Fusion of memristor and digital compute-in-memory processing for energy-efficient edge computing.

Artificial intelligence (AI) edge devices prefer employing high-capacity nonvolatile compute-in-memory (CIM) to achieve high energy efficiency and rapid wakeup-to-response with sufficient accuracy. Most previous works are based on either memristor-based CIMs, which suffer from accuracy loss and do not support training as a result of limited endurance, or digital static random-access memory (SRAM)-based CIMs, which suffer from large area requirements and volatile storage. We report an AI edge processor that uses a memristor-SRAM CIM-fusion scheme to simultaneously exploit the high accuracy of the digital SRAM CIM and the high energy-efficiency and storage density of the resistive random-access memory memristor CIM. This also enables adaptive local training to accommodate personalized characterization and user environment. The fusion processor achieved high CIM capacity, short wakeup-to-response latency (392 microseconds), high peak energy efficiency (77.64 teraoperations per second per watt), and robust accuracy (<0.5% accuracy loss). This work demonstrates that memristor technology has moved beyond in-lab development stages and now has manufacturability for AI edge processors.

Global trends and hotspots in research on acupuncture for stroke: a bibliometric and visualization analysis.

Acupuncture has been widely used in stroke and post-stroke rehabilitation (PSR), but there is no literature on the bibliometric analysis of acupuncture for stroke. This study aimed to characterize the global publications and analyze the trends of acupuncture for stroke in the past 40 years. We identified 1157 publications from the Web of Science Core Collection. The number of publications grew slowly in the first three decades from 1980 until it started to grow after 2010, with significant growth in 2011-2012 and 2019-2020. China, the USA, and South Korea are the top three countries in this field, and China has formed good internal cooperative relations. Early studies focused on the clinical efficacy of acupuncture for stroke. In the last five years, more emphasis has been placed on the effectiveness of acupuncture in treating sequelae and complications, combined with neuroimaging studies to explore the mechanisms of brain injury repair and neurological recovery. Acupuncture for stroke has a vast research potential, and researchers from different countries/regions and organizations still need to remove academic barriers to enhance communication and collaboration.

High-precision Fourier ptychographic microscopy based on Gaussian apodization coherent transfer function constraints.

Fourier ptychographic microscopy (FPM) combines the concepts of phase retrieval algorithms and synthetic apertures and can solve the problem in which it is difficult to combine a large field of view with high resolution. However, the use of the coherent transfer function in conventional calculations to describe the linear transfer process of an imaging system can lead to ringing artifacts. In addition, the Gerchberg-Saxton iterative algorithm can cause the phase retrieval part of the FPM algorithm to fall into a local optimum. In this paper, Gaussian apodization coherent transfer function is proposed to describe the imaging process and is combined with an iterative method based on amplitude weighting and phase gradient descent to reduce the presence of ringing artifacts while ensuring the accuracy of the reconstructed results. In simulated experiments, the proposed algorithm is shown to give a smaller mean square error and higher structural similarity, both in the presence and absence of noise. Finally, the proposed algorithm is validated in terms of giving reconstruction results with high accuracy and high resolution, using images acquired with a new microscope system and open-source images.

Acupuncture for Parkinson's disease-related constipation: current evidence and perspectives.

Parkinson's disease-related constipation (PDC) is commonly associated with impaired dopamine transmission and gastrointestinal dysfunction. Current pharmacological treatments have limited efficacy and potential side effects. Acupuncture has shown promise as an alternative or adjunct therapy by modulating the brain-gut axis, gastrointestinal hormones, and autonomic function. Preliminary randomized trials have shown that acupuncture significantly improves constipation symptoms, bowel movements, and comfort compared to sham or drug treatments and is well-tolerated. The mechanisms of action may involve regulating the gut microbiota and mucosal immunity to improve dysbiosis and gastrointestinal motility. However, more rigorous studies are required to optimize acupuncture protocols and determine long-term efficacy and safety. In summary, acupuncture shows promise as an adjunct therapy for PDC, but further research is needed to confirm its efficacy and safety.

Characteristics of the school adaptation of college freshmen during the COVID-19 epidemic.

