Impact of the COVID-19 pandemic on the codification of China's civil code.

The COVID-19 pandemic has spread widely around the world since 2019, wreaking havoc on social order in a global context. In China, the pandemic has not only provided new challenges to the government's capacity but also provided new issues for the Civil Code that is being compiled. The study adopts the research method of comparative analysis and combines the case study method, aiming to study the impact of the epidemic on the compilation of China's Civil Code. We found that the official Civil Code adds, deletes, and adjusts several articles compared to the Civil Code (Draft), five of which are relevant to the COVID-19 pandemic. The Civil Code was enacted at the time of the COVID-19 pandemic, which led to some of its provisions being affected by the COVID-19; the "COVID-19 provisions" not only provided legitimacy for the prevention and control of the pandemic but also improved China's system of governance of public health emergencies. This study exposes the legal loophole in the "COVID-19 provisions" in China's Civil Code and further suggests ways to fill the legal loophole.

Real-world evidence comparing early and late pancreatic stent placement to prevent post-ERCP pancreatitis.

Background and study aims Pancreatic stenting effectively lowers the occurrence of post-ERCP pancreatitis (PEP) and reduces its severity. However, limited research has been conducted to determine the optimal timing for pancreatic stent placement. Our objective was to evaluate whether early pancreatic stent placement (EPSP) is more effective than late pancreatic stent placement (LPSP) in preventing PEP among patients with naive papilla. Patients and methods We conducted a retrospective cohort study that analyzed 590 patients with difficult biliary cannulation using the pancreatic guidewire technique, who were divided into EPSP and LPSP groups. In the EPSP group, a pancreatic stent was placed immediately before/after endoscopic retrograde cholangiography (ERC) or endoscopic sphincterotomy (EST). Conversely, in the LPSP group, a pancreatic stent was placed after partial/all completion of major endoscopic procedures. Results From November 2017 to May 2023, 385 patients were in the EPSP group and 205 in the LPSP group. EPSP was associated with a decreased PEP occurrence compared with LPSP (2.9% vs. 7.3%; P = 0.012). Similarly, hyperamylasemia was lower in the EPSP group (19.7% vs. 27.8%; P = 0.026). Furthermore, sensitivity analysis using multivariable analysis and propensity score-matched (PSM) analysis also validated these findings. Conclusions Early pancreatic stent placement reduced the incidence of PEP and hyperamylasemia compared with late pancreatic stent placement. Our findings favor pancreatic stenting immediately before/after ERC or EST.

Voltage-dependent anion channel 1 mediates mitochondrial fission and glucose metabolic reprogramming in response to ionizing radiation.

The ionizing radiation (IR) represents a formidable challenge as an environmental factor to mitochondria, leading to disrupt cellular energy metabolism and posing health risks. Although the deleterious impacts of IR on mitochondrial function are recognized, the specific molecular targets remain incompletely elucidated. In this study, HeLa cells subjected to γ-rays exhibited concomitant oxidative stress, mitochondrial structural alterations, and diminished ATP production capacity. The γ-rays induced a dose-dependent induction of mitochondrial fission, simultaneously manifested by an elevated S616/S637 phosphorylation ratio of the dynamin-related protein 1 (DRP1) and a reduction in the expression of the mitochondrial fusion protein mitofusin 2 (MFN2). Knockdown of DRP1 effectively mitigated γ-rays-induced mitochondrial network damage, implying that DRP1 phosphorylation may act as an effector of radiation-induced mitochondrial damage. The mitochondrial outer membrane protein voltage-dependent anion channel 1 (VDAC1) was identified as a crucial player in IR-induced mitochondrial damage. The VDAC1 inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), counteracts the excessive mitochondrial fission induced by γ-rays, consequently rebalancing the glycolytic and oxidative phosphorylation equilibrium. This metabolic shift was uncovered to enhance glycolytic capacity, thus fortifying cellular resilience and elevating the radiosensitivity of cancer cells. These findings elucidate the intricate regulatory mechanisms governing mitochondrial morphology under radiation response. It is anticipated that the development of targeted drugs directed against VDAC1 may hold promise in augmenting the sensitivity of tumor cells to radiotherapy and chemotherapy.

