The ortholog of human REEP1-4 is required for autophagosomal enclosure of ER-phagy/nucleophagy cargos in fission yeast.

Selective macroautophagy of the endoplasmic reticulum (ER) and the nucleus, known as ER-phagy and nucleophagy, respectively, are processes whose mechanisms remain inadequately understood. Through an imaging-based screen, we find that in the fission yeast Schizosaccharomyces pombe, Yep1 (also known as Hva22 or Rop1), the ortholog of human REEP1-4, is essential for ER-phagy and nucleophagy but not for bulk autophagy. In the absence of Yep1, the initial phase of ER-phagy and nucleophagy proceeds normally, with the ER-phagy/nucleophagy receptor Epr1 coassembling with Atg8. However, ER-phagy/nucleophagy cargos fail to reach the vacuole. Instead, nucleus- and cortical-ER-derived membrane structures not enclosed within autophagosomes accumulate in the cytoplasm. Intriguingly, the outer membranes of nucleus-derived structures remain continuous with the nuclear envelope-ER network, suggesting a possible outer membrane fission defect during cargo separation from source compartments. We find that the ER-phagy role of Yep1 relies on its abilities to self-interact and shape membranes and requires its C-terminal amphipathic helices. Moreover, we show that human REEP1-4 and budding yeast Atg40 can functionally substitute for Yep1 in ER-phagy, and Atg40 is a divergent ortholog of Yep1 and REEP1-4. Our findings uncover an unexpected mechanism governing the autophagosomal enclosure of ER-phagy/nucleophagy cargos and shed new light on the functions and evolution of REEP family proteins.

Orientation Manipulation and Defect Passivation for Perovskite Solar Cells by a Natural Compound.

Different facets in perovskite crystals exhibit distinct atomic arrangements, influencing their electronic, physical, and chemical properties. Perovskite films incorporating tin oxide (SnO2) as the electron transport layer face challenges in facet regulation. This study reveals that tea saponin (TS), a natural compound serves as a SnO2 modifier, facilitates optimal growth of perovskite crystals on the (111) facet. The modification promotes preferential crystal orientation through hydrogen bond and Lewis coordination. TS forms a chelate with SnO2, resulting in a smoother film and n-type doping, leading to improved carrier extraction and reduced defects. The TS-modified perovskite solar cells achieve a champion efficiency of 24.2%, leveraging from an obvious enhancement of open-circuit voltage (Voc) of 1.18 V and fill factor (FF) of 82.8%. The devices also demonstrate enhanced humidity tolerance and storage stability, ensuring improved stability without encapsulation.

Preliminary results of randomized phase II study of etoposide plus lobaplatin or etoposide plus cisplatin with concurrent thoracic radiotherapy in the treatment of limited-stage small cell lung cancer.

The purpose is to compare the clinical efficacy and toxicity of etoposide plus lobaplatin (EL) or etoposide plus cisplatin (EP) with concurrent thoracic radiotherapy during the treatment of limited-stage small cell lung cancer (LS-SCLC). Forty-two patients with LS-SCLC were randomly divided into EL ( n = 19) or EP ( n = 23) regimens combined with thoracic intensity-modulated radiotherapy. The primary endpoint was 1-year progression-free survival (PFS) rate. The 1-, 2-, and 3-year PFS rates in the EL and EP cohorts were 50.8, 38.1, and 12.7%; and 56.5, 43.5, and 29.0%, respectively ( P = 0.527), whereas the 1-, 2-, and 3-year overall survival (OS) rates were 72.2, 52.5, and 43.8%; and 73.9, 48.4, and 48.4%, respectively ( P = 0.923). The hematological toxicities were similar in two cohorts. However, gastrointestinal reactions were more severe in the EP group. The incidence of nausea and vomiting in EL and EP cohorts were 31.6% vs. 73.9% ( P = 0.006) and 20.1% vs. 60.9% ( P = 0.009), respectively. The two cohorts did not show ≥grade 4 radiation esophagitis and ≥grade 3 radiation pneumonitis. The incidence of acute radiation esophagitis in EL group was lower ( P = 0.038), both groups showed a similar incidence of radiation pneumonitis ( P = 1.000). EL or EP chemotherapy with concurrent thoracic radiotherapy showed similar PFS and OS. The EL group showed milder gastrointestinal toxicity and radiation esophagitis. Radiation pneumonitis and hematological toxicity were similar in the two regimens, which can be tolerated by patients.

