Risk Factors for Isolated Sphenoid Sinusitis after Endoscopic Endonasal Transsphenoidal Pituitary Surgery.

(1) Background: Transsphenoidal pituitary surgery can be conducted via microscopic or endoscopic approaches, and there has been a growing preference for the latter in recent years. However, the occurrence of rare complications such as postoperative sinusitis remains inadequately documented in the existing literature. (2) Methods: To address this gap, we conducted a comprehensive retrospective analysis of medical records spanning from 2018 to 2023, focusing on patients who underwent transsphenoidal surgery for pituitary neuroendocrine tumors (formerly called pituitary adenoma). Our study encompassed detailed evaluations of pituitary function and MRI imaging pre- and postsurgery, supplemented by transnasal endoscopic follow-up assessments at the otolaryngology outpatient department. Risk factors for sinusitis were compared using univariate and multivariate logistic regression analyses. (3) Results: Out of the 203 patients included in our analysis, a subset of 17 individuals developed isolated sphenoid sinusitis within three months postoperation. Further scrutiny of the data revealed significant associations between certain factors and the occurrence of postoperative sphenoid sinusitis. Specifically, the classification of the primary tumor emerged as a notable risk factor, with patients exhibiting nonfunctioning pituitary neuroendocrine tumors with 3.71 times the odds of developing sinusitis compared to other tumor types. Additionally, postoperative cortisol levels demonstrated a significant inverse relationship, with lower cortisol levels correlating with an increased risk of sphenoid sinusitis postsurgery. (4) Conclusions: In conclusion, our findings underscore the importance of considering tumor classification and postoperative cortisol levels as potential predictors of postoperative sinusitis in patients undergoing transsphenoidal endoscopic pituitary surgery. These insights offer valuable guidance for clinicians in identifying at-risk individuals and implementing tailored preventive and management strategies to mitigate the occurrence and impact of sinusitis complications in this patient population.

Photoresponsive CHA-Integrated Self-Propelling 3D DNA Walking Amplifier within the Concentration Localization Effect of DNA Molecular Framework Enables Highly Efficient Fluorescence Bioimaging.

While three-dimensional (3D) DNA walking amplifiers hold considerable promise in the construction of advanced DNA-based fluorescent biosensors for bioimaging, they encounter certain difficulties such as inadequate sensitivity, premature activation, the need for exogenous propelling forces, and low reaction rates. In this contribution, a variety of profitable solutions have been explored. First, a catalytic hairpin assembly (CHA)-achieved nonenzymatic isothermal nucleic acid amplification is integrated to enhance sensitivity. Subsequently, one DNA component is simply functionalized with a photocleavage-bond to conduct a photoresponsive manner, whereby the target recognition occurs only when the biosensor is exposed to an external ultraviolet light source, overcoming premature activation during biodelivery. Furthermore, a special self-propelling walking mechanism is implemented by reducing biothiols to MnO2 nanosheets, thereby propelling forces that are self-supplied to a Mn2+-reliant DNAzyme. By carrying the biosensing system with a DNA molecular framework to induce a unique concentration localization effect, the nucleic acid contact reaction rate is notably elevated by 6 times. Following these, an ultrasensitive in vitro detection performance with a limit of detection down to 2.89 fM is verified for a cancer-correlated microRNA biomarker (miRNA-21). Of particular importance, our multiple concepts combined 3D DNA walking amplifier that enables highly efficient fluorescence bioimaging in live cells and even bodies, exhibiting a favorable application prospect in disease analysis.

Genetic tools for the study of the mangrove killifish, Kryptolebias marmoratus, an emerging vertebrate model for phenotypic plasticity.

