Hot Deformation Behavior and Processing Map Considering Strengthening Effect for Al-10.0Zn-3.0Mg-2.8Cu Alloy.

In this paper, a hot processing map that takes into the strengthening effect into account is optimized for the Al-10.0Zn-3.0Mg-2.8Cu alloy, mainly considering the crushing and dissolving behavior of the insoluble phase. The hot deformation experiments were performed by compression testing with strain rates ranging from 0.001 to 1 s-1 and the temperature ranging from 380 to 460 °C. The hot processing map was established at the strain of 0.9. It exhibits that the appropriate hot processing region is located at the temperature from 431 to 456 °C and its strain rate is within 0.004-0.108 s-1. The recrystallization mechanisms and insoluble phase evolution were demonstrated using the real-time EBSD-EDS detection technology for this alloy. It is verified that the work hardening can also be consumed by the coarse insoluble phase refinement with the strain rate increasing from 0.001 to 0.1 s-1, besides the traditional recovery and recrystallization, but the effect of the insoluble phase crushing was weakened when strain rate increased over 0.1 s-1. Better refinement of the insoluble phase was around strain rate in 0.1 s-1, which exhibits adequate dissolving during the solid solution treatment, leading to excellent aging strengthen effects. Finally, the hot processing region was further optimized, so that the strain rate approaches 0.1 s-1 instead of 0.004-0.108 s-1. This will provide a theoretical support for the subsequent deformation of the Al-10.0Zn-3.0Mg-2.8Cu alloy and its' engineering application in aerospace, defense and military fields.

Size-resolved gas-particle partitioning characteristics of typical semi-volatile organic compounds in urban atmosphere.

Understanding particle size distribution and size-resolved gas-particle partitioning of semi-volatile organic compounds (SVOCs) is important for characterizing their fate in atmosphere. However, the size-resolved gas-particle partitioning characteristics of SVOCs has not been adequately considered. To address this issue, the present study collected gaseous and size-fractioned particulate samples both in and outside of schools, offices, and residences in three districts of different urbanization levels in a megacity, Guangzhou, South China during two seasons. Typical SVOCs, including 15 polycyclic aromatic hydrocarbons (PAHs), six organophosphate esters and seven phthalic acid esters were measured. Emission sources, physicochemical properties, and environmental conditions at the sampling sites considerably impacted the spatiotemporal distribution patterns and particle size distribution of target SVOCs. Not all observed gas-particle partition coefficients (Kp) of target SVOCs were negatively correlated with subcooled liquid-vapor pressures (PL0), probably because certain factors, such as the non-exchangeable part of the particle-bound SVOCs, were not considered in traditional gas-particle partition theories. Particle size was an important factor affecting gas-particle partitioning. Adsorption was the dominant mechanism for PAHs with high molecular weight in different particle modes. A new model was established to predict size-resolved Kp of PAHs with high molecular weight based on PL0 and particle size.

Targeting GSTP1 as Therapeutic Strategy against Lung Adenocarcinoma Stemness and Resistance to Tyrosine Kinase Inhibitors.

Glutathione S-transferase pi (GSTP1), a phase II detoxification enzyme, is known to be overexpressed and mediates chemotherapeutic resistance in lung cancer. However, whether GSTP1 supports cancer stem cells (CSCs) and the underlying mechanisms in lung adenocarcinoma (LUAD) remain largely unknown. This study unveiled that GSTP1 is upregulated in lung CSCs and supports tumor self-renewal, metastasis, and resistance to targeted tyrosine kinase inhibitors of LUAD both in vitro and in vivo. Mechanistically, CaMK2A (calcium/calmodulin-dependent protein kinase 2 isoform A)/NRF2 (nuclear factor erythroid 2-related factor 2)/GSTP1 is uncovered as a regulatory axis under hypoxia. CaMK2A increased GSTP1 expression through phosphorylating the Sersine558 residue of NRF2 and promoting its nuclear translocation, a novel mechanism for NRF2 activation apart from conventional oxidization-dependent activation. Upregulation of GSTP1 in turn suppressed reactive oxygen species levels and supported CSC phenotypes. Clinically, GSTP1 analyzed by immunohistochemistry is upregulated in a proportion of LUAD and serves as a prognostic marker for survival. Using patient-derived organoids from an ALK-translocated LUAD, the therapeutic potential of a specific GSTP1 inhibitor ezatiostat in combination treatment with the ALK inhibitor crizotinib is demonstrated. This study demonstrates GSTP1 to be a promising therapeutic target for long-term control of LUAD through targeting CSCs.

