Association of serum vitamin C levels with Asthma in adults: results of NHANES 2003-2006 and mendelian randomization study.

BACKGROUND: The protective effect of vitamin C as an antioxidant against asthma in adults remains controversial. This study used an observational study and Mendelian randomization (MR) analysis to investigate the association between adult asthma and serum vitamin C levels. METHODS: Using information from the National Health and Nutrition Examination Survey (NHANES) 2003-2006, we carried out an observational study. A multivariate logistic regression model was employed to examine the connection between adult asthma and serum vitamin C levels. We used the inverse-variance weighted (IVW) method of MR analysis as the primary method to analyze the causal effect of serum vitamin C levels on asthma in adults. RESULTS: A total of 8,504 participants were included in the observational study, including 639 in the asthma group and 7,865 in the non-asthma group. Before sample weighting, serum vitamin C was associated with a reduced risk of asthma in adults (OR = 0.798, 95% CI: 0.673-0.945, P = 0.009). After sample weighting, serum vitamin C was not associated with adult asthma risk (OR = 0.829, 95% CI: 0.660 ~ 1.042, P = 0.104). MR analysis showed no causal relationship between serum vitamin C and adult asthma in either the UK Biobank (OR = 0.957, 95% CI: 0.871 ~ 1.053, P = 0.370) or FinnGen (OR = 0.973, 95% CI: 0.824 ~ 1.149, P = 0.750) cohorts. CONCLUSION: Our study did not support a causal association between serum vitamin C levels and adult asthma risk. The relationship between serum vitamin C and adult asthma requires further research.

The association between prothrombin time-international normalized ratio and long-term mortality in patients with coronary artery disease: a large cohort retrospective study with 44,662 patients.

BACKGROUND: The association between prothrombin time-international normalized ratio (PT-INR) and long-term prognosis among patients with coronary artery disease (CAD) without atrial fibrillation or anticoagulant therapy was still unclear. We analyzed the association of PT-INR levels and long-term mortality in a large cohort of CAD patients without atrial fibrillation or using of anticoagulant drugs. METHODS: We obtained data from 44,662 patients who were diagnosed with CAD and had follow-up information from January 2008 to December 2018. The patients were divided into 4 groups (Quartile 1: PT-INR ≤ 0.96; Quartile2: 0.96 < PT-INR ≤ 1.01; Quartile3: 1.01 < PT-INR ≤ 1.06; Quartile4: PT-INR > 1.06). The main endpoint was long-term all-cause death. Kaplan-Meier curve analysis and Cox proportional hazards models were used to investigate the association between quartiles of PT-INR levels and long-term all-cause mortality. RESULTS: During a median follow-up of 5.25 years, 5613 (12.57%) patients died. We observed a non-linear shaped association between PT-INR levels and long-term all-cause mortality. Patients in high PT-INR level (Quartile4: PT-INR > 1.06) showed a significantly higher long-term mortality than other groups (Quartile2 or 3 or 4), (Compared with Quartile 1, Quartile 2 [0.96 < PT-INR ≤ 1.01], aHR = 1.00, 95% CI 0.91-1.00, P = 0.99; Quartile 3 [1.01 < PT-INR ≤ 1.06], aHR = 1.10, 95% CI 1.01-1.20, P = 0.03; Quartile 4 [PT-INR > 1.06], aHR = 1.33, 95% CI 1.22-1.45, P < 0.05). CONCLUSIONS: Our study demonstrates high levels of PT-INR were associated with an increased risk of all-cause mortality.

High Nitrate Accumulation in the Vadose Zone after Land-Use Change from Croplands to Orchards.

Additional evidence indicates that the nitrate stored in the deep soil profile has an important role in regulating the global nitrogen (N) cycle. This study assessed the effects of land-use changes from croplands to intensive orchards (LUCO) on N surplus, nitrate accumulation in deep soil, and groundwater quality in the kiwifruit belt of the northern slope region of the Qinling Mountains, China. LUCO resulted in comparatively high N surplus in orchards (282 vs 1206 kg ha-1 yr-1, respectively). The average nitrate accumulation within the 0-10 m profiles of orchards was 7113 kg N ha-1, which was equal to approximately the total N surplus of 6 years of the orchards. The total nitrate stock within 0-10 m soil profiles of the kiwifruit belt was 266.5 Gg N, which was 3.5 times higher than the total annual N input. The nitrate concentrations of 97% of groundwater samples exceeded the WHO standard. The LUCO resulted in large nitrate storage in the vadose zone and caused serious contamination of groundwater. Our study highlights that nitrate accumulation in the vadose zone of an intensive land-use system is one of the main fates of surplus N and also a hotspot of nitrate accumulation.

