Application of problem-based self-designed experiments in physiology laboratory teaching.

A physiology laboratory course plays an important role in improving the scientific abilities of medical students. This study involved a teaching reform based on problem-based self-designed experiments in a physiology laboratory course. The study subjects were divided into two groups, i.e., students enrolled in 2019 were assigned to the traditional course control group (n = 146) and students enrolled in 2021 were assigned to the improved course test group (n = 128). Students in the test group were required to conduct self-designed experiments based on the questions for each experimental theme, in addition to completing the specified experimental items. At the end of the course, the differences in academic achievements between the two groups were compared. The results showed that compared to the control group, the students in the test group spent less time finishing the specified experimental items (P < 0.05). More students in the test group obtained good results in the operation assessment for the specified experiments (P < 0.05), and a significant increase in the number of winners in discipline-wise competitions, participants in scientific research projects, and academic publications was observed in the test group. Most of the students in the test group agreed that the self-designed experiment promoted their scientific thinking, helped them better understand theoretical knowledge, and improved their hands-on operation and team cooperation abilities. Our research showed that our teaching reform promoted students' self-directed learning and problem-solving abilities, stimulated their enthusiasm for scientific research, and was conducive to the cultivation of innovative medical talents.NEW & NOTEWORTHY This study involved a teaching reform based on problem-based self-designed experiments in a physiology laboratory course. Students in the test group were required to conduct self-designed experiments based on questions for each experimental theme, in addition to completing the specified experimental items. The results showed that the teaching reform promoted the students' self-directed learning and problem-solving ability, stimulated their enthusiasm for scientific research, and was conducive to cultivating innovative medical talents.

Prenatal exposure to di (2-ethylhexyl) phthalate causes autism-like behavior through inducing Nischarin expression in the mouse offspring.

Epidemiologic evidence has suggested a relationship between di (2-ethylhexyl) phthalate (DEHP) prenatal exposure and autism spectrum disorders (ASD), but the underlying mechanisms are still at large unknown. In this study, pregnant mice were intragastrically administered with DEHP once a day from GD 3 to GD 17 and the neurobehavioral changes of offspring were evaluated. In addition to the repetitive stereotyped behaviors, DEHP at the concentration of 50 mg/kg/day and above significantly impaired the sociability of the offspring (P < 0.05) and decreased the density of dendritic spines of pyramidal neurons in the prefrontal cortex (P < 0.05). At the same time, the expression of Nischarin protein in prefrontal lobe increased (P < 0.05). Similarly, after 12-h incubation of DEHP at the concentration of 100 nM, the total spine density, especially the mushroom and stubby spine populations, significantly decreased in the primary cultured prefrontal cortical neurons (P < 0.05). However, the inhibitory effect of DEHP were reversed by knockdown of Nischarin expression. Collectively, these results suggest that prenatal DEHP exposure induces Nischarin expression, causes dendritic spine loss, and finally leads to autism-like behavior in mouse offspring.

Effects of stem cells on non-ischemic cardiomyopathy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AIMS: To assess the impacts of stem cell therapy on clinical outcomes in patients with non-ischemic cardiomyopathy (NICM). The effect of stem cell therapy on prognosis is unclear and controversial. METHODS: The authors performed a systematic review and meta-analysis of the effects of autologous stem cell transplantation in patients with NICM on a composite outcome of all-cause mortality and heart transplantation, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), New York Heart Association (NYHA) classification, 6-minute walk test (6-MWT) distance and serum brain natriuretic peptide (BNP) level, considering studies published before March 19, 2020. RESULTS: Twelve trials with 623 subjects met inclusion criteria. Compared with the control group, stem cell therapy improved LVEF (weighted mean difference [WMD], 4.08%, 95% confidence interval [CI], 1.93-6.23, P = 0.0002) and 6-MWT distance (WMD, 101.49 m, 95% CI, 45.62-157.35, P = 0.0004) and reduced BNP level (-294.94 pg/mL, 95% CI, -383.97 to -205.90, P < 0.00001) and NYHA classification (-0.70, 95% CI, -0.98 to -0.43, P < 0.00001). However, LVEDD showed no significant difference between the two groups (WMD, -0.09 cm, 95% CI, -0.23 to 0.06, P = 0.25). In 10 studies (535 subjects) employing the intracoronary route for cell delivery, mortality and heart transplantation were decreased (risk ratio [RR], 0.73, 95% CI, 0.52-1.00, P = 0.05). Furthermore, in four studies (248 subjects) with peripheral CD34+ cells, either all-cause mortality (RR, 0.44, 95% CI, 0.23-0.86, P = 0.02) or mortality and heart transplantation (RR, 0.45, 95% CI, 0.27-0.77, P = 0.003) improved in the treatment group compared with the control. The trial sequential analysis suggested the information size of LVEF, 6-WMT and BNP has been adequate for evidencing the benefits of stem cells on NICM. However, to determine the potential survival benefit, more clinical data are required to make the statistical significance in meta-analysis more conclusive. CONCLUSIONS: This meta-analysis demonstrates that stem cell therapy may improve survival, exercise capacity and cardiac ejection fraction in NICM, which suggests that stem cells are a promising option for NICM treatment.

