Effects of Priming Intermittent Theta Burst Stimulation With High-Definition tDCS on Upper Limb Function in Hemiparetic Patients With Stroke: A Randomized Controlled Study.

BACKGROUND: Preconditioning with cathodal high-definition transcranial direct current stimulation (HD-tDCS) can potentiate cortical plasticity induced by intermittent theta burst stimulation (iTBS) and enhance the after-effects of iTBS in healthy people. However, it is unclear whether this multi-modal protocol can enhance upper limb function in patients with stroke. OBJECTIVE: The aim of this study was to investigate whether priming iTBS with cathodal HD-tDCS over the ipsilesional M1 can augment upper limb motor recovery in poststroke patients. METHODS: A total of 66 patients with subacute stroke were randomly allocated into 3 groups. Group 1 received priming iTBS with HD-tDCS (referred to as the tDCS + iTBS group), Group 2 received non-priming iTBS (the iTBS group), and Group 3 received sham stimulation applied to the ipsilesional M1. One session was performed per day, 5 days per week, for 3 consecutive weeks. In Group 1, iTBS was preceded by a 20-minute session of cathodal HD-tDCS at a 10-minute interval. The primary outcome measure was the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score. Moreover, the secondary outcome measures for muscle strength and spasticity were the Motricity Index-Upper Extremity (MI-UE) and the Modified Ashworth Scale Upper-Extremity (MAS-UE), respectively, and the Hong Kong Version of the Functional Test for the Hemiplegic Upper Extremity (FTHUE-HK) and the Modified Barthel Index (MBI) for activity and participation. RESULTS: Significant differences were detected in the changes in FMA-UE, MI-UE, and MBI scores between the 3 groups from baseline to post-intervention (χ2FMA-UE = 10.856, P = .004; χ2MI-UE = 6.783, P = .034; χ2MBI = 9.608, P = .008). Post hoc comparisons revealed that the priming iTBS group demonstrated substantial improvements in FMA-UE (P = .004), MI-UE (P = .028), and MBI (P = 0.006) compared with those in the sham group. However, no significant difference was observed between the iTBS group and the sham group. Moreover, no significant differences were found in the changes in MAS-UE or FTHUE-HK between the groups. CONCLUSIONS: Priming iTBS with HD-tDCS over the ipsilesional M1 cortex had beneficial effects on augmenting upper limb motor recovery and enhancing daily participation among subacute stroke patients.

Carbon monoxide-releasing nanomotors based on endogenous biochemical reactions for tumor therapy.

The lack of selective release ability in the tumor microenvironment and the limited efficacy of monotherapy are important factors that limit the current use of carbon monoxide (CO) donors for tumor therapy. Herein, inspired by endogenous biochemical reactions in vivo, one kind of CO-releasing nanomotor was designed for the multimodal synergistic treatment of tumor. Specifically, glucose oxidase (GOx) and 5-aminolevulinic acid (5-ALA) were co-modified onto metal-organic framework material (MIL-101) to obtain MIL-GOx-ALA nanomotors (M-G-A NMs), which exhibit excellent biocompatibility and degradation ability in tumor microenvironment. Subsequently, the released 5-ALA generates CO in the tumor microenvironment through an endogenous reaction and further acts on mitochondria to release large amounts of reactive oxygen species (ROS), which directly kill tumor cells. Furthermore, the produced ROS and the degradation products of M-G-A NMs can also provide the reaction substrate for the Fenton reaction, thereby enhancing chemodynamic therapy (CDT) and inducing apoptosis of tumor cells. Both in vitro and in vivo experimental data confirm the successful occurrence of the above process, and the combination of CO gas therapy/enhanced CDT can effectively inhibit tumor growth. This CDT-enhancing agent designed based on endogenous biochemical reactions has good prospects for tumor treatment application.