Kryptolebias marmoratus (Kmar), a teleost fish of the order Cyprinodontiformes, has a suite of unique phenotypes and behaviors not observed in other fishes. Many of these phenotypes are discrete and highly plastic-varying over time within an individual, and in some cases reversible. Kmar and its interfertile sister species, K. hermaphroditus, are the only known self-fertile vertebrates. This unusual sexual mode has the potential to provide unique insights into the regulation of vertebrate sexual development, and also lends itself to genetics. Kmar is easily adapted to the lab and requires little maintenance. However, its internal fertilization and small clutch size limits its experimental use. To support Kmar as a genetic model, we compared alternative husbandry techniques to maximize recovery of early cleavage-stage embryos. We find that frequent egg collection enhances yield, and that protease treatment promotes the greatest hatching success. We completed a forward mutagenesis screen and recovered several mutant lines that serve as important tools for genetics in this model. Several will serve as useful viable recessive markers for marking crosses. Importantly, the mutant kissylips lays embryos at twice the rate of wild-type. Combining frequent egg collection with the kissylips mutant background allows for a substantial enhancement of early embryo yield. These improvements were sufficient to allow experimental analysis of early development and the successful mono- and bi-allelic targeted knockout of an endogenous tyrosinase gene with CRISPR/Cas9 nucleases. Collectively, these tools will facilitate modern developmental genetics in this fascinating fish, leading to future insights into the regulation of plasticity.

Long-term outcomes of coils embolization for superior hypophyseal artery aneurysms.

Objective: Superior hypophyseal artery (SHA) aneurysms are intradural, and their rupture can result in subarachnoid hemorrhage. Considering the related surgical difficulty and anatomical restrictions, endovascular treatment (EVT) is considered the most favorable modality for SHA aneurysms; however, the long-term outcomes of EVT have rarely been reported. The study assessed the incidence of and risk factors for recurrence of SHA aneurysms after EVT as well as the correlation factors for SHA aneurysm rupture. Methods: We included 112 patients with SHA aneurysms treated with EVT at our facility between 2009 and 2020. Here, EVT included non-stent-assisted (simple or balloon-assisted) or stent-assisted coiling. Flow diverter was not included because it was barely used due to its high cost under our national insurance's limitation, and a high proportion of ruptured aneurysms in our series. Univariate and multivariate logistic regression was performed to evaluate the correlation factors for SHA aneurysm rupture, along with the incidence of and risk factors for post-EVT SHA aneurysm recurrence and re-treatment. Results: In our patients, the mean angiographic follow-up period was 3.12 years. The presence of type IA or IB cavernous internal carotid artery (cICA) was strongly correlated with SHA aneurysm rupture. Recurrence occurred in 17 (13.4%) patients, of which only 1 (1.4%) patient had received stent-assisted coiling. All cases of recurrence were observed within 2 years after EVT. The multivariate logistic regression results showed that ruptured aneurysm and non-stent-assisted coiling were independent risk factors for aneurysm recurrence. Of the 17 cases of aneurysm recurrence, 9 (52.9%) received re-treatment. Moreover, aneurysm rupture was the only factor significantly correlated with re-treatment in multivariate logistic regression. No re-recurrence was observed when a recurrent aneurysm was treated with stent-assisted coiling. Conclusion: Type I cICA was common factor for aneurysm rupture. Although flow-diverter treatment serves as another suitable technique that was not compared with, coils embolization was effective treatment modality for SHA aneurysms, leading to low recurrence and complication rates, especially with stent use. All cases of recurrence occurred within 2 years after EVT; they were strongly associated with prior aneurysm rupture. Further stent-assisted coiling was noticed to prevent re-recurrence.

Light-Driven and Metal-Organic Framework Synergetic Loaded DNA Tetrahedral Amplifier for Exonuclease III-Powered All-in-One Biosensing and Chemotherapy in Live Biosystems.

