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Among many unexpected phenomena of active matter is the recently observed superfluid-like thinning (viscosity drop) behavior of bacteria suspensions. Understanding this peculiar self-propelled thinning by active matter is of theoretical and practical importance. Here, we find that, although distinct in driving mechanisms, active matter and shear flows exhibit similar thinning behaviors upon the increase of self-propulsion and shear forces, respectively. Our structural characterizations reveal that they actually share the same cluster-breaking mechanism of thinning. How fast and how shattered the cluster is broken determines the (dis)continuity of the thinning. This explains why adding active particles to Newtonian fluids can cause thinning, in which rotation of active particles play a key role in breaking clusters. Our work proposes a mechanism of self-propelled thinning and further establishes the underlying connections between active matter and shear flows.
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Protein solubility plays a crucial role in various biotechnological, industrial, and biomedical applications. With the reduction in sequencing and gene synthesis costs, the adoption of high-throughput experimental screening coupled with tailored bioinformatic prediction has witnessed a rapidly growing trend for the development of novel functional enzymes of interest (EOI). High protein solubility rates are essential in this process and accurate prediction of solubility is a challenging task. As deep learning technology continues to evolve, attention-based protein language models (PLMs) can extract intrinsic information from protein sequences to a greater extent. Leveraging these models along with the increasing availability of protein solubility data inferred from structural database like the Protein Data Bank holds great potential to enhance the prediction of protein solubility. In this study, we curated an Updated Escherichia coli protein Solubility DataSet (UESolDS) and employed a combination of multiple PLMs and classification layers to predict protein solubility. The resulting best-performing model, named Protein Language Model-based protein Solubility prediction model (PLM_Sol), demonstrated significant improvements over previous reported models, achieving a notable 6.4% increase in accuracy, 9.0% increase in F1_score, and 11.1% increase in Matthews correlation coefficient score on the independent test set. Moreover, additional evaluation utilizing our in-house synthesized protein resource as test data, encompassing diverse types of enzymes, also showcased the good performance of PLM_Sol. Overall, PLM_Sol exhibited consistent and promising performance across both independent test set and experimental set, thereby making it well suited for facilitating large-scale EOI studies. PLM_Sol is available as a standalone program and as an easy-to-use model at https://zenodo.org/doi/10.5281/zenodo.10675340.
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Bases de Datos de Proteínas , Proteínas de Escherichia coli , Solubilidad , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Benchmarking , Escherichia coli/genética , Escherichia coli/metabolismo , Biología Computacional/métodos , Aprendizaje ProfundoRESUMEN
Tandem repeat proteins (TRPs) are widely distributed and bind to a wide variety of ligands. DNA-binding TRPs such as zinc finger (ZNF) and transcription activator-like effector (TALE) play important roles in biology and biotechnology. In this study, we first conducted an extensive analysis of TRPs in public databases, and found that the enormous diversity of TRPs is largely unexplored. We then focused our efforts on identifying novel TRPs possessing DNA-binding capabilities. We established a protein language model for DNA-binding protein prediction (PLM-DBPPred), and predicted a large number of DNA-binding TRPs. A subset was then selected for experimental screening, leading to the identification of 11 novel DNA-binding TRPs, with six showing sequence specificity. Notably, members of the STAR (Short TALE-like Repeat proteins) family can be programmed to target specific 9 bp DNA sequences with high affinity. Leveraging this property, we generated artificial transcription factors using reprogrammed STAR proteins and achieved targeted activation of endogenous gene sets. Furthermore, the members of novel families such as MOON (Marine Organism-Originated DNA binding protein) and pTERF (prokaryotic mTERF-like protein) exhibit unique features and distinct DNA-binding characteristics, revealing interesting biological clues. Our study expands the diversity of DNA-binding TRPs, and demonstrates that a systematic approach greatly enhances the discovery of new biological insights and tools.
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The criticality of the jamming transition responsible for amorphous solidification has been theoretically linked to the marginal stability of a thermodynamic Gardner phase. While the critical exponents of jamming appear independent of the preparation history, the pertinence of Gardner physics far from equilibrium is an open question. To fill this gap, we numerically study the nonequilibrium dynamics of hard disks compressed toward the jamming transition using a broad variety of protocols. We show that dynamic signatures of Gardner physics can be disentangled from the aging relaxation dynamics. We thus define a generic dynamic Gardner cross-over regardless of the history. Our results show that the jamming transition is always accessed by exploring increasingly complex landscape, resulting in anomalous microscopic relaxation dynamics that remains to be understood theoretically.