Dramatic loss of inorganic carbon by nitrogen-induced soil acidification in Chinese croplands.

Intensive crop production systems worldwide, particularly in China, rely heavily on nitrogen (N) fertilization, but left more than 50% of fertilizer N in the environment. Nitrogen (over) fertilization and atmospheric N deposition induce soil acidification, which is neutralized by soil inorganic carbon (SIC; carbonates), and carbon dioxide (CO2 ) is released to the atmosphere. For the first time, the loss of SIC stocks in response to N-induced soil acidification was estimated for Chinese croplands from 1980 to 2020 and forecasts were made up to 2100. The SIC stocks in croplands in 1980 were 2.16 Pg C (16.3 Mg C/ha) in the upper 40 cm, 7% (0.15 Pg C; 1.1 Mg C/ha) of which were lost from 1980 to 2020. During these 40 years, 7 million ha of cropland has become carbonate free. Another 37% of the SIC stocks may be lost up to 2100 in China, leaving 30 million ha of cropland (37.8%) without carbonates if N fertilization follows the business-as-usual (BAU) scenario. Compared to the BAU scenario, the reduction in N input by 15%-30% after 2020 (scenarios S1 and S2) will decrease carbonate dissolution by 18%-41%. If N input remains constant as noted in 2020 (S3) or decreases by 1% annually (S4), a reduction of up to 52%-67% in carbonate dissolution is expected compared to the BAU scenario. The presence of CaCO3 in the soil is important for various processes including acidity buffering, aggregate formation and stabilization, organic matter stabilization, microbial and enzyme activities, nutrient cycling and availability, and water permeability and plant productivity. Therefore, optimizing N fertilization and improving N-use efficiency are important for decreasing SIC losses from acidification. N application should be strictly calculated based on crop demand, and any overfertilization should be avoided to prevent environmental problems and soil fertility decline associated with CaCO3 losses.

Do soil property variations affect dicyandiamide efficiency in inhibiting nitrification and minimizing carbon dioxide emissions?

Nitrification inhibitors (NIs) are used to retard the nitrification process and reduce nitrogen (N) losses. However, the effects of soil properties on NI efficacy are less clear. Moreover, the direct and indirect effects of soil property variations on NI efficiency in minimizing carbon dioxide (CO2) emissions have not been previously studied. An incubation experiment was conducted for 40 days with two treatments, N (200 mg N-urea kg-1) and N + dicyandiamide (DCD) (20 mg DCD kg-1), and a control group (without the N) to investigate the response of ammonia-oxidizing bacteria (AOB) and archaea (AOA) to DCD application and the consequences for CO2, nitrous oxide (N2O) and ammonia (NH3) emissions from six soils from the Loess Plateau with different properties. The nitrification process completed within 6-18 days for the N treatment and within 30->40 days for the N + DCD treatment. AOB increased significantly with N fertilizer application, while this effect was inhibited in soils when DCD was applied. AOA was not sensitive to N fertilizer and DCD application. The nitrification rate was positively correlated with the clay (p < 0.05) and SOM contents (p < 0.01); DCD was more effective in loam soil with low SOM and high soil pH. Soil pH significantly was decreased with N fertilizer application, while it increased when DCD was applied. Moreover, DCD application decreased CO2 emissions from soils by 22%-172%; CO2 emissions were negatively correlated with the clay and SOM contents. DCD application decreased N2O emissions in each soil by 1.0- to 94-fold compared with those after N fertilizer application. In contrast, DCD application increased NH3 release from soils by 59-278%. NH3 volatilization was negatively correlated with clay (p < 0.05) and SOM (p < 0.01) contents and positively correlated with soil pH (p < 0.01). Therefore, soil texture, SOM and soil pH have significant effects on the DCD performance, nitrification process and gaseous emissions.

