LINC00460/miR-186-3p/MYC feedback loop facilitates colorectal cancer immune escape by enhancing CD47 and PD-L1 expressions.

BACKGROUND: Long non-coding RNAs (LncRNAs) have been implicated as critical regulators of cancer tumorigenesis and progression. However, their functions and molecular mechanisms in colorectal cancer (CRC) still remain to be further elucidated. METHODS: LINC00460 was identified by differential analysis between human CRC and normal tissues and verified by in situ hybridization (ISH) and qRT-PCR. We investigated the biological functions of LINC00460 in CRC by in vitro and in vivo experiments. We predicted the mechanism and downstream functional molecules of LINC00460 by bioinformatics analysis, and confirmed them by dual luciferase reporter gene assay, RNA immunoprecipitation (RIP), RNA pull-down, etc. RESULTS: LINC00460 was found to be significantly overexpressed in CRC and associated with poor prognosis. Overexpression of LINC00460 promoted CRC cell immune escape and remodeled a suppressive tumor immune microenvironment, thereby promoting CRC proliferation and metastasis. Mechanistic studies showed that LINC00460 served as a molecular sponge for miR-186-3p, and then promoted the expressions of MYC, CD47 and PD-L1 to facilitate CRC cell immune escape. We also demonstrated that MYC upregulated LINC00460 expression at the transcriptional level and formed a positive feedback loop. CONCLUSIONS: The LINC00460/miR-186-3p/MYC feedback loop promotes CRC cell immune escape and subsequently facilitates CRC proliferation and metastasis. Our findings provide novel insight into LINC00460 as a CRC immune regulator, and provide a potential therapeutic target for CRC patients.

Nursing management of intracranial hypertension in adults with severe brain injury in a neurosurgery intensive care unit: a best practice implementation project.

INTRODUCTION: The nursing management of intracranial hypertension in adult patients with severe brain injury is crucial for maintaining the stability of intracranial pressure, which ultimately improves patient outcomes. OBJECTIVES: This project aimed to implement evidence-based practices for the nursing management of intracranial hypertension in adult patients with severe brain injury. METHODS: This evidence implementation project was conducted in a neurosurgery intensive care unit in a large tertiary hospital in Guangzhou, China. The project was guided by the JBI Evidence Implementation Framework, which is an audit and feedback model with seven stages. The Ottawa Model of Research Use was used to identify barriers and facilitators to best practices and to develop improvement strategies. RESULTS: Thirty-three nurses and 50 patients with severe brain injury participated in the baseline and follow-up audits. After project implementation, follow-up audits revealed significantly improved compliance with best practices compared with baseline. Nurses' awareness of best practices increased (41% to 96%); nursing assessment, monitoring, and interventions related to intracranial hypertension rose significantly (from 82%, 75%, and 59% to 98%, 84%, and 87%, respectively); and patients' optic nerve sheath diameter was notably lower (6.002±0.677 mm to 5.698±0.730 mm). CONCLUSIONS: The systematic integration of consistent training and education, together with the refinement of care processes and the creation of relevant tools, led to a significant improvement in awareness and adherence to best practices. Further testing of this program in more hospitals is needed. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A243.

Trilobatin suppresses aging-induced cognitive impairment by targeting SIRT2: Involvement of remodeling gut microbiota to mediate the brain-gut axis.