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Under a sufficiently large load, a solid material will flow via rearrangements, where particles change neighbors. Such plasticity is most easily described in the athermal, quasistatic limit of zero temperature and infinitesimal loading rate, where rearrangements occur only when the system becomes mechanically unstable. For disordered solids, the instabilities marking the onset of rearrangements have long been believed to be fold instabilities, in which an energy barrier disappears and the frequency of a normal mode of vibration vanishes continuously. Here, we report that there exists another, anomalous, type of instability caused by the breaking of a "stabilizing bond," whose removal creates an unstable vibrational mode. For commonly studied systems, such as those with harmonic finite-range interparticle interactions, such "discontinuous instabilities" are not only inevitable, they often dominate the modes of failure. Stabilizing bonds are a subset of all the bonds in the system and are prevalent in disordered solids generally. Although they do not trigger discontinuous instabilities in systems with vanishing stiffness at the interaction cutoff, they are, even in those cases, local indicators of incipient mechanical failure. They therefore provide an accurate structural predictor of instabilities not only of the discontinuous type but of the fold type as well.
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Stomatal immunity plays an important role during bacterial pathogen invasion. Abscisic acid (ABA) induces plants to close their stomata and halt pathogen invasion, but many bacterial pathogens secrete phytotoxin coronatine (COR) to antagonize ABA signaling and reopen the stomata to promote infection at early stage of invasion. However, the underlining mechanism is not clear. SAD2 is an importin ß family protein, and the sad2 mutant shows hypersensitivity to ABA. We discovered ABI1, which negatively regulated ABA signaling and reduced plant sensitivity to ABA, was accumulated in the plant nucleus after COR treatment. This event required SAD2 to import ABI1 to the plant nucleus. Abolition of SAD2 undermined ABI1 accumulation. Our study answers the long-standing question of how bacterial COR antagonizes ABA signaling and reopens plant stomata during pathogen invasion.
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Ácido Abscísico , Aminoácidos , Proteínas de Arabidopsis , Arabidopsis , Indenos , Estomas de Plantas , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Estomas de Plantas/fisiología , Arabidopsis/microbiología , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/fisiología , Ácido Abscísico/metabolismo , Indenos/metabolismo , Indenos/farmacología , Aminoácidos/metabolismo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Pseudomonas syringae/fisiología , Pseudomonas syringae/patogenicidad , Transducción de Señal , Regulación de la Expresión Génica de las Plantas , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Núcleo Celular/metabolismo , Fosfoproteínas FosfatasasRESUMEN
BACKGROUND: Trichinella spiralis (T. spiralis) is a parasitic helminth that causes a globally prevalent neglected zoonotic disease, and worms at different developmental stages (muscle larvae, adult worms, newborn larvae) induce immune attack at different infection sites, causing serious harm to host health. Several innate immune cells release extracellular traps (ETs) to entrap and kill most pathogens that invade the body. In response, some unicellular pathogens have evolved a strategy to escape capture by ETs through the secretion of nucleases, but few related studies have investigated multicellular helminths. RESULTS: In the present study, we observed that ETs from neutrophils capture adult worms of T. spiralis, while ETs from macrophages trap muscle larvae and newborn larvae, and ETs had a killing effect on parasites in vitro. To defend against this immune attack, T. spiralis secretes plancitoxin-1, a DNase II-like protein, to degrade ETs and escape capture, which is essential for the survival of T. spiralis in the host. CONCLUSIONS: In summary, these findings demonstrate that T. spiralis escapes ET-mediated capture by secreting deoxyribonuclease as a potential conserved immune evasion mechanism, and plancitoxin-1 could be used as a potential vaccine candidate.
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Trampas Extracelulares , Evasión Inmune , Trichinella spiralis , Animales , Trichinella spiralis/fisiología , Trichinella spiralis/inmunología , Trampas Extracelulares/inmunología , Trampas Extracelulares/metabolismo , Ratones , Proteínas del Helminto/metabolismo , Larva/inmunología , Larva/parasitologíaRESUMEN
Water, covering over two-thirds of the Earth's surface, holds immense potential for generating clean water, sustainable energy, and metal resources, which are the cornerstones of modern society and future development. It is highly desired to produce these crucial elements through eco-friendly processes with minimal carbon footprints. Interfacial solar evaporation, which utilizes solar energy at the air-liquid interface to facilitate water vaporization and solute separation, offers a promising solution. In this review, we systematically report the recent progress of the cogeneration of clean water and energy/resources including electricity, hydrogen, and metal resources via interfacial solar evaporation. We first gain insight into the energy and mass transport for a typical interfacial solar evaporation system and reveal the residual energy and resources for achieving the cogeneration goal. Then, we summarize the recent advances in materials/device designs for efficient cogeneration. Finally, we discuss the existing challenges and potential opportunities for the further development of this field.
