A whole-slide foundation model for digital pathology from real-world data.

Digital pathology poses unique computational challenges, as a standard gigapixel slide may comprise tens of thousands of image tiles1-3. Prior models have often resorted to subsampling a small portion of tiles for each slide, thus missing the important slide-level context4. Here we present Prov-GigaPath, a whole-slide pathology foundation model pretrained on 1.3 billion 256 × 256 pathology image tiles in 171,189 whole slides from Providence, a large US health network comprising 28 cancer centres. The slides originated from more than 30,000 patients covering 31 major tissue types. To pretrain Prov-GigaPath, we propose GigaPath, a novel vision transformer architecture for pretraining gigapixel pathology slides. To scale GigaPath for slide-level learning with tens of thousands of image tiles, GigaPath adapts the newly developed LongNet5 method to digital pathology. To evaluate Prov-GigaPath, we construct a digital pathology benchmark comprising 9 cancer subtyping tasks and 17 pathomics tasks, using both Providence and TCGA data6. With large-scale pretraining and ultra-large-context modelling, Prov-GigaPath attains state-of-the-art performance on 25 out of 26 tasks, with significant improvement over the second-best method on 18 tasks. We further demonstrate the potential of Prov-GigaPath on vision-language pretraining for pathology7,8 by incorporating the pathology reports. In sum, Prov-GigaPath is an open-weight foundation model that achieves state-of-the-art performance on various digital pathology tasks, demonstrating the importance of real-world data and whole-slide modelling.

STEAP3 promotes colon cancer cell proliferation and migration via regulating histone acetylation.

Colorectal cancer (CRC) is the third most prevalent diagnosed cancer in men and second most prevalent cancer in women. H3K27ac alterations are more commonly than gene mutations in colorectal cancer. Most colorectal cancer genes have significant H3K27ac changes, which leads to an over-expression disorder in gene transcription. Over-expression of STEAP3 is involved in a variety of tumors, participating in the regulation of cancer cell proliferation and migration. The purpose of this work is to investigate the role of STEAP3 in the regulation of histone modification (H3K27ac) expression in colon cancer. Bioinformatic ChIP-seq, ChIP-qPCR and ATAC-seq were used to analyze the histone modification properties and gene accessibility of STEAP3. Western blot and qRT-PCR were used to evaluate relative protein and gene expression, respectively. CRISPR/Cas9 technology was used to knockout STEAP3 on colon cancer cells to analyze the effect of ATF3 on STEAP3. STEAP3 was over-expressed in colon cancer and associated with higher metastases and more invasive and worse stage of colon cancer. ChIP-seq and ChIP-qPCR analyses revealed significant enrichment of H3K27ac in the STEAP3 gene. In addition, knocking down STEAP3 significantly inhibits colon cancer cell proliferation and migration and down-regulates H3K27ac expression. ChIP-seq found that ATF3 is enriched in the STEAP3 gene and CRISPR/Cas9 technology used for the deletion of the ATF3 binding site suppresses the expression of STEAP3. Over-expression of STEAP3 promotes colon cancer cell proliferation and migration. Mechanical studies have indicated that H3K27ac and ATF3 are significantly enriched in the STEAP3 gene and regulate the over-expression of STEAP3.

Versatile Types of Inorganic/Organic NIR-IIa/IIb Fluorophores: From Strategic Design toward Molecular Imaging and Theranostics.

In vivo imaging in the second near-infrared window (NIR-II, 1000-1700 nm), which enables us to look deeply into living subjects, is producing marvelous opportunities for biomedical research and clinical applications. Very recently, there has been an upsurge of interdisciplinary studies focusing on developing versatile types of inorganic/organic fluorophores that can be used for noninvasive NIR-IIa/IIb imaging (NIR-IIa, 1300-1400 nm; NIR-IIb, 1500-1700 nm) with near-zero tissue autofluorescence and deeper tissue penetration. This review provides an overview of the reports published to date on the design, properties, molecular imaging, and theranostics of inorganic/organic NIR-IIa/IIb fluorophores. First, we summarize the design concepts of the up-to-date functional NIR-IIa/IIb biomaterials, in the order of single-walled carbon nanotubes (SWCNTs), quantum dots (QDs), rare-earth-doped nanoparticles (RENPs), and organic fluorophores (OFs). Then, these novel imaging modalities and versatile biomedical applications brought by these superior fluorescent properties are reviewed. Finally, challenges and perspectives for future clinical translation, aiming at boosting the clinical application progress of NIR-IIa and NIR-IIb imaging technology are highlighted.

p53-dependent HIF-1α /autophagy mediated glycolysis to support Cr(VI)-induced cell growth and cell migration.