Effect of aerobic exercise on cardiotoxic outcomes in women with breast cancer undergoing anthracycline or trastuzumab treatment: a systematic review and meta-analysis.

PURPOSE: We aimed to assess the impact of aerobic exercise (AE) on parameters related to cardiotoxicity in breast cancer (BC) patients receiving anthracycline or trastuzumab. METHODS: We performed a systematic review and meta-analysis of comparative studies on AE via the screening of standard databases from their inception to January 18, 2022. The risk of bias was assessed qualitatively using the domains outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Data were analyzed quantitatively using fixed effects meta-analysis and subgroup analysis in RevMan software. Notable outcomes included imaging outcomes of cardiotoxicity, cardiorespiratory fitness, and cardiac biomarkers. RESULTS: A meta-analysis of the pooled evidence obtained from seven studies revealed that AE significantly increased peak oxygen consumption (VO2 peak) and E/A values, compared to the values observed during usual care. Moreover, AE was safe and feasible, and was associated with a lower risk of adverse effects, a higher participation rate, and better results, when combined with resistance exercise. CONCLUSION: In BC patients receiving anthracyclines or trastuzumab, the effects of AE on the levels of cardiotoxicity were mixed; the diastolic functions and VO2 peak values were improved, biomarkers were not affected, and the overall improvements in the levels of cardiotoxicity were promising, despite the use of different exercise parameters.

Fatty acid desaturase 2 affects the milk-production traits in Chinese Holsteins.

As a member of the fatty acid desaturase family, fatty acid desaturase 2 (FADS2) gene is a rate-limiting enzyme in the synthesis of unsaturated fatty acids and within/near to the reported QTL regions for milk-production traits. We previously found that FADS2 is differentially expressed during different lactations of Chinese Holstein cows, and participates in lipid metabolic processes by influencing the insulin, PI3K-Akt, MAPK, AMPK, mTOR and PPAR signaling pathways. Therefore, we considered this gene as a candidate gene for milk-production traits. In this study, we identified 12 SNPs in FADS2 by re-sequencing, including two SNPs in the 5' flanking region, one in the seventh exon, five in introns, two in the 3' untranslated region and two in the 3' flanking region. The 29:g.40378819C>T is a missense mutation that causes alanine (GCG) to be replaced with valine (GTG). Through single marker association analysis, we found that all of the 12 SNPs were significantly associated with 305 day milk yield, fat yield, fat percentage, protein yield or protein percentage (p < 0.0493). The results of the subsequent haplotype association analysis also confirmed the associations between the gene and milk-production traits. In summary, this study suggests that there is a significant genetic association between FADS2 and milk-production traits, and that the SNPs with significant genetic effects can provide important molecular information for the development of a genomic selection chip in dairy cattle.

Determination of genetic effects and functional SNPs of bovine HTR1B gene on milk fatty acid traits.

BACKGROUND: Our previous genome-wide association study (GWAS) on milk fatty acid traits in Chinese Holstein cows revealed, the SNP, BTB-01556197, was significantly associated with C10:0 at genome-wide level (P = 0.0239). It was located in the down-stream of 5-hydroxytryptamine receptor 1B (HTR1B) gene that has been shown to play an important role in the regulation of fatty acid oxidation. Hence, we considered it as a promising candidate gene for milk fatty acids in dairy cattle. In this study, we aimed to investigate whether the HTR1B gene had significant genetic effects on milk fatty acid traits. RESULTS: We re-sequenced the entire coding region and 3000 bp of 5' and 3' flanking regions of HTR1B gene. A total of 13 SNPs was identified, containing one in 5' flanking region, two in 5' untranslated region (UTR), two in exon 1, five in 3' UTR, and three in 3' flanking region. By performing genotype-phenotype association analysis with SAS9.2 software, we observed that 13 SNPs were significantly associated with medium-chain saturated fatty acids such as C6:0, C8:0 and C10:0 (P < 0.0001 ~ 0.042). With Haploview 4.1 software, linkage disequilibrium (LD) analysis was performed. Two haplotype blocks formed by two and ten SNPs were observed. Haplotype-based association analysis indicated that both haplotype blocks were strongly associated with C6:0, C8:0 and C10:0 as well (P < 0.0001 ~ 0.0071). With regards to the missense mutation in exon 1 (g.17303383G > T) that reduced amino acid change from alanine to serine, we predicted that it altered the secondary structure of HTR1B protein with SOPMA. In addition, we predicted that three SNPs in promoter region, g.17307103A > T, g.17305206 T > G and g.17303761C > T, altered the binding sites of transcription factors (TFs) HMX2, PAX2, FOXP1ES, MIZ1, CUX2, DREAM, and PPAR-RXR by Genomatix. Of them, luciferase assay experiment further confirmed that the allele T of g.17307103A > T significantly increased the transcriptional activity of HTR1B gene than allele A (P = 0.0007). CONCLUSIONS: In conclusion, our findings provided first evidence that the HTR1B gene had significant genetic effects on milk fatty acids in dairy cattle.