BACKGROUND: Aging is associated with learning and memory disorder, affecting multiple brain areas, especially the hippocampus. Previous studies have demonstrated trilobatin (TLB), as a natural food additive, can extend the life of Caenorhabditis elegans and exhibit neuroprotection in Alzheimer's disease mice. However, the possible significance of TLB in anti-aging remains elusive. PURPOSE: This study aimed to delve into the physiological mechanism by which TLB ameliorated aging-induced cognitive impairment in senescence-accelerated mouse prone 8 (SAMP8) mice. METHODS: 6-month-old SAMP8 mice were administrated with TLB (5, 10, 20 mg/kg/day, i.g.) for 3 months. The therapeutic effect of TLB on aging-induced cognitive impairment was assessed in mice using behavioral tests and aging score. The gut microbiota composition in fecal samples was analyzed by metagenomic analysis. The protective effects of TLB on blood-brain barrier (BBB) and intestinal barrier were detected by transmission electron microscope, H&E staining and western blot (WB) assay. The inhibitive effects of TLB on inflammation in brain and intestine were assessed using immunofluorescence, WB and ELISA assay. Molecular docking and surface plasma resonance (SPR) assay were utilized to investigate interaction between TLB and sirtuin 2 (SIRT2). RESULTS: Herein, the findings exhibited TLB mitigated aging-induced cognitive impairment, neuron injury and neuroinflammation in hippocampus of aged SAMP8 mice. Moreover, TLB treatment repaired imbalance of gut microbiota in aged SAMP8 mice. Furthermore, TLB alleviated the damage to BBB and intestinal barrier, concomitant with reducing the expression of SIRT2, phosphorylated levels of c-Jun NH2 terminal kinases (JNK) and c-Jun, and expression of MMP9 protein in aged SAMP8 mice. Molecular docking and SPR unveiled TLB combined with SIRT2 and down-regulated SIRT2 protein expression. Mechanistically, the potential mechanism of SIRT2 in TLB that exerted anti-aging effect was validated in vitro. As expected, SIRT2 deficiency attenuated phosphorylated level of JNK in HT22 cells treated with d-galactose. CONCLUSION: These findings reveal, for the first time, SIRT2-mediated brain-gut barriers contribute to aging and aging-related diseases, and TLB can rescue aging-induced cognitive impairment by targeting SIRT2 and restoring gut microbiota disturbance to mediate the brain-gut axis. Overall, this work extends the potential application of TLB as a natural food additive in aging-related diseases.

Identification of novel variations in three cases with rare inherited neuromuscular disorder.

Inherited neuromuscular disorder (IND) is a broad-spectrum, clinically diverse group of diseases that are caused due to defects in the neurosystem, muscles and related tissue. Since IND may originate from mutations in hundreds of different genes, the resulting heterogeneity of IND is a great challenge for accurate diagnosis and subsequent management. Three pediatric cases with IND were enrolled in the present study and subjected to a thorough clinical examination. Next, a genetic investigation was conducted using whole-exome sequencing (WES). The suspected variants were validated through Sanger sequencing or quantitative fluorescence PCR assay. A new missense variant of the Spastin (SPAST) gene was found and analyzed at the structural level using molecular dynamics (MD) simulations. All three cases presented with respective specific clinical manifestations, which reflected the diversity of IND. WES detected the diagnostic variants in all 3 cases: A compound variation comprising collagen type VI α3 chain (COL6A3) (NM_004369; exon19):c.6322G>T(p.E1208*) and a one-copy loss of COL6A3:exon19 in Case 1, which are being reported for the first time; a de novo SPAST (NM_014946; exon8):c.1166C>A(p.T389K) variant in Case 2; and a de novo Duchenne muscular dystrophy (NM_004006; exon11):c.1150-17_1160delACTTCCTTCTTTGTCAGGGGTACATGATinsC variant in Case 3. The structural and MD analyses revealed that the detected novel SPAST: c.1166C>A(p.T389K) variant mainly altered the intramolecular hydrogen bonding status and the protein segment's secondary structure. In conclusion, the present study expanded the IND mutation spectrum. The study not only detailed the precise diagnoses of these cases but also furnished substantial grounds for informed consultations. The approach involving the genetic evaluation strategy using WES for variation screening followed by validation using appropriate methods is beneficial due to the considerable heterogeneity of IND.

Factors influencing spontaneous hypothermia after emergency trauma and the construction of a predictive model.

This study aimed to investigate spontaneous hypothermia among emergency trauma patients and develop a predictive model. A cohort of 162 emergency trauma patients was categorized into hypothermic (n = 61) and control (n = 101) groups, with trauma severity assessed using the modified Glasgow Coma Scale (GCS). Univariate analysis revealed significant differences between the groups in trauma severity, posture, garment wetness, warming measures, pre-hospital fluid resuscitation, and modified GCS scores (P < 0.05). The hypothermic group exhibited lower prothrombin time compared to the control group (P < 0.05). A logistic regression model was constructed, expressed as Y = 25.76 - 1.030X 1 + 0.725X 2 + 0.922X 3 - 0.750X 4 - 0.57X 6, and its fit was evaluated using the Hosmer-Lemeshow test. The receiver operating characteristic curve demonstrated an area under the curve of 0.871, with 81.2% sensitivity and 79.5% specificity. The Youden index identified the optimal predictive cut-off at its highest (0.58). Validation results included 86.21% sensitivity, 82.93% specificity, and 84.29% accuracy. Risk factors for spontaneous hypothermia after emergency trauma encompassed trauma severity, posture during consultation, clothing dampness upon admission, warming measures during transfer, pre-hospital fluid resuscitation, and modified GCS scores. The risk prediction model demonstrated high accuracy, enabling effective assessment of spontaneous hypothermia risk in emergency trauma patients and facilitating preventive measures.

