Pemetrexed plus Platinum as the First-Line Treatment Option for Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials

To compare the efficacy and toxicities of pemetrexed plus platinum with other platinum regimens in patients with previously untreated advanced non-small cell lung cancer (NSCLC). Methods: A meta-analysis was performed using trials identified through PubMed, EMBASE, and Cochrane databases. Two investigators independently assessed the quality of the trials and extracted data. The outcomes included overall survival (OS), progression-free survival (PFS), response rate (RR), and different types of toxicity. Hazard ratios (HRs), odds ratios (ORs) and their 95% confidence intervals (CIs) were pooled using RevMan software. Results: Four trials involving 2,518 patients with previously untreated advanced NSCLC met the inclusion criteria. Pemetrexed plus platinum chemotherapy (PPC) improved survival compared with other platinum-based regimens (PBR) in patients with advanced NSCLC (HR = 0.91, 95% CI: 0.83–1.00, p = 0.04), especially in those with non-squamous histology (HR = 0.87, 95% CI: 0.77–0.98, p = 0.02). No statistically significant improvement in either PFS or RR was found in PPC group as compared with PBR group (HR = 1.03, 95% CI: 0.94–1.13, p = 0.57; OR = 1.15, 95% CI: 0.95–1.39, p = 0.15, respectively). Compared with PBR, PPC led to less grade 3–4 neutropenia and leukopenia but more grade 3–4 nausea. However, hematological toxicity analysis revealed significant heterogeneities. Conclusion: Our results suggest that PPC in the first-line setting leads to a significant survival advantage with acceptable toxicities for advanced NSCLC patients, especially those with non-squamous histology, as compared with other PRB. PPC could be considered as the first-line treatment option for advanced NSCLC patients, especially those with non-squamous histology

Study on mass transfer property of oxygen molecules and kinetic regimes of pressured pulverized coal combustion

The effects of pressure on diffusion of oxygen molecules during the coal combustion could not be ignored. The compressibility factor of real oxygen is investigated to evaluate the deviation between real and ideal oxygen, and obtain the mean free path of real oxygen. Comparing the Knudsen pore diameter with the minimum pore diameter, it is found that with the increase of pressure, Knudsen diffusion cannot exist at low pressure and may delay to occur at higher temperature. When pressure exceeds 3.5 MPa, no Knudsen diffusion occurs within the whole temperature range of our research. Comparing the diffusion rate at 1 MPa with the burning rate, one can conclude that the combustion mainly take place on the internal and external surfaces, and the reaction is controlled by the chemical kinetics below 1400 K. When themperature is between 1400 K and 1600 K, the reaction is controlled by both the diffusion and the chemical kinetics. When the temperature is more than 1600 K, the combustion primarily happens on the external surfaces and is controlled by the diffusion

Experimental Investigation of Gaseous Sodium Release in Slag-Tapping Coal-Fired Furnaces by Spontaneous Emission Spectroscopy

High-alkali coal is rich in alkali metals, which can cause serious effects such as slagging and corrosion on the heating surface during combustion and utilization. A portable spectral system was utilized to simultaneously measure gaseous Na concentration and temperature in a 20 kW slag-tapping combustor and a slagging boiler furnace of a 300 MW power generation unit by flame spontaneous emission spectroscopy (FES) for simultaneous measuring. The result shows that both ZD-FK and ZD-HSQ (Fukang coal and Hongshaquan coal, Xinjiang Zhundong high-alkali coal) combustion flame temperatures are around 1400 °C at the outlet of the cyclone burner while the latter is slightly higher. The sodium concentration in the gas phase increases with the rising of the initial combustion temperature and unit load for one kind of coal, and the level of sodium concentration has a strong correlation with the Na content for different coal. Most of the sodium in the high temperature zone of the furnace exists in the form of gas phase, and more sodium migrates to fly ash. Combined with the analysis of fly ash and liquid slag samples, a closed-loop analysis of the Na migration path could be established

A Proteomic Study of the Effect of N-acetylcysteine on the Regulation of Early Pregnancy in Goats

