The effect and mechanism of combined exposure of MC-LR and NaNO2 on liver lipid metabolism.

Microcystin-LR (MC-LR) and sodium nitrite (NaNO2) co-exist in the environment and are hepatotoxic. The liver has the function of lipid metabolism, but the impacts and mechanisms of MC-LR and NaNO2 on liver lipid metabolism are unclear. Therefore, we established a chronic exposure model of Balb/c mice and used LO2 cells for in vitro verification to investigate the effects and mechanisms of liver lipid metabolism caused by MC-LR and NaNO2. The results showed that after 6 months of exposure to MC-LR and NaNO2, the lipid droplets content was increased, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were raised in the liver (P < 0.05). Moreover, MC-LR and NaNO2 synergistically induced hepatic oxidative stress by decreasing total superoxide dismutase (T-SOD) activity and glutathione (GSH) levels and increasing malondialdehyde (MDA) content levels. In addition, the levels of Nrf2, HO-1, NQO1 and P-AMPK was decreased and Keap1 was increased in the Nrf2/HO-1 pathway. The key factors of lipid metabolism, SREBP-1c, FASN and ACC, were up-regulated in the liver. More importantly, there was a combined effect on lipid deposition of MC-LR and NaNO2 co-exposure. In vitro experiments, MC-LR and NaNO2-induced lipid deposition and changes in lipid metabolism-related changes were mitigated after activation of the Nrf2/HO-1 signaling pathway by the Nrf2 activator tertiary butylhydroquinone (TBHQ). Additionally, TBHQ alleviated the rise of reactive oxygen species (ROS) in LO2 cells induced by MC-LR and NaNO2. Overall, our findings indicated that MC-LR and NaNO2 can cause abnormal liver lipid metabolism, and the combined effects were observed after MC-LR and NaNO2 co-exposure. The Nrf2/HO-1 signal pathway may be a potential target for prevention and control of liver toxicity caused by MC-LR and NaNO2.

The cytotoxicity of microcystin-LR: ultrastructural and functional damage of cells.

Microcystin-LR (MC-LR) is a toxin produced by cyanobacteria, which is widely distributed in eutrophic water bodies and has multi-organ toxicity. Previous cytotoxicity studies have mostly elucidated the effects of MC-LR on intracellular-related factors, proteins, and DNA at the molecular level. However, there have been few studies on the adverse effects of MC-LR on cell ultrastructure and function. Therefore, research on the cytotoxicity of MC-LR in recent years was collected and summarized. It was found that MC-LR can induce a series of cytotoxic effects, including decreased cell viability, induced autophagy, apoptosis and necrosis, altered cell cycle, altered cell morphology, abnormal cell migration and invasion as well as leading to genetic damage. The above cytotoxic effects were related to the damage of various ultrastructure and functions such as cell membranes and mitochondria. Furthermore, MC-LR can disrupt cell ultrastructure and function by inducing oxidative stress and inhibiting protein phosphatase activity. In addition, the combined toxic effects of MC-LR and other environmental pollutants were investigated. This review explored the toxic targets of MC-LR at the subcellular level, which will provide new ideas for the prevention and treatment of multi-organ toxicity caused by MC-LR.

Does climate change increase the risk of marine toxins? Insights from changing seawater conditions.

Marine toxins produced by marine organisms threaten human health and impose a heavy public health burden on coastal countries. Lately, there has been an emergence of marine toxins in regions that were previously unaffected, and it is believed that climate change may be a significant factor. This paper systematically summarizes the impact of climate change on the risk of marine toxins in terms of changes in seawater conditions. From our findings, climate change can cause ocean warming, acidification, stratification, and sea-level rise. These climatic events can alter the surface temperature, salinity, pH, and nutrient conditions of seawater, which may promote the growth of various algae and bacteria, facilitating the production of marine toxins. On the other hand, climate change may expand the living ranges of marine organisms (such as algae, bacteria, and fish), thereby exacerbating the production and spread of marine toxins. In addition, the sources, distribution, and toxicity of ciguatoxin, tetrodotoxin, cyclic imines, and microcystin were described to improve public awareness of these emerging marine toxins. Looking ahead, developing interdisciplinary cooperation, strengthening monitoring of emerging marine toxins, and exploring more novel approaches are essential to better address the risks of marine toxins posed by climate change. Altogether, the interrelationships between climate, marine ecology, and marine toxins were analyzed in this study, providing a theoretical basis for preventing and managing future health risks from marine toxins.