Indomethacin Does Not Reduce Post-ERCP Pancreatitis in High-Risk Patients Receiving Pancreatic Stenting.

BACKGROUND: Rectal indomethacin reduces pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). However, there is insufficient evidence regarding its added benefits in patients already receiving prophylactic pancreatic stenting. Our goal was to evaluate the impact of indomethacin in high-risk patients undergoing pancreatic stenting. METHODS: A cohort study was conducted on all patients who underwent the rescue cannulation technique for challenging bile duct cannulation (selected high-risk patients). Patients were split into two groups based on the prophylaxis method for post-ERCP pancreatitis (PEP): one receiving a combination of indomethacin and pancreatic stenting, while the other received pancreatic stenting alone. Comparative analyses were carried out on PEP, hyperamylasemia, gastrointestinal bleeding, and postoperative hospital stay among post-ERCP pancreatitis patients. RESULTS: Between November 2017 and May 2023, a total of 607 patients with native papillae were enrolled, with 140 grouped into the indomethacin plus stent group and 467 into the stent alone group. The overall PEP rate was 4.4% in the entire cohort, with no statistical differences observed between the groups in terms of PEP rates (P = 0.407), mild PEP (P = 0.340), moderate to severe PEP (P = 1.000), hyperamylasemia (P = 0.543), gastrointestinal bleeding (P = 0.392), and postoperative hospital stay (P = 0.521). Furthermore, sensitivity analysis using multivariable analysis also validated these findings. CONCLUSIONS: Indomethacin did not reduce the incidence or severity of PEP in high-risk patients who routinely received prophylactic pancreatic stent placement. Therefore, the additional administration of rectal indomethacin to further mitigate PEP appears to be not necessary.

Low-dose radiation promotes high-fat diet-induced atherosclerosis by activating cGAS signal pathway.

BACKGROUND: Atherosclerosis (AS) is the most prevalent cardiovascular disease, with an exceptionally high burden. High-fat diet (HFD) is a popular diet behavior, whereas low-dose radiation (LDR) is an environmental physical factor. There is evidence to suggest that an HFD may exacerbate the onset of atherosclerosis. Whether the combination effect of HFD and LDR would have potential on atherosclerosis development remains incompletely unclear. METHODS: In this study, ApoE-/- mice were used as atherosclerosis model animals to investigate the combination effects of HFD and LDR (10 × 0.01Gy, or 20 × 0.01Gy) on vascular lesions. Doppler ultrasound imaging, H&E staining, oil red O staining, western blotting, and immunohistochemistry (IHC) were used to assess the pro-atherosclerotic effects. LC-MS was used to detect the non-targeted lipidomic. RESULTS: Long-term exposure of low-dose radiation at an accumulated dose of 0.2Gy significantly increased the occurrence of vascular stiffness and the aortic lesion in ApoE-/- mice. The synergistic effect of HFD and LDR was observed in the development of atherosclerosis, which might be linked to both the dysbiosis of lipid metabolism and the stimulation of the inflammatory signaling system. Moreover, LDR but not HFD can activate the cGAS-STING signaling through increasing the yield of cytosolic mitochondrial DNAs as well as the expression of cGAS protein. The activation of cGAS-STING signal triggers the release of IFN-α/-ß, which functions as an inflammatory amplifier in the formation of atherosclerotic plaque. CONCLUSION: The current study offers fresh insights into the risks and mechanism that underlie the development of atherosclerosis by LDR, and there is a combination effect of LDR and HFD with the involvement of cGAS-STING signal pathway.

Effect of nitrogen oxides and sulfur oxides to triphenyl phosphate degradation and cytotoxicity on surface of different transition metal salts.