Will income inequality influence the abatement effect of renewable energy technological innovation on carbon dioxide emissions?

Environmental pollution and income inequality have become two salient issues in China. To achieve a green economic transformation, China urgently needs to develop renewable energy technologies to reduce carbon dioxide (CO2) emissions. However, the relationship among income inequality, renewable energy technological innovation (RETI) and CO2 emissions has not received sufficient attention in the current literature. Based on Chinese provincial panel data from 2000 to 2015, this paper adopts a panel fixed effect regression model and a panel threshold model to perform an analysis on the nonlinear relationship among these factors. The results show that (1) RETI is conducive to reducing per capita CO2 emissions (PCE). However, with an increase in income inequality, the abatement effect of RETI on per capita CO2 emissions will be hindered, and RETI will even positively contribute to PCE. (2) The panel threshold model shows that the impact of RETI on PCE has a significant single-threshold effect with regard to income inequality. When income inequality is lower than the threshold value, the impact of RETI on PCE is not significant. However, above the threshold value, that is, within the interval of higher income inequality, an increase in RETI will positively contribute to PCE. Finally, from the perspectives of income inequality and RETI, relevant policy implications are put forward for achieving the transformation of a low-carbon economy.

How much nitrogen does Africa need to feed itself by 2050?

Nitrogen (N) fertilizers are very important for global food self-sufficiency (FSS), particularly for Africa, where the N input in agriculture is very low. This is the first work which studies and calculates the amount of N fertilizer that each country in Africa needs to feed itself by 2050. In this study, we used five different scenarios of inorganic fertilizer N (IFN) use and human diets to calculate the amount of N fertilizer needed to achieve FSS in Africa by 2050 and analyze the changes in N budget; N losses and N use efficiency (NUE). These scenarios include 1) business as usual (BAU), 2) equitable diet (EqD; self-sufficiency), 3) an IFN input 20% less than the EqD (S1), 4) an IFN input 40% less than the EqD (S2), and 5) a 20% increase in IFN input relative to the EqD (S3). Under the BAU scenario, production trends continue as they have over the past five decades, including an unhealthy human diet. In the EqD scenario, the priority is to meet the local demand for both animal and plant proteins with a healthy human diet. Under the EqD scenario, increasing the total N input from 35 kg N ha-1 yr-1 to 181 kg N ha-1 yr-1 during 2016-2050 is needed to achieve FSS in Africa. This increase in N fertilizer use represents unprecedented N inputs to African terrestrial ecosystems - at least 52 Tg N yr-1 - which would lead to inevitable increases in N losses. We also found that the NUE would decrease from 63% during 2010-2016 to 50% by 2050, whereas the total N surplus would increase from 13 kg N ha-1 yr-1 to 90 kg N ha-1 yr-1 by 2050. The estimated gaseous emissions would increase from 8 kg N ha-1 yr-1 to 61 kg N ha-1 yr-1 by 2050. Our findings conclude that, it is very important to consider the high N losses in Africa if the EqD scenario is applied. The S1 and S2 scenarios result in much less environmental N loss, and better NUE compared with the EqD scenario. Therefore, based on these findings we can recommend the implementation of the S2 scenario with an IFN dose of 77 kg N ha-1 yr-1, in parallel with the use of modern agricultural techniques and the increased use of organic inputs.

Crystal structure of PA0833 periplasmic domain from Pseudomonas aeruginosa reveals an unexpected enlarged peptidoglycan binding pocket.

PA0833 of Pseudomonas aeruginosa is recently identified as an OmpA C-like protein that is able to interact with bacterial peptidoglycan (PGN). In this study, we reported the biochemical and structural characterization of the PGN-binding periplasmic-domain of PA0833 (PA0833-PD). Via mutagenesis, key residues responsible for engaging PGN were identified, which also enables us to localize the PGN-binding pocket in a 2.0 Šcrystal structure solved in this study. In contrast to its homologous proteins (as represented by AbOmpA-PD of Acinetobacter baumannii) that interact with PGN by directly engaging the DAP (diaminopimelate) moiety, PA0833-PD exhibits an enlarged PGN-binding pocket due to residue insertions and the formation of an extra α-helix in one lateral side of the pocket. Accordingly, single DAP molecule does not show detectable interactions with PA0833-PD in solution, highlighting that other PGN-components, in addition to DAP, are also required to restore the full binding capacity observed between PA0833 and PGN.

