Novel pyxinol amide derivatives bearing an aliphatic heterocycle as P-glycoprotein modulators for overcoming multidrug resistance.

P-glycoprotein (Pgp) modulators are promising agents for overcoming multidrug resistance (MDR) in cancer chemotherapy. In this study, via structural optimization of our lead compound S54 (nonsubstrate allosteric inhibitor of Pgp), 29 novel pyxinol amide derivatives bearing an aliphatic heterocycle were designed, synthesized, and screened for MDR reversal activity in KBV cells. Unlike S54, these active derivatives were shown to transport substrates of Pgp. The most potent derivative 4c exhibited promising MDR reversal activity (IC50 of paclitaxel = 8.80 ± 0.56 nM, reversal fold = 211.8), which was slightly better than that of third-generation Pgp modulator tariquidar (IC50 of paclitaxel = 9.02 ± 0.35 nM, reversal fold = 206.6). Moreover, the cytotoxicity of this derivative was 8-fold lower than that of tariquidar in human normal HK-2 cells. Furthermore, 4c blocked the efflux function of Pgp and displayed high selectivity for Pgp but had no effect on its expression and distribution. Molecular docking revealed that 4c bound preferentially to the drug-binding domain of Pgp. Overall, 4c is a promising lead compound for developing Pgp modulators.

Nurses' self-regulation after engaging in end-of-life conversations with advanced cancer patients: a qualitative study.

BACKGROUND: Self-regulation is crucial for nurses who engage in in-depth end-of-life conversations with advanced cancer patients, especially in cultural contexts featuring death taboos. An improved understanding of the self-regulation process of nurses can help them address negative emotions and promote self-growth more effectively. Therefore, this study aimed to explore nurses' self-regulation process after end-of-life conversations with advanced cancer patients. METHODS: This study employed a descriptive, qualitative approach. Seventeen nurses from four hospitals and a hospice unit in mainland China were interviewed between September 2022 and June 2023. Data were collected through face-to-face semistructured interviews. A thematic analysis method was used to analyse the data following the guidance of regulatory focus theory. RESULTS: Three main themes were developed: self-regulation antecedents include personality, experience, and support; promotion or prevention is a possible self-regulation process for nurses; both self-exhaustion and self-growth may be the outcomes of self-regulation, as did seven subthemes. Personality tendencies, life experience, and perceived support may affect nurses' self-regulation, thereby affecting their self-regulation outcomes. CONCLUSIONS: Nurses exhibit different self-regulatory tendencies and self-regulation outcomes. The provision of peer support and counselling support to nurses is highly important with regard to achieving good self-regulation outcomes.

Differential expression profiles and bioinformatics analysis of tRNA-derived small RNAs in epicardial fat of patients with atrial fibrillation.

The exact processes underlying atrial fibrillation (AF) are still unclear. It has been suggested that epicardial adipose tissue (EAT) may contribute to arrhythmias and can release various bioactive molecules, including exosomes containing tRNA-derived small RNAs (tsRNAs). Numerous studies have indicated that these tsRNAs can significantly affect key cellular functions. However, there is currently no research investigating the relationship between tsRNAs from EAT and AF. In order to explore the regulatory mechanisms of tsRNAs from EAT associated with AF, we conducted RNA-sequencing analysis on EAT samples collected from 6 AF patients and 6 control subjects with sinus rhythm. Our analysis revealed an upregulation of 146 tsRNAs and a downregulation of 126 tsRNAs in AF. Furthermore, we randomly selected four tsRNAs (tRF-SeC-TCA-001, tiRNA-Gly-CCC-003, tRF-Gly-GCC-002, and tRF-Tyr-GTA-007) for validation using quantitative reverse transcription-polymerase chain reaction. Following this, bioinformatic analyses revealed that the target genes of these tsRNAs were prominently involved in the regulation of cell adhesion and various cellular processes mediated by plasma membrane adhesion molecules. Additionally, based on KEGG analysis, it was suggested that the majority of these target genes might contribute to the pathogenesis of AF through processes such as glycosaminoglycan biosynthesis, AMP-activated protein kinase activity, and the insulin signaling pathway. Our results elucidate changes in the expression profiles of tsRNAs within EAT samples obtained from AF patients, and they forecast potential target genes and interactions between tsRNAs and mRNA within EAT that could contribute to the pathogenesis of AF.