Few studies have actually explored the impact of the COVID-19 pandemic on mental health in college students, although many studies have suggested that the COVID-19 pandemic poses a great threat to people's mental health in many cohorts. Furthermore, college students may be a particularly vulnerable cohort that needs more attention and access to psychological services due to the psychological changes involved in the transition to college and the characteristics of college students' study habits and lifestyle. Therefore, investigating the basic characteristics of the impact of the COVID-19 pandemic on college freshmen is of great practical importance and has theoretical implications for the identification and provisioning of services to vulnerable cohorts. A total of 5,818 college freshmen completed the College Student Adaptability Inventory. The results suggest that the mean detection rate of the seven dimensions of undergraduate maladjustment to university is 27.13%. Specifically, livelihood self-management adaptability has the highest detection rate (48.93%), while environmental general evaluation has the lowest detection rate (9.81%). Moreover, the school adaptation of college freshmen is impacted by gender, number of siblings, and family socioeconomic status (SES). Specifically, students who are female, an only child, and have a lower SES have lower levels of school adaptation. However, the school adaptation of college freshmen is not influenced by minority status or left-behind status. The findings of the present study suggest that the maladaptation of college freshmen has been a common phenomenon in China during the COVID-19 epidemic. Prevention programs may be most helpful if they pay more attention to effective intervention efforts for students who are female, an only child, and have a lower SES.

Analysis of Key Genes for Slow Transit Constipation Based on RNA Sequencing.

Purpose: This study aims to identify key genes in slow transit constipation (STC). We also sought to explore the potential link between STC and colorectal cancer. Patients and Methods: mRNA expression profiles were obtained by RNA sequencing, and differentially expressed genes were identified. Functional enrichment analysis and a protein-protein interaction (PPI) network was explored, and differentially expressed genes common to STC and colorectal cancer were examined. Analysis of the effect of constipation and colorectal cancer common genes on the overall survival of colorectal cancer patients based on GEPIA database. Results: Functional enrichment showed that significantly different genes are related to lymphocyte chemotaxis, positive regulation of inflammatory response, cellular response to tumor necrosis factor, extracellular region, extracellular space and chemokine activity. The hub gene for STC was found in the PPI network. In addition, AQP8 and CFD were common differential genes for STC and colorectal cancer. AQP8 affects overall survival in patients with colorectal cancer. Conclusion: Our findings will contribute to understanding the pathology of STC at the molecular level, with the first discovery that AQP8 may be a hub gene in the transition from STC to colorectal cancer.

Nonbiodegradable Spiegelmer-Driven Colorimetric Biosensor for Bisphenol A Detection.

Spiegelmers are enantiomers of natural D-oligonucleotides that bind to targets with distinct structures such as aptamers. The high susceptibility of natural D-form aptamers to nucleases greatly hinders their application in biological environments. Here, a nonbiodegradable spiegelmer-based platform for the sensitive detection of bisphenol A (BPA) was developed. Due to the symmetric molecule of BPA, the D-form aptamer can be directly converted into mirror forms via chemical synthesis. Aptamer-target interactions that involve chemically synthesized spiegelmers were characterized by biolayer interferometry, and their stabilities were tested in various biological fluids by exposure to nucleases. We demonstrate for the first time the use of a nuclease-resistant spiegelmer in a simple, label-free gold nanoparticle-based colorimetric assay to detect BPA in a highly sensitive and selective manner. The aptasensor exhibits an LOD of 0.057 ng/mL and dynamic range of 105 (100 pg/mL to 10 mg/mL). With sensing capacity and biological stability, the developed aptasensor shows great potential to utilize in in-field applications such as water quality monitoring.

Dictamnine inhibits pancreatic cancer cell growth and epithelial-mesenchymal transition by blocking the PI3K/AKT signaling pathway.

Many different treatments are available for pancreatic cancer (PC), including surgical resection, chemotherapy, radiotherapy, and immunotherapy, but these treatments are often ineffective at curing PC. Hence, identifying new and effective agents or strategies to improve therapeutic effects is critical. This study focused on the efficacy of dictamnine (DTM), a furan quinoline alkaloid extracted from Dictamnus dasycarpus Turcz., in treating PC. Our in vitro results showed that DTM can mitigate cell proliferation and induce cell cycle arrest and apoptosis in two different human PC cell lines. Moreover, epithelial-mesenchymal transition (EMT) was prevented during DTM treatment, reflected by reduced cell migration and invasion abilities. In vivo studies demonstrated that DTM treatment led to a remarkable inhibition of tumor growth in a xenograft nude mouse model. Mechanistic investigation showed that DTM might act by restraining constitutive and induced PI3K/AKT activity. In summary, our results demonstrated that DTM slows PC progression by inhibiting the activity of the PI3K/AKT signaling pathway and its downstream effectors and that DTM is effective as a pathway-specific cancer therapy. These findings could provide a greater understanding of the function of anticancer drugs and new options for PC treatment.

