Comprehensive Utilization of Formation Water Scale to Prepare Controllable Size CaCO3 Nanoparticles: A New Method to Improve Oil Recovery.

Formation water scale blocks pipelines and results in oil/gas production decreasing and energy consumption increasing. Many methods have been developed to inhibit scale formation. However, these previous methods are limited by their complications and low efficiency. A new method is proposed in this paper that uses the scale in formation water as a nanomaterial to improve oil recovery via controlling particle size. A series of ligands were synthesized and characterized. Micrometer-CaCO3 was formed and accumulated to form scale of a large size under uncontrolled conditions. The tetradentate ligands (L4) exhibited an excellent capturing yield of Ca2+ (87%). The particle size was very small, but they accumulated to form large particles (approximately 1300 nm) in the presence of Na2CO3. The size of the CaCO3 could be further controlled by poly(aspartic acid) to form sizes of about 700 nm. The flooding test showed that this material effectively improved oil recovery from 55.2% without nano CaCO3 to 61.5% with nano CaCO3. This paves a new pathway for the utilization of Ca2+ in formation water.

Association of triglyceride-glucose index with helicobacter pylori infection and mortality among the US population.

BACKGROUND: Limited research has explored the potential association between the Triglyceride-Glucose (TyG) and mortality, especially in individuals with Helicobacter pylori (H. pylori) infection. This study seeks to investigate the correlation between the TyG index and H. pylori infection and investigate whether the associations between the TyG index exposure and all-cause mortality are mediated by H. pylori infection. METHODS: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, incorporating a final sample size of 2,187 participants. Both univariable and multivariable-adjusted logistic regression analyses were employed to examine the relationship between H. pylori infection and relevant covariates. To assess the association between TyG index, and all-cause mortality in individuals with or without H. pylori infection, Cox regression analysis, and restricted regression cubic spline analysis were implemented. RESULTS: A significant positive correlation was observed between the TyG index and an elevated risk of H. pylori infection [OR 1.157, 95% CI (1.383 ~ 1.664)]. This correlation persisted even after adjusting for confounding factors [OR 1.189, 95% CI (1.003, 1.411), P < 0.05]. Furthermore, in patients with positive H. pylori infection, a noteworthy nonlinear correlation between the TyG index and all-cause mortality was identified (P = 0.0361). With an increase in the TyG index, all-cause mortality exhibited a corresponding rise, particularly following adjustment for all potential confounding factors. Conversely, in patients with negative H. pylori infection, no significant association was observed between the TyG index and all-cause mortality after adjusting for potential confounding factors. CONCLUSION: A higher TyG index was linked to increased H. pylori infection risks. Participants in the higher quantile group of the TyG index are positively associated with higher all-cause mortality compared to the higher quantile group of the TyG index in H. pylori-positive participants instead of H. pylori-negative participants.

Association of frailty index with all-cause and cardiovascular mortality with different diabetic status: NHANES 1999-2018.

AIMS: The relationship between frailty and mortality among individuals with varying diabetic statuses represents a burgeoning area of concern and scholarly interest within the medical community. However, there are limited studies that explore the relationship between frailty and mortality, as well as cause-specific mortality among individuals with non-diabetes, prediabetes, and diabetes patients. Hence, this study aims to investigate the relationship between the frailty statues and all-cause mortality, as well as cause-specific mortality in individuals with varying diabetic statuses using the data in the NHANES database. METHODS: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, incorporating a final sample size of 57, 098 participants. Both univariable and multivariable-adjusted logistic regression analyses, as well as Cox regression analysis were employed to examine the relationship between frailty index (FI) and mortality. RESULTS: This study, found a significant positive correlation between the frailty and the increased risk of all-cause mortality non-diabetic [OR 4.277, 95%CI (3.982, 4.594), P < 0.001], prediabetic [OR 2.312, 95%CI (2.133, 2.506), P < 0.001], and diabetic patients [OR 3.947, 95%CI (3.378, 4.611), P < 0.001]. This correlation still existed even after adjusting for confounding factors including age, sex, BMI, poverty, fasting insulin, education, smoke, alcohol drink, waist, hypertension, hyperlipidemia, fasting glucose, HbA1c, eGFR, creatinine and total bilirubin. Our result also suggested a significant positive correlation between the frailty index and the increased risk of CVD mortality among non-diabetic [OR 3.095, 95%CI (2.858, 3.352), P < 0.001] and prediabetic [OR 5.985, 95%CI (5.188, 6.904), P < 0.001] individuals. However, in patients with diabetes, the correlation between frailty and CVD mortality lost significance after adjusting for possible confounding factors [OR 1.139, 95%CI (0.794, 1.634), P > 0.05]. CONCLUSION: A nonlinear relationship has been identified between the FI and all-cause mortality, as well as CVD mortality in non-diabetic and pre-diabetic population. In diabetic patients, there was a significant positive correlation between the frailty and the increased risk of all-cause mortality, but not with CVD mortality. Renal function and liver function might potentially acted as an intermediary factor that elevated the risk of CVD mortality in frail patients with diabetes.