[Effect of Danzhi Xiaoyao Powder on behavior and mitochondrial morphology and function of anxiety model rats].

Danzhi Xiaoyao Powder is a classical prescription for anxiety. This study aims to analyze the effect of this medicine on mitochondrial morphology and function of anxiety rats and explore the mechanism of it against anxiety. Specifically, uncertain empty bottle drinking water stimulation(21 days) was employed to induce anxiety in rats. The elevated plus-maze test and open field test were respectively performed on the 7 th, the 14 th, and the 21 st days of the stimulation, so as to detect the anxiety-related protein index brain-derived neurotrophic factor(BDNF) and evaluate the anxiety level of animals. On this basis, the effect of this prescription on anxiety rats was preliminarily evaluated. After the behavioral test on the 21 st day, rats were killed and the brain tissues were separated for the observation of the mitochondrial morphology and the determination of mitochondrial function-related indicators and the adenosine 5'-monophosphate-activated protein kinase(AMPK) level. The results showed that Danzhi Xiaoxiao Powder could alleviate the anxiety-like behavior of rats, significantly increase the percentage of time in open arm in elevated plus-maze test and the ration of activity time in the central area of the field, dose-dependently raise the activity levels of respiratory chain complex Ⅰ,Ⅱ,Ⅲ and Ⅳ and the adenosine triphosphate(ATP) content, and elevate the levels of BDNF and phosphorylated AMPK(p-AMPK). Clear structure and intact morphology of mitochondrial cristae in medial prefrontal cortex cells and amygdala were observed in the Danzhi Xiaoyao Powder group. In summary, Danzhi Xiaoyao Powder exerts therapeutic effect on anxiety, and the mechanism is the likelihood that p-AMPK protects the structure and maintains the function of mitochondria.

Identification of cystic fibrosis transmembrane conductance regulator as a prognostic marker for juvenile myelomonocytic leukemia via the whole-genome bisulfite sequencing of monozygotic twins and data mining.

Background: Linked deoxyribonucleic acid (DNA) hypermethylation investigations of promoter methylation levels of candidate genes may help to increase the progressiveness and mortality rates of juvenile myelomonocytic leukemia (JMML), which is a unique myelodysplastic/myeloproliferative neoplasm caused by excessive monocyte and granulocyte proliferation in infancy/early childhood. However, the roles of hypermethylation in this malignant disease are uncertain. Methods: Bone marrow samples from a JMML patient and peripheral blood samples from a healthy monozygotic twin and an unrelated healthy donor were collected with the informed consent of the participant's parents. Whole-genome bisulfite sequencing (WGBS) was then performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to analyze specific differentially methylated region (DMG) related genes. The target genes were screened with Cytoscape and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), which are gene/protein interaction databases. A data mining platform was used to examine the expression level data of the healthy control and JMML patient tissues in Gene Expression Omnibus data sets, and a survival analysis was performed for all the JMML patients. Results: The STRING analysis revealed that the red node [i.e., the cystic fibrosis transmembrane conductance regulator (CFTR)] was the gene of interest. The gene-expression microarray data set analysis suggested that the CFTR expression levels did not differ significantly between the JMML patients and healthy controls (P=0.81). A statistically significant difference was observed in the CFTR promoter methylation level but not in the CFTR gene body methylation level. The overall survival analysis demonstrated that a high level of CFTR expression was associated with a worse survival rate in patients with JMML (P=0.039). Conclusions: CFTR promoter hypermethylation may be a novel biomarker for the diagnosis, monitoring of disease progression, and prognosis of JMML.