Cr(VI) is known to be seriously toxic and carcinogenic. Hypoxia-inducible factor-1α (HIF-1α) is a crucial regulator to promote tumor development. In this study, we found that Cr(VI) significantly increased the expression of HIF-1α in A549 cells and in lung of BALB/c mice but not in HELF cells. Treatment with Lificiguat (YC-1), HIF-1α inhibitor, or CoCl2, HIF-1α inducer, could alter Cr(VI)-induced autophagy, glycolysis, and cell growth in A549 cells but not in HELF cells, validating the involvement of HIF-1α in these effects of Cr(VI) in A549 cells. Co-treatments of pcATG4B with YC-1, or siATG4B with CoCl2 demonstrated the role of HIF-1α / autophagy axis in inducing glycolysis and cell growth in A549 cells. In HELF cells, however, only autophagy but not HIF-1α played a role in inducing glycolysis. The protein level of p53 was significantly lower in A549 cells than in HELF cells. RITA, a p53 inducer, attenuated Cr(VI)-induced HIF-1α and LC3-II in A549 cells, suggesting that p53 might be the mechanism underlying the different effects of Cr(VI) on HIF-1α in A549 and HELF cells. Thus, p53-dependent HIF-1α / autophagy-mediated glycolysis plays a role in facilitating Cr(VI)-induced carcinogenesis.

Anthropogenic heat variation during the COVID-19 pandemic control measures in four Chinese megacities.

Anthropogenic heat (AH) is an important input for the urban thermal environment. While reduction in AH during the Coronavirus disease 2019 (COVID-19) pandemic may have weakened urban heat islands (UHI), quantitative assessments on this are lacking. Here, a new AH estimation method based on a remote sensing surface energy balance (RS-SEB) without hysteresis from heat storage was proposed to clarify the effects of COVID-19 control measures on AH. To weaken the impact of shadows, a simple and novel calibration method was developed to estimate the SEB in multiple regions and periods. To overcome the hysteresis of AH caused by heat storage, RS-SEB was combined with an inventory-based model and thermal stability analysis framework. The resulting AH was consistent with the latest global AH dataset and had a much higher spatial resolution, providing objective and refined features of human activities during the pandemic. Our study of four Chinese megacities (Wuhan, Shanghai, Beijing, and Guangzhou) indicated that COVID-19 control measures severely restricted human activities and notably reduced AH. The reduction was up to 50% in Wuhan during the lockdown in February 2020 and gradually decreased after the lockdown was eased in April 2020, similar to that in Shanghai during the Level 1 pandemic response. In contrast, AH was less reduced in Guangzhou during the same period and increased in Beijing owing to extended central heating use in winter. AH decreased more in urban centers and the change in AH varied in terms of urban land use between cities and periods. Although UHI changes during the COVID-19 pandemic cannot be entirely attributed to AH changes, the considerable reduction in AH is an important feature accompanying the weakening of the UHI.

Nomogram for predicting prolonged postoperative ileus after laparoscopic low anterior resection for rectal cancer.

