Response time of an electron inside a molecule to light in strong-field ionization.

We study ionization of aligned H2+ in strong elliptically polarized laser fields numerically and analytically. The calculated offset angle in photoelectron momentum distribution is several degrees larger for the molecule than a model atom with similar ionization potential at diverse laser parameters. Using a strong-field model that considers the properties of multi-center and single-center Coulomb potentials, we are able to quantitatively reproduce this angle difference between the molecule and the atom. Further analyses based on this model show that the response time of electron to light which is encoded in the offset angle and is manifested as the time spent in tunneling ionization, is about 15 attoseconds longer for the molecule than the atom. This time difference is further enlarged when increasing the internuclear distance of the molecule.

[Relationship between serum procalcitonin level and severity and prognosis in patients with traumatic brain injury in plateau areas].

OBJECTIVE: To analyze the changes rule of serum procalcitonin (PCT) levels in patients with traumatic brain injury in plateau areas, and to evaluate its value in assessing the severity and prognosis of the patients. METHODS: A prospective cohort study was conducted. The patients with traumatic brain injury admitted to the critical care medicine departments of Xining Third People's Hospital (at an altitude of 2 260 metres) and Golmud City People's Hospital (at an altitude of 2 780 metres) from May 2018 to September 2022 were enrolled. According to the Glasgow coma scale (GCS) score at admission, the patients were divided into mild injury group (GCS score 13-15), severe injury group (GCS score 9-12), and critical injury group (GCS score 3-8). All patients received active treatment. Chemiluminescence immunoassay was used to measure the serum PCT levels of patients on the 1st, 3rd, 5th, and 7th day of admission. The Kendall tau-b correlation method was used to analyze the correlation between serum PCT levels at different time points and the severity of the disease. The patients were followed up until October 30, 2022. The prognosis of the patients was collected. The baseline data of patients with different prognosis were compared. The Cox regression method was used to analyze the relationship between baseline data, serum PCT levels at different time points and prognosis. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of serum PCT levels at different time points for death during follow-up. RESULTS: Finally, a total of 120 patients with traumatic brain injury were enrolled, including 52 cases in the mild injury group, 40 cases in the severe injury group, and 28 cases in the critical injury group. The serum PCT levels of patients in the mild injury group showed a continuous downward trend with the prolongation of admission time. The serum PCT levels in the severe injury and critical injury groups reached their peak at 3 days after admission, and were significantly higher than those in the mild injury group (µg/L: 3.53±0.68, 4.47±0.63 vs. 0.40±0.14, both P < 0.05), gradually decreasing thereafter, but still significantly higher than the mild injured group at 7 days. Kendall tau-b correlation analysis showed that there was a significant positive correlation between serum PCT levels on days 1, 3, 5, and 7 of admission and the severity of disease (r value was 0.801, 0.808, 0.766, 0.528, respectively, all P < 0.01). As of October 30, 2022, 92 out of 120 patients with traumatic brain injury survived and 28 died, with a mortality of 23.33%. Compared with the survival group, the GCS score, serum interleukin-6 (IL-6) levels, white blood cell count (WBC) in peripheral blood, and PCT levels in cerebrospinal fluid at admission in the death group were significantly increased [GCS score: 5.20±0.82 vs. 4.35±0.93, IL-6 (ng/L): 1.63±0.45 vs. 0.95±0.27, blood WBC (×109/L): 14.31±2.03 vs. 11.95±1.98, PCT in cerebrospinal fluid (µg/L): 11.30±1.21 vs. 3.02±0.68, all P < 0.01]. The serum PCT levels of patients in the survival group showed a continuous downward trend with prolonged admission time. The serum PCT level in the death group peaked at 3 days after admission and was significantly higher than that in the survival group (µg/L: 4.11±0.62 vs. 0.52±0.13, P < 0.01), gradually decreasing thereafter, but still significantly higher than the survival group at 7 days. Cox regression analysis showed that serum IL-6 levels [hazard ratio (HR) = 17.347, 95% confidence interval (95%CI) was 5.874-51.232], WBC in peripheral blood (HR = 1.383, 95%CI was 1.125-1.700), PCT levels in cerebrospinal fluid (HR = 1.952, 95%CI was 1.535-2.482) at admission and serum PCT levels on admission days 1, 3, 5, and 7 [HR (95%CI) was 6.776 (1.844-24.906), 1.840 (1.069-3.165), 3.447 (1.284-9.254), and 6.666 (1.214-36.618), respectively] were independent risk factors for death during follow-up in patients with traumatic brain injury (all P < 0.05). ROC curve analysis showed that the AUC of serum PCT levels on days 1, 3, 5, and 7 for predicting death during follow-up in patients with traumatic brain injury was all > 0.8 [AUC (95%CI) was 0.898 (0.821-0.975), 0.800 (0.701-0.899), 0.899 (0.828-0.970), 0.865 (0.773-0.958), respectively], indicating ideal predictive value. The optimal cut-off value for serum PCT level at 3 days of admission was 1.88 µg/L, with the sensitivity of 78.6% and specificity of 88.0% for predicting death during follow-up. CONCLUSIONS: Abnormal expression of serum PCT levels in patients with traumatic brain injury on the 3rd day of admission was found. The serum PCT levels greater than 3 µg/L may be related to severe illness. The serum PCT levels greater than 1.88 µg/L can predict the poor prognosis of patients. Dynamic observation of changes in serum PCT levels has good evaluation value for the severity and prognosis of patients with traumatic brain injury in plateau areas.

