[Comparison of Clinical Characteristics of JAK2, CALR and Tri-Negative Driving Mutant Type in Patients with Essential Thrombocythemia].

OBJECTIVE: To investigate the relationship between mutated genes and clinical features in patients with essential thrombocythemia (ET). METHODS: The clinical data of 69 patients with ET from October 2018 to March 2022 were retrospectively analyzed. According to driver mutation type, patients were divided into JAK2 group, CALR group and triple-negative group. The sex, age, cardiovascular risk factors, thrombosis, splenomegaly, routine blood test and coagulation status of patients in three groups were analyzed. RESULTS: Among 69 ET patients, 46 cases were associated with JAK2 mutation, 14 cases with CALR mutation, 8 cases with triple-negative mutation, and one with MPL gene mutation. There were no significant differences in age and sex among the three groups (P >0.05). The highest thrombotic rate was 26.09% (12/46) in JAK2 group, then 12.5% (1/8) in triple-negative group, while no thrombotic events occurred in CALR group. The incidence of splenomegaly was the highest in JAK2 group (34.78%), while no splenomegaly occurred in triple-negative group. The white blood cell (WBC) count in JAK2 group was (9.00±4.86)×109/L, which was significantly higher than (6.03±2.32)×109/L in CALR group (P <0.05). The hemoglobin (Hb) and hematocrit (HCT) in JAK2 group were (148.42±18.79) g/L and (0.44±0.06)%, respectively, which were both significantly higher than (131.00±15.17) g/L and (0.39±0.05)% in triple-negative group (P <0.05). The platelet (PLT) in JAK2 group was (584.17±175.77)×109/L, which was significantly lower than (703.07±225.60)×109/L in CALR group (P <0.05). The fibrinogen (Fg) in JAK2 and triple-negative group were (2.64±0.69) g/L and (3.05±0.77) g/L, respectively, which were both significantly higher than (2.24±0.47) g/L in CALR group (P <0.05, P <0.01). The activated partial thromboplastin time (APTT) in triple-negative group was (28.61±1.99) s, which was significantly decreased compared with (31.45±3.35) s in CALR group (P <0.05). CONCLUSIONS: There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations. Among ET patients, JAK2 mutation is most common. Compared with CALR group, the thrombotic rate, WBC and Fg significantly increase in JAK2 group, while PLT decrease. Compared with triple-negative group, the incidence of splenomegaly and HCT significantly increase. Compared with CALR group, Fg significantly increases but APTT decreases in triple-negative group.

Antiviral Therapy Favors a Lower Risk of Liver Cirrhosis in HBeAg-negative Chronic Hepatitis B with Normal Alanine Transaminase and HBV DNA Positivity.

Background and Aims: Direct evidence on the outcomes of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal alanine transaminase after long-term antiviral treatment is lacking. Methods: HBeAg-negative patients with normal ALT and positive HBV DNA (≥20 IU/mL) were retrospectively enrolled. The endpoints included virological response (HBV DNA<100 IU/mL), changes in aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 index (FIB-4), and the incidence of liver nodules, cirrhosis, and hepatocellular carcinoma (HCC). Results: This cohort (n=194) was divided into three subgroups, untreated (n=67), treatment-continued (n=87), and treatment-discontinued patients (n=40), with a median follow-up of 54 months. The treatment-continued group achieved 100% (95% CI: 94.7-100) virological response, and significantly reduced APRI and FIB-4 scores (both p<0.001). The risk of liver nodules and cirrhosis in that group was reduced by 76% (HR: 0.24, 95% CI: 0.11-0.54, p<0.001) and 89% (HR: 0.11, 95% CI: 0.14-0.91, p=0.041) vs. the untreated group and by 77% (HR: 0.23, 95% CI: 0.10-0.49, p<0.001) and 95% (HR: 0.05, 95% CI: 0.01-0.44, p=0.006) vs. the treatment-discontinued group. For patients with HBV DNA≥2,000 IU/mL, adherence to treatment lowered the risks of liver cirrhosis by 92% (95% CI: 0.01-0.67) and 93% (95% CI: 0.01-0.53) vs. the untreated and treatment-discontinued patients, respectively. No patient adhering to treatment developed HCC, but one in each of the remaining groups did. Conclusions: Continuous nucleos(t)ide analog (NA) treatment has a satisfactory effectiveness and helps to lower the risk of liver cirrhosis in HBeAg-negative CHB patients with normal alanine transaminase, especially in those with HBV DNA≥2,000 IU/mL.

