USP28 Serves as a Key Suppressor of Mitochondrial Morphofunctional Defects and Cardiac Dysfunction in the Diabetic Heart.

BACKGROUND: The majority of people with diabetes are susceptible to cardiac dysfunction and heart failure, and conventional drug therapy cannot correct diabetic cardiomyopathy progression. Herein, we assessed the potential role and therapeutic value of USP28 (ubiquitin-specific protease 28) on the metabolic vulnerability of diabetic cardiomyopathy. METHODS: The type 2 diabetes mouse model was established using db/db leptin receptor-deficient mice and high-fat diet/streptozotocin-induced mice. Cardiac-specific knockout of USP28 in the db/db background mice was generated by crossbreeding db/m and Myh6-Cre+/USP28fl/fl mice. Recombinant adeno-associated virus serotype 9 carrying USP28 under cardiac troponin T promoter was injected into db/db mice. High glucose plus palmitic acid-incubated neonatal rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes were used to imitate diabetic cardiomyopathy in vitro. The molecular mechanism was explored through RNA sequencing, immunoprecipitation and mass spectrometry analysis, protein pull-down, chromatin immunoprecipitation sequencing, and chromatin immunoprecipitation assay. RESULTS: Microarray profiling of the UPS (ubiquitin-proteasome system) on the basis of db/db mouse hearts and diabetic patients' hearts demonstrated that the diabetic ventricle presented a significant reduction in USP28 expression. Diabetic Myh6-Cre+/USP28fl/fl mice exhibited more severe progressive cardiac dysfunction, lipid accumulation, and mitochondrial disarrangement, compared with their controls. On the other hand, USP28 overexpression improved systolic and diastolic dysfunction and ameliorated cardiac hypertrophy and fibrosis in the diabetic heart. Adeno-associated virus serotype 9-USP28 diabetic mice also exhibited less lipid storage, reduced reactive oxygen species formation, and mitochondrial impairment in heart tissues than adeno-associated virus serotype 9-null diabetic mice. As a result, USP28 overexpression attenuated cardiac remodeling and dysfunction, lipid accumulation, and mitochondrial impairment in high-fat diet/streptozotocin-induced type 2 diabetes mice. These results were also confirmed in neonatal rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes. RNA sequencing, immunoprecipitation and mass spectrometry analysis, chromatin immunoprecipitation assays, chromatin immunoprecipitation sequencing, and protein pull-down assay mechanistically revealed that USP28 directly interacted with PPARα (peroxisome proliferator-activated receptor α), deubiquitinating and stabilizing PPARα (Lys152) to promote Mfn2 (mitofusin 2) transcription, thereby impeding mitochondrial morphofunctional defects. However, such cardioprotective benefits of USP28 were largely abrogated in db/db mice with PPARα deletion and conditional loss-of-function of Mfn2. CONCLUSIONS: Our findings provide a USP28-modulated mitochondria homeostasis mechanism that involves the PPARα-Mfn2 axis in diabetic hearts, suggesting that USP28 activation or adeno-associated virus therapy targeting USP28 represents a potential therapeutic strategy for diabetic cardiomyopathy.

Electroacupuncture attenuates nociceptive behaviors in a mouse model of cancer pain.

Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture in treatment of cancer pain and try to explore the underlying analgesic mechanisms. Nude mice were inoculated with cancer cells into the left distal femur to establish cancer pain model. Electroacupuncture (EA) treatment was applied for the xenograft animals. Pain behaviors of mice were evaluated, followed by the detections of neuropeptide-related and inflammation-related indicators in peripheral and central levels. EA treatment alleviated cancer-induced pain behaviors covering mechanical allodynia, thermal hyperalgesia and spontaneous pain, and also down-regulated immunofluorescence expressions of neuropeptide CGRP and p75 in the skin of affected plantar area in xenograft mice, and inhibited expressions of overexpressed neuropeptide-related and inflammation-related protein in the lumbar spinal cord of xenograft mice. Overall, our findings suggest that EA treatment ameliorated cancer-induced pain behaviors in the mouse xenograft model of cancer pain, possibly through inhibiting the expressions of neuropeptide-related and inflammation-related protein in central level following tumor cell xenografts.