Characteristics and phylogenetic analysis of the complete chloroplast genome of Rosa glomerata (Rosaceae).

Rosa glomerata is a diffuse shrub belonging to Rosa sect. Synstylae. It is endemic to Southwest China and of high ornamental and economic value. However, its systematic position remains unclear. Here, the complete chloroplast genome of R. glomerata was assembled using high-throughput sequencing data. The cp genome is 157,064 bp in length with a large single-copy region (LSC) of 86,216 bp, a small single-copy region (SSC) of 18,752 bp, and a pair of inverted repeats (IRs) of 26,048 bp. The overall GC content is 37.2%. A total of 137 genes were annotated, including 90 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Phylogenetic analysis revealed that R. glomerata is closely related to R. praelucens of R. sect. Microphyllae rather than species of R. sect. Synstylae.

Effect of manual soft tissue therapy on the pain in patients with chronic neck pain: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the impact of manual soft tissue therapy (MSTT) on the degree of pain in patients with chronic neck pain (CNP). METHODS: Trials included in the meta-analysis were identified by searching 5 English databases, including the PubMed, Embase, Cochrane Library, Web of Science and U.S. Clinical Trial Registry databases. The search was conducted with the subject terms neck pain, soft tissue treatment, massage, and myofascial release. We assessed the included trials using the Cochrane risk-of-bias tool. STATA statistical software version 16.0 was used for statistical analysis. Additionally, subgroup analysis and sensitivity analysis were performed to analyze the sources of heterogeneity and assess the stability of the research results. Begg's funnel plot and Egger's publication bias plot were used to assess potential publication bias. RESULTS: This systematic review included a total of 12 randomized controlled trials (566 patients in total). The participants were between 18 and 85 years old. Most of the included studies were of medium quality. This meta-analysis validated the effectiveness of MSTT in alleviating pain symptoms in patients with CNP (ES: 0.83; 95% CI: 1.15 to -0.51; P = 0.001). Egger's publication bias plot and Begg's funnel plot indicated that there may be potential publication bias. CONCLUSION: This meta-analysis found that MSTT has a significant effect on alleviating the pain of patients with CNP. In addition, the use of different pain measurement tools may influence effect of the intervention, but more clinical studies are needed in the future to determine the specific effect.

[Effect of Down-Regulation of ANRIL on Proliferation and Apoptosis of Kasumi-1 Cells and Its Potential Mechanism].

OBJECTIVE: To investigate the down-regulation of ANRIL (Antisense non-coding RNA in the INK4 Locus) effects on proliferation and apoptosis of Kasumi-1 cells and its related molecular mechanism. METHODS: Recombinant lentivirus was used to construct ANRIL down-regulation Kasumi-1 cells (sh-ANRIL group) and its control cells (sh-NC group). A fluorescence microscope was used to observe the transfection efficiency, RT-qPCR was used to detect knockdown efficiency and ANRIL expression in PBMCs and MBMCs of patients with acute myeloid leukemia (AML). Proliferation and apoptosis of Kasumi-1 cells were assayed by CCK-8 method and flow cytometry. Western blot was employed to detect the expression of PI3K, AKT, p-AKT, and relevant protein after down-regulation of ANRIL in Kasumi-1 cells. RESULTS: ANRIL overexpressed significantly in PBMCs and MBMCs of patients with AML, the transfection efficiency of recombinant lentivirus carrying sh-ANRIL and sh-NC on Kasumi-1 cells exceeded 90%, and the knockdown efficiency was 70%. When DNR was administrated for 24, 48, and 72 hours, the cell inhibition rate of the sh-ANRIL group was (47.40±1.49)%, (69.11±0.51)% and (91.82±1.10)%, which were significantly higher than those of the sh-NC group, respectively (P<0.05). The apoptotic rate in the sh-ANRIL group was (10.29±0.58)%, which was significantly higher than (5.42±0.67)% of the sh-NC group (P<0.01). After DNR treatment for 24 hours, the apoptotic rate of the sh-ANRIL group was (54.41±1.69)%, which was significantly higher than (38.28±1.42)% of sh-NC group (P<0.001). Western blot revealed that the protein levels of PI3K, p-AKT, PCNA, and BCL-2 in the sh-ANRIL group were reduced significantly than those in the sh-NC group, while the BAX protein expression increased. CONCLUSION: ANRIL may affect the proliferation and apoptosis of Kasumi-1 cells through PI3K/AKT signaling pathway. ANRIL is a potential therapeutic target for AML.