Effects of repetitive transcranial magnetic stimulation over the contralesional dorsal premotor cortex on upper limb function in severe ischaemic stroke: study protocol for a randomised controlled trial.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment widely recommended to promote hand motor recovery after ischaemic stroke. However, the therapeutic efficacy of rTMS over the motor cortex in stroke patients is currently restricted and heterogeneous. This study aimed to determine whether excitatory rTMS over the contralesional dorsal premotor cortex (cPMd) facilitates the functional recovery of the upper limbs during the postacute stage of severe ischaemic stroke. METHODS AND ANALYSIS: This study will be conducted as a single-blind, controlled, randomised study, in which 44 patients with poststroke hemiplegia with a course of disease ranging from 1 week to 3 months and Fugl-Meyer upper limb score ≤22 will be enrolled. The study participants will be randomly assigned to groups A (n=22) and B (n=22). The two groups are based on routine rehabilitation training and drug treatment; group A will be treated with low-frequency (1 Hz) rTMS over the contralesional primary motor cortex (cM1), and group B will be treated with high-frequency (10 Hz) rTMS over cPMd. For 2 weeks, rTMS will be administered once a day, 5 days a week. The primary outcome is the Fugl-Meyer assessment of the upper limb. The secondary outcomes include the Arm Subscore of the Motricity Index, Hong Kong edition of Functional Test for the Hemiplegic Upper Extremity, Modified Barthel Index and Modified Ashworth Scale score of the paralysed pectoralis major and biceps brachii. Furthermore, data of diffusion tensor imaging and functional MRI will be collected. These outcomes will be assessed before and after the completion of the intervention. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (2020 SR-266). The findings of this study will be spread through networks of scientists, professionals and the general public as well as peer-reviewed scientific papers and presentations at pertinent conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000038049.

Progress in the Treatment of Peritoneal Metastatic Cancer and the Application of Therapeutic Nanoagents.

Peritoneal metastatic cancer is a cancer caused by the direct growth of cancer cells from the primary site through the bloodstream, lymph, or peritoneum, which is a difficult part of current clinical treatment. In the abdominal cavity of patients with metastatic peritoneal cancer, there are usually nodules of various sizes and malignant ascites. Among them, nodules of different sizes can obstruct intestinal movement and form intestinal obstruction, while malignant ascites can cause abdominal distension and discomfort, and even cause patients to have difficulty in breathing. The pathology and physiology of peritoneal metastatic cancer are complex and not fully understood. The main hypothesis is "seed" and "soil"; i.e., cells from the primary tumor are shed and implanted in the peritoneal cavity (peritoneal metastasis). In the last two decades, the main treatment modalities used clinically are cytoreductive surgery (CRS), systemic chemotherapy, intraperitoneal chemotherapy, and combined treatment, all of which help to improve patient survival and quality of life (QOL). However, the small-molecule chemotherapeutic drugs used clinically still have problems such as rapid drug metabolism and systemic toxicity. With the rapid development of nanotechnology in recent years, therapeutic nanoagents for the treatment of peritoneal metastatic cancer have been gradually developed, which has improved the therapeutic effect and reduced the systemic toxicity of small-molecule chemotherapeutic drugs to a certain extent. In addition, nanomaterials have been developed not only as therapeutic agents but also as imaging agents to guide peritoneal tumor CRS. In this review, we describe the etiology and pathological features of peritoneal metastatic cancer, discuss in detail the clinical treatments that have been used for peritoneal metastatic cancer, and analyze the advantages and disadvantages of the different clinical treatments and the QOL of the treated patients, followed by a discussion focusing on the progress, obstacles, and challenges in the use of therapeutic nanoagents in peritoneal metastatic cancer. Finally, therapeutic nanoagents and therapeutic tools that may be used in the future for the treatment of peritoneal metastatic cancer are prospected.

Research Progress on the Effect of Nitrogen on Rapeseed between Seed Yield and Oil Content and Its Regulation Mechanism.