Retrospectively analyze and compare the efficacy and safety of thoracoscopic-assisted Nuss repair of pectus excavatum under intubation anesthesia and non-intubation anesthesia.

Background: Thoracoscopic-assisted Nuss repair is a commonly used method for treating pectus excavatum, which has always been performed under tracheal intubation and general anesthesia. However, general anesthesia with endotracheal intubation can produce intubation and anesthetic drug related complications. In non-intubation anesthesia, laryngeal mask is used instead of tracheal intubation without muscle relaxants and small doses of sedative and analgesic drugs. Therefore, non-intubation anesthesia can reduce complications and speed up postoperative recovery. This study retrospectively analyzed the clinical impact of these two anesthesia methods on thoracoscopic-assisted Nuss repair for the treatment of pectus excavatum. Methods: A total of 115 pectus excavatum patients who underwent thoracoscopic-assisted Nuss procedure repair in the Department of Thoracic Surgery of Yunnan First People's Hospital from January 2017 to January 2022 were included. All subjects in this study underwent thoracoscopic assisted Nuss repair in the same thoracic surgical team. According to different anesthesia methods, they were divided into non-intubation anesthesia group (n=62) and intubation anesthesia group (n=53). The intubation time, intraoperative mean heart rate, postoperative complications, postoperative first oral food intake, water intake, ambulation, defecation time, postoperative blood drawing results, postoperative hospital stay and total hospitalization cost were compared between the two groups. Results: There were no significant differences in clinical characteristics and preoperative examination indexes between the two groups, which were comparable. Compared with the intubation anesthesia group, the non-intubation anesthesia group had less anesthesia intubation time, lower intraoperative mean heart rate, less postoperative complications, such as pneumothorax, pleural effusion, and lung infection. In the non-intubation anesthesia group, the first time to eat, drink, get out of bed, and defecate were all earlier. Routine blood results 24 h after surgery indicated that the non-intubation anesthesia group had lower white blood cell, neutrophil and lymphocyte, an earlier postoperative discharge time, and lower total hospitalization expenses. Conclusions: Non-intubation anesthesia in thoracoscopic-assisted Nuss procedure for the repair of pectus excavatum can make the postoperative recovery of patients faster and has better safety and efficacy.

Linezolid-Induced Pancytopenia in Patients Using Dapagliflozin: A Case Series.

Background: Linezolid is classed as oxazolidinone antibiotics which can be used to treat severe infections caused by vancomycin-resistant Enterococcus faecium, hospital-acquired pneumonia caused by Staphylococcus aureus, complicated skin, and uncomplicated skin structure infections (SSSIs) caused by methicillin-susceptible S. aureus or Streptococcus pyogenes, and community-acquired pneumonia caused by Streptococcus pneumoniae. However, many studies have suggested it can also cause thrombocytopenia and pancytopenia. Patients and Methods: We report on three patients with linezolid-pancytopenia. Patients in cases 1 and 2 were diagnosed with heart failure with preserved ejection fraction (HFpEF) and were both administered with dapagliflozin, one of the sodium-dependent glucose transporters 2 inhibitors (SHLT-2i). Results: Two patients were diagnosed with type 2 diabetes, pneumonia, and hyponatremia. Severe myelosuppression occurred in both patients, with a severe decrease in leukocytes and platelets and a moderate decrease in hemoglobin, who eventually passed away despite the discontinuation of linezolid and adopting appropriate treatment measures. The patient in case 3 was diagnosed with pneumonia, type 2 diabetes, and sequelae of cerebral thrombosis. After twelve days of treatment, the patient developed moderate thrombocytopenia and anemia. She recovered without any additional treatment after the discontinuation of linezolid. Conclusion: In this case series, two patients with irreversible myelosuppression were treated with both linezolid and SGLT-2i, and one diabetic patient with single linezolid use presented with reversible pancytopenia, suggesting that SGLT-2i may exacerbate myelosuppression of linezolid. Linezolid should be used with caution in infectious patients with a history of SGLT-2i. We will conduct relevant animal experiments to clarify the interaction between the two drugs.

