Calculation and characteristic analysis of water vapor content in the north slope of the Middle Kunlun Mountains

The water vapor changes in arid areas could affect the structure and evolution of water resource systems in their surrounding areas. Based on the precipitable atmospheric water vapor (GPS-PWV) of 4 ground-based GPS stations, the observation data of 2 sounding stations and the hourly surface pressure water vapor data of 108 meteorological observation stations on the north slope of the Middle Kunlun Mountains from January 2020 to December 2022, this study established the atmospheric water vapor content and surface water vapor pressure (W-e) model suitable for the north slope of the Middle Kunlun Mountains using the unary linear fitting method. The results of water vapor content calculated by this model were verified. Then we analyzed the distribution characteristics of atmospheric water vapor content in the western section, the middle section, and the eastern section of the study area, as well as the relationship between the beginning time of precipitation and the W-PWV peak value. The results show that: (1) The annual mean W-PWV is largest in the western section of the study area, followed by the middle section, and the smallest in the eastern section which located in the southern edge of the desert. The W-PWV of the stations with altitude greater than 1 500 m gradually decrease with altitude increasing. The average W-PWV of each meteorological observation station in summer is about twice than that in spring and autumn. (2) The monthly variation of W-PWV shows a unimodal distribution characteristic. The W-PWV of the stations with an altitude higher than 1 300 m but lower than 1 500 m reached its peak in July and August, while that of the other stations reached its peak in August. The W-PWV of stations with an altitude below 2 000 m and above 2 000 m maintained a high value at night and during the day, respectively, which may be related to the thermal difference between mountain and basin from daytime to nighttime. (3) There is a good correspondence between the W-PWV calculated by W-e model and the beginning time of precipitation. Before precipitation, the W-PWV of each station is jumped varying degrees, and the peak value of W-PWV within 1-2 h before the precipitation is more than 1.5 times of the monthly average value of W-PWV

The Zinc Content of HIV-1 NCp7 Affects Its Selectivity for Packaging Signal and Affinity for Stem-Loop 3

The nucleocapsid (NC) protein of human immunodeficiency (HIV) is a small, highly basic protein containing two CCHC zinc-finger motifs, which is cleaved from the NC domain of the Gag polyprotein during virus maturation. We previously reported that recombinant HIV-1 Gag and NCp7 overexpressed in an E. coli host contains two and one zinc ions, respectively, and Gag exhibited much higher selectivity for packaging signal (Psi) and affinity for the stem-loop (SL)-3 of Psi than NCp7. In this study, we prepared NCp7 containing 0 (0NCp7), 1 (NCp7) or 2 (2NCp7) zinc ions, and compared their secondary structure, Psi-selectivity and SL3-affinity. Along with the decrease of the zinc content, less ordered conformations were detected. Compared to NCp7, 2NCp7 exhibited a much higher Psi-selectivity and SL3-affinity, similar to Gag, whereas 0NCp7 exhibited a lower Psi-selectivity and SL3-affinity, similar to the H23&H44K double mutant of NCp7, indicating that the different RNA-binding property of Gag NC domain and the mature NCp7 may be resulted, at least partially, from their different zinc content. This study will be helpful to elucidate the critical roles that zinc played in the viral life cycle, and benefit further investigations of the functional switch from the NC domain of Gag to the mature NCp7

Effects of Pre-Injection Strategy on Combustion Characteristics of Ammonia/Diesel Dual-Fuel Compression Ignition Mode

As a zero-carbon clean fuel, the use of ammonia in internal combustion engines is of great significance to achieve the “two-carbon” goal. This paper investigates the effect of the ammonia energy ratio and diesel injection timing on combustion and emissions. Based on Computational fluid dynamics (CFD) and the simulation analysis software, Converge, three-dimensional modeling is carried out for a direct injection diesel engine with a Compression Ignition (CI) mode. Under the initial full-load conditions of 1200 r/min, the engine simulation was calculated. The results show that the peak cylinder pressure increases and then decreases as the ammonia energy ratio increases, the ignition delay time increases, and the CO2 and N2O emissions decrease. With pre-injection, the peak cylinder pressure increases at the same energy ratio and the combustion stage advances, resulting in improved indicated thermal efficiency. In comparison to the pure diesel mode, the pre-injection strategy shows an obvious reduction in greenhouse gas (GHG) emissions with a decrease of 40.9% by adjusting the injection timing, while the single injection strategy shows a reduction of 36.5%. The soot emission peak occurs in the diesel-only mode with 98.13% and 99.6% reductions in emissions under single and pre-injection, respectively. The ammonia–diesel dual-fuel (ADDF) engine with an ammonia-to-energy ratio of 70% and optimized ammonia and diesel injection timing significantly reduces the NH3 emissions and GHG emissions by 69.34%