As a result of inaccurate biosensing and difficult synergetic loading, it is challenging to further impel DNA amplifiers to perform therapeutic application. Herein, we introduce some innovative solutions. First, a smart light-driven biosensing concept based on embedding nucleic acid modules with a simple photocleavage-linker is proposed. In this system, the target identification component is exposed on irradiation with ultraviolet light, thus avoiding an always-on biosensing response during biological delivery. Further, in addition to providing controlled spatiotemporal behavior and precise biosensing information, a metal-organic framework is used for the synergetic loading of doxorubicin in the internal pores, whereafter a rigid DNA tetrahedron-sustained exonuclease III-powered biosensing system is attached to prevent drug leakage and enhance resistance to enzymatic degradation. By selecting a next-generation breast cancer correlative noncoding microRNA biomarker (miRNA-21) as a model low-abundance analyte, a highly sensitive in vitro detection ability even allowing to distinguish single-base mismatching is demonstrated. Moreover, the all-in-one DNA amplifier shows excellent bioimaging competence and good chemotherapy efficacy in live biosystems. These findings will drive research into the use of DNA amplifiers in diagnosis and therapy integrated fields.

Prenylated PALM2 Promotes the Migration of Esophageal Squamous Cell Carcinoma Cells Through Activating Ezrin.

Proteins containing a CAAX motif at the C-terminus undergo prenylation for localization and activity and include a series of key regulatory proteins, such as RAS superfamily members, heterotrimeric G proteins, nuclear lamina protein, and several protein kinases and phosphatases. However, studies of prenylated proteins in esophageal cancer are limited. Here, through research on large-scale proteomic data of esophageal cancer in our laboratory, we found that paralemmin-2 (PALM2), a potential prenylated protein, was upregulated and associated with poor prognosis in patients. Low-throughput verification showed that the expression of PALM2 in esophageal cancer tissues was higher than that in their paired normal esophageal epithelial tissues, and it was generally expressed in the membrane and cytoplasm of esophageal cancer cells. PALM2 interacted with the two subunits of farnesyl transferase (FTase), FNTA and FNTB. Either the addition of an FTase inhibitor or mutation in the CAAX motif of PALM2 (PALM2C408S) impaired its membranous localization and reduced the membrane location of PALM2, indicating PALM2 was prenylated by FTase. Overexpression of PALM2 enhanced the migration of esophageal squamous cell carcinoma cells, whereas PALM2C408S lost this ability. Mechanistically, PALM2 interacted with the N-terminal FERM domain of ezrin of the ezrin/radixin/moesin (ERM) family. Mutagenesis indicated that lysine residues K253/K254/K262/K263 in ezrin's FERM domain and C408 in PALM2's CAAX motif were important for PALM2/ezrin interaction and ezrin activation. Knockout of ezrin prevented enhanced cancer cell migration by PALM2 overexpression. PALM2, depending on its prenylation, increased both ezrin membrane localization and phosphorylation of ezrin at Y146. In summary, prenylated PALM2 enhances the migration of cancer cells by activating ezrin.

Age-dependent winner-loser effects in a mangrove rivulus fish, Kryptolebias marmoratus.

The outcomes of recent fights can provide individuals information about their relative fighting ability and affect their contest decisions (winner-loser effects). Most studies investigate the presence/absence of the effects in populations/species, but here we examine how they vary between individuals of a species in response to age-dependent growth rate. Many animals' fighting ability is highly dependent on body size, so rapid growth makes information from previous fights unreliable. Furthermore, fast-growing individuals are often at earlier developmental stages and are relatively smaller and weaker than most other individuals but are growing larger and stronger quickly. We therefore predicted winner-loser effects to be less detectable in individuals with high than low growth rates and to decay more quickly. Fast-growing individuals should also display stronger winner than loser effects, because a victory when small indicates a strength which will grow, whereas a loss might soon become irrelevant. We tested these predictions using naïve individuals of a mangrove killifish, Kryptolebias marmoratus, in different growth stages. Measures of contest intensity revealed winner/loser effects only for slow-growth individuals. Both fast- and slow-growth fish with a winning experience won more of the subsequent non-escalated contests than those with a losing experience; in fast-growth individuals this effect disappeared in 3 days, but in slow-growth fish it did not. Fast-growth individuals also displayed winner effects but not loser effects. The fish therefore responded to their contest experiences in a way which reflected value of the information from these experiences to them, consistent with our predictions.

