Structural insights into the N-terminal APHB domain of HrpA: mediating canonical and i-motif recognition.

RNA helicases function as versatile enzymes primarily responsible for remodeling RNA secondary structures and organizing ribonucleoprotein complexes. In our study, we conducted a systematic analysis of the helicase-related activities of Escherichia coli HrpA and presented the structures of both its apo form and its complex bound with both conventional and non-canonical DNAs. Our findings reveal that HrpA exhibits NTP hydrolysis activity and binds to ssDNA and ssRNA in distinct sequence-dependent manners. While the helicase core plays an essential role in unwinding RNA/RNA and RNA/DNA duplexes, the N-terminal extension in HrpA, consisting of three helices referred to as the APHB domain, is crucial for ssDNA binding and RNA/DNA duplex unwinding. Importantly, the APHB domain is implicated in binding to non-canonical DNA structures such as G-quadruplex and i-motif, and this report presents the first solved i-motif-helicase complex. This research not only provides comprehensive insights into the multifaceted roles of HrpA as an RNA helicase but also establishes a foundation for further investigations into the recognition and functional implications of i-motif DNA structures in various biological processes.

Gestational Diabetes Mellitus-Induced Milk Fat Globule Membrane Protein Changes of Human Mature Milk Based on TMT Proteomic Analysis.

Breastfeeding by mothers with gestational diabetes mellitus (GDM) has been shown to reduce maternal insulin demands and diminish the risks of diabetes in infants, leading to improved long-term health outcomes. Milk fat globule membrane (MFGM) proteins play a crucial role in influencing the immunity and cognitive development of infants. Understanding the alterations in MFGM proteins in breastmilk from mothers with GDM is essential for enhancing their self-efficacy and increase breastfeeding rates. The objective of this study is to investigate and compare MFGM proteins in milk from mothers with GDM and without based on tandem mass tag (TMT) labeling and liquid chromatography tandem mass spectrometry (LC-MS) techniques. A total of 5402 proteins were identified, including 4 upregulated proteins and 24 downregulated proteins. These significantly altered proteins were found to be associated with human diseases, cellular processes, and metabolism pathways. Additionally, the oxidative phosphorylation pathway emerged as the predominant pathway through Gene Set Enrichment Analysis (GSEA) involving all genes.

Endoplasmic reticulum stress-related protein GRP78 and CHOP levels in synovial fluid correlate with disease progression of primary knee osteoarthritis: A cross-sectional study.

BACKGROUND: Endoplasmic reticulum (ER) stress has been shown to play an important role in osteoarthritis (OA). OBJECTIVE: This study was aimed at assessing the relationship of endoplasmic reticulum (ER) stress-related glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) concentrations in the serum/synovial fluid (SF) with disease severity of primary knee osteoarthritis (pkOA). METHODS: Patients with pkOA together with healthy individuals were consecutively recruited from our hospital. The levels of GRP78 and CHOP in serum / SF were detected using enzyme-linked immunosorbent assay. The levels of IL-6 and MMP-3 were also examined. Radiographic progression of pkOA was evaluated based on Kellgren-Lawrence (K-L) grades. Receiver Operating Characteristic (ROC) curves were used to assess the diagnostic value of GRP78/CHOP levels with regard to K-L grades. The assessment of clinical severity was conducted using the visual analogue scale (VAS), Oxford knee score (OKS), and Lequesne algofunctional index (LAI). RESULTS: A total of 140 pkOA patients and 140 healthy individuals were included. Serum GRP78 and CHOP levels in pkOA patients were not significantly different from those in healthy individuals. The SF GRP78 and CHOP levels in healthy controls were not detected due to ethical reasons. Compared to those with K-L grade 2 and 3, the pkOA patients with K-L grade 4 had higher GRP78 and CHOP levels in the SF with statistical significance. In addition, the pkOA patients with K-L grade 3 exhibited drastically upregulated GRP78 and CHOP concentrations in the SF compared to those with K-L grade 2. Positive correlations of GRP78 and CHOP levels with K-L grades, IL-6, and MMP-3 levels in the SF were observed. ROC curve analysis indicated that both GRP78 and CHOP levels may act as decent indicators with regard to OA. GRP78 and CHOP concentrations in the SF were positively correlated with VAS/LAI score and negatively associated with OKS score. CONCLUSION: The study indicated that GRP78 and CHOP levels in the SF but not the serum were positively correlated with disease severity of pkOA.

Risk Factors of the Totally Implantable Venous Access Device-Related Infection in Patients With Brain Tumors Undergoing Chemotherapy After Surgery.