Rapeseed (Brassica napus L.) is one of the most important oil crops in China. Improving the oil production of rapeseed is an important way to ensure the safety of edible oil in China. Oil production is an important index that reflects the quality of rapeseed and is determined by the oil content and yield. Applying nitrogen is an important way to ensure a strong and stable yield. However, the seed oil content has been shown to be reduced in most rapeseed varieties after nitrogen application. Thus, it is critical to screen elite germplasm resources with stable or improved oil content under high levels of nitrogen, and to investigate the molecular mechanisms of the regulation by nitrogen of oil accumulation. However, few studies on these aspects have been published. In this review, we analyze the effect of nitrogen on the growth and development of rapeseed, including photosynthetic assimilation, substance distribution, and the synthesis of lipids and proteins. In this process, the expression levels of genes related to nitrogen absorption, assimilation, and transport changed after nitrogen application, which enhanced the ability of carbon and nitrogen assimilation and increased biomass, thus leading to a higher yield. After a crop enters the reproductive growth phase, photosynthates in the body are transported to the developing seed for protein and lipid synthesis. However, protein synthesis precedes lipid synthesis, and a large number of photosynthates are consumed during protein synthesis, which weakens lipid synthesis. Moreover, we suggest several research directions, especially for exploring genes involved in lipid and protein accumulation under nitrogen regulation. In this study, we summarize the effects of nitrogen at both the physiological and molecular levels, aiming to reveal the mechanisms of nitrogen regulation in oil accumulation and, thereby, provide a theoretical basis for breeding varieties with a high oil content.

Selenium-enriched Polysaccharides from Pyracantha fortuneana (SePFP) Ameliorated Hepatic Lipid Accumulation through Enhancing Mitochondrial Fatty Acid ß-Oxidation in Aging Mice.

Selenium-enriched polysaccharides from Pyracantha fortuneana (SePFP) has many beneficial physiological activities, but how it improves the aging associated abnormal lipid metabolism is still unclear. Therefore, we explored the mechanisms of the regulatory role of SePFP on liver lipid accumulation in aging mice. METHODS: 60 naturally aged C57BL/6J male mice were divided into 6 groups: adult group, aging group (21-month-old mice), aging mice treated with low-, medium- and high-doses of SePFP (SePFP-L, SePFP-M, SePFP-H), and aging mice treated with resveratrol (RSV). SePFP and RSV were administrated daily via oral gavage from 16 to 21 months old. The parameters of energy metabolism were measured in all mice before sacrifice, and liver tissues were collected to determine the levels of metabolism-related enzymes by real-time PCR and Western blot. RESULTS: We found that SePFP significantly reduced the body weight, liver to bodyweight ratio, and white fat to body weight ratio in aging mice. SePFP also down-regulated the triglycerides and cholesterol levels in liver and serum, and decreased respiratory quotient in aging mice. The mechanism of SePFP regulating lipid metabolism was mainly through promoting fatty acid transportation to mitochondria and enhancing mitochondrial ß-oxidation and ketone body production. CONCLUSION: SePFP attenuates liver lipid deposition in aging mice by enhancing hepatic mitochondrial ß-oxidation.

Brain activation of the PFC during dual-task walking in stroke patients: A systematic review and meta-analysis of functional near-infrared spectroscopy studies.

Background: Dual-task walking is a good paradigm to measure the walking ability of stroke patients in daily life. It allows for a better observation of brain activation under dual-task walking to assess the impact of the different tasks on the patient when combining with functional near-infrared spectroscopy (fNIRS). This review aims to summarize the cortical change of the prefrontal cortex (PFC) detected in single-task and dual-task walking in stroke patients. Methods: Six databases (Medline, Embase, PubMed, Web of Science, CINAHL, and Cochrane Library) were systematically searched for relevant studies, from inception to August 2022. Studies that measured the brain activation of single-task and dual-task walking in stroke patients were included. The main outcome of the study was PFC activity measured using fNIRS. In addition, a subgroup analysis was also performed for study characteristics based on HbO to analyze the different effects of disease duration and the type of dual task. Results: Ten articles were included in the final review, and nine articles were included in the quantitative meta-analysis. The primary analysis showed more significant PFC activation in stroke patients performing dual-task walking than single-task walking (SMD = 0.340, P = 0.02, I 2 = 7.853%, 95% CI = 0.054-0.626). The secondary analysis showed a significant difference in PFC activation when performing dual-task walking and single-task walking in chronic patients (SMD = 0.369, P = 0.038, I 2 = 13.692%, 95% CI = 0.020-0.717), but not in subacute patients (SMD = 0.203, P = 0.419, I 2 = 0%, 95% CI = -0.289-0.696). In addition, performing walking combining serial subtraction (SMD = 0.516, P < 0.001, I 2 = 0%, 95% CI = 0.239-0.794), obstacle crossing (SMD = 0.564, P = 0.002, I 2 = 0%, 95% CI = 0.205-0.903), or a verbal task (SMD = 0.654, P = 0.009, I 2 = 0%, 95% CI = 0.164-1.137) had more PFC activation than single-task walking, while performing the n-back task did not show significant differentiation (SMD = 0.203, P = 0.419, I 2 = 0%, 95% CI = -0.289-0.696). Conclusions: Different dual-task paradigms produce different levels of dual-task interference in stroke patients with different disease durations, and it is important to choose the matching dual-task type in relation to the walking ability and cognitive ability of the patient, in order to better improve the assessment and training effects. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022356699.