Genetic variation and evolutionary characteristics of Echovirus 11: new variant within genotype D5 associated with neonatal death found in China.

Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. From 2018 to 2023, a surge in severe neonatal cases and fatalities linked to a novel variant of genotype D5 was documented in China, France, and Italy. However, the prevention and control of E11 variants have been hampered by limited background data on the virus circulation and genetic variance. Therefore, the present study investigated the circulating dynamics of E11 and the genetic variation and molecular evolution of genotype D5 through the collection of strains from the national acute flaccid paralysis (AFP) and hand, foot, and mouth disease (HFMD) surveillance system in China during 2000-2022 and genetic sequences published in the GenBank database. The results of this study revealed a prevalent dynamic of E11 circulation, with D5 being the predominant genotype worldwide. Further phylogenetic analysis of genotype D5 indicated that it could be subdivided into three important geographic clusters (D5-CHN1: 2014-2019, D5-CHN2: 2016-2022, and D5-EUR: 2022-2023). Additionally, variant-specific (144) amino acid mutation sites and positive-selection pressure sites (132, 262) were identified in the VP1 region. Cluster-specific recombination patterns were also identified, with CVB5, E6, and CVB4 as the major recombinant viruses. These findings provide a preliminary landscape of E11 circulation worldwide and basic scientific data for further study of the pathogenicity of E11 variants.

A new subspecies of Aporia procris Leech, 1890 hidden in Sichuan, China (Lepidoptera, Pieridae).

Further information on the distribution of Aporia procris Leech, 1890 is provided. The population of A. procris from the upper Dadu River, W. Sichuan, previously recognized as ssp. yaozhui Huang, 2021, is treated as a new subspecies, viz., A. p. huangsiyaoi ssp. nov., based upon evidence from external features, with its genital and molecular characters given.

A new species of the genus Celaenorrhinus Hbner, [1819] from Hainan, China (Lepidoptera, Hesperiidae).

A new species, Celaenorrhinus qianhanae Li & Liu sp. nov., is described from Hainan, China. Its unique genital characteristics and wing markings are compared with other congeneric species from this island and adjacent regions, including Vietnam and China, etc. In addition, its COI gene is sequenced for molecular analysis, and the secondary sexual character, hair tufts on hind tibiae, is discussed for comparison.

Discovery of novel Akt1 inhibitors by an ensemble-based virtual screening method, molecular dynamics simulation, and in vitro biological activity testing.

