Smart Galactosidase-Responsive Antimicrobial Dendron: Towards More Biocompatible Membrane-Disruptive Agents.

Antimicrobial resistance is a global healthcare challenge that urgently needs the development of new therapeutic agents. Antimicrobial peptides and mimics thereof are promising candidates but mostly suffer from inherent toxicity issues due to the non-selective binding of cationic groups with mammalian cells. To overcome this toxicity issue, this work herein reports the synthesis of a smart antimicrobial dendron with masked cationic groups (Gal-Dendron) that could be uncaged in the presence of ß-galactosidase enzyme to form the activated Enz-Dendron and confer antimicrobial activity. Enz-Dendron show bacteriostatic activity toward Gram-negative (P. aeruginosa and E. coli) and Gram-positive (S. aureus) bacteria with minimum inhibitory concentration values of 96 µm and exerted its antimicrobial mechanism via a membrane disruption pathway, as indicated by inner and outer membrane permeabilization assays. Crucially, toxicity studies confirmed that the masked prodrug Gal-Dendron exhibited low hemolysis and is at least 2.4 times less toxic than the uncaged cationic Enz-Dendron, thus demonstrating the advantage of masking the cationic groups with responsive immolative linkers to overcome toxicity and selectivity issues. Overall, this study highlights the potential of designing new membrane-disruptive antimicrobial agents that are more biocompatible via the amine uncaging strategy.

Longitudinal test of the social cognitive model of well-being among Chinese college students.

Since the social cognitive model of well-being in academic\work settings was proposed, more and more studies have supported its validity. Nevertheless, most studies failed to test the temporal precedence of its core variables related to individual career development. Thus, we aimed to test this model among 1512 Chinese college students with a longitudinal perspective. They completed the Career-related Parental Support Inventory, Career Exploration and Decision Self-Efficacy-Brief Decision Scale, Career Commitment Making Scale, and Multiple Happiness Questionnaire three times being a four-month interval. The result indicated that there were more positive predicting associations between career-related parental support, career decision self-efficacy (CDSE), career commitment making, and well-being. Moreover, the longitudinal mediation analyses indicated that T1 career-related parental support was linked to T3 well-being via T2 career commitment making, and that T1 CDSE was linked to T3 well-being via T2 career commitment making. The implications of these findings for further research, practices, and policy-making were discussed.

Vertebral HU value and the pectoral muscle index based on chest CT can be used to opportunistically screen for osteoporosis.

BACKGROUND: Existing studies have shown that computed tomography (CT) attenuation and skeletal muscle tissue are strongly associated with osteoporosis; however, few studies have examined whether vertebral HU values and the pectoral muscle index (PMI) measured at the level of the 4th thoracic vertebra (T4) are strongly associated with bone mineral density (BMD). In this study, we demonstrate that vertebral HU values and the PMI based on chest CT can be used to opportunistically screen for osteoporosis and reduce fracture risk through prompt treatment. METHODS: We retrospectively evaluated 1000 patients who underwent chest CT and DXA scans from August 2020-2022. The T4 HU value and PMI were obtained using manual chest CT measurements. The participants were classified into normal, osteopenia, and osteoporosis groups based on the results of dual-energy X-ray (DXA) absorptiometry. We compared the clinical baseline data, T4 HU value, and PMI between the three groups of patients and analyzed the correlation between the T4 HU value, PMI, and BMD to further evaluate the diagnostic efficacy of the T4 HU value and PMI for patients with low BMD and osteoporosis. RESULTS: The study ultimately enrolled 469 participants. The T4 HU value and PMI had a high screening capacity for both low BMD and osteoporosis. The combined diagnostic model-incorporating sex, age, BMI, T4 HU value, and PMI-demonstrated the best diagnostic efficacy, with areas under the receiver operating characteristic curve (AUC) of 0.887 and 0.892 for identifying low BMD and osteoporosis, respectively. CONCLUSIONS: The measurement of T4 HU value and PMI on chest CT can be used as an opportunistic screening tool for osteoporosis with excellent diagnostic efficacy. This approach allows the early prevention of osteoporotic fractures via the timely screening of individuals at high risk of osteoporosis without requiring additional radiation.