Multivariate analysis for organic milk authentication.

To differentiate organic milk (OM) from conventional milk (CM), an orthogonal projection to latent structure-discriminant analysis (OPLS-DA) model was constructed using δ13C, δ15N, δ18O, 51 elements and 35 fatty acids (FAs) as the variables. So far, most reported studies barely use three or more types of variables, but more variables could avoid one-sidedness and get stabler models. Our multivariate model combines geographical and nutritional parameters and displays better explanatory and predictive abilities (R2X = 0.647, R2Y = 0.962 and Q2 = 0.821) than models based on fewer variables for differentiating OM and CM. In particular, δ15N, Se, δ13C, Eu, K and α-Linolenic acid (ALA) are found to be critical parameters for the discrimination of OM. These results show that the multivariate model based on stable isotopes, elements and FAs can be used to identify OM, and can potentially expand the global databases for quality and authenticity of milk.

Correction: Determining the geographical origin of milk by multivariate analysis based on stable isotope ratios, elements and fatty acids.

Correction for 'Determining the geographical origin of milk by multivariate analysis based on stable isotope ratios, elements and fatty acids' by Siyan Xu et al., Anal. Methods, 2021, DOI: .

Determining the geographical origin of milk by multivariate analysis based on stable isotope ratios, elements and fatty acids.

To construct a reliable discrimination model for determining milk geographical origin, stable isotope ratios including δ13C, δ15N and δ18O, 51 elements and 35 fatty acids (FAs) in milk samples from Australia, New Zealand and Austria were detected and analyzed. It is found that all of the stable isotope ratios in the milk samples of Australia are the highest, followed by those of the samples from New Zealand and Austria. In addition, 14 elements and 8 FAs show different contents in the samples of different countries at the significance level of P < 0.05. Based on these results, a multivariate model with good robustness and predictive ability for authenticating milk origin (R2X = 0.693, Q2 = 0.854) was successfully constructed. Element contents and stable isotope ratios are more reliable variables for milk origin discrimination and Rb, δ18O, Tl, Ba, Mo, Sr, δ15N, Cs, As, Eu, C20:4n6, Sc, C13:0, K, Ca and C16:1n7 are the critical markers in the multivariate model for verifying milk origin.

Fangchinoline exerts antitumour activity by suppressing the EGFR­PI3K/AKT signalling pathway in colon adenocarcinoma.

Fangchinoline (FAN), an alkaloid extracted from Stephania tetrandra, has a variety of biological and pharmacological activities, but evidence of its effects on colon adenocarcinoma (COAD) is limited. Therefore, the present study aimed to elucidate the molecular mechanisms by which FAN affects COAD. The cytotoxicity, viability and proliferation of DLD­1 and LoVo cells were assessed in the presence of FAN using MTT and colony formation assays. The effects of FAN on apoptosis and the cell cycle in COAD cells were analysed by flow cytometry, and the migration and invasion of these cells were assessed by wound healing and Transwell experiments. Furthermore, a network pharmacological analysis was conducted to investigate the target of FAN and the results were confirmed by western blotting. In addition, a xenograft model was established in nude mice, and ultrasound imaging was used to assess the preclinical therapeutic effects of FAN in vivo. To the best of our knowledge, the results of this study provided the first evidence that FAN inhibited cellular proliferation, stemness, migration, invasion, angiogenesis and epithelial­mesenchymal transition (EMT), and induced apoptosis and G1­phase cell cycle arrest. Network pharmacological analysis further confirmed that FAN prevented EMT through the epidermal growth factor receptor (EGFR)­phosphoinositide 3­kinase (PI3K)/AKT signalling pathway. Finally, FAN significantly repressed tumour growth and promoted apoptosis in xenografts. Thus, targeting EGFR with FAN may offer a novel therapeutic approach for COAD.

Fraxetin inhibits the growth of colon adenocarcinoma cells via the Janus kinase 2/signal transducer and activator of transcription 3 signalling pathway.