Background: The complication of totally implantable venous access device (TIVAD) is an infection, which causes the death of patients. Therefore, it is critical to identify risk factors for TIVAD infection to prevent death. Patients and Methods: The enrolled patients were divided into two groups and subsequently divided into subgroups according to various factors in which the correlation between infection and risk factors was analyzed. Multivariable logistic analysis of odds ratios (ORs) for seven risk factors was performed, meanwhile, the receiver operating characteristic (ROC) curve analysis of neutrophil and serum albumin was conducted for the prediction of TIVAD infection occurrence. Results: Catheter-related blood stream infection was the common infection type, which was dominantly caused by Staphylococcus aureus. Removal of TIVAD and antibiotic therapy were the preferred approaches for the treatment of infection. Seven risk factors were closely associated with the TIVAD infection, however, two risk factors, including age and outpatient, were excluded according to the multivariate logistic analysis of ORs. Receiver operating characteristic curve analysis revealed neutrophil count and serum albumin could predict the occurrence of TIVAD infection. Conclusions: Five risk factors were positively related to TIVAD infection; neutrophil and serum albumin could be used to predict the occurrence of TIVAD infection.

The NLRP3 inflammasome in burns: a novel potential therapeutic target.

Burns are an underestimated serious injury negatively impacting survivors physically, psychologically and economically, and thus are a considerable public health burden. Despite significant advancements in burn treatment, many burns still do not heal or develop serious complications/sequelae. The nucleotide-binding oligomerization domain-like receptors (NLRs) family pyrin domain-containing 3 (NLRP3) inflammasome is a critical regulator of wound healing, including burn wound healing. A better understanding of the pathophysiological mechanism underlying the healing of burn wounds may help find optimal therapeutic targets to promote the healing of burn wounds, reduce complications/sequelae following burn, and maximize the restoration of structure and function of burn skin. This review aimed to summarize current understanding of the roles and regulatory mechanisms of the NLRP3 inflammasome in burn wound healing, as well as the preclinical studies of the involvement of NLRP3 inhibitors in burn treatment, highlighting the potential application of NLRP3-targeted therapy in burn wounds.

Meaning matters: linking proactive vitality management to subjective well-being.

Prior research has indicated that positive affect, energy, and vitality are positively related to subjective well-being. Unfortunately, most scholars have overlooked the possibility that individuals may proactively manage their energetic, affective, and cognitive resources to boost their subjective well-being. Grounded in social cognitive theory, the current research focuses on explaining why students' proactive vitality management (PVM) leads to positive outcomes (i.e., meaning in life, subjective well-being) and considers how school support climate moderates these effects. One experimental study (Study 1) and a three-wave lagged survey (Study 2) were conducted to examine the benefits of PVM. The results demonstrated that PVM was positively related to students' meaning in life, further promoting their subjective well-being. Moreover, school support climate accentuated PVM's effect on meaning in life and its indirect effect on subjective well-being via meaning in life. Implications for research and practice are also discussed, along with study limitations and future research directions.

Association between cognitive function and body composition in older adults: data from NHANES (1999-2002).

Aim: To investigate the association between cognitive function and body composition in older adults. Methods: We collected data on 2080 older adults (>60 years of age) from the National Health and Nutrition Examination Survey (NHANES) for the years 1999-2000 and 2001-2002. Candidate variables included: demographic data (sex, age, race, education level, marital status, poverty-to-income ratio), alcohol consumption, cardiovascular disease, diabetes, osteoporosis, total bone mineral density, and total fat mass. A logistic regression model was established to analyze the association between cognitive function and body composition in older adults. In addition, stratified logics regression analysis was performed by sex and age. Results: Bone mineral density significantly affects cognitive function in older adults (p<0.01). When examining the data according to sex, this correlation is present for women (p < 0.01). For men, though, it is not significant (p = 0.081). Stratified by age, total bone mineral density was significantly correlated with cognitive function in 60-70 and 70-80 years old people, but not in older adults older than 80 years(for 60-70 years old, p = 0.019; for 70-80 years old, p = 0.022). There was no significant correlation between total bone mineral density and cognitive function (p = 0.575). Conclusion: The decrease of total bone mineral density was significantly correlated with cognitive decline in the older adults, especially among women and older people in the 60 to 80 age group. There was no connection between total fat mass, total percent fat, total lean mass, appendicular lean mass, appendicular lean mass /BMI and cognitive function in the older adults.

Exploring the effects of negative supervisory feedback on creativity among research and development personnel: challenge or threat?