Genome-Wide Identification and Functional Characterization of Stress Related Glyoxalase Genes in Brassica napus L.

Rapeseed (Brassica napus L.) is not only one of the most important oil crops in the world, but it is also an important vegetable crop with a high value nutrients and metabolites. However, rapeseed is often severely damaged by adverse stresses, such as low temperature, pathogen infection and so on. Glyoxalase I (GLYI) and glyoxalase II (GLYII) are two enzymes responsible for the detoxification of a cytotoxic metabolite methylglyoxal (MG) into the nontoxic S-D-lactoylglutathione, which plays crucial roles in stress tolerance in plants. Considering the important roles of glyoxalases, the GLY gene families have been analyzed in higher plans, such as rice, soybean and Chinese cabbage; however, little is known about the presence, distribution, localizations and expression of glyoxalase genes in rapeseed, a young allotetraploid. In this study, a total of 35 BnaGLYI and 30 BnaGLYII genes were identified in the B. napus genome and were clustered into six and eight subfamilies, respectively. The classification, chromosomal distribution, gene structure and conserved motif were identified or predicted. BnaGLYI and BnaGLYII proteins were mainly localized in chloroplast and cytoplasm. By using publicly available RNA-seq data and a quantitative real-time PCR analysis (qRT-PCR), the expression profiling of these genes of different tissues was demonstrated in different developmental stages as well as under stresses. The results indicated that their expression profiles varied among different tissues. Some members are highly expressed in specific tissues, BnaGLYI11 and BnaGLYI27 expressed in flowers and germinating seed. At the same time, the two genes were significantly up-regulated under heat, cold and freezing stresses. Notably, a number of BnaGLY genes showed responses to Plasmodiophora brassicae infection. Overexpression of BnGLYI11 gene in Arabidopsis thaliana seedlings confirmed that this gene conferred freezing tolerance. This study provides insight of the BnaGLYI and BnaGLYII gene families in allotetraploid B. napus and their roles in stress resistance, and important information and gene resources for developing stress resistant vegetable and rapeseed oil.

Anodal high-definition transcranial direct current stimulation reduces heart rate and modulates heart-rate variability in healthy young people: A randomized cross-controlled trial.

Objective: To investigate whether anodal high-definition transcranial current stimulation (HD-tDCS) over the left dorsolateral pre-frontal cortex (DLPFC) could modulate the heart rate (HR) and heart-rate variability (HRV) in healthy young people. Methods: Forty healthy young people were enrolled in this randomized crossover trial. The participants were randomized to receive anodal HD-tDCS (n = 20) or sham HD-tDCS (n = 20) over the left DLPFC with a washout period of 1 week. Electrocardiogram (ECG) data were continuously recorded 20 min before the stimulation, during the session (20 min), and 20 min after the session. HR and the time- and frequency-domain indices of the HRV were measured to investigate the activity of the sympathetic and parasympathetic nervous systems. Results: Anodal HD-tDCS over the left DLPFC induced a significant decrease in HR and a significant increase in the average of normal-to-normal intervals (AVG NN), low-frequency (LF) power, total power (TP), and LF/high-frequency (HF) ratio in comparison with the sham stimulation and the baseline. However, sham HD-tDCS over the left DLPFC had no significant effect on HR or HRV. Conclusions: Anodal HD-tDCS over the left DLPFC could reduce HR and modulate the HRV in healthy young people. HD-tDCS may show some potential for acutely modulating cardiovascular function.

