilitation therapies improved daytime micturition frequency and nocturia frequency in OAB patients. Percutaneous tibial nerve stimulation (PTNS), BT + ES, and BT + BF + ES are better interventions for OAB treatment. There were no significant differences in PTNS, BT + ES, and BT + BF + ES. Conclusion: All physical and rehabilitation therapies can improve daytime micturition and nocturia frequency in OAB. PTNS, BT + ES, and BT + BF + ES were the priority therapies.

Optimization of ultrasound-assisted aqueous two-phase extraction of polysaccharides from seabuckthorn fruits using response methodology, physicochemical characterization and bioactivities.

BACKGROUND: Seabuckthorn fruits contains many active subtances, among them, the seabuckthorn polysaccharide is one of the main active ingredients, and exhibits diverse bioactivities. The extraction of polysaccharides from seabuckthorn fruits is the most important step for their wide applications. Ultrasound-assisted aqueous two-phase extraction (UA-ATPE) is a promising green method for extracting polysaccharides. Additionally, physicochemical characterization and antioxidant activities can evaluate the potential functions and applications in the food and medicine industries. RESULTS: Based on the single-factor experiments, 20.70% (w/w) ammonium sulfate ((NH4 )2 SO4 ) and 27.56% (w/w) ethanol were determined as the suitable composition for aqueous two-phase. The optimum conditions of UA-ATPE obtained by response surface methodology were as follows: ultrasonic power (390 W), extraction time (41 min), liquid-to-material ratio (72: 1 mL/g), and the total yield of the polysaccharides reached 34.14 ± 0.10%, The molecular weights of the purified upper-phase seabuckthorn polysaccharide (PUSP) and the purified lower-phase seabuckthorn polysaccharide (PLSP) were 65 525 and 26 776 Da, respectively. PUSP and PLSP contained the same six monosaccharides (galacturonic acid, rhamnose, xylose, mannose, glucose and galactose), but with different molar ratios. Furthermore, PUSP and PLSP displayed certain viscoelastic property, had no triple helical structure, possessed different thermal stability, surface morphology and conformation in aqueous solution. PUSP and PLSP displayed strong antioxidant properties by the assays of scavenging ability of ABTS+ ·, the protection of DNA damage and erythrocyte hemolysis. CONCLUSION: UA-ATPE significantly increased the yield of seabuckthorn polysaccharides. PUSP and PLSP were different in many aspects, such as molar ratio, surface shape and antioxidant activities. Seabuckthornpolysaccharides possess great potential in medicine and functional foods. © 2022 Society of Chemical Industry.