Laser frequency stabilization via bichromatic Doppler-free spectroscopy of an 87Rb D1 line.

We demonstrate a bichromatic Doppler-free spectroscopy of an 87RbD1 line by using a dual-frequency, counterpropagating laser field with orthogonal linear polarizations. A reversed Doppler-free resonance dip is observed in the dual-frequency scheme, and a significant improvement of frequency discrimination curve is acquired due to the coherent population trapping (CPT) effect. The influence of the static magnetic field and laser intensity on the spectroscopy is studied in both single- and dual-frequency schemes. After locking the laser frequency to the 87RbD1 line in the dual-frequency stabilization scheme, the beat note fractional frequency stability is at the level of 7×10-12 at 1 s integration time. This technique can be used in various applications, such as CPT atomic clocks, laser spectroscopy, quantum optics, and laser-cooling experiments.

Transformation of ginsenoside via deep eutectic solvents based on choline chloride as an enzymatic reaction medium.

Ginsenoside compound K (CK) with a wide range of pharmacological activities has been widely used in the healthcare product industry. However, the application of CK is limited by low productivity and difficult separation. The purpose of this study is to convert ginsenoside Rb1 into CK by improving conversion efficiency in novel "green" reaction medium-deep eutectic solvent (DES). Talaromyces purpureogenus was selected from ginseng rhizosphere soil to produce ß-glucosidase with high activity and purity to transform ginsenosides, and Mn2+ was found to be an enzyme promoter. Among the DES based on choline chloride as hydrogen-bond receptor, choline chloride:ethylene glycol (ChCl:EG = 2:1) was the most promising solvent in maintaining enzyme activity and stability. In the presence of 30% v/v ChCl:EG = 2:1, the half-life of ß-glucosidase was increased by 96%, the solubility of F2 was increased by 120%, and CK yield was increased by 54% compared with those in the buffer. Fourier transform infrared, circular dichroism, and fluorescence spectroscopy confirmed that DES did not destroy the structure and conformation of ß-glucosidase. In addition, 80.6% CK conversion was obtained at 60 °C, pH 4.5, 48 h and 8 mM Rb1, which provided a feasible method for efficiently producing CK.

A post-GWAS confirming effects of PRKG1 gene on milk fatty acids in a Chinese Holstein dairy population.

BACKGROUND: We previously conducted a genome-wide association study (GWAS) strategy for milk fatty acids in Chinese Holstein, and identified 83 genome-wide significant single nucleotide polymorphisms (SNPs) and 314 suggestive significant SNPs. Among them, two SNPs, BTB-01077939 and BTA-11275-no-rs associated with C10:0, C12:0, and C14 index (P = 0.000014 ~ 0.000024), were within and close to (0.85 Mb) protein kinase, cGMP-dependent, type І (PRKG1) gene on BTA26, respectively. PRKG1 gene plays a key role in lipolysis to release fatty acids and glycerol through the hydrolysis of triacyglycerol in adipocytes. We herein considered it as a promising candidate for milk fatty acids. The purpose of this study was to investigate whether PRKG1 had effects on milk fatty acids. RESULTS: By direct sequencing the PCR products of pooled DNA, we identified a total of six SNPs, including one in 5' flanking region, four in 3' untranslated region (UTR), and one in 3' flanking region. The single-locus association analysis was carried out, and showed that the six SNPs mainly had significant associations with C6:0, C8:0 and C17:1 (P < 0.0001 ~ 0.0035). In addition, we observed a haplotype block formed by g.6903810G > A and g.6904047G > T with Haploview 4.1, and it was strongly associated with C8:0, C10:0, C16:1, C17:1, C20:0 and C16 index (P = < 0.0001 ~ 0.0123). The SNP, g.8344262A > T, was predicted to alter the binding site (BS) of transcription factor (TF) GAGA box with Genomatix software, and the subsequent luciferase assay verified that it really changed the transcriptional activity of PRKG1 gene (P = 0.0009). CONCLUSION: In conclusion, to our best of knowledge, we are the first who identified the significant effects of PRKG1 on milk fatty acids in dairy cattle.