Neutrophil-to-platelet ratio predicts mortality following percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction.

This study aimed to evaluate the value of neutrophil-to-platelet ratio (NPR) in predicting all-cause mortality in patients with ST-elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI). We enrolled 186 patients with STEMI who underwent primary PCI in the Third Affiliated Hospital of Guangzhou Medical University between January 2017 and December 2018. Based on the NPR values, the patients were divided into two groups: the NPR >0.035 group (n = 82) and the NPR ≤0.035 group (n = 104). All-cause mortality of the patients was followed up for 3 years. By the end of 3 years, 109 (58.6%) patients survived, 53 (28.5%) died, and 24 (12.9%) were lost to follow-up. Univariate analyses found that NPR was associated with all-cause mortality (p < 0.05). In COX regression analyses, patients in the high NPR group had a higher risk of all-cause death than those in the low NPR group (HR = 2.296, 95% CI: 1.150-4.582). These results indicate that NPR could predict all-cause death in 3 years after primary PCI in patients STEMI. NPR values may be useful in risk stratification and in specifying individualized treatment in patients with STEMI. In addition, NPR is a low-cost and easily accessible indicator, if its strong predictive value is confirmed in further studies of other large populations, it can be introduced into clinical practice for effective application.

Effects of rTMS treatment on global cognitive function in Alzheimer's disease: A systematic review and meta-analysis.

Background: Although repetitive transcranial magnetic stimulation (rTMS) has been extensively studied in patients with Alzheimer's disease (AD), the clinical evidence remains inconsistent. The purpose of this meta-analysis was to evaluate the effects of rTMS on global cognitive function in patients with AD. Methods: An integrated literature search using 4 databases (PubMed, Web of Science, Embase, and Cochrane Library) was performed to identify English language articles published up to October 6, 2021. We pooled Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) scores using a random-effects model via RevMan 5.4 software. We calculated estimates of mean differences (MD) with 95% confidence intervals (CI). The primary outcomes were pre-post treatment changes in global cognition as measured using MMSE and ADAS-Cog immediately after rTMS treatment, and the secondary outcome was duration of cognitive improvement (1-1.5 and ≥3 months). Results: Nine studies with 361 patients were included in this meta-analysis. The results showed that rTMS significantly improved global cognitive function immediately following rTMS treatment [(MD) 1.82, 95% confidence interval (CI) 1.41-2.22, p < 0.00001, MMSE; 2.72, 95% CI, 1.77-3.67, p < 0.00001, ADAS-Cog], and the therapeutic effects persisted for an extended duration (2.20, 95% CI, 0.93-3.47, p =0.0007, MMSE; 1.96, 95% CI, 0.96-2.95, p = 0.0001, ADAS-Cog). Subgroup analyses showed that high frequency rTMS targeted to the left dorsolateral prefrontal cortex (DLPFC) for over 20 sessions induced the greatest cognitive improvement, with effects lasting for more than 1 month after the final treatment. There were no significant differences in dropout rate (p > 0.05) or adverse effect rate (p > 0.05) between the rTMS and control groups. Conclusions: Repetitive TMS is a potentially effective treatment for cognitive impairment in AD that is safe and can induce long-lasting effects. Our results also showed that ADAS-cog and MMSE differed in determination of global cognitive impairment. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO, PROSPERO CRD42022315545.

High-frequency repetitive transcranial magnetic stimulation improves spatial episodic learning and memory performance by regulating brain plasticity in healthy rats.

