Bimetallic Nanozyme: A Credible Tag for In Situ-Catalyzed Reporter Deposition in the Lateral Flow Immunoassay for Ultrasensitive Cancer Diagnosis.

The lateral flow immunoassay (LFIA) is a sought-after point-of-care testing platform, yet the insufficient sensitivity of the LFIA limits its application in the detection of tumor biomarkers. Here, a colorimetric signal amplification method, bimetallic nanozyme-mediated in situ-catalyzed reporter deposition (BN-ISCRD), was designed for ultrasensitive cancer diagnosis. The bimetallic nanozyme used, palladium@iridium core-shell nanoparticles (Pd@Ir NPs), had ultrahigh enzyme-like activity, which was further explained by the electron transfer of Pd@Ir NPs and the change in the Gibbs free energy during catalysis through density functional theory calculations. With gastric cancer biomarkers pepsinogen I and pepsinogen II as model targets, this assay could achieve a cutoff value of 10 pg/mL, which was 200-fold lower than that without signal enhancement. The assay was applied to correctly identify 8 positive and 28 negative clinical samples. Overall, this BN-ISCRD-based LFIA showed great merits and potential in the application of ultrasensitive disease diagnosis.

TEAD4 antagonizes cellular senescence by remodeling chromatin accessibility at enhancer regions.

Dramatic alterations in epigenetic landscapes are known to impact genome accessibility and transcription. Extensive evidence demonstrates that senescent cells undergo significant changes in chromatin structure; however, the mechanisms underlying the crosstalk between epigenetic parameters and gene expression profiles have not been fully elucidated. In the present study, we delineate the genome-wide redistribution of accessible chromatin regions that lead to broad transcriptome effects during senescence. We report that distinct senescence-activated accessibility regions (SAAs) are always distributed in H3K27ac-occupied enhancer regions, where they are responsible for elevated flanking senescence-associated secretory phenotype (SASP) expression and aberrant cellular signaling relevant to SASP secretion. Mechanistically, a single transcription factor, TEAD4, moves away from H3K27ac-labled SAAs to allow for prominent chromatin accessibility reconstruction during senescence. The enhanced SAAs signal driven by TEAD4 suppression subsequently induces a robust increase in the expression of adjacent SASP genes and the secretion of downstream factors, which contribute to the progression of senescence. Our findings illustrate a dynamic landscape of chromatin accessibility following senescence entry, and further reveal an insightful function for TEAD4 in regulating the broad chromatin state that modulates the overall transcriptional program of SASP genes.

Exploring the relationship between malnutrition and the systemic immune-inflammation index in older inpatients: a study based on comprehensive geriatric assessment.

BACKGROUND: Malnutrition is a prevalent and major challenge among senior citizens, possibly due to the continual low-grade inflammatory state of the body. A novel inflammatory parameter, the systemic immune-inflammation index (SII), is highly valuable in evaluating and predicting the prognosis of a wide range of diseases. This study aims to explore the significance of the SII in assessing malnutrition in older inpatients. METHODS: This retrospective study included 500 senior hospitalized patients who met the inclusion and exclusion criteria from the Comprehensive Geriatric Assessment database of the First Hospital of Jilin University. The Mini-Nutritional Assessment (MNA) questionnaire was used to evaluate the nutritional status of patients. The SII was calculated using complete blood counts, and we performed natural logarithm transformation of the SII [ln(SII)]. Multivariable logistic regression analysis was used to identify the association between ln(SII) and malnutrition. To ensure the stability of the findings, a sensitivity analysis was conducted. RESULTS: The 500 patients had a mean age of 77.29 ± 9.85 years, and 68.6% were male. In accordance with the MNA, 30.4% of the patients were malnourished or at risk of malnutrition, and patients in this group had considerably greater levels of ln(SII) than patients with adequate nutrition (P < 0.001). The optimum ln(SII) cutoff value for patients with malnutrition or at risk of malnutrition was 6.46 (SII = 635.87) with 46.7% sensitivity and 80.2% specificity [95% CI: 0.613-0.721, AUC: 0.667, P < 0.001]. Multivariable logistic regression demonstrated that ln(SII) was an independent risk factor for the risk of malnutrition or malnutrition in older individuals (OR 3.984, 95% CI: 2.426-6.543, P < 0.001). Other metrics from the geriatric comprehensive assessment, including body mass index, calf circumference, fat ratio, activities of daily living and instrumental activities of daily living, and geriatric depression scale scores, were also independently correlated with nutritional status. CONCLUSIONS: According to our research, a high SII is an independent predictor of older inpatient malnutrition, and the SII aids in screening for malnutrition and may be a potential target for intervention. Comprehensive geriatric assessment parameters such as BMI, calf circumference, fat ratio, activities of daily living and depression were also linked to malnutrition.

