Di-2-pyridylhydrazone Dithiocarbamate Butyric Acid Ester Exerted Its Proliferative Inhibition against Gastric Cell via ROS-Mediated Apoptosis and Autophagy

Diversified biological activities of dithiocarbamates have attracted widespread attention; improving their feature or exploring their potent action of mechanism is a hot topic in medicinal research. Herein, we presented a study on synthesis and investigation of a novel dithiocarbamate, DpdtbA (di-2-pyridylhydrazone dithiocarbamate butyric acid ester), on antitumor activity. The growth inhibition assay revealed that DpdtbA had important antitumor activity for gastric cancer (GC) cell lines (IC50 = 4.2 ± 0.52 μM for SGC-7901, 3.80 ± 0.40 μM for MGC-803). The next study indicated that growth inhibition is involved in ROS generation in mechanism; accordingly, the changes in mitochondrial membrane permeability, apoptotic genes, cytochrome c, bax, and bcl-2 were observed, implying that the growth inhibition of DpdtbA is involved in ROS-mediated apoptosis. On the other hand, the upregulated p53 upon DpdtbA treatment implied that p53 could also mediate the apoptosis. Yet the excess generation of ROS induced by DpdtbA led to cathepsin D translocation and increase of autophagic vacuoles and LC3-II, demonstrating that autophagy was also a contributor to growth inhibition. Further investigation showed that DpdtbA could induce cell cycle arrest at the G1 phase. This clearly indicated the growth inhibition of DpdtbA was via triggering ROS formation and evoking p53 response, consequently leading to alteration in gene expressions that are related to cell survival

Crystal Structures of Fusion Cores from CCoV-HuPn-2018 and SADS-CoV

Cross-species spillover to humans of coronaviruses (CoVs) from wildlife animal reservoirs poses marked and global threats to human and animal health. Recently, sporadic infection of canine coronavirus–human pneumonia-2018 (CCoV-HuPn-2018) in hospitalized patients with pneumonia genetically related to canine and feline coronavirus were identified. In addition, swine acute diarrhea syndrome coronavirus (SADS-CoV) had the capability of broad tropism to cultured cells including from humans. Together, the transmission of Alphacoronaviruses that originated in wildlife to humans via intermediate hosts was responsible for the high-impact emerging zoonosis. Entry of CoV is mainly mediated by Spike and formation of a typical six helix bundle (6-HB) structure in the postfusion state of Spike is pivotal. Here, we present the complete fusion core structures of CCoV-HuPn-2018 and SADS-CoV from Alphacoronavirus at 2.10 and 2.59 Å, respectively. The overall structure of the CCoV-HuPn-2018 fusion core is similar to Alphacoronavirus like HCoV-229E, while SADS-CoV is analogous to Betacoronavirus like SARS-CoV-2. Collectively, we provide a structural basis for the development of pan-CoV small molecules and polypeptides based on the HR1-HR2 complex, concerning CCoV-HuPn-2018 and SADS-CoV

Resistant dextrin protects against pathological bone loss in ovariectomized rats and inhibits RANKL-induced osteoclastogenesis

Background. Osteoporosis is a common disease in postmenopausal women characterized by systemic bone mass loss, microstructure fragility and increased incidence of fractures. Resistant dextrin (RD) is a soluble fiber with beneficial metabolic effects. However, the beneficial effect of RD in osteoporosis remains to be determined. Methods. In this study, we investigated the effect of dietary RD supplement on osteoporosis in ovariectomized (OVX) rats. Both the control (sham) and OVX group rats were gavaged with RD (10 g/kg/d) or equal amount of saline for 12 weeks, and histological and biomechanical analyses were conducted to evaluate bone microstructure and strength. Furthermore, we also evaluated the effects of RD on osteoclastogenesis in bone marrow macrophages (BMMs) by detecting the expression of osteoclast-related genes using qRT-PCR and Western blot analysis. Results. The results showed that in OVX rats the bone strength and microstructure characteristics were significantly improved with RD supplement for 12 weeks. Additionally, the mRNA and protein expression of osteoclast markers, such as CTSK, NF-κB and NFATC1, were significantly down-regulated in BMMs isolated from RD supplement group. RD also suppressed RANKL-induced osteoclastogenesis in BMMs. Conclusion. These findings suggest that RD ameliorates osteoporosis in OVX rats by inhibiting osteoclast differentiation. RD suppresses RANKLinduced osteoclastogenesis possibly through modulating Akt and NF-κB signaling pathways. These data indicate that a dietary supplement of RD might serve as an intervention strategy for menopausal osteoporosi