Background: Repetitive transcranial magnetic stimulation (rTMS) is an effective way to stimulate changes in structural and functional plasticity, which is a part of learning and memory. However, to our knowledge, rTMS-induced specific activity and neural plasticity in different brain regions that affect cognition are not fully understood; nor are its mechanisms. Therefore, we aimed to investigate rTMS-induced cognition-related neural plasticity changes and their mechanisms in different brain regions. Methods: A total of 30 healthy adult rats were randomly divided into the control group and the rTMS group (n = 15 rats per group). The rats in the control and the rTMS group received either 4 weeks of sham or high-frequency rTMS (HF-rTMS) over the prefrontal cortex (PFC). Cognitive function was detected by Morris water maze. Functional imaging was acquired by resting-state functional magnetic resonance imaging (rs-fMRI) before and after rTMS. The protein expressions of BDNF, TrkB, p-Akt, Akt, NR1, NR2A, and NR2B in the PFC, hippocampus, and primary motor cortex (M1) were detected by Western blot following rTMS. Results: After 4 weeks of rTMS, the cognitive ability of healthy rats who underwent rTMS showed a small but significant behavioral improvement in spatial episodic learning and memory performance. Compared with the pre-rTMS or the control group, rats in the rTMS group showed increased regional homogeneity (ReHo) in multiple brain regions in the interoceptive/default mode network (DMN) and cortico-striatal-thalamic network, specifically the bilateral PFC, bilateral hippocampus, and the left M1. Western blot analyses showed that rTMS led to a significant increase in the expressions of N-methyl-D-aspartic acid (NMDA) receptors, including NR1, NR2A, and NR2B in the PFC, hippocampus, and M1, as well as an upregulation of BDNF, TrkB, and p-Akt in these three brain regions. In addition, the expression of NR1 in these three brain regions correlated with rTMS-induced cognitive improvement. Conclusion: Overall, these data suggested that HF-rTMS can enhance cognitive performance through modulation of NMDA receptor-dependent brain plasticity.

Evaluation of p16/Ki-67 dual-stain as triage test for high-risk HPV-positive women: A hospital-based cross-sectional study.

BACKGROUND: Most human papillomavirus (HPV)-positive women recover from infections and do not develop cervical intraepithelial neoplasia (CIN) and cervical cancer. Additional triage approaches are needed to reduce unnecessary colposcopy referrals. The aim of this study is to determine the high-risk HPV prevalence in a hospital-based population and to evaluate the performance of p16/Ki-67 dual-stain test for the triage of high-risk HPV-positive women to detect precursor lesions and cervical cancer compared with the ThinPrep cytologic test (TCT). METHODS: In a hospital-based population, 100,801 women were provided with a primary HPV DNA test and only women with high-risk HPV infections were triaged using TCT and p16/Ki-67 dual-stain test. CIN2 or worse (≥CIN2) or CIN3 or worse (≥CIN3) were defined as the clinical end points. RESULTS: The p16/Ki-67 dual-stain indicated a statistically significant higher sensitivity (82.8% vs. 66.7%%), specificity (51.6% vs. 44.4%), positive predictive value (33.2% vs. 25.8%), negative predictive value (91.2% vs. 82.1%), and accuracy (58.6% vs. 49.4%) compared with TCT examination within ≥CIN2 cases. Similar patterns were observed for the ≥CIN3 end point. CONCLUSIONS: Our study demonstrated that p16/Ki-67 dual-stain test could achieve better performance compared with TCT examination for ≥CIN2 or ≥ CIN3 detection, representing a promising approach as a specific and efficient triage strategy for high-risk HPV-positive women.

Preconditioning with Cathodal High-Definition Transcranial Direct Current Stimulation Sensitizes the Primary Motor Cortex to Subsequent Intermittent Theta Burst Stimulation.

Noninvasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can induce long-term potentiation-like facilitation, but whether the combination of TMS and tDCS has additive effects is unclear. To address this issue, in this randomized crossover study, we investigated the effect of preconditioning with cathodal high-definition (HD) tDCS on intermittent theta burst stimulation- (iTBS-) induced plasticity in the left motor cortex. A total of 24 healthy volunteers received preconditioning with cathodal HD-tDCS or sham intervention prior to iTBS in a random order with a washout period of 1 week. The amplitude of motor evoked potentials (MEPs) was measured at baseline and at several time points (5, 10, 15, and 30 min) after iTBS to determine the effects of the intervention on cortical plasticity. Preconditioning with cathodal HD-tDCS followed by iTBS showed a greater increase in MEP amplitude than sham cathodal HD-tDCS preconditioning and iTBS at each time postintervention point, with longer-lasting after-effects on cortical excitability. These results demonstrate that preintervention with cathodal HD-tDCS primes the motor cortex for long-term potentiation induced by iTBS and is a potential strategy for improving the clinical outcome to guide therapeutic decisions.