Diagnostic performance of DCE-MRI, multiparametric MRI and multimodality imaging for discrimination of breast non-mass-like enhancement lesions.

OBJECTIVE: The aim of this study was to investigate and compare the diagnostic performance of dynamic contrast-enhanced (DCE)-MRI, multiparametric MRI (mpMRI), and multimodality imaging (MMI) combining mpMRI and mammography (MG) for discriminating breast non-mass-like enhancement (NME) lesions. METHODS: This retrospective study enrolled 193 patients with 199 lesions who underwent 3.0 T MRI and MG from January 2017 to December 2019. The features of DCE-MRI, turbo inversion recovery magnitude (TIRM), and diffusion-weighted imaging (DWI) were assessed by two breast radiologists. Then, all lesions were divided into microcalcification and non-microcalcification groups to assess the features of MG. Comparisons were performed between groups using univariate analyses. Then, multivariate analyses were performed to construct diagnostic models for distinguishing NME lesions. Diagnostic performance was evaluated by using the area under the curve (AUC) and the differences between AUCs were evaluated by using the DeLong test. RESULTS: Overall (n = 199), mpMRI outperformed DCE-MRI alone (AUCmpMRI = 0.924 vs. AUCDCE-MRI = 0.884; p = 0.007). Furthermore, MMI outperformed both mpMRI and MG (the microcalcification group [n = 140]: AUCMMI = 0.997 vs. AUCmpMRI = 0.978, p = 0.018 and AUCMMI = 0.997 vs. AUCMG = 0.912, p < 0.001; the non-microcalcification group [n = 59]: AUCMMI = 0.857 vs. AUCmpMRI = 0.768, p = 0.044 and AUCMMI = 0.857 vs. AUCMG = 0.759, p = 0.039). CONCLUSION & ADVANCES IN KNOWLEDGE: DCE-MRI combined with DWI and TIRM information could improve the diagnostic performance for discriminating NME lesions compared with DCE-MRI alone. Furthermore, MMI combining mpMRI and MG showed better discrimination than both mpMRI and MG.

Oleanolic acid combined with olaparib enhances radiosensitization in triple negative breast cancer and hypoxia imaging with 18F-FETNIM micro PET/CT.