Nitrogen oxides and sulfur oxides, as the dominant toxic gases in the atmosphere, can induce severe human health problems under the composite pollutant conditions. Currently the effect of nitrogen or sulfur oxides in atmospheric environment to the degradation and cytotoxicity of triphenyl phosphate (TPhP) on atmospheric particle surfaces still remain poorly understood. Hence, laboratory simulation methods were used in this study to investigate the effect and related mechanism. First, particle samples were prepared with the TPhP coated on MnSO4, CuSO4, FeSO4 and Fe2(SO4)3 surface. The results showed that, when nitrogen or sulfur oxides were present, more significant TPhP degradation on all samples can be observed under both light and dark conditions. The results proved nitrogen oxides and sulfur oxides were the vital influence factors to the degradation of TPhP, which mainly promoted the OH generation in the polluted atmosphere. The mechanism study indicated that diphenyl hydrogen phosphate (DPhP) and OH-DPhP were two main stable degradation products. These degradation products originated from the phenoxy bond cleavage and hydroxylation of TPhP caused by hydroxyl radicals. In addition, no TPhP related organosulfates (OSs) or organic nitrates (ON) formation were observed. Regarding the cytotoxicity, all the particles can induce more significant cellular injury and apoptosis of A549 cells, which may be relevant to the adsorbed nitrogen oxides or sulfur oxides on particles surfaces. The superfluous reactive oxygen species (ROS) generation was the possible reason of cytotoxicity. This research can supply a comprehensive understanding of the promoting effect of nitrogen and sulfur oxides to TPhP degradation and the composite cytotoxicity of atmospheric particles.

Understanding the global subnational migration patterns driven by hydrological intrusion exposure.

Amid the escalating global climatic challenges, hydrological risks significantly influence human settlement patterns, underscoring the imperative for an in-depth comprehension of hydrological change's ramifications on human migration. However, predominant research has been circumscribed to the national level. The study delves into the nonlinear effects of hydrological risks on migration dynamics in 46,776 global subnational units. Meanwhile, leveraging remote sensing, we procured globally consistent metrics of hydrological intrusion exposure, offering a holistic risk assessment encompassing hazard, exposure, and vulnerability dimensions, thus complementing previous work. Here, we show that exposure is the primary migration driver, surpassing socioeconomic factors. Surrounding disparities further intensified exposure's impact. Vulnerable groups, especially the economically disadvantaged and elderly, tend to remain in high-risk areas, with the former predominantly migrating within proximate vicinities. The nonlinear analysis delineates an S-shaped trajectory for hydrological exposure, transitioning from resistance to migration and culminating in entrapment, revealing dependence on settlement resilience and adaptability.

Paroxetine alleviates dendritic cell and T lymphocyte activation via GRK2-mediated PI3K-AKT signaling in rheumatoid arthritis.

BACKGROUND: G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA). METHODS: The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism. RESULTS: In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (Tregs), an increase in the cluster of differentiation 8 positive (CD8+) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8+ T cells, and induced the proportion of Tregs. Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells. CONCLUSION: Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cell in RA.

Effects of lactic acid and ascorbic acid electrostatic spraying on the physicochemical attributes and microbial diversity of beef aged at mild temperature (10 °C).

This study aimed to clarify the effect of electrostatic spraying of lactic acid (LE) and ascorbic acid (AE) on vacuum-packaged beef aged at 10 °C. The physicochemical attributes, flavor profiles, and microbial diversities were evaluated. Beef steaks were electrostatically sprayed twice with 4% LE, 0.5% AE, or a mixture of them (LAE). Afterward, the beef was vacuum-packaged and aged. All treated beef exhibited a decrease in quality and sensory scores over time. At the end of the study period, the total viable count (TVC) and the total volatile basic nitrogen values in the control group (7.34 log CFU/g and 15.52 mg/100 g, respectively) were higher than those in the acid-treated groups. The LAE group exhibited the best color stability and the lowest TVC and Enterobacteriaceae counts after aging. High-throughput sequencing analysis revealed that acid types and electrostatic spray could change the microbiota structure. Leuconostoc was the dominant bacteria in the AE and LAE groups, while Enterococcus became the predominant bacteria in the NLE and LE groups with aging. This indicates that electrostatic spray combined with acid treatment can ensure beef quality and microbiological safety at mild temperatures.