Synthesis and Properties of a Novel Reactive and Low-Migration-Resistant Antioxidant and Its Application in Rubber Composites.

The addition of antioxidants to rubber is one of the most economical and effective methods for delaying rubber aging. However, antioxidant migration can cause environmental pollution. To address this issue, a new reactive antioxidant was synthesized via the chemical bonding of glycidyl methacrylate (GMA) and p-aminodiphenylamine (PPDA). The product was characterized by Fourier-transform infrared spectroscopy, which confirmed the successful reaction between GMA and PPDA, resulting in a compound with the expected structure. The mixture was then combined with a composite of styrene-butadiene rubber and carbon black. The tensile strength, antioxidant properties, migration, and RPA of the resulting materials were tested and compared with those of the commercial antioxidants N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine, N-isopropyl-N'-phenyl-1,4-phenylenediamine, and poly(1,2-dihydro-2,2,4-trimethylquinoline). After the glycidyl methacrylate antioxidant was grafted onto p-aminodiphenylamine, it became highly compatible with and dispersed in the rubber matrix. The antiaging and antimigration properties of the rubber antioxidants were enhanced without damaging the mechanical properties of the rubber matrix. The short-term and long-term antiaging and antimigration properties of this antioxidant are superior to those of commercially available antioxidants.

Functional assessment of a novel biallelic MYH3 variation causing CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B).

BACKGROUND: The MYH3-associated myosinopathies comprise a spectrum of rare neuromuscular disorders mainly characterized by distal arthrogryposis with or without other features like pterygia and vertebrae fusion. CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B) is the only known autosomal recessiveMYH3-associated myosinopathy so far, with no more than two dozen cases being reported. MATERIALS AND METHODS: A boy with CPSKF1B was recruited and subjected to a comprehensive clinical and imaging evaluation. Genetic detection with whole-exome sequencing (WES) was performed on the patient and extended family members to identify the causative variation. A series of in silico and in vitro investigations were carried out to verify the pathogenicity of the two variants of the identified compound heterozygous variation. RESULTS: The patient exhibited moderate CPSKF1B symptoms including multiarticular contractures, webbed neck, and spondylocarpotarsal fusion. WES detected a compound heterozygous MYH3 variation consisting of two variants, namely NM_002470.4: c.3377A>G; p. (E1126G) and NM_002470.4: c.5161-2A>C. It was indicated that the NM_002470.4: c.3377A>G; p. (E1126G) variant mainly impaired the local hydrogen bond formation and impacted the TGF-B pathway, while the NM_002470.4: c.5161-2A>C variant could affect the normal splicing of pre-mRNA, resulting in the appearance of multiple abnormal transcripts. CONCLUSIONS: The findings of this study expanded the mutation spectrum of CPSKF1B, provided an important basis for the counseling of the affected family, and also laid a foundation for the functional study of MYH3 mutations.

Efficacy of neuroendoscopic-assisted surgery in the management of symptomatic sacral perineural (Tarlov) cysts: a technical report.

Introduction: The Tarlov cysts are pathological enlargements of the cerebrospinal fluid spaces between the endoneurium and perineurium, which can cause intolerable sciatic pain, motor impairment of lower limbs, and bladder/bowel dysfunction. Currently, the treatment results are unsatisfactory due to the low cure rates and extensive surgical trauma. Thus, there is an ongoing exploration of surgical techniques for Tarlov treatment. In the current study, we present a novel neuroendoscopic-assisted technique that combines the fenestration, leakage sealing, and tamponade of the Tarlov cyst. Methods: Between January 2020 and December 2021, a total of 32 Tarlov patients were enrolled and received neuroendoscopic-assisted surgery. Their pre- and post-surgical Visual Analogue Scale (VAS) scores, major complaints, and MR imaging were recorded for comparison. Results: 27 of 32 patients (84.4%) patients demonstrated immediate pain relief as their VAS scores decreased from 5.6 ± 1.5 to 2.5 ± 1.1 (p < 0.01) on the first day after surgery. At the 3-month follow-up, the patients' average VAS score continued to decrease (1.94 ± 0.8). Meanwhile, saddle paresthesia, urinary incontinence, and constipation were relieved in 6 (50%), 4 (80%), and 5 (41.7%), respectively, according to patients self-report. No surgical-related complication was observed in any of the cases. Discussion: We conclude that neuroendoscopic-assisted surgery is an effective surgical method for symptomatic Tarlov cysts with minimized complications.