Pheromone Perception in Fish: Mechanisms and Modulation by Internal Status.

Pheromones are chemical signals that facilitate communication between animals, and most animals use pheromones for reproduction and other forms of social behavior. The identification of key ligands and olfactory receptors used for pheromonal communication provides insight into the sensory processing of these important cues. An individual's responses to pheromones can be plastic, as physiological status modulates behavioral outputs. In this review, we outline the mechanisms for pheromone sensation and highlight physiological mechanisms that modify pheromone-guided behavior. We focus on hormones, which regulate pheromonal communication across vertebrates including fish, amphibians, and rodents. This regulation may occur in peripheral olfactory organs and the brain, but the mechanisms remain unclear. While this review centers on research in fish, we will discuss other systems to provide insight into how hormonal mechanisms function across taxa.

NIR Photocontrolled Fluorescent Nanosensor under a Six-Branched DNA Nanowheel-Induced Nucleic Acid Confinement Effect for High-Performance Bioimaging.

Although DNA nanotechnology is a promising option for fluorescent biosensors to perform bioimaging, the uncontrollable target identification during biological delivery and the spatially free molecular collision of nucleic acids may cause unsatisfactory imaging precision and sensitivity, respectively. Aiming at solving these challenges, we herein integrate some productive notions. On the one hand, the target recognition component is inserted with a photocleavage bond and a core-shell structured upconversion nanoparticle with a low thermal effect is further employed to act as the ultraviolet light generation source, under which a precise near-infrared photocontrolled sensing is achieved through a simple external 808 nm light irradiation. On the other hand, the collision of all of the hairpin nucleic acid reactants is confined by a DNA linker to form a six-branched DNA nanowheel, after which their local reaction concentrations are vastly enhanced (∼27.48 times) to induce a special nucleic acid confinement effect to guarantee highly sensitive detection. By selecting a lung cancer-associated short noncoding microRNA sequence (miRNA-155) as a model low-abundance analyte, it is demonstrated that the newly established fluorescent nanosensor not only presents good in vitro assay performance but also exhibits a high-performance bioimaging competence in live biosystems including cells and mouse body, propelling the progress of DNA nanotechnology in the biosensing field.

Using time-shared scanning optical tweezers assisted two-photon fluorescence imaging to establish a versatile CRISPR/Cas12a-mediated biosensor.

Based on the admirable precision to identify target nucleic acids and the particular trans-cleavage feature, CRISPR/Cas12a system is a useful means to further improve the sensing accuracy and the design flexibility of fluorescence biosensors. However, the current construction concepts still suffer from insufficient sensitivity, unsuitable for complicated real samples and limited detection species. In this work, much efforts are achieved to address these obstacles. At first, we adopt a microsphere sustained signal enrichment, under which a home-made time-shared scanning optical tweezers assisted fluorescence imaging is employed to guarantee a stable excitation and also realize multiflux measurement. Furthermore, by taking advantage of the low background merit of the near-infrared light excited two-photon fluorescence, a commendable anti-interference capability is endowed to operate in complex media. After utilizing a functional DNA (e.g. aptamer and DNAzyme) regulated mediation pathway to respond non-nucleic acid analytes (alpha fetal protein and Pb2+), the newly-established CRISPR/Cas12a-mediated fluorescence biosensor is found to display favorable assay performance. More importantly, our analytical methodology can act as a versatile and reliable toolbox in various applications such as disease diagnosis and environmental analysis, propelling the development of CRISPR system in biosensing field.

Intercross population study reveals that co-mutation of mitfa genes in two subgenomes induces red skin color in common carp ( Cyprinus carpio wuyuanensis).