The heterogeneity of triple negative breast cancer (TNBC) results in the worst prognosis among breast cancer types, making its treatment strategy very challenging. A recent study showed that oleanolic acid (OA) has a radiosensitizing effect on tumor cells, but it does not show a good clinical effect when used alone in radiotherapy. The cytotoxicity of radiotherapy can be enhanced by modulating DNA repair, so new treatment options are being investigated to inhibit DNA repair pathways and sensitize tumors to radiation. Radiation induces DNA double-strand breaks (DSBs), and inhibition of Poly (ADP-Ribose) polymerase (PARP) can prevent the repair of these lesions. Hence, we evaluated the radiosensitization and the underlying mechanism of combination treatment with OA and olaparib in TNBC. Meanwhile, tumor hypoxia was monitored with 18F-Fluoroerythronitroimidazole (FETNIM) positron emission tomography/computed tomography (PET/CT) during radiosensitization therapy. Here, we found that OA and olaparib in combination with radiotherapy significantly inhibited cell proliferation compared with other groups. The results were observed using colony formation assays [sensitization enhancement ratios (SER) 1.16-1.65]. In vivo, tumor growth was significantly delayed in transplanted tumors receiving irradiation (IR) with OA and olaparib. 18F-FETNIM PET/CT can be utilized for tumor hypoxia monitoring and radiosensitization response evaluation. In conclusion, these results suggest that the combination of OA and olaparib with IR enhances the inhibition of MDA-MB-231 in cell culture and in mice, providing a potentially novel combination for the effective treatment of TNBC patients.

Maximizing Performance of a Hybrid MnO2/Ni Electrochemical Actuator through Tailoring Lattice Tunnels and Cation Vacancies.

Electrochemical actuators play a key role in converting electrical energy to mechanical energy. However, a low actuation stress and an unsatisfied strain response rate strongly limit the extensive applications of the actuators. Here, we report hybrid manganese dioxide (MnO2) fabricated by introducing ramsdellite (R-MnO2) and Mn vacancies into birnessite (δ-MnO2) nanosheets, which in situ grew on the surface of a nickel (Ni) film, forming a hybrid MnO2/Ni actuator. The actuator demonstrated a rapid strain response of 0.88% s-1 (5.3% intrinsic strain in 6 s) and a large actuation stress of 244 MPa owing to the special R-MnO2 with a high density of sodium ion (Na+)-accessible lattice tunnels, Mn vacancies, and also a high Young's modulus of the hybrid MnO2/Ni composite. Besides, the cyclic stability of the actuator was realized after 1.2 × 104 cycles of electric stimulation under a frequency of 0.05 Hz. The finding of the novel hybrid MnO2/Ni actuator may provide a new strategy to maximize the actuating performance evidently through tailoring the lattice tunnel structure and introducing cation vacancies into electrochemical electrode materials.

[Effect of manual acupuncture on expression of BDNF/TrkB/ERK/CREB signaling in infarcted tissue of cerebral ischemia rats].

OBJECTIVE: To observe the effect of acupuncture on the expression of cortical brain-derived neurothrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) mRNAs, and phosphorylated extracellular regulated protein kinases (p-ERK) 1/2 and phosphorylated cAMP response element binding protein (p-CREB) proteins in cerebral ischemia (CI) rats, so as to explore its neuroprotective mechanism on ischemic brain tissue. METHODS: Thirty male SD rats were randomly divided into sham-operation (control), model and acupuncture groups, with 10 rats in each group. The CI model was established by occlusion of the left middle cerebral artery (MCAO) using thread embolization method. Manual acupuncture was applied to"Baihui"(GV20),"Quchi"(LI11),"Neiguan"(PC6),"Hegu"(LI4),"Zusanli"(ST36),"Sanyinjiao"(SP6) and"Shenmai"(BL62) once daily, 6 days a week for 2 weeks. The modified neurological severity score (mNSS) including motor, sensation, balance, and neural reflex functions (0 point, normal; 18 points, maximal deficit) was used to assess the neurological impairment state. The expression levels of p-ERK 1/2 and p-CREB proteins, and BDNF and TrkB mRNAs in the ischemic cerebral cortex were measured by Western blot and real-time fluorescence quantitative PCR, respectively. RESULTS: The mNSS was significantly increased on day 1, 7 and 14 in the model group compared with the control group (P<0.01), and evidently decreased on day 14 in the acupuncture group in contrast to the model group (P<0.05). The expression levels of BDNF and TrkB mRNAs, and p-ERK1, p-ERK2 and p-CREB proteins on day 7 and 14 were significantly lower in the model group than in the control group (P<0.001). Following acupuncture treatment, the down-regulated expression levels of the two genes and the three proteins on day 14 were reversed (P<0.001, P<0.05, P<0.01). CONCLUSION: Acupuncture may promote neurological recovery in rats with cerebral ischemia, which may be related to its function in up-regulating the activities of BDNF/TrkB-ERK-CREB signaling in the cerebral cortex on the ischemic side.