The neuroprotective effect of apigenin against OGD/R injury in rat hippocampal neurons.

To investigate the effects of apigenin on the injury caused by oxygen and glucose deprivation in neurons and the underlying mechanisms, primary cultured rat hippocampal neurons were incubated with apigenin for 90 min before a 2-h oxygen and glucose deprivation followed by a 24-h reperfusion (OGD/R). Subsequently, cell viability, lactate dehydrogenase (LDH) leakage rate, apoptotic rate of neurons and activity of the sodium pump were assessed. In addition, activity of the sodium pump was also examined in the hippocampus of SD rats injected intraperitoneally with apigenin 90 min before a 10-min global cerebral ischemia/24-h reperfusion. The results showed that cell viability and activity of the sodium pump markedly decreased but LDH leakage rate and apoptotic rate significantly increased in OGD/R-treated neurons. However, pretreatment with apigenin (20-50µmol/L) reversed the changes dose-dependently. Compared to sham controls, activity of the sodium pump was significantly suppressed in global ischemia/reperfusion rats; application of apigenin (200mg/kg) restored the activity of the sodium pump. Furthermore, the neuroprotective effect of apigenin was blocked partly by the sodium pump inhibitor ouabain. Our findings provide the evidence that apigenin has a neuroprotective effect against OGD/R injury and the protective effect may be associated with its ability to improve sodium pump activity.

Local Delivery of ß-Elemene Improves Locomotor Functional Recovery by Alleviating Endoplasmic Reticulum Stress and Reducing Neuronal Apoptosis in Rats with Spinal Cord Injury.

BACKGROUND/AIMS: Spinal cord injury (SCI) is a serious global problem that leads to permanent motor and sensory deficits. This study explores the anti-apoptotic and neuroprotective effects of the natural extract ß-elemene in vitro and in a rat model of SCI. METHODS: CCK-8 assay was used to evaluate cell viability and lactate dehydrogenase assay was used to evaluate cytotoxicity. A model of cell injury was established using cobalt chloride. Apoptosis was evaluated using a fluorescence-activated cell sorting assay of annexin V-FITC and propidium iodide staining. A rat SCI model was created via the modified Allen's method and Basso, Beattie, and Bresnahan (BBB) scores were used to assess locomotor function. Inflammatory responses were assessed via enzyme-linked immunosorbent assay (ELISA). Apoptotic and surviving neurons in the ventral horn were respectively observed via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Nissl staining. Western blotting was used to measure protein expression. RESULTS: ß-elemene (20 µg/ml) promoted cell viability by activating phosphorylation of the PI3K-AKT-mTOR pathway. ß-elemene reduced CoCl2-induced cellular death and apoptosis by suppressing the expression levels of CHOP, cleaved-caspase 12, 78-kilodalton glucose-regulated protein, cleaved-caspase 3, and the Bax/Bcl-2 ratio. In the rat model of SCI, Nissl and TUNEL staining showed that ß-elemene promoted motor neuron survival and reduced neuronal apoptosis in the spinal cord ventral horn. BBB scores showed that ß-elemene significantly promoted locomotor behavioral recovery after SCI. In addition, ß-elemene reduced the ELISA-detected secretion of interleukin (IL)-6 and IL-1ß. CONCLUSION: ß-elemene reduces neuronal apoptosis by alleviating endoplasmic reticulum stress in vitro and in vivo. In addition, ß-elemene promotes locomotor function recovery and tissue repair in SCI rats. Thus, our study provides a novel encouraging strategy for the potential treatment of ß-elemene in SCI patients.