A novel fast hybrid capture sequencing method for high-efficiency common human coronavirus whole-genome acquisition.

Rapid and accurate sequencing of the entire viral genome, coupled with continuous monitoring of genetic changes, is crucial for understanding the epidemiology of coronaviruses. We designed a novel method called micro target hybrid capture system (MT-Capture) to enable whole-genome sequencing in a timely manner. The novel design of probes used in target binding exhibits a unique and synergistic "hand-in-hand" conjugation effect. The entire hybrid capture process is within 2.5 hours, overcoming the time-consuming and complex operation characteristics of the traditional liquid-phase hybrid capture (T-Capture) system. By designing specific probes for these coronaviruses, MT-Capture effectively enriched isolated strains and 112 clinical samples of coronaviruses with cycle threshold values below 37. Compared to multiplex PCR sequencing, it does not require frequent primer updates and has higher compatibility. MT-Capture is highly sensitive and capable of tracking variants.IMPORTANCEMT-Capture is meticulously designed to enable the efficient acquisition of the target genome of the common human coronavirus. Coronavirus is a kind of virus that people are generally susceptible to and is epidemic and infectious, and it is the virus with the longest genome among known RNA viruses. Therefore, common human coronavirus samples are selected to evaluate the accuracy and sensitivity of MT-Capture. This method utilizes innovative probe designs optimized through probe conjugation techniques, greatly shortening the time and simplifying the handwork compared with traditional hybridization capture processes. Our results demonstrate that MT-Capture surpasses multiplex PCR in terms of sensitivity, exhibiting a thousandfold increase. Moreover, MT-Capture excels in the identification of mutation sites. This method not only is used to target the coronaviruses but also may be used to diagnose other diseases, including various infectious diseases, genetic diseases, or tumors.

Effect of the mitochondrial transaminase (GOT2) on membrane potential-sensitive respiration in mitochondria of differentiated C2C12 muscle cells.

We previously showed that the transaminase inhibitor, aminooxyacetic acid, reduced respiration energized at complex II (succinate dehydrogenase, SDH) in mitochondria isolated from mouse hindlimb muscle. The effect required a reduction in membrane potential with resultant accumulation of oxaloacetate (OAA), a potent inhibitor of SDH. To specifically assess the effect of the mitochondrial transaminase, glutamic oxaloacetic transaminase (GOT2) on complex II respiration, and to determine the effect in intact cells as well as isolated mitochondria, we performed respiratory and metabolic studies in wildtype (WT) and CRISPR-generated GOT2 knockdown (KD) C2C12 myocytes. Intact cell respiration by GOT2KD cells versus WT was reduced by adding carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) to lower potential. In mitochondria of C2C12 KD cells, respiration at low potential generated by 1 µM FCCP and energized at complex II by 10 mM succinate + 0.5 mM glutamate (but not by complex I substrates) was reduced versus WT mitochondria. Although we could not detect OAA, metabolite data suggested that OAA inhibition of SDH may have contributed to the FCCP effect. C2C12 mitochondria differed from skeletal muscle mitochondria in that the effect of FCCP on complex II respiration was not evident with ADP addition. We also observed that C2C12 cells, unlike skeletal muscle, expressed glutamate dehydrogenase, which competes with GOT2 for glutamate metabolism. In summary, GOT2 KD reduced C2C12 respiration in intact cells at low potential. From differential substrate effects, this occurred largely at complex II. Moreover, C2C12 versus muscle mitochondria differ in complex II sensitivity to ADP and differ markedly in expression of glutamate dehydrogenase.NEW & NOTEWORTHY Impairment of the mitochondrial transaminase, GOT2, reduces complex II (succinate dehydrogenase, SDH)-energized respiration in C2C12 myocytes. This occurs only at low inner membrane potential and is consistent with inhibition of SDH. Incidentally, we observed that C2C12 mitochondria compared with muscle tissue mitochondria differ in sensitivity of complex II respiration to ADP and in the expression of glutamate dehydrogenase.

Oat protein modulates cholesterol metabolism and improves cardiac systolic function in high fat, high sucrose fed rats.