Differences in complications between hepatitis B-related cirrhosis and alcohol-related cirrhosis.

OBJECTIVES: This study aimed to investigate the differences in complications between hepatitis B virus (HBV)-related and alcohol-related cirrhoses. METHODS: Medical records of patients with HBV-related and alcohol-related cirrhoses treated from January 2014 to January 2021 were, retrospectively, reviewed. The unadjusted rate and adjusted risk of cirrhotic complications between the two groups were assessed. RESULTS: The rates of hepatocellular carcinoma (HCC) and hypersplenism were higher in HBV-related cirrhosis (both P < 0.05), whereas the rates of hepatic encephalopathy (HE) and acute-on-chronic liver failure (ACLF) were higher in alcohol-related cirrhosis (both P < 0.05). After adjusting for potential confounders, HBV-related cirrhotic patients had higher risks of HCC (odds ratio [OR] = 34.06, 95% confidence interval [CI]: 4.61-251.77, P = 0.001) and hypersplenism (OR = 2.29, 95% CI: 1.18-4.42, P = 0.014), whereas alcohol-related cirrhotic patients had higher risks of HE (OR = 0.22, 95% CI: 0.06-0.73, P = 0.013) and ACLF (OR = 0.30, 95% CI: 0.14-0.73, P = 0.020). CONCLUSION: Cirrhotic patients with different etiologies had different types of complications: HBV-related cirrhotic patients exhibited increased risks of HCC and hypersplenism and alcohol-related cirrhotic patients more readily developing HE and ACLF.

Diagnosis and genetic analysis of a case of Waardenburg syndrome type 2 with hypogonadotropic hypogonadism caused by SOX10 gene deletion.

Hypogonadotropic hypogonadism (HH) is a disease defined by dysfunction of the hypothalamic- pituitary-gonadal hormone axis, leading to low sex hormone levels and impaired fertility. HH with anosmia or hyposmia is known as Kallmann syndrome (KS). Waardenburg syndrome (WS) is a rare autosomal dominant genetic disorder characterized by sensorineural hearing loss and abnormal pigmentation. In this report, we collected the clinical data of a patient with hypogonadotropic hypogonadism and congenital hearing loss of unknown cause. The patient had no obvious secondary sexual characteristics development after puberty, and had a heterozygous deletion (at least 419 kb) in 22q13.1 region (Chr.22:38106433-38525560), which covered the SOX10 gene. The abnormalities were not found in gene sequencing analysis of both the parents and sister of the proband. By summarizing and analyzing the characteristics of this case, we further discussed the molecular biological etiological association between HH and WS type 2. This case also enriches the clinical data of subsequent genetic studies, and provides a reference for the diagnosis and treatment of such diseases.

The effect of anemia on the severity and prognosis of patients with acute pancreatitis: A single-center retrospective study.