The prediction model of the short-term outcome in elderly heart failure patients.

This study was designed to investigate the effect of the comprehensive geriatric assessment on the short-term prognosis of the elderly heart failure patients (EHFP), analyze the relevant risk factors, and construct an effective risk prediction model. According to the selection and exclusion criteria, 617 patients were filtered from 800 patients from the cadre ward database of the first Hospital of Jilin University. The EHFP were randomly divided into the model group (432 cases) and the validation group (185 cases). A retrospective study on the general clinical data of patients in the model group was conducted to analyze the risk factors associated with the short-term outcomes of EHFP. Based on the risk factors, the risk prediction model was established and validated through the validation group. In the model group, the following independent risk factors were identified for the short-term outcomes in EHFP in the light of univariate logistic and cox regression analysis: female (ß = 0.989, OR = 1.277, 95% CI: 1.090-1.847, P = 0.024), age (65-75 years, ß = 0.654, OR = 2.320, 95% CI: 1.135-3.136, P = 0.012; 75-85 years, ß = 1.123, OR = 3.159, 95% CI: 1.532-5.189, P = 0.001; age > 85 years old, ß = 1.513, OR = 4.895, 95% CI: 1.866-979, P = 0.001), frailty (ß = 1.015, OR = 2.761, 95% CI: 1.097-6.945, P = 0.031), malnutrition (ß = 1.271, OR = 3.560, 95% CI: 1.122-11.325, P = 0.002), and EF≦40% (ß = 1.250, OR = 3.498, 95% CI: 1.898-6.447, P = 0.001). The simple risk prediction score was set up in line with the five risk factors, including range (1-7), the area under ROC curve (0.771, 95% CI: 0.723-0.819), and H-L test (P = 0.393), so patients were divided into the low-risk group (1-3) and the high-risk group (4-8). As a result, the number of EHFP in the high-risk group was significantly much more than that in the low-risk group (70.1% versus 29.9%, P < 0.001). Besides, the area under ROC curve (0.758, 95% CI: 0.682-0.835) and H-L test (P = 0.669) of the validation group indicated that this model could be a promising prediction model for the short-term outcomes of EHFP. Female, age, frailty, malnutrition, and EF ≦ 40% are independent risk factors for short-term outcomes of EHFP. The risk prediction model based on the five risk factors provided compelling clinic predictive value for the short-term prognosis of EHFP.

A Universal Bacterial Catcher Au-PMBA-Nanocrab-Based Lateral Flow Immunoassay for Rapid Pathogens Detection.

In traditional lateral flow immunoassays (LFIA) for pathogens detection, capture antibody (CA) is necessary and usually conjugated to Au nanoparticles (NPs) in order to label the target analyte. However, the acquisition process of the Au-CA nanoprobe is relatively complicated and costly, which will limit the application of LFIA. Herein, p-mercaptophenylboronic acid-modified Au NPs (namely Au-PMBA nanocrabs), were synthesized and applied for a new CA-independent LFIA method. The stable Au-PMBA nanocrabs showed outstanding capability to capture both Gram-negative bacteria and Gram-positive bacteria through covalent bonding. The acquired Au-PMBA-bacteria complexes were dropped onto the strip, and then captured by the detection antibody on the test line (T-line). Take Escherichia coli O157:H7 as an example, the gray value of T-line was proportional to the bacteria concentration and the linear range was 103-107 cfu·mL-1. This CA-independent strategy exhibited higher sensitivity than the traditional CA-dependent double antibody sandwich method, because detection limit of the former one was 103 cfu·mL-1 only by visual observation, which was reduced by 3 orders of magnitude. Besides, this platform successfully screened E. coli O157:H7 in four food samples with recoveries ranging from 90.25% to 107.25%. This CA-independent LFIA showed great advantages and satisfactory potential for rapid foodborne pathogens detection in real samples.