Prognostic and clinicopathological significance of C-reactive protein in patients with ovarian cancer: a meta-analysis.

BACKGROUND: Many studies have explored the relationship between C-reactive protein (CRP) levels and survival outcomes in patients with ovarian cancer (OC); however, consistent results have not been reported. As such, this meta-analysis was performed to accurately assess the prognostic and clinicopathological roles of CRP in OC. METHODS: The PubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched for relevant studies published from inception to April 7, 2023. The effect of CRP level(s) and OC prognostic outcomes was analyzed by computing the combined hazard ratio (HR) and corresponding 95% confidence interval (CI). Thereafter, the association between CRP level(s) and clinicopathological factors was evaluated using a combined odds ratio (OR) and corresponding 95% CI. RESULTS: The present meta-analysis included 15 studies comprising 3202 subjects. According to the combined data, higher CRP levels were markedly associated with unfavorable overall survival (OS) (HR 1.23 [95% CI 1.11-1.37]; p < 0.001) and progression-free survival (PFS) (HR 1.55 [95% CI 1.30-1.84]; p < 0.001) in patients with OC. Furthermore, the results indicated that high CRP levels were significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stages III-IV (p < 0.001), residual tumor size ≥ 1 cm (p < 0.001), histological grade 3 (p = 0.040), and ascites volume ≥ 500 mL (p < 0.001). CONCLUSION: The results of this meta-analysis demonstrated that higher serum CRP levels were strongly associated with dismal OS and PFS in subjects with OC. High CRP levels were also significantly associated with clinical factors implicated in tumor aggressiveness and the development of OC.

Prognostic value of pretreatment lymphocyte-to-monocyte ratio in patients with glioma: a meta-analysis.

BACKGROUND: Many studies have explored the prognostic role of the lymphocyte-to-monocyte ratio (LMR) in patients with glioma, but the results have been inconsistent. We therefore conducted the current meta-analysis to identify the accurate prognostic effect of LMR in glioma. METHODS: The electronic databases of PubMed, Web of Science, Embase, and Cochrane Library were thoroughly searched from inception to July 25, 2023. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to estimate the prognostic role of LMR for glioma. RESULTS: A total of 16 studies comprising 3,407 patients were included in this meta-analysis. A low LMR was significantly associated with worse overall survival (OS) (HR = 1.35, 95% CI = 1.13-1.61, p = 0.001) in glioma. However, there was no significant correlation between LMR and progression-free survival (PFS) (HR = 1.20, 95% CI = 0.75-1.91, p = 0.442) in glioma patients. Subgroup analysis indicated that a low LMR was significantly associated with inferior OS and PFS in glioma when using a cutoff value of ≤ 3.7 or when patients received mixed treatment. CONCLUSIONS: This meta-analysis demonstrated that a low LMR was significantly associated with poor OS in glioma. There was no significant correlation between LMR and PFS in glioma patients. The LMR could be a promising and cost-effective prognostic biomarker in patients with glioma in clinical practice.

Research on the pre-pulses caused by post-pulses in the optical parametric chirped-pulse amplifier.

Pre-pulses caused by the post-pulses in the optical parametric chirped-pulse amplifier were comprehensively studied for the first time, including the underlying mechanism for the delay-shift of pre-pulses, the intensity variation of pre-pulses affected by the initial delay of post-pulses and the pump energy, and also the nonlinear beat noise. The simulation and measurement confirmed that the high-order dispersion of the pulse stretcher was the main cause for the delay-shift of pre-pulses, which should be similar with the chirped-pulse amplifiers. The intensity of pre-pulses would decrease significantly as the initial delay of post-pulses increased, but would increase with the growth of pump energy. Moreover, the temporal position of the nonlinear beat noise in the experiment was successfully predicted by our simulation. This work could help us better understand the pre-pulses in OPCPA and provide helpful guidance for designing high-contrast laser systems.