Antibody-Protein-Aptamer Electrochemical Biosensor based on Highly Efficient Proximity-Induced DNA Hybridization on Tetrahedral DNA Nanostructure for Sensitive Detection of Insulin-like Growth Factor-1.

Herein, an antibody-protein-aptamer electrochemical biosensor was designed by highly efficient proximity-induced DNA hybridization on a tetrahedral DNA nanostructure (TDN) for ultrasensitive detection of human insulin-like growth factor-1 (IGF-1). Impressively, the IGF-1 antibody immobilized on the top vertex of the TDN could effectively capture the target protein with less steric effect, and the ferrocene-labeled signal probe (SP) bound on the bottom vertex of the TDN was close to the electrode surface for generating a strong initial signal. In the presence of target protein IGF-1 and an aptamer strand, an antibody-protein-aptamer sandwich could be formed on the top vertex of TDN, which would trigger proximity-induced DNA hybridization to release the SP on the bottom vertex of TDN; therefore, the signal response would decrease dramatically, enhancing the sensitivity of the biosensor. As a result, the linear range of the proposed biosensor for target IGF-1 was 1 fM to 1 nM with the limit of detection down to 0.47 fM, which was much lower than that of the traditional TDN designs on electrochemical biosensors. Surprisingly, the use of this approach offered an innovative approach for the sensitive detection of biomarkers and illness diagnosis.

Factors that determine glucose variability, defined by the coefficient of variation in continuous glucose monitoring values, in a Chinese population with type 2 diabetes.

AIMS: To elucidate the clinical determinants of the coefficient of variation (CV) of glucose by analysing the pancreatic ß-cell function of subjects with type 2 diabetes mellitus (T2DM). METHODS: A total of 716 Chinese subjects with T2DM were included. Continuous glucose monitoring (CGM) was used to assess blood glucose, and the CV was calculated. C-peptide concentration at 0, 0.5, 1, 2 and 3 hours (Cp0h, Cp0.5h, Cp1h, Cp2h and Cp3h, respectively) was measured after a standard 100-g steamed bun meal test to assess pancreatic ß-cell function. The determinants of glucose variability defined by the CV of CGM values were explored from two perspectives: the CV of qualitative variables and the CV of quantitative variables. RESULTS: Our data revealed that C-peptide concentration (Cp0h, Cp0.5h, Cp1h, Cp2h, Cp3h), area under the curve for C-peptide concentration at 0.5 and 3 hours (AUC-Cp0.5h and AUC-Cp3h) decreased with increasing CV quartile (P < 0.05). The CV was negatively correlated with homeostatic model assessment of ß-cell function index, C-peptide concentration at all timepoints, and AUC-Cp0.5h and AUC-Cp3h (P < 0.001). Quantile regression analysis showed that AUC-Cp0.5h had an overall negative effect on the CV in the 0.05 to 0.95 quartiles, and AUC-Cp3h tended to have a negative effect on the CV in the 0.2 to 0.65 quartiles. After adjusting for confounders, multinomial logistic regression showed that each 1-unit increase in AUC-Cp0.5h was associated with a 31.7% reduction in the risk of unstable glucose homeostasis (CV > 36%; P = 0.036; odds ratio 0.683; 95% confidence interval 0.478-0.976). We also identified the AUC-Cp0.5h (0.735 ng/mL) and AUC-Cp3h (13.355 ng/mL) cut-off values for predicting unstable glucose homeostasis (CV >36%) in T2DM subjects. CONCLUSION: Our study suggests that impaired pancreatic ß-cell function may be a clinical determining factor of CV of glucose in people with T2DM.

Tissue Accumulation and Biotransformation of 6PPD-Quinone in Adult Zebrafish and Its Effects on the Intestinal Microbial Community.