Oats are recognized to provide many health benefits that are mainly associated with its dietary fibre, ß-glucan. However, the protein derived from oats is largely understudied with respect to its ability to maintain health and attenuate risk factors of chronic diseases. The goal of the current study was to investigate the metabolic effects of oat protein consumption in lieu of casein as the protein source in high fat, high sucrose (HF/HS) fed Wistar rats. Four-week-old rats were divided into three groups and were fed three different experimental diets: a control diet with casein as the protein source, an HF/HS diet with casein, or an HF/HS diet with oat protein for 16 weeks. Heart structure and function were determined by echocardiography. Blood pressure measurements, an oral glucose tolerance test, and markers of cholesterol metabolism, oxidative stress, inflammation, and liver and kidney damage were also performed. Our study results show that incorporation of oat protein in the diet was effective in preserving systolic heart function in HF/HS fed rats. Oat protein significantly reduced serum total and low-density lipoprotein cholesterol levels. Furthermore, oat protein normalized liver HMG-CoAR activity, which, to our knowledge, is the first time this has been reported in the literature. Therefore, our research suggests that oat protein can provide hypocholesterolemic and cardioprotective benefits in a diet-induced model of metabolic syndrome.

An antigen-specific immunotherapeutic, AKS-107, deletes insulin-specific B cells and prevents murine autoimmune diabetes.

Introduction: The antigen-presenting cell function of insulin-reactive B cells promotes type 1 diabetes (T1D) in non-obese diabetic (NOD) mice by stimulating pathogenic T cells leading to destruction of insulin-producing ß-cells of pancreatic islets. Methods/Results: To target insulin-reactive B cells, AKS-107, a human IgG1 Fc molecule fused with human insulin A and B chains, was engineered to retain conformational insulin epitopes that bound mouse and human B cell receptors but prevented binding to the insulin metabolic receptor. AKS-107 Fc-mediated deletion of insulin-reactive B cells was demonstrated via ex vivo and in vivo experiments with insulin-reactive B cell receptor transgenic mouse strains, VH125Tg/NOD and Tg125(H+L)/NOD. As an additional immune tolerance feature, the Y16A mutation of the insulin B(9-23) dominant T cell epitope was engineered into AKS-107 to suppress activation of insulin-specific T cells. In mice and non-human primates, AKS-107 was well-tolerated, non-immunogenic, did not cause hypoglycemia even at high doses, and showed an expectedly protracted pharmacokinetic profile. AKS-107 reproducibly prevented spontaneous diabetes from developing in NOD and VH125Tg/NOD mice that persisted for months after cessation of treatment, demonstrating durable immune tolerance. Discussion: These preclinical outcomes position AKS-107 for clinical development in T1D prevention settings.

Age-specific differences in the association between prediabetes and cardiovascular diseases in China: A national cross-sectional study.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide, the global burden of which is rising. It is still unclear the extent to which prediabetes contributes to the risk of CVD in various age brackets among adults. To develop a focused screening plan and treatment for Chinese adults with prediabetes, it is crucial to identify variations in the connection between prediabetes and the risk of CVD based on age. AIM: To examine the clinical features of prediabetes and identify risk factors for CVD in different age groups in China. METHODS: The cross-sectional study involved a total of 46239 participants from June 2007 through May 2008. A thorough evaluation was conducted. Individuals with prediabetes were categorized into two groups based on age. Chinese atherosclerotic CVD risk prediction model was employed to evaluate the risk of developing CVD over 10 years. Random forest was established in both age groups. SHapley Additive exPlanation method prioritized the importance of features from the perspective of assessment contribution. RESULTS: In total, 6948 people were diagnosed with prediabetes in this study. In pre-diabetes, prevalences of CVD were 5 (0.29%) in the younger group and 148 (2.85%) in the older group. Overall, 11.11% of the younger group and 29.59% of the older group were intermediate/high-risk of CVD for prediabetes without CVD based on the Prediction for ASCVD Risk in China equation in ten years. In the younger age group, the 10-year risk of CVD was found to be more closely linked to family history of CVD rather than lifestyle, whereas in the older age group, resident status was more closely linked. CONCLUSION: The susceptibility to CVD is age-specific in newly diagnosed prediabetes. It is necessary to develop targeted approaches for the prevention and management of CVD in adults across various age brackets.

Community-based rehabilitation services implemented by multidisciplinary teams among adults with stroke: a scoping review with a focus on Chinese experience.