Polymorphisms and genetic effects of PRLR, MOGAT1, MINPP1 and CHUK genes on milk fatty acid traits in Chinese Holstein.

BACKGROUND: Our initial genome-wide association study (GWAS) identified 20 promising candidate genes for milk fatty acid (FA) traits in a Chinese Holstein population, including PRLR, MOGAT1, MINPP1 and CHUK genes. In this study, we performed whether they had significant genetic effects on milk FA traits in Chinese Holstein. RESULTS: We re-sequenced the entire exons and 3000 bp of the 5' and 3' flanking regions, and identified 11 single nucleotide polymorphisms (SNPs), containing four in PRLR, two in MOGAT1, two in MINPP1, and three in CHUK. The SNP-based association analyses showed that all the 11 SNPs were significantly associated with at least one milk FA trait (P = 0.0456 ~ < 0.0001), and none of them had association with C11:0, C13:0, C15:0 and C16:0 (P > 0.05). By the linkage disequilibrium (LD) analyses, we found two, one, one, and one haplotype blocks in PRLR, MOGAT1, MINPP1, and CHUK, respectively, and each haplotype block was significantly associated with at least one milk FA trait (P = 0.0456 ~ < 0.0001). Further, g.38949011G > A in PRLR, and g.111599360A > G and g.111601747 T > A in MOGAT1 were predicted to alter the transcription factor binding sites (TFBSs). A missense mutation, g.39115344G > A, could change the PRLR protein structure. The g.20966385C > G of CHUK varied the binding sequences for microRNAs. Therefore, we deduced the five SNPs as the potential functional mutations. CONCLUSION: In summary, we first detected the genetic effects of PRLR, MOGAT1, MINPP1 and CHUK genes on milk FA traits, and researched the potential functional mutations. These data provided the basis for further investigation on function validation of the four genes in Chinese Holstein.

Pemetrexed plus cisplatin versus docetaxel plus cisplatin for stage IV lung adenocarcinoma based on propensity score matching.

The aim of this study was to compare the clinical efficacy of pemetrexed+cisplatin (PP) versus docetaxel+cisplatin (DP) for the treatment of stage IV lung adenocarcinoma. We retrospectively analyzed the clinical data of 147 patients with stage IV lung adenocarcinoma treated between January 2011 and December 2015, 100 of which were in the DP group whereas 47 were in the DP group. Main inclusion criteria were treatment-naive patients, first-line treatment with PP or DP with no molecular targeted therapy during treatment, 2-6 cycles of first-line chemotherapy with unknown status of epidermal growth factor receptor (EGFR) mutation, 18-75 years of age, and Karnofsky performance status score of at least 70. Prognostic factors for survival were identified by using univariate and multivariate analyses. Propensity score matching was performed to further adjust for confounding. A total of 47 pairs were successfully matched between the two groups. The median overall survival was 9.0 months in the DP group and 17.0 months in the PP group; the 1-year survival rate was 29.8 and 59.6%, respectively; the 2-year survival rate was 12.8 and 21.1%, respectively (χ=4.128, P=0.042); and median progression-free survival was 6.0 and 8.0 months, respectively (χ=4.839, P=0.028). Cox multivariate analysis showed that chemotherapy regimen and number of metastatic organs were independent factors for OS. The effect of the radiotherapy dose on the primary tumor on OS was close to statistically significant. The incidence of grade 3-4 neutropenia was more significantly reduced in the DP group than in the PP group after matching (61.7 vs. 27.7%, P=0.002), with no between-group difference for adverse effects on platelets or hemoglobin. For patients with stage IV lung adenocarcinoma and unknown EGFR mutation status, PP was more effective than DP in prolonging survival and had a less adverse effect on neutrophils.