BACKGROUND: Prolonged postoperative ileus (PPOI) is a common complication after colorectal surgery that increases patient discomfort, hospital stay, and financial burden. However, predictive tools to assess the risk of PPOI in patients undergoing laparoscopic low anterior resection have not been developed. Thus, the purpose of this study was to develop a nomogram to predict PPOI after laparoscopic low anterior resection for rectal cancer. METHODS: A total of 548 consecutive patients who underwent laparoscopic low anterior resection for mid-low rectal cancer at a single tertiary medical center were retrospectively enrolled between January 2019 and January 2023. Univariate and multivariate logistic regression analysis was performed to analyze potential predictors of PPOI. The nomogram was constructed using the filtered variables and internally verified by bootstrap resampling. Model performance was evaluated by receiver operating characteristic curve and calibration curve, and the clinical usefulness was evaluated by the decision curve. RESULTS: Among 548 consecutive patients, 72 patients (13.1%) presented with PPOI. Multivariate logistic analysis showed that advantage age, hypoalbuminemia, high surgical difficulty, and postoperative use of opioid analgesic were independent prognostic factors for PPOI. These variables were used to construct the nomogram model to predict PPOI. Internal validation, conducted through bootstrap resampling, confirmed the great discrimination of the nomogram with an area under the curve of 0.738 (95%CI 0.736-0.741). CONCLUSIONS: We created a novel nomogram for predicting PPOI after laparoscopic low anterior resection. This nomogram can assist surgeons in identifying patients at a heightened risk of PPOI.

Transcriptomic analysis revealing the molecular response to arsenic stress in desert Eremostachys moluccelloides Bunge.

The saline, alkaline environment of arid soils is conducive to the diffusion of the metalloid arsenic (As). Desert plants in this area are of great ecological importance and practical value. However, there are few studies on the mechanism of arsenic action in desert plants. Therefore, in this study, Eremostachys moluccelloides Bunge was treated with different concentrations of As2O5 [As(V)] to analyze the physiological, biochemical, and transcriptomic changes of its roots and leaves and to explore the molecular mechanism of its response to As(Ⅴ) stress. The activities of catalase, superoxidase, peroxidase, and the contents of malondialdehyde and proline in roots and leaves first increased and then decreased under the As(Ⅴ) stress of different concentrations. The content of As was higher in roots than in leaves, and the As content was positively correlated with As(Ⅴ) stress concentration. In the differentially expressed gene analysis, the key enzymes of the oxidative stress response in roots and leaves were significantly enriched in the GO classification. In the KEGG pathway, genes related to the abscisic acid signal transduction pathway were co-enriched and up-regulated in roots and leaves. The related genes in the phenylpropanoid biosynthesis pathway were significantly enriched and down-regulated only in roots. In addition, the transcription factors NAC, HB-HD-ZIP, and NF-Y were up-regulated in roots and leaves. These results suggest that the higher the As(V) stress concentration, the more As is taken up by roots and leaves of E. molucelloides Bunge. In addition to causing greater oxidative damage, this may interfere with the production of secondary metabolites. Moreover, it may improve As(V) tolerance by regulating abscisic acid and transcription factors. The results will deepen our understanding of the molecular mechanism of As(Ⅴ) response in E. moluccelloides Bunge, lay the foundation for developing and applying desert plants, and provide new ideas for the phytoremediation of As pollution in arid areas.

[Research progress on the effects and mechanisms of electroacupuncture on radiation-induced brain injury].

Radiation-induced brain injury is a serious complication after cranio-cerebral radiotherapy, which affects the patient's quality of life and survival. A large number of studies have shown that various mechanisms such as neuronal apoptosis, blood-brain barrier damage, and synaptic dysfunction may be related to radiation-induced brain injury. Acupuncture has an important role in clinical rehabilitation of various brain injuries. As a new type of acupuncture, electroacupuncture has the characteristics of strong control ability, uniform and long-lasting stimulation, and is widely used in clinic. This article reviews the effects and mechanisms of electroacupuncture on radiation-induced brain injury, in order to provide a theoretical basis and experimental support for reasonable clinical application.

Wound complications frequency in heart transplant recipients on mammalian target of rapamycin inhibitors: A meta-analysis.

A meta-analysis investigation was executed to measurethe wound complications (WCs) frequency in heart transplant (HT) recipients on mammalian target of rapamycin inhibitors (MTRIs). A comprehensive literature investigation till February 2023 was applied and 978 interrelated investigations were reviewed. The 10 chosen investigations enclosed 2173 individuals with HT were in the chosen investigations' starting point, 1164 of them were utilising MTRIs, and 1009 were utilising control. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were utilised to compute the value of the WCs frequency in HT recipients on MTRIs by the dichotomous approaches and a fixed or random model. MTRIs had significantly higher WCs (OR, 1.53; 95% CI, 1.19-1.98, P = .001) compared with those with control in individuals with HT. MTRIs had significantly higher WCs compared with those with control in individuals with HT. However, care must be exercised when dealing with its values because of the low number of the nominated investigations and the low sample size of some of the nominated investigations for the meta-analysis.