Improved Multitarget Tracking in Clutter Using Bearings-Only Measurements.

Multitarget tracking in clutter using bearings-only measurements is a challenging problem. In this paper, a performance improved nonlinear filter is proposed on the basis of the Random Finite Set (RFS) theory and is named as Gaussian mixture measurements-based cardinality probability hypothesis density (GMMbCPHD) filter. The GMMbCPHD filter enables to address two main issues: measurement-origin-uncertainty and measurement nonlinearity, which constitutes the key problems in bearings-only multitarget tracking in clutter. For the measurement-origin-uncertainty issue, the proposed filter estimates the intensity of RFS of multiple targets as well as propagates the posterior cardinality distribution. For the measurement-origin-nonlinearity issue, the GMMbCPHD approximates the measurement likelihood function using a Gaussian mixture rather than a single Gaussian distribution as used in extended Kalman filter (EKF). The superiority of the proposed GMMbCPHD are validated by comparing with several state-of-the-art algorithms via intensive simulation studies.

Identification of COL1A1 and COL1A2 as candidate prognostic factors in gastric cancer.

BACKGROUND: The role of type I collagen, composed of collagen type I alpha 1 (COL1A1) and collagen type I alpha 2 (COL1A2), has been studied in several cancers. However, the expression of COL1A1 and COL1A2 in malignant, premalignant, and normal gastric tissues and their clinical significances in gastric cancer have not been elucidated. METHODS: Real-time quantitative PCR was performed in 55 malignant, 27 premalignant, and 19 normal tissues to measure COL1A1 and COL1A2 messenger RNA (mRNA) expression, and the correlations between COL1A1 and COL1A2 expression and clinicopathological parameters and patients' survival rate were analyzed. RESULTS: We found that COL1A1 mRNA expression was significantly upregulated in premalignant and malignant tissues than in normal tissues, whereas COL1A2 mRNA expression was significantly higher in malignant tissues than in premalignant and normal tissues. Moreover, COL1A1 expression was unrelated to clinicopathological parameters, while COL1A2 expression was positively related to tumor size and depth of invasion. Besides, higher COL1A1 and COL1A2 expression levels were related to lower overall survival. CONCLUSIONS: We find that COL1A1 might have its potential as a monitoring factor to screen early gastric cancer, and COL1A1 and COL1A2 might predict poor clinical outcomes in gastric cancer patients.

[Progress on matrix metalloproteinase in axonal regeneration].

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases. MMPs can degrade and remodel extracellular matrix, also active or inactive many molecules attaching to matrix including receptors, growth factors and cytokines, so that injury-induced MMPs can change the extracellular environment to affect the axonal regeneration in central nervous system. In this review, with spinal cord injury (SCI) as an example we discuss the effects of MMPs on inflammation, neuronal viability, extracellular molecules, glial scar and axonal remyelination, which are all important to axonal regeneration.

[LIM kinases and their roles in the nervous system].

LIM kinase-1 (LIMK1) and LIM kinase-2 (LIMK2) are kinases that have serine/threonine and tyrosine dual specificity. Although they show significant structural similarity, LIMK1 and LIMK2 have different expression patterns, subcellular localization, and functions. Activation of LIM kinases regulates the downstream of Rho GTPases, and influences the architecture of the actin cytoskeleton by regulating the activity of cofilin. Recent studies have shown that LIM kinases play important roles in the nervous system. For example, development of the central nervous system is reliant upon the presence of LIMK1, and deletion of Limk1 gene is involved in the development of the human genetic disorder Williams syndrome. Therefore, it is of vital physiological significance to investigate the neuronal function of LIM kinases. In this review, we outline the structure, phosphorylation regulation and neuronal function of LIM kinases, so as to provide new ideas for the treatment of these neurological diseases.

A Novel Sequence-to-Sequence-Based Deep Learning Model for Multistep Load Forecasting.

