Novel pleuromutilin derivatives conjugated with phenyl-sulfide and boron-containing moieties as potent antibacterial agents against antibiotic-resistant bacteria.

In response to the escalating threat of microbial resistance, a series of novel pleuromutilin derivatives, conjugated with phenyl-sulfide and boron-containing moieties, were designed and synthesized. Most derivatives, especially 14b and 16b, demonstrated significant efficacy against Gram-positive bacteria, including multidrug-resistant strains, as well as pleuromutilin-resistant strains. Compound 16b showed high stability in the liver microsomes of rats and humans, along with acceptable tolerance in vitro and in vivo. Additionally, compound 16b exhibited promising efficacy in MRSA-infected mouse models. Our data highlight the potential of conjugated pleuromutilin derivatives as valuable agents against drug-resistant bacteria.

Top coal drawing law for an extra thick coal seam under the single round group drawing method.

To solve the problems of poor top coal drawing, lagging collapse, and difficulty in parallel operation of mining and drawing in extra-thick coal seams, considering the 8222 working face of the Tashan Mine as the engineering background, we first investigate the basic problems of fully mechanized top coal drawing mining in extra-thick coal seams using the single-round group drawing method (GDM). We then analyze the drawing law of top coal with different thicknesses under the single-round GDM from the aspects of top coal recovery (TCR) and drawing efficiency, coal loss mechanism, and the relation between TCR and gangue content (GC), providing a basis for determining the process parameters of GDM. Results indicate that as the top coal thickness increases, the number of drawing openings considerably influences drawing efficiency and top coal loss. And there is a notable thickness effect of the number of drawing openings on the top coal loss. There is a quantitative relationship among TCR, cumulative GC (CGC) and instantaneous GC (IGC), and CGC and TCR can be predicted based on the IGC. Consequently, theoretical analysis and numerical simulation results indicate that the optimal IGC threshold at the coal drawing openings between 31.2 and 40%. Through optimizing the coal drawing method and strictly controlling the IGC at the coal drawing openings on-site, the measured working face TCR increased from 75.25 to 90.12%, and CGC was controlled at approximately 9%. Meanwhile, the average coordination efficiency of mining and drawing time reaches 68.2%, effectively ensuring the construction of a coal mine with an annual output of 15 million tons.

Image features and clinical analysis of retroperitoneal pelvic schwannoma: a case report.

BACKGROUND: Schwannomas are benign usually encapsulated nerve sheath tumors derived from the Schwann cells, and affecting single or multiple nerves. The tumors commonly arise from the cranial nerves as acoustic neurinomas but they are extremely rare in the pelvis and the retroperitoneal area. Retroperitoneal pelvic schwannomas often present with non-specific symptoms leading to misdiagnosis and prolonged morbidity. CASE PRESENTATION: We report the case of a 59-year-old woman presenting with a feeling of heaviness in the lower abdomen who was found to have a retroperitoneal pelvic schwannoma originating from the right femoral nerve. She had a history of two resections of peripheral schwannomas at four different sites of limbs. After conducting magnetic resonance imaging, this pelvic schwannoma was misdiagnosed as a gynecological malignancy. The tumor was successfully removed by laparoscopic surgery. Pathological analysis of the mass revealed a benign schwannoma of the femoral nerve sheath with demonstrating strong, diffuse positivity for S-100 protein. CONCLUSIONS: Although retroperitoneal pelvic schwannoma is rare, it should be considered in the differential diagnosis of pelvic masses, especially in patients with a history of neurogenic mass or the presence of neurogenic mass elsewhere.

Derived from fangchinoline, LYY-35 exhibits an inhibiting effect on human NSCLC cancer A549 cells.