Transpancreatic Sphincterotomy After Double Guidewire Technique Was Noninferior to Primary Transpancreatic Sphincterotomy in Difficult Biliary Cannulation.

BACKGROUND: When unintentional pancreatic duct access occurs during difficult biliary cannulation, the double guidewire (DGW) or transpancreatic sphincterotomy (TPS) may be utilized. DGW can be easily switched to TPS due to the existing guidewire in the pancreatic duct. However, the efficacy of TPS after DGW, named sequential DGW-TPS technique, versus primary TPS has not been assessed. AIMS: Our aim was to compare the benefits and adverse events of sequential DGW-TPS technique and primary TPS. METHODS: We performed a comparative retrospective cohort study that enrolled a total of 117 patients with native papillae. The patients were divided into one of 2 groups according to the primary bile duct access technique (sequential DGW-TPS or primary TPS), both with pancreatic stenting. RESULTS: Between November 2017 and May 2023, a total of 84 patients were grouped into sequential DGW-TPS and 33 into primary TPS. The overall post-ERCP pancreatitis (PEP) rate was 4.3% in the entire cohort, with no statistical differences were observed between the groups in terms of PEP rates (P = 0.927), PEP severity (P = 1.000), first biliary cannulation success (P = 0.621), overall cannulation success (P = 1.000), hyperamylasemia incidence (P = 0.241), elevated amylase levels (P = 0.881), and postoperative hospital stay (P = 0.185). Furthermore, these results remained consistent in multivariable regression analysis. CONCLUSIONS: The sequential DGW-TPS technique showed a comparable safety and biliary cannulation success rate to primary TPS in difficult biliary cannulation. Given the potential long-term complications associated with TPS, DGW should be first if inadvertent pancreatic access occurs, with TPS serving as second only if DGW fails.

Determination of Methamphetamine by High-Performance Liquid Chromatography in Odor-Adsorbent Material Used for Training Drug-Detection Animals.

The objective of the present report was to develop and validate a simple, sensitive, and selective analytical method for the determination of methamphetamine in an odor-adsorbent material (gauze) which was used to improve and standardize the training method used for drug-detection animals. High-performance liquid chromatography (HPLC) was performed using a Spherisorb ODS2 C18 column (200 mm × 4.6 mm, 5 µm), with a mobile phase consisting of a 0.25% methanol/triethylamine aqueous solution (V:V = 20:80), the pH of which was adjusted to 3.1 using glacial acetic acid, at a flow rate of 1.0 mL/min. The column temperature was 25 °C, and the detection of the analytes was performed at a wavelength of 260 nm. Methamphetamine showed good linearity (R2 = 0.9999) in the range of 4.2~83.2 mg/mL. The stability of the test material was good over 24 h. The precision of the method was good, with an average spiked recovery of 86.2% and an RSD of 2.9%. The methamphetamine content in the gauze sample was determined to be 7.8 ± 2.2 µg/sample. A high-performance liquid chromatography (HPLC) method was optimized and validated for the determination of methamphetamine in adsorbent materials (gauze). Validation data in terms of specificity, linearity, the limit of detection and the limit of quantification, reproducibility, precision, stability, and recovery indicated that the method is suitable for the routine analysis of methamphetamine in adsorbent materials (gauze) and provided a basis for training drug-detection animals.

Association Between Long-Term Exposure to Ambient Air Pollution and the Risk of Mild Cognitive Impairment in a Chinese Urban Area: A Case-Control Study.

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina. Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study. Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk. Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants. Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.

Sporadic gastrinoma with refractory benign esophageal stricture: A case report.