The pronounced lethality of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone or 6PPDQ) toward specific salmonids, while sparing other fish species, has received considerable attention. However, the underlying cause of this species-specific toxicity remains unresolved. This study explored 6PPDQ toxicokinetics and intestinal microbiota composition in adult zebrafish during a 14-day exposure to environmentally realistic concentrations, followed by a 7-day recovery phase. Predominant accumulation occurred in the brain, intestine, and eyes, with the lowest levels in the liver. Six metabolites were found to undergo hydroxylation, with two additionally undergoing O-sulfonation. Semiquantitative analyses revealed that the predominant metabolite featured a hydroxy group situated on the phenyl ring adjacent to the quinone. This was further validated by assessing enzyme activity and determining in silico binding interactions. Notably, the binding affinity between 6PPDQ and zebrafish phase I and II enzymes exceeded that with the corresponding coho salmon enzymes by 1.04-1.53 times, suggesting a higher potential for 6PPDQ detoxification in tolerant species. Whole-genome sequencing revealed significant increases in the genera Nocardioides and Rhodococcus after exposure to 6PPDQ. Functional annotation and pathway enrichment analyses predicted that these two genera would be responsible for the biodegradation and metabolism of xenobiotics. These findings offer crucial data for comprehending 6PPDQ-induced species-specific toxicity.

Relationship Analysis Between Pericoronary Fat Attenuation Index and Parameters of Single Plaque.

OBJECTIVE: The aim of the study is to investigate the relationship between plaque parameters and pericoronary fat attenuation index (FAI). METHODS: A retrospective collection was performed on 227 patients with coronary heart disease who underwent coronary computed tomography angiography examinations in our hospital from May 2021 to April 2023, with a total of 254 right coronary or left anterior descending coronary arteries exhibiting solitary plaques within the FAI measurement area. Based on whether the proximal coronary FAI value was ≥ -70.0 HU, patients and coronary arteries were divided into FAI-positive group (67 cases, 73 coronary arteries) and FAI-negative group (160 cases, 181 coronary arteries). Quantitative parameters of coronary solitary plaques were collected, including stenosis severity, plaque length, plaque volume, plaque composition ratios, minimal luminal area, and calcification score, as well as qualitative parameters such as plaque types and high-risk plaques. Differences in plaque parameters between the FAI-positive and FAI-negative groups were compared. RESULTS: The proportion of positive remodeling in the FAI-positive group (73 coronary arteries) was higher than that in the FAI-negative group (181 coronary arteries) with statistical significance (89.0% vs 78.5%, P = 0.049). Multivariate analysis revealed that positive remodeling was a risk factor for abnormal FAI values in solitary plaques (odds ratio, 2.271, P = 0.049). CONCLUSIONS: The FAI-positive group had a higher proportion of positive remodeling, and positive remodeling was an independent risk factor for positive FAI values.

The safety and efficacy of five surgical treatments in prostate enucleation: a network meta-analysis.

PURPOSE: The aim of our study was to investigate the comparative outcomes of five different energy types on surgical efficacy and postoperative recovery in patients with benign prostate hyperplasia. METHODS: The literature was systematically reviewed on December 1st, 2023, encompassing studies retrieved from PubMed, Embase, Web of Science, and The Cochrane Library databases that incorporated clinical studies of holmium laser enucleation of the prostate (HoLEP), Thulium:YAG laser enucleation of the prostate (ThuLEP), transurethral plasmakinetic enucleation of prostate (PKEP), diode laser enucleation of the prostate (DiLEP) and thulium fiber laser enucleation of the prostate (ThuFLEP) in the treatment of prostatic hyperplasia. Two independent reviewers extracted study data and conducted quality assessments using the Cochrane Collaboration's Risk of Bias tool and Newcastle-Ottawa Scale (NOS). Network meta-analysis (NMA) was employed to indirectly analyze the outcomes of endoscopic enucleation of the prostate (EEP) techniques. RESULTS: The study included a total of 38 studies, comprising 21 non-randomized controlled trials (nRCTs) and 17 randomized controlled trials (RCTs), incorporating five distinct techniques: holmium laser, Thulium:YAG laser, bipolar plasma, diode laser and thulium fiber laser. In comparing treatment durations, ThuLEP and HoLEP had shorter overall hospital stays than PKEP, while the enucleation time of ThuLEP and HoLEP was shorter than that of ThuFLEP. Moreover, the enucleation tissue weight of both thulium fiber laser and holmium laser was heavier than bipolar plasma. However, the analysis did not reveal any statistically significant variation in complications among the various types of enucleation. In postoperative follow-up, the IPSS at 3 months post-operation was superior in the Thulium:YAG laser group compared to the holmium laser group. The thulium fiber laser technique demonstrated significant advantages over other enucleation methods in terms of QoL and PVR at 12 months after surgery. CONCLUSION: Theoretical properties may vary among different energy sources; however, there are no discernible clinical differences in operation-related parameters, postoperative complications, and postoperative follow-up. Therefore, the choice of laser does not significantly impact the outcome. However, due to the limited number of included studies, future research should focus on larger sample sizes and multicenter investigations to further validate the findings of this study.