Although fangchinoline has been widely used as an adjunct therapy for a variety of inflammatory and cancerous diseases, its mechanism of action on tumor cells remains unclear. Fangchinoline derivative LYY-35 reduced the number of A549 cells, deformed cell morphology and increased cell debris. Cell viability was significantly reduced, while the same concentration of LYY-35 had little effect on BEAS-2B viability of normal lung epithelial cells. In addition, LYY-35 can also reduce the migration, proliferation and invasion ability of A549 cells. Levels of ß-catenin, ZO-1 and ZEB-1 proteins, biomarkers of cell adhesion and epithelial mesenchymal transformation, were significantly reduced. The levels of superoxide dismutase and lactate dehydrogenase decreased gradually, while the levels of glutathione, malondialdehyde and intracellular and extracellular ROS increased significantly. At the same time, LYY-35 induced increased apoptosis, increased expression of Bax, cleaved caspase3, cleaved PARP1, and decreased expression of Bcl-xl, which blocked the cell cycle to G0/G1 phase. The expressions of cell cycle checkpoint proteins Cyclin B1, Cyclin E1, CDK6, PCNA and PICH were significantly decreased. With the increase of LYY-35 concentration, the trailing phenomenon was more obvious in single cell gel electrophoresis. DNA damage repair proteins: BLM, BRCA-1 and PARP-1 expression decreased gradually.LYY-35 can inhibit the proliferation of non-small cell lung cancer A549 cells, block cell cycle, promote apoptosis, increase ROS production, cause DNA damage and interfere with DNA replication. LYY-35 is promising for the treatment of non-small cell lung cancer in the future.

[Material basis and mechanism of Bletillae Rhizoma for melasma, gastrointestinal hemorrhage, lung cancer and bronchoplumonary inflammation as "homotherapy for heteropathy" based on UHPLC-Q-Exactive Orbitrap HRMS coupled with network pharmacology and molecular docking].

Based on UHPLC-Q-Exactive Orbitrap HRMS coupled with the network pharmacology and molecular docking, the common material basis and molecular mechanisms of Bletillae Rhizoma for melasma, gastrointestinal hemorrhage, lung cancer and bronchoplumonary inflammation as "homotherapy for heteropathy" were explored. The fingerprint of 17 batches of Bletillae Rhizoma from different areas was established using HPLC, and the similarity analysis was carried out. The common chemical components of the 17 batches of Bletillae Rhizoma were identified using UHPLC-Q-Exactive Orbitrap HRMS. Depending on the bioavailability and drug-like properties of the common components, the active chemical components were screened, and then their protein targets were collected using the Traditional Chinese Medicine Database and Analysis Platform(TCMSP) and SwissTargetPrediction database. The protein targets related to diseases were retrieved from the databases DrugBank, TTD and GeneCards to produce a Venn diagram. The shared targets were obtained between drugs and diseases as "homotherapy for heteropathy" targets. The protein-protein interaction(PPI) was analyzed with the STRING database, and KEGG and GO analyses of the "homotherapy for heteropathy" targets were performed using the Bioconductor database. Cytoscape 3.7.2 software was employed to construct the "chemical components of Bletillae Rhizoma-homotherapy for heteropathy targets" network and PPI network, and topological analysis was conducted to screen out the key active chemical components and core targets. Finally, the affinity between the active components and core targets was evaluated using the molecular docking by AutoDock Vina 4.2.6, which verified the interaction between them. Thirteen common peaks were identified by fingerprint chromatography, and the similarity between different batches was 0.941-0.998. Fifty-three chemical components were identified by mass spectrometry in Bletillae Rhizoma, and 18 common chemical constituents were obtained in the 17 batches of Bletillae Rhizoma. Network pharmacologic screening showed that the pharmacodynamic substances of Bletillae Rhizoma for melasma, gastrointestinal hemo-rrhage, lung cancer and bronchoplumonary inflammation with "homotherapy for heteropathy" were 11 compounds, such as polysaccharides, biphenanthrenes, dihydrophenanthrenes and bibenzyls. There were 42 common targets identified for the treatment of different diseases. These targets were involved in biological processes such as cell response to chemical stress, reactive oxygen species and positive regulation of protein kinase B signal transduction. They were also involved in 121 signaling pathways, encompassing vital pathways such as PI3K-Akt, ErbB, Rap1, FoxO, MAPK and estrogen. Molecular docking results showed a strong affinity between the key active components and the core targets. This study provides a preliminary explanation of how Bletillae Rhizoma exerts its therapeutic effect on chloasma, gastrointestinal hemorrhage, lung cancer, and bronchopneumonic lesions as "homotherapy for heteropathy" through a combined action involving multiple components, targets, and pathways. These findings offer a certain theoretical basis for the further deve-lopment and application of Bletillae Rhizoma.