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BACKGROUND: There is an increase in the global incidence of allergies. The hygiene hypothesis and the old friend hypothesis reveal that helminths are associated with the prevalence of allergic diseases. The therapeutic potential of Trichinella spiralis is recognized; however, the stage at which it exerts its immunomodulatory effect is unclear. METHODS: We evaluated the differentiation of bone marrow-derived macrophages stimulated with T spiralis excretory-secretory products. Based on an ovalbumin-induced murine model, T spiralis was introduced during 3 allergy phases. Cytokine levels and immune cell subsets in the lung, spleen, and peritoneal cavity were assessed. RESULTS: We found that T spiralis infection reduced lung inflammation, increased anti-inflammatory cytokines, and decreased Th2 cytokines and alarms. Recruitment of eosinophils, CD11b+ dendritic cells, and interstitial macrophages to the lung was significantly suppressed, whereas Treg cells and alternatively activated macrophages increased in T spiralis infection groups vs the ovalbumin group. Notably, when T spiralis was infected prior to ovalbumin challenge, intestinal adults promoted proportions of CD103+ dendritic cells and alveolar macrophages. CONCLUSIONS: T spiralis strongly suppressed type 2 inflammation, and adults maintained lung immune homeostasis.
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Hipersensibilidad , Trichinella spiralis , Ratones , Humanos , Animales , Trichinella spiralis/metabolismo , Ovalbúmina/metabolismo , Inflamación , Citocinas/metabolismoRESUMEN
Plant pattern recognition receptors (PRRs) perceive pathogen-associated molecular patterns (PAMPs) to activate immune responses. Medium-chain 3-hydroxy fatty acids (mc-3-OH-FAs), which are widely present in Gram-negative bacteria, were recently shown to be novel PAMPs in Arabidopsis thaliana. The Arabidopsis PRR LIPOOLIGOSACCHARIDE-SPECIFIC REDUCED ELICITATION (LORE) is a G-type lectin receptor-like kinase that recognizes mc-3-OH-FAs and subsequently mounts an immune response; however, the mechanisms underlying LORE activation and downstream signaling are unexplored. Here, we report that one of the mc-3-OH-FAs, 3-OH-C10:0, induces phosphorylation of LORE at tyrosine residue 600 (Y600). Phosphorylated LORE subsequently trans-phosphorylates the receptor-like cytoplasmic kinase PBL34 and its close paralogs, PBL35 and PBL36, and therefore activates plant immunity. Phosphorylation of LORE Y600 is required for downstream phosphorylation of PBL34, PBL35, and PBL36. However, the Pseudomonas syringae effector HopAO1 targets LORE, dephosphorylating the tyrosine-phosphorylated Y600 and therefore suppressing the immune response. These observations uncover the mechanism by which LORE mediates signaling in response to 3-OH-C10:0 in Arabidopsis.
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Arabidopsis/inmunología , Enfermedades de las Plantas/inmunología , Inmunidad de la Planta/genética , Pseudomonas syringae/inmunología , Arabidopsis/genética , Arabidopsis/microbiología , Regulación de la Expresión Génica de las Plantas , Lectinas/metabolismo , Lipopolisacáridos/administración & dosificación , Fosforilación , Enfermedades de las Plantas/microbiología , Receptores de Reconocimiento de Patrones/genética , Receptores de Reconocimiento de Patrones/metabolismo , Transducción de Señal , Tirosina/metabolismoRESUMEN
Nucleic acid is one of the most important substances in organisms, and its dynamic changes are closely related to physiological processes. Nucleic acid labeling is conducive to providing important information for the early diagnosis and treatment of pathophysiological processes. Here, we utilized the transfer mechanism between carbon sources and CDs to synthesize wavelength-adjustable N-CDs for the nucleic acid image. Along with the increased graphite nitrogen (from 10.6 to 30.1%) gradually by the precise design of the nitrogen structure in carbon sources (e.g., primary amines, secondary amines, tertiary amines, and liking graphite-nitrogen), the energy gap of CDs reduced, resulting in adjustable wavelength from visible to near-infrared range (from 461 nm/527 nm to 650 nm/676 nm). Furthermore, N-CDs exhibited a selective affinity for nucleic acids, especially RNA. Therefore, N-CDs support an efficient platform for real-time tracking of RNA dynamic changes in cells.