Clinical Implications of Contrast-Induced Nephropathy in Patients Without Baseline Renal Dysfunction Undergoing Coronary Angiography.

BACKGROUND: The clinical implications of different definitions of contrast-induced nephropathy (CIN) in patients without baseline renal dysfunction are not well defined. METHODS: Consecutive patients at a single centre without baseline renal dysfunction (estimated glomerular filtration rate, eGFR≥60ml/min/1.73m2) undergoing coronary angiography or percutaneous coronary intervention (PCI), were systematically evaluated for long-term risk of mortality following CIN using two broad definitions: an absolute increase from baseline in serum creatinine (SCr) ≥0.3mg/dl (mild to severe absolute CIN) and a relative increase from baseline of 25% (mild to severe relative CIN) within 72hours. RESULT: Of 2,823 subjects alive before discharge following coronary angiography there were 320 episodes of mild to severe relative CIN (11.3%) and 125 of mild to severe absolute CIN (4.4%). During a median follow-up of 2.3years, 73 patients (3.2%) died. After adjustment for confounders, mild to severe absolute CIN was associated with an adjusted hazard ratio (HR) (95% confidence interval) for all-cause mortality of 3.31 (1.74-6.30) (p<0.0001) and relative CIN with an adjusted HR of 1.92 (1.09, 3.38) (p=0.024). The risk of mortality rose with severity of CIN. Two commonly used definitions of CIN combining absolute and relative terms (increase ≥ 0.3mg/dl or 50%, and ≥ 0.5mg/dl or 25% from the baseline) confirmed these results. CONCLUSION: Among patients without baseline renal dysfunction undergoing coronary angiography, the incidence of CIN can range widely depending on definition. Absolute CIN is less common than relative CIN. Regardless of definition, CIN is associated with a markedly increased risk of long-term mortality. This finding requires confirmation in multicentre studies.

Crystal structure of Usutu virus envelope protein in the pre-fusion state.

BACKGROUND: Usutu virus (USUV) is a mosquito-born flavivirus that can infect multiple avian and mammalian species. The viral surface envelope (E) protein functions to initiate the viral infection by recognizing cellular receptors and mediating the subsequent membrane fusion, and is therefore a key virulence factor involved in the pathogenesis of USUV. The structural features of USUV-E, however, remains un-investigated thus far. FINDINGS: Using the crystallographic method, we determined the structure of USUV-E in the pre-fusion state at 2.0 angstrom. As expected, the overall fold of USUV-E, with three ß-barrel domains (DI, DII, and DIII), resembles those of other flaviviral E proteins. In comparison to other pre-fusion E structures, however, USUV-E exhibits an apparently enlarged inter-domain angle between DI and DII, leading to a more extended conformation. Using our structure and other reported pre-fusion E structures, the DI-DII domain-angle difference was analyzed in a pairwise manner. The result shows a much higher degree of variations for USUV-E, indicating the potential for remarkable DI-DII domain angle plasticity among flaviviruses. CONCLUSION: We report the crystal structure of USUV-E and show that its pre-fusion structure has an enlarged DI-DII domain-angle which has not been observed in other reported flaviviral E-structures.

Crystal structure of herpes simplex virus 2 gD bound to nectin-1 reveals a conserved mode of receptor recognition.