Common carp are among the oldest domesticated fish in the world. As such, there are many food and ornamental carp strains with abundant phenotypic variations due to natural and artificial selection. Hebao red carp (HB, Cyprinus carpio wuyuanensis), an indigenous strain in China, is renowned for its unique body morphology and reddish skin. To reveal the genetic basis underlying the distinct skin color of HB, we constructed an improved high-fidelity (HiFi) HB genome with good contiguity, completeness, and correctness. Genome structure comparison was conducted between HB and a representative wild strain, Yellow River carp (YR, C. carpio haematopterus), to identify structural variants and genes under positive selection. Signatures of artificial selection during domestication were identified in HB and YR populations, while phenotype mapping was performed in a segregating population generated by HB×YR crosses. Body color in HB was associated with regions with fixed mutations. The simultaneous mutation and superposition of a pair of homologous genes ( mitfa) in chromosomes A06 and B06 conferred the reddish color in domesticated HB. Transcriptome analysis of common carp with different alleles of the mitfa mutation confirmed that gene duplication can buffer the deleterious effects of mutation in allotetraploids. This study provides new insights into genotype-phenotype associations in allotetraploid species and lays a foundation for future breeding of common carp.

Prostaglandin F2α drives female pheromone signaling in cichlids, revealing a basis for evolutionary divergence in olfactory signaling.

Pheromones play essential roles in reproduction in many species. Prostaglandin F2α (PGF2α) acts as a female reproductive hormone and as a sex pheromone in some species. An olfactory receptor (OR) for PGF2α was recently discovered in zebrafish, but this signaling pathway is evolutionarily labile. To understand the evolution of signals that attract males to fertile females, we used the African cichlid Astatotilapia burtoni and found that adult males strongly prefer fertile female odors. Injection of a prostaglandin synthesis inhibitor abolishes this attractivity of fertile females, indicating these hormones are necessary for pheromonal signaling. Unlike zebrafish, A. burtoni males are insensitive to PGF2α, but they do exhibit strong preference for females injected with PGF2α. This attractiveness is independent of the PGF2α hormonal receptor Ptgfr, indicating that this pheromone signaling derives from PGF2α metabolization into a yet-undiscovered pheromone. We further discovered that fish that are insensitive to PGF2α lack an ortholog for the OR Or114 that zebrafish use to detect PGF2α. These results indicate that PGF2α itself does not directly induce male preference in cichlids. Rather, it plays a vital role that primes females to become attractive via an alternative male OR.

Astragaloside IV - mediated endothelial progenitor cell exosomes promote autophagy and inhibit apoptosis in hyperglycemic damaged endothelial cells via miR-21/PTEN axis.

INTRODUCTION: As one of the basic components of Astragalus, Astragaloside IV (AS-IV) has a protective effect on endothelial injury caused by diabetes. AS-IV stimulated endothelial progenitor cells (EPCs) to secrete exosomes loaded with miR-21. This study aimed to investigate the effects of AS-IV-mediated EPCs exosomal miR-21 (EPC-exos-miR-21) on high glucose (HG) damaged endothelial cells. MATERIALS AND METHODS: After the isolation of EPCs derived from fetal umbilical cord blood, exosomes of EPCs were obtained by differential centrifugation. The morphology of exosomes was observed by electron microscopy. The particle size distribution of exosomes was detected by Nanoparticle Tracking Analysis. Human umbilical vein endothelial cells (HUVECs) were treated with 33 mM glucose to establish an HG injury model. Flow cytometry and TUNEL assay were used to characterize the surface markers of primary EPCs and the apoptosis of HUVECs. The gene and protein expression were detected by qPCR, immunofluorescence, and Western blotting. A dual luciferase assay was used to verify the targeting relationship of miR-21 with PTEN. RESULTS: HG environment led to time- and dose-dependent inhibition and enhancement of autophagy and apoptosis in HUVECs. AS-IV stimulated EPCs to secrete exosomes loaded with miR-21. Exosomes secreted by EPCs pretreated with AS-IV [EPC-exo(ASIV)] promoted autophagy and inhibited apoptosis in HG-impaired HUVECs. PTEN is a target of miR-21. MiR-21 carried by EPC-exo(ASIV) repressed PTEN expression in HG-impaired HUVECs. In contrast, p-AKT, p-mTOR, p-PI3K, cleaved PARP and PARP levels were upregulated. Compared to the HG group, the expression of autophagy regulatory genes (ATG5, beclin1 and LC3) was enhanced in the EPC-exo(ASIV) group and EPC-exo(ASIV)-miR-21 mimic group. In contrast, apoptosis-positive regulatory genes (Bax, caspase-3 and caspase-9) were attenuated. Further overexpression of PTEN reversed the expression of these genes. CONCLUSIONS: AS-IV-mediated EPC-exos-miR-21 could enhance autophagy and depress apoptosis in HG-damaged endothelial cells via the miR-21/PTEN axis.