[Analysis of Differential Proteins Related to Platelet Activation in Patients with Essential Thrombocythemia Based on Label-Free Quantitative Technology].

OBJECTIVE: To analysis the specific protein markers of essential thrombocythemia (ET) based on proteomics technology, to explore and verify the differential protein related to platelet activation. METHODS: Blood samples were obtained from ET patients and healthy people and a certain protein mass spectrometry was detected using label-free quantitative technology. The proteins relative abundance increased or down-regulated by 1.3 times in the disease group compared with the control group, and the protein abundance in the two groups t test P＜0.05 were defined as differential proteins. Bioinformatics analysis of the differential proteins was performed using GO and KEGG. The difference in the average protein abundance between the two groups was analyzed by t test and P＜0.05 was considered statistically significant. Differential proteins were selected for verification by parallel reaction monitoring (PRM) technology. RESULTS: A total of 140 differential proteins were found, of which 72 were up-regulated and 68 were down-regulated. KEGG enrichment showed that the differential protein expression was related to the platelet activation pathway. The differential proteins related to platelet activation were GPV, COL1A2, GP1bα, COL1A1 and GPVI. Among them, the expressions of GPV, GP1bα and GPVI were up-regulated, and the expressions of COL1A2 and COL1A1 were down-regulated. PRM verification of COL1A1, GP1bα, GPVI and GPV was consistent with LFP proteomics testing. CONCLUSION: Differential proteins in ET patients are related to platelet activation pathway activation.Differential proteins such as GPV, GPVI, COL1A1 and GP1bα can be used as new targets related to ET platelet activation.

[Analysis of DNA Methylation Gene Mutations and Clinical Features in Patients with Myeloproliferative Neoplasm].

AbstractObjective: To analyze the DNA methylation gene mutations of myeloproliferative neoplasm (MPN), and preliminarily explore its clinical features. METHODS: Next-generation sequencing technology was used to detect 31 MPN-related genes in 105 cases of MPN patients ï¼»40 cases of polycythaemia vera (PV), 65 cases of essential thrombocythemia (ET)ï¼½, and to analyze the relationship between DNA methylation gene mutations and clinical features. RESULTS: 15 mutation types were detected in 105 patients (88 mutations in total), and the total mutation detection rate was 87.6% (92/105). A total of 23 mutations in 4 DNA methylation genes (TET2, DNMT3A, IDH1, IDH2) were detected in 22 patients. The mutation rate of DNA methylation genes was 21.0%, mainly in the form of double mutations, including JAK2 V617F and TET2 (n=10), JAK2 V617F and DNMT3A (n=4), CALR and TET2 (n=2), JAK2 V617F and IDH1 (n=1). Compared with MPN patients without DNA methylation gene mutations, the proportion of women with DNA methylation gene mutations and the white blood cell count (WBC) were significantly higher (P<0.05). Compared with MPN patients with triple-negative driver genes, the proportion of women with DNA methylation gene mutations, age, WBC, platelet count (PLT), and neutrophil-to-lymphocyte ratio (NLR) were significantly higher (P<0.05). The remaining difference was not statistically significant (P>0.05). The MPN10 score, the incidence of thrombotic events, and the proportion of medium-risk and high-risk patients with DNA methylation gene mutations were significantly higher than those of MPN patients without DNA methylation gene mutations (P<0.05). CONCLUSION: The mutation rate of DNA methylation genes was 21.0%, mainly coexisting in the form of double mutations. The proportion of women with DNA methylation gene mutations in MPN patients and WBC is high, the symptom load is heavy, the incidence of thrombosis is high, and the proportion of medium-high-risk patients is high, suggesting that their prognosis may be poor.