Akt1, as an important member of the Akt family, plays a controlled role in cancer cell growth and survival. Inhibition of Akt1 activity can promote cancer cell apoptosis and inhibit tumor growth. Therefore, in this investigation, a multilayer virtual screening approach, including receptor-ligand interaction-based pharmacophore, 3D-QSAR, molecular docking, and deep learning methods, was utilized to construct a virtual screening platform for Akt1 inhibitors. 17 representative compounds with different scaffolds were identified as potential Akt1 inhibitors from three databases. Among these 17 compounds, the Hit9 exhibited the best inhibitory activity against Akt1 with inhibition rate of 33.08% at concentration of 1 µM. The molecular dynamics simulations revealed that Hit9 and Akt1 could form a compact and stable complex. Moreover, Hit9 interacted with some key residues by hydrophobic, electrostatic, and hydrogen bonding interactions and induced substantial conformation changes in the hinge region of the Akt1 active site. The average binding free energies for the Akt1-CQU, Akt1-Ipatasertib, and Akt1-Hit9 systems were - 34.44, - 63.37, and - 39.14 kJ mol-1, respectively. In summary, the results obtained in this investigation suggested that Hit9 with novel scaffold may be a promising lead compound for developing new Akt1 inhibitor for treatment of various cancers with Akt1 overexpressed.

Detection and genotyping of enteroviruses in 3 960 influenza-negativeinfluenza-like illness cases in Chongqing / 公共卫生与预防医学

Objective To understand the epidemiological characteristics and genotype distribution of enterovirus (EV) in influenza-negative influenza-like illness (ILI) cases in Chongqing, and to provide a scientific basis for EV prevention and control. Methods Throat swab samples of influenza-negative ILI cases were collected from surveillance sites. The samples were detected for EV using real-time RT-PCR. The VP4 regions of positive samples were amplified and sequenced for genotyping. Results A total of 3 960 influenza-negative ILI samples were collected from January to December 2021, and 316 (7.98%) of them were EV-positive. EV could be detected in influenza-negative ILI cases in Chongqing all year round. The months with high EV-positive rates were January (11.60%), April (10.56%), May (11.79%), June (12.62%), and July (10.33%). There was a statistically significant difference in the detection rate of EV in ILI cases in different regions, gender, and age groups (χ2=29.647，χ2=4.192，χ2=69.176，P<0.05). A total of 213 EV-positive cases were successfully genotyped, including 17 genotypes of EV-A, EV-B, and EV-C and 5 genotypes of HRV-B. The dominant genotypes were CV-A4 (32.86%), CV-A2 (23.00%), CA-6 (12.21%), and CA-10 (11.74%). EV-D and novel EV were not identified in this study. Conclusion EV is an important pathogen in ILI cases in Chongqing. The prevalence of EV in ILI cases in Chongqing has typical regional, seasonal and population characteristics. Prevention and control should be carried out in Chongqing according to the epidemic characteristics of EV.

Establishment of pharmaceutical care pathway based on the problems related to chemotherapy / 中国药房

OBJECTIVE To design pharmaceutical care pathway for the problems related to chemotherapy， and to evaluate whether it contributes to the detection and intervention of drug-related problems （DRPs） in chemotherapy patients. METHODS The pharmaceutical care pathway table and flow charts were constructed and implemented by pharmaceutical care practice experience. The patients who were admitted to our hospital for chemotherapy before and after the implementation of the pharmaceutical care pathway were divided into control group （before the implementation，60 cases） and observation group （after the implementation，64 cases）， respectively； the relevant medical records of patients in the control group were extracted to evaluate DRPs， and pharmaceutical care of chemotherapy-related problems was performed for patients in observation group to extract DRPs. The basic condition， chemotherapy condition， DRPs classification and intervention status， adverse reactions induced by chemotherapy， PCNE classification of DRPs， occurrence time of DRPs， and drug classes related to DRPs were compared between 2 groups. RESULTS There was no statistical significance in the basic situation， chemotherapy regimen and chemotherapy drug category between the two groups （P＞0.05）. DRPs occurred in 46 and 37 patients in control group and observation group， respectively. In both groups， DRPs mainly occurred during chemotherapy， and mainly in the early stage of chemotherapy. Using the new pathway， the detection of DRPs significantly increased from 52.17% in the control group to 91.89% in the observation group （P＜0.05）. The successful intervention rate of DRPs was significantly increased from 32.61% in the control group to 72.97% in the observation group （P＜ 0.05）. The incidence of adverse drug reactions significantly decreased from 28.33% in the control group to 12.50% in the observation group（P＜0.05）. The main problem type of DRPs in the control group was treatment effectiveness， which mainly involved adjuvant antitumor drugs， mainly due to the use of adjuvant anti-tumor drugs for off-label prescribing； that of the observation group was treatment effectiveness and treatment safety， which mainly involved vomiting drugs， mainly due to insufficient medication to prevent nausea and vomiting caused by chemotherapy. CONCLUSIONS The implementation of the pathway helps clinical pharmacists to detect and intervene in DRPs among chemotherapy patients， and reduces the occurrence of chemotherapy-induced adverse reactions.

