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While numerous methods exist for diagnosing tumors through the detection of miRNA within tumor cells, few can simultaneously achieve both tumor diagnosis and treatment. In this study, a novel graphene oxide (GO)-based DNA nanodevice (DND), initiated by miRNA, was developed for fluorescence signal amplification imaging and photodynamic therapy in tumor cells. After entering the cells, tumor-associated miRNA drives DND to Catalyzed hairpin self-assembly (CHA). The CHA reaction generated a multitude of DNA Y-type structures, resulting in a substantial amplification of Ce6 fluorescence release and the generation of numerous singlet oxygen (1O2) species induced by laser irradiation, consequently inducing cell apoptosis. In solution, DND exhibited high selectivity and sensitivity to miRNA-21, with a detection limit of 11.47 pM. Furthermore, DND discriminated between normal and tumor cells via fluorescence imaging and specifically generated O21 species in tumor cells upon laser irradiation, resulting in tumor cells apoptosis. The DND offer a new approach for the early diagnosis and timely treatment of malignant tumors.

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Objective: Current scoring systems for short-term prognosis in patients with acute myocardial infarction (AMI) lack coverage of risk factors and have limitations in risk stratification. The aim of this study was to develop a novel assessment system based on laboratory indicators and frailty quantification to better infer short-term prognosis and risk indication in patients with AMI. Methods: A total of 365 patients with MI from January 2022 to June 2023 in Northern Jiangsu Province Hospital were included. The primary endpoint was all-cause mortality and major adverse cardiac events (MACE) during follow-up. A novel scoring model ranging from 0 to 12 was constructed, and the predictive ability of this scoring system was evaluated using the area under the receiver operating characteristic curve (AUC). Results: During follow-up, 68 patients experienced MACE. Five scoring indicators were selected through multivariate logistic regression analysis, resulting in a composite score with an AUC of 0.925, demonstrating good prognostic accuracy. Conclusion: The novel prognostic assessment system, which integrates age, Stress Hyperglycemia Ratio (SHR), Neutrophil to Lymphocyte Ratio (NLR), lactate, and frailty score, exhibits good predictive value for short-term MACE in patients with acute myocardial infarction and may enable more accurate risk classification for future use in MI patient risk management.

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Treating bone infections with common antibiotics is challenging, since pathogens like Staphylococcus aureus can reside inside macrophages. To target these intracellular bacteria, we have proposed nanoparticles (NPs) as drug carriers. This study aims to investigate the efficacy of hydroxyapatite and gelatin NPs, selected in view of their bone mimicry and potential for targeted delivery, as carriers for the antibacterial agents zinc and vancomycin. Therefore, two distinct NPs are fabricated: zinc-doped hydroxyapatite (ZnHA) and vancomycin-loaded gelatin (VGel) NPs. The NPs are characterized based on morphology, size, chemical composition, cellular internalization, and intracellular bactericidal efficacy. Specifically, the intracellular bactericidal efficacy is tested using a validated coculture model of human THP-1 derived macrophages and phagocytosed S. aureus bacteria. Scanning electron microscopy (SEM) and Fourier transform-infrared spectroscopy (FTIR) results show that the spherical NPs are synthesized successfully. These NPs are internalized by THP-1 cells and show >75% colocalization with lysosomes without compromising the viability of the THP-1 cells. Both ZnHA and VGel NPs substantially reduce the intracellular survival of S. aureus compared to the direct addition of dissolved zinc and vancomycin. Concluding, our NPs are highly effective drug delivery vehicles to kill intracellular S. aureus, which stress the potential of these NPs for future clinical translation.

