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Nitidine chloride (NC) is effective on cancer in many tumors, but its effect on bladder cancer (BC) is unknown. We conducted cell function experiments to verify the antineoplastic effect of NC on BC cell lines (5637, T24, and UM-UC-3) in vitro. Then, mRNAs of NC-treated and NC-untreated BC cells were extracted for mRNA sequencing. Differentially expressed genes (DEGs), expression analysis, and drug molecular docking were conducted to discover the target gene of NC. Finally, functional enrichment was analyzed to explore the underlying mechanisms. NC dramatically inhibited proliferation, migration, and invasion, and it induced apoptosis and arrested the S and G2/M phases of BC cell lines. Lymphocyte antigen 75 (LY75) appeared to be the target of NC. LY75 was highly expressed and had the ability to distinguish BC tissue from non-cancerous tissue. Then, drug molecular docking confirmed the targeting relationship between NC and LY75. Gene enrichment analysis showed that the downregulated genes, after being treated with NC, were mainly enriched in pathways relevant to cell pathophysiological processes. NC inhibits BC cell proliferation, migration, and invasion, induces apoptosis, and arrests cell cycles by downregulating the expression of LY75. This study provides molecular and theoretical bases for NC treatment of BC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rhizoma Drynariae (RD) was used clinically to treat osteoporosis in China due to stimulating bone formation and inhibiting bone resorption, however, the bioactive constituents with the dual effect on bone are still unknown exactly. Disease-causing mutations in calcium sensing receptor (CaSR) can alter parathyroid hormone secretion and affect Ca 2+ release from bone and Ca 2+ reabsorption from kidney, which gives an indication that CaSR is a potential target for developing therapeutics to manage osteoporosis. Herein, a chromatographic approach was established, by immobilizing the mutant CaSR onto the surface of silica gels as stationary phase in a one-step procedure and then adding the different amino acids into mobile phase as competitors, for exploring the binding features of the known agonists and further screening ligands from RD. The mutant CaSR-coated column was prepared rapidly without the complicated purification and separation of the receptor, which had the large capacity of 13.1 mg CaSR /g silica gels and kept a good stability and specificity for at least 35 days. The CaSR mutation can weaken the binding affinities for three agonists, and the largest decreases occurred on the mutational site Thr151Met for neomycin, on the two sites of Asn118Lys and Glu191Lys for gentamicin-C, and on the site Phe612Ser for kanamycin, which gained new insights into their structure-function relationship. The potential bioactive compounds from RD were screened using the mutant CaSR-coated column and were recognized as coumaric acid 4-O-β-D-glucopyranoside, caffeic acid, and naringin using UPLC-MS. Among them, naringin targeting CaSR gives a possible explanation that RD could manage osteoporosis. These results indicated that, such a rapid and simple method, utilizing disease-associated mutation in CaSR to alter the binding affinity for agonists, can be applied in capturing the potential bioactive compounds efficiently from complex matrices like herb medicines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Consistently, the multiple heart-kidney interactions make pharmaceutical research for cardiorenal syndrome difficult and complex. Guanxinning Injection (GXN) has been reported to provide unique advantage for treating cardiac and renal diseases compared to typical monotherapies. However, the protection mechanism of GXN is largely unknown. This study explored the acting mechanism of GXN on heart failure with renal dysfunction from a metabolic perspective. Transverse aortic constriction (TAC) surgery was performed on C57/BL/6 mice to induce heart failure with renal dysfunction. Using telmisartan as a positive control, GXN treatment was applied during the 12th to 16th week after TAC. Cardiac function and structure were examined using M-mode echocardiography, and renal function was evaluated via representative biochemical parameters and hematoxylin-eosin staining. Moreover, untargeted metabolomic analyses of urine were conducted to screen for differential substances associated with the cardiorenal protection effect of GXN. As a result, GXN provided good cardioprotective effects on left ventricular ejection fraction elevation, fractional shortening, internal diastolic, and mass maintenance. GXN also reduced TAC-induced elevation of blood urea nitrogen, and serum Cystatin C and relieved kidney pathological damage. Metabolomic analyses identified 21 differential metabolites in the TAC model group. Ten metabolites involving the metabolic pathways of carnitine synthesis, valine, leucine and isoleucine degradation, and glutamate metabolism, taurine and hypotaurine metabolism, tryptophan metabolism, arginine and proline metabolism, and purine metabolism were restored by GXN. The main cardiorenal protection mechanism of GXN was found to be related to energy metabolism and oxidative stress. Taken together, this study provides the first evidence of the metabolic protection mechanism of GXN on heart failure with renal dysfunction for the first time and provides a research basis for the application of GXN in CRS-2 pharmaceuticals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The existence of an inflection point between fullerene and nonfullerene molecules was demonstrated using bowl-nonfullerene models, which were proposed to explore the key points relating to the different properties. This study explains the differences in the stacking configurations of the inflection points and reveals the reason for the inversion of properties, which is caused by small structural differences.

Background: The One-Child Policy led to the imbalance of the sex ratio at birth (SRB) in China. After that, Two-Child Policy was introduced and gradually liberalized at three stages. If both the husband and wife of one couple were the only child of their parents, they were allowed to have two children in policy (BTCP). If only one of them was the only child, they were allowed to have two children in policy (OTCP). The Universal Two-Child Policy (UTCP) allowed every couple to have two children. The objective of this study was to explore the changing trend of SRB at the stages of Two-Child Policy, to analyze the effect of population policy on SRB in terms of maternal age, delivery mode, parity, maternal education, delivery hospital, and to figure out what factors have greater impact on the SRB., Methods: The data of the study came from Hebei Province Maternal Near Miss Surveillance System, covered the parturients delivered at 28 gestation weeks or more in 22 hospitals from January 1, 2013 to December 31, 2017. We compared the SRB at different policy stages, analyzed the relationship between the SRB and population policy by logistic regression analysis., Results: Total 270,878 singleton deliveries were analyzed. The SRB, 1.084 at BTCP, 1.050 at OTCP, 1.047 at UTCP, declined rapidly (χ 2  = 15.97, P < 0.01). With the introduction of Two-Child Policy, the percentage of parturients who were 30-34, ≥35 years old rose significantly, and the percentage of multiparous women increased significantly (40.7, 47.2, 56.6%). The neonatal mortality declined significantly (8.4‰, 6.7‰, 5.9‰, χ 2  = 44.49, P < 0.01), the mortality rate of female infant gradually declined (48.2, 43.7, 43.9%). The logistic regression analysis showed the SRB was correlated to the three population policy stages in terms of maternal age, delivery mode, parity, maternal education, delivery hospital., Conclusions: The SRB has declined to normal level with the gradually liberalizing of Two-Child Policy in China. Advanced maternal age, cesarean delivery, multiparous women, middle level education, rural hospital are the main factors of effect on the decline of the SRB.

Gray relational analysis is employed to analyze the effects of nano-drug features on phagocytosis of macrophages, including zeta potential, shape factor and scale size of drug particle, the correlation among such factors and macrophage cell is calculated. The results showed that the internalization processe is affected significantly by the zeta potential of the drug in the process of phagocytosis of macrophages, followed by the impact particle shape, and the effect of particle scale behaves relatively small.

In the title compound, C(10)H(12)O(5), the dihedral angle between the benzene ring is almost coplanar with the attached C(O)-O-C group [dihedral angle = 0.32 (15)°]. In the crystal, two intermolecular O-H⋯O hydrogen bonds make R(4) (4)(26) ring mofits.