[Design and Implementation of Remote Firmware Update System Based on IAP Technology].

This paper introduces a network remote firmware update system based on IAP technology, which aims to solve the problems of low efficiency and high cost in the traditional upgraded medical device firmware (lower computer program) mode, and to improve the portability of the lower computer program upgrade maintenance. In order to better cope with market changes, customer needs, and solve software failures in medical devices, it is necessary to update and upgrade medical device software in a timely manner. Through the IAP technology and Internet communication technology of STM32 platform, this solution can complete the update of all instrument firmware in a short time, which not only saves a lot of travel expenses, mailing costs and labor costs, but also greatly shortens the update time.

Potential accumulation of protopanaxadiol-type ginsenosides in six-months toxicokinetic study of SHENMAI injection in dogs.

SHENMAI injection (SMI), derived from famous Shen Mai San, is a herbal injection widely used in China. Ginsenosides are the major components of SMI. To monitor the exposure level of SMI during long-term treatment, a 6-month toxicokinetic experiment was performed. Twenty-four beagle dogs were dived into four groups (n = 6 in each group): a control group (0.9% NaCl solution) and three SMI groups (2, 6 or 3 mg/kg). The dogs were i.v. infused with vehicle or SMI daily for 180 d. Blood samples for analysis were collected at specific time points as follows: pre-dose (0 h); at 10, 30, and 60 min during infusion; and at 10, 30, 60, 90, 120, 240, and 300 min post-administration. Concentrations of ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1 in the plasma were determined simultaneously by liquid chromatography-tandem mass spectrometry. Non-compartmental parameters were further calculated and analyzed. Significant differences were found between the kinetic behavior of 20(S)-protopanaxadiol-type (PPD-type) and 20(S)-protopanaxatriol-type (PPT-type) ginsenosides. Increasing in the exposure level of PPD-type ginsenosides was observed in dogs during the experiment. Therefore, PPD-type ginsenosides are closely related to the immunity modulation effect of SMI. Increased PPD-type ginsenoside exposure level may present potential toxicity and induce drug-drug interaction risks during SMI administration. As such, PPD-type ginsenoside accumulation must be carefully monitored in future SMI research.

Might radiation therapy in addition to chemotherapy improve overall survival of patients with non-oligometastatic Stage IV non-small cell lung cancer?: Secondary analysis of two prospective studies.

BACKGROUND: The role of radiation therapy in addition to chemotherapy has not been well established in non-oligometastatic Stage IV non-small cell lung cancer (NSCLC). We aimed to investigate overall survival (OS) of non-oligometastatic Stage IV NSCLC treated with chemotherapy with concurrent radiation to the primary tumor. METHODS: Eligible patients were screened from two prospective studies. Oligometastatic and non-oligometastatic NSCLC were defined as having < 5 and ≥5 metastatic lesions, respectively. Prognostic factors for OS were identified by using univariate and multivariate analysis. Landmark analysis and propensity-score matching (PSM) were each performed to further adjust for confounding. RESULTS: A total of 274 patients were identified as the study cohort: 183 had non-oligometastatic disease. For all 274 patients, those who received a radiation dose ≥63 Gy to the primary tumor and had oligometastatic disease had better OS (P < 0.001 and P = 0.017, respectively). When patients were subdivided into those with oligometastatic or non-oligometastatic disease, a radiation dose ≥ 63 Gy remained a significant prognostic factor for better OS. For non-oligometastatic patients, multivariate analysis showed that receiving ≥63 Gy radiation, having a GTV <146 cm3, having response to chemotherapy, and having stable or increased post-treatment KPS independently predicted better OS (P = 0.018, P = 0.014, P = 0.014, and P = 0.001). After PSM in non-oligometastatic patients, a higher radiation dose (≥63 Gy) remained to be correlated with better OS. By landmark analysis, aggressive radiation (≥63 Gy) remained to be correlated with better OS in Pre-PSM cohort (P = 0.005) and Post-PSM cohort (P = 0.004). CONCLUSIONS: Radiation dose, primary tumor volume, response to chemotherapy and KPS after treatment are associated with OS in patients with non-oligometastatic disease; on basis of effective system chemotherapy, aggressive thoracic radiotherapy may prolong OS.

Atmospheric and Aqueous Deposition of Polycrystalline Metal Oxides Using Mist-CVD for Highly Efficient Inverted Polymer Solar Cells.