Ras inhibitor CAPRI enables neutrophil-like cells to chemotax through a higher-concentration range of gradients.

Neutrophils sense and migrate through an enormous range of chemoattractant gradients through adaptation. Here, we reveal that in human neutrophils, calcium-promoted Ras inactivator (CAPRI) locally controls the GPCR-stimulated Ras adaptation. Human neutrophils lacking CAPRI (caprikd ) exhibit chemoattractant-induced, nonadaptive Ras activation; significantly increased phosphorylation of AKT, GSK-3α/3ß, and cofilin; and excessive actin polymerization. caprikd cells display defective chemotaxis in response to high-concentration gradients but exhibit improved chemotaxis in low- or subsensitive-concentration gradients of various chemoattractants, as a result of their enhanced sensitivity. Taken together, our data reveal that CAPRI controls GPCR activation-mediated Ras adaptation and lowers the sensitivity of human neutrophils so that they are able to chemotax through a higher-concentration range of chemoattractant gradients.

De novo transcriptome analysis of Protohermes xanthodes Navás (Megaloptera: Corydalidae) reveling the effects of sublethal chlorpyrifos on the expression of cholinergic neuronal genes.

The insect cholinergic neuron system is the target for various pesticides, including organophosphate, carbamate and neonicotinoid pesticides. In this study, we conducted a de novo transcriptome analysis on the aquatic insect Protohermes xanthodes and identified for the first time presenting sixteen genes encoding cholinergic neuronal proteins (PxanChaT, PxanVAChT, PxanmAChR, PxannAChRs, and PxanAChEs), which are candidates for acetylcholine synthesis, transport, reception and degradation in cholinergic synapse. FPKM analysis revealed that these genes are primarily expressed in head and nerve cord of P. xanthodes larvae, and some of them are also abundant in hindgut, malpighian tubules and tracheae. After exposed to different concentrations of sublethal chlorpyrifos (CPF), expression of these cholinergic neuronal genes are generally increased and then decreased with the increase of CPF concentration, except PxannAChRα9 which is increased in both 4.2 and 8.4 µg/L CPF groups. Short-term (96 h) CPF exposure resulted in significant up-regulation of PxanAChE1 expression in P. xanthodes larvae exposed to 0.42 and 4.2 µg/L CPF concentrations, while PxanAChE2 was up-regulated only in 0.42 µg/L CPF group. After long-term (14 d) CPF exposure, PxanAChE1 expression was down-regulated in 0.168 and 0.42 µg/L CPF groups. PxanAChE2 expression was dramatically decreased in all CPF groups. Moreover, acetylcholinesterase (AChE) activity was significantly decreased across all long-term CPF exposure groups. These results suggested that sublethal exposure to CPF can disrupt the expression of cholinergic neuronal genes in P. xanthodes larvae, and implied that long-term sublethal CPF exposure may cause toxic effects on P. xanthodes larvae by inhibiting AChE activity. Furthermore, identification of cholinergic neuronal genes in P. xanthodes provided candidate molecular markers for study the toxic effects of environmental pollutants on the neuron system of an aquatic predatory insect with ecological importance.

The relationship between self-esteem and happiness of college students in China:A moderated mediation model.

The objective of the study is to explore the influence of self-esteem on the happiness levels of college students and the mediating roles of social avoidance and loneliness. 1021 college students between 18 and 24 years of age completed the Self-esteem Scale, General Well-being Scale, Social Avoidance and Distress Scale, UCLA Loneliness Scale and Interpersonal Trust Scale.And descriptive statistical analysis and correlation analysis, structural equation model analysis were conducted. The result turns out that Self-esteem negatively predicted the happiness levels of college students. Self-esteem indirectly predicted happiness through three paths: mediating the roles of social avoidance, mediating the roles of loneliness and the chain-mediated roles of social avoidance and loneliness in college students.Interpersonal Trust moderated the relationship between loneliness and happiness.The higher the self-esteem levels of the college students, the less happiness they experienced.