Metal and Metal Oxide Nanomaterials for Fighting Planktonic Bacteria and Biofilms: A Review Emphasizing on Mechanistic Aspects.

The misuse and mismanagement of antibiotics have made the treatment of bacterial infections a challenge. This challenge is magnified when bacteria form biofilms, which can increase bacterial resistance up to 1000 times. It is desirable to develop anti-infective materials with antibacterial activity and no resistance to drugs. With the rapid development of nanotechnology, anti-infective strategies based on metal and metal oxide nanomaterials have been widely used in antibacterial and antibiofilm treatments. Here, this review expounds on the state-of-the-art applications of metal and metal oxide nanomaterials in bacterial infective diseases. A specific attention is given to the antibacterial mechanisms of metal and metal oxide nanomaterials, including disrupting cell membranes, damaging proteins, and nucleic acid. Moreover, a practical antibiofilm mechanism employing these metal and metal oxide nanomaterials is also introduced based on the composition of biofilm, including extracellular polymeric substance, quorum sensing, and bacteria. Finally, current challenges and future perspectives of metal and metal oxide nanomaterials in the anti-infective field are presented to facilitate their development and use.

The correlation between nutrition and frailty and the receiver operating characteristic curve of different nutritional indexes for frailty.

BACKGROUND: Frailty is a kind of geriatric syndrome, which is very common in the elderly. Patients with malnutrition are at higher risk of frailty. This study explored the correlation between nutrition and frailty and compared the receiver operating characteristic curve of different nutritional indexes for frailty. METHODS: This cross-sectional study included 179 inpatients aged ≥65 years old. Frailty was measured using Fried Frailty Phenotype, handgrip strength was measured using JAMAR@Plus and the 4.57 m usual gait speed was measured using a stopwatch. Comprehensive nutritional assessment refers to the application of Mini Nutritional Assessment (MNA) to assess the nutritional status of patients. RESULTS: Compared with the non-frailty group, the upper arm circumference, calf circumference, hemoglobin, albumin, prealbumin, cholesterol and low density lipoprotein in the frailty group were lower (P < 0.05). Comprehensive nutritional assessment, whether as a categorical variable or a continuous variable, was significantly correlated with frailty (P < 0.05). Model1 showed that the risk of frailty in malnourished patients was 3.381 times higher than that in well nourished patients (P = 0.036). Model2 showed that the risk of frailty decreased by 13.8% for every 1 point increase in MNA score (P = 0.009). The area under the curves of albumin, prealbumin and hemoglobin was larger (AUC > 0.65), AUC was 0.718, 0.693 and 0.743, respectively. CONCLUSIONS: Our results suggest that malnutrition is closely related to frailty. As for single nutritional indexes, albumin, prealbumin and hemoglobin were found to be associated with frailty. Further cohort studies are needed to verify their ability to screen for frailty.

Magnetic Nanomaterials: Chemical Design, Synthesis, and Potential Applications.