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Importance: In May 2021, the US Preventive Services Task Force (USPSTF) issued a grade B recommendation encouraging colorectal cancer (CRC) screening among average-risk individuals aged 45 to 49 years. The patterns of screening uptake and possible socioeconomic disparities in screening in this age group remain unknown. Objective: To evaluate changes in CRC screening uptake among average-risk individuals aged 45 to 49 years after the USPSTF recommendation was issued in 2021. Design, Setting, and Participants: This retrospective cohort study used deidentified claims data from commercially insured Blue Cross Blue Shield beneficiaries aged 45 to 49 years across the US between January 1, 2017, and December 31, 2022. Exposure: Publication of the May 2021 USPSTF CRC screening recommendation for adults aged 45 to 49 years. Main Outcomes and Measures: Absolute and relative changes in screening uptake were compared between a 20-month period preceding (May 1, 2018, to December 31, 2019) and a 20-month period following (May 1, 2021, to December, 31, 2022) the USPSTF recommendation. Interrupted time-series analysis and autoregressive integrated moving average models were used to evaluate changes in screening rates, adjusting for temporal autocorrelation and seasonality. Results: In this cohort study of 10 221 114 distinct beneficiaries aged 45 to 49 years (mean [SD] age, 47.04 [1.41] years; 51.04% female), bimonthly mean (SD) numbers of average-risk beneficiaries were 3 213 935 (31 508) and 2 923 327 (105 716) in the prerecommendation and postrecommendation periods, respectively. Mean (SD) screening uptake increased from 0.50% (0.02%) to 1.51% (0.59%) between the 2 periods (P < .001), representing an absolute change of 1.01 percentage points (95% CI, 0.62-1.40 percentage points) but no significant relative change (202.51%; 95% CI, -30.59% to 436.87%). Compared with average-risk beneficiaries residing in areas with the lowest socioeconomic status (SES), those residing in areas with the highest SES experienced the largest absolute change in screening (1.25 [95% CI, 0.77-1.74] percentage points vs 0.75 [95% CI, 0.47-1.02] percentage points), but relative changes were not significant (214.01% [95% CI, -30.91% to 461.15%] vs 167.73% [95% CI, -16.30% to 352.62%]). After the recommendation was issued, the screening uptake rate also increased fastest among average-risk beneficiaries residing in the areas with highest SES (0.24 [95% CI, 0.23-0.25] percentage points every 2 months) and metropolitan areas (0.20 [95% CI, 0.19-0.21] percentage points every 2 months). Conclusions and Relevance: This study found that among privately insured beneficiaries aged 45 to 49 years, CRC screening uptake increased after the USPSTF recommendation, with potential disparities based on SES and locality.

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Botulinum neurotoxins (BoNTs), including serotypes A and E, are potent biotoxins known to cause human poisoning. In addition to the critical protective antigen found in the full BoNT molecule, the receptor binding domain (Hc domain), BoNTs also harbour another essential protective antigen-the light chain-translocation domain (L-HN domain). Leveraging these pivotal protective antigens, we genetically engineered a series of inactivated chimeric molecules incorporating L-HN and Hc domains of BoNT/A and E. The structure of these chimeric molecules, mirror BoNT/A and E, but are devoid of enzyme activity. Experimental findings demonstrated that a lead candidate mEL-HN-mAHc harnessing the inactivated protease LCHN/E with the mutated gangliosides binding site Hc/A (mE-mA) elicited robust immune protection against BoNT/A and E simultaneously in a mouse model, requiring low immune dosages and minimal immunisations. Moreover, mE-mA exhibited high protective efficacy against BoNT/A and E in guinea pigs and New Zealand white rabbits, resulting in elevated neutralising antibody titres. Furthermore, mE-mA proved to be a more stable and safer vaccine compared to formaldehyde-inactivated toxoid. Our data underscore the genetically engineered mE-mA as a highly effective bivalent vaccine against BoNT/A and E, paving the way for the development of polyvalent vaccines against biotoxins.