Methylated derivatives of polycyclic aromatic hydrocarbons in road dust, green belt soil and parking lot dust: occurrence, spatial distribution and emission sources.

Convenient transportation facilities not only bring the higher standard of living to big cities, but also bring some environmental pollution problems. In order to understand the presence and sources of methylated polycyclic aromatic hydrocarbons (Me-PAHs) in environmental samples and their association with total organic carbon (TOC), 49 Me-PAHs were analyzed in road dust, green belt soil and parking lot dust samples in Harbin. The results showed that the ranges of the total Me-PAHs (ΣMe-PAHs) content in road dust were 221-5826 ng/g in autumn and 697-7302 ng/g in spring, and those in green belt soil were 170-2509 ng/g and 155-9215 ng/g in autumn and spring, respectively. And ΣMe-PAHs content in parking lot dust ranged from 269 to 2515 ng/g in surface parking lots and from 778 to 10,052 ng/g in underground parking lots. In these samples, the composition profile of Me-PAHs was dominated by 4-ring Me-PAHs. The results of diagnostic ratios and principal component analysis (PCA) indicated that petrogenic and pyrogenic sources were the main sources of Me-PAHs in the samples. Spearman correlation analysis showed that there was no correlation for Me-PAHs in road dust and green belt soil on the same road. Furthermore, there was a significant positive relationship (0.12 ≤ R2 ≤ 0.67, P < 0.05) between Me-PAHs concentrations and the TOC content. This study demonstrated the presence of Me-PAHs with high concentrations in the road environment samples of Harbin.

Bifunctional Chiral Electrocatalysts Enable Enantioselective α-Alkylation of Aldehydes.

Herein, we describe an innovative approach to the asymmetric electrochemical α-alkylation of aldehydes facilitated by a newly designed bifunctional chiral electrocatalyst. The highly efficient bifunctional chiral electrocatalyst combines a chiral aminocatalyst with a redox mediator. It plays a dual role as a redox mediator for electrooxidation, while simultaneously providing remarkable asymmetric induction for the stereoselective α-alkylation of aldehydes. Additionally, this novel catalyst exhibits enhanced catalytic activity and excellent stereoselective control comparable to conventional catalytic systems. As a result, this strategy provides a new avenue for versatile asymmetric electrochemistry. The electrooxidation of diverse phenols enables the C-H/C-H oxidative α-alkylation of aldehydes in a highly chemo- and stereoselective fashion. Detailed mechanistic studies by control experiments and cyclic voltammetry analysis demonstrate possible reaction pathways and the origin of enantio-induction.

Transferrin promotes chondrogenic differentiation in condylar growth through inducing autophagy via ULK1-ATG16L1 axis.

Skeletal mandibular hypoplasia (SMH) is one of the most common skeletal craniofacial deformities in orthodontics, which was often accompanied by impaired chondrogenesis and increasing apoptosis of condylar chondrocytes. Therefore, protecting chondrocytes from apoptosis and promoting chondrogenesis in condylar growth is vital for treatment of SMH patients. Transferrin (TF) was highly expressed in condylar cartilage of newborn mice and was gradually declined as the condyle ceased growing. Interestingly, serum level of TF in SMH patients was significantly lower than normal subjects. Hence, the aim of our study was to investigate the effect of TF on survival and differentiation of chondrocytes and condylar growth. First, we found that TF protected chondrogenic cell line ATDC5 cells from hypoxia-induced apoptosis and promoted proliferation and chondrogenic differentiation in vitro. Second, TF promoted chondrogenic differentiation and survival through activating autophagic flux. Inhibiting autophagic flux markedly blocked the effects of TF. Third, TF significantly activated ULK1-ATG16L1 axis. Silencing either transferrin receptor (TFRC), ULK1/2 or ATG16 significantly blocked the autophagic flux induced by TF, as well as its effect on anti-apoptosis and chondrogenic differentiation. Furthermore, we established an organoid culture model of mandible ex vivo and found that TF significantly promoted condylar growth. Taken together, our study unraveled a novel function of TF in condylar growth that TF protected chondrocytes from hypoxia-induced apoptosis and promoted chondrogenic differentiation through inducing autophagy via ULK1-ATG16L1 axis, which demonstrated that TF could be a novel growth factor of condylar growth and shed new light on developing treatment strategy of SMH patients.