Anemia was a risk factor for a worse prognosis of many diseases. This study aims to investigate the relationship between anemia and the severity and prognosis of acute pancreatitis (AP). Inpatients hospitalized at the First Affiliated Hospital of Guangdong Pharmaceutical University with a primary diagnosis of AP between 1st July 2016 to 31st December 2020 were enrolled. Subsequently, disease severity, the incidence of complications, and the prognosis of patients with AP were compared between the anemic group and the non-anemic group. A total of 282 patients with acute pancreatitis were enrolled; 68.43% of them were also diagnosed with anemia. Notably, these patients had more severe disease (higher RANSON, acute physiologic assessment and chronic health evaluation-II, bedside index for severity in acute pancreatitis, and multiple organ dysfunction syndrome scores); higher incidence of organ failure (acute kidney injury [AKI] and acute heart failure); worse prognosis (higher incidence of vasoactive and diuretic agent use, longer hospital stays, and higher hospital costs) compared to that of patients without anemia (all P < .05). After adjusting for potential confounders, acute physiologic assessment and chronic health evaluation-II, bedside index for severity in acute pancreatitis, multiple organ dysfunction syndrome scores, hospital stay, and hospital costs in anemic patients were higher than those in non-anemic patients; besides, the incidence of AKI and using a diuretic agent in anemic patients was 6.645 and 4.053 times that of non-anemic patients in AP, respectively (all P < .05). Acute pancreatitis patients with anemia have more disease severity, higher incidence of AKI, and worse prognosis compared to those without anemia.

[Application of pelvic sentinel lymph node tracing technique in radical prostatectomy].

Pelvic lymph node dissection is an important step in radical prostatectomy (RP). Extended pelvic lymph node dissection (ePLND), currently employed for patients with intermediate- or high-risk PCa, may lead to overtreatment, prolong the operation time, and increase the risks of complications. Sentinel lymph node (SLN) is defined as the first metastasis lymph node from the primary tumor. In addition, SLN distribution is essential for overall lymph node dissection. However, due to the complex and diverse lymphatic drainage pathways and the inaccuracy of lymphatic tracing technology, SLN distribution and dissection have always been controversial. This review focuses on the application of pelvic SLN tracing technique in radical prostatectomy.

Physical exercise rescues cocaine-evoked synaptic deficits in motor cortex.

Drug exposure impairs cortical plasticity and motor learning, which underlies the reduced behavioral flexibility in drug addiction. Physical exercise has been used to prevent relapse in drug rehabilitation program. However, the potential benefits and molecular mechanisms of physical exercise on drug-evoked motor-cortical dysfunctions are unknown. Here we report that 1-week treadmill training restores cocaine-induced synaptic deficits, in the form of improved in vivo spine formation, synaptic transmission, and spontaneous activities of cortical pyramidal neurons, as well as motor-learning ability. The synaptic and behavioral benefits relied on de novo protein synthesis, which are directed by the activation of the mechanistic target of rapamycin (mTOR)-ribosomal protein S6 pathway. These findings establish synaptic functional restoration and mTOR signaling as the critical mechanism supporting physical exercise training in rehabilitating the addicted brain.

Photosynthetically physiological mechanism of Stipa krylovii withered and yellow phenology response to precipitation under the background of warming.

We examined the photosynthetically physiological mechanism of Stipa krylovii response to warming and precipitation changes, based on an experiment with the treatments of warming by infrared radiator and precipitation treatments by irrigation water. Under the warming background, precipi-tation was the main influencing factor of the withered and yellow phenology. Increasing precipitation postponed the occurrence time of both the beginning and the peak of the withered and yellow phenology, and prolonged the duration of the withered and yellow phenology. The effect of decreasing precipitation on prolonging the duration of the withered and yellow phenology was much stronger. Under the background of warming, the changes of precipitation markedly affected the physiological and ecological characteristics of the withered and yellow phenology, with the effect being the most significant at the beginning of the withered and yellow phenology. The net photosynthetic rate (Pn), stomatal conductance (gs), transpiration rate (Tr), and the maximum ribulose 1,5-bisphosphate (RuBP) carboxylation rate (Vc max), RuBP regeneration capacity (Jmax) were positively correlated with precipitation. Results of the pathway analysis showed that the photosynthetically physiological mechanism of withered and yellow phenology of S. krylovii would be different under different conditions of precipitation and temperature. Under the current environmental condition, Jmax was the main influencing factor of the withered and yellow phenology, and Vc max was the main limiting factor. Under the scenarios of warm and dry climate and warm and wet climate, Vc max become the main influencing factor of the withered and yellow phenology. Jmax would be the main limiting factor in the warm and dry climate conditions, and there would be no limiting factor in the warm and wet climate conditions. Our findings indicated that the withered and yellow phenological changes of S. krylovii depend on the photosynthetical capacity limitation resulted from meteorological conditions.