Meliasanines A-L, tirucallane-type triterpenoids from Melia toosendan with anti-inflammatory properties via NF-κB signaling pathway.

Meliasanines A-L, twelve previously unreported tirucallane-type triterpenoids, together with fifteen known ones, have been isolated from the stem bark of Melia toosendan. Their structures and absolute configurations were determined based on HRESIMS, and NMR, combined with calculated ECD and single-crystal X-ray diffraction analyses. Subsequently, all compounds except 10 were evaluated for their inhibitory effect on the production of nitric oxide induced by lipopolysaccharide in RAW264.7 macrophage cells. The results indicated that seven compounds (1, 13, 14, 16, 20, 22, and 23) exhibited significant NO inhibitory effects, with IC50 values ranging from 1.35 to 5.93 µM, which were more effective than the positive control indomethacin (IC50 = 13.18 µM). Moreover, the corresponding results of Western blot analysis revealed that meliasanine A (1) can significantly suppress the protein expression of inducible nitric oxide synthase and cyclooxygenase 2 in a concentration-dependent manner. The mechanism study suggested that meliasanine A exerts an anti-inflammatory effect via the nuclear factor-κB signaling pathway by suppressing phosphorylation of P65 and IκBα.

A novel L-shaped ortho-quinone analog suppresses glioblastoma progression by targeting acceleration of AR degradation and regulating PI3K/AKT pathway.

Glioblastoma (GBM) is a primary intracranial malignant tumor with the highest mortality and morbidity among all malignant central nervous system tumors. Tanshinone IIA is a fat-soluble active ingredient obtained from Salvia miltiorrhiza, which has an inhibitory effect against various cancers. We designed and synthesized a novel L-shaped ortho-quinone analog TE5 with tanshinone IIA as the lead compound and tested its antitumor activity against GBM. The results indicated that TE5 effectively inhibited the proliferation, migration, and invasion of GBM cells, and demonstrated low toxicity in vitro. We found that TE5 may bind to androgen receptors and promote their degradation through the proteasome. Inhibition of the PI3K/AKT signaling pathway was also observed in TE5 treated GBM cells. Additionally, TE5 arrested the cell cycle at the G2/M phase and induced mitochondria-dependent apoptosis. In vivo experiments further confirmed the anti-tumor activity, safety, and effect on androgen receptor level of TE5 in animal models of GBM. Our results suggest that TE5 may be a potential therapeutic drug to treat GBM.

Regulation of cerebral blood flow boosts precise brain targeting of vinpocetine-derived ionizable-lipidoid nanoparticles.

Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug carrier does not enhance its brain biodistribution; and second, many brain diseases are intricately linked to microcirculation disorders that significantly impede drug accumulation within brain lesions even after they cross the barrier. Inspired by the neuroprotective properties of vinpocetine, which regulates cerebral blood flow, we propose a molecular library design centered on this class of cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system. Our findings reveal that: (i) vinpocetine-derived ionizable-lipidoid nanoparticles efficiently breach the blood-brain barrier; (ii) they have high gene-loading capacity, facilitating endosomal escape and intracellular transport; (iii) their administration is safe with minimal immunogenicity even with prolonged use; and (iv) they have potent pharmacologic brain-protective activity and may synergize with treatments for brain disorders as demonstrated in male APP/PS1 mice.

Reactive Oxygen Species Activate a Ferritin-Linked TRPV4 Channel under a Static Magnetic Field.

Magnetogenetics has shown great potential for cell function and neuromodulation using heat or force effects under different magnetic fields; however, there is still a contradiction between experimental effects and underlying mechanisms by theoretical computation. In this study, we aimed to investigate the role of reactive oxygen species (ROS) in mechanical force-dependent regulation from a physicochemical perspective. The transient receptor potential vanilloid 4 (TRPV4) cation channels fused to ferritin (T4F) were overexpressed in HEK293T cells and exposed to static magnetic fields (sMF, 1.4-5.0 mT; gradient: 1.62 mT/cm). An elevation of ROS levels was found under sMF in T4F-overexpressing cells, which could lead to lipid oxidation. Compared with the overexpression of TRPV4, ferritin in T4F promoted the generation of ROS under the stimulation of sMF, probably related to the release of iron ions from ferritin. Then, the resulting ROS regulated the opening of the TRPV4 channel, which was attenuated by the direct addition of ROS inhibitors or an iron ion chelator, highlighting a close relationship among iron release, ROS production, and TRPV4 channel activation. Taken together, these findings indicate that the produced ROS under sMF act on the TRPV4 channel, regulating the influx of calcium ions. The study would provide a scientific basis for the application of magnetic regulation in cellular or neural regulation and disease treatment and contribute to the development of the more sensitive regulatory technology.