Platelet-rich plasma influence on the sternal wounds healing: A meta-analysis.

A meta-analysis research was executed to appraise the effect of platelet-rich plasma (PRP) on sternal wound healing (SWH). Inclusive literature research till April 2023 was done and 1098 interconnected researches were revised. The 11 picked researches, enclosed 8961 cardiac surgery (CS) persons were in the utilised researchers' starting point, 3663 of them were utilising PRP, and 5298 were control. Odds ratio (OR) and 95% confidence intervals (CIs) were utilised to appraise the effect of PRP on the SWH by the dichotomous approach and a fixed or random model. PRP had significantly lower sternal wound infection (SWI) (OR, 0.11; 95% CI, 0.03-0.34, p < 0.001), deep SWI (OR, 0.29; 95% CI, 0.16-0.51, p < 0.001), and superficial SWI (OR, 0.20; 95% CI, 0.13-0.33, p < 0.001), compared to control in CS persons. PRP had significantly lower SWI, deep SWI, and superficial SWI, compared to control in CS persons. However, caution must be taken when interacting with its values since there was a low sample size of some of the nominated research found for the comparisons in the meta-analysis.

Effect of minimally invasive versus conventional aortic root replacement on transfusion and postoperative wound complications in patients: A meta-analysis.

We examined whether small incision aortic root replacement could reduce the amount of blood transfusion during operation and the risk of postoperative complications. An extensive e-review of the 4 main databases (PubMed, Cochrane, Web of Science and EMBASE) was carried out to determine all the published trials by July 2023. The search terms used were associated with partial versus full sternotomy and aortic root. This analysis only included the study articles that compared partial and full sternotomy. After excluding articles based on titles or abstracts, selected full-text articles had reference lists searched for any potential further articles. We analysed a total of 2167 subjects from 10 comparable trials. The minimally invasive aortic root graft in breastbone decreased the duration of hospitalization (MD, -2.58; 95% CI, -3.15, -2.01, p < 0.0001) and intraoperative red blood cell transfusion (MD, -1.27; 95% CI, -2.34, -0.19, p = 0.02). However, there were no significant differences in wound infection (OR, 0.88; 95% CI, 0.16, 4.93, p = 0.88), re-exploration for bleeding (OR, 0.96; 95% CI, 0.60, 1.53, p = 0.86), intraoperative blood loss (MD, -259.19; 95% CI, -615.11, 96.73, p = 0.15) and operative time (MD, -7.39; 95% CI, -19.10, 4.32, p = 0.22); the results showed that the microsternotomy did not differ significantly from that of the routine approach. Small sternotomy may be an effective and safe substitute for the treatment of the aorta root. Nevertheless, the wide variety of data indicates that larger, well-designed studies are required to back up the current limited literature evidence showing a benefit in terms of complications like postoperative wound infections or the volume of intraoperative red blood cell transfusion.

Φ-OTDR Signal Identification Method Based on Multimodal Fusion.

Distributed fiber optic sensing (DFS) systems are an effective method for long-distance pipeline safety inspections. Highly accurate vibration signal identification is crucial to DFS. In this paper, we propose an end-to-end high-accuracy fiber optic vibration signal detection and identification algorithm by extracting features from the time domain and frequency domain by a one-dimensional convolutional neural network and two-dimensional convolutional neural network, respectively, and introducing a self-attentive mechanism to fuse the features of multiple modes. First, the raw signal is segmented and normalized according to the statistical characteristics of the vibration signal combined with the distribution of noise. Then, the one-dimensional sequence of vibration signal and its two-dimensional image generated by short-time Fourier transform are input to the one-dimensional convolutional neural network and two-dimensional neural network, respectively, for automatic feature extraction, and the features are combined by long and short-time memory. Finally, the multimodal features generated from the time and frequency domains are fused by a multilayer TransformerEncoder structure with a multiheaded self-attentive mechanism and fed into a multilayer perceptron for classification. Experiments were conducted on an urban field database with complex noise and achieved 98.54% accuracy, which demonstrates the effectiveness of the proposed algorithm.