UNLABELLED: Herpes simplex virus 1 (HSV-1) and HSV-2 are among the most prevalent human pathogens. Both viruses can recognize, via the surface envelope glycoprotein D (gD), human nectin-1 as a functional receptor. Previous studies have successfully elucidated the molecular basis of the binding between HSV-1 gD and nectin-1 by cocrystallography. Despite a high sequence identity between HSV-1 and HSV-2 gDs, the atomic intermolecule details for the HSV-2-gD/nectin-1 interaction remain elusive. Here, we report the crystal structures of both the unbound and the nectin-1-bound HSV-2 gDs. The free-gD structure expectedly comprises an IgV-like core and the surface-exposed terminal extensions as observed in its HSV-1 counterpart but lacks traceable electron densities for a large portion of the terminal elements. These terminal residues were clearly traced in the complex structure as a definitive loop in the N terminus and an α-helix in the C terminus, thereby showing a conserved nectin-1-binding mode as reported for HSV-1 gD. The interface residues in nectin-1 were further mutated and tested for the gD interaction by surface plasmon resonance. The resultant binding patterns were similar for HSV-1 and HSV-2 gDs, further supporting a homologous receptor-binding basis by the two viruses for nectin-1. These data, together with a cell-based fusion assay showing a cross-inhibition of the gD/nectin-1-mediated cell-cell fusion by soluble HSV-1 and HSV-2 gDs, provided solid structural and functional evidence that HSV-1 and HSV-2 recognize nectin-1 via the same binding mode. Finally, we also demonstrated that nectin-1 I80 is an important residue involved in gD interaction. IMPORTANCE: Despite intensified studies, a detailed picture of the molecular features in the HSV-2-gD/nectin-1 interaction remains unavailable. Previous work focused on HSV-1 gD, which folds into an IgV-like core with large terminal extensions and utilizes the extension elements to engage nectin-1. Here, we report the crystal structures of HSV-2 gD in both the free and the nectin-1-bound forms. The atomic intermolecule details for HSV-2-gD/nectin-1 interaction are clearly presented. The observed binding mode is identical to that reported for its HSV-1 counterpart. This structural observation was further supported by our comparative functional assays showing that nectin-1 mutations similarly affect the ligand-receptor interaction of both virus gDs. Taken together, we provide comprehensive structural and functional data demonstrating a conserved receptor-binding mode between HSV-1 and HSV-2 for nectin-1. Our results also indicate that the tropism difference between the two viruses likely arises from aspects other than the gD/nectin-1 binding features.

Conserved epitopes dominate cross-CD8+ T-cell responses against influenza A H1N1 virus among Asian populations.

Novel strains of influenza A viruses (IAVs) have emerged with high infectivity and/or pathogenicity in recent years, causing worldwide concern. T cells are correlated with protection in humans through cross-reactive immunity against heterosubtypes of IAV. However, the different hierarchical roles of IAV-derived epitopes with distinct levels of polymorphism in the cross-reactive T-cell responses against IAV remain elusive. In this study, immunodominant epitopes scattered throughout the entire proteome of 2009 pandemic influenza A H1N1 virus and seasonal IAVs were synthesized and divided into different pools depending on their conservation. The overall profile of the IAV-specific CD8(+) T-cell immunity was detected by utilizing these peptide pools and also individual peptides. A dominant role of the conserved peptide-specific T-cell immunity was illuminated within the anti-IAV responses, while the CD8(+) T-cell responses against the variable epitopes were lower than the conserved peptides. As previously demonstrated within a Caucasian population, we determined that GL9-specific T cells, which also utilize Vß 17 TCR (BV19), play a pivotal role in IAV-specific T-cell immunity within an HLA-A2(+) Asian population. Our study objectively reveals the different predominant roles of T-cell epitopes among IAV-specific cross-reactive cellular immunity. This may guide the development of vaccines with cross-T-cell immunogenicity against heterosubtypes of IAV.

Crystal structure of cell adhesion molecule nectin-2/CD112 and its binding to immune receptor DNAM-1/CD226.

The nectin and nectin-like molecule (Necl) family includes important cell adhesion molecules (CAMs) characterized by their Ig-like nature. Such CAMs regulate a broad spectrum of cell-cell interactions, including the interaction between NK cells and cytotoxic T lymphocytes (CTLs) and their target cells. CAM members nectin-2 (CD112) and Necl-5 (CD155) are believed to form homodimers (for nectin-2) or heterodimers in their functions for cell adhesion, as well as to interact with immune costimulatory receptor DNAX accessory molecule 1 (DNAM-1) (CD226) to regulate functions of both NK and CTL cells. However, the structural basis of the interactive mode of DNAM-1 with nectin-2 or Necl-5 is not yet understood. In this study, a soluble nectin-2 Ig-like V-set domain (nectin-2v) was successfully prepared and demonstrated to bind to both soluble ectodomain and cell surface-expressed full-length DNAM-1. The 1.85-Å crystal structure of nectin-2v displays a perpendicular homodimer arrangement, revealing the homodimer characteristics of the nectin and Necls. Further mutational analysis indicated that disruption of the homodimeric interface of nectin-2v led to a failure of the homodimer formation, as confirmed by crystal structure and biochemical properties of the mutant protein of nectin-2v. Interestingly, the monomer mutant also loses DNAM-1 binding, as evidenced by cell staining with tetramers and surface plasmon resonance assays. The data indicate that interaction with DNAM-1 requires either the homodimerization or engagement of the homodimeric interface of nectin-2v. These results have implications for immune intervention of tumors or autoimmune diseases in the DNAM-1/nectin-2-dependent pathway.