Label-Free Proteomic Analysis of Molecular Effects of 2-Methoxy-1,4-naphthoquinone on Penicillium italicum

Penicillium italicum is the principal pathogen causing blue mold of citrus. Searching for novel antifungal agents is an important aspect of the post-harvest citrus industry because of the lack of higher effective and low toxic antifungal agents. Herein, the effects of 2-methoxy-1,4-naphthoquinone (MNQ) on P. italicum and its mechanism were carried out by a series of methods. MNQ had a significant anti-P. italicum effect with an MIC value of 5.0 µg/mL. The label-free protein profiling under different MNQ conditions identified a total of 3037 proteins in the control group and the treatment group. Among them, there were 129 differentially expressed proteins (DEPs, up-regulated > 2.0-fold or down-regulated < 0.5-fold, p < 0.05), 19 up-regulated proteins, 26 down-regulated proteins, and 67 proteins that were specific for the treatment group and another 17 proteins that were specific for the control group. Of these, 83 proteins were sub-categorized into 23 hierarchically-structured GO classifications. Most of the identified DEPs were involved in molecular function (47%), meanwhile 27% DEPs were involved in the cellular component and 26% DEPs were involved in the biological process. Twenty-eight proteins identified for differential metabolic pathways by KEGG were sub-categorized into 60 classifications. Functional characterization by GO and KEGG enrichment results suggests that the DEPs are mainly related to energy generation (mitochondrial carrier protein, glycoside hydrolase, acyl-CoA dehydrogenase, and ribulose-phosphate 3-epimerase), NADPH supply (enolase, pyruvate carboxylase), oxidative stress (catalase, glutathione synthetase), and pentose phosphate pathway (ribulose-phosphate 3-epimerase and xylulose 5-phosphate). Three of the down-regulated proteins selected randomly the nitro-reductase family protein, mono-oxygenase, and cytochrome P450 were verified using parallel reaction monitoring. These findings illustrated that MNQ may inhibit P. italicum by disrupting the metabolic processes, especially in energy metabolism and stimulus response that are both critical for the growth of the fungus. In conclusion, based on the molecular mechanisms, MNQ can be developed as a potential anti-fungi agent against P. italicum

LncRNA CCAT1 facilitates the progression of gastric cancer via PTBP1-mediated glycolysis enhancement

Abstract Background Gastric cancer (GC) is one of the most prevalent malignant tumors of the digestive system. As a hallmark of cancer, energy-related metabolic reprogramming is manipulated by multiple factors, including long non-coding RNAs (lncRNAs). Notably, lncRNA CCAT1 has been identified as a crucial regulator in tumor progression. Nevertheless, the precise molecular mechanisms underlying the involvement of CCAT1 in metabolic reprogramming of GC remain unclear. Methods Gain- and loss-of-function experiments were performed to evaluate the roles of CCAT1 in tumorigenesis and glycolysis of GC. Bioinformatics analyses and mechanistic experiments, such as mass spectrometry (MS), RNA-pulldown, and RNA immunoprecipitation (RIP), were employed to reveal the potential interacting protein of CCAT1 and elucidate the regulatory mechanism of CCAT1 in GC glycolysis. Moreover, the nude mice xenograft assay was used to evaluate the effect of CCAT1 on GC cells in vivo. Results In this study, we identified that CCAT1 expression was significantly elevated in the tissues and plasma exosomes of GC patients, as well as GC cell lines. Functional experiments showed that the knockdown of CCAT1 resulted in a substantial decrease in the proliferation, migration and invasion of GC cells both in vitro and in vivo through decreasing the expression of glycolytic enzymes and glycolytic rate. Conversely, overexpression of CCAT1 exhibited contrasting effects. Mechanistically, CCAT1 interacted with PTBP1 and effectively maintained its stability by inhibiting the ubiquitin-mediated degradation process. As a critical splicing factor, PTBP1 facilitated the transition from PKM1 to PKM2, thereby augmenting the glycolytic activity of GC cells and ultimately fostering the progression of GC. Conclusions Our findings demonstrate that CCAT1 plays a significant role in promoting the proliferation, migration, and invasion of GC cells through the PTBP1/PKM2/glycolysis pathway, thus suggesting CCAT1’s potential as a biomarker and therapeutic target for GC

Copper induces mitochondria-mediated apoptosis via AMPK-mTOR pathway in hypothalamus of Pigs