Large scale, cost-effective processing of metal oxide thin films is critical for the fabrication of many novel thin film electronics. To date, however, most of the reported solution-based techniques require either extended thermal anneals or additional synthetic steps. Here we report mist chemical vapor deposition as a solution-based, readily scalable, and open-air method to produce high-quality polycrystalline metal oxide thin films. Continuous, smooth, and conformal deposition of metal oxide thin films is achieved by tuning the solvent chemistry of Leidenfrost droplets to promote finer control over the surface-local dissociation process of the atomized zinc-bearing precursors. We demonstrate the deposited ZnO as highly efficient electron transport layers for inverted polymer solar cells to show the power of the approach. A highest efficiency of 8.7% is achieved with a fill factor of 73%, comparable to that of conventional so-gel ZnO, which serves as an indication of the efficient vertical transport and electron collection achievable using this material.

Bilateral Medial Medullary Infarction with Nondominant Vertebral Artery Occlusion.

Bilateral medial medullary infarction (MMI) is a rare stroke subtype. Here, we report a case with bilateral MMI caused by nondominant vertebral artery occlusion confirmed by brain digital subtraction angiography and magnetic resonance imaging basi-parallel-anatomical-scanning. We highlight that anterior spinal arteries could originate from a unilateral vertebral artery (VA). Radiologists and neurologists should pay attention to the nondominant VA as bilateral MMI may be induced by occlusion of nondominant VA that supplies the bilateral anteromedial territories of the medulla.

[The effect of edaravone on MAPKs signal pathway associated with Abeta(25-35) treatment in PC12 cells].

OBJECTIVE: To explore whether edaravone protects cells damage via mitogen-activated protein kinases (MAPKs) signal pathway, and which procedure of p38 be affected so as to add theories for AD pathogenesis and treatments. METHODS: According to different drugs treated, PC12 cells in vitro were divided into four groups. Negative control group: cells were treated with media alone. AD model group: cells were treated with 30 pmol/L Abeta(25-35). Inhibitor control group: cells were treated with 10 micromol/L SB203580 Cp38 mitogen-activated protein kinase (p38) inhibitor], 10 micromol/L SP600125 [c-Jun NH2 terminal kinase (JNK) inhibitor], or 10 micromol/L PD98059 extracelular signal regulated kinase (ERK) inhibitor]. Low-dose, middle-dose and high-dose edaravone group: cells plated for 24 hours treated with 30 micromol/L Abeta(25-35) and co-treated with 20, 40, 80 micromol/L edaravone 3 hours, respectively. The morphology of the treated cells were observed, the p-p38, p-JNK and p-ERK proteins in each group were tested by the Western blot. The p38 mRNA were tested in each group above (only add SB203580 10 micromol/L in third group) by the real time PCR. RESULTS: (1) The p-p38 protein was significantly increased in model control group compared with that in negative control group (P<0.05). The p-p38 protein in the inhibitor group and edaravone groups was decreased significantly (P<0.05) when compared with that in model control group. The p-p38 proteins were significantly increased in the three edaravone groups compared with that in inhibiter control group (P<0.05). The p-p38 protein in middle-dose edaravone group was decreased compared with that in low-dose edaravone group (P<0.05). There was no relationship in dose-dependent manner about edaravone. Compared with three edaravone groups, the p-p38 protein was lower than it in high-dose edaravone & inhibiter group (P<0.05). (2) The p-JNK protein was significantly increased in model control group compared with that in negative control group (P<0.05). The p-JNK protein in the inhibitor group was decreased compared with that in model control group (P<0.05). (3) No significantly difference of p-ERK protein concentration was observed in other groups when compared with that in negative control group (P>0.05 each). (4) Compared with negative control group, the p38 mRNA in model control group was significantly increased, and it was significantly decreased in inhibitor control group (P<0.05 each). In 40 micromol/L and 80 micromol/L edaravone groups, the p38 mRNA was significantly decreased compared with that in model control group, and it still was decreased compared with that in inhibitor control group (P<0.05). The p38 mRNA in 40 micromol/L edaravone group was the lowest among three edaravone groups, and it was obviously different from that in 20 micromol/L and 80 micromol/L edaravone groups (P<0.05). CONCLUSION: Abeta(25-35) could increase the p-p38 and p-JNK protein expression in cultured PC12 cells, but there was no obviously expression of p-ERK protein. These indicated that Abeta(25-35) might activate MAPKs signal pathway, especially p38 and JNK, and lead to PC12 cell damage. Edaravone could decrease p38 mRNA induced-Abeta(25-35), which indicated edaravone could protect PC12 cell damage via blocking p38 signal pathway in mRNA stage and protein stage simultaneously. Hence, it is promising that edaravone would be a new medicine for AD.