[Effects of electroacupuncture with different courses on the synaptic structure and synaptic function-related proteins in mice with radiation-induced brain injury].

The aim of the present study was to investigate the effects of different courses of electroacupuncture on synaptic structure and synaptic function-related proteins expression in the hippocampal CA1 region of radiation-induced brain injury mice. Sixty C57BL/6J male mice were randomly divided into control group, radiation-induced brain injury model group, 1-week electroacupuncture group (EA1), 2-week electroacupuncture group (EA2), 3-week electroacupuncture group (EA3), and electroacupuncture-control (EA-Ctrl) group. The mice in model group were exposed to X-ray irradiation (8 Gy, 10 min) to establish radiation-induced brain injury model. The mice in EA groups were acupunctured at electroacupuncture points (Baihui, Fengfu and bilateral Shenshu) for 1 week, 2 weeks and 3 weeks respectively after radiation. Immunohistochemistry was used to observe synaptic structure in hippocampal CA1 region. The expressions of brain-derived neurotrophic factor (BDNF), synapsin-1 and postsynaptic density 95 (PSD95) in the hippocampal CA1 region of each group were detected by RT-PCR and Western blotting. The results showed that the nuclear gap in model and EA-Ctrl groups was significantly decreased compared to control group, however nucleus to cytoplasm ratio was significantly increased. The synaptic cleft, postsynaptic density (PSD) thickness, the mitochondrial surface density, volume density and specific surface area were significantly reduced. Compared with model group, the nucleus to cytoplasm ratio of EA2 group was significantly decreased, the PSD thickness and mitochondrial volume density were significantly increased; the nuclear gap of EA3 group was significantly increased, nucleus to cytoplasm ratio was significantly decreased, synaptic cleft and PSD thickness were significantly increased, and the mitochondrial surface density and specific surface area were all increased significantly. In addition, compared with the control group, the gene and protein expressions of BDNF, synapsin-1 and PSD95 in the hippocampal CA1 region of the model group and EA-Ctrl group were significantly decreased. However, compared with the model group, the gene expression of synapsin-1 in EA groups was significantly up-regulated, the gene expression of BDNF in EA1 and EA2 groups was significantly up-regulated, and the gene expression of PSD95 in EA2 group was significantly up-regulated. Moreover, the protein expressions of BDNF, synapsin-1 and PSD95 of EA groups were significantly up-regulated compared with the model group. These results indicate that the synaptic structure and the expression of synaptic function-related proteins in hippocampal CA1 region were injured by radiation exposure, whereas electroacupuncture intervention can significantly improve the synaptic structure and function damage caused by radiation.

[Role of calcitonin gene-related peptide in regulation of synaptic plasticity and process of the emotional memory].

Calcitonin gene-related peptide (CGRP) is a neuropeptide coded by the calcitonin gene and divided into α and ß subtypes. CGRP is widely distributed throughout the human body and highly expressed in the peripheral and central nervous system. Studies have shown that CGRP plays a role in a variety of physiological and pathophysiological activities, such as the formation and transmission of nociceptive signal, as well as the regulation of cardiovascular function. Recently, more and more researches have shown that CGRP is involved in the regulation of synaptic plasticity, cognitive function and learning memory in the central nervous system. This paper reviews the role of CGRP in regulation of synaptic plasticity and process of emotional memory, hoping to provide a new molecular target and theoretical basis for clinical treatment of neurological diseases.

Monochromophore-Based Phosphorescence and Fluorescence from Pure Organic Assemblies for Ratiometric Hypoxia Detection.