Development of molecular markers specific to petaloid-type cytoplasmic male sterility in tuber mustard (Brassica juncea var. tumida Tsen et Lee).

To establish a simple and rapid method for isolating mitochondrial DNA (mtDNA) from Brassica vegetables, the effects of different factors on mtDNA extraction were investigated firstly. A new protocol includes five steps: organelle isolation, deoxyribonuclease treatment, lysis, RNase treatment, and deproteinization. Results indicate that a 15 min-lysis time can achieve higher mtDNA yields from etiolated seedlings. Moreover, it is found that the inflorescence of the cytoplasmic male sterile (CMS) line is unfit for the isolation of mtDNA. The mtDNA isolated using this method is intact and pure, and can be used for further molecular analysis. Subsequently, the genomic and transcriptional differences of atps and coxs genes on the mitochondria between the petaloid-type CMS line and its maintainer line have been identified. RFLP analysis revealed that out of the five atps and three coxs genes, except of atp4 and cox3, the others mtDNA protein coding genes exhibited polymorphisms, respectively. This results suggest that atps and coxs genes are located in a long mtDNA fragment, and the mtDNA evolves rapidly in structure between the CMS line and its maintainer line in tuber muster. Northern blot analysis showed that the expression level of these genes in flower bud is higher than that of leaf and flower, and that, alternative splicing have been found among the atp6, atp8 and cox3 genes, respectively. Our results modified a efficient protocol for isolating the mtDNA, and provided some novel molecular markers indicating the CMS trait in tuber mustard. The comparative analysis presented in this study allows a more comprehensive understanding of the molecular mechanism on CMS in Brassica crops.

Extreme precipitation accelerates nitrate leaching in the intensive agricultural region with thick unsaturated zones.

Nitrate accumulation in the soil profile in the intensive agricultural region has been widely concerned in the world. However, the changes in nitrate accumulation characteristics caused by climate change, such as extremely high precipitation, are not well quantified, particularly for the regions with thick unsaturated zones. Here, we resampled the soil profiles taken in normal year (2020) after extreme precipitation year (2021) (>800 cm) in three regions in the southern Loess Plateau (LP) with three different water managements including rainfed orchards (n = 10), well-irrigated orchards (n = 4) and canal-irrigated orchards (n = 8). The accumulation amounts, peak depths, and accumulation depths of nitrate soil profiles of the different regions of two years were compared. The results showed that average nitrate accumulation in normal year at the rainfed region (800-cm depth), well-irrigated region (800-cm depth) and canal-irrigated region (1400-cm depth) were 5995 kg N ha-1, 9765 kg N ha-1, and 19,608 kg N ha-1, respectively. Compared with 2020, extreme precipitation in 2021 led to 56-91% reductions (2060-3702 kg N ha-1) in nitrate accumulation in 0-200 cm soil layer, and average nitrate leaching into the aquifer was >1390 kg N ha-1 in the canal-irrigated region. Average migration depths of nitrate peak in rainfed, well-irrigated and canal-irrigated regions were 92 cm, 115 cm, and 188 cm, respectively; as for nitrate accumulation depths, they were 10 cm, 80 cm and 108 cm, respectively. Vertically, the dried soil layer and paleosol layer (high clay content) in the canal-irrigated region significantly hindered nitrate deep migration caused by the extreme precipitation. The result highlights that extreme precipitation significantly accelerated nitrate leaching in the deep soil profiles, and future vulnerability and risk assessment studies must account for the impacts of extreme precipitation on nitrate leaching.