Multifunctional Lanthanide Metal-Organic Frameworks Based on -NH2 Modified Ligand: Fluorescent Ratio Probe, CrO42- Ions Adsorption, and Photocatalytic Property.

In response to the growing concern for environmental pollution, two lanthanide compounds {[Ln(L)(H2O)]·4H2O}n (where Ln = Tb and Gd, H3L = 1-amino-2,4,6-benzene tricarboxylic acid) were synthesized using a -NH2 modified ligand and systematically characterized. Both compounds exhibit remarkable fluorescence response, adsorption of CrO42- ions, and photocatalytic degradation properties, as well as exceptional acid-base and thermal stability. Remarkably, the pH-dependent 1-Tb exhibits exceptional performance as a fluorescent probe for detecting Fe3+ and CrO42-/Cr2O72- ions in aqueous solutions, while also serving as a ratiometric fluorescent probe for the detection of Cr3+, offering rapid response, high sensitivity, selectivity, and recoverability advantages in application. Moreover, 1-Tb exhibits excellent detection capabilities and displays effective adsorption of CrO42- ions, with a maximum adsorption capacity of 230.71 mg/g. On the other hand, 1-Gd exhibits superior performance compared to 1-Tb in the photocatalytic degradation of antibiotics. The degradation mechanism is further elucidated by conducting experiments with DFT theoretical calculations.

Delay-shift and asymmetric broadening of pre-pulses by post-pulses in a petawatt laser facility.

The temporal contrast of high-peak-power lasers is usually limited by pre-pulses, which are generally produced by post-pulses due to the nonlinearity of the active medium. The reason for the conversion between pre-pulse and post-pulse is now well known, but the mechanisms for the delay-shift and asymmetric broadening of the newly generated pre-pulse are not yet clear. In this work, a novel, to the best of our knowledge, numerical model combining the nonlinear Schrödinger equation and the Frantz-Nodvik equation is proposed to investigate the underlying mechanisms for the "distortion" of the pre-pulse. Numerical results show that the gain characteristics of Ti:sapphire amplifiers can only make a minor change on the temporal profile of the pre-pulse, but the high-order dispersion is the main cause for the delay-shift and asymmetric broadening of the pre-pulse, and the effects are more significant for the initial post-pulse with a relatively larger delay.

Angular dispersion compensation for ultra-broadband pulses by using a cascaded prism and hollow-core fiber configuration.

In this paper, we report that the angular dispersion of the output pulses in a nonlinear process can be efficiently compensated by using a cascaded prism(s) and short hollow-core fiber (HCF) configuration. Here, the prism(s) is used to suppress the angular dispersion and transform it into spatial chirp, while the HCF is used for removing this spatial chirp and the residual angular dispersion, which can also significantly improve the beam quality. The feasibility of this novel method is numerically and experimentally investigated with the ultra-broadband idler pulses centered at 1250 nm wavelength and generated by an LBO crystal based non-collinear optical parametric amplifier. The proof-of-principle experiment shows that the angular dispersion can be effectively removed and ultra-broadband idler pulses with good spectral quality and spatial profile can be obtained. The total transmission efficiency in the experiment is around 67% and the measured M x2 and M y2 can reach 1.12 and 1.04, respectively. To the best of our knowledge, this is the first reported ultra-broadband angular dispersion compensation scheme combining prism(s) and HCF, which can remarkably eliminate the angular dispersion while simultaneously possesses high efficiency, good spectral and beam spatial quality.

Suppressing scattering-induced nanosecond pre-pulses in Ti:sapphire multi-pass amplifiers.

In this Letter, we experimentally investigate a new kind of nanosecond pre-pulse, which originates from the bidirectional scattering of crystals in traditional Ti:sapphire multi-pass amplifiers. The experimental results demonstrate that the intensity of scattering-induced pre-pulses is very sensitive to the scattering angle, and the delay time between the pre-pulse and the main pulse is an integer multiple of the light path in each pass of the amplifier. An optimized multi-pass amplifier configuration is proposed, for what is believed to be the first time, to suppress the scattering-induced pre-pulses. The contrast ratio between pre-pulses and the main pulse is enhanced by more than two orders of magnitude, reaching a level of 10-10. This novel multi-pass amplifier configuration is very simple and economical, and provides an effective solution for the temporal contrast enhancement in the nanosecond range.