Acupuncture for Low Back Pain: Reevaluation of Systematic Reviews and Meta-analyses.

PURPOSE OF REVIEW: This overview aims to reevaluate the methodological quality, report quality, and evidence quality of systematic reviews (SRs)/meta-analyses (MAs) of acupuncture for low back pain to determine whether acupuncture effectively treats low back pain (LBP). RECENT FINDINGS: Twenty-three SRs/MAs were deemed eligible for the present overview. The AMSTAR 2 score showed that the methodological quality of one SR/MA was of medium quality, one was of low quality, and 21 were of critically low quality. Based on the results of the PRISMA evaluation, there are certain areas for improvement in the quality of reporting of SRs/MAs. There were some reporting flaws in the topic of search strategy (8/23, 34.78%), certainty assessment (4/23, 17.39%), the certainty of evidence (4/23, 17.39%), registration and protocol (3/23, 13.04%), and availability of data, code, and other material (1/23, 4.35%). Results from the GRADE evaluation indicated that 13 of 255 outcomes were rated as moderate, 88 were low, and 154 were very low. Acupuncture effectively treated LBP in the SRs/MAs included in the reevaluation. However, the methodological, report, and evidence-based quality of the SRs/MAs on acupuncture for LBP was low. Therefore, further rigorous and comprehensive studies are warranted to improve the quality of SRs/MAs in this field.

Prognostic value of hysterosalpingography after salpingostomy in patients with hydrosalpinx.

To assess whether post-hysterosalpingography evaluation was associated with pregnancy rate and to identify independent risk factors for pregnancy success after salpingostomy in patients with hydrosalpinx. A retrospective analysis was conducted on the clinical data of 47 patients diagnosed with hydrosalpingography (HSG) in our hospital from 2015 to 2018. These patients received laparoscopic surgery and another salpingography within 2 months after surgery. According to the fallopian tube conditions evaluated by HSG before and after surgery, the patients could be divided into two groups. According to the pregnancy rate and postoperative HSG of patients with hydrosalpinx after laparoscopy, the total pregnancy rate of the tubal improved group was 65.62%, while that of the non-improved group was 20%, with statistical significance (p < 0.05). We found that hysterosalpingography after salpingostomy in patients with hydrosalpinx can provide reference for clinical treatment and improve the prognosis of patients.

Postoperative HSG improvement was an independent risk factor for pregnancy rate in patients with hydrosalpinx after laparoscopic surgery. Impact statementWhat is already known on this subject? Fallopian tube obstruction is an important cause of female infertility. Current studies have shown that most spontaneous pregnancies in patients with hydrosalpinx after salpingostomy occur within 18 months, however, pregnancy rates and outcomes vary from report to report.What do the results of this study add? Many studies have shown that hydrosalpinx reduces the success rate of natural pregnancy and embryo transfer, but the mechanism of hydrosalpinx affecting pregnancy remains unclear. This study explored the mechanism of successful pregnancy through hysterosalpingography after salpingostomy in patients with hydrosalpinx.What are the implications of these findings for clinical practice and/or further research? To evaluate the prognosis of patients with hydrosalpinx after laparoscopic salpingostomy by hysterosalpingography (HSG), and to reflect the improvement according to the postoperative pregnancy rate of the patients. To provide clinical personalized treatment plan.

Level of humanistic care ability and its influencing factors among nursing aides in long-term care facilities.

OBJECTIVE: To determine the level and influencing factors of the humanistic care ability (HCA) in nursing aides, thus providing a baseline for its improvement. METHODS: This study investigated 302 nursing aides in six long-term care facilities (LTCFs) in Suzhou between December 2021 and June 2022 by convenience sampling. A descriptive questionnaire and the Caring Ability Inventory were applied in this study. RESULTS: The HCA was at a low level, and its influencing factors were education level, marital status, personality, reason for employment, and the degree of perceived care from colleagues (p<0.05). CONCLUSIONS: Nursing aides' HCA needs to be strengthened urgently. Nursing aides with poor education, widowed, single, and an introversion type of personality should receive more attention. Additionally, creating a warm atmosphere among colleagues and cultivating the nursing aides' motivation for eldercare will help improve their HCA.

The maternal-to-zygotic transition revisited.