Magnetic nanomaterials (MNMs) have attracted significant interest in the past few decades because of their unique properties such as superparamagnetism, which results from the influence of thermal energy on a ferromagnetic nanoparticle. In the superparamagnetic size regime, the moments of nanoparticles fluctuate as a result of thermal energy. To understand the fundamental behavior of superparamagnetism and develop relevant potential applications, various preparation routes have been explored to produce MNMs with desired properties and structures. However, some challenges remain for the preparation of well-defined magnetic nanostructures, including exchange-coupled nanomagnets, which are considered as the next generation of advanced magnets. In such a case, effective synthetic methods are required to achieve control over the chemical composition, size, and structure of MNMs. For instance, liquid-phase chemical syntheses, a set of emerging approaches to prepare various magnetic nanostructures, facilitate precise control over the nucleation and specific growth processes of nanomaterials with diverse structures. Among them, the high-temperature organic-phase method is an indispensable one in which the microstructures and physical/chemical properties of MNMs can be tuned by controlling the reaction conditions such as precursor, surfactant, or solvent amounts, reaction temperature or time, reaction atmosphere, etc. In this Account, we present an overview of our progress on the chemical synthesis of various MNMs, including monocomponent nanostructures (e.g., metals, metal alloys, metal oxides/carbides) and multicomponent nanostructures (heterostructures and exchange-coupled nanomagnets). We emphasize the high-temperature organic-phase synthetic method, on which we have been focused over the past decade. Notably, multicomponent nanostructures, obtained by growing or incorporating different functional components together, not only retain the functionalities of each single component but also possess synergic properties that emerge from interfacial coupling, with improved magnetic, optical, or catalytic features. Herein, potential applications of MNMs are covered in three representative areas: biomedicine, catalysis, and environmental purification. Regarding biomedicine, MNMs can detect or target biological entities after being modified with specific biomolecules, and they can be applied to magnetic resonance imaging, imaging-guided drug delivery, and photothermal therapy. Apart from their magnetic features, the catalytic performance of some MNMs resulting from their highly specific chemical components and surface structure will be briefly introduced, highlighting its impact in the methanol oxidation reaction, the oxygen reduction reaction, the oxygen and hydrogen evolution reactions, and the Fischer-Tropsch synthesis. Finally, environmental purification, primarily for water remediation, will be highlighted with two main aspects: the effective capture of bacteria and the removal of adverse ions in wastewater. We hope that this Account will clarify the progress on the controllable preparation of MNMs with specific compositions, sizes, and structures and generate broad interest in the realms of biomedicine and catalysis as well as in environmental issues and other potential applications.

Reversible Response of Luminescent Terbium(III)-Nanocellulose Hydrogels to Anions for Latent Fingerprint Detection and Encryption.

Fingerprint fluorescence imaging has become one of the most prominent technologies in the field of forensic medicine, but it seldom considers the security protection of detection information, which is of great importance in modern society. Herein we demonstrate that luminescent TbIII -carboxymethyl cellulose (CMC) complex binding aptamer hydrogels that are reversibly responsive to ClO- /SCN- can be used for the selective detection, protection, and storage of fingerprint information. The imaging information of the fingerprint can be quenched and recovered by ClO- /SCN- regulation, respectively, resulting in reversible on/off conversion of the luminescence signals for the encryption and decryption of multiple levels of information. The present study opens new avenues for multilevel imaging, data recording, and security protection of fingerprint information with tunable fluorescent hydrogels.

Multifunctional nanoparticle-mediated combining therapy for human diseases.

Combining existing drug therapy is essential in developing new therapeutic agents in disease prevention and treatment. In preclinical investigations, combined effect of certain known drugs has been well established in treating extensive human diseases. Attributed to synergistic effects by targeting various disease pathways and advantages, such as reduced administration dose, decreased toxicity, and alleviated drug resistance, combinatorial treatment is now being pursued by delivering therapeutic agents to combat major clinical illnesses, such as cancer, atherosclerosis, pulmonary hypertension, myocarditis, rheumatoid arthritis, inflammatory bowel disease, metabolic disorders and neurodegenerative diseases. Combinatorial therapy involves combining or co-delivering two or more drugs for treating a specific disease. Nanoparticle (NP)-mediated drug delivery systems, i.e., liposomal NPs, polymeric NPs and nanocrystals, are of great interest in combinatorial therapy for a wide range of disorders due to targeted drug delivery, extended drug release, and higher drug stability to avoid rapid clearance at infected areas. This review summarizes various targets of diseases, preclinical or clinically approved drug combinations and the development of multifunctional NPs for combining therapy and emphasizes combinatorial therapeutic strategies based on drug delivery for treating severe clinical diseases. Ultimately, we discuss the challenging of developing NP-codelivery and translation and provide potential approaches to address the limitations. This review offers a comprehensive overview for recent cutting-edge and challenging in developing NP-mediated combination therapy for human diseases.