Investigation and suppression of pre-pulses on nanosecond time scale in the SULF-1PW laser.

It is of crucial significance to investigate and suppress pre-pulses on nanosecond time scale because the intense pre-plasma generated by them may have enough time to expand and, thus, cause fatal impact on laser-matter interactions. In this research, we analyze the potential origins of pre-pulses on nanosecond time scale in a typical Ti:sapphire chirped pulse amplification laser system. Based on the analysis, the initial status of these generated pre-pulses in the SULF-1PW laser is measured and investigated. Then different measures, including fine control on the time synchronization and the replacement for the Ti:sapphire, are adopted in the SULF-1PW laser to suppress these pre-pulses with respective origins, which can promote the energy ratio between the main pulse and these pre-pulses by 2-3 orders of magnitude. This research not only improves the temporal contrast of the SULF-1PW laser on nanosecond time scale but also provides beneficial guidance for the design and construction of similar laser facilities.

Tail Risk Early Warning System for Capital Markets Based on Machine Learning Algorithms.

Scientific and effective tail risk measurement and early warning are key points and difficulties in the identification and control of major risks in capital markets. In this paper, we use the autoregressive conditional Fréchet model (AcF) to construct a tail risk measurement index for the capital market in China. The tail risk status identified by the scientific index method is used as a monitoring anchor to construct and optimize a tail risk early warning model based on machine learning algorithms. The study yields three findings. (1) The AcF model can overcome the shortcomings of traditional models in tail risk measurement and significantly improve the tail risk measurement efficiency of the capital market. (2) Tail risk synergies between equity and bond markets are significantly stronger than yield synergies, and the tail risk measure index has the role of a leading indicator of significant risk in capital markets. (3) Based on the joint test of risk status and crisis identification efficiency, the Logit model of crisis identification fails whereas the tail risk warning model optimized by machine learning algorithms can accurately identify crises and significant risks. The optimal early warning model pairings for the stock market and bond market are the oversampling-random forest algorithm and the double sampling-random forest algorithm, respectively, with out-of-sample crisis warning accuracies of 81.94% and 90.20%, respectively.

Performance improvement of a nonlinear temporal filter by using cascaded femtosecond optical parametric amplification.

In this paper, we report that the conversion efficiency and spectrum of femtosecond optical parametric amplification (fs-OPA) can be significantly enhanced by employing a compact cascaded femtosecond OPA (CF-OPA) scheme with the self-compensation of the temporal walk-off between two nonlinear gain media. Correspondingly, the gain related temporal contrast can also be improved. The feasibility of the CF-OPA method using three cascaded BBO crystals is numerically and experimentally analyzed. Moreover, by replacing the conventional fs-OPA with the CF-OPA and optimizing the design, the performance of a nonlinear temporal filter combining cross-polarized wave generation and fs-OPA is comprehensively improved. The experimental results demonstrate the superiority of the CF-OPA scheme, which can generate high-performance cleaned pulses at 1 kHz repetition rate with energy of 340µJ, energy fluctuation below 0.9% (RMS), spectral width of 97 nm (FWHM), Fourier-transform-limited pulse width of 12 fs and temporal contrast better than 10-12. To the best of our knowledge, this is the first reported temporal walk-off self-compensated quasi-collinear CF-OPA geometry adopting three cascaded BBO crystals, which can be easily generalized to other wavelengths or nonlinear crystals. The above nonlinear temporal filter with a CF-OPA scheme has the rarest comprehensive parameters, which can provide excellent seed pulses for PW and 10 PW class femtosecond laser systems.

Pretreatment Prognostic Nutritional Index (PNI) as a Prognostic Factor in Patients with Biliary Tract Cancer: A Meta-Analysis.