Effect of modified radical mastectomy combined with latissimus dorsi musculocutaneous flap breast reconstruction on patients' psychology and quality of life.

BACKGROUND: Breast carcinoma (BC) is a commonly seen malignancy in women. Although traditional radical mastectomy can improve the survival of patients, it can cause breast loss and chest wall deformities, which seriously affects the daily life of patients and causes anxiety and depression. The purpose of this research project is to investigate the effect of breast reconstruction with latissimus dorsi myocutaneous flap (LDMF) after nipple- and areola-sparing modified radical mastectomy (MRM) on the psychological mood and quality of life (QoL) of patients with stage I BC. METHODS: A total of 102 patients with BC (research group, RG) treated in the Shanghai Fifth People's Hospital, Fudan University from January 2018 to December 2020 were selected for phase I breast reconstruction with LDMF after nipple- and areola-sparing MRM. Concurrently, 50 BC patients (control group, CG) who underwent traditional total mastectomy in our hospital were collected. The activities of daily living (ADL), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores were observed before and 1 month after treatment. The intraoperative indicators, postoperative complications, postoperative satisfaction rate and overall survival rate were compared. RESULTS: The Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) score was higher after treatment, while SAS and SDS scores were lower in RG than in CG (P<0.05). No statistical difference was observed in intraoperative blood loss, wound drainage time, operation time, postoperative complications and overall survival rate between the two cohorts (P>0.05). RG showed higher satisfaction degree and overall satisfaction rate, as well as better QoL than CG (P<0.05). CONCLUSIONS: Breast reconstruction with LDMF after nipple- and areola-sparing MRM can alleviate adverse emotions of patients with stage I BC and improve their QoL.

Effect of Bonding Strength on Electromigration Failure in Cu-Cu Bumps.

In microelectronic packaging technology for three-dimensional integrated circuits (3D ICs), Cu-to-Cu direct bonding appears to be the solution to solve the problems of Joule heating and electromigration (EM) in solder microbumps under 10 µm in diameter. However, EM will occur in Cu-Cu bumps when the current density is over 106 A/cm2. The surface, grain boundary, and the interface between the Cu and TiW adhesion layer are the three major diffusion paths in EM tests, and which one may lead to early failure is of interest. This study showed that bonding strength affects the outcome. First, if the bonding strength is not strong enough to sustain the thermal mismatch of materials during EM tests, the bonding interface will fracture and lead to an open circuit of early failure. Second, if the bonding strength can sustain the bonding structure, voids will form at the passivation contact area between the Cu-Cu bump and redistribution layer (RDL) due to current crowding. When the void grows along the passivation interface and separates the Cu-Cu bump and RDL, an open circuit can occur, especially when the current density and temperature are severe. Third, under excellent bonding, when the voids at the contact area between the Cu-Cu bump and RDL do not merge together, the EM lifetime can be more than 5000 h.

Failure Mechanisms of Cu-Cu Bumps under Thermal Cycling.

The failure mechanisms of Cu-Cu bumps under thermal cycling test (TCT) were investigated. The resistance change of Cu-Cu bumps in chip corners was less than 20% after 1000 thermal cycles. Many cracks were found at the center of the bonding interface, assumed to be a result of weak grain boundaries. Finite element analysis (FEA) was performed to simulate the stress distribution under thermal cycling. The results show that the maximum stress was located close to the Cu redistribution lines (RDLs). With the TiW adhesion layer between the Cu-Cu bumps and RDLs, the bonding strength was strong enough to sustain the thermal stress. Additionally, the middle of the Cu-Cu bumps was subjected to tension. Some triple junctions with zig-zag grain boundaries after TCT were observed. From the pre-existing tiny voids at the bonding interface, cracks might initiate and propagate along the weak bonding interface. In order to avoid such failures, a postannealing bonding process was adopted to completely eliminate the bonding interface of Cu-Cu bumps. This study delivers a deep understanding of the thermal cycling reliability of Cu-Cu hybrid joints.