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With rapid advancements in health and human-computer interaction, wearable electronic skins (e-skins) designed for application on the human body provide a platform for real-time detection of physiological signals. Wearable strain sensors, integral functional units within e-skins, can be integrated with Internet of Things (IoT) technology to broaden the applications for human body monitoring. A significant challenge lies in the reliance of most existing wearable strain sensors on rigid external power supplies, limiting their practical flexibility. In this study, we present an innovative strategy to fabricate glutaraldehyde (GA)-poly(vinyl alcohol) (PVA)/cellulose nanocrystals (CNC)/Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) conductive hydrogels through multiple hydrogen bonding systems. Combining the advantageous rheological properties of the precursor solution and the high specific surface area after freeze-thaw cycling, we have created a self-powered sensing system prepared by large-area printing using direct ink writing (DIW) printing. The resulting conductive hydrogel exhibits commendable mechanical properties (411 KPa), impressive stretchability (580 %), and robust self-healing capabilities (>98.3 %). The strain sensor, derived from the conductive hydrogel, demonstrates a gauge factor (GF) of 2.5 within a stretching range of 0-580 %. Additionally, the resultant supercapacitor displays a peak energy density of 0.131 mWh/cm3 at a power density of 3.6 mW/cm3. Benefiting from its elevated strain response and remarkable power density features, this self-powered strain sensing system enables the real-time monitoring of human joint motion. The incorporation of a 5G transmission module enhances its capabilities for remote data monitoring, thereby contributing to the progress of wireless tracking technologies for self-powered electronic skin.

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Despite the widespread detection of polybrominated diphenyl ethers in aquatic ecosystems, their long-term effects on sediment multifunctionality remain unclear. Herein, a 360-day microcosm experiment was conducted to investigate how decabromodiphenyl ether (BDE-209) contamination at different levels (0.2, 2, and 20 mg/kg dry weight) affects sediment multifunctionality, focusing on carbon (C), nitrogen (N), phosphorus (P), and sulfur (S) cycling. Results showed that BDE-209 significantly increased sediment total organic carbon, nitrate, ammonium, available phosphorus, and sulfide concentrations, but decreased sulfate. Additionally, BDE-209 significantly altered key enzyme activities related to nutrient cycling. Bacterial community dissimilarity was positively correlated with nutrient variability. Long-term BDE-209 exposure inhibited C degradation, P transport and regulation, and most N metabolic pathways, but enhanced C fixation, methanogenesis, organic P mineralization, inorganic P solubilization, and dissimilatory sulfate reduction pathways. These changes were mainly regulated by microbial ecological clusters and keystone taxa. Overall, sediment multifunctionality declined under BDE-209 stress, primarily related to microbial co-occurrence network complexity and ecological cluster diversity. Interestingly, sediment C and N cycling had greater impacts on multifunctionality than P and S cycling. This study provides crucial insights into the key factors altering multifunctionality in contaminated sediments, which will aid pollution control and mitigation in aquatic ecosystems.

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Botulinum toxin (BoNT) from Clostridium botulinum is the most toxic biotoxin known and is also an important bioterrorism agent. After poisoning, the only effective treatment is injection of antitoxin. However, neutralizing nanoantibodies are safer and more effective, representing a promising therapeutic approach. Therefore, it is important to obtain effective neutralizing nanoantibodies. Hence, the present study aimed to construct a phage antibody library by immunizing a camel and screening specific clones that bind to the L-HN domain of BoNT/F and constructing chimeric heavy-chain antibodies by fusing them with a human Fc fragment. The antibodies' affinity and in vivo neutralizing activities were evaluated. The results showed that 2 µg of F20 antibody could completely neutralize 20 × the median lethal dose (LD50) of BoNT/F in vitro. Injection of 5 mg/kg F20 at 1 h, 2 h, 3 h, and 4 h into mice after BoNT/F challenge resulted in complete survival in vivo. Overall, the antibody might be a candidate for the development of new drugs to treat botulism.