Efficacy of Sucralfate-Combined Quadruple Therapy on Gastric Mucosal Injury Induced by Helicobacter pylori and Its Effect on Gastrointestinal Flora

Background. This study explored the therapeutic efficacy of standard triple therapy combined with sucralfate suspension gel as well as the mechanisms of action in mouse models of H. pylori infection. Materials and Methods. C57BL/6J mice were randomly divided into 5 groups: NC (natural control), HP (H. pylori infection), RAC (rabeprazole, amoxicillin, and clarithromycin), RACS (RAC and sucralfate suspension gel), and RACB (RAC and bismuth potassium citrate). HE staining and electron microscopy were performed to estimate histological and ultrastructural damages. The IL-8, IL-10, and TNF-α of gastric antrum tissues were measured by immunohistochemistry and qRT-PCR. ZO-1 and Occludin were also detected with immunohistochemistry. The genomes of gastric and fecal microbiota were sequenced. Results. The eradication rate of H. pylori in the RACS group was higher than the RAC group. RACS therapy had protective effects on H. pylori-induced histological and ultrastructural damages, which were superior to the RAC group. RACS therapy reduced the protein and mRNA levels of IL-8 compared with the RAC group. The expression of Occludin in the RACS group was significantly higher than that of the RAC group. The composition of gastric and fecal microbiota for RACS was similar to the RACB group according to PCA. Conclusions. The RACS regimen eradicated H. pylori infection effectively and showed RACS had protective effects against H. pylori-induced histological and ultrastructural damage. The mechanisms of RACS effects included decreasing IL-8, enhancing Occludin, and transforming gastric microbiota. Moreover, RACS and RACB have a similar effect on gastrointestinal flora

Key Amino Acid Residues Involved in Binding Interactions between <i>Bactrocera minax</i> Odorant-Binding Protein 3 (BminOBP3) and Undecanol

Insect odorant-binding proteins (OBPs) are significant in binding and transporting odorants to specific receptors. Our previous study demonstrated that BminOBP3 exhibited a strong affinity with undecanol. However, the binding mechanism between them remains unknown. Here, using homology modeling and molecular docking, we found that the C-terminus (I116-P122), especially the hydrogenbonds formed by the last three amino acid residues (V120, F121, and P122) of the C-terminus, is essential for BminOBP3′s ligand binding. Mutant binding assays showed that the mutant T-OBP3 that lacks C-terminus (I116-P122) displayed a significant decrease in affinity to undecanol (Ki = 19.57 ± 0.45) compared with that of the wild-type protein BminOBP3 (Ki = 11.59 ± 0.51). In the mutant 3D2a that lacks F121 and P122 and the mutant V120A in which V120 was replaced by alanine, the bindings to undecanol were completely abolished. In conclusion, the C-terminus plays a crucial role in the binding interactions between BminOBP3 and undecanol. Based on the results, we discussed the ligand-binding process of BminOBP3

Excessive Nitrogen Fertilization Favors the Colonization, Survival, and Development of Sogatella furcifera via Bottom-Up Effects

Fertilization can trigger bottom-up effects on crop plant–insect pest interactions. The intensive use of nitrogen fertilizer has been a common practice in rice production, while the yield has long been challenged by the white-backed planthopper, Sogatella furcifera (Horváth). High nitrogen fertilization can facilitate S. furcifera infestation, however, how nitrogen fertilizer leads to high S. furcifera infestation and the nutritional interactions between rice and S. furcifera are poorly understood. Here, we evaluated the effects of various levels of nitrogen fertilizer application (0–350 kg/ha) on rice, and subsequently on S. furcifera performance. We found that higher nitrogen fertilizer application: (1) increases the preference of infestation behaviors (feeding and oviposition), (2) extends infestation time (adult lifespan), and (3) shortens generation reproduction time (nymph, pre-oviposition, and egg period), which explain the high S. furcifera infestation ratio on rice paddies under high nitrogen conditions. Moreover, high nitrogen fertilizer application increased all tested rice physical indexes (plant height, leaf area, and leaf width) and physiological indexes (chlorophyll content, water content, dry matter mass, and soluble protein content), except for leaf thickness, which was reduced. Correlation analysis indicated that the specific rice physical and/or physiological indexes were conducive to the increased infestation behavior preference, extended infestation time, and shortened generation reproduction time of S. furcifera. The results suggested that nitrogen fertilizer triggers bottom-up effects on rice and increases S. furcifera populations. The present study provides an insight into how excess nitrogen fertilization shapes rice–planthopper interactions and the consequent positive effect on S. furcifera infestation

Deviatoric Stress Evolution Laws and Control in Surrounding Rock of Soft Coal and Soft Roof Roadway under Intense Mining Conditions