BACKGROUND: Despite the growing interest in hospital rehabilitation services for communities, studies on existing community-based rehabilitation (CBR) services remain scarce owing to limitations in the development of community health services and regional cultural diversity. As a guaranteed measure for ensuring the quality of rehabilitation services and achieving the desired service outcomes, clear roles and responsibilities in multidisciplinary teams and effective service delivery are particularly important. OBJECTIVE: This scoping review aimed to determine the scope of community stroke rehabilitation programs involving existing multidisciplinary teams and to analyze the implementation content and implementers' functional roles to provide guidance for future CBR programs. METHODS: The scoping review design followed the methodology of the Joanna Briggs Institute and was based on the normative scoping review framework proposed by Arksey and O'Malley. The comprehensive CBR framework was proposed by World Health Organization-guided data charting and analysis. RESULTS: Of the 22,849 identified citations, 74 studies were included, consisting of 6,809 patients with stroke and 49 primary caregivers, most of whom were from China. The most common working mode in CBR programs was a dual approach involving both healthcare professionals in medical institutions and community healthcare professionals. The number of programs in each discipline was in the following descending order: nursing, medical care, rehabilitation, psychology, nutrition, and public health. Among these, multidisciplinary teams comprising medical, nursing, and rehabilitation disciplines were the most common, with a total of 29 programs. Disciplinary members were mainly responsible for implementing their respective disciplinary content, with physicians providing guidance for the programs. More than 82.4% of the studies reported 2-4 intervention strategies. The intervention forms of rehabilitation content were the most diverse, whereas preventive interventions were more homogeneous than others. Physical function and socio-psychological measurements were the most commonly reported outcomes. CONCLUSION: CBR services implemented by multidisciplinary teams can effectively achieve functional and emotional improvement in patients with stroke, and nurses are the most involved in implementation, especially in community settings. The results further emphasize the importance of strengthening the exploration of nurses' maximum potential to implement CBR plans in future practice. TRIAL REGISTRATION: The registration information for this scoping review can be found at osf.io/pv7tg.

Cell-Surface ZnT8 Antibody Prevents and Reverses Autoimmune Diabetes in Mice.

Type 1 diabetes (T1D) is an autoimmune disease in which pathogenic lymphocytes target autoantigens expressed in pancreatic islets, leading to the destruction of insulin-producing ß-cells. Zinc transporter 8 (ZnT8) is a major autoantigen abundantly present on the ß-cell surface. This unique molecular target offers the potential to shield ß-cells against autoimmune attacks in T1D. Our previous work showed that a monoclonal antibody (mAb43) against cell-surface ZnT8 could home in on pancreatic islets and prevent autoantibodies from recognizing ß-cells. This study demonstrates that mAb43 binds to exocytotic sites on the ß-cell surface, masking the antigenic exposure of ZnT8 and insulin after glucose-stimulated insulin secretion. In vivo administration of mAb43 to NOD mice selectively increased the proportion of regulatory T cells in the islet, resulting in complete and sustained protection against T1D onset as well as reversal of new-onset diabetes. The mAb43-induced self-tolerance was reversible after treatment cessation, and no adverse effects were exhibited during long-term monitoring. Our findings suggest that mAb43 masking of the antigenic exposure of ß-cells suppresses the immunological cascade from B-cell antigen presentation to T cell-mediated ß-cell destruction, providing a novel islet-targeted and antigen-specific immunotherapy to prevent and reverse clinical T1D.

Implementation of type 1 diabetes genetic risk screening in children in diverse communities: the Virginia PrIMeD project.