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Purpose: Cough and sputum are the most common clinical symptoms of acute respiratory tract infection. Ambroxol is a mucolytic expectorant commonly used in clinical practice. This study aimed to evaluate the efficacy, safety, and compliance of ambroxol hydrochloride spray (Luo Runchang ®) for the treatment of acute respiratory tract diseases in children. Methods: This was a multicenter, open-labeled, randomized controlled study. The experimental group received ambroxol hydrochloride oral sprays, and the control group received ambroxol hydrochloride oral solutions. The primary endpoint was the change in cough symptom scores from baseline. Secondary endpoints include changes in cough severity score, quality of life, adherence, and adverse events. Results: A total of 154 subjects were randomized and included in the analysis. The mean change of total cough symptom score of the spray group at the end of treatment was -4.7 (1.54) compared to -4.2 (1.62) in the solution group (P = 0.0005). The mean change of cough severity score was -5.7 (2.09) in the spray group compared to -5.2(2.04) in the solution group (P = 0.012). Quality of life scores significantly improved in the spray group (P < 0.0001) compared to the oral solution group. Medication adherence markers were significantly better in the spray group (P < 0.0001). The incidence of adverse events in the experimental group (1.33%) was lower than that in the control group (6.33%), but the difference between the groups was not statistically significant. Conclusion: Ambroxol hydrochloride spray significantly improved cough symptom score, cough severity score, and quality of life score compared to ambroxol hydrochloride oral solution.

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BACKGROUND: Catheter-related bladder discomfort (CRBD) commonly occurs in patients who have indwelling urinary catheters while under general anesthesia. And moderate-to-severe CRBD can lead to significant adverse events and negatively impact patient health outcomes. However, current screening studies for patients experiencing moderate-to-severe CRBD after waking from general anesthesia are insufficient. Constructing predictive models with higher accuracy using multiple machine learning techniques for early identification of patients at risk of experiencing moderate-to-severe CRBD during general anesthesia resuscitation. METHODS: Eight hundred forty-six patients with indwelling urinary catheters who were resuscitated in a post-anesthesia care unit (PACU). Trained researchers used the CRBD 4-level assessment method to evaluate the severity of a patient's CRBD. They then inputted 24 predictors into six different machine learning algorithms. The performance of the models was evaluated using metrics like the area under the curve (AUC). RESULTS: The AUCs of the six models ranged from 0.82 to 0.89. Among them, the RF model displayed the highest predictive ability, with an AUC of 0.89 (95%CI: 0.87, 0.91). Additionally, it achieved an accuracy of 0.93 (95%CI: 0.91, 0.95), 0.80 sensitivity, 0.98 specificity, 0.94 positive predictive value (PPV), 0.92 negative predictive value (NPV), 0.87 F1 score, and 0.07 Brier score. The logistic regression (LR) model has achieved good results (AUC:0.87) and converted into a nomogram. CONCLUSIONS: The study has successfully developed a machine learning prediction model that exhibits excellent predictive capabilities in identifying patients who may develop moderate-to-severe CRBD after undergoing general anesthesia. Furthermore, the study also presents a nomogram, which serves as a valuable tool for clinical healthcare professionals, enabling them to intervene at an early stage for better patient outcomes.

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Current studies have not clarified the relationship between riboflavin intake and all-cause mortality in patients with chronic kidney disease (CKD). The aim of this study is to investigate whether there is an association between riboflavin intake and the risk of all-cause mortality in patients with CKD. This was a retrospective cohort study with data extracted from the National Health and Nutrition Examination Survey (NHANES). The study was conducted using Cox regression analysis to calculate hazard ratio (HR) and 95% confidence interval (CI) to assess the association between riboflavin intake and risk of all-cause mortality. Subgroup analyses were performed regarding gender, CKD stage, hypertension, hyperlipidemia and cardiovascular disease (CVD). A total of 3750 patients were ultimately included in the analyses. After excluding potential confounders, lower intake of riboflavin was associated with the higher risk of all-cause mortality (Q1: HR = 1.33, 95% CI: 1.05-1.69). The similar association was also found in patients at mild/moderate stage (HR = 1.32, 95% CI: 1.05-1.66), in female (HR = 1.35, 95% CI: 1.01-1.81), with hypertension (HR = 1.37, 95% CI: 1.07-1.75), CVD (HR = 1.48, 95% CI: 1.08-2.03), and dyslipidemia (HR = 1.29, 95% CI: 1.01-1.66). This study found the association between low riboflavin intake and high risk of all-cause mortality, indicating a potential beneficial role of riboflavin in CKD patients.