OBJECTIVE: Many reports have shown that the prognostic nutritional index (PNI) is associated with the clinical outcomes of patients with biliary tract cancer (BTC), with the results being inconsistent. We therefore comprehensively evaluated the prognostic significance of the PNI in BTC by performing a meta-analysis. METHODS: We identified relevant studies by searching PubMed, Embase, Web of Science and, the Cochrane Library. The combined hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI) were used to evaluate the association between PNI and overall survival (OS) and the clinical characteristics of BTC. RESULTS: We included seven studies with 1608 patients in this meta-analysis. The pretreatment low PNI correlated significantly with worse OS (HR = 1.65, 95%CI = 1.42-1.93, p < 0.001). In addition, the prognostic effect of PNI are reliable in different subgroups of ethnicity, sample size, histology, treatment, PNI cutoff, and cutoff determination. The low PNI was also related to poor differentiation (OR = 1.95, 95%CI = 1.34-2.85, p = 0.001) as well as higher T stage (OR = 2.51, 95%CI = 1.69-3.74, p < 0.001) in BTC. CONCLUSION: The low PNI is significantly associated with inferior prognosis of patients with BTC and aggressive clinical factors. The PNI could be applied as an independent prognostic marker for patients with BTC.

Numerical analysis of the DKDP-based high-energy optical parametric chirped pulse amplifier for a 100 PW class laser.

An optical parametric chirped pulse amplifier (OPCPA) based on a large-aperture DKDP crystal and pumped by a 10 kJ level Nd:glass laser can serve as the final amplifier for a 100 PW level laser. A comprehensive numerical investigation on such a high-energy OPCPA is presented in this work. The effects on the efficiency-bandwidth product induced by the deuteration level, absorption loss, temperature variation, and optimization of zero-phase-mismatch wavelength (ZPMW) are analyzed in detail. Based on the analysis above, a three-dimensional numerical simulation taking into account the effects of pumping depletion, diffraction, and walk-off shows that, by optimization of ZPMW, broadband (over 210 nm spectral width in FWHM) and high efficiency (${\gt}37\%$) amplification can be realized in the DKDP crystal even with a moderate deuteration level of 70%, which can relax the requirement of a high deuteration level in a large-aperture DKDP crystal. The numerical analysis can provide meaningful guidance for the design and construction of 100 PW class laser systems.

A novel design of double chirped pulse amplification laser systems for fourth-order dispersion control.

A novel design of double chirped pulse amplification laser systems implementing a combination of negatively and positively chirped pulse amplification is proposed for the first time. Without utilizing any extra dispersion compensation element, this design can sufficiently cancel out the second-, third- and especially fourth-order dispersion simultaneously, just by optimizing the parameters of the stretcher and compressor in first chirped pulse amplification stage which applies negatively chirped pulse amplification. The numerical results indicate that near Fourier-transform-limited pulse duration about 20fs can be achieved in high-peak-power femtosecond laser systems up to multi-Petawatt level. This design not only provides a feasible solution for the dispersion control in high-contrast and high-peak-power femtosecond laser systems, but also can avoid the degradation of temporal contrast induced by seed energy loss in the presence of additional dispersion compensation components.

Etiological analysis of virus, mycoplasma pneumoniae and chlamydia pneumoniae in hospitalized children with acute respiratory infections in Huzhou.

BACKGROUND: Acute respiratory infections are a common disease in children with high mortality and morbidity. Multiple pathogens can cause acute respiratory infections. A 2-year survey of hospitalized children was conducted to understand the epidemic situation, seasonal spread of pathogens and the improvement of clinical diagnosis, treatment and prevention of disease in Huzhou, China. METHODS: From September 2017 to August 2019, 3121 nasopharyngeal swabs from hospitalized children with acute respiratory infections were collected, and real-time PCR was used to detect various pathogens. Then, pathogen profiles, frequency and seasonality were analyzed. RESULTS: Of the 3121 specimens, 14.45% (451/3121) were positive for at least one pathogen. Of the single-pathogen infections, RSV (45.61%, 182/399) was the most frequent pathogen, followed by PIVs (14.79%, 59/399), ADV (14.54%, 58/399), MP (10.78%, 43/399), and IAV (5.26%, 21/399). Of the 52 coinfections, RSV + PIVs viruses were predominantly identified and accounted for 40.38% (21/52) of cases. RSV was the most frequent pathogen in all four groups. The highest positive rate of the pathogens occurred in the winter (21.26%), followed by autumn (14.98%), the summer (14.11%) and the spring (12.25%). CONCLUSION: Viruses are the main pathogens in hospitalized children with acute respiratory infections in Huzhou city, Zhejiang Province, China. Among the pathogens, RSV had the highest detection rate, and MP is also a common pathogen among children with acute respiratory infections. This study provided a better understanding of the distribution of pathogens in children of different ages and seasons, which is conducive to the development of more reasonable treatment strategies and prevention and control measures.