Analysis of micronucleus rate in 394 radiation workers with cytokinesis-block micronucleus method / 中国辐射卫生

Objective To analyze the micronucleus rate of radiation workers and to provide accurate occupational health monitoring basis in radiation workers exposed to low-level ionizing radiation for a long time. Methods The radiation group consisted of 353 radiation workers who had been exposed to ionizing radiation during work, while the control group consisted of 41 radiation workers who had not yet been exposed to ionizing radiation before work. The cytokinesis-block micronucleus method was used to determine the micronucleus rate. Results The average micronucleus rate in the radiation group was significantly higher than that in the control group (t = −2.95, P < 0.05). In the radiation group, the micronucleus rate gradually increased with age, and the difference was statistically significant (F = 8.36, P < 0.05). The micronucleus rates of workers with > 10 and > 30 years of service were significantly higher than those of workers with < 10 years of service (χ2 = −44.79, −60.47, P < 0.05). The micronucleus rate in females was significantly higher than that in males (t = 3.93, P < 0.05). The micronucleus rates in the diagnostic radiology group and the industrial detection group were significantly higher than that in the control group (t = 3.51, 3.65, P < 0.05). Conclusion The micronucleus rate has increased among the radiation workers exposed to low-level ionizing radiation for a long time. It is necessary to further strengthen occupational health monitoring and radiation protection education for radiation workers, especially the medical workers that constitute the largest population of radiation exposure workers.

Analysis of epidemiological and clinical characteristics of 1247 cases of infectious diseases of the central nervous system / 解放军医学杂志

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

Effect of NF-κB-regulated Drp-1 and PGC-1α in lung tissue of neonatal rats with meconium aspiration syndrome and its mechanism / 解放军医学杂志

Objective To investigate the role of dynamin-related protein 1(Drp-1)and peroxisome proliferator-activated receptor γ coactivator 1-α(PGC-1α)in the lung tissues of neonatal rats with meconium aspiration syndrome(MAS)and its mechanism.Methods Fifty 2-3-week-old SD neonatal rats were randomly divided into five groups(n=10):control group,model group and SN50 low,medium and high concentration groups.In control group,2 ml/kg of saline was injected into the trachea after tracheal exposure,and 2 ml/kg of meconium suspension was injected into the trachea of the rest of groups;after 24 h,control and model groups were left untreated,and 100 μl of each of SN50 concentrations of 10,30,and 60 μg/ml was injected into SN50 low,medium,and high concentration groups intraperitoneally;the rats of each group were killed after 6 h,and the chest X-rays,the gross views of the lungs,the lung wet/dry weight ratios(W/D),and the lungs of the rats in control group and model group were examined.After 6 h,the rats in each group were executed,and the pathological changes of lung tissue were observed by chest radiographs,lung gross view,lung wet/dry weight ratio(W/D)and HE staining;Western blotting was used to detect the changes of nuclear factor κB(NF-κB)(p65),p-NF-κB p65(p-p65),Drp-1,and PGC-1α proteins expression in neonatal rat lung tissues,and immuno-histochemistry was used to observe the expression of p65,Drp-1,and PGC-1α related proteins expression in neonatal rat lung tissues.Results Compared with control group,model group showed inflammatory infiltration in the chest radiograph and gross view,and the W/D and lung injury pathology scores were significantly higher(P＜0.05);compared with model group,the chest radiograph and gross view of inflammation were slightly reduced in SN50 low,medium and high concentration groups,and the W/D and lung injury pathology scores were significantly lower(P＜0.05).Western blotting showed that,compared with control group,the protein expression levels of p-p65 and Drp-1 in the lung tissues of neonatal rats were significantly higher in model group(P＜0.05),and the protein expression level of PGC-1α was significantly lower(P＜0.05);compared with model group,the protein expression levels of p-p65 and Drp-1 were significantly lower in SN50 low,medium,and high concentration groups(P＜0.05),and the difference in the protein expression level of PGC-1α in SN50 low concentration group was not statistically significant(P＞0.05),whereas the PGC-1α expression levels in SN50 medium and high concentration groups were significantly higher(P＜0.05);the difference in the total p65 protein expression levels in each group was not statistically significant(P＞0.05).Immunohistochemical assay results showed that,compared with control group,p65 and Drp-1 protein expression levels were significantly higher in model group(P＜0.05),and PGC-1α protein expression level was significantly lower(P＜0.05);compared with model group,p65 protein expression level was significantly lower in SN50 low concentration group(P＜0.05),and the difference in Drp-1 and PGC-1α protein expression levels were not statistically significant(P＞0.05),Drp-1 protein expression level was significantly lower(P＜0.05),and PGC-1α protein expression level was significantly higher(P＜0.05)in SN50 middle and high concentration groups.Conclusion Fecal inhalation can induce lung tissue inflammation in neonatal rats,and the mechanism may be related to enhanced oxidative stress,promotion of mitochondrial dysfunction,activation of the Drp-1/NF-κB signaling pathway,and inhibition of PGC-1α protein expression.