Applying image features of proximal paracancerous tissues in predicting prognosis of patients with hepatocellular carcinoma.

BACKGROUND: Most of the methods using digital pathological image for predicting Hepatocellular carcinoma (HCC) prognosis have not considered paracancerous tissue microenvironment (PTME), which are potentially important for tumour initiation and metastasis. This study aimed to identify roles of image features of PTME in predicting prognosis and tumour recurrence of HCC patients. METHODS: We collected whole slide images (WSIs) of 146 HCC patients from Sun Yat-sen Memorial Hospital (SYSM dataset). For each WSI, five types of regions of interests (ROIs) in PTME and tumours were manually annotated. These ROIs were used to construct a Lasso Cox survival model for predicting the prognosis of HCC patients. To make the model broadly useful, we established a deep learning method to automatically segment WSIs, and further used it to construct a prognosis prediction model. This model was tested by the samples of 225 HCC patients from the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC). RESULTS: In predicting prognosis of the HCC patients, using the image features of manually annotated ROIs in PTME achieved C-index 0.668 in the SYSM testing dataset, which is higher than the C-index 0.648 reached by the model only using image features of tumours. Integrating ROIs of PTME and tumours achieved C-index 0.693 in the SYSM testing dataset. The model using automatically segmented ROIs of PTME and tumours achieved C-index of 0.665 (95% CI: 0.556-0.774) in the TCGA-LIHC samples, which is better than the widely used methods, WSISA (0.567), DeepGraphSurv (0.593), and SeTranSurv (0.642). Finally, we found the Texture SumAverage Skew HV on immune cell infiltration and Texture related features on desmoplastic reaction are the most important features of PTME in predicting HCC prognosis. We additionally used the model in prediction HCC recurrence for patients from SYSM-training, SYSM-testing, and TCGA-LIHC datasets, indicating the important roles of PTME in the prediction. CONCLUSIONS: Our results indicate image features of PTME is critical for improving the prognosis prediction of HCC. Moreover, the image features related with immune cell infiltration and desmoplastic reaction of PTME are the most important factors associated with prognosis of HCC.

Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 3: Alleviation of hypoxia, muscle-wasting, and modulation of redox functions in amyotrophic lateral sclerosis.

OBJECTIVE: The aim of this clinical study is to obtain evidence for the clinical efficacy of Bu-Shen-Jian-Pi formula (BSJP), a traditional Chinese medicine, used for the treatment of amyotrophic lateral sclerosis, a relatively rare, progressive and usually fatal disease possibly associated with alterations in tissue redox status, hypoxia, and muscular injury. BACKGROUND: The active agents in BSJP formula† causing apoptosis, modulation of redox changes, and alterations in the immune status have been studied previously by us using cell cultures. The findings from these investigations have been incorporated into pharmacology databases employed in our analysis of BSJP using network pharmacology analysis/artifical intelligence. This information has been used here in the design of the investigation and to optimize evaluation of the clinical efficacy and usefulness of this herbal medicine, as far as possible using evidence-based medicine criteria. MATERIALS AND METHODS: The design of the study was a randomized multi-center, controlled clinical trial in 127 patients with confirmed diagnoses of amyotrophic lateral sclerosis. Patients and investigator were double-blinded. Clinical efficacy was determined using the Amyotrophic Lateral Sclerosis Symptom Score in Integrative Treatment Scale (ALS-SSIT) and the Amyotrophic Lateral Sclerosis Rating Scale-Revised (ALSFRS-R), together with tests of limb muscle strength using the manual muscle test (MMT), forced vital capacity (FVC), and clinical chemistry laboratory tests over a 20-week observation period. RESULTS: The scores of ALS-SSIT in the BSJP group increased significantly (22%) after treatment. The ALSFRS-R score in the BSJP group decreased significantly after treatment (19%). The rate of decrease in muscle function (MMT score) in most BSJP patients was lower than that in the control group, where the differences in the scores for the trapezius and triceps brachii were statistically significant compared to the control group. The fall in FVC in the BJSP group was significantly slower than in the control group. There were no marked differences observed in the frequency of side effects. Serum vitamin D3 levels in the BSJP group showed greater increases compared to the control group. CONCLUSION: BSJP treatment reduced the rate of progression of amyotrophic lateral sclerosis according to the ALS-SSITS and ALSFRS scores and significantly reduced the rate of deterioration in muscle function in the limbs of amyotrophic lateral sclerosis patients. The modes of action of BSJP in treating amyotrophic lateral sclerosis are probably diverse and multi targeted, some of which may involve regulation of serum vitamin D3 and alleviation of the impairments in liver and kidney function.

Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 2: Modulation of hypoxia, redox status, and mitochondrial protection in a neuroblastoma cell line, SH-SY5Y.

OBJECTIVE: To examine the mitochondrial protective effects of icariin, naringenin, kaempferol, and formononetin, potentially active agents in Bu-Shen-Jian-Pi formula (BSJP) identified using network pharmacology analysis. MATERIALS AND METHODS: Mitochondrial protection activity was determined using a hypoxia-reoxygenation in vitro model based on the neuroblastoma cell line SH-SY5Y and measurements of anti-ferroptotic activity. RESULTS: Icariin, naringenin, kaempferol, and formononetin showed mitochondrial protective activity involving diverse signaling pathways. The cytoprotective effects of formononetin depended on the inhibition of ferroptosis. Hypoxia-reoxygenation stimulation induced ferroptosis in SH-SY5Y cells. DISCUSSION: Ferroptosis is a key mechanism in nervous system diseases and is associated with hypoxia-reoxygenation injury. Naringenin and kaempferol were devoid of anti-ferroptotic activity. CONCLUSION: Evidence has been obtained showing that the core components: icariin, naringenin, kaempferol, and formononetin in BSJP formula have anti-hypoxic and mitochondrial protective activity of potential clinical importance in the treatment of amyotrophic lateral sclerosis and patients with symptoms of hypoxia.

Tanshinone analog inhibits castration-resistant prostate cancer cell growth by inhibiting glycolysis in an AR-dependent manner.

Androgen receptor (AR) is one of the key targets for the treatment of castration-resistant prostate cancer (CRPC). Current endocrine therapy can greatly improve patients with CRPC. However, with the change of pathogenic mechanism, acquired resistance often leads to the failure of treatment. Studies have shown that tanshinone IIA (TS-IIA) and its derivatives have significant antitumor activity, and have certain AR-targeting effects, but the mechanism is unknown. In this study, the TS-IIA analog TB3 was found to significantly inhibit the growth of CRPC in vitro and in vivo. Molecular docking, cellular thermal shift assay, and cycloheximide experiments confirmed that AR was the target of TB3 and promoted the degradation of AR. Furthermore, TB3 can significantly inhibit glycolysis metabolism by targeting the AR/PKM2 axis. The addition of pyruvic acid could significantly alleviate the inhibitory effect of TB3 on CRPC cells. Besides, the knockdown of AR or PKM2 also could reverse the effect of TB3 on CRPC cells. Taken together, our study suggests that TS-IIA derivative TB3 inhibits glycolysis to prevent the CRPC process by targeting the AR/PKM2 axis.

Synthesis and in†vitro Anti-Inflammatory Activity of Novel Dendrobine Amide/Sulfonamide Derivatives.

A traditional Chinese medicine ingredient, dendrobine, has been demonstrated to have anti-inflammatory properties. However, due to its poor anti-inflammatory properties, its clinical use is limited. Consequently, we have designed and synthesized 32 new amide/sulfonamide dendrobine derivatives and screened their anti-inflammatory activities in vitro. Experiments showed that nitric oxide (NO) generation in lipopolysaccharide (LPS)-induced RAW264.7 cells was