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Mitochondrial dysfunction is a significant contributor to podocyte injury in diabetic kidney disease (DKD). While previous studies have shown that PVT1 might play a vital role in DKD, the precise molecular mechanisms are largely unknown. By analyzing the plasma and kidney tissues of DKD patients, we observed a significant upregulation of PVT1 expression, which exhibited a positive correlation with albumin/creatinine ratios and serum creatinine levels. Then, we generated mice with podocyte-specific deletion of PVT1 (Nphs2-Cre/Pvt1flox/flox) and confirmed that the deletion of PVT1 suppressed podocyte mitochondrial dysfunction and inflammation in addition to ameliorating diabetes-induced podocyte injury, glomerulopathy, and proteinuria. Subsequently, we cultured podocytes in vitro and observed that PVT1 expression was upregulated under hyperglycemic conditions. Mechanistically, we demonstrated that PVT1 was involved in mitochondrial dysfunction by interacting with TRIM56 post-transcriptionally to modulate the ubiquitination of AMPKα, leading to aberrant mitochondrial biogenesis and fission. Additionally, the release of mtDNA and mtROS from damaged mitochondria triggered inflammation in podocytes. Subsequently, we verified the important role of TRIM56 in vivo by constructing Nphs2-Cre/Trim56flox/flox mice, consistently with the results of Nphs2-Cre/Pvt1flox/flox mice. Together, our results revealed that upregulation of PVT1 could promote mitochondrial dysfunction and inflammation of podocyte by modulating TRIM56, highlighting a potential novel therapeutic target for DKD.

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Flavonoids, the largest class of polyphenols, exhibit substantial structural and functional diversity, yet their evolutionary diversification and specialized functions remain largely unexplored. The genus Scutellaria is notable for its rich flavonoid diversity, particularly the 6/8-hydroxylated variants biosynthesized by the cytochrome P450 subfamily CYP82D. Our study analyzes metabolic differences between Scutellaria baicalensis and Scutellaria barbata, suggesting that CYP82Ds have acquired a broad range of catalytic functions over their evolution. By integrating analyses of metabolic networks and gene evolution across 22 Scutellaria species, we rapid identified 261 flavonoids and delineated five clades associated with various catalytic functions of CYP82Ds. This approach uncovered a unique catalytic mode for 6/8-hydroxylated function under flavanone substrates and the first instance of 7-O-demethylation of flavonoid substrates catalyzed by cytochrome P450. Ancestral sequence reconstruction and functional validation demonstrated that gradual neofunctionalization of CYP82Ds has driven the chemical diversity of flavonoids in Scutellaria throughout its evolutionary history. Our study enhances the understanding of flavonoid diversity, elucidates the intricate roles of CYP82Ds in Scutellaria plants, and underscores the extensive catalytic versatility of cytochrome P450 members within plant taxa.

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Myocardial infarction (MI) is the primary source of death in cardiovascular diseases. Myricitrin (MYR) is a phenolic compound known for its antioxidant properties. This study aimed to investigate the impact of MYR alone or combined with exercise on a rat model of MI and its underlying mechanism. Sprague-Dawley rats were randomized into 5 groups: sham-operated (Sham), MI-sedentary (MI-Sed), MI-exercise (MI-Ex), MI-sedentary + MYR (MI-Sed-MYR) and MI-exercise + MYR (MI-Ex-MYR). MI was induced through ligation of left anterior descending coronary artery. The treatment with exercise or MYR (30 mg/kg/d) gavage began one week after surgery, either individually or in combination. After 8 weeks, the rats were assessed for cardiac function. Myocardial injuries were estimated using triphenyltetrazolium chloride, sirius red and Masson staining. Changes in reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), apoptosis and Nrf2/HO-1 pathway were analyzed by ROS kit, JC-1 kit, TUNEL assay, Western blot and immunohistochemistry. Both MYR and exercise treatments improved cardiac function, reduced infarct size, suppressed collagen deposition, and decreased myocardial fibrosis. Additionally, both MYR and exercise treatments lowered ROS production induced by MI, restored ΔΨm, and attenuated oxidative stress and apoptosis in cardiomyocytes. Importantly, the combination of MYR and exercise showed greater efficacy compared to individual treatments. Mechanistically, the combined intervention activated the Nrf2/HO-1 signaling pathway. These findings suggest that the synergistic effect of MYR and exercise may offer a promising therapeutic approach for alleviating MI.