[Clinical Characteristics of Patients with JAK2 Gene Mutation Myeloproliferative Neoplasms].

OBJECTIVE: To investigate the relationship between JAK2 gene mutation and clinical indicators in patients with myeloproliferative neoplasms (MPN). METHODS: 122 MPN patients in the Department of Hematology, Xiyuan Hospital, China Academy of Chinese Medical Sciences from September 2017 to January 2020 were retrospectively analyzed. The relationship between JAK2 gene mutation and sex, age, peripheral blood cell count, splenomegaly, and thrombosis and bleeding events were analyzed. RESULTS: In 122 patients with MPN, the patients with polycythemia vera (PV) accounted for 36 (29.5%), the patients with essential thrombocythemia (ET) accounted for 56 (45.9%), the patients with myelofibrosis (MF) accounted for 30 (24.6%). The JAK2 gene mutation rate in MPN patients was 64.6% (79/122), and the JAK2 gene mutation rate in PV, ET and MF groups were 77.7% (28/36), 60.7% (34/56) and 56.7% (17/30), the JAK2 gene mutation rate of the patients in PV group was statistically significant as compared with those in the ET group (P＜0.05). The hemoglobin (Hb) count of the patients in JAK2 gene mutation group was higher than those in wild-type group ï¼»(150.0±39.6)g/L vs (129.4±38.9)g/L, P＜0.05ï¼½; the white blood cell (WBC) count of the patients in JAK2 gene mutation group was higher than those in the wild type group ï¼»(9.5±4.7)×109/L vs (8.4±46.9)×109/L, P＜0.05ï¼½. As for the patients in PV group, the platelet count of the patients in JAK2 gene mutation group was higher than those in the wild type group ï¼»(370.2±113.1)×109/L vs (264.8±63.9)×109/L, P＜0.05ï¼½. The incidence of splenomegaly in MPN patients was 35.2% (43/122), and the incidence of splenomegaly in MF patients was 63.3% (19/30), and the incidence of splenomegaly in the patients in JAK2 gene mutation group in MF group (82.4%, 12/17) was significantly higher than those in the wild-type group (38.5%, 5/13) (P<0.05). CONCLUSION: The mutation rate of JAK2 gene in MPN patients is higher, and the mutation rate of JAK2 gene in PV patients is higher than that in ET and MF patients; JAK2 gene mutations in MPN patients are related to hemogram index; the incidence of splenomegaly is the highest in MF patients, and splenomegaly is related to the occurrence of JAK2 gene mutations in MF patients.

SV-VATS exhibits dual intraoperative and postoperative advantages.

BACKGROUND: The merits of spontaneous ventilation video-assisted thoracic surgery (SV-VATS) are still controversial. Our team retrospectively evaluated the intraoperative and postoperative advantages of this surgical approach, comparing with mechanical ventilation video-assisted thoracic surgery (MV-VATS). METHODS: We did a single center retrospective study at the First Affiliated Hospital of Yunnan Province. 244 patients were eventually assigned to the SV-group and MV-group, and their intraoperative indicators and thoracic surgery postoperative data were included in the comparison. RESULTS: The SV-group exhibited markedly less intraoperative bleeding and postoperative thoracic drainage, and the bleeding volume was correlated with the volume and duration of drainage. Further analysis showed that, patients undergoing SV-VATS had less activation of white blood cells and neutrophils after surgery, but they also had lower serum albumin concentrations. Risks of short-term postoperative complications, including inflammatory reactions, malignant arrhythmias, constipation, and moderate or more pleural effusions, were also significantly reduced in the SV-group. Additionally, hospitalization cost was lower in the SV-group than that in the MV-group. CONCLUSIONS: SV-VATS is suitable for various types of thoracic surgery, and effectively reduce intraoperative bleeding and postoperative thoracic drainage. With less postoperative inflammatory response, it reduces the risk of short-term postoperative complications. It is also able to help to reduce the financial burden of patients.