Hypoxia is a parameter related to many diseases. Ratiometric hypoxia probes often rely on a combination of an O2 -insensitive fluorophore and an O2 -sensitive phosphor in a polymer matrix, which require high cost and multi-step synthesis of transition metal complexes. The two-chromophore hypoxia probes encounter unfavorable energy transfer processes and different stabilities of the chromophores. Reported herein is a pure organic ratiometric hypoxia nanoprobe, assembled by a monochromophore, naphthalimide ureidopyrimidinone (BrNpA-UPy), bridged by a bis-UPy-functionalized benzyl skeleton. The joint factors of quadruple hydrogen bonding, the rigid backbone of UPy, and bromine substitution of the naphthalimide derivative facilitate bright phosphorescence (ΦP =7.7 %, τP =3.2 ms) and fluorescence of the resultant nanoparticles (SNPs) at room temperature, which enable accurate, ratiometric, sensitive oxygen detection (Ksv =189.6 kPa-1 ) in aqueous solution as well as in living HeLa cells.

miR-545 promoted enterovirus 71 replication via directly targeting phosphatase and tensin homolog and tumor necrosis factor receptor-associated factor 6.

Enterovirus 71 (EV71) is a small, nonenveloped icosahedral RNA virus and is the predominant causative pathogen of hand-foot-and-mouth disease. Recently, microRNAs (miRNAs) are reported to play important roles in the pathogenesis of EV71 replication. This study investigated the role of miR-545 in the EV71 replication and explored the underlying molecular mechanisms. We showed that miR-545 was upregulated in the EV71-infected human embryonic kidney (HEK) 293 cells and rhabdomyosarcoma (RD) cells. Overexpression of miR-545 promoted the viral replication of EV71 and attenuated the inhibitory effects of EV71 on cell viability in HEK293 and RD cells; while knockdown of miR-545 significantly suppressed the EV71 replication in these two cell lines. Bioinformatics analysis and luciferase reporter assay showed that miR-545 directly targeted the 3'untranslated region of phosphatase and tensin homolog (PTEN) and tumor necrosis factor receptor-associated factor 6 (TRAF6) in HEK293 cells. Furthermore, miR-545 negatively regulated the messenger RNA (mRNA) and protein expression of PTEN and TRAF6. The mRNA and protein expression of PTEN and TRAF6 was also suppressed by EV71 infection, which was attenuated by miR-545 knockdown in HEK293 cells. Overexpression of PTEN and TRAF6 both suppressed the EV71 replication in HKE293 cells, and also attenuated the enhanced effects of miR-545 overexpression on the EV71 replication in HEK293 cells. Collectively, our study for the first time showed that miR-545 had an enhanced effect on the EV71 replication in HEK293 and RD cells. Further mechanistic results indicated that miR-545 promoted EV71 replication at least partly via targeting PTEN and TRAF6.

miRNA-206 regulates human pulmonary microvascular endothelial cell apoptosis via targeting in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death due to tis high morbidity and mortality. microRNAs have emerged as new biomarkers for the prognosis and diagnosis of patients with COPD. In this study, we aimed to investigate the expression of microRNA-206 (miR-206) in lung tissues from COPD patients and to explore the regulatory role of miR-206 in the human pulmonary microvascular endothelial cells (HPMECs). Our results showed that cigarette smoke extract (CSE) promoted cell apoptosis, increased caspase-3 activity, and upregulated the expression of miR-206 in HPMECs, which was significantly reversed by the miR-206 knockdown. Transfection with miR-206 mimics led to cell apoptosis and was closely related to changes in the protein expression levels of caspase-3, caspase-9, and Bcl-2 in HPMECs. Further bioinformatics prediction analysis revealed that the 3'-untranslated region (3'UTR) of Notch3 and vascular endothelial growth factor-A (VEGFA) harbored miR-206-binding sites, and overexpression of miR-206 repressed the luciferase activity of the vectors containing Notch3 and VEGFA 3'UTR. Overexpression of either Notch3 or VEGFA attenuated miR-206-induced cell apoptosis in HPMECs. More importantly, miR-206 expression was upregulated in the lung tissues from COPD patients and was positively corrected with forced expiratory volume 1% predicted in COPD patients, while Notch3 and VEGFA mRNA levels were downregulated and were negatively correlated with the expression level of miR-206 in the lung tissues from COPD patients. In conclusion, our results showed that miR-206 was upregulated in COPD patients and CSE-treated HPMECs, promoted cell apoptosis via directly targeting Notch3 and VEGFA in HPMECs.

Using response surface methodology optimize culture conditions for human lactoferrin production in desert Chlorella.