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Nitrate (NO3-) is an important contributor to PM2.5 which can adversely affect the environment and human health. A noticeable decrease in NOx concentrations has been reported due to the lockdown measures implemented to curb the spread of Corona Virus Disease 2019 (COVID-19). However, questions remain, regarding the nonlinear relationship between NOx and NO3-. Here, we collected PM2.5 samples in two periods, before and during the lockdown of COVID-19 in Shanghai. Dual isotopes (δ18O-NO3- and δ15N-NO3-) of NO3- were measured to investigate the formation pathways and potential sources of NO3-. The results showed that the concentration of NO3- decreased significantly during the lockdown period compared to the period before the lockdown. Additionally, the hydroxyl pathway was the dominant contributor to NO3- production during the lockdown period, while N2O5 hydrolyses dominated the formation of NO3- before the lockdown. This change is largely attributable to alterations in the oxidative potential of the environment. In comparison to the period preceding the lockdown, the relative contributions of each NOx source remained largely unchanged throughout the lockdown periods. Nevertheless, the concentration of NO3- contributed by each NOx source exhibited a notable decline, particularly the mobile sources and coal combustion. Furthermore, the reduction extent of NO3- due to the lockdown period was also greater than the reduction during the Clean Air Actions (2013-2017). Our findings provide evidence that the COVID-19 lockdown led to a decrease in NO3- concentration due to changes in the formation pathway and reductions in NOx emissions from various sources.

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The aim of this report was to evaluate the efficacy of nasal reconstruction using auricular cartilage combined with auricular full-thickness skin graft and a local flap from the right nasal ala for correcting complex nasal defects, and its impact on the patient's quality of life and psychological well-being. We present the case of a 50-year-old female with a severe nasal deformity due to a car accident, characterized by a missing right alar flap and an exposed right nostril. The patient underwent nasal reconstructive surgery using auricular cartilage combined with an auricular full-thickness skin graft and a local flap from the right nasal ala. Detailed records of the patient's postoperative recovery, surgical outcomes, and satisfaction were made at follow-up. The survival rate of the grafted skin and flaps on the nasal ala, septum, and dorsum was high. The reconstructed right nasal ala closely resembled the left, and the patient was very satisfied. In patients with complex nasal deformities, nasal reconstruction using ear cartilage combined with auricular full-thickness skin grafts and local flaps can achieve satisfactory aesthetic and functional outcomes. The high level of postoperative satisfaction suggests that this technique significantly improves patients' quality of life and psychological well-being.