Two-color attosecond chronoscope.

We study ionization of atoms in strong orthogonal two-color (OTC) laser fields numerically and analytically. The calculated photoelectron momentum distribution shows two typical structures: a rectangular-like one and a shoulder-like one, the positions of which depend on the laser parameters. Using a strong-field model which allows us to quantitatively evaluate the Coulomb effect, we show that these two structures arise from attosecond response of electron inside an atom to light in OTC-induced photoemission. Some simple mappings between the locations of these structures and response time are derived. Through these mappings, we are able to establish a two-color attosecond chronoscope for timing electron emission, which is essential for OTC-based precise manipulation.

Improvement of Antialveolar echinococcosis efficacy of novel Albendazole-Bile acids Derivatives with Enhanced Oral Bioavailability.

Alveolar echinococcosis (AE) is a chronic and fatal infectious parasitic disease, which has not been well-researched. Current recommended therapies for AE by the World Health Organization include complete removal of the infected tissue followed by two years of albendazole (ABZ), administered orally, which is the only effective first-line anti-AE drug. Unfortunately, in most cases, complete resection of AE lesions is impossible, requiring ABZ administration for even longer periods. Only one-third of patients experienced complete remission or cure with such treatments, primarily due to ABZ's low solubility and low bioavailability. To improve ABZ bioavailability, albendazole bile acid derivative (ABZ-BA) has been designed and synthesized. Its structure was identified by mass spectrometry and nuclear magnetic resonance. Its physicochemical properties were evaluated by wide-angle X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and polarizing microscopy; it was compared with ABZ to assess its solubilization mechanism at the molecular level. To avoid the effects of bile acid on the efficacy of albendazole, the inhibitory effect of ABZ-BA on protoscolex (PSCs)s was observed in vitro. The inhibitory effect of ABZ-BA on PSCs was evaluated by survival rate, ultrastructural changes, and the expression of key cytokines during PSC apoptosis. The results showed that ABZ-BA with 4-amino-1-butanol as a linker was successfully prepared. Physicochemical characterization demonstrated that the molecular arrangement of ABZ-BA presents a short-range disordered amorphous state, which changes the drug morphology compared with crystalline ABZ. The equilibrium solubility of ABZ-BA was 4-fold higher than ABZ in vitro. ABZ-BA relative bioavailability (Frel) in Sprague-Dawley (SD) rats was 26-fold higher than ABZ in vivo. The inhibitory effect of ABZ-BA on PSCs was identical to that of ABZ, indicating that adding bile acid did not affect the efficacy of anti-echinococcosis. In the pharmacodynamics study, it was found that the ABZ-BA group had 2.7-fold greater than that of Albenda after 1 month of oral administration. The relative bioavailability of ABZ-BA is significantly better than ABZ due to the transformation of the physical state from a crystalline state to an amorphous state. Furthermore, sodium-dependent bile acid transporter (ASBT) expressed in the apical small intestine has a synergistic effect through the effective transport of bile acids. Therefore, we concluded that the NC formulation could potentially be developed to improve anti-AE drug therapy.