Glutamate Receptor-like (GLR) Family in Brassica napus: Genome-Wide Identification and Functional Analysis in Resistance to Sclerotinia sclerotiorum.

Plant glutamate receptor-like channels (GLRs) are homologs of animal ionotropic glutamate receptors. GLRs are critical in various plant biological functions, yet their genomic features and functions in disease resistance remain largely unknown in many crop species. Here, we report the results on a thorough genome-wide study of the GLR family in oilseed rape (Brassica napus) and their role in resistance to the fungal pathogen Sclerotinia sclerotiorum. A total of 61 GLRs were identified in oilseed rape. They comprised three groups, as in Arabidopsis thaliana. Detailed computational analyses, including prediction of domain and motifs, cellular localization, cis-acting elements, PTM sites, and amino acid ligands and their binding pockets in BnGLR proteins, unveiled a set of group-specific characteristics of the BnGLR family, which included chromosomal distribution, motif composition, intron number and size, and methylation sites. Functional dissection employing virus-induced gene silencing of BnGLRs in oilseed rape and Arabidopsis mutants of BnGLR homologs demonstrated that BnGLR35/AtGLR2.5 positively, while BnGLR12/AtGLR1.2 and BnGLR53/AtGLR3.2 negatively, regulated plant resistance to S. sclerotiorum, indicating that GLR genes were differentially involved in this resistance. Our findings reveal the complex involvement of GLRs in B. napus resistance to S. sclerotiorum and provide clues for further functional characterization of BnGLRs.

The paradox of bone mineral density and fracture risk in type 2 diabetes.

Fracture risk in type 2 diabetes (T2D) patients is paradoxically increased despite no decrease in areal bone mineraldensity (BMD). This phenomenon, known as the "diabetic bone paradox", has been attributed to various factorsincluding alterations in bone microarchitecture and composition, hyperinsulinemia and hyperglycemia, advancedglycation end products (AGEs), and comorbidities associated with T2D. Zhao et al. recently investigated therelationship between T2D and fracture risk using both genetic and phenotypic datasets. Their findings suggest thatgenetically predicted T2D is associated with higher BMD and lower fracture risk, indicating that the bone paradox isnot observed when confounding factors are controlled using Mendelian randomization (MR) analysis. However, inprospective phenotypic analysis, T2D remained associated with higher BMD and higher fracture risk, even afteradjusting for confounding factors. Stratified analysis revealed that the bone paradox may disappear when T2Drelatedrisk factors are eliminated. The study also highlighted the role of obesity in the relationship between T2Dand fracture risk, with BMI mediating a significant portion of the protective effect. Overall, managing T2D-relatedrisk factors may be crucial in preventing fracture risk in T2D patients.

Biochar-enhanced three-dimensional conductive network thick electrodes for efficient lithium extraction from salt lake brines with high Magnesia-lithium ratios.

Enhancing the kinetic performance of thick electrodes is essential for improving the efficiency of lithium extraction processes. Biochar, known for its affordability and unique three-dimensional (3D) structure, is utilized across various applications. In this study, we developed a biochar-based, 3D-conductive network thick electrode (∼20 mg cm-2) by in-situ deposition of LiFePO4 (LFP) onto watermelon peel biomass (WB). Utilizing Density Functional Theory (DFT) calculations complemented by experimental data, we confirmed that this The thick electrode exhibits outstanding kinetic properties and a high capacity for lithium intercalation in brines, even in environments where the Magnesia-lithium ratios are significantly high. The electrode showed an impressive intercalation capacity of 30.67 mg g-1 within 10 min in a pure lithium solution. It also maintained high intercalation performance (31.17 mg g-1) in simulated brines with high Magnesia-lithium ratios. Moreover, in actual brine, it demonstrated a significant extraction capacity (23.87 mg g-1), effectively lowering the Magnesia-lithium ratio from 65 to 0.50. This breakthrough in high-conductivity thick electrode design offers new perspectives for lithium extraction technologies.