Copper (Cu), one of the heavy metals, is far beyond the carrying capacity of the environment with Cu mining, industrial wastewater discharging and the use of Cu-containing pesticides. Intaking excess Cu can cause toxic effects on liver, kidney, heart, but few studies report Cu toxicity on brain tissue. It is noteworthy that most toxicity tests are based on rodent models, but large mammals chosen as animal models has no reported. To explore the relationship of the Cu toxicity and mitochondria-mediated apoptosis on hypothalamus in pigs, the content of Cu, histomorphology, mitochondrial related indicators, apoptosis, and AMPK-mTOR signaling pathway were detected. Results showed that Cu could accumulate in hypothalamus and lead to mitochondrial dysfunction, evidenced by the decrease of ATP production, activities of respiratory chain complex I-IV, and mitochondrial respiratory function in Cu-treated groups. Additionally, the genes and proteins expression of Bax, Caspase-3, Cytc in treatment group were higher than control group. Furthermore, the protein level of p-AMPK was enhanced significantly and p-mTOR was declined, which manifested that AMPK-mTOR signaling pathway was activated in Cu-treated groups. In conclusion, this study illuminated that the accumulation of Cu could cause mitochondrial dysfunction, induce mitochondria-mediated apoptosis and activate AMPK-mTOR pathway in hypothalamus

Additional file 1 of LncRNA CCAT1 facilitates the progression of gastric cancer via PTBP1-mediated glycolysis enhancement

Additional file 1: Supplementary Table S1. The siRNAs. Supplementary Table S2. The primers. Fig. S1. CCAT1 was increased in many cancers. A. The TCGA and GTEx databases showed that CCAT1 was significantly upregulated across many cancers. B. The morphology of exosomes under transmission electron microscope. C. The size distribution of EVs. Fig. S2. The proliferation, migration and invasion of GC cells with CCAT1 stable low-expression. A. The expression of CCAT1 in stable CCAT1 knockdown GC cells using lentiviral shRNA. B. The proliferation, C. migration and D. invasion were decreased in GC cells with CCAT1 knockdown. E. The cell cycle was arrested in G0/G1 phase in CCAT1-depleted GC cells. F. The apoptosis was increased in GC cells with CCAT1 knockdown. The statistical data are from three independent experiments and the bar indicates the SD values. Data were statistically evaluated using the Multiple unpaired t-tests (A, C and D), 2-way ANOVA with Tukey's multiple comparisons test (B). *p < 0.05, **p < 0.01. Fig. S3. A. Lnc2cancer3.0 database showed that the interacting proteins of CCAT1 were enriched in metabolic pathways. B-C. ECAR was reduced in GC cells with CCAT1 knockdown while that was elevated in GC cells with CCAT1 overexpression. D. Lnc2cancer3.0 database showed that CCAT1 interacted with PTBP1 protein. Data were statistically evaluated using the unpaired t-tests (B and C) with GraphPad Prism 9 software. *p < 0.05, **p < 0.01. Fig. S4. The role of PTBP1 in the proliferation, migration and invasion of GC cells. A. The TCGA and GTEx databases showed that the expression of PTBP1 was significantly upregulated across many cancers. B. The proliferation, C. migration, and D. invasion were decreased in GC cells with PTBP1 knockdown and those properties were increased in GC cells with PTBP1 overexpression. E. ECAR was reduced in GC cells with PTBP1 knockdown while that was elevated in PTBP1-overexpressing GC cells. The statistical data are from three independent experiments and the bar indicates the SD values. Data were statistically evaluated using the 2-way ANOVA with Tukey's multiple comparisons tests (B) and Multiple unpaired t-tests (E, C and D). *p < 0.05, **p < 0.01

Quality uniformity evaluation of Babao Dan capsule based on its 14 main chemical compounds and in vitro anti-inflammatory activity

Babao Dan capsule (BBDC) is a state secrecy traditional Chinese medicine patent prescription (TCMPP) that is widely used for hepatobiliary and urinary diseases. However, its quality uniformity evaluation (QUE) is lacking. It is necessary to develop a novel and multi–dimensional QUE strategy for BBDC based on chemical properties and bioactivities. An ultrahigh performance liquid chromatography–triple quadrupole–mass spectrometry (UHPLC–QQQ–MS/MS) was developed to quantify 14 compounds, and a QUE strategy was to assess intra–batch and inter–batches consistency. Furthermore, the anti-inflammatory activities were measured in vitro by RAW264.7 cell and NF-κB-RE-luc HEK293 cell. The results indicated that 14 compounds from 16 samples (10 batches) were accurately quantified. And the intra–batch consistency values were less than or equal to 20.1%, whereas the largest inter–batches consistency value was 167.5% of glycocholic acid. 10 batches were divided into three categories to distinction inter–batches differences. BBDC had anti-inflammatory activities including inhibition of LPS–induced NO production and TNF α–activated luciferase counts. The NO inhibition difference of 10 batches was 10.87 μM and accounted for 49.8%. Briefly, the anti-inflammatory activities of 10 batches were different, but the dynamic trends within the same batch were similar, which was supported by luciferase counts. And the correlation was confirmed that the main compounds related to anti-inflammatory in BBDC were bile acids and saponins. Hence, a QUE strategy for BBDC was proposed to improve quality and ensure efficacy. This strategy can be utilized as a reference for consistency evaluations of TCMPPs