Temporary or Permanent? A Clinical Challenge in the Evaluation of Traumatic Brain Injury Patients with Unconsciousness and Normal Initial Head CT.

BACKGROUND: Traumatic brain injury (TBI) patients with unconsciousness and normal initial head computed tomography (CT) present a clinical dilemma for physicians and neurosurgeons in the emergency department (ED). We recorded how long it took for patients to regain consciousness and evaluated the patients' characteristics. METHODS: From 2018 to 2020, TBI patients with unconsciousness and normal initial head CT [Glasgow coma scale (GCS) score < 13, negative CT scan and normal laboratory test results] were evaluated. Patients who regained consciousness were analyzed. Multivariate logistic regression (MLR) analyses were used to evaluate independent factors for regaining consciousness. RESULTS: A total of 77 patients were included in this study. Fifty-eight (75.3%) patients regained consciousness, most within one day (43.1%). Nineteen (24.7%) patients never regained consciousness. MLR analysis showed that initial GCS score (odds 1.85, p = 0.017), early airway protection in ED (odds 25.02, p = 0.018) and 72-h GCS score improvement by two points (odds 0.02, p = 0.001) were independent factors for regaining consciousness. Overall, 94.1% of patients who received early airway protection and improved 2 points in 72-h GCS score regained consciousness. The association between days to M5 status and days to M6 status (consciousness) was highly significant. Fewer days to M5 status were highly associated with needing fewer days to regain consciousness. CONCLUSIONS: For TBI patients with unconsciousness and normal initial head CT, a higher probability of regaining consciousness was observed in those who underwent early airway protection and who improved 2 points in 72-h GCS score. Regaining consciousness within a short period could be expected in patients with M5 status.

Smart NIR light-gated CRISPR/Cas12a fluorescent biosensor with boosted biological delivery and trans-cleavage activity for high-performance in vivo operation.

Despite the in vitro usage of CRISPR/Cas12a system in fluorescent biosensors has made remarkable achievements, many challenges such as poor biological delivery, insufficient sensitivity, and uncontrollable initiation compel them hard to conduct in vivo analysis. Thus, we propose here some fruitful sensing concepts. First, the multiple biomolecular components of CRISPR/Cas12a system are collectively carried by MnO2 nanosheets via a simple physical absorption to achieve a highly-efficient biological uptake. Under the reduction of widespread biothiols, not only the sensing frame is easily released but also sufficient Mn2+ is produced to serve as an effective trans-cleavage accelerator. Furthermore, a photocleavge-linker induced smart near-infrared (NIR) light-gated manner is designed to offer a spatiotemporal target recognition, for which a 808 nm NIR light transduced ultraviolet upconversion luminescence with weak thermal effect is employed to completely prevent the sensing flow from pre-initiating during the biological delivery. As a conceptual validation, this biosensor has satisfactory sensitivity and specificity to survivn messenger RNA (a broad-spectrum cancer biomarker). More importantly, it can work as a reliable imaging platform for differentiating cancers in live cellular level and also presents a high-performance operation ability for analyzing live mice, greatly promoting the CRISPR technology in biosensing field.