Palladium-catalyzed dearomative allylation of indoles with cyclopropyl acetylenes: access to indolenine derivatives.

A palladium-catalyzed redox-neutral allylic alkylation of indoles with cyclopropyl acetylenes has been disclosed. Various 1,3-diene indolenine framework bearing a quaternary stereocenter at the C3 position were synthesized straightforwardly in good to excellent yields with high regio- and stereoselectivities. The reaction could be further expanded to the dearomatization of naphthols to synthesize functionalized cyclohexadienones with 1,3-diene motifs. The reaction exhibited high atom economy and good functional group tolerance.

Tensile Properties of <111>-Oriented Nanotwinned Cu with Different Columnar Grain Structures.

We performed tensile tests on highly <111>-oriented nanotwinned copper (nt-Cu) foils with different columnar grain structures. For a systematic study, we altered the microstructure of the foils by tuning the electroplating electrolyte and annealing temperatures under a nitrogen atmosphere. The results show that the yield strength ranges from 300 to 700 MPa, and elongation spans from 5% to 25%. Knowing the measured twin spacing and average grain size, and combining the confined layer slip with the Hall-Petch equation, we calculated the theoretical yield strength of the nt-Cu with different microstructures, and the theoretic values match the experiment results. Owing to the unique crystal orientation properties of <111>-oriented columnar grains, dislocations induced by slip are very limited. The Schmid factor of grains along the tensile axis direction is highly identical, so the plastic deformation is much more suitably explained by the Schmid factor model. Thus, we replace the Taylor factor with the Schmid factor in the slip model of nt-Cu.

Tensile Properties and Thermal Stability of Unidirectionally <111>-Oriented Nanotwinned and <110>-Oriented Microtwinned Copper.

Tensile tests on two kinds of electroplated copper foils with twins before and after annealing were performed. One electroplating parameter results in a microstructure of <110>-oriented microtwinned Cu (mt-Cu), and the other is <111>-oriented nanotwinned Cu (nt-Cu). The latter shows higher thermal stability than the former after annealing. Though the toughness for the two as-plated foils are quite close, the toughness for the <111> oriented nt-Cu increased from 34 to 74 MJ/m3 after annealing at 250 °C for 3 h. In comparison, the toughness of the <110>-oriented mt-Cu remained almost the same after annealing.

Increased TRPM4 Activity in Cerebral Artery Myocytes Contributes to Cerebral Blood Flow Reduction After Subarachnoid Hemorrhage in Rats.

Cerebral blood flow (CBF) reduction underlies unfavorable outcomes after subarachnoid hemorrhage (SAH). Transient receptor potential melastatin-4 (TRPM4) has a pivotal role in cerebral artery myogenic tone maintenance and CBF regulation under physiological conditions. However, the role of TRPM4 in CBF reduction after SAH is unclear. In this study, we aimed at testing whether TRPM4 would contribute to CBF reduction after SAH in vivo and determining underlying mechanisms. Rat SAH model was established by stereotaxic injection of autologous nonheparinized arterial blood at the suprasellar cistern. A TRPM4 blocker, 9-phenanthrol (9-Phe), was infused through an intraventricular catheter connected to a programmed subcutaneous pump to evaluate the contribution of TRPM4 to SAH outcomes. TRPM4 expression and translocation in cerebral artery myocytes were detected by immunoblotting. Macroscopic currents in cerebral artery myocytes were determined by whole-cell patch clamp. Myogenic tone of cerebral arteries was studied by pressurized myography. Cortical and global CBFs were measured via laser Doppler flowmetry and fluorescent microspheres, respectively. After SAH, TRPM4 translocation and macroscopic current density increased significantly. Furthermore, TRPM4 accounted for a greater proportion of myogenic tone after SAH, suggesting an upregulation of TRPM4 activity in response to SAH. Cortical and global CBFs were reduced after SAH, but were restored significantly by 9-Phe, implying that TRPM4 contributed to CBF reduction after SAH. Collectively, these discoveries show that increased TRPM4 activity has a pivotal role in CBF reduction after SAH, and provide a novel target for the management of cerebral perfusion dysfunction following SAH.