The Role of Matrix Metalloproteinases in Thoracic Aortic Disease: Are They Indicators for the Pathogenesis of Dissections?

The pathogenesis of aortic aneurysm and dissection continues to be under discussion. Extracellular matrix (ECM) remodeling processes in the aortic wall are hypothesized to be involved in the development of the disorders. Therefore, in a histological study, we investigated the expression of metalloproteases 1 and 9 (MMP1 and MMP9) and their inhibitors (TIMP 1 and TIMP 2) in cardiac surgery patients. In parallel, we studied the aortic roots by echocardiography. Clinical reports of 111 patients (30 women and 81 men) who suffered from aortic aneurysms and aortic dissection were evaluated and studied by transesophageal echocardiography. Seven patients who had coronary heart disease served as "healthy controls". All patients underwent the necessary surgical procedure according to the diagnosed aortic disease in the period from 2007 to 2015. A tissue sample of the aortic biopsies was collected from each patient during surgery. Immunohistochemical staining was performed for MMP1 and MMP9 and TIMP1 and TIMP2 as well. Vascularization was monitored by a CD 31 antibody. In direct comparison, the expressions are not homogeneous. We found the smallest changes in the intima area at all. TIMP 1 and TIMP 2 distribution increases from the lumen of the vessel outward in the wall layers of the aorta. In the case of arteriosclerotic changes, intima had a capillarization, but not in the media. An opposite pattern was found in the dissected aortas. There are differences in the vascularization between the aneurysm and dissection and the different layers, respectively. A different remodeling process of the ECM in comparison to the vascular layers must be hypothesized. Reading the patterns of staining and with regard to the known inhibitory effect of MMP9 on ECM remodeling, but especially TIMP 2 on neoangiogenesis, disturbed nutrition, and dysfunctional vasa vasorum remodeling must be assumed as causes of dissection.

Implementation and effectiveness of a nurse navigation programme based on noddings' care theory in first-year undergraduate nursing students for professional identity and career planning: A quasi-experimental study.

AIMS: Development and evaluation of the effectiveness of a Nurse Navigation programme based on Noddings' Care theory on two dependent variables which were professional identity and career planning among first-year undergraduate nursing students. BACKGROUND: First-year undergraduate nursing students generally have a low sense of professional identity and career planning, resulting in a loss of nursing power after graduation. Implemention of a Nurse Navigation program based on Noddings' Care theory may be potentially useful in cultivating their professional identity and career planning. DESIGN: A quasi-experimental study. METHODS: A convenience sample of 122 first-year undergraduate nursing students from two medical universities was recruited between September 2021 and June 2022. Students in the experimental group (n = 63) participated in the Nurse Navigation programme based on Noddings' Care theory, which contained four core components, spreading over 50 lessons. Those in the control group (n = 59) underwent a traditional training programme with five components across 44 lessons. The two groups were compared in terms of their level of professional identity by Professional identity questionnaire for nurse students (PIQNS) and career planning by Career planning questionnaire (CPQ) after the training using the t-test. RESULTS: The mean score of professional identity in the experimental group increased significantly from 51.02 ± 8.46 at baseline to 58.02 ± 8.81 after the intervention (p < 0.001), with a large effect size (Cohen's d=0.810). Also, this post-intervention score was statistically significantly higher than that (52.86 ± 9.27) in the control group (p = 0.002), with a medium effect size (Cohen's d=0.571). The mean score of career planning in the experimental group increased significantly from 81.76 ± 9.86 at baseline to 94.52 ± 10.81 after the intervention (p < 0.001), with a large effect size (Cohen's d = 1.233). Also, this post-intervention score was statistically significantly higher than that (88.25 ± 9.30) in the control group (p < 0.001), with a medium effect size (Cohen's d=0.623). CONCLUSIONS: The Nurse Navigation programme based on Noddings' Care theory showed effectiveness in enhancing professional identity and career planning among first-year undergraduate nursing students in China. Further rigorous studies are needed to examine its effectiveness and long-term impacts on these students.