BACKGROUND: Gastrinoma is characterized by an excessive release of gastrin, leading to hypersecretion of gastric acid, subsequently resulting in recurrent peptic ulcers, chronic diarrhea, and even esophageal strictures. This case report aims to improve awareness and facilitate early diagnosis and treatment of gastrinoma by presenting a rare case of gastrinoma with refractory benign esophageal stricture (RBES). Additionally, it highlights the persistent challenges that gastroenterologists encounter in managing RBES. CASE SUMMARY: This case demonstrates a patient with gastrinoma who developed RBES and complete esophageal obstruction despite management with maximal acid suppressive therapy, multiple endoscopic bougie dilations and endoscopic incisional therapy (EIT). CONCLUSION: It is essential to diagnose gastrinoma as early as possible, as inadequately controlled acid secretion over an extended period increases the risk of developing severe esophageal strictures. In patients with esophageal strictures causing complete luminal obstruction, blind reopening EIT presents challenges and carries a high risk of perforation.

Characteristics of Lactic Acid Bacteria as Potential Probiotic Starters and Their Effects on the Quality of Fermented Sausages.

The aim of this study was to explore the potential of commercial lactic acid bacteria (LAB) as probiotic starters in fermented sausages. We initially investigated the growth activity, acid production capability, and tolerance to fermentation conditions of Lactobacillus sakei, Lactiplantibacillus plantarum, and Pediococcus pentosaceus. All three LAB strains proved viable as starters for fermented sausages. Subsequently, we explored their potential as probiotics based on their antibacterial and antioxidant capabilities. L. plantarum exhibited stronger inhibition against Escherichia coli and Staphylococcus aureus. All three strains displayed antioxidant abilities, with cell-free supernatants showing a higher antioxidant activity compared to intact cells and cell-free extracts. Moreover, the activities of superoxide dismutase, glutathione peroxidase, and catalase were stronger in the cell-free supernatant, cell-free extract, and intact cell, respectively. Finally, we individually and collectively inoculated these three LAB strains into sausages to investigate their impact on quality during the fermentation process. External starters significantly reduced pH, thiobarbituric acid reactive substances, and sodium nitrite levels. The improvements in color and texture had positive effects, with the L. plantarum inoculation achieving higher sensory scores. Overall, all three LAB strains show promise as probiotic fermentation starters in sausage production.

Painterly Style Transfer With Learned Brush Strokes.

Real-world paintings are made, by artists, using brush strokes as the rendering primitive to depict semantic content. The bulk of the Neural Style Transfer (NST) is known transferring style using texture patches, not strokes. The output looks like the content image, but some are traced over using the style texture: it does not look painterly. We adopt a very different approach that uses strokes. Our contribution is to analyse paintings to learn stroke families-that is, distributions of strokes based on their shape (a dot, straight lines, curved arcs, etc.). When synthesising a new output, these distributions are sampled to ensure the output is painted with the correct style of stroke. Consequently, our output looks more "painterly" than NST output based on texture. Furthermore, where strokes are placed is an important contributing factor in determining output quality, and we have also addressed this aspect. Humans place strokes to emphasize salient semantically meaningful image content. Conventional NST uses a content loss premised on filter responses that is agnostic to salience. We show that replacing that loss with one based on the language-image model benefits the output through greater emphasis of salient content.

Natural Course of Common Bile Duct Microlithiasis.

BACKGROUND: Common bile duct microlithiasis (CBDM) with a diameter of ≤ 3 mm can pass spontaneously without causing any symptoms, but in some cases, it can also cause severe cholangitis and pancreatitis. The optimal strategy for managing CBDM is yet to be determined. METHODS: Data of 154 patients with CBDM were collected and divided into two groups: with endoscopic retrograde cholangiopancreatography (with ERCP, n = 82) and without ERCP (n = 72). Clinical outcomes, including the incidence of unfavorable outcomes (UOs), such as cholangitis and pancreatitis, were observed and compared between the two groups. RESULTS: The incidence of UOs was significantly lower in the ERCP group than in the without ERCP group (3.7% vs. 23.6%, respectively, p < 0.001). Moreover, the total number of readmissions was also lower in the ERCP group than in the without ERCP group (p < 0.001). A multivariate analysis adjusted for age, sex, and the American Society of Anesthesiologists (ASA) class revealed that endoscopic sphincterotomy (EST) and cholecystectomy were associated with a lower risk of UOs. CONCLUSION: The high rate of UOs in CBDM patients without ERCP suggests that its natural clinical course may not be as favorable as previously suggested. This finding implies that efforts should be made to clear the bile ducts.