Use of the contrast volume or grams of iodine-to-creatinine clearance ratio to predict mortality after percutaneous coronary intervention.

BACKGROUND: Few studies have assessed the predictive value of the ratio of the contrast media volume or grams of iodine to the creatinine clearance (V/CrCl or g-I/CrCl, respectively) for the risk of contrast-induced nephropathy (CIN) and mortality after percutaneous coronary intervention (PCI). METHODS: The association between V/CrCl and mortality was prospectively evaluated in 1,135 consecutive patients undergoing PCI. Cox regression models were used to adjust for the V/CrCl ratio and other confounding factors for risk of death within 1 year. RESULTS: Fifty-five patients (4.84%) developed CIN. The 1-year mortality was higher in patients with a V/CrCl ratio >2.62 (g-I/CrCl >0.97) than in others (4.44% vs 0.40%; P < .001). After adjusting for other risk factors, the 1-year mortality risk remained associated with increased V/CrCl ratio. The risk of death was significant for V/CrCl >2.62 (adjusted risk ratio [RR] for death 2.605, 95% CI 1.040-6.529, P = .041), V/CrCl >3.0 (g-I/CrCl >1.11) (adjusted RR 4.338, 95% CI 1.689-11.142, P = .002), and V/CrCl >3.7 (g-I/CrCl >1.37) (adjusted RR 2.557, 95% CI 1.162-5.627, P = .002). CONCLUSION: The data further support the prognostic significance of calculating the V/CrCl ratio to predict the relative maximum contrast volume during PCI. Use of a contrast dose determined based on the estimated renal function with a planned V/CrCl ratio <3.7 (g-I/CrCl <1.37) and preferably <2.62 (g-I/CrCl <0.97) might be valuable in reducing the risks of CIN and even death after PCI.

Lack of association between lipoprotein(a) genetic variants and subsequent cardiovascular events in Chinese Han patients with coronary artery disease after percutaneous coronary intervention.

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] levels predict cardiovascular events incidence in patients with coronary artery disease (CAD). Genetic variants in the rs3798220, rs10455872 and rs6415084 single-nucleotide polymorphisms (SNPs) in the Lp(a) gene (LPA) correlate with elevated Lp(a) levels, but whether these SNPs have prognostic value for CAD patients is unknown. The present study evaluated the association of LPA SNPs with incidence of subsequent cardiovascular events in CAD patients after percutaneous coronary intervention (PCI). METHODS: TaqMan SNP genotyping assays were performed to detect the rs6415084, rs3798220 and rs10455872 genotypes in 517 Chinese Han patients with CAD after PCI. We later assessed whether there was an association of these SNPs with incidence of major adverse cardiovascular events (MACE: cardiac death, nonfatal myocardial infarction, ischemic stroke and coronary revascularization). Serum lipid profiles were also determined using biochemical methods. RESULTS: Only the rs6415084 variant allele was associated with higher Lp(a) levels [41.3 (20.8, 74.6) vs. 18.6 (10.3, 40.9) mg/dl, p < 0.001]. During a 2-year follow-up period, 102 patients suffered MACE, and Cox regression analysis demonstrated that elevated Lp(a) (≥30 mg/dl) levels correlated with increased MACE (adjusted HR, 1.69; 95% CI 1.13-2.53), but there was no association between LPA genetic variants (rs6415084 and rs3798220) and MACE incidence (p > 0.05). CONCLUSIONS: Our data did not support a relationship between genetic LPA variants (rs6415084 and rs3798220) and subsequent cardiovascular events after PCI in Chinese Han CAD patients.

BRCA2 mutation in advanced lung squamous cell carcinoma treated with Olaparib and a PD-1 inhibitor: a case report.