Efficacy of early hyperbaric oxygen combined with median nerve electrical stimulation in the treat-ment of severe traumatic brain injury and its impact on hemodynamics,coma degree and neurologi-cal function / 新乡医学院学报

Objective To explore the efficacy of early hyperbaric oxygen therapy(HBOT)combined with median nerve electrical stimulation(MNES)in the treatment of severe traumatic brain injury(sTBI)and its impact on hemodynamics,coma degree,and neurological function of patients.Methods A total of 78 patients with sTBI admitted to the General Hospital of Western Theater Command from March 2020 to October 2021 were selected as the research subjects.The patients were randomly divided into the control group and the observation group,with 39 patients in each group.The patients in both groups underwent basic treatments such as water,electrolyte and acid-base balance,nutritional support,anti-infection,and decompressive craniectomy.On this basis,patients in the control group received early HBOT,while patients in the observation group received both HBOT and MNES.Their clinical efficacy was compared between the two groups.Before and after treatment,dual-channel transcranial Doppler ultrasound was performed to detect hemodynamic indicators such as peak systolic blood flow velocity(Vs),mean blood flow velocity(Vm),and pulsatility index(PI)in the middle cerebral artery of patients in the two groups.The Glasgow Coma Scale(GCS)score was used to evaluate the degree of coma of patients in the two groups,the National Institutes of Health Stroke Scale(NIHSS)score was used to assess the neurological deficits of patients in the two groups,and the enzyme-linked immunosorbent assay was used to measure the levels of central nervous system specific protein(S100-β),glial fibrillary acidic protein(GFAP),and myelin basic protein(MBP).Complications during treatment of patients in the two groups were recorded,and their incidence was compared.Results The total effective rate of patients in the control and observation groups was 79.49％(31/39)and 92.31％(36/39),respectively.The total effective rate in the observation group was significantly higher than that in the control group(x2=8.971,P＜0.05).There was no significant difference in Vm,Vs,and PI between the two groups before treatment(P＞0.05).After treatment,the Vm and Vs in both groups were significantly higher than those before treatment,while the PI was significantly lower than that before treatment(P＜0.05);and the Vm and Vs in the observation group were signifi-cantly higher than that those in the control group,while the PI was significantly lower than that in the control group(P＜0.05).There was no significant difference in GCS and NIHSS scores between the two groups before treatment(P＞0.05).After treatment,the GCS score in both groups was significantly higher than that before treatment,while the NIHSS score was significantly lower than that before treatment(P＜0.05);and the GCS score in the observation group was significantly higher than that in the control group,while the NIHSS score was significantly lower than that in the control group(P＜0.05).There was no significant difference in S100-β,GFAP,and MBP levels between the two groups before treatment(P＞0.05).After treatment,the S100-β,GFAP,and MBP levels in both groups were significantly lower than those before treatment(P＜0.05),and the S100-β,GFAP,and MBP levels in the observation group were significantly lower than those in the control group(P＜0.05).During treatment,the incidence of complications in the control and observation groups was 23.08％(9/39)and 20.51％(8/39),respectively,showing no significant difference(x2=2.328,P＞0.05).Conclusion Early HBOT combined with MNES shows good efficacy in treating sTBI,which can effectively improve the patients'hemodynamic level,alleviate the severity of coma,enhance neurological function,and promote early recovery of consciousness,without increased risk of complications.

Combining network pharmacology and experimental verification to reveal the mechanism of Chaigui granules in the treatment of depression through PI3K/Akt/mTOR signaling pathways.