Novel strategy for Poxviridae prevention: Thermostable combined subunit vaccine patch with intense immune response.

Poxviruses gained international attention due to the sharp rise in monkeypox cases in recent years, highlighting the urgent need for the development of a secure and reliable vaccine. This study involved the development of an innovative combined subunit vaccine (CSV) targeting poxviruses, with lumpy skin disease virus (LSDV) serving as the model virus. To this end, the potential sites for poxvirus vaccines were fully evaluated to develop and purify four recombinant proteins. These proteins were then successfully delivered to the dermis in a mouse model by utilizing dissolvable microneedle patches (DMPs). This approach simplified the vaccination procedure and significantly mitigated the associated risk. CSV-loaded DMPs contained four recombinant proteins and a novel adjuvant, CpG, which allowed DMPs to elicit the same intensity of humoral and cellular immunity as subcutaneous injection. Following immunization with SC and DMP, the mice exhibited notable levels of neutralizing antibodies, albeit at a low concentration. It is noteworthy that the CSV loaded into DMPs remained stable for at least 4 months at room temperature, effectively addressing the storage and transportation challenges. Based on the study findings, CSV-loaded DMPs are expected to be utilized worldwide as an innovative technique for poxvirus inoculation, especially in underdeveloped regions. This novel strategy is crucial for the development of future poxvirus vaccines.

Epidemiological characteristics of SHV, cmlv, and FosA6-producing carbapenem-resistant Klebsiella pneumoniae based on whole genome sequences in Jiangsu, China.

Carbapenem-resistant Klebsiella pneumoniae (CRKP), particularly those with high virulence, cause invasive disease in clinical settings. An epidemiological investigation was conducted on the evolution, virulence, and antimicrobial resistance of CRKP isolates in two tertiary teaching hospitals in Jiangsu, China from November 2020 to December 2021. There were 31 different CRKP strains discovered. We performed whole genome sequencing (WGS) on 13 SHV, cmlv, and FosA6-producing CRKP to reveal molecular characteristics. Five ST15/ST11 isolates had CRISPR-Cas systems. By conjugation tests, KPC-2 can be transmitted horizontally to E. coil. A conjugative pHN7A8-related multi-resistance plasmid (KPC-2, blaCTX-M-65, blaTEM-1, fosA3, catII, and rmtB) was first discovered in CRKP clinical isolates. Using bacteriological testing, a serum killing assay, and an infection model with Galleria mellonella, three ST11-K64 KPC-2 generating carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) were identified. These strains harbored a virulent plasmid and an IncFII-family pKPC/pHN7A8 conjugative plasmid, which led to hypervirulence and resistance. One of these CR-hvKPs, which co-harbored KPC-2, NDM-6, SHV-182, SHV-64, and blaCTX-M-122 genes, was first discovered. Importantly, this CR-hvKP strain also produced biofilm and had non-inferior fitness. The widespread use of ceftazidime/avibactam might provide this CR-hvKP with a selective advantage; hence, immediate action is required to stop its dissemination. Another important finding is the novel ST6136 in K. pneumoniae. Finally, the sterilization efficiency rates of Fe2C nanoparticles in CRKP were more than 98%. Furthermore, our novel antibacterial Fe2C nanoparticles may also provide a therapeutic strategy for infections.

Correlation analysis between body composition, serological indices and the risk of falls, and the receiver operating characteristic curve of different indexes for the risk of falls in older individuals.