Load forecasting is critical to the task of energy management in power systems, for example, balancing supply and demand and minimizing energy transaction costs. There are many approaches used for load forecasting such as the support vector regression (SVR), the autoregressive integrated moving average (ARIMA), and neural networks, but most of these methods focus on single-step load forecasting, whereas multistep load forecasting can provide better insights for optimizing the energy resource allocation and assisting the decision-making process. In this work, a novel sequence-to-sequence (Seq2Seq)-based deep learning model based on a time series decomposition strategy for multistep load forecasting is proposed. The model consists of a series of basic blocks, each of which includes one encoder and two decoders; and all basic blocks are connected by residuals. In the inner of each basic block, the encoder is realized by temporal convolution network (TCN) for its benefit of parallel computing, and the decoder is implemented by long short-term memory (LSTM) neural network to predict and estimate time series. During the forecasting process, each basic block is forecasted individually. The final forecasted result is the aggregation of the predicted results in all basic blocks. Several cases within multiple real-world datasets are conducted to evaluate the performance of the proposed model. The results demonstrate that the proposed model achieves the best accuracy compared with several benchmark models.

Association between COVID-19 vaccination and hair cortisol concentrations.

BACKGROUND: Cortisol is a steroid hormone secreted mainly by the adrenal cortex and is associated with chronic stress levels in the body. Hair cortisol concentration (HCC) is a reliable index to assess human stress levels. So far, no study has reported whether COVID-19 vaccination is associated with the changes of HCC. METHODS: Hair samples were collected from 114 college students at Hangzhou City University and Zhejiang University. Among them, 57 cases completed COVID-19 vaccination and others did not. HCCs were measured by the chemiluminescence immunoassay (CLIA). The psychological stress levels were evaluated using the Chinese College Student Psychological Stress Scale (CCSPSS). General information and adverse reactions of the subjects were collected by questionnaire. RESULTS: Compared with the vaccinated college students, the unvaccinated students had higher HCC levels in both A and B hair segments respectively corresponding older or six weeks before and newer or six weeks after vaccination (p < 0.05), reflecting higher stress levels. Besides, the vaccinated group had significantly higher HCCs in segment B compared with segment A (p < 0.05). Further analysis showed that the value of ΔHCC (HCCseg.B - HCCseg.A) of the vaccinated group was strongly associated with COVID-19 vaccination (p < 0.05), but was not associated with age, gender, BMI, CCSPSS score, hormone use, exercise frequency, hair washing frequency, or hair treatment. Finally, the number of self-reported systemic adverse reactions in the vaccinated group was associated with ΔHCC (p < 0.01). CONCLUSION: The COVID-19 vaccination had an impact on the value of HCC, which might be linked to the occurrence of systemic adverse effects following vaccinations.

Targeting the dynamics of cancer metabolism in the era of precision oncology.

Cancer metabolic reprogramming is a promising target for cancer therapy. The progression of tumors, including their growth, development, metastasis, and spread, is a dynamic process that varies over time and location. This means that the metabolic state of tumors also fluctuates. A recent study found that energy production efficiency is lower in solid tumors but increases significantly in tumor metastasis. Despite its importance for targeted tumor metabolism therapy, few studies have described the dynamic metabolic changes of tumors. In this commentary, we discuss the limitations of past targeted tumor metabolism therapy and the key findings of this study. We also summarize its immediate clinical implications for dietary intervention and explore future research directions for understanding the dynamic changes in tumor metabolic reprogramming.

Disulfidptosis: a new target for metabolic cancer therapy.

Altered metabolism is a hallmark of cancer and presents a vulnerability that can be exploited in cancer treatment. Regulated cell death (RCD) plays a crucial role in cancer metabolic therapy. A recent study has identified a new metabolic-related RCD known as disulfidptosis. Preclinical findings suggest that metabolic therapy using glucose transporter (GLUT) inhibitors can trigger disulfidptosis and inhibit cancer growth. In this review, we summarize the specific mechanisms underlying disulfidptosis and outline potential future research directions. We also discuss the challenges that may arise in the clinical translation of disulfidptosis research.

Contribution of Nischarin/IRAS in CNS development, injury and diseases.