BACKGROUND: Population screening for risk of type 1 diabetes (T1D) has been proposed to identify those with islet autoimmunity (presence of islet autoantibodies). As islet autoantibodies can be transient, screening with a genetic risk score has been proposed as an entry into autoantibody testing. METHODS: Children were recruited from eight general pediatric and specialty clinics across Virginia with diverse community settings. Recruiters in each clinic obtained informed consent/assent, a medical history, and a saliva sample for DNA extraction in children with and without a history of T1D. A custom genotyping panel was used to define T1D genetic risk based upon associated SNPs in European- and African-genetic ancestry. Subjects at "high genetic risk" were offered a separate blood collection for screening four islet autoantibodies. A follow-up contact (email, mail, and telephone) in one half of the participants determined interest and occurrence of subsequent T1D. RESULTS: A total of 3818 children aged 2-16 years were recruited, with 14.2% (n = 542) having a "high genetic risk." Of children with "high genetic risk" and without pre-existing T1D (n = 494), 7.0% (34/494) consented for autoantibody screening; 82.4% (28/34) who consented also completed the blood collection, and 7.1% (2/28) of them tested positive for multiple autoantibodies. Among children with pre-existing T1D (n = 91), 52% (n = 48) had a "high genetic risk." In the sample of children with existing T1D, there was no relationship between genetic risk and age at T1D onset. A major factor in obtaining islet autoantibody testing was concern over SARS-CoV-2 exposure. CONCLUSIONS: Minimally invasive saliva sampling implemented using a genetic risk score can identify children at genetic risk of T1D. Consent for autoantibody screening, however, was limited largely due to the SARS-CoV-2 pandemic and need for blood collection.

Measuring 3D shape and deformation in the presence of extremely strong ambient light and thermal radiation with a single time-gated camera.

Monochromatic light-illuminated active-imaging stereo-digital image correlation (stereo-DIC) has been extensively used for measuring the surface deformation of materials and structures at elevated temperatures. Despite the improvements in the image acquisition techniques or devices, it is still challenging to measure the 3D deformation of materials and structures in the presence of strong, time-varying ambient light and thermal radiation. In this study, we present what we believe to be a novel dual-filtering single-camera stereo-DIC technique for full-field 3D high-temperature deformation measurement, even in the case of extremely intense ambient light and thermal radiation. In contrast to conventional active-imaging stereo-DIC that only suppresses the thermal radiations in the spectral domain, the proposed technique utilized a dual-filtering strategy (i.e., narrow bandpass optical filtering and ultrashort exposing) to suppress the strong ambient light and thermal radiation in both time and spectral domains. Besides, a four-mirror adapter is adopted to realize 3D shape and deformation measurement using a compact single time-gated camera. Experimental verifications, including assessments with laboratory experiments and validations on real thermal deformation tests under transient aerodynamic heating and direct ohmic heating, convincingly demonstrated that the proposed single-camera dual-filtering stereo-DIC method can achieve accurate 3D shape, motion and deformation measurement, even with strong light and thermal radiation from the quartz lamps and the heated sample.

Transcriptome Analysis Reveals the Molecular Mechanisms of BR Negative Regulatory Factor StBIN2 Maintaining Tuber Dormancy.

Potato is an important food crop. After harvest, these tubers will undergo a period of dormancy. Brassinosteroids (BRs) are a new class of plant hormones that regulate plant growth and seed germination. In this study, 500 nM of BR was able to break the dormancy of tubers. Additionally, exogenous BR also upregulated BR signal transduction genes, except for StBIN2. StBIN2 is a negative regulator of BR, but its specific role in tuber dormancy remains unclear. Transgenic methods were used to regulate the expression level of StBIN2 in tubers. It was demonstrated that the overexpression of StBIN2 significantly prolonged tuber dormancy while silencing StBIN2 led to premature sprouting. To further investigate the effect of StBIN2 on tuber dormancy, RNA-Seq was used to analyze the differentially expressed genes in OE-StBIN2, RNAi-StBIN2, and WT tubers. The results showed that StBIN2 upregulated the expression of ABA signal transduction genes but inhibited the expression of lignin synthesis key genes. Meanwhile, it was also found that StBIN2 physically interacted with StSnRK2.2 and StCCJ9. These results indicate that StBIN2 maintains tuber dormancy by mediating ABA signal transduction and lignin synthesis. The findings of this study will help us better understand the molecular mechanisms underlying potato tuber dormancy and provide theoretical support for the development of new varieties using related genes.

Mixed Enthalpy-Entropy Descriptor for the Rational Design of Synthesizable High-Entropy Materials Over Vast Chemical Spaces.