A Self-Made Optical Tweezers Integrated Upconversion Luminescence Confocal Scanning Instrument Enables Stable and Noninvasive Long-Term In Situ Imaging a Single Suspension Cell Under Exceptionally Efficient Luminescent Resonance Energy Transfer Sensing.

It is necessary to explore labeling probes with worthy optical properties and a noninvasive fluorescence imaging manner for stable long-term in situ measuring a single suspension cell. In response to these goals, we herein make a breakthrough on two fronts. On one hand, a co-sensitizer-induced efficient 808 nm near-infrared light-excited luminescence-confined upconversion nanoparticle with a low thermal effect is fabricated by employing a layer-by-layer seed growing approach to develop a sandwich structure, under which the luminescence domain is vastly restricted into an extremely thin inner shell (∼ 2.77 nm) to finally bring about a high-efficiency luminescent resonance energy transfer (LRET) sensing behavior. On the other hand, a self-made optical tweezers integrated upconversion luminescence confocal scanning instrument is applied to enhance the imaging accuracy, after which the liquid viscous force is sufficiently overcome by the resulting single beam gradient force and the analyzed suspension cell is always immobilized to the focal plane to ensure a constant luminescence excitation condition. By making use of a metal ion-dependent DNAzyme and a hairpin DNA strand to design a corresponding LRET sensing system, our nanoprobe shows satisfactory assay performance for two model biomolecules (Ca2+ and TK1 messenger RNA). Following the optical trapping-assisted imaging, this exceptional measurement method is capable of effectively monitoring the intracellular target changes in different physiological states, endowing a powerful toolbox for single cell analysis.

The Role of Intraventricular Hemorrhage in Traumatic Brain Injury: A Novel Scoring System.

Traumatic intraventricular hemorrhage (tIVH) is associated with increased mortality and disability in traumatic brain injury (TBI). However, the significance of tIVH itself remains unclear. Our goal is to assess whether tIVH affects in-hospital mortality and short-term functional outcomes. We retrospectively reviewed the records of 5048 patients with TBI during a 5-year period, and 149 tIVH patients were analyzed. Confounding was reduced using the inverse probability of treatment weighting (IPTW) based on propensity score. The association between IVH and outcomes was investigated using logistic regression in the IPTW-adjusted cohort. In our study, after adjustment for analysis, the in-hospital mortality rate (11.4% vs. 9.2%) and the poor functional outcome rate (37.9% vs.10.6%) were significantly higher in the tIVH group than in the non-tIVH group. Factors independently associated with outcomes were age ≥ 65 years, Glasgow Coma Scale (GCS) severity score, and the Graeb score. The Traumatic Graeb Score, a novel scoring system for predicting functional outcomes associated with tIVH, comprised the sum of the following components: GCS scores of 3 to 4 (=2 points), 5 to 12 (=1 point), 13 to 15 (=0 points); age ≥ 65 years, yes (=1 point), no (=0 points); Graeb score (0-12 points). A Traumatic Graeb Score ≥ 4 is an optimal cutoff value for poor short-term functional outcomes.

Upconversion Luminescence-Initiated and GSH-Responsive Self-Driven DNA Motor for Automatic Operation in Living Cells and In Vivo.