OBJECTIVE: Fraxetin, extracted from the bark of Fraxinus rhynchophylla, has been shown to exhibit antitumour and anti-inflammatory pharmacological properties. However, the mechanism underlying its anticancer activity towards colon adenocarcinoma (COAD) is not well understood. We aimed to determine the antitumour effect of fraxetin on COAD cell lines and elucidate its biochemical and molecular targets. METHODS: The cell lines HCT116 and DLD-1 were used to evaluate the in vitro antitumour efficacy of fraxetin. Cytotoxicity and viability were assessed by CCK-8 and plate colony formation assays. Flow cytometry was used to assess apoptosis and cell cycle progression in fraxetin-treated COAD cells. Western blot, RT-qPCR, molecular docking, immunohistochemical, and immunofluorescence analyses were used to gain insights into cellular and molecular mechanisms. Preclinical curative effects were evaluated in nude mouse xenograft models. RESULTS: Fraxetin significantly inhibited COAD cell proliferation in both dose- and time-dependent manners, specifically by inducing S-phase cell cycle arrest and triggering intrinsic apoptosis. Additionally, the level of p-JAK2 was decreased by fraxetin via the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signalling pathway. Interestingly, in COAD cells, fraxetin directly targeted the Y1007 and Y1008 residues of JAK2 to suppress its auto- or transphosphorylation, leading to decreased activation of its downstream effector STAT3 and blocking its nuclear translocation. Finally, fraxetin exhibited good tumour growth suppression activity and low toxicity. CONCLUSIONS: Fraxetin inhibits the proliferation of COAD cells by regulating the JAK2/STAT3 signalling pathway, providing evidence that targeting JAK2 with fraxetin may offer a novel potential auxiliary therapy for COAD treatment.

Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1­AKT/ERK­Snail signaling pathway.

Cyclovirobuxine D (CVB­D) is an alkaloid, which is mainly derived from Buxus microphylla. It has been reported that CVB­D has positive effects on breast cancer, gastric cancer and other malignant tumors. However, to the best of our knowledge, there are no reports regarding the effects of CVB­D on colorectal cancer (CRC). The purpose of the present study was to determine the anticancer effects of CVB­D and further elucidate its molecular mechanism(s). DLD­1 and LoVo cell lines were selected to evaluate the antitumor effect of CVB­D. Cytotoxicity, viability and proliferation were evaluated by the MTT and colony formation assays. Flow cytometry was used to detect the effects on apoptosis and the cell cycle in CVB­D­treated CRC cells. The migration and invasion abilities of CRC cells were examined by wound healing and Transwell assays. In addition, RNA sequencing, bioinformatics analysis and western blotting were performed to investigate the target of drug action and clarify the molecular mechanisms. A xenograft model was established using nude mice, and ultrasound was employed to assess the preclinical therapeutic effects of CVB­D in vivo. It was identified that CVB­D inhibited the proliferation, migration, stemness, angiogenesis and epithelial­mesenchymal transition of CRC cells, and induced apoptosis and S­phase arrest. In addition, CVB­D significantly inhibited the growth of xenografts. It is notable that CVB­D exerted anticancer effects in CRC cells partly by targeting collagen triple helix repeat containing 1 (CTHRC1), which may be upstream of the AKT and ERK pathways. CVB­D exerted anticancer effects through the CTHRC1­AKT/ERK­Snail signaling pathway. Targeted therapy combining CTHRC1 with CVB­D may offer a promising novel therapeutic approach for CRC treatment.

Influence of volatile anesthesia versus total intravenous anesthesia on chronic postsurgical pain after cardiac surgery using the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials criteria: study protocol for a prospective randomized controlled trial.

BACKGROUND: Many patients develop chronic postsurgical pain (CPSP) after cardiac surgery, which interferes with their sleep, mood, and quality of life. Studies have suggested that propofol improves postoperative analgesia compared with volatile anesthetics, but its preventive effect on CPSP following cardiac surgery is still unknown. This study compares the incidence of CPSP following cardiac surgery for those receiving volatile anesthesia and those receiving propofol-based total intravenous anesthesia (TIVA) using criteria recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). METHODS/DESIGN: This is a prospective randomized controlled trial. In total, 500 adults undergoing cardiac surgery will be randomly allocated to the volatile or the TIVA group. The volatile group will receive sevoflurane or desflurane during surgery as general anesthesia. The TIVA group will receive propofol-based intravenous agents and no volatile agents during surgery. The primary outcomes will be the frequency of CPSP at 3 months, 6 months, and 1 year after surgery. In this case, CPSP is sternal or thoracic pain. It is defined as either (1) numerical rating scale (NRS) > 0 or (2) meeting all six IMMPACT criteria for CPSP. The IMMPACT criteria are validated pain instruments. DISCUSSION: To our knowledge, this is the first prospective randomized controlled trial to investigate the prevention of CPSP following cardiac surgery for patients receiving volatile anesthesia compared to those receiving propofol-based TIVA using validated pain instruments in accordance with the IMMPACT recommendations. This study will provide important information on which of these two anesthetic regimens is better for preventing CPSP after cardiac surgery. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR1900020747. Registered on 16 January 2019.