Objective: This study assessed the risk factors for falls and evaluated the correlation between body composition, serological indices, and the risk of falls in older individuals. Method: This cross-sectional study included 387 individuals ≥60 years of age in the cadre ward of the First Hospital of Jilin University. The information used in this study was obtained from the comprehensive geriatric assessment database of the cadre ward. The body composition of the individuals was measured by bioelectrical impedance analysis using an InBody S10 device. We assessed fall risk using the fall risk assessment tool. Individuals with ≤2 points were placed in the low-risk group, those with 3-9 points were placed in the medium-risk group, and those with ≥10 points were placed in the high-risk group. Results: Differences in age, educational background, height, cognitive impairment, malnutrition, ability of daily living, depression, diastolic blood pressure, heart rate, intracellular water, total body moisture, water ratio, limb moisture (right and left, upper and lower), trunk moisture, fat-free weight, arm girth, body cell mass, skeletal muscle mass, limb muscle (right and left, upper and lower), appendicular skeletal muscle mass index (ASMI), sarcopenia, hemoglobin level, hematocrit level, aspartate aminotransferase level, albumin level, anemia, and hypoproteinemia were observed among the three groups (p < 0.001, p = 0.002, p = 0.006, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.008, p = 0.010). Ordinal logistic regression analysis showed that the probability of the fall risk increasing by one level was 1.902 times higher for each unit of decrease in educational background, respectively. In addition, the probability of the fall risk increasing by one level was 2.971, 3.732, 3.804, 1.690 and 2.155 times higher for each additional unit of age, cognitive impairment, lower limb edema, decreased skeletal muscle mass, and sarcopenia, respectively. Conclusion: Our findings suggest that educational background, age, cognitive impairment, lower limb edema, decreased skeletal muscle mass, and sarcopenia were associated with falls in older individuals. Body composition and serological indices can assist in the early identification of falls in the older people.

An Integrated Therapeutic and Preventive Nanozyme-Based Microneedle for Biofilm-Infected Diabetic Wound Healing.

The healing of biofilm-infected diabetic wounds characterized by a deteriorative tissue microenvironment represents a substantial clinical challenge. Current treatments remain unsatisfactory due to the limited antibiofilm efficacy caused by weak tissue and biofilm permeability of drugs and the risk of reinfection during the healing process. To address these issues, an integrated therapeutic and preventive nanozyme-based microneedle (denoted as Fe2 C/GOx@MNs) is engineered. The dissolvable tips with enough mechanical strength can deliver and rapidly release Fe2 C nanoparticles (NPs)/glucose oxidase (GOx) in the biofilm active regions, enhancing tissue and biofilm permeability of Fe2 C NPs/GOx, ultimately achieving highly efficient biofilm elimination. Meanwhile, the chitosan backing layer can not only act as an excellent physical barrier between the wound bed and the external environment, but also prevent the bacterial reinvasion during wound healing with its superior antibacterial property. Significantly, the biofilm elimination and reinfection prevention abilities of Fe2 C/GOx@MNs on wound healing are proved on methicillin-resistant Staphylococcus aureus-biofilm-infected diabetic mouse model with full-thickness wound. Together, these results demonstrate the promising clinical application of Fe2 C/GOx@MNs in biofilm-infected wound healing.

The role of comprehensive geriatric assessment in the identification of different nutritional status in geriatric patients: a real-world, cross-sectional study.

Background: Malnutrition is an often unrecognized problem, but it is common in older patients and leads to adverse outcomes. Aims: The purpose of this study is to analyze the prevalence of the risk of undernutrition in elderly patients and the correlation between CGA and nutritional status, and to determine the nutritional status of elderly patients. Methods: This is a real-world cross-sectional study of continuously enrolled elderly patients aged 65 years or older with a complete CGA database. CGA inventory was prepared by compiling and screening general information, body composition and blood biochemical results. MNA was also conducted for each elderly patient to screen for malnutrition. A multivariable logistic regression analysis was used to determine the association between the CGA and nutritional assessment. Result: The average age of the 211 selected elderly patients (160 men and 51 women) was 79.60 ± 9.24 years, and their ages ranged from 65 to 96 years. After controlling for confounders, patients with a history of PUD (OR = 2.353, p = 0.044), increased ADLs & IADLs scores (OR = 1.051, p = 0.042) or GDS scores (OR = 6.078, p < 0.001) may increase the incidence of the risk of undernutrition respectively, while an increase in BMI (OR = 0.858, p = 0.032) may lower the incidence of malnutrition risk. In addition, increased ADLs & IADLs scores (OR = 1.096, p = 0.002) or GDS scores (OR = 11.228, p < 0.001) may increase the incidence of undernutrition. However, increased MMSE (OR = 0.705, p < 0.001), BMI (OR = 0.762, p = 0.034), UAC (OR = 0.765, p = 0.048) and CC (OR = 0.721, p = 0.003) may decrease the incidence of undernutrition, respectively. Conclusion: The study found that the prevalence of risk of undernutrition in elderly patients was the highest. Risk of undernutrition was independently associated with peptic ulcer disease, ADLs & IADLs, GDS and BMI. However, we found that when the nutritional status reached the level of undernutrition, it was related to more factors, including ADLs & IADLs, MMSE, GDS, BMI, UAC and CC. Determining the level of malnutrition through CGA may help to prevent and intervene malnutrition as early as possible.