Protective effect of Nr4a2 (Nurr1) against LPS-induced depressive-like behaviors via regulating activity of microglia and CamkII neurons in anterior cingulate cortex

Neuroinflammation is tightly associated with onset of depression. The nuclear receptor related 1 protein (Nurr1, also called Nr4a2), its roles in dopaminergic neurons is well understood, which can alleviate inflammation. Nevertheless, potential effects of Nr4a2 on neuroinflammation associated with depression still remains unclear. Chronic lipopolysaccharides (LPS) stress induced depressive-behaviors were confirmed via behavioral tests. Differentially expressed genes were detected by using RNA-sequencing. The anterior cingulate cortex (ACC) tissues were collected for biochemical experiments. The Golgi-Cox staining and virus labeling were used to evaluate the dendritic spines. We applied fluoxetine (FLX) and amodiaquine dihydrochloride (AQ, a highly selective agonist of Nr4a2) in mice. Overexpression experiments were performed by injecting with AAV-Nr4a2-EGFP into ACC. Chemogenetic activation of CamkII neurons via injecting the hM3Dq virus. Mice treated with LPS displayed depressive- and anxiety-like behaviors. The reduction of Nr4a2 and FosB induced by LPS were rescued by pretreatment with FLX or AQ. More importantly, LPS-induced behavior deficits in mice were also alleviated via fluoxetine treatment and pharmacological activation the expression of Nr4a2. Meanwhile, enhancing the level of Nr4a2 could improve dendritic spines loss of neuron and morphological changes in microglia. Overexpression of Nr4a2 in ACC reversed the depressive- and anxiety-like behaviors caused by LPS administration. Activation of CamkII neurons in ACC could robustly increase the expression of Nr4a2 and improve LPS-induced behavior deficits. Our findings demonstrate that the Nr4a2 may regulate depressive-like behaviors via alleviating the impairment of morphology and function on microglia and CamkII neurons induced by chronic neuroinflammation

Impact of TMPRSS2 Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2

As a cellular protease, transmembrane serine protease 2 (TMPRSS2) plays roles in various physiological and pathological processes, including cancer and viral entry, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we conducted expression, mutation, and prognostic analyses for the TMPRSS2 gene in pan-cancers as well as in COVID-19-infected lung tissues. The results indicate that TMPRSS2 expression was highest in prostate cancer. A high expression of TMPRSS2 was significantly associated with a short overall survival in breast invasive carcinoma (BRCA), sarcoma (SARC), and uveal melanoma (UVM), while a low expression of TMPRSS2 was significantly associated with a short overall survival in lung adenocarcinoma (LUAD), demonstrating TMPRSS2 roles in cancer patient susceptibility and severity. Additionally, TMPRSS2 expression in COVID-19-infected lung tissues was significantly reduced compared to healthy lung tissues, indicating that a low TMPRSS2 expression may result in COVID-19 severity and death. Importantly, TMPRSS2 mutation frequency was significantly higher in prostate adenocarcinoma (PRAD), and the mutant TMPRSS2 pan-cancer group was significantly associated with long overall, progression-free, disease-specific, and disease-free survival rates compared to the wild-type (WT) TMPRSS2 pan-cancer group, demonstrating loss of functional roles due to mutation. Cancer cell lines were treated with small molecules, including cordycepin (CD), adenosine (AD), thymoquinone (TQ), and TQFL12, to mediate TMPRSS2 expression. Notably, CD, AD, TQ, and TQFL12 inhibited TMPRSS2 expression in cancer cell lines, including the PC3 prostate cancer cell line, implying a therapeutic role for preventing COVID-19 in cancer patients. Together, these findings are the first to demonstrate that small molecules, such as CD, AD, TQ, and TQFL12, inhibit TMPRSS2 expression, providing novel therapeutic strategies for preventing COVID-19 and cancers