Background: Mutations in the human breast cancer susceptibility gene 2 (breast cancer 2, BRCA2) increase the risk of breast, ovarian and other cancers. Olaparib, an oral poly[adenosine diphosphate (ADP)-ribose] polymerase (PARP) inhibitor, is usually prescribed to treat BRCA mutated tumors, especially breast and ovarian cancers. Programmed cell death-1 (PD-1) inhibitors have revolutionized the treatment of lung cancer and many other cancers by destroying the interaction between receptors with ligands in the tumor-immune microenvironment and enabling T cells to recognize and attack cancer cells. Case description: In our study, we report a patient with advanced BRCA2 lung squamous cell carcinoma who received platinum-based chemotherapy combined with paclitaxel. Seven months later, the disease progressed. BRCA2 mutations were detected in peripheral blood by next-generation sequencing. After 2 months of treatment with Olaparib combined with Cindilimab, the patient was in partial remission and the progression-free survival (PFS) lasted for 6 months, but the patient developed immune renal damage. Conclusions: This study adds to the clinical data for the treatment of BRCA2 mutant non-small cell lung cancer by demonstrating that lung squamous cell carcinoma has a good response to PARP inhibitors. It also serves as a reminder that there may still be some negative effects from targeted superimposed immunotherapy.

Soil aggregation is more important than mulching and nitrogen application in regulating soil organic carbon and total nitrogen in a semiarid calcareous soil.

Evaluating soil aggregation and microbial activities within soil aggregates contributes to understanding carbon (C) and nitrogen (N) cycling. Here we examined soil aggregate distribution, C and N pools, and extracellular enzymatic activities (EEAs) in soil aggregates after 16-year mulching (CT, no mulch; RF, plastic-mulched ridges and straw-mulched furrows; SM, straw mulch) and N fertilization (0, 120, and 240 kg ha-1). RF and SM significantly increased macroaggregate formation and aggregate stability (MWD, mean weight diameter) but N rate did not. Mulching had similar effects on aggregate-associated SOC (soil organic C) and TN (total N), with the order SM > RF > CT in macroaggregates and macroaggregate-occluded microaggregates. N input significantly increased TN in most cases, whereas its effect on SOC was only significant in SM. Notably, the majority of SOC and TN was isolated in the macroaggregate-occluded silt and clay fractions. SOC, TN, microbial biomass C (MBC), and microbial biomass N (MBN) decreased as aggregate-size decreased, whereas C- and N-acquiring enzymes varied greatly across aggregate fractions. Mulching had greater effects than N-fertilization on soil C and N pools and EEAs, whilst SM performed more beneficial effects than RF on SOC, TN, MBC, MBN, and EEAs. MBC rather than SOC was associated with MWD in bulk soil, while significant relations between MWD and SOC were observed in macroaggregates and macroaggregate-occluded microaggregates. Partial least squares path modeling illustrated that soil aggregation was the most important factor affecting SOC and TN, followed by mulching and N addition. Regression analysis further revealed that α-glucosidase and leucine aminopeptidase were major variables mediating SOC and TN dynamics at the aggregate scale. This study highlights the importance of macroaggregate-occluded microaggregate fraction sensitively evaluating soil C and N dynamics, and straw mulch can effectively increase soil aggregation and stabilization of C and N in semiarid areas with infertile soils.

Competitive proton-trapping strategy enhanced anti-freezing organohydrogel fibers for high-strain-sensitivity wearable sensors.

Stretchable organohydrogel fibers are attracting considerable interest for next-generation flexible and wearable soft strain sensors due to their excellent stability in harsh environments. However, due to the uniformly distributed ions and reduced number of carriers in the whole material, the sensitivity of organohydrogel fibers under subzero temperature is not desirable, which significantly hinders their practical application. Herein, a newly competitive proton-trapping strategy was designed to obtain anti-freezing organohydrogel fibers for high-performance wearable strain sensors via a simple freezing-thawing process, in which tetraaniline (TANI), serving as the proton trapper, and representing the shortest repeated structural unit of polyaniline (PANI), was physically crosslinked with polyvinyl alcohol (PVA) (PTOH). The as-prepared PTOH fiber exhibited an outstanding sensing performance at -40 °C due to the unevenly distributed ion carriers and the highly breakable proton-migration pathways, with a high gauge factor of 24.6 at a strain of 200-300%. Moreover, the existence of hydrogen bonds between the TANI and PVA chains endowed PTOH with a high tensile strength (1.96 MPa) and toughness (8.0 MJ m-3). Accordingly, strain sensors made from PTOH fibers and knitted textiles could monitor human motions rapidly and sensitively, demonstrating their potential as wearable anti-freezing anisotropic strain sensors.