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The varied functions of lipid droplets, which encompass the regulation of lipid and energy homeostasis, as well as their association with the occurrence of various metabolic diseases, are intricately linked to their dynamic properties. Super-resolution imaging techniques have emerged to decipher physiological processes and molecular mechanisms on the nanoscale. However, achieving long-term dynamic super-resolution imaging faces challenges due to the need for fluorescent probes with high photostability. This paper introduces LD-CF, a "buffering probe" for imaging lipid droplet dynamics using structured illumination microscopy (SIM). The polarity-sensitive LD-CF eliminates background fluorescence with a "cyan filter" strategy, enabling wash-free imaging of lipid droplets. In the fluorescent "off" state outside droplets, the probes act as a "buffering pool", replacing photobleached probes inside droplets and enabling photostable long-term SIM imaging. With this probe, three modes of lipid droplet fusion were observed, including the discovery of fusion from large to small lipid droplets. Fluorescence intensity tracking also revealed the direction of lipid transport during the lipid droplet fusion.
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Colorantes Fluorescentes , Gotas Lipídicas , Colorantes Fluorescentes/metabolismo , Gotas Lipídicas/metabolismo , Microscopía Fluorescente/métodos , Transporte Biológico , LípidosRESUMEN
BACKGROUND: The tumor microenvironment (TME) encompasses a variety of cells that influence immune responses and tumor growth, with tumor-associated macrophages (TAM) being a crucial component of the TME. TAM can guide prostate cancer in different directions in response to various external stimuli. METHODS: First, we downloaded prostate cancer single-cell sequencing data and second-generation sequencing data from multiple public databases. From these data, we identified characteristic genes associated with TAM clusters. We then employed machine learning techniques to select the most accurate TAM gene set and developed a TAM-related risk label for prostate cancer. We analyzed the tumor-relatedness of the TAM-related risk label and different risk groups within the population. Finally, we validated the accuracy of the prognostic label using single-cell sequencing data, qPCR, and WB assays, among other methods. RESULTS: In this study, the TAM_2 cell cluster has been identified as promoting the progression of prostate cancer, possibly representing M2 macrophages. The 9 TAM feature genes selected through ten machine learning methods and demonstrated their effectiveness in predicting the progression of prostate cancer patients. Additionally, we have linked these TAM feature genes to clinical pathological characteristics, allowing us to construct a nomogram. This nomogram provides clinical practitioners with a quantitative tool for assessing the prognosis of prostate cancer patients. CONCLUSION: This study has analyzed the potential relationship between TAM and PCa and established a TAM-related prognostic model. It holds promise as a valuable tool for the management and treatment of PCa patients.
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Macrófagos , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/genética , Macrófagos Asociados a Tumores , Aprendizaje Automático , Nomogramas , Microambiente Tumoral/genéticaRESUMEN
PURPOSE: The significance of postmastectomy radiotherapy (PMRT) in breast cancer patients who initially have clinically node-positive (cN +) status but achieve downstaging to ypN0 following neoadjuvant chemotherapy (NAC) remains uncertain. This study aims to assess the impact of PMRT in this patient subset. METHODS: Patients were enrolled from West China Hospital, Sichuan University from 2008 to 2019. Overall survival (OS), Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS) were estimated using the Kaplan-Meier method and assessed with the log-rank test. The impact of PMRT was further analyzed by the Cox proportional hazards model. Propensity score matching (PSM) was performed to reduce the selection bias. RESULTS: Of the 333 eligible patients, 189 (56.8%) received PMRT, and 144 (43.2%) did not. At a median follow-up period of 71 months, the five-year LRFS, DMFS, BCSS, and OS rates were 99.1%, 93.4%, 96.4%, and 94.3% for the entire cohort, respectively. Additionally, the 5-year LRFS, DMFS, BCSS, and OS rates were 98.9%, 93.8%, 96.7%, and 94.5% with PMRT and 99.2%, 91.3%, 94.9%, and 92.0% without PMRT, respectively (all p-values not statistically significant). After multivariate analysis, PMRT was not a significant risk factor for any of the endpoints. When further stratified by stage, PMRT did not show any survival benefit for patients with stage II-III diseases. CONCLUSION: In the context of comprehensive treatments, PMRT might be exempted in ypN0 breast cancer patients. Further large-scale, randomized controlled studies are required to investigate the significance of PMRT in this patient subset.