[Clinical Characteristics of CD4-CD56+ Blastic Plasmacytoid Dendritic Cell Neoplasm].

OBJECTIVE: To explore the clinical manifestations, pathological features, immunophenotype, as well as diagnosis, treatment and prognosis of patients with CD4-CD56+ blastic plasmacytoid dendritic cell neoplasm (BPDCN), in order to further understand the rare disease. METHODS: The clinical data, laboratory examinations and treatment regimens of two patients with CD4-CD56+ BPDCN in the First Affiliated Hospital of Wannan Medical College were retrospectively analyzed. RESULTS: The two patients were both elderly males with tumor involved in skin, bone marrow, lymph nodes, etc. Immunohistochemical results of skin lesions showed that both CD56 and CD123 were positive, while CD4, CD34, TdT, CD3, CD20, MPO and EBER were negative. Flow cytometry of bone marrow demonstrated that CD56, CD123, and CD304 were all positive, while specific immune markers of myeloid and lymphoid were negative. Two patients were initially very sensitive to acute lymphoblastic leukemia or lymphomatoid chemotherapy regimens, but prone to rapid relapse. The overall survival of both patients was 36 months and 4 months, respectively. CONCLUSION: CD4-CD56+ BPDCN is very rare and easily misdiagnosed as other hematological tumors with poor prognosis. Acute lymphoblastic leukemia or lymphomatoid therapy should be used first to improve the poor prognosis.

Identification of ALDOB as a novel prognostic biomarker in kidney clear cell renal cell carcinoma.

Kidney clear cell renal cell carcinoma (KIRC) is also the most lethal subtype among all kidney cancer subtypes, posing a severe threat to public health. Therefore, it is crucial to identify new, reliable biomarkers in KIRC. Therefore, it is crucial to identify novel, reliable biomarkers associated with KIRC. We analyzed RNA sequence results from TCGA and several GEO datasets. The commonly deregulated gene, ALDOB, was found in multiple data and confirmed its important prognostic value. Subsequently, we explored the specific mechanism by which ALDOB regulates anti-tumor immunity through in vivo and in vitro experiments. We found that ALDOB may play a role in regulating tumor growth by regulating CD8+ T cell infiltration. This is consistent with the results of our immune infiltration-related analysis. In addition, we have also discovered the effect of ALDOB in previous studies on other cancer types. Finally, we concluded that ALDOB may have potential reference value for immunotherapy and can also be used as an independent predictor of prognosis in KIRC.

Heterointerface-Rich Ni3N/WO3 Hierarchical Nanoarrays for Efficient Glycerol Oxidation-Assisted Alkaline Hydrogen Evolution.

Glycerol oxidation-assisted water electrolysis has emerged as a cost-effective way of co-producing green hydrogen and HCOOH. Still, preparing highly selective and stable nickel-based metal electrocatalysts remains a challenge. Herein, heterostructure Ni3N/WO3 nanosheet arrays of bifunctional catalysts with large specific surface areas loaded on nickel foam (denoted as Ni3N/WO3/NF) were synthesized. This catalyst was for glycerol oxidation reaction (GOR) and hydrogen evolution reaction (HER) with excellent catalytic performance, a voltage saving of 267 mV compared to oxygen evolution reaction (OER), and a HER overpotential of 104 mV at 100 mA cm-2. The cell voltage in the assembled GOR//HER hybrid electrolysis system reaches 100 mA cm-2 at 1.50 V, 296 mV lower than the potential required for overall water splitting. This work demonstrates that replacing GOR with OER using a cost-effective and highly active Ni-based bifunctional electrocatalyst can make hybrid water electrolysis an energy-efficient, sustainable, and green strategy for hydrogen production.