BACKGROUND: Murine Nischarin and its human homolog IRAS are scaffold proteins highly expressed in the central nervous system (CNS). Nischarin was initially discovered as a tumor suppressor protein, and recent studies have also explored its potential value in the CNS. Research on IRAS has largely focused on its effect on opioid dependence. Although the role of Nischarin/IRAS in the physiological function and pathological process of the CNS has gradually attracted attention and the related research results are expected to be applied in clinical practice, there is no systematic review of the role and mechanisms of Nischarin/IRAS in the CNS so far. AIM OF REVIEW: This review will systematically analyze the role and mechanism of Nischarin/IRAS in the CNS, and provide necessary references and possible targets for the treatment of neurological diseases, thereby broadening the direction of Nischarin/IRAS research and facilitating clinical translation. KEY SCIENTIFIC CONCEPTS OF REVIEW: The pathophysiological processes affected by dysregulation of Nischarin/IRAS expression in the CNS are mainly introduced, including spinal cord injury (SCI), opioid dependence, anxiety, depression, and autism. The molecular mechanisms such as factors regulating Nischarin/IRAS expression and signal transduction pathways regulated by Nischarin/IRAS are systematically summarized. Finally, the clinical application of Nischarin/IRAS has been prospected.

New insights into the biological roles of immune cells in neural stem cells in post-traumatic injury of the central nervous system.

Traumatic injuries in the central nervous system, such as traumatic brain injury and spinal cord injury, are associated with tissue inflammation and the infiltration of immune cells, which simultaneously affect the self-renewal and differentiation of neural stem cells. However, the tissue repair process instigated by endogenous neural stem cells is incapable of restoring central nervous system injuries without external intervention. Recently, resident/peripheral immune cells have been demonstrated to exert significant effects on neural stem cells. Thus, the restoration of traumatic injuries in the central nervous system by the immune intervention in neural stem cells represents a potential therapeutic method. In this review, we discuss the roles and possible mechanisms of immune cells on the self-renewal and differentiation of neural stem cells along with the prognosis of central nervous system injuries based on immune intervention. Finally, we discuss remaining research challenges that need to be considered in the future. Further elucidation of these challenges will facilitate the successful application of neural stem cells in central nervous system injuries.

Nanopore sequencing technology and its applications.

Since the development of Sanger sequencing in 1977, sequencing technology has played a pivotal role in molecular biology research by enabling the interpretation of biological genetic codes. Today, nanopore sequencing is one of the leading third-generation sequencing technologies. With its long reads, portability, and low cost, nanopore sequencing is widely used in various scientific fields including epidemic prevention and control, disease diagnosis, and animal and plant breeding. Despite initial concerns about high error rates, continuous innovation in sequencing platforms and algorithm analysis technology has effectively addressed its accuracy. During the coronavirus disease (COVID-19) pandemic, nanopore sequencing played a critical role in detecting the severe acute respiratory syndrome coronavirus-2 virus genome and containing the pandemic. However, a lack of understanding of this technology may limit its popularization and application. Nanopore sequencing is poised to become the mainstream choice for preventing and controlling COVID-19 and future epidemics while creating value in other fields such as oncology and botany. This work introduces the contributions of nanopore sequencing during the COVID-19 pandemic to promote public understanding and its use in emerging outbreaks worldwide. We discuss its application in microbial detection, cancer genomes, and plant genomes and summarize strategies to improve its accuracy.

[P21-activated kinases and their role in the nervous system].

P21-activated kinases (PAK) participate in a variety of important cellular activities, such as cytoskeleton remodeling, cell migration, cell cycle regulation, and apoptosis or survival. PAK also has an important impact on brain development, neuronal differentiation, and regulation of synaptic plasticity in the nervous system. PAK abnormalities result in diseases including cancer, Parkinson's disease (PD), Alzheimer's disease (AD) and neural retardation. Therefore, it is of vital physiological significance to investigate the neuronal function of PAK. In this paper we review the advancement of research on the neuronal biological function and the underlying mechanisms of PAK.

[Comparison of mannitol and hypertonic saline in treatment of intracranial hypertension of rabbits].