Inhibitory Mechanism of Prenylated Flavonoids Isolated from Mulberry Leaves on α-Glucosidase by Multi-Spectroscopy and Molecular Dynamics Simulation.

Flavonoids have always been considered as the chemical basis for the hypoglycemic effect of mulberry leaves. In the course of our search for hypoglycemic effect agents from natural sources, a systematic study was launched to explore prenylated flavonoids from mulberry leaves. Herein, chemical investigation led to the isolation of 10 characteristic prenylated flavonoids, including two new compounds (1 and 3). Their structures were elucidated based on spectroscopic data. All compounds exhibited good α-glucosidase inhibitory activity in vitro, among which compound 2 had the best activity (IC50 = 2.6 µM), better than acarbose (IC50 = 19.6 µM). Additional in vivo tests have further demonstrated compound that compound 2 has a good ability to reduce postprandial blood glucose. Then, multi-spectroscopic methods and molecular simulation studies were used to study the inhibition mechanism. The results showed that compound 2 was a mixed inhibition of α-glucosidase and the binding process was spontaneous, with van der Waals forces as the main driving force, followed by hydrogen bonding and electrostatic forces. The above studies enriched the chemical basis of mulberry leaves, and the application of computational chemistry also provided a reference for future research on such structures.

Cytosolic Release of Mitochondrial DNA and Associated cGAS Signaling Mediates Radiation-Induced Hematopoietic Injury of Mice.

Mitochondrion is an important organelle of eukaryotic cells and a critical target of ionizing radiation (IR) outside the nucleus. The biological significance and mechanism of the non-target effect originating from mitochondria have received much attention in the field of radiation biology and protection. In this study, we investigated the effect, role, and radioprotective significance of cytosolic mitochondrial DNA (mtDNA) and its associated cGAS signaling on hematopoietic injury induced by IR in vitro culture cells and in vivo total body irradiated mice in this study. The results demonstrated that γ-ray exposure increases the release of mtDNA into the cytosol to activate cGAS signaling pathway, and the voltage-dependent anion channel (VDAC) may contribute to IR-induced mtDNA release. VDAC1 inhibitor DIDS and cGAS synthetase inhibitor can alleviate bone marrow injury and ameliorate hematopoietic suppression induced by IR via protecting hematopoietic stem cells and adjusting subtype distribution of bone marrow cells, such as attenuating the increase of the F4/80+ macrophage proportion in bone marrow cells. The present study provides a new mechanistic explanation for the radiation non-target effect and an alternative technical strategy for the prevention and treatment of hematopoietic acute radiation syndrome.

Novel hybrid virtual screening protocol based on pharmacophore and molecular docking for discovery of GSK-3ß inhibitors.

GSK-3ß is a member of the GSKs subfamily and plays a major role in the regulation of transcriptional elongation, which has attracted widespread attention as a therapeutic target for AD. In this study, by combining pharmacophore-based virtual screening and kinase inhibition assays, we have successfully identified four small molecules that inhibit GSK-3ß activity at micromolar potency. These hit compounds showed drug-like properties according to Lipinski's rule of five and ADMET. An inter-complex interaction study showed that all hit compounds adapted well to the ATP pocket of the GSK-3ß protein. Among them, hits 2 and 4 displayed considerable inhibitory activities with IC50 value of 0.74 ± 0.04 µM and 2.32 ± 0.84 µM respectively. Overall, the discovered GSK-3ß inhibitors act as new chemical leads to develop improved inhibitors that block the interaction of GSK-3ß, and the hybrid virtual screening strategy designed in this study provides an important reference for design and synthesis novel selective GSK-3ß inhibitors.