Erratum: [Corrigendum] Chloroquine potentiates the anticancer effect of sunitinib on renal cell carcinoma by inhibiting autophagy and inducing apoptosis.

[This corrects the article DOI: 10.3892/ol.2017.7635.].

High-Performance Flexible Ionically Conductive Superhydrophobic Papers via Deep Eutectic Polymer-Enhanced Interfacial Interactions.

Endowing paper with highly flexible, conductive, and superhydrophobic properties will effectively expand its applications in fields such as green packaging, smart sensing, and paper-based electronics. Herein, a multifunctional superhydrophobic paper is reported in which a highly flexible transparent conductive substrate is prepared by introducing a hydrophobic deep eutectic polymer into the ethylcellulose network via a matrix swelling-polymerization strategy, and then the substrate is modified using fluorinated silica to impart superhydrophobicity. By introducing soft deep eutectic polymers, (1) the superhydrophobic paper can efficiently dissipate energy during deformation, (2) intrinsically ion-conducting deep eutectic polymers can endow the material with good electrical sensing properties, and (3) meanwhile, enhanced interfacial interactions can anchor inorganic particles, thereby improving the coating stability. The prepared superhydrophobic paper has an ultrahigh water contact angle (contact angle ≈ 162.2°) and exhibits a stable electrical response signal to external deformation/pressure, and the electrical properties are almost unaffected by external water molecules. In addition, the superhydrophobic paper was able to withstand 5000 bending-recovery cycles at a large angle of 150°, exhibiting stable electrical performance. The design concepts demonstrated here will provide insights into the development of superhydrophobic paper-based flexible electronic devices.

Lateral wall thickness is not associated with revision risk of medially stable intertrochanteric fractures fixed with a sliding hip screw.

Aims: This study aimed to determine whether lateral femoral wall thickness (LWT) < 20.5 mm was associated with increased revision risk of intertrochanteric fracture (ITF) of the hip following sliding hip screw (SHS) fixation when the medial calcar was intact. Additionally, the study assessed the association between LWT and patient mortality. Methods: This retrospective study included ITF patients aged 50 years and over treated with SHS fixation between 2019 and 2021 at a major trauma centre. Demographic information, fracture type, delirium status, American Society of Anesthesiologists grade, and length of stay were collected. LWT and tip apex distance were measured. Revision surgery and mortality were recorded at a mean follow-up of 19.5 months (1.6 to 48). Cox regression was performed to evaluate independent risk factors associated with revision surgery and mortality. Results: The cohort consisted of 890 patients with a mean age of 82 years (SD 10.2). Mean LWT was 27.0 mm (SD 8.6), and there were 213 patients (23.9%) with LWT < 20.5 mm. Overall, 20 patients (2.2%) underwent a revision surgery following SHS fixation. Adjusting for covariates, LWT < 20.5 mm was not independently associated with an increased revision or mortality risk. However, factors that were significantly more prevalent in LWT < 20.5 mm group, which included residence in care home (hazard ratio (HR) 1.84; p < 0.001) or hospital (HR 1.65; p = 0.005), and delirium (HR 1.32; p = 0.026), were independently associated with an increased mortality risk. The only independent factor associated with increased risk of revision was older age (HR 1.07; p = 0.030). Conclusion: LWT was not associated with risk of revision surgery in patients with an ITF fixed with a SHS when the calcar was intact, after adjusting for the independent effect of age. Although LWT < 20.5 mm was not an independent risk factor for mortality, patients with LWT < 20.5 mm were more likely to be from care home or hospital and have delirium on admission, which were associated with a higher mortality rate.