OBJECTIVE: To compare the effects of mannitol and hypertonic saline (HS) in treatment of intracranial hypertension (ICH) of rabbits. METHODS: The animal mode of ICH was established by perfusing artificial cerebrospinal fluids (aCSF) with controlled pressure into the cerebral ventricles of rabbits. The mean arterial pressure, respiratory rate, tidal volume, perfusion rate of aCSF and water content of cerebrum were investigated in rabbits with ICH after a single bolus of 20% mannitol (5 ml/kg), 7.5% HS (2.2 ml/kg) or 23.4% HS (2.2 ml/kg). RESULTS: After the intracranial pressure was elevated from 15 cmH2O to 75 cmH2O, the mean arterial pressure was increased and the tidal volume was decreased. After treatment by 20% mannitol, 7.5% HS or 23.4% HS, the increased percentage of mean arterial pressure and the decreased percentage of tidal volume were similar to the changes in control group. However, the perfusion rate of CSF was increased and water content of cerebrum was decreased after treatment by either 20% mannitol or 23.4% HS, but not by 7.5% HS. No different effects were found between 20% mannitol and 23.4% HS. CONCLUSION: With the similar osmotic burden, 20% mannitol is more effective in treating ICH than 7.5% HS. With higher osmotic load, the efficacy of HS is enhanced, and 23.4% HS may be used as an alternative to mannitol in treatment of ICH.

Elesclomol: a copper ionophore targeting mitochondrial metabolism for cancer therapy.

Elesclomol is an anticancer drug that targets mitochondrial metabolism. In the past, elesclomol was recognized as an inducer of oxidative stress, but now it has also been found to suppress cancer by inducing cuproptosis. Elesclomol's anticancer activity is determined by the dependence of cancer on mitochondrial metabolism. The mitochondrial metabolism of cancer stem cells, cancer cells resistant to platinum drugs, proteasome inhibitors, molecularly targeted drugs, and cancer cells with inhibited glycolysis was significantly enhanced. Elesclomol exhibited tremendous toxicity to all three kinds of cells. Elesclomol's toxicity to cells is highly dependent on its transport of extracellular copper ions, a process involved in cuproptosis. The discovery of cuproptosis has perfected the specific cancer suppressor mechanism of elesclomol. For some time, elesclomol failed to yield favorable results in oncology clinical trials, but its safety in clinical application was confirmed. Research progress on the relationship between elesclomol, mitochondrial metabolism and cuproptosis provides a possibility to explore the reapplication of elesclomol in the clinic. New clinical trials should selectively target cancer types with high mitochondrial metabolism and attempt to combine elesclomol with platinum, proteasome inhibitors, molecularly targeted drugs, or glycolysis inhibitors. Herein, the particular anticancer mechanism of elesclomol and its relationship with mitochondrial metabolism and cuproptosis will be presented, which may shed light on the better application of elesclomol in clinical tumor treatment.

Single-cell transcriptome analysis reveals the immune heterogeneity and the repopulation of microglia by Hif1α in mice after spinal cord injury.

Neuroinflammation is regarded as a vital pathological process in spinal cord injury (SCI), which removes damaged tissue, secretes cytokines, and facilitates regeneration. Repopulation of microglia has been shown to favor recovery from SCI. However, the origin and regulatory factors of microglia repopulation after SCI remain unknown. Here, we used single-cell RNA sequencing to portray the dynamic transcriptional landscape of immune cells during the early and late phases of SCI in mice. B cells and migDCs, located in the meninges under physiological conditions, are involved in immune surveillance. Microglia quickly reduced, and peripheral myeloid cells infiltrated three days-post-injury (dpi). At 14 dpi, microglia repopulated, myeloid cells were reduced, and lymphocytes infiltrated. Importantly, genetic lineage tracing of nestin+ and Cx3cr1+ cells in vivo showed that the repopulation of microglia was derived from residual microglia after SCI. We found that residual microglia regress to a developmental growth state in the early stages after SCI. Hif1α promotes microglial proliferation. Conditional ablation of Hif1α in microglia causes larger lesion sizes, fewer axon fibers, and impaired functional recovery in the late stages after SCI. Our results mapped the immune heterogeneity in SCI and raised the possibility that targeting Hif1α may help in axon regeneration and functional recovery after SCI.