A universal boronate affinity capture-antibody-independent lateral flow immunoassay for point-of-care glycoprotein detection.

Protein glycosylation and other post-translational modifications are involved in many biological processes including growth, development and immune responses, and glycoproteins are also known as biomarkers for cancer, diabetes and cardiovascular diseases. In traditional lateral flow immunoassay (LFIA) for glycoprotein detection, capture antibody (CA) is often required to label targets. However, the production of CA is complicated and expensive, restricting the wide application of LFIA. In this study, we developed a universal boronate affinity CA-independent LFIA method for glycoprotein detection. 4-Mercaptophenylboronic acid (4-MPBA)-modified Au nanoparticles (namely 4-MPBA-AuNPs) were used as LFIA labels, which could generate colorimetric signal and showed outstanding capability to bind glycoprotein. Compared with CA, 4-MPBA molecular as a glycoprotein recognition element had more prominent advantages, e.g., low cost, easy availability and good quality controllability. Take carcinoembryonic antigen (CEA) as model glycoprotein, the limit of detection of this CA-independent LFIA was 1.25 ng/mL by naked eyes, which was 8-fold lower than conventional CA-dependent sandwich LFIA. Significantly, the developed 4-MPBA-AuNPs-based CA-independent LFIA successfully detected 23 CEA-positive samples from 64 suspected human serum samples within 50 min in a nonlaboratory environment, with a 100% accuracy compared to clinical detection method. Therefore, this diagnostic platform could provide an effective tool for point-of-care glycoprotein detection with excellent reproducibility and high specificity.

Personalized demand-responsive biphasic microneedle patch for smart drug administration.

Many patients, especially those with chronic diseases, would benefit from personalized drugs that could modulate the treatment regimen. Tailored drug delivery via microneedle patches (MNPs) has emerged as a promising technology to address this problem. However, it is still difficult to modulate the treatment regimen in one MNP. Here, multiple treatment regimens were achieved by the same MNP functionalized with modifiable nanocontainers (NCs). The MNPs were biphasic in design, resulting in approximately a twice as high drug loading capacity than that of traditional dissolving MNPs. The drug-loaded NCs could have a zero-order release rate for at least 20 d in vitro. Furthermore, three model MNPs, Type-A (100% drug), Type-B (50% drug and 50% NCs) and Type-C (100% NCs) were generated to simulate various personalized dosing needs. In vivo application of these models could achieve effective therapeutic drug concentrations in the first 12 h and adjusted the duration of effective drug action from 24 h to 96 h and 144 h, respectively, with outstanding biocompatibility. These findings indicate that this device holds significant promise for personalized drug delivery.

A Novel Methacryloyl Chitosan Hydrogel Microneedles Patch with Sustainable Drug Release Property for Effective Treatment of Psoriasis.