MicroRNA-128 Protects Dopamine Neurons from Apoptosis and Upregulates the Expression of Excitatory Amino Acid Transporter 4 in Parkinson's Disease by Binding to AXIN1.

BACKGROUND/AIMS: Parkinson's disease (PD) is a frequently occurring condition that resulted from the loss of midbrain neurons, which synthesize the neurotransmitter dopamine. In this study, we established mouse models of PD to investigate the expression of microRNA-128 (miR-128) and mechanism through which it affects apoptosis of dopamine (DA) neurons and the expression of excitatory amino acid transporter 4 (EAAT4) via binding to axis inhibition protein 1 (AXIN1). METHODS: Gene expression microarray analysis was performed to screen differentially expressed miRNAs that are associated with PD. The targeting relationship between miR-128 and AXIN1 was verified via a bioinformatics prediction and dual-luciferase reporter gene assay. After separation, DA neurons were subjected to a series of inhibitors, activators and shRNAs to validate the mechanisms of miR-128 in controlling of AXIN1 in PD. Positive protein expression of AXIN1 and EAAT4 in DA neurons was determined using immunocytochemistry. miR-128 expression and the mRNA and protein levels of AXIN1 and EAAT4 were evaluated via RT-qPCR and Western blot analysis, respectively. DA neuron apoptosis was evaluated using TUNEL staining. RESULTS: We identified AXIN1 as an upregulated gene in PD based on the microarray data of GSE7621. AXIN1 was targeted and negatively mediated by miR-128. In the DA neurons, upregulated miR-128 expression or sh-AXIN1 increased the positive expression rate of EAAT4 together with mRNA and protein levels, but decreased the mRNA and protein levels of AXIN1, apoptosis rate along with the positive expression rate of AXIN1; however, the opposite trend was found in response to transfection with miR-128 inhibitors. CONCLUSION: Evidence from experimental models revealed that miR-128 might reduce apoptosis of DA neurons while increasing the expression of EAAT4 which might be related to the downregulation of AXIN1. Thus, miR-128 may serve as a potential target for the treatment of PD.

Correlation between the Microstructures of Bonding Interfaces and the Shear Strength of Cu-to-Cu Joints Using (111)-Oriented and Nanotwinned Cu.

Highly (111)-oriented Cu pillar-bumps were bonded to highly (111)-oriented Cu films at temperatures ranging from 200 °C/100 °C to 350 °C/100 °C in N2 ambient conditions. The microstructures of the bonded interfaces affected the shear strength performance of the bonded Cu joints. The bonded interfaces at 300 °C/100 °C and 350 °C/100 °C had far fewer voids than interfaces bonded at 200 °C/100 °C and 250 °C/100 °C. In addition, grain growth took place across the bonding interfaces at temperatures above 300 °C/100 °C. The corresponding orientation map (OIM) showed the preferred orientation of large grown grains to be <100>. Shear tests revealed that the fracture mode was brittle for joints bonded at 200 °C/100 °C, but became ductile after bonded above 300 °C/100 °C. Based on the results, we found that voids and grain growth behavior play import roles in the shear strength performance of bonded Cu joints.

Photovoltage response of (XZn)Fe2O4-BiFeO3 (X=Mg, Mn or Ni) interfaces for highly selective Cr3+, Cd2+, Co2+ and Pb2+ ions detection.