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Neoplasias de la Mama , Mastectomía , Terapia Neoadyuvante , Estadificación de Neoplasias , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Adulto , Anciano , Estudios Retrospectivos , Radioterapia Adyuvante/métodos , Quimioterapia Adyuvante/métodos , Metástasis Linfática , Recurrencia Local de Neoplasia/patologíaRESUMEN
BACKGROUND: Prediction of lymph node metastasis (LNM) is critical for individualized management of papillary thyroid carcinoma (PTC) patients to avoid unnecessary overtreatment as well as undesired under-treatment. Artificial intelligence (AI) trained by thyroid ultrasound (US) may improve prediction performance. METHODS: From September 2017 to December 2018, patients with suspicious PTC from the first medical center of the Chinese PLA general hospital were retrospectively enrolled to pre-train the multi-scale, multi-frame, and dual-direction deep learning (MMD-DL) model. From January 2019 to July 2021, PTC patients from four different centers were prospectively enrolled to fine-tune and independently validate MMD-DL. Its diagnostic performance and auxiliary effect on radiologists were analyzed in terms of receiver operating characteristic (ROC) curves, areas under the ROC curve (AUC), accuracy, sensitivity, and specificity. RESULTS: In total, 488 PTC patients were enrolled in the pre-training cohort, and 218 PTC patients were included for model fine-tuning (n = 109), internal test (n = 39), and external validation (n = 70). Diagnostic performances of MMD-DL achieved AUCs of 0.85 (95% CI: 0.73, 0.97) and 0.81 (95% CI: 0.73, 0.89) in the test and validation cohorts, respectively, and US radiologists significantly improved their average diagnostic accuracy (57% vs. 60%, P = 0.001) and sensitivity (62% vs. 65%, P < 0.001) by using the AI model for assistance. CONCLUSIONS: The AI model using US videos can provide accurate and reproducible prediction of cervical lymph node metastasis in papillary thyroid carcinoma patients preoperatively, and it can be used as an effective assisting tool to improve diagnostic performance of US radiologists. TRIAL REGISTRATION: We registered on the Chinese Clinical Trial Registry website with the number ChiCTR1900025592.
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Inteligencia Artificial , Neoplasias de la Tiroides , Humanos , Metástasis Linfática/diagnóstico por imagen , Estudios Prospectivos , Estudios Retrospectivos , Cáncer Papilar Tiroideo/diagnóstico por imagen , Neoplasias de la Tiroides/diagnóstico por imagenRESUMEN
A simple, reliable method for identifying ß-lactoglobulin (ß-LG) in dairy products is needed to protect those with ß-LG allergies. A common, practical strategy for target detection is designing simplified nucleic acid nanodevices by integrating functional components. This work presents a label-free modular ß-LG aptasensor consisting of an aptamer-loop G-quadruplex (G4), the working conformation of which is regulated by conformational antagonism to ensure respective module functionality and the related signal transduction. The polymorphic conformations of the module-fused sequence are systematically characterized, and the cause is revealed as shifting antagonistic equilibrium. Combined with conformational folding dynamics, this helped regulate functional conformations by fine-tuning the sequences. Furthermore, the principle of specific ß-LG detection by parallel G4 topology is examined as binding on the G4 aptamer loop by ß-LG to reinforce the G4 topology and fluorescence. Finally, a label-free, assembly-free, succinct, and turn-on fluorescent aptasensor is established, achieving excellent sensitivity across five orders of magnitude, rapidly detecting ß-LG within 22-min. This study provides a generalizable approach for the conformational regulation of module-fused G4 sequences and a reference model for creating simplified sensing devices for a variety of targets.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , G-Cuádruplex , Lactoglobulinas , Lactoglobulinas/química , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodosRESUMEN
OBJECTIVES: To develop a novel ultrasound scoring system for the major salivary glands in patients with immunoglobulin G4-related sialadenitis (IgG4-RS) and assess its diagnostic value in a multicenter cohort of Chinese patients. METHODS: Twenty clinicians (rheumatologists, stomatologists, and radiologists) participated. The study was conducted in four steps: (1) defining the ultrasonography (US) elements, (2) developing a novel ultrasound scoring system for US of the salivary glands, (3) evaluation of inter- and intra-reader reliabilities using the new ultrasound scoring system, and (4) assessing the diagnostic value of this novel ultrasound scoring system in IgG4-RS patients in a Chinese multicenter cohort. RESULTS: A novel ultrasound scoring system for the salivary glands was developed, with total scores ranging from 0 to 34. The inter- and intra-reader reliabilities of the ultrasound scoring system were excellent (0.972 and 0.940, respectively). A total of 470 people were recruited in this study; 187 patients were diagnosed with IgG4-RS, and the remaining 283 people were diagnosed with non-IgG4-RS. Patients with IgG4-RS had significantly higher US scores than the non-IgG4-RS group (mean US score=16 vs. 4, P < 0.001). The calculated area under the curve (AUC) for the total US score was 0.852 (95% CI: 0.814-0.891). The total US scores≥9 showed a sensitivity of 75.4% and a specificity of 91.9%. Association analysis showed a positive correlation between total US scores and serum IgG4 levels and hypocomplementemia (r=0.221, r=0.349; P = 0.002) and a negative correlation between total US scores and serum C3 and C4 levels (r=-0.210, r=-0.303; P = 0.005, P < 0.001). CONCLUSIONS: A novel semiquantitative ultrasound scoring system for patients with IgG4-RS was developed, with good diagnostic performance. The inter- and intra-reader reliabilities were excellent. US scores were correlated with IgG4, C3, and C4 levels and hypocomplementemia.