Overexpression of GmMYB14 improves high-density yield and drought tolerance of soybean through regulating plant architecture mediated by the brassinosteroid pathway.

MYB transcription factors (TFs) have been reported to regulate the biosynthesis of secondary metabolites, as well as to mediate plant adaption to abiotic stresses, including drought. However, the roles of MYB TFs in regulating plant architecture and yield potential remain poorly understood. Here, we studied the roles of the dehydration-inducible GmMYB14 gene in regulating plant architecture, high-density yield and drought tolerance through the brassinosteroid (BR) pathway in soybean. GmMYB14 was shown to localize to nucleus and has a transactivation activity. Stable GmMYB14-overexpressing (GmMYB14-OX) transgenic soybean plants displayed a semi-dwarfism and compact plant architecture associated with decreased cell size, resulting in a decrease in plant height, internode length, leaf area, leaf petiole length and leaf petiole angle, and improved yield in high density under field conditions. Results of the transcriptome sequencing suggested the involvement of BRs in regulating GmMYB14-OX plant architecture. Indeed, GmMYB14-OX plants showed reduced endogenous BR contents, while exogenous application of brassinolide could partly rescue the phenotype of GmMYB14-OX plants. Furthermore, GmMYB14 was shown to directly bind to the promoter of GmBEN1 and up-regulate its expression, leading to reduced BR content in GmMYB14-OX plants. GmMYB14-OX plants also displayed improved drought tolerance under field conditions. GmBEN1 expression was also up-regulated in the leaves of GmMYB14-OX plants under polyethylene glycol treatment, indicating that the GmBEN1-mediated reduction in BR level under stress also contributed to drought/osmotic stress tolerance of the transgenic plants. Our findings provided a strategy for stably increasing high-density yield and drought tolerance in soybean using a single TF-encoding gene.

Rapid detection of SARS-CoV-2 with CRISPR-Cas12a.

The recent outbreak of betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is responsible for the Coronavirus Disease 2019 (COVID-19) global pandemic, has created great challenges in viral diagnosis. The existing methods for nucleic acid detection are of high sensitivity and specificity, but the need for complex sample manipulation and expensive machinery slow down the disease detection. Thus, there is an urgent demand to develop a rapid, inexpensive, and sensitive diagnostic test to aid point-of-care viral detection for disease monitoring. In this study, we developed a clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated proteins (Cas) 12a-based diagnostic method that allows the results to be visualized by the naked eye. We also introduced a rapid sample processing method, and when combined with recombinase polymerase amplification (RPA), the sample to result can be achieved in 50 minutes with high sensitivity (1-10 copies per reaction). This accurate and portable detection method holds a great potential for COVID-19 control, especially in areas where specialized equipment is not available.

Effect of puerarin on action potential and sodium channel activation in human hypertrophic cardiomyocytes.

OBJECTIVE: To study the effect of puerarin on electrophysiology using a hypertrophic cardiomyocyte (HC) model. MATERIALS AND METHODS: Human urine epithelial cells were used to generate the HC model (hiPSC-CM). Cardiomyocyte hypertrophy was induced by applying 10 nM endothelin-1 (ET-1). Effects of puerarin pre-treatment (PPr) and post-treatment (PPo) on action potential, sodium current (INa) activation and inactivation, and recovery following INa inactivation were tested using patch clamp electrophysiology. RESULTS: Depolarization to repolarization 50% time (APD50) and repolarization 30% time (APD30) were significantly prolonged in the PPo and PPr groups compared with the controls. However, there were no significant differences in the action potential depolarization amplitude (APA) or the maximum depolarization velocity (Vmax) in phase 0. The PPr group had a slightly shortened APD90, and an extended APD50 and APD30, but did not exhibit any significant changes in stage A of APA and Vmax. The PPo group did not exhibit any significant changes in INa, while 12 h of PPr improved INa. However, puerarin did not significantly affect the activation, inactivation, or recovery of the sodium channel. CONCLUSIONS: Cardiomyocyte hypertrophy significantly decreased the Vmax of the action potential and the peak density of INa. PPr inhibited the decrease in Vmax and increased the peak density of INa. Thus, puerarin could be used to stabilize the electrophysiological properties of hypertrophic cardiomyocytes and reduce arrhythmias.