Efficacy of metoprolol versus ivabradine in treatment of POTS in elderly patients after COVID-19 infection / 中华老年心脑血管病杂志

Objective To explore the difference in efficacy of metoprolol versus ivabradine in the treatment of postural orthostatic tachycardia syndrome(POTS)in the elderly after COVID-19 infection.Methods A total of 110 patients diagnosed with POTS at our department from Decem-ber 1,2022 to January 31,2023 were included.According to their drug regimen,they were divided into metoprolol group(62 patients)and ivabradine group(48 patients).On the 28th day of out-patient follow-up,the resting heart rate,heart rate of 10 min of standing,symptom disappearance rate,hospitalization rate,and mortality rate were compared between the two groups.Results On the 28th day of treatment,the resting heart rate and postural heart rate for 10 min were decreased in both groups when compared with the levels at initial diagnosis(P＜0.01).And there were no significant differences in the two types of heart rate between the two groups on the 28th day(71.0±7.0 vs 72.1±7.0,P=0.401;76.5±7.2 vs 77.4±7.6,P=0.573).No obvious differences were observed between the two groups in symptom disappearance rate,hospitalization rate,or mortality rate(88.7％vs 89.6％,3.2％vs2.1％,0％vs 0％,P＞0.05).Conclusion Metoprolol and ivabradine can effectively treat POTS in the elderly patients after COVID-19 infection.

Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC).@*METHODS@#The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay.@*RESULTS@#The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.@*CONCLUSION@#Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.

Study on OS-induced DNA damage from X-ray activation and cellular premature aging of HaCaT cells / 中国医学装备