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BACKGROUND: Despite the increased accessibility and availability of technology in recent years, equality and access to health-related technology remain limited to some demographics. In particular, patients who are older or from rural communities represent a large segment of people who are currently underusing mobile health (mHealth) solutions. System usability continues to hinder mHealth adoption among users with nontraditional digital literacy. OBJECTIVE: This study aims to investigate if state-of-the-art mobile app interfaces from open-source libraries provide sufficient usability for rural patients with cancer, with minimal design changes and forgoing the co-design process. METHODS: We developed Assuage (Network Reconnaissance Lab) as a research platform for any mHealth study. We conducted a pilot study using Assuage to assess the usability of 4 mobile user interfaces (UIs) based on open-source libraries from Apple's ResearchKit and CareKit. These UIs varied in complexity for reporting distress symptoms. Patients with cancer were recruited at the Markey Cancer Center, and all research procedures were conducted in person. Participants completed the distress assessment using a randomly selected UI in Assuage with little to no assistance. Data were collected on participant age, location, mobile app use, and familiarity with mHealth apps. Participants rated usability with the System Usability Scale (SUS), and usability issues were documented and compared. A one-way ANOVA was used to compare the effect of the UIs on the SUS scores. RESULTS: We recruited 30 current or postsurgery patients with cancer for this pilot study. Most participants were aged >50 years (24/30, 80%), from rural areas (25/30, 83%), had up to a high school education (19/30, 63%), and were unfamiliar with mHealth apps (21/30, 70%). General mobile app use was split, with 43% (14/30) of the patients not regularly using mobile apps. The mean SUS score across the UIs was 75.8 (SD 22.2), with UI 3 and UI 4 achieving an SUS score ≥80, meeting the industry standard for good usability of 80. Critical usability issues were related to data input and navigation with touch devices, such as scale-format questions, vertical scrolling, and traversing multiple screens. CONCLUSIONS: The findings from this study show that most patients with cancer (20/30, 67%) who participated in this study rated the different interfaces of Assuage as above-average usability (SUS score >68). This suggests that Apple's ResearchKit and CareKit libraries can provide usable UIs for older and rural users with minimal interface alterations. When resources are limited, the design stage can be simplified by omitting the co-design process while preserving suitable usability for users with nontraditional technical proficiency. Usability comparable to industry standards can be achieved by considering heuristics for interface and electronic survey design, specifically how to segment and navigate surveys, present important interface elements, and signal gestural interactions.

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The subcellular localization of messenger RNA (mRNA) not only helps us to understand the localization regulation of gene expression but also helps to understand the relationship between RNA localization pattern and human disease mechanism, which has profound biological and medical significance. Several predictors have been proposed for predicting the subcellular localization of mRNA. However, there is still considerable room for improvement in their predictive performance, especially regarding multi-label prediction. This study proposes a novel multi-label predictor, DRpred, for mRNA subcellular localization prediction. This predictor first utilizes Bayesian networks to capture the dependencies among labels. Subsequently, it combines these dependencies with features extracted from mRNA sequences using Word2vec, forming the input for the predictor. Finally, it employs a neural network combining BiLSTM and an attention mechanism to capture the internal relationships of the input features for mRNA subcellular localization. The experimental validation on an independent test set demonstrated that DRpred obtained a competitive predictive performance in multi-label prediction and outperformed state-of-the-art predictors in predicting single subcellular localizations, obtaining accuracies of 82.14%, 93.02%, 80.37%, 94.00%, 90.58%, 84.53%, 82.01%, 79.71%, and 85.67% for the chromatin, cytoplasm, cytosol, exosome, membrane, nucleolus, nucleoplasm, nucleus, and ribosome, respectively. It is anticipated to offer profound insights for biological and medical research.

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Local delivery of messenger ribonucleic acid (mRNA) is increasingly being advocated as a promising new strategy to enhance the performance of biomaterials. While extensive research has been dedicated to the complexation of these oligonucleotides into nanoparticles to facilitate systemic delivery, research on developing suitable biomaterial carriers for the local delivery of mRNA is still scarce. So far, mRNA-nanoparticles (mRNA-NPs) are mainly loaded into traditional polymeric hydrogels. Here, we show that calcium phosphate nanoparticles can be used for both reinforcement of nanoparticle-based hydrogels and the complexation of mRNA. mRNA was incorporated into lipid-coated calcium phosphate nanoparticles (LCPs) formulated with a fusogenic ionizable lipid in the outer layer of the lipid coat. Nanocomposites of gelatin and hydroxyapatite nanoparticles were prepared at various ratios. Higher hydroxyapatite nanoparticle content increased the viscoelastic properties of the nanocomposite but did not affect its self-healing ability. Combination of these nanocomposites with peptide, lipid, and the LCP mRNA formulations achieved local mRNA release as demonstrated by protein expression in cells in contact with the biomaterials. The LCP-based formulation was superior to the other formulations by showing less sensitivity to hydroxyapatite and the highest cytocompatibility.

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