Dietary supplementation with N-acetyl-L-cysteine (NAC) may support early pregnancy regulation and fertility in female animals. The purpose of this study was to investigate the effect of supplementation with 0.07% NAC on the expression of the uterine keratin gene and protein in Qianbei-pockmarked goats during early pregnancy using tandem mass spectrometry (TMT) relative quantitative proteomics. The results showed that there were significant differences in uterine keratin expression between the experimental group (NAC group) and the control group on day 35 of gestation. A total of 6271 proteins were identified, 6258 of which were quantified by mass spectrometry. There were 125 differentially expressed proteins (DEPs), including 47 upregulated and 78 downregulated proteins, in the NAC group. Bioinformatic analysis showed that these DEPs were mainly involved in the transport and biosynthesis of organic matter and were related to the binding of transition metal ions, DNA and proteins and the catalytic activity of enzymes. They were enriched in the Jak-STAT signalling pathway, RNA monitoring pathway, amino acid biosynthesis, steroid biosynthesis and other pathways that may affect the early pregnancy status of does through different pathways and thus influence early embryonic development. Immunohistochemistry, real-time quantitative PCR and Western blotting were used to verify the expression and localization of glial fibrillary acidic protein (GFAP) and pelota mRNA surveillance and ribosomal rescue factor (PELO) in uterine horn tissue. The results showed that both PELO and GFAP were localized to endometrial and stromal cells, consistent with the mass spectrometry data at the transcriptional and translational levels. Moreover, NAC supplementation increased the levels of the reproductive hormones follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol (E2), progesterone (P4), superoxide dismutase (SOD), glutamate peroxidase (GSH-Px) and nitric oxide (NO) in the serum of does. These findings provide new insight into the mechanism by which NAC regulates early pregnancy and embryonic development in goats

Bioinformatic and Functional Analysis of a Key Determinant Underlying the Substrate Selectivity of the Al Transporter, Nrat1

Nrat1 is a member of the natural resistance-associated macrophage protein (Nramp) family of metal ion transporters in all organisms. Different from other Nramp members capable of transporting divalent metals, Nrat1 specifically transports trivalent aluminum (Al) ion. However, molecular mechanism underlying the Al transport selectivity of Nrat1 remains unknown. Here, we performed structure-function analyses of Nrat1 and other Nramp members to gain insights into the determinants of ion selectivity. A phylogenetic analysis showed that plant Nramp transporters could be divided into five groups. OsNrat1 was found in one of the individual clades and clustered with SbNrat1 and ZmNrat1 on the evolutionary tree. Structural modeling revealed that Nrat1 transporters adopted a common LeuT fold shared by many Nramp-family transporters that likely employed an identical transport mechanism. Sequence alignment and evolutionary conservation analysis of amino acids identified a metal-permeation pathway of Nrat1 centered at the metal binding site. The metal binding site of Nrat1 was characterized by two conserved sequence motifs, i.e., the Asp-Pro-Ser-Asn motif (motif A) and the Ala-Ile-Ile-Thr motif (motif B). Replacement of the Ala-Met-Val-Met motif B of the OsNramp3 manganese (Mn) transporter to that of Nrat1 resulted in a partial gain of Al transport activity and a total loss of Mn in yeast. Conversely, substitution of the motif B of OsNrat1 with that of OsNramp3 altered the Al transport activity. These observations indicated the metal binding site, particularly the motif B, as a key determinant of Al selectivity of Nrat1

Effects of N Acetylcysteine on the Expression of Genes Associated with Reproductive Performance in the Goat Uterus during Early Gestation

N acetylcysteine (NAC) affects antioxidation and reactive oxygen species scavenging in the body and thereby promotes embryonic development and implantation and inhibits inflammation. The mechanism through which NAC regulates reproductive performance in the uteri of goats during early gestation remains unclear. In this study, the treatment group was fed 0.07% NAC for the first 35 days of gestation, whereas the control group received no NAC supplementation. The regulatory genes and key pathways associated with goat reproductive performance under NAC supplementation were identified by RNA-seq. RT–qPCR was used to verify the sequencing results and subsequently construct tissue expression profiles of the relevant genes. RNA-seq identified 19,796 genes coexpressed in the control and treatment groups and 1318 differentially expressed genes (DEGs), including 787 and 531 DEGs enriched in the treatment and control groups, respectively. A GO analysis revealed that the identified genes mapped to pathways such as cell activation, cytokine production, cell mitotic processes, and angiogenesis, and a KEGG enrichment analysis showed that the DEGs were enriched in pathways associated with reproductive regulation, immune regulation, resistance to oxidative stress, and cell adhesion. The RT–qPCR analysis showed that BDNF and CSF-1 were most highly expressed in the uterus, that WIF1 and ESR2 showed low expression in the uterus, and that CTSS, PTX3, and TGFβ-3 were most highly expressed in the oviduct, which indicated that these genes may be directly or indirectly involved in the modulation of reproduction in early-gestation goats. These findings provide fundamental data for the NAC-mediated modulation of the reproductive performance of goats during early gestation