Investigation of spatio-temporal stretching in a duplex grating compressor.

We employ the modified 6×6 matrix formalism to describe a pulsed Gaussian beam diffracted by a grating with arbitrary orientation. The matrix treatment is used to analyze the evolution of a pulsed beam propagating in a duplex grating compressor (DGC). For chirped pulse incidence, the inclination angle required in DGC setups will introduce several kinds of first-order spatio-temporal couplings (STCs). We found that temporal stretching due to spatial chirp is suppressed with enlarged beam diameter. Pulse-front tilt and residual frequency chirp in the compressed pulse will be eliminated simultaneously. Pulse with the transform-limited duration can be expected in ultra-intense and ultra-short pulse laser systems employing DGC.

Investigation of the temporal contrast evolution in a 10-PW-level Ti:sapphire laser facility.

We have theoretically and experimentally investigated the evolution of the temporal contrast in a 10-PW-level Ti:sapphire laser in the Shanghai Superintense Ultrafast Laser Facility (SULF). The effects induced by the grism pair, spectral shaping filter, and increase in gain on the temporal contrast were investigated. First, it was found that the energy loss of clean seed pulses in the grism pair is a major factor in contrast degradation. Because of the low transmission efficiency of the grism pair (~10%), the temporal contrast is degraded by one order of magnitude. Second, the spectral shaping filter in the regenerative amplifier degrades the temporal contrast by increasing the intracavity loss. Finally, as the amplified spontaneous emission pedestal experiences gain more than the main pulse in Ti:sapphire amplifiers, particularly during saturated amplification, the temporal contrast will further deteriorate as the gain increases in multi-stage Ti:sapphire amplifiers. In addition, the effect on the temporal contrast induced by the extraction during pumping technique in large-aperture Ti:sapphire amplifiers has been considered. According to the investigations described above, the design of the SULF can be further improved. It is predicted that a temporal contrast of over 10-11 can be achieved at a peak power of 10 PW following the improvements. The investigations conducted in this study can provide guidelines for improving the temporal contrast in ultrahigh-peak-power Ti:sapphire lasers.

Prognostic impact of platelet-to-lymphocyte ratio on diffuse large B-cell lymphoma: a meta-analysis.

BACKGROUND: Recently, some studies reported the prognostic value of platelet-to-lymphocyte ratio (PLR) in patients with diffuse large B-cell lymphoma (DLBCL), however, the results varied from different studies. Therefore, we performed a meta-analysis to explore the prognostic value of PLR in DLBCL. METHODS: A comprehensive literature retrieval was conducted by using PubMed, Embase, Web of Science, the Cochrane Library, the China National Knowledge Infrastructure (CNKI), and Wanfang. Pooled hazard ratio (HR) and 95% confidence interval (CI) were used to evaluate the association of PLR and overall survival (OS) and progression-free survival (PFS). Odd ratios (ORs) and 95% CIs for clinicopathological characteristics were statistically analyzed. RESULTS: Eight studies with 1931 patients were included for meta-analysis. The pooled analysis indicated that elevated PLR was significantly associated with poor OS (HR = 1.73, 95% CI 1.29-2.31, p < 0.001), but not PFS (HR = 0.85, 95% CI 0.57-1.27, p = 0.438). Furthermore, elevated PLR was significantly associated with presentation of B symptoms (OR = 2.27, 95% CI 1.29-3.98, p = 0.004), elevated lactate dehydrogenase (LDH) (OR = 2.76, 95% CI 2.05-3.72, p < 0.001), higher tumor stage (OR = 2.22, 95% CI 1.66-2.98, p < 0.001), and Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥ 2 (OR = 1.71, 95% CI 1.09-2.69, p = 0.019). However, elevated PLR was not significantly correlated with gender, age or cell of origin. CONCLUSION: This meta-analysis revealed that PLR may be an effective and noninvasive biomarker for poor prognosis and aggressive disease characteristics for patients with DLBCL.