INTRODUCTION: Chaigui granules are a novel manufactured traditional Chinese antidepressant medicine, which is originated from the ancient classical prescription of Xiaoyaosan. It ameliorated depression-like behavior and concomitant symptoms in animal models. But its antidepressant mechanism is still unclear. Therefore, network pharmacology and molecular biology were used to explore underlying antidepressant mechanism in this study. METHODS: Firstly, network pharmacology was used to screen main active ingredients and potential targets in the treatment of depression with Chaigui granules, and to perform pathway enrichment analysis. Secondly, chronic and unpredictable mild stress-induced depression model rats were used, and behavioral tests were used to evaluate the antidepressant effect of Chaigui granules. Finally, the core targets and key pathways predicted by network pharmacology were validated by qRT-PCR and Western blot to determine the relevant gene and protein expression levels in rat hippocampus. RESULTS: The results of network pharmacology indicated that the PI3K/Akt signaling pathway may play a key role in antidepressant of Chaigui granules. The results of animal experiments showed that Chaigui granules significantly modulated behavioral indicators. Subsequently, the upregulation of relative mRNA levels of mTOR, Akt and PI3K and downregulation of GSK-3ß and FoxO3a were observed in rat hippocampus by molecular biology diagnosis. In addition, the decreased expression of Akt and mTOR in CUMS rats hippocampus was significantly reversed, and the expression levels of GSK-3ß and FoxO3a were upregulated. CONCLUSIONS: Based on the results of network pharmacology and animal experiment validation, Chaigui granules may reverse CUMS-induced depression-like behavior in rats through PI3K/Akt/mTOR signaling pathway.

RBM25 induces trophoblast epithelial-mesenchymal transition and preeclampsia disorder by enhancing the positive feedback loop between Grhl2 and RBM25.

Defects in migration and invasion caused by dysregulation of trophoblast epithelial-mesenchymal transformation (EMT) are one of the key factors in the pathogenesis of preeclampsia (PE). RNA-binding motif protein 25 (RBM25) is an RNA-binding protein involved in a variety of cellular processes, including cell proliferation, apoptosis, cell migration and invasion, and EMT. However, the expression and function of RBM25 in placental of PE remain unclear. In this study, we reveal that the expression of RBM25 is significantly elevated in PE placental tissue. RBM25 depletion and over-expression in trophoblast cells increase and decrease, respectively, cell migration and invasion by regulating EMT marker E-cadherin and Vimentin expression. Mechanistically, Grhl2 is involved in RBM25-regulated trophoblast cell migration, invasion, and EMT through RBM25-facilitated mRNA stabilization. Furthermore, the upregulation of Grhl2 enhances the expression of RBM25 through transcription and forms a positive feedback regulation in the progression of PE. These findings suggest that upregulation of RBM25 induces dysregulation of trophoblast EMT by enhancing positive feedback regulation of Grhl2 and RBM25, leading to defects in cell migration and invasion. Targeting this newly identified regulatory axis may provide benefits in the prevention and treatment of PE.

The associations between spiritual well-being, hope and psychological symptoms in Chinese childhood cancer patients: A path analysis.

AIMS: We aimed to test a model in which hope and spiritual well-being acted as protective factors against anxiety and depressive symptoms in childhood cancer patients (CCPs). We hypothesized that hope and spiritual well-being were mutually reinforcing factors that would both reduce anxiety and depressive symptoms. METHODS: Using path analysis, the hypothetical model was tested on a cross-sectional sample of 412 Chinese CCPs aged 8-17 years. Self-reported measures were used to obtain data on participants' social and clinical characteristics, spiritual well-being, hope, anxiety and depressive symptoms. RESULTS: The hypothetical model was supported. Results suggested that sex, treatment type and diagnosis predicted spiritual well-being; diagnosis and time since diagnosis predicted hope. Spiritual well-being and hope were mutually predictive and mutually reinforcing, and were both negatively associated with anxiety and depressive symptoms. This model predicted 40% of the variance in spiritual well-being, 37% in hope, 39% in depressive symptoms, and 28% in anxiety. CONCLUSION: Spiritual well-being and hope were mutually reinforcing and served as protective factors against anxiety and depressive symptoms. These support the value for integrating spiritual and hope elements in developing interventions for CCPs to improve their spiritual and psychological well-being along the disease trajectory.

Modulating the resistive switching stability of HfO2-based RRAM through Gd doping engineering: DFT+U.

Oxide-based resistive random access memory (RRAM) is standing out in both non-volatile memory and the emerging field of neuromorphic computing, with the consequence of increasing performance demands. Rare-earth doping is often used as an effective means for performance modulation. In this work, the modulation mechanism of the resistive switching (RS) behaviors in trivalent rare-earth Gd-doped HfO2-based RRAM has been carefully investigated using first-principles calculations. The results of electronic structure analysis show that Gd doping would lead to a change in the local geometry of the m-HfO2 defect system and would enhance the Coulomb interaction between the atoms around Gd and oxygen vacancy (VO), which may be one of the reasons for the enhanced conductivity of the HfO2-based RRAM after Gd doping. Thermodynamic and kinetic study results indicate that there is a strong interaction between Gd and its surrounding VO defects, and this strong interaction would not only attract more oxygen vacancies (VOs) to be generated near the dopant Gd, but also increase the migration energy barrier of the +2 charged VOs around the Gd doping site, thus suppressing the random generation of VO filaments, which leads to a better uniformity of the switching parameters during the RS process and improves the performance stability of the devices. The results of this work will provide new insights into modulating the RS behaviors and improving the device performance of HfO2-based RRAM through doping engineering.