Radiation dose and survival of patients with stage IV non-small cell lung cancer undergoing concurrent chemotherapy and thoracic three-dimensional radiotherapy: reanalysis of the findings of a single-center prospective study.

BACKGROUND: The objective of this study was to evaluate the radiation dose and response in terms of local-regional progression-free survival (LRPFS) and overall survival (OS) of patients with stage IV non-small cell lung cancer (NSCLC) undergoing concurrent chemotherapy and thoracic three-dimensional radiotherapy. METHODS: In all, we enrolled 201 patients with stage IV NSCLC in this study and analyzed OS in 159 patients and LRPFS in 120. RESULTS: The 1-, 2-, 3-, and 5-year OS rates were 46.2%, 19.5%, 11.7%, and 5.8%, respectively, the median survival time being 12 months. The median survival times in differential treatment response of primary tumors were 19 of complete response, 13 of partial response, 8 of stable disease, and 6 months of progressive disease, respectively (P = 0.000). The 1-, 2-, 3-, and 5-year LRPFS rates of patients undergoing four to five cycles with doses ≥63 Gy and <63 Gy were 77.4% and 32.6%, 36.2% and 21.7%, 27.2% and 0, and 15.9% and 0, respectively (P = 0.002). According to multivariate analyses, four to five cycles of chemotherapy, gross tumor volume <175.00 cm3 and post-treatment Karnofsky Performance Status score stable or increased by at least 10 units were independent prognostic factors for better OS (P = 0.035, P = 0.008, and P = 0.000, respectively). Radiation dose to the primary tumor ≥63 Gy resulted in better OS (P = 0.057) and LRPFS (P = 0.051), both findings being of borderline significance. CONCLUSIONS: Treatment of IV NSCLC with joint administration of four to five cycles of chemotherapy and three-dimensional radiotherapy may prolong survival, particularly in patients receiving ≥63 Gy radiotherapy, with gross tumor volume <175.00 cm3 and post-treatment Karnofsky Performance Status score not lower than pretreatment values.

A study on the impact of housing prices on residents' travel frequency and transportation resilience in 35 Chinese cities.

As urbanization proceeds, urban transportation resilience suffers greater challenges. Covering panel data for 35 Chinese cities from 2006 to 2019, after controlling for other variables that may affect urban residents' transportation volumes, this paper finds that rising houseing prices have a significant positive effect on urban residents' traffic frequency. As frequent traffic trips increase the probability of urban residents experiencing disruptions, rising housing purchase prices would have a negative impact on Chinese urban residents' transportation resilience. The regional comparison analysis finds that the regression coefficients of coastal and eastern cities with more expensive housing price are significantly higher than those of non-coastal and western cities with lower housing price, further validating the findings of this paper.

Hierarchical attention-guided multiscale aggregation network for infrared small target detection.

All man-made flying objects in the sky, ships in the ocean can be regarded as small infrared targets, and the method of tracking them has been received widespread attention in recent years. In search of a further efficient method for infrared small target recognition, we propose a hierarchical attention-guided multiscale aggregation network (HAMANet) in this thesis. The proposed HAMANet mainly consists of a compound guide multilayer perceptron (CG-MLP) block embedded in the backbone net, a spatial-interactive attention module (SiAM), a pixel-interactive attention module (PiAM) and a contextual fusion module (CFM). The CG-MLP marked the width-axis, height-axis, and channel-axis, which can result in a better segmentation effect while reducing computational complexity. SiAM improves global semantic information exchange by increasing the connections between different channels, while PiAM changes the extraction of local key information features by enhancing information exchange at the pixel level. CFM fuses low-level positional information and high-level channel information of the target through coding to improve network stability and target feature utilization. Compared with other state-of-the-art methods on public infrared small target datasets, the results show that our proposed HAMANet has high detection accuracy and a low false-alarm rate.