AEBP1, a prognostic indicator, promotes colon adenocarcinoma cell growth and metastasis through the NF-κB pathway.

The abnormal expression of adipocyte enhancer binding protein 1 (AEBP1) has been implicated in the carcinogenesis and progression of various types of human tumors. However, the role of AEBP1 in colon adenocarcinoma (COAD) remains largely unelucidated. In this study, we explored the clinical significance and biological function of AEBP1 in COAD. We observed that AEBP1 was overexpressed in COAD tissues and cells and that the expression of AEBP1 was correlated with tumor size, the level of histologic differentiation, lymph node metastasis, and cancer stage in COAD patients. In addition, univariate and multivariate Cox regression analyses revealed that high AEBP1 expression suggested poor prognosis in COAD. Moreover, AEBP1 silencing suppressed COAD cell proliferation, migration, and invasion, whereas the upregulation of AEBP1 promoted these behaviors. Additionally, mechanistic studies further demonstrated that AEBP1 promoted COAD cell proliferation, migration, and invasion by upregulating the expression of matrix metalloproteinase-2, vimentin, and TWIST whereas downregulating that of E-cadherin through the nuclear factor-κB pathway. Collectively, these data indicated that AEBP1 may be a new prognostic factor and a potential gene therapy target in COAD.

Metals in wild fish from Gaotang Lake in the area of coal mining, China: assessment of the risk to human health.

Environmental pollution can cause metal accumulation in aquatic organisms, but information on metal bioaccumulation in wild fish from coal mining areas is limited. We investigated tissue-specific metal accumulation in six economically important fish species common to Gaotang Lake, China, located in a coal mining area. We also conducted an assessment of potential risks to human health from consumption of these fish. Mean concentrations of arsenic, cadmium, cobalt, copper, mercury, lead, and antimony in the muscle of six fish species were below the corresponding Chinese maximum allowable concentrations except chromium and generally comparable with levels in fish reported by other studies. Tissue distribution patterns suggested that chromium and mercury were easily transported to the muscle, but concentrations of the other six metals were higher in the liver and gills. The daily intake of each metal was estimated at 0.002-0.220 g/day/kg body weight, and the non-carcinogenic health risks associated with the consumption of the fish from Gaotang Lake were acceptable. The results suggest that metal bioaccumulation in wild fish is not high in this coal mining area.

ZNF692 promotes colon adenocarcinoma cell growth and metastasis by activating the PI3K/AKT pathway.

Despite considerable recent advancements in colorectal cancer (CRC) therapy, the prognosis of patients with advanced disease remains poor. Further understanding of the molecular mechanisms and treatment strategies of this disease is required. Zinc finger protein 692 (ZNF692), also known as AREBP and Zfp692, was first reported to have an important role in gluconeogenesis. A recent study demonstrated that ZNF692 is overexpressed in lung adenocarcinoma (LUAD) tissues and that ZNF692 knockdown inhibited LUAD cell proliferation, migration, and invasion both in vitro and in vivo. However, the role of ZNF692 in colon adenocarcinoma (COAD) remains unclear. The present study revealed that ZNF692 was upregulated in COAD tissues and cells and that high ZNF692 expression was significantly correlated with lymph node metastasis, distant metastasis and tumor stage in COAD patients. Gain­ and loss­of­function experiments were employed to identify the function of ZNF692 in COAD progression. In vitro and in vivo assays revealed that ZNF692 promoted COAD cell proliferation, migration and invasion. Furthermore, western blot analysis demonstrated that the effects of ZNF692 were mediated by upregulating cyclin D1, cyclin­dependent kinase 2 (CDK2) and matrix metalloproteinase­9 (MMP­9) and by downregulating p27Kip1 through the phosphoinositide 3­kinase/AKT signaling pathway. Collectively, these data indicated that ZNF692 may serve as a novel oncogene and a potential treatment target in COAD patients.

Inhalation versus intravenous anesthesia for adults undergoing heart valve surgery: a systematic review and meta-analysis.