Implementation of a motivational programme based on existence- relatedness-growth theory in nursing undergraduate interns: A quasi-experimental study.

BACKGROUND: Currently, a paramount issue in nursing education is to motivate nursing undergraduate interns to develop self-directed learning skills and improve their practice satisfaction and professional identity, so as to meet the growing demands in healthcare. OBJECTIVES: This study aimed to examine the effectiveness of a motivational programme based on the Existence-Relatedness-Growth (ERG) theory in developing self-directed learning skills, improving practice satisfaction and promoting the professional identity of nursing undergraduate interns in China. DESIGN: A quasi-experimental study design. SETTING: A government-funded tertiary teaching hospital in Guangzhou, Guangdong province, China. METHODS: This study was conducted with 99 nursing undergraduate interns in a hospital between June 2020 and April 2022. The interns in the experimental group (n = 50) participated in the motivational programme based on ERG theory, while those in the control group (n = 49) underwent a traditional training programme. The interns in the two groups were compared in terms of their degree of self-directed learning, practice satisfaction and professional identity after the training, using independent samples t-test. RESULTS: After the internship, interns in the experimental group showed a statistically significantly higher level of self-directed learning and practice satisfaction than those in the control group (p < 0.05). However, no significant difference was observed in professional identity between the two groups after the internship. CONCLUSIONS: The motivational programme based on ERG theory was shown to be effective in improving self-directed learning and practice satisfaction in nursing undergraduate interns. A large-scale randomized controlled trial is warranted to confirm the results.

Small change, big difference: A promising praziquantel derivative designated P96 with broad-spectrum antischistosomal activity for chemotherapy of schistosomiasis japonica.

BACKGROUND: Praziquantel (PZQ) has been the first line antischistosomal drug for all species of Schistosoma, and the only available drug for schistosomiasis japonica, without any alternative drugs since the 1980s. However, PZQ cannot prevent reinfection, and cannot cure schistosomiasis thoroughly because of its poor activity against juvenile schistosomes. In addition, reliance on a single drug is extremely dangerous, the development and spread of resistance to PZQ is becoming a great concern. Therefore, development of novel drug candidates for treatment and control of schistosomiasis is urgently needed. METHODOLOGYS/PRINCIPAL FINDINGS: One of the PZQ derivative christened P96 with the substitution of cyclohexyl by cyclopentyl was synthesized by School of Pharmaceutical Sciences of Shandong University. We investigated the in vitro and in vivo activities of P96 against different developmental stages of S. japonicum. Parasitological studies and scanning electron microscopy were used to study the primary action characteristics of P96 in vitro. Both mouse and rabbit models were employed to evaluate schistosomicidal efficacy of P96 in vivo. Besides calculation of worm reduction rate and egg reduction rate, quantitative real-time PCR was used to evaluate the in vivo antischistosomal activity of P96 at molecular level. In vitro, after 24h exposure, P96 demonstrated the highest activities against both juvenile and adult worm of S. japonicum in comparison to PZQ. The antischistosomal efficacy was concentration-dependent, with P96 at 50µM demonstrating the most evident schistosomicidal effect. Scanning electron microscopy demonstrated that P96 caused more severe damages to schistosomula and adult worm tegument compared to PZQ. In vivo, our results showed that P96 was effective against S. japonicum at all developmental stages. Notably, its efficacy against young stage worms was significantly improved compared to PZQ. Moreover, P96 retained the high activity comparable to PZQ against the adult worm of S. japonicum. CONCLUSIONS: P96 is a promising drug candidate for chemotherapy of schistosomiasis japonica, which has broad spectrum of action against various developmental stage, potentially addressing the deficiency of PZQ. It might be promoted as a drug candidate for use either alone or in combination with PZQ for the treatment of schistosomiasis.