Optimization of supercritical-CO2 extraction and pharmacokinetics in SD rats of alkaloids form Sophora moorcroftiana seed.

The total alkaloids extracted from the seeds of Sophora moorcroftiana (TAs-SM) have the potential to treat alveolar echinococcosis, a disease included by the WHO in a list of 17 key neglected diseases world-wide. The aims of the current study were first to develop a supercritical fluid extraction (SFE) method for optimizing TAs-SM extraction, and second, to develop an optimized method for evaluating TAs-SM pharmacokinetics in vivo. The Box-Behnken response surface method was used to optimize the extraction process, and ultra-high liquid chromatography coupled with high resolution electrospray mass spectrometry (UPLC-HR-ESI-MS) was used to determine the pharmacokinetics of TAs-SM in SD rats. The results indicated the following optimal SFE extraction conditions: pressure = 31 MPa, temperature = 70 °C, time = 162.18 min. With these parameters, total alkaloids could be extracted from each gram of S. moorcroftiana, with the total content being 68.88 µg. The linear range of UPLC-HR-ESI-MS is 0.78-200.00 ng/ml, R2 > 0.99, and the sample recovery is 99-113%. The precision, accuracy, selectivity and stability of the method meet the requirements of US FDA guidelines. To our knowledge this study is the first to establish an SFE method for extracting TAs-SM and the first to employ UPLC-HR-ESI-MS for measuring TAs-SM in rats. These findings provide important contributions for using TAs-SM in further drug development and clinical applications.

The Association Between Depressive Symptoms and Insomnia in College Students in Qinghai Province: The Mediating Effect of Rumination.

Background: This study investigates the mediating effect of rumination on the associations between depressive symptoms and insomnia. Methods: This is a cross-sectional study. Insomnia Severity Index (ISI), Ruminant Response Scale (RRS) and Beck Depression Inventory (BDI) were determined in 12,178 college students in Qinghai province by a questionnaire network platform. Results: The prevalence of insomnia was 38.6% in the participants. Insomnia symptoms [interquartile range: 6 (3, 9)], depressive symptoms [interquartile range: 5 (1, 9)], and rumination [interquartile range: 22 (20, 26)] were positively correlated (r = 0.25-0.46, p < 0.01). Mediation effect analysis showed that the depressive symptoms affected insomnia directly and indirectly. The direct effect and the indirect effect through rumination account for 92.4 and 7.6% of the total effect, respectively. Conclusion: The study shows that insomnia, depressive symptoms, and rumination are related constructs in college students in Qinghai province. It demonstrates the direct effects and the rumination-mediated indirect effects between depressive symptoms and insomnia; the direct effects seem to be dominant.

Improvement of the Bioavailability and Anti-hepatic Alveolar Echinococcosis Effect of Albendazole-Isethionate/Hypromellose Acetate Succinate (HPMC-AS) Complex.

Maximizing the pharmacodynamics of albendazole (ABZ), which is used to treat echinococcoses, is essential for the long-term treatment of echinococcosis patients. ABZ is a weak base whose solubility depends on the pH value of the solvent. After it has been orally administered, its solubility drops sharply from when it is in gastric juices (pH 1.4) to when it is in intestinal juices (pH 6.5) and is subsequently absorbed in the ileum and jejunum. This results in low solubility and poor bioavailability of the drug. In this study, we developed an orally administered albendazole-isethionate (ABZ-HES)/hypromellose acetate succinate (HPMC-AS) complex tablet (TABZ-HES-H) with improved solubility and bioavailability. Previous studies demonstrated that ABZ-HES has a higher intrinsic dissolution rate under pH 1.4 than the ABZ free base used in the commercial product Albenda and that HPMC-AS can effectively inhibit ABZ crystallization, which could be due to the hydrophobic interaction between ABZ and HPMC-AS in an aqueous environment. In this study, the dissolution behavior of TABZ-HES-Hin vitro was studied by the two-step pH conversion method. Our results demonstrated that the oral bioavailability of TABZ-HES-H was approximately 2.6 times higher than that of ABZ. More importantly, in the rat model of secondary hepatic alveolar echinococcosis, the anti-hepatic alveolar echinococcosis effect of TABZ-HES-H was 3.4 times higher than that of a commercial product. The improved preparation with salt and polymer has proven to be a feasible method of improving the oral bioavailability and pharmacodynamics of ABZ.