To optimize the expression conditions for human lactoferrin production, we have constructed the transgenic chlorella with human lactoferrin named as GTD8A1-HLF, the original chlorella was separated from Gurbantunggut Desert in Xinjiang China. To further improve the production of human lactoferrin, a sequential methodology was used to optimize human lactoferrin production by GTD8A1-HLF. First, a screening trial using a Plackett-Burman design was done, and variables with statistically significant effects on human lactoferrin bio-production were identified. These were further optimized by central composite design experiments and response surface methodology. Finally, we found that the maximum human lactoferrin production (52.70 mg/L) was achieved under the following optimized conditions: Initial pH 5.0, NaNO3 concentration of 0.600 mol/L, FeSO4 concentration of 0.006 mol/L, and a CuSO4 concentration of 0.002 mol/L, with the other medium components constituting the basal culture medium BBM. The yield of HLF protein under optimized culture conditions was approximately 4-fold higher than that obtained by using the basal culture medium BBM. The findings are significant for the potential industrial use of GTD8A1-HLF.

[Effects of different concentrations of calcitonin gene-related peptide on long-term depression of hippocampus in mice].

The purpose of this study was to explore the effects of calcitonin gene-related peptide (CGRP) on the long-term depression (LTD) of hippocampus in mice. Sixty C57BL/6J mice (30 days old) were randomly divided into control group, three CGRP (50, 100, and 200 nmol/L) groups, CGRP + CGRP8-37 group and CGRP + APV group (10 mice for each group). The effects of exogenous application of different concentrations of CGRP on synaptic plasticity and LTD in hippocampus of mice were detected by in vitro recording of local field potential. The results showed that higher doses (100 and 200 nmol/L) of CGRP significantly enhanced the induction of LTD in the hippocampus. Moreover, CGRP increased the magnitude of N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic currents. The above-mentioned effects of CGRP were blocked by either CGRP selective antagonist CGRP8-37 or NMDA receptor antagonist APV. These results suggest that CGRP can dose-dependently enhance the induction of LTD in hippocampus of mice, and the underlying mechanism involves the mediation of NMDA receptor function.

[Effects and mechanisms of electro-acupuncture on proliferation and differentiation of neural stem cells in C57 mice exposed to different doses of X-ray radiation].

The present study was aimed to investigate the effects and mechanisms of electro-acupuncture (EA) on proliferation and differentiation of neural stem cells in the hippocampus of C57 mice exposed to different doses of X-ray radiation. Thirty-day-old C57BL/6J mice were randomly divided into control, irradiation, and EA groups. The control group was not treated with irradiation. The irradiation groups were exposed to different doses of X-ray (4, 8 or 16 Gy) for 10 min. The EA groups were electro-acupunctured at Baihui, Fengfu and bilateral Shenyu for 3 courses of treatment after X-ray radiation. Immunohistochemistry was used to evaluate proliferation and differentiation of the hippocampal neural stem cell. RT-PCR and Western blot were used to detect mRNA and protein expressions of Notch1 and Mash1 in the hippocampus, respectively. The results showed that, compared with the control group, the numbers of BrdU positive cells (4, 8 Gy subgroup) and BrdU/NeuN double-labeling positive cells (3 dose subgroups) were decreased significantly in the irradiation group, but the above changes could be reversed by EA. Compared with the control group, the number of BrdU/GFAP double-labeling positive cells in each dose subgroup of irradiation group was decreased significantly, while EA could reverse the change of 4 and 8 Gy dose subgroups. In addition, compared with the control group, the expression levels of Notch1 mRNA and protein in hippocampus were up-regulated, and the expression levels of Mash1 mRNA and protein were significantly decreased in each dose subgroup of irradiation group. Compared with irradiation group, the expression levels of Notch1 mRNA and protein in hippocampus of EA group were decreased significantly in each dose subgroup, and the expression levels of Mash1 mRNA and protein were increased significantly in 4 and 8 Gy subgroups. These results suggest that irradiation affects the proliferation and differentiation of neural stem cells in hippocampus of mice, whereas EA may significantly increase the proliferation and differentiation of hippocampal neural stem cells via the regulation of Notch signaling pathway.