Aiming at the problem of large deformation and instability failure and its control of soft coal and soft roof roadway under intense mining, laboratory experiments, theoretical calculations, Flac3D numerical simulation, borehole peeping, and pressure observation were used to study the deflection characteristics of the deviatoric stress of the gas tailgate and the distribution and failure characteristics of the plastic zone in the mining face considering the strain softening characteristics of the roof and coal of roadway, and then the truss anchor cable-control technology is proposed. The results show the following: (1) The intense mining influence on the working face will deflect the peak deviatoric stress zone (PDSZ) of the surrounding rock of the gas tailgate. The influence distance of PDSZ is about 20 m in advance and 60 m in lag; the PDSZ at the gob side of the roadway is located in the range of 3–5.5 m from the surface of the coal pillar, while the coal wall side is mainly located in the range of 3–4.5 m at the shoulder corner and bottom corner of the solid coal. (2) The intense mining in the working face caused the nonuniform expansion of the surrounding rock plastic area of the gas tailgate. The two shoulder angles of the roadway and the bottom of the coal pillar have the largest damage range, and the maximum damage location is the side angle of the coal pillar (5 m). Angle and bottom angle of coal pillar are the key points of support control. (3) The plastic failure line of the surrounding rock of the gas tailgate is always between the inner and outer contours of the PDSZ, and the rock mass in the PDSZ is in a stable and unstable transition state, so the range of anchor cable support should be cross plastic failure line. (4) The theoretical calculations and numerical simulation results agree well with the drilling peep results. Based on the deflection law of the PDSZ and the expansion characteristics of the plastic zone, a truss anchor cable supporting system with integrated locking and large-scale support function is proposed to jointly control the roof and the two sides, which effectively solves the problem of weak surrounding rock roadway under severe mining deformation control problems realizing safety and efficient production in coal mines under intense mining

Study on deflection of principal stress and deformation characteristics of roadway surrounding rock under mining action in close-distance coal seams

AbstractThe traditional index to determine the width of the stopping coal pillar (WSCP) is generally only the front abutment pressure, but the direction of the principal stress will deflect due to the mining action, which brings significant challenges to controlling the surrounding rock. Based on theoretical calculation and numerical simulation, we studied the deflection law of principal stress under mining action, quantified the bearing capacity of roadway surrounding rock, and determined WSCP. The results show that: (1) With the deflection of the principal stress, the distribution of the surrounding rock plastic zone also rotates; (2) [Formula: see text] and repeated mining dominate and aggravate the deflection angle and range of the principal stress in front of the working face, respectively. When [Formula: see text] is close to 1, the deflection of principal stress should be paid attention to in determining WSCP; (3) The anchorage composite bearing structure (ACBS) provides a scientific basis for quantifying the bearing capacity of surrounding rock. WSCP of the lower coal seam is determined to be 60–75 m, and the corresponding principal stress deflection is about 135°. The control of the surrounding rock in the diagonal direction where the maximum principal stress is concentrated should be paid attention to

Roadway Surrounding Rock under Multi-Coal-Seam Mining: Deviatoric Stress Evolution and Control Technology

Multi-coal-seam mining creates surrounding rock control difficulties, because the mining of a coal face in one seam can affect coal faces in another. We examine the effects of multi-coal-seam mining on the evolution of the deviatoric stress distribution and plastic zone in the roadway surrounding rock. In particular, we use numerical simulation, theoretical calculation, drilling detection, and mine pressure observation to study the distribution and evolution characteristics of deviatoric stress on Tailgate 8709 in No. 11 coal seam in Jinhuagong mine when the N8707 and N8709 coal faces in No. 7-4 coal seam and the N8707 and N8709 coal faces in No. 11 coal seam are mined. The evolution laws of deviatoric stress and the plastic zone of roadway surrounding rock in the advance and behind sections of the coal face are studied, and a corresponding control technology is proposed. The results show that the peak value of deviatoric stress increases with the advance of the coal face, and the positions of the peak value of deviatoric stress and the plastic zone become deeper. The deflection angle of the peak stress after mining at each coal face and the characteristics of the peak zone of deviatoric stress and the plastic zone of the roadway surrounding rock under the disturbance of multi-coal-seam mining are determined. In conclusion, the damage range in the roadway roof in the solid-coal side and coal pillar is large and must be controlled. A combined support technology based on high-strength and high pretension anchor cables and truss anchor cables is proposed; long anchor cables are used to strengthen the support of the roadway roof in the solid-coal side and coal pillar. The accuracy of the calculated plastic zone range and the reliability of the combined support technology are verified through drilling detection and mine pressure observation on site. This research can provide a point of reference for roadway surrounding rock control under similar conditions