Evaluation of Drug Dissolution Rate in Co-amorphous and Co-crystal Binary Drug Delivery Systems by Thermodynamic and Kinetic Methods.

In order to better explain and predict the dissolution characteristics of binary drug delivery systems (BDDSs), the dissolution behaviors of co-crystal (CC) and co-amorphous (CA) systems of sacubitril (SCB) and valsartan (VST) were evaluated in vitro and in vivo by thermodynamic and kinetic methods. The CCs of SCB and VST were prepared into a CA state through rotary evaporation. Solid-state properties were systematically evaluated. Herein, based on the results from previous studies of single-phase systems, we used thermodynamic methods to evaluate the increase in drug dissolution rate after BDDSs change from the crystalline to the amorphous state. After comparing the predicted and measured dissolution rate enhancement of the CC and CA systems, this paper attempts to explain the dissolution rate characteristics of the BDDSs. We then evaluated the bioavailability of two BDDSs in beagle dogs to confirm that there was no discrepancy in vivo with the results obtained in vitro. The results exhibited that there is strong intermolecular interaction between SCB and VST and good physical stability for the CA system. Compared with the CC, the bioavailability of SCB and VST in the CA system increased by 313.9% and 130.5%, respectively. The predicted dissolution rate ratio between CC and CA systems and their actual intrinsic dissolution rates differed by only a factor of 2.5, demonstrating the good correlation between the predicted and measured values. In the future, this method could be expanded to a variety of new samples and exciting drug prospects.

Effects of health education on HIV/AIDS related knowledge among first year university students in China.

BACKGROUND: The number of new HIV infections has increased and implementation of school-based health education programs on AIDS have been advocated for a long time. OBJECTIVE: This study aimed to explore the effectiveness of an intervention of HIV/AIDS on the knowledge of HIV/AIDS prevention and control among first year university students. METHODS: An awareness questionnaire was adopted to assess awareness and knowledge of HIV/AIDS pre- and post-health education among first year university students in Qinghai, China. Independent sample t-test, chi-square test, and multiple logistic regression analyses were used. RESULTS: A total of 2,165 and 2,062 first year university students were respectively recruited pre- and post- HIV/AIDS health education. The awareness rate increased significantly after the health education intervention (from 48.59%, 95%CI: 46.47%-50.72% to 76.24%, 95%CI: 74.35%-78.06%). Students from Hui and Tibetan ethnicities, and those holding prejudices against AIDS patients were less knowledgeable than their counterparts regarding HIV/AIDS related knowledge, whereas urban-dwellers and those with higher paternal education were positively associated with awareness of HIV/AIDS related knowledge (p <0.05). CONCLUSION: HIV/AIDS awareness among first year university students improved greatly after receiving an education intervention, which underscores its utility as part of the approaches of HIV/AIDS control and prevention.

The Investigation of the Effect and Mechanism of Sophora moorcroftiana Alkaloids in Combination with Albendazole on Echinococcosis in an Experimental Rats Model.

Echinococcosis is a worldwide anthropozoonosis which is highly endemic over large animal husbandry areas in northwestern China. The current clinical therapeutic medicine against echinococcosis is albendazole, although it caused serious side effects in patients. The component in traditional Chinese herb medicine, Sophora moorcroftiana alkaloids (SA), is thought to be a potential drug to treat echinococcosis. In order to explore the effect and mechanism of SA treatment against echinococcosis, we established animal echinococcosis model and treated rats with albendazole alone, alkaloids alone, and combined therapy. The combined treatment showed effective inhibition against parasite infection due to induction of host response and alleviated liver injury; meanwhile albendazole caused serious liver problem. The proteomics study revealed that the combined therapy might induce complement activation through C3, C4, C5, SERPINA1, and SERPINC1 proteins and cell adhesion by ANXA2, EZR, YWHAB, HSP90AN1, and PRKAR2A proteins, while albendazole treatment could induce liver injury through CRYAB, YWHAZ, SLC25A24, and HSPA1B proteins that were involved in cell death. In all, we consider that the combinational treatment displayed better therapeutic effects against liver echinococcosis as well as alleviated liver injury, which could be considered as an effective strategy to treat echinococcosis clinically.