Entecavir-induced interferon-λ1 suppresses type 2 innate lymphoid cells in patients with hepatitis B virus-related liver cirrhosis.

The immunomodulatory effects of entecavir (ETV) in anti-hepatitis B virus (HBV) therapy have long been recognized. This study aimed to determine the effects of ETV on non-natural killer innate lymphoid cells (non-NK ILCs) in HBV-related liver disease progression. We enrolled treatment-naïve chronic hepatitis B (CHB) and HBV-related liver cirrhosis (LC) patients treated with ETV for 24 months. Before and after therapy, the frequency and cytokine profiles of ILC2s and non-NK ILCs subset homeostasis and their clinical significance were determined, and serial serum interferon (IFN)-λ levels were analysed. Peripheral blood mononuclear cells (PBMCs) of untreated LC patients were cultured with serum from untreated and ETV-treated LC patients in addition to being subject to IFN-λ1 neutralization and stimulation, and the frequency and cytokine production of ILC2s as well as non-NK ILCs subset ratios were calculated. Furthermore, IFN-λ receptor expression on non-NK ILCs and dendritic cells (DCs) was measured. After 24 months of ETV treatment, the frequency and cytokine production of ILC2s (IL-4, IL-13, IFN-γ, TNF-α) decreased with increased ILC1/ILC2 and decreased ILC2/ILC3 ratios, revealing a close association with disease status in LC patients. Long-term ETV administration-induced serum IFN-λ1 levels were negatively correlated with ILC2s. ETV-treated LC serum culture and IFN-λ1 stimulation yielded similar effects on suppression of ILC2s, and IFN-λ1 neutralization in serum culture partly inhibited this effect. The IFN-λ receptor was detected on DCs but not on non-NK ILCs. In conclusion, ETV suppresses the frequency and cytokine profiles of ILC2s by increasing IFN-λ1 in LC patients.

ABCC9 Is Downregulated and Prone to Microsatellite Instability on ABCC9tetra in Canine Breast Cancer.

Tumorigenesis is associated with metabolic abnormalities and genomic instability. Microsatellite mutations, including microsatellite instability (MSI) and loss of heterozygosity (LOH), are associated with the functional impairment of some tumor-related genes. To investigate the role of MSI and LOH in sporadic breast tumors in canines, 22 tumors DNA samples and their adjacent normal tissues were evaluated using polyacrylamide gel electrophoresis and silver staining for 58 microsatellites. Quantitative real-time polymerase chain reaction, promoter methylation analysis and immunohistochemical staining were used to quantify gene expression. The results revealed that a total of 14 tumors (6 benign tumors and 8 breast cancers) exhibited instability as MSI-Low tumors. Most of the microsatellite loci possessed a single occurrence of mutations. The maximum number of MSI mutations on loci was observed in tumors with a lower degree of differentiation. Among the unstable markers, FH2060 (4/22), ABCC9tetra (4/22) and SCN11A (6/22) were high-frequency mutation sites, whereas FH2060 was a high-frequency LOH site (4/22). The ABCC9tetra locus was mutated only in cancerous tissue, although it was excluded by transcription. The corresponding genes and proteins were significantly downregulated in malignant tissues, particularly in tumors with MSI. Furthermore, the promoter methylation results of the adenosine triphosphate binding cassette subfamily C member 9 (ABCC9) showed that there was a high level of methylation in breast tissues, but only one case showed a significant elevation compared with the control. In conclusion, MSI-Low or MSI-Stable is characteristic of most sporadic mammary tumors. Genes associated with tumorigenesis are more likely to develop MSI. ABCC9 protein and transcription abnormalities may be associated with ABCC9tetra instability.