Objective:To explore the changes of oxidative stress(OS),DNA damage and the occurrence of cellular premature aging of human immortalized keratinocytes(HaCaT)after that was radiated by X-ray with different doses.Methods:HaCaT cells were radiated by X-ray,and they were divided into 0 Gy group,5 Gy group and 10 Gy group according to the irradiation dose.The levels of intracellular reactive oxygen species(ROS)were detected by 2,7-Dichlorofluorescein diacetate(DCFH-DA)fluorescent probe,and the intracellular content of malondialdehyde(MDA)of lipid peroxidation products and the activity of superoxide dismutase(SOD)were measured by colorimetry.Immunofluorescence staining was used to detect the phosphorylated histone 2A variant(γ-H2AX)in HaCaT cells that were radiated by X-ray with different doses.Cell count kit-8(CCK-8)was used to detect the effect of X-ray with different doses on the proliferation of HaCaT cells after X-ray with different doses radiated them.β-Galactosidase staining was used to detect the proportion of premature aging cells.The changes of p21 and p53 protein expressions after X-ray irradiation were detected by Western blot.Results:After HaCaT cells were radiated by X-ray for 24h,the fluorescence intensity of 2',7'-Dichlorofluorescein(DCF)in 5 Gy and 10 Gy groups were significantly higher than that in the 0 Gy group,and the MDA contents of them were significantly higher than that in the control group,and the SOD activities of them were significantly lower than that in the control group(F=38.35,92.22,5.22,P<0.05),respectively.The change of γ-H2AX focus showed a dose-dependent significant increase at 1 h after irradiation,and the difference between them and control group was statistically significant(F=129.3,P<0.05).At 6h,24h and 48h after X-ray radiated HaCaT cells,the cell proliferation abilities of 5 Gy group and 10 Gy group were significantly decreased than that of 0 Gy group(F=116.41,62.20,34.29,P<0.01),and the β-Galactosidase activity of the two groups were significantly increased than that of 0 Gy group,and the difference was significant(F=1629.22,P<0.01).At 72h after X-ray with different doses radiated HaCaT cells,the expression levels of p21 and p53 proteins of 5 Gy group and 10 Gy group increased,and the differences of them among three groups were significant(F=104.4,66.69,P<0.01),respectively.Conclusion:Ionizing radiation can induce the occurrences of oxidative stress and DNA damage in HaCaT cells,and cause the occurrence of cellular premature aging.

Analysis of radiological health standards related to biodosimetry / 中华放射医学与防护杂志

Based on an overreview of Chinese radiological health standards, the Chinese radiological health standards currently in effect for biodosimetry were analyzed with respect to their current status, application and existing problems. Furthermore the improvement measures and development trends were put forward.

Weight-dependent Fluorescence Lifetime Imaging for Viscosity Detection in Glycerol-water Mixtures / 生物化学与生物物理进展

ObjectiveBased on fluorescence lifetime imaging technology, a novel method for viscosity detection is proposed and the capability of different weighting of fluorescence lifetimes in distinguishing the viscosity of glycerol-water mixtures is evaluated, aiming to enhance the accuracy and reliability of viscosity differentiation. MethodsThis approach incorporates the principles of electronic weighting, introducing both amplitude-weighted average fluorescence lifetime (τm) and intensity-weighted average fluorescence lifetime (τi). Viscosity changes in glycerol-water mixtures are detected through τm and τi. τm Reflects the relationship between fluorescence signal amplitude and time, while τi focuses on the time-varying characteristics of fluorescence signal intensity. ResultsThe results of both τm and τi mutually corroborate each other, not only enhancing the reliability in detecting viscosity changes in glycerol-water mixtures but also revealing their unique roles in the detection process. Although τm plays a crucial role in capturing changes in fluorescence signal amplitude, τi exhibits higher accuracy in viscosity detection when considering the time-varying characteristics of fluorescence signal intensity. It is particularly noteworthy that, due to τi’s greater sensitivity, microenvironment viscosity detection can be directly analyzed using τi. This provides a more convenient approach for real-time, highly sensitive microfluidic viscosity monitoring. Therefore, through the comprehensive utilization of τm and τi, a more thorough and accurate understanding of the viscosity information in glycerol-water mixtures can be obtained, and specific parameters can be selected for in-depth analysis based on specific needs. ConclusionThe combination of amplitude weighting and intensity weighting allows for a more sensitive identification of subtle changes in viscosity under different conditions. The innovation of this method lies in its simultaneous consideration of multiple parameters, enhancing sensitivity and distinguishability to variations in viscosity. Therefore, this weighted-dependent fluorescence lifetime imaging technique not only introduces a novel approach for viscosity detection in glycerol-water mixtures but also provides a powerful analytical tool for various fields, including microfluidics, rheology, and research on novel functional materials.

Discovery of novel S6K1 inhibitors by an ensemble-based virtual screening method and molecular dynamics simulation.