Supervisory feedback to stimulate research and development (R&D) employee creativity is a management issue that concerns scholars and practitioners. However, there are divergences and contradictions regarding whether negative feedback promotes or hinders employee creativity. Integrating the feedback intervention and cognitive appraisal theories, we developed a double-edged sword model for negative supervisory feedback's influence on creativity. We tested the proposed model using a field sample of 513 R&D employees from seven science and technology enterprises. The results indicated that R&D employee challenge and threat appraisal moderated negative supervisory feedback's effect on prevention focus and the distal consequences for creativity. Individuals with high (low) levels of challenge (threat) appraisal have decreased prevention focus, thereby increasing their creativity when receiving negative supervisory feedback. In contrast, individuals with low (high) challenge (threat) appraisal have increased prevention focus, thereby decreasing their creativity when receiving negative supervisory feedback. These findings offer interesting implications for research on negative feedback and stimulation of science and technology R&D employee creativity in organizations.

Application of Biologic Graft in Nasal Septal Perforation Repair.

Objective: To explore the clinical outcome when biomaterials are used to repair nasal septal perforations. Methods: A total of 12 patients were treated. The nasal septum was dissected via endoscopic approach. A 4 cm × 7 cm biologic graft (Biodesign® Tissue Graft) was folded to form a double layer, was placed over the perforation, and was affixed into place using suture. Results: Follow-up ranged from 2 to 8 months after the operation. One patient was not completely healed and presented with a remaining defect of about 2 mm × 8 mm in the upper part of the nasal septum. The remaining 11 patients healed completely. Conclusion: Using a biologic graft to repair nasal septal perforations is an easy operation as it prevents the need to take autologous tissue from the patient, allows for a repair to be performed without creating septal flaps, and has good histocompatibility. It is a safe and effective method that can be used clinically.

Four Parallel Pathways in T4 Ligase-Catalyzed Repair of Nicked DNA with Diverse Bending Angles.

The structural diversity of biological macromolecules in different environments contributes complexity to enzymological processes vital for cellular functions. Fluorescence resonance energy transfer and electron microscopy are used to investigate the enzymatic reaction of T4 DNA ligase catalyzing the ligation of nicked DNA. The data show that both the ligase-AMP complex and the ligase-AMP-DNA complex can have four conformations. This finding suggests the parallel occurrence of four ligation reaction pathways, each characterized by specific conformations of the ligase-AMP complex that persist in the ligase-AMP-DNA complex. Notably, these complexes have DNA bending angles of ≈0°, 20°, 60°, or 100°. The mechanism of parallel reactions challenges the conventional notion of simple sequential reaction steps occurring among multiple conformations. The results provide insights into the dynamic conformational changes and the versatile attributes of T4 DNA ligase and suggest that the parallel multiple reaction pathways may correspond to diverse T4 DNA ligase functions. This mechanism may potentially have evolved as an adaptive strategy across evolutionary history to navigate complex environments.

circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models.

Chronic wounds are a major complication in patients with diabetes. Here, we identify a therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic wounds in preclinical models. We show that circCDK13 can stimulate the proliferation and migration of human dermal fibroblasts and human epidermal keratinocytes by interacting with insulin-like growth factor 2 mRNA binding protein 3 in an N6-Methyladenosine-dependent manner to enhance CD44 and c-MYC expression. We engineered sEVs that overexpress circCDK13 and show that local subcutaneous injection into male db/db diabetic mouse wounds and wounds of streptozotocin-induced type I male diabetic rats could accelerate wound healing and skin appendage regeneration. Our study demonstrates that the delivery of circCDK13 in sEVs may present an option for diabetic wound treatment.

The catalytic triad of rice NARROW LEAF1 involves H234.

NARROW LEAF1 (NAL1) exerts a multifaceted influence on leaf morphology and crop yield. Recent crystal study proposed that histidine 233 (H233) is part of the catalytic triad. Here we report that unlike suggested previously, H234 instead of H233 is a component of the catalytic triad alongside residues D291 and S385 in NAL1. Remarkably, residue 233 unexpectedly plays a pivotal role in regulating NAL1's proteolytic activity. These findings establish a strong foundation for utilizing NAL1 in breeding programs aimed at improving crop yield.

Spiral wave chimeras in nonlocally coupled bicomponent oscillators.

Chimera states in nonidentical oscillators have received extensive attention in recent years. Previous studies have demonstrated that chimera states can exist in a ring of nonlocally coupled bicomponent oscillators even in the presence of strong parameter heterogeneity. In this study, we investigate spiral wave chimeras in two-dimensional nonlocally coupled bicomponent oscillators where oscillators are randomly divided into two groups, with identical oscillators in the same group. Using phase oscillators and FitzHugh-Nagumo oscillators as examples, we numerically demonstrate that each group of oscillators supports its own spiral wave chimera and two spiral wave chimeras coexist with each other. We find that there exist three heterogeneity regimes: the synchronous regime at weak heterogeneity, the asynchronous regime at strong heterogeneity, and the transition regime in between. In the synchronous regime, spiral wave chimeras supported by different groups are synchronized with each other by sharing a same rotating frequency and a same incoherent core. In the asynchronous regime, the two spiral wave chimeras rotate at different frequencies and their incoherent cores are far away from each other. These phenomena are also observed in a nonrandom distribution of the two group oscillators and the continuum limit of infinitely many phase oscillators. The transition from synchronous to asynchronous spiral wave chimeras depends on the component oscillators. Specifically, it is a discontinuous transition for phase oscillators but a continuous one for FitzHugh-Nagumo oscillators. We also find that, in the asynchronous regime, increasing heterogeneity leads irregularly meandering spiral wave chimeras to rigidly rotating ones.