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BACKGROUND: This study was designed to develop an innovative classification and guidance system for renal hilar tumors and to assess the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) for managing such tumors. METHODS: A total of 179 patients undergoing RAPN for renal hilar tumors were retrospectively reviewed. A novel classification system with surgical techniques was introduced and the perioperative features, tumor characteristics, and the efficacy and safety of RAPN were compared within subgroups. RESULTS: We classified the tumors according to our novel system as follows: 131 Type I, 35 Type II, and 13 Type III. However, Type III had higher median R.E.N.A.L., PADUA, and ROADS scores compared with the others (all p < 0.001), indicating increased operative complexity and higher estimated blood loss [180.00 (115.00-215.00) ml]. Operative outcomes revealed significant disparities between Type III and the others, with longer operative times [165.00 (145.00-200.50) min], warm ischemia times [24.00 (21.50-30.50) min], tumor resection times [13.00 (12.00-15.50) min], and incision closure times [22.00 (20.00-23.50) min] (all p < 0.005). Postoperative outcomes also showed significant differences, with longer durations of drain removal (77.08 ± 18.16 h) and hospitalization for Type III [5.00 (5.00-6.00) d] (all p < 0.05). Additionally, Type I had a larger tumor diameter than the others (p = 0.009) and pT stage differed significantly between the subtypes (p = 0.020). CONCLUSIONS: The novel renal hilar tumor classification system is capable of differentiating the surgical difficulty of RAPN and further offers personalized surgical steps tailored to each specific classification. It provides a meaningful tool for clinical practice.
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Neoplasias Renales , Nefrectomía , Procedimientos Quirúrgicos Robotizados , Humanos , Neoplasias Renales/cirugía , Neoplasias Renales/clasificación , Neoplasias Renales/patología , Femenino , Masculino , Nefrectomía/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Procedimientos Quirúrgicos Robotizados/métodos , Estudios de Seguimiento , Anciano , Tempo Operativo , Pronóstico , Complicaciones Posoperatorias/clasificación , Complicaciones Posoperatorias/etiología , Tiempo de Internación/estadística & datos numéricos , Adulto , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/clasificación , Isquemia Tibia , Pérdida de Sangre Quirúrgica/estadística & datos numéricosRESUMEN
Type IV collagen is an integral component of basement membranes. Mutations in COL4A1, one of the key genes encoding Type IV collagen, can result in a variety of diseases. It is clear that a significant proportion of mutations that affect splicing can cause disease directly or contribute to the susceptibility or severity of disease. Here, we analyzed exonic mutations and intronic mutations described in the COL4A1 gene using bioinformatics programs and identified candidate mutations that may alter the normal splicing pattern through a minigene system. We identified seven variants that induce splicing alterations by disrupting normal splice sites, creating new ones, or altering splice regulatory elements. These mutations are predicted to impact protein function. Our results help in the correct molecular characterization of variants in COL4A1 and may help develop more personalized treatment options.
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Colágeno Tipo IV , Mutación , Empalme del ARN , Humanos , Colágeno Tipo IV/genética , Empalme del ARN/genética , Exones/genética , Intrones/genética , Sitios de Empalme de ARN/genética , Biología Computacional/métodosRESUMEN
OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.