Psoriasis is a chronic and recurrent skin disease that often requires long-term treatment, and topical transdermal drug delivery can reduce systemic side effects. However, it is still a challenge in efficient transdermal drug delivery for psoriasis treatment due to low penetration efficiency of most drugs and the abnormal skin conditions of psoriasis patients. Here, a safe and effective methacryloyl chitosan hydrogel microneedles (CSMA hMNs) patch is developed and served as a sustained drug release platform for the treatment of psoriasis. By systematically optimizing the CSMA preparation, CSMA hMNs with excellent morphological characteristics and strong mechanical properties (0.7 N needle-1 ) are prepared with a concentration of only 3% (w/v) CSMA. As a proof-of-concept, methotrexate (MTX) and nicotinamide (NIC) are loaded into CSMA hMNs patch, which can produce a sustained drug release of 80% within 24 h in vitro. In vivo experiments demonstrated that the CSMA hMNs patch can effectively inhibit the skin thickening and spleen enlargement of psoriatic mice and has a good biosafety profile at sufficient therapeutic doses. This study provides a new idea for the preparation of hMN systems using modified CS or other biocompatible materials and offers an effective therapeutic option for psoriasis treatment.

The relationship between Comprehensive Geriatric Assessment parameters and depression in elderly patients.

Background: Depression is common and serious among elderly patients. The treatment of elderly depression is often delayed owing to insufficient diagnosis, which eventually leads to adverse consequences. Aims: To explore the association between the parameters of the Comprehensive Geriatric Assessment and depression in elderly patients. Methods: A cross-sectional study of 211 outpatients and inpatients aged ≥ 65 years from the Comprehensive Geriatric Assessment database was conducted. A Comprehensive Geriatric Assessment inventory was prepared by compiling and screening general characteristics, chronic diseases (cardiovascular disease, diabetes, and peptic ulcer disease), nutritional status, daily living ability, anthropometric measurements (body mass index (BMI), upper arm circumference, and calf circumference), and blood biochemical indicators (hemoglobin, albumin, prealbumin, triglycerides, and low-density lipoprotein cholesterol). The Geriatric Depression Scale was also conducted for each elderly patient to screen for depression. A multivariable logistic regression analysis was used to determine the association between the parameters of the Comprehensive Geriatric Assessment and geriatric depression. Results: There were 63 patients in the depression group with a median age of 84.00 years, and 148 patients in the non-depression group with a median age of 78.50 years. After controlling for confounders, the risk of depression in elderly patients with cardiovascular diseases was 6.011 times higher than that in those without cardiovascular diseases (p < 0.001); and the risk of depression in elderly patients with peptic ulcer diseases was 4.352 times higher than that in those without peptic ulcer diseases (p < 0.001); the risk of depression in elderly patients decreased by 22.6% for each 1-point increase in the Mini Nutritional Assessment (p < 0.001). The risk of depression in elderly patients decreased by 19.9% for each 1-point increase in calf circumference (p = 0.002), and by 13.0% for each 1-point increase in albumin (p = 0.014). Conclusion: Our findings suggest that Comprehensive Geriatric Assessment parameters, such as cardiovascular disease, peptic ulcer disease, Mini Nutritional Assessment score, calf circumference, and albumin, were associated with depression. The Comprehensive Geriatric Assessment can assist in the early identification of depression in the elderly population.

Gold Nanomaterial Engineering for Macrophage-Mediated Inflammation and Tumor Treatment.

Macrophages play an important role in the body's immune defense process. Phenotype imbalance between M1 and M2 macrophages induced by inflammation-related disorders and tumor can also be reversibly converted to treat these diseases. As exogenous substances, a large part of gold-based nanomaterials interact with macrophages once they enter the body, which provides gold nanomaterials a huge advantage to act as imaging contrasts, active substance carriers, and therapeutic agents for macrophage modulation. By cutting off macrophage recruitment, inhibiting macrophage activities, and modulating M1/M2 polarization, gold nanomaterial engineering exerts therapeutic effects on inflammation-related diseases at target sites. In this review, biological functions of macrophages in inflammation-related diseases are introduced, the effect of physicochemical factors of gold nanomaterials including size, shape, and surface chemistry is focused on the interaction between macrophages and gold nanomaterials, and the applications of gold nanomaterials are elaborated for tracking and treating these diseases by macrophages. The rational and smart engineering of gold nanomaterials allows a promising platform for macrophage-mediated inflammation and tumor imaging and treatment.