Ribosomal protein S6 kinase beta-1 (S6K1) is considered a potential target for the treatment of various diseases, such as obesity, type II diabetes, and cancer. Development of novel S6K1 inhibitors is an urgent and important task for the medicinal chemists. In this research, an effective ensemble-based virtual screening method, including common feature pharmacophore model, 3D-QSAR pharmacophore model, naïve Bayes classifier model, and molecular docking, was applied to discover potential S6K1 inhibitors from BioDiversity database with 29,158 compounds. Finally, 7 hits displayed considerable properties and considered as potential inhibitors against S6K1. Further, carefully analyzing the interactions between these 7 hits and key residues in the S6K1 active site, and comparing them with the reference compound PF-4708671, it was found that 2 hits exhibited better binding patterns. In order to further investigate the mechanism of the interactions between 2 hits and S6K1 at simulated physiological conditions, the molecular dynamics simulation was performed. The ΔGbind energies for S6K1-Hit1 and S6K1-Hit2 were - 111.47 ± 1.29 and - 54.29 ± 1.19 kJ mol-1, respectively. Furthermore, deep analysis of these results revealed that Hit1 was the most stable complex, which can stably bind to S6K1 active site, interact with all of the key residues, and induce H1, H2, and M-loop regions changes. Therefore, the identified Hit1 may be a promising lead compound for developing new S6K1 inhibitor for various metabolic diseases treatment.

Discovery of potent microtubule-destabilizing agents targeting for colchicine site by virtual screening, biological evaluation, and molecular dynamics simulation.

Microtubule has been considered as attractive therapeutic target for various cancers. Although numerous of chemically diverse compounds targeting to colchicine site have been reported, none of them was approved by Food and Drug Administration. In this investigation, the virtual screening methods, including pharmacophore model, molecular docking, and interaction molecular fingerprints similarity, were applied to discover novel microtubule-destabilizing agents from database with 324,474 compounds. 22 compounds with novel scaffolds were identified as microtubule-destabilizing agents, and then submitted to the biological evaluation. Among these 22 hits, hit4 with novel scaffold represents the best anti-proliferative activity with IC50 ranging from 4.51 to 14.81 µM on four cancer cell lines. The in vitro assays reveal that hit4 can effectively inhibit tubulin assembly, and disrupt the microtubule network in MCF-7 cell at a concentration-dependent manner. Finally, the molecular dynamics simulation analysis exhibits that hit4 can stably bind to colchicine site, interact with key residues, and induce αT5 and ßT7 regions changes. The values of ΔGbind for the tubulin-colchicine and tubulin-hit4 are -172.9±10.5 and -166.0±12.6 kJ·mol-1, respectively. The above results indicate that the hit4 is a novel microtubule destabilizing agent targeting to colchicine-binding site, which could be developed as a promising tubulin polymerization inhibitor with higher activity for cancer therapy.

Effect of Age and Sex on Stroke Mortality of Young and Middle-aged Adults in China, 2002-2019, and Predictions to 2030 / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to examine the trends in stroke mortality among young and middle-aged adults in China.@*METHODS@#Data were obtained from the China national vital registration system. Significant changes in mortality were assessed by Joinpoint regression. Age-period-cohort analysis was used to explain the reasons for the changes. Future mortality and counts were predicted by the Bayesian age-period-cohort model.@*RESULTS@#Between 2002 and 2019, a total of 6,253,951 stroke mortality in young and middle-aged adults were recorded. The age-adjusted mortality rates (AAMRs) of women showed a downward trend. The annual percent changes (APC) were -3.5% (-5.2%, -1.7%) for urban women and -2.8% (-3.7%, -1.9%) for rural women. By contrast, the AAMRs per 100,000 for rural men aged 25-44 years continued to rise from 9.40 to 15.46. The AAMRS for urban men aged 25-44 years and urban and rural men aged 45-64 years did not change significantly. Between 2020 and 2030, the projected stroke deaths are 1,423,584 in men and 401,712 in women.@*CONCLUSION@#Significant sex and age disparities in the trends of stroke mortality among young and middle-aged adults were identified in China. Targeted health policy measures are needed to address the burden of stroke in the young generation, especially for rural men, with a focus on the prevention and management of high risk factors.