High-photostability fluorescent (XZn)Fe2O4 (X=Mg, Mn or Ni) embedded in BiFeO3 spinel-perovskite nanocomposites were successfully fabricated via a novel bio-induced phase transfer method using shewanella oneidensis MR-1. These nanocomposites have the near-infrared fluorescence response (XZn or Fe)-O-O-(Bi) interfaces (785/832nm), and the (XZn)Fe2O4/BiFeO3 lattices with high/low potentials (572.15-808.77meV/206.43-548.1meV). Our results suggest that heavy metal ion (Cr3+, Cd2+, Co2+ and Pb2+) d↓ orbitals hybridize with the paired-spin X-Zn-Fe d↓-d↓-d↑↓ orbitals to decrease the average polarization angles (-29.78 to 44.71°), qualitatively enhancing the photovoltage response selective potentials (39.57-487.84meV). The fluorescent kinetic analysis shows that both first-order and second-order equilibrium adsorption isotherms are in line and meet the Langmuir and Freundlich modes. Highly selective fluorescence detection of Co2+, Cr3+ and Cd2+ can be achieved using Fe3O4-BiFeO3 (Langmuir mode), (MgZn)Fe2O4-BiFeO3 and (MnZn)Fe2O4-BiFeO3 (Freundlich mode), respectively. Where the corresponding max adsorption capacities (qmax) are 1.5-1.94, 35.65 and 43.7 multiple, respectively, being more competitive than that of other heavy metal ions. The present bio-synthesized method might be relevant for high-photostability fluorescent spinel-perovskite nanocomposites, for design of heavy metal ion sensors.

Enhanced Photovoltage Response of Hematite-X-Ferrite Interfaces (X = Cr, Mn, Co, or Ni).

High-fluorescent p-X-ferrites (XFe2O4; XFO; X = Fe, Cr, Mn, Co, or Ni) embedded in n-hematite (Fe2O3) surfaces were successfully fabricated via a facile bio-approach using Shewanella oneidensis MR-1. The results revealed that the X ions with high/low work functions modify the unpaired spin Fe2+-O2- orbitals in the XFe2O4 lattices to become localized paired spin orbitals at the bottom of conduction band, separating the photovoltage response signals (73.36~455.16/-72.63~-32.43 meV). These (Fe2O3)-O-O-(XFe2O4) interfacial coupling behaviors at two fluorescence emission peaks (785/795 nm) are explained via calculating electron-hole effective masses (Fe2O3-FeFe2O4 17.23 × 10-31 kg; Fe2O3-CoFe2O4 3.93 × 10-31 kg; Fe2O3-NiFe2O4 11.59 × 10-31 kg; Fe2O3-CrFe2O4 -4.2 × 10-31 kg; Fe2O3-MnFe2O4 -11.73 × 10-31 kg). Such a system could open up a new idea in the design of photovoltage response biosensors.

Spinal TRPC6 channels contributes to morphine-induced antinociceptive tolerance and hyperalgesia in rats.

The chronic administration of opioids results in the development of morphine analgesic tolerance and withdrawl-induced hyperalgesia, which limits their clinical utility in pain treatment. However, the cellular mechanisms underlying opioid-induced tolerance and hyperalgesia are not fully understood. The transient receptor potential canonical channel TRPC6 is important for brain development and function, as it regulates cytosolic, endoplasmic reticulum, and mitochondrial Ca2+ levels in neural cells. Here, we report that TRPC6 expression in the spinal cord was up-regulated after chronic morphine treatment. Furthermore, inhibition of TRPC6 in the spinal cord blocked the induction of morphine tolerance and hyperalgesia without affecting basal pain perception. These effects were attributed to the attenuation of morphine-induced neuroimmune activation and increased levels of CaMKIIα and nNOS in the spinal cord. This data suggests that specific TRPC6 inhibitors could be utilized for the prevention of morphine-induced antinociceptive tolerance and hyperalgesia in chronic pain management.