Total flavonoids of Astragalus protects glomerular filtration barrier in diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is a prevalent complication of diabetes and the leading cause of end-stage renal disease. Recent evidence suggests that total flavonoids of Astragalus (TFA) has promising effects on diabetes; however, its influence on DKD and the underlying mechanism remains unclear. METHODS: In this study, we induced the DKD model using streptozotocin (STZ) in male C57BL/6J mice and utilized glomerular endothelial cell (GEC) lines for in vitro investigations. We constructed a network pharmacology analysis to understand the mechanism of TFA in DKD. The mechanism of TFA action on DKD was investigated through Western blot analysis and multi-immunological methods. RESULTS: Our findings revealed that TFA significantly reduced levels of urinary albumin (ALB). Network pharmacology and intracellular pathway experiments indicated the crucial involvement of the PI3K/AKT signaling pathway in mediating these effects. In vitro experiments showed that TFA can preserve the integrity of the glomerular filtration barrier by inhibiting the expression of inflammatory factors TNF-alpha and IL-8, reducing oxidative stress. CONCLUSION: Our findings demonstrated that TFA can ameliorates the progression of DKD by ameliorating renal fibrosis and preserving the integrity of the kidney filtration barrier. These results provide pharmacological evidence supporting the use of TFA in the treatment of kidney diseases.

Plasmon-Switched Kinetics for Formic Acid Dehydrogenation: Selective Adsorption Driven by Local Field and Hot Carriers.

Understanding illumination-mediated kinetics is essential for catalyst design in plasmon catalysis. Here we prepare Pd-based plasmonic catalysts with tunable electronic structures to reveal the underlying illumination-enhanced kinetic mechanisms for formic acid (HCOOH) dehydrogenation. We demonstrate a kinetic switch from a competitive Langmuir-Hinshelwood adsorption mode in dark to a non-competitive type under irradiation triggered by local field and hot carriers. Specifically, the electromagnetic field induces a spatial-temporal separation of dehydrogenation-favorable configurations of reactant molecule HCOOH and HCOO- due to their natural different polarities. Meanwhile, the generated energetic carriers can serve as active sites for selective molecular adsorption. The hot electrons act as adsorption sites for HCOOH, while holes prefer to adsorb HCOO-. Such unique non-competitive adsorption kinetics induced by plasmon effects serves as another typical characteristic of plasmonic catalysis that remarkably differs from thermocatalysis. This work unravels unique adsorption transformations and a kinetic switching driven by plasmon nonthermal effects.

Mobile cognitive behavioral therapy for insomnia: analysis of factors affecting treatment prognosis.

This study aims to explore the factors that affect the prognosis of patients with insomnia who are treated with mobile cognitive behavioral therapy. Patients with insomnia who visited the sleep disorders clinic were selected and completed mobile Cognitive behavioral therapy. Patients completed at least three evaluations (including baseline, monthly evaluations thereafter, and a final evaluation at the end of one year) and responded well to treatment within one year of follow-up. Insomnia, anxiety, and depression symptoms were evaluated using the Pittsburgh Sleep Quality Index (PSQI), the Generalized Anxiety Disorder 7-item (GAD-7) scale, and the 9-item Patient Health Questionnaire (PHQ-9), respectively. Treatment prognosis including relapse, recurrence, and remission group. These 339 patients were divided into three groups: 160 patients who remission, 100 patients who relapsed, and 79 patients who experienced recurrence after remission. Demographic characteristics of the 339 patients showed no significant difference in gender between the three groups (P = 0.978). However, significant differences were found in age (P = 0.006) and onset time (P = 0.000) among the three groups. The remission group had a higher average age than the recurrence group and the relapse group, and the onset time was slower than the other two groups. Multivariate logistic regression analysis showed that age and delayed onset time were protective factors for good treatment prognosis, while low educational level and high GAD-7 scores were independent risk factors for poor prognosis. There are many factors that affect the treatment prognosis of insomnia. Age, low educational level, high GAD-7 scores, and delayed onset time can be used to predict the prognosis of insomnia treatment.