Mesenchymal stem cell-derived exosomes ameliorate TGF-ß1-induced endometrial fibrosis by altering their miRNA profile.

OBJECTIVE: Mesenchymal stem cell (MSC)-derived exosomes (MSC-exo) can treat reproductive disorders. However, the action of microRNAs (miRNAs) in this mechanism has yet to be systematically investigated. This study aimed to explore the effect of MSC-exo on TGF-ß1-induced endometrial fibrosis in intrauterine adhesions and elucidate the regulatory mechanisms involved in key genes by comparing miRNA expression profiles. METHODS: MSC-exo were isolated and identified based on particle size and protein marker detection. Cell counting kit-8, flow cytometry, and western blotting were used to determine the effects of MSC-exo on cell function and fibrosis in human endometrial epithelial cells (hEECs). Subsequently, we sequenced and annotated the small RNA in MSC-exo and TGF-ß1-induced MSC-exo to screen for differentially expressed (DE) miRNAs. After the prediction and functional enrichment of target genes of DE miRNAs, key genes were selected for functional experiments. RESULTS: TGF-ß1 inhibited the proliferation of hEECs and promoted apoptosis and fibrosis. However, these effects were significantly reversed by the addition of MSC and MSC-exo. Fifteen DE miRNAs were identified by comparing the miRNA profiles of MSC-exo and TGF-ß1-induced MSC-exo. Among these, miR-145-5p was found to be significantly upregulated in TGF-ß1-induced MSC-exo. Furthermore, the addition of miR-145-5p mimic was found to reverse fibrosis in hEECs while promoting the expression of key autophagy protein P62. CONCLUSION: MSC-exo ameliorated TGF-ß1-induced endometrial fibrosis. RNA sequencing, bioinformatic analysis, and functional experiments revealed that miR-145-5p may exert its action through the P62-dependent autophagy pathway.

Effectiveness of spiritual interventions on psychological outcomes and quality of life among paediatric patients with cancer: a study protocol for a systematic review.

INTRODUCTION: Cancer and its treatment affect children's physical, psychological and social well-being throughout the disease trajectory. Spiritual well-being is a fundamental dimension of people's overall health and is considered a source of strength to motivate patients to cope with and adapt to their disease. Appropriate spiritual interventions are important to mitigate the psychological impact of cancer on children, with an ultimate goal of improving their quality of life (QoL) throughout the treatment course. However, the overall effectiveness of spiritual interventions for paediatric patients with cancer remains unclear. This paper describes a protocol to systematically summarise the characteristics of studies related to existing spiritual interventions and synthesise their effectiveness on psychological outcomes and QoL among children with cancer. METHODS AND ANALYSIS: Ten databases will be searched to identify appropriate literature: MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, PsycINFO, LILACS, OpenSIGLE, the Chinese Biomedical Literature Database, the Chinese Medical Current Contents and the Chinese National Knowledge Infrastructure. All randomised controlled trials that meet our inclusion criteria will be included. The primary outcome will be QoL as evaluated by self-reported measures. The secondary outcomes will be self-reported or objectively measured psychological outcomes, including anxiety and depression. Review Manager V.5.3 will be used to synthesise the data, calculate treatment effects, perform any subgroup analyses and assess the risk of bias in included studies. ETHICAL AND DISSEMINATION: The results will be presented at international conferences and published in peer-reviewed journals. As no individual data will be involved in this review, ethical approval is not required.

Mitochondria on the move: Horizontal mitochondrial transfer in disease and health.

Mammalian genes were long thought to be constrained within somatic cells in most cell types. This concept was challenged recently when cellular organelles including mitochondria were shown to move between mammalian cells in culture via cytoplasmic bridges. Recent research in animals indicates transfer of mitochondria in cancer and during lung injury in vivo, with considerable functional consequences. Since these pioneering discoveries, many studies have confirmed horizontal mitochondrial transfer (HMT) in vivo, and its functional characteristics and consequences have been described. Additional support for this phenomenon has come from phylogenetic studies. Apparently, mitochondrial trafficking between cells occurs more frequently than previously thought and contributes to diverse processes including bioenergetic crosstalk and homeostasis, disease treatment and recovery, and development of resistance to cancer therapy. Here we highlight current knowledge of HMT between cells, focusing primarily on in vivo systems, and contend that this process is not only (patho)physiologically relevant, but also can be exploited for the design of novel therapeutic approaches.