In light of the worthy design flexibility and the good signal amplification capacity, the recently developed DNA motor (especially the DNA walker)-based fluorescent biosensors can offer an admirable choice for realizing bioimaging. However, this attractive biosensing strategy not only has the disadvantage of uncontrollable initiation but also usually demands the supplement of exogenous driving forces. To handle the above obstacles, some rewarding solutions are proposed here. First, on the surface of an 808 nm near-infrared light-excited low-heat upconversion nanoparticle, a special ultraviolet upconversion luminescence-initiated three-dimensional (3D) walking behavior is performed by embedding a photocleavage linker into the sensing elements, and such light-controlled target recognition can perfectly overcome the pre-triggering of the biosensor during the biological delivery to significantly boost the sensing precision. After that, a peculiar self-driven walking pattern is constructed by employing MnO2 nanosheets as an additional nanovector to physically absorb the sensing frame, for which the reduction of the widespread glutathione in the biological medium can bring about sufficient self-supplied Mn2+ to guarantee the walking efficiency. By selecting an underlying next-generation broad-spectrum cancer biomarker (survivin messenger RNA) as the model target, we obtain that the newly formed autonomous 3D DNA motor shows a commendable sensitivity (where the limit of detection is down to 0.51 pM) and even an outstanding specificity for distinguishing single-base mismatching. Beyond this sound assay performance, our sensing approach is capable of working as a powerful imaging platform for accurately operating in various living specimens such as cells and bodies, showing a favorable diagnostic ability for cancer care.

Monitoring of viral myocarditis injury using an energy-confined upconversion nanoparticle and nature-inspired biochip combined CRISPR/Cas12a-powered biosensor.

The early diagnosis and timely intervention of viral myocarditis urgently require a noninvasive detection approach. Therefore, we present a CRISPR/Cas12a-powered biosensor that integrates an exceptionally efficient upconversion luminescent resonance energy transfer (LRET) with a nature-inspired biochip to determine a golden-standard cardiac biomarker (cardiac troponin I). First, a unique sandwich-structured energy-confined upconversion nanoparticle (acting as the energy donor) is synthesized to dramatically reinforce the LRET's ability. Such a structural improvement endows a relatively high quenching efficiency (as much as 93.8%) toward the surface acceptors and enhances the working adaption in complicated biological media. Moreover, a three-dimensional photonic crystal fabricated using a self-assembly of nanospheres is employed to construct a biochip interface, under which the upconversion luminescence is prominently boosted to approximately 27-fold to achieve signal amplification. Finally, the newly developed luminescence sensing method exhibits remarkable assay performance after introducing these attempts into a dual-aptamer-regulated CRISPR/Cas12a system to transduce the target. More importantly, this biosensor can primarily be a quite useful tracer tool to allow dynamic monitoring of the entire myocardial injury process in a coxsackievirus B3 infected mouse model, paving an attractive venue for medical diagnostic techniques.

A Photoresponsive and Metal-Organic Framework Encapsulated DNA Tetrahedral Entropy-Driven Amplifier for High-Performance Imaging Intracellular MicroRNA.

The further development of high-performance fluorescent biosensors to image intracellular microRNAs is beneficial to cancer medicine. By virtue of the need for enzymes and hairpin DNA probes, the entropy-driven reaction-assisted signal amplification strategy has shown an enormous potential to accomplish this task. Nevertheless, this good option still meets with poor biostability, low cell uptake efficiency, and unsatisfactory accuracy. On the basis of these challenges, we put forward here a battery of solving pathways. First, the straight DNA probes are anchored onto the vertexes of dual DNA tetrahedrons, and thus the enzyme resistance of the whole sensing system is observably enhanced. A metal-organic framework (ZIF-8 nanoparticle), which can be effectively dissociated into a weakly acidic environment, then is employed as an additional delivery vehicle to encapsulate such a DNA tetrahedron sustained biosensor and finally bring about a more efficient endocytosis. Last, a kind of photocleavage-linker triggered photoresponsive manner is incorporated to achieve an exceptional precise target identification, by which the biosensor can only be initiated under the irradiation of an externally mild 365 nm ultraviolet light source. In accordance with the above efforts, worthy assay performance toward microRNA-196a has given rise to this newly constructed biosensor, whose sensitivity is down to 2.7 pM and also able to distinguish single-base variation. Beyond that, the amplifier can work as a powerful imaging toolbox to accurately determine the targets in living cells, providing a promising intracellular sensing platform.