The development of animal embryos is initially directed by maternal gene products. Then, during the maternal-to-zygotic transition (MZT), developmental control is handed to the zygotic genome. Extensive research in both vertebrate and invertebrate model organisms has revealed that the MZT can be subdivided into two phases, during which very different modes of gene regulation are implemented: initially, regulation is exclusively post-transcriptional and post-translational, following which gradual activation of the zygotic genome leads to predominance of transcriptional regulation. These changes in the gene expression program of embryos are precisely controlled and highly interconnected. Here, we review current understanding of the mechanisms that underlie handover of developmental control during the MZT.

Coordination-Directed Construction of Molecular Links.

Since the emergence of the concept of chemical topology, interlocked molecular assemblies have graduated from academic curiosities and poorly defined species to become synthetic realities. Coordination-directed synthesis provides powerful, diverse, and increasingly sophisticated protocols for accessing interlocked molecules. Originally, metal ions were employed solely as templates to gather and position building blocks in entwined or threaded arrangements. Recently, metal centers have increasingly featured within the backbones of the integral structural elements, which in turn use noncovalent interactions to self-assemble into intricate topologies. By outlining ingenious recent examples as well as seminal classic cases, this Review focuses on the role of metal-ligand paradigms in assembling molecular links. In addition, the ever-evolving approaches to efficient assembly, the structural features of the resulting architectures, and their prospects for the future are also presented.

Novel melatonin-trientine conjugate as potential therapeutic agents for Alzheimer's disease.

Researchers continue to explore drug targets to treat the characteristic pathologies of Alzheimer's disease (AD). Some drugs relieve the pathological processes of AD to some extent, but the failed clinical trials indicate that multifunctional agents seem more likely to achieve the therapy goals for this neurodegenerative disease. Herein, a novel compound named melatonin-trientine (TM) has been covalently synthesized with the natural antioxidant compounds melatonin and the metal ion chelator trientine. After toxicological and pharmacokinetic verification, we elucidated the effects of intraperitoneal administration of TM on AD-like pathology in 6-month-old mice that express both the ß-amyloid (Aß) precursor protein and presenilin-1 (APP/PS1). We found that TM significantly decreased Aß deposition and neuronal degeneration in the brains of the APP/PS1 double transgenic mice. This result may be due to the upregulation of iron regulatory protein-2 (IRP2), insulin degrading enzyme (IDE), and low density lipoprotein receptor related protein 1 (LRP1), which leads to decreases in APP and Aß levels. Additionally, TM may promote APP non-amyloidogenic processing by activating the melatonin receptor-2 (MT2)-dependent signaling pathways, but not MT1. In addition, TM plays an important role in blocking γ-secretase, tau hyperphosphorylation, neuroinflammation, oxidative stress, and metal ion dyshomeostasis. Our results suggest that TM may effectively maximize the therapeutic efficacy of targeting multiple mechanisms associated with AD pathology.

Effect of doxofylline on pulmonary inflammatory response and oxidative stress during mechanical ventilation in rats with COPD.

OBJECTIVE: To evaluate the effects of doxofylline on inflammatory responses and oxidative stress during mechanical ventilation in rats with chronic obstructive pulmonary disease (COPD). METHODS: Eight-week-old male Sprague Dawley rats were selected, and the COPD rat model was constructed. The rats were randomly divided into a model group (group M), a model + normal saline group (group N), a doxofylline group (group D), and a control group fed with conventional chow and given normal oxygen supply (group C) (n = 12 in each group). Tracheal intubation and mechanical ventilation were conducted in the rats in each group after anesthesia. A real-time intravenous infusion with 50 mg/kg of doxofylline was conducted in group D, and there was no drug intervention in groups C, N and M. Pathological manifestations of the pulmonary tissues were observed and compared among the groups. And some indicators were evaluated. RESULTS: (1) The pulmonary tissues of the rats in groups M, N, and D exhibited typical pathological histological changes of COPD. (2) Groups M, N, and D showed increased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue and BALF, and decreased PaO2 and IL-10 and SOD levels, compared with group C. (3). Group D showed decreased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue, and increased PaO2 and IL-10 and SOD levels, compared with group N or M. CONCLUSION: Doxofylline was shown to improve ventilation and air exchange during mechanical ventilation in rats with COPD, reduce the inflammatory response and oxidative stress, and mitigate the degree of pulmonary tissue injury.