Effect of Rapid Hollow Cathode Plasma Nitriding Treatment on Corrosion Resistance and Friction Performance of AISI 304 Stainless Steel.

Low-temperature plasma nitriding of austenitic stainless steel can ensure that its corrosion resistance does not deteriorate, improving surface hardness and wear performance. Nevertheless, it requires a longer processing time. The hollow cathode discharge effect helps increase the plasma density quickly while radiatively heating the workpiece. This work is based on the hollow cathode discharge effect to perform a rapid nitriding strengthening treatment on AISI 304 stainless steels. The experiments were conducted at three different temperatures (450, 475, and 500 °C) for 1 h in an ammonia atmosphere. The samples were characterized using various techniques, including SEM, AFM, XPS, XRD, and micro-hardness measurement. Potentiodynamic polarization and electrochemical impedance spectroscopy methods were employed to assess the electrochemical behavior of the different samples in a 3.5% NaCl solution. The finding suggests that rapid hollow cathode plasma nitriding can enhance the hardness, wear resistance, and corrosion properties of AISI 304 stainless steel.

Prognostic value of serum ammonia in critical patients with non-hepatic disease: A prospective, observational, multicenter study.

Background and Objectives: Non-hepatic hyperammonemia can damage the central nervous system (CNS), and possible prognostic factors are lacking. This study aimed to investigate the prognostic and risk factors for patients admitted to the intensive care unit (ICU). Materials and Methods: This prospective, observational, multicenter study was conducted between November and December 2019 at 11 ICUs in the Chinese Heilongjiang province. Changes in blood ammonia level during and after ICU admission were continuously monitored and expressed as the high level (H-), mean level (M-), and initial level (I-) of ammonia. The risk factors of poor prognosis were investigated by conducting univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive ability of Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE-II) score, lactic acid, total bilirubin (TBil), and M-ammonia. Results: A total of 1060 patients were included in this study, of which 707 (67%) had a favorable prognosis and 353 (33%) had a poor prognosis. As shown by univariate models, a poor prognosis was associated with elevated serum levels of lactic acid, TBil, and ammonia (P < 0.05) and pathologic scores from three assessments: APACHE-II, Glasgow Coma Scale (GCS), and Sequential Organ Failure Assessment (SOFA). Multivariate analysis revealed that circulating mean ammonia levels in ICU patients were independently associated with a poor prognosis (odds ratio [OR] = 1.73, 95% confidence interval [CI]: 1.07-2.80, P = 0.02). However, the APACHE-II score (area under the curve [AUC]: 0.714, sensitivity: 0.86, specificity: 0.68, P < 0.001) remained the most predictive factor for patient prognosis by ROC analysis. Conclusion: Elevated serum levels of ammonia in the blood were independently prognostic for ICU patients without liver disease.

Foxa1 mediates eccrine sweat gland development through transcriptional regulation of Na-K-ATPase expression

Eccrine sweat glands (ESGs) perform critical functions in temperature regulation in humans. Foxa1 plays an important role in ESG maturation and sweat secretion. Its molecular mechanism, however, remains unknown. This study investigated the expression of Foxa1 and Na-K-ATPase (NKA) in rat footpads at different development stages using immunofluorescence staining, qRT-PCR, and immunoblotting. Also, bioinformatics analysis and Foxa1 overexpression and silencing were employed to evaluate Foxa1 regulation of NKA. The results demonstrated that Foxa1 was consistently expressed during the late stages of ESGs and had a significant role in secretory coil maturation during sweat secretion. Furthermore, the mRNA abundance and protein expression of NKA had similar accumulation trends to those of Foxa1, confirming their underlying connections. Bioinformatics analysis revealed that Foxa1 may interact with these two proteins via binding to conserved motifs in their promoter regions. Foxa1 gain-of-function and loss-of-function experiments in Foxa1-modified cells demonstrated that the activities of NKA were dependent on the presence of Foxa1. Collectively, these data provided evidence that Foxa1 may influence ESG development through transcriptional regulation of NKA expression.