Cardioprotective effects of anisodamine against myocardial ischemia/reperfusion injury through the inhibition of oxidative stress, inflammation and apoptosis.

The aim of the present study was to investigate the cardioprotective effects of anisodamine against myocardial ischemia/reperfusion (I/R) injury and the molecular mechanisms involved. The present results demonstrated that anisodamine attenuated myocardial infarct sizes, decreased the levels of creatine kinase and lactate dehydrogenase, whereas it increased the left ventricular (LV) systolic pressure, the LV end­diastolic pressure, and the LV pressure maximum rising and falling rates in a myocardial I/R rat model. In addition, anisodamine was revealed to suppress oxidative stress, inflammatory factor production and myocardial cell apoptosis, as demonstrated by the downregulation of caspase­3 and apoptosis regulator BAX protein expression. The production of reactive oxygen species was decreased and the protein expression of inducible nitric oxide synthase (iNOS) was downregulated, whereas the expression of endothelial NOS was enhanced. In addition, the activity of nicotinamide­adenine dinucleotide phosphate oxidase (Nox) was suppressed and the expression of Nox4 was downregulated in rats with myocardial I/R injury. In conclusion, the results of the present study suggested that anisodamine exerted a cardioprotective effect against myocardial I/R injury in rats, through the inhibition of oxidative stress, the suppression of inflammatory processes and the inhibition of myocardial cell apoptosis.

Renal denervation attenuates cardiac hypertrophy in spontaneously hypertensive rats via regulation of autophagy.

It has been suggested that renal denervation (RD) may attenuate left ventricular (LV) hypertrophy. However, the role that autophagy serves in this process is currently unclear. In the present study, utilizing a model of hypertension­induced cardiac hypertrophy in spontaneous hypertensive rats, it was demonstrated that RD was significantly associated with a reduction in LV hypertrophy. Furthermore, a decrease in the myocardial mRNA of hypertrophy­associated genes was demonstrated in RD rats compared with sham controls. In addition, RD in hypertension­induced LV hypertrophy rats was associated with the attenuation of cellular autophagic response over activation at a physiological level. This was indicated by a reduction in the expression of Beclin­1, autophagy related 9A and microtubule­associated protein 1A/1B-light chain 3 II/I in RD rats to physiological levels that are observed in control rats. Furthermore, the number of autophagosomes was restored to physiological levels in the cardiomyocytes of RD rats. The results of the current study suggest that RD may attenuate LV hypertrophy via the regulation of autophagic responses.

Detection of circulating tumour cells in patients with epithelial ovarian cancer by a microfluidic system.

Ovarian cancer is a gynaecological cancer with a high mortality rate. In recent years, circulating tumour cells (CTCs) have attracted attention from scientists because of their significant association with metastasis. However, due to the low CTC enrichment rate of the conventional CellSearch system and limited clinical sample sizes, only a small number of studies have focused on CTCs and epithelial ovarian cancer (EOC). Here, we apply a microfluidic system with immunomagnetic beads preconjugated with an anti-EpCAM antibody to enrich CTCs from whole blood and then analyse the enriched cells by immunofluorescence staining and automatic fluorescence microscope scanning. The average recovery rate of SK-OV-3 EOC cells was 70.2%±13.3%. When using blood samples from EOC patients and healthy volunteers, CTC counts of more than 8 cells were detected in 20 of 23 EOC patients (87.0%) but in none of the 16 healthy volunteers (0%). Total CTC counts were found to be significantly (P<0.05) elevated in the EOC group (median =55.0 [29.5, 123.0] CTCs/7.5 mL) compared with the healthy control group (median =0.5 [0,3.5] CTCs/7.5 mL). In conclusion, this is the first study to use the IsoFlux system on ovarian cancer samples. This system can efficiently capture EOC CTCs from a majority of patients and may provide a potential tool for further biological studies and for the development of in vitro EOC diagnostic products.