The practically unlimited high-dimensional composition space of high-entropy materials (HEMs) has emerged as an exciting platform for functional material design and discovery. However, the identification of stable and synthesizable HEMs and robust design rules remains a daunting challenge. Here, we propose a mixed enthalpy-entropy descriptor (MEED) that enables highly efficient, robust, high-throughput prediction of synthesizable HEMs across vast chemical spaces from first-principles. The MEED is based on two parameters: the relative formation enthalpy with respect to the most stable competing compound and the spread of the point-defect formation energy spectrum. The former measures the relative synthesizability of an HEM to its most stable competing phase, going beyond the conventional thermodynamic understanding. The latter gauges the relative entropy forming ability of an HEM, entailing no sampling over numerous alloy configurations. By applying the MEED to two structurally distinct representative material systems (i.e., 3D rocksalt carbides and 2D layered sulfides), we not only successfully identify all experimentally reported HEMs within these systems but also reveal a cutoff criterion for assessing their relative synthesizability within each system. By the MEED, tens of new high-entropy carbides and 2D high-entropy sulfides are also predicted, which have the potential for a wide variety of applications such as coating in aerospace devices, energy conversion and storage, and flexible electronics.

Beneficial Effects of Dietary Flaxseed on Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD), a significant cause of chronic liver disease, presents a considerable public health concern. Despite this, there is currently no treatment available. This study aimed to investigate dietary flaxseed in the JCR:LA-corpulent rat strain model of NAFLD. Both obese male and female rats were studied along with their lean counterparts after 12 weeks of ingestion of a control diet, or control diet with flaxseed, or high fat, high sucrose (HFHS), or HFHS plus flaxseed. Obese rats showed higher liver weight and increased levels of cholesterol, triglyceride, and saturated fatty acid, which were further elevated in rats on the HFHS diet. The HFHS diet induced a significant two-fold elevation in the plasma levels of both aspartate aminotransferase and alanine aminotransferase in the obese male and female rats. Including flaxseed in the HFHS diet significantly lowered liver weight, depressed the plasma levels of both enzymes in the obese male rats, and reduced hepatic cholesterol and triglyceride content as well as improving the fatty acid profile. In summary, including flaxseed in the diet of male and female obese rats led to an improved lipid composition in the liver and significantly reduced biomarkers of tissue injury despite consuming a HFHS chow.

Influence of a diet and/or exercise intervention on long-term mortality and vascular complications in people with impaired glucose tolerance: Da Qing Diabetes Prevention Outcome study.

AIM: We aimed to investigate the long-term influence of a diet and/or exercise intervention on long-term mortality and cardiovascular disease (CVD) events. METHODS: The Da Qing Diabetes Prevention Study had 576 participants with impaired glucose tolerance (IGT) randomized to diet-only, exercise-only and diet-plus-exercise intervention group and control group. The participants underwent lifestyle interventions for 6 years. The subsequent Da Qing Diabetes Prevention Outcome Study was a prospective cohort study to follow-up the participants for up to 24 years after the end of 6-year intervention. In total, 540 participants completed the follow-up, while 36 subjects lost in follow-up. Cox proportional hazards analysis was applied to assess the influence of lifestyle interventions on targeted outcomes. RESULTS: Compared with controls, the diet-only intervention in people with IGT was significantly associated with a reduced risk of all-cause death [hazard ratio (HR) 0.77, 95% confidence interval (CI) (0.61-0.97)], CVD death [HR 0.67, 95% CI (0.46-0.97)] and CVD events [HR 0.72, 95% CI (0.54-0.96)]. The diet-plus-exercise intervention was significantly associated with a decreased risk of all-cause death [HR 0.64, 95% CI (0.48-0.84)], CVD death [HR 0.54, 95% CI (0.30-0.97)] and CVD events [HR 0.68, 95% CI (0.52-0.90)]. Unexpectedly, the exercise-only intervention was not significantly associated with the reduction of any of these outcomes, although there was a consistent trend towards reduction. CONCLUSIONS: A diet-only intervention and a diet-plus-exercise intervention in people with IGT were significantly associated with a reduced risk of all-cause death, CVD death and CVD events, while an exercise-only intervention was not. It suggests that diet-related interventions may have a potentially more reliable influence on long-term vascular complications and mortality.

The Development of Multisensory Integration at the Neuronal Level.