INTRODUCTION: Many studies have found that volatile anesthetics are associated with improved clinical outcomes for adults undergoing coronary artery bypass grafting. However, the effect of volatile anesthetics for adults after heart valve surgery has been unclear. So we conducted a meta-analysis of randomized controlled trials (RCTs) to explore whether the choice of an anesthetic regimen might influence patients' outcomes after valve surgery. EVIDENCE ACQUISITION: PubMed, Embase, and Cochrane Library were searched from inception to June 2018. We included eligible research comparing inhalation anesthesia with total intravenous anesthesia (TIVA) in adult patients undergoing valve surgery. The major endpoints involved mortality, postoperative arrhythmia, acute kidney injury, pulmonary complications, neurological events, myocardial infarction, reoperation for bleeding. The postoperative peak troponin release, hospital stay, Intensive Care Unit (ICU) stay and ventilation time were also analyzed. EVIDENCE SYNTHESIS: After screening through 243 potentially relevant articles, we included 13 RCTs with 962 patients. The inhalation anesthesia group revealed comparable mortality (inhalation group 12/249 [4.8%] vs. TIVA group 13/247 [5.3%], RR=0.97; 95% CI: 0.45 to 2.09; P=0.93; P for heterogeneity=0.66, I2=0%) and other postoperative complications with no heterogeneity. The postoperative peak troponin release, hospital/ICU stay and ventilation time were comparable between two groups with considerable heterogeneity. CONCLUSIONS: Among patients undergoing heart valve surgery, the use of inhalation anesthesia compared with TIVA failed to demonstrate superiority for survival and major postoperative complications, and the evidence was insufficient to draw firm conclusions due to the limited sample size. A determination of equivalence or superiority between these two anesthetic regimens requires further researches.

Early constraint-induced movement therapy affects behavior and neuronal plasticity in ischemia-injured rat brains.

Constraint-induced movement therapy is an effective rehabilitative training technique used to improve the restoration of impaired upper extremity movement after stroke. However, whether constraint-induced movement therapy is more effective than conventional rehabilitation in acute or sub-acute stroke remains controversial. The aim of the present study was to identify the optimal time to start constraint-induced movement therapy after ischemic stroke and to explore the mechanisms by which constraint-induced movement therapy leads to post-stroke recovery. Sixty-four adult male Sprague-Dawley rats were randomly divided into four groups: sham-surgery group, cerebral ischemia/reperfusion group, early constraint-induced movement therapy group, and late constraint-induced movement therapy group. Rat models of left middle cerebral artery occlusion were established according to the Zea Longa line embolism method. Constraint-induced movement therapy was conducted starting on day 1 or day 14 in the early constraint-induced movement therapy and late constraint-induced movement therapy groups, respectively. To explore the effect of each intervention time on neuromotor function, behavioral function was assessed using a balance beam walking test before surgery and at 8 and 21 days after surgery. The expression levels of brain-derived neurotrophic factor, nerve growth factor and Nogo receptor were evaluated using real time-polymerase chain reaction and western blot assay to assess the effect of each intervention time. The results showed that the behavioral score was significantly lower in the early constraint-induced movement therapy group than in the cerebral ischemia/reperfusion and late constraint-induced movement therapy groups at 8 days. At 21 days, the scores had significantly decreased in the early constraint-induced movement therapy and late constraint-induced movement therapy groups. At 8 days, only mild pyknosis appeared in neurons of the ischemic penumbra in the early constraint-induced movement therapy group, which was distinctly better than in the cerebral ischemia/reperfusion group. At 21 days, only a few vacuolated cells were observed and no obvious inflammatory cells were visible in late constraint-induced movement therapy group, which was much better than at 8 days. The mRNA and protein expression levels of brain-derived neurotrophic factor and nerve growth factor were significantly higher, but expression levels of Nogo receptor were significantly lower in the early constraint-induced movement therapy group compared with the cerebral ischemia/reperfusion and late constraint-induced movement therapy groups at 8 days. The changes in expression levels at 21 days were larger but similar in both the early constraint-induced movement therapy and late constraint-induced movement therapy groups. Besides, the protein nerve growth factor level was higher in the late constraint-induced movement therapy group than in the early constraint-induced movement therapy group at 21 days. These results suggest that both early (1 day) and late (14 days) constraint-induced movement therapy induces molecular plasticity and facilitates functional recovery after ischemic stroke, as illustrated by the histology. The mechanism may be associated with downregulation of Nogo receptor expression and upregulation of brain-derived neurotrophic factor and nerve growth factor expression.