Multisensory integration is a fundamental function of the brain. In the typical adult, multisensory neurons' response to paired multisensory (e.g., audiovisual) cues is significantly more robust than the corresponding best unisensory response in many brain regions. Synthesizing sensory signals from multiple modalities can speed up sensory processing and improve the salience of outside events or objects. Despite its significance, multisensory integration is testified to be not a neonatal feature of the brain. Neurons' ability to effectively combine multisensory information does not occur rapidly but develops gradually during early postnatal life (for cats, 4-12 weeks required). Multisensory experience is critical for this developing process. If animals were restricted from sensing normal visual scenes or sounds (deprived of the relevant multisensory experience), the development of the corresponding integrative ability could be blocked until the appropriate multisensory experience is obtained. This section summarizes the extant literature on the development of multisensory integration (mainly using cat superior colliculus as a model), sensory-deprivation-induced cross-modal plasticity, and how sensory experience (sensory exposure and perceptual learning) leads to the plastic change and modification of neural circuits in cortical and subcortical areas.

Clinical predictors of prognosis in stroke patients after endovascular therapy.

Endovascular therapy (EVT) is effective in the treatment of large vascular occlusive stroke. However, many factors are associated with the outcomes of acute ischemic stroke (AIS) after EVT. This study aimed to identify the main factors related to the prognosis of AIS patients after EVT. We analyzed the clinical data of AIS patients in the neurology department of our medical center from June 2017 to August 2021 following treatment with EVT. The data included the patients' blood pressure upon admission, blood glucose concentration, National Institutes of Health Stroke Scale (NIHSS) score, 90-day modified Rankin scale (mRs) score follow-up data, and time from LKN to the successful groin puncture (GP). A good outcome was defined as a 90-day mRs score of 0-2, and a poor outcome was defined as a 90-day mRs score of 3-6. A total of 144 patients were included in the study. Admission, smoking, and LKN-to-GP time, NIHSS score of 6-12 was found to be relevant to the prognosis. The results of multivariate analysis showed that prognosis was significantly influenced by baseline NIHSS (odds ratio = 3.02; 95% confidence interval, 2.878-4.252; P = 0.001), LKN-to-GP time (odds ratio = 2.17; 95% confidence interval, 1.341-2.625; P = 0.003), and time stratification (6-12 h) (odds ratio = 4.22; 95% confidence interval, 2.519-5.561; P = 0.001). Our study indicated that smoking, baseline NIHSS score, and LKN-to-GP time were the risk factors for a poor outcome in stroke patients following an EVT. Quitting smoking and shortening LKN time to GP should improve the outcome of AIS after EVT.

Contribution of non-socioeconomic factors to healthy quality of life in socioeconomically deprived patients with advanced gastrointestinal cancer: Measuring attributable fraction.

BACKGROUND: The quality of life of patients with advanced gastrointestinal cancer is seriously impaired, and socioeconomic deprivation often has a serious impact on their quality of life. However, little is known about the relative contribution of non-socioeconomic factors to the quality of life of patients with advanced gastrointestinal cancer with socioeconomic deprivation. AIM: This study aims to investigate the situation and predictors of quality of life of patients with socioeconomic deprivation and evaluate the independent effects of some non-socioeconomic factors. DESIGN: A retrospective study based on cross-sectional design. METHODS: Data were obtained from 1075 patients with advanced gastrointestinal cancer who received family palliative treatment in the hospice ward of Zhongnan Hospital of Wuhan University from March 2010 to October 2020, including demographic and clinical questionnaires, Karnofsky Performance Status scale and Cancer Pain and Quality of Life Questionnaire of Chinese Cancer Patients. RESULTS: The quality of life of patients with advanced gastrointestinal cancer with socioeconomic deprivation is impaired and is affected by gait, self-care ability, abdominal distension, nutritional status, weight loss, constipation and posture. Improvement in six of these factors-gait, self-care ability, abdominal distension, nutritional status, weight loss and posture-has an independent positive impact on the development of a healthy quality of life for patients. CONCLUSIONS: Gait, self-care ability, abdominal distension, nutritional status, weight loss and posture are important determinants of healthy quality of life in patients with advanced gastrointestinal cancer with socioeconomic deprivation, and early identification and strength management of these non-socioeconomic factors may neutralize the negative impact of socioeconomic factors on the quality of life. IMPLICATIONS FOR PRACTICE: This study provides new ideas and intervention entry points for global nurses in practice innovations to improve the quality of life of socioeconomically deprived patients with advanced gastrointestinal cancer. It enables them to focus on the effectiveness of non-socioeconomic factors in the development and implementation of targeted care plans for patients with advanced gastrointestinal cancer experiencing socioeconomic deprivation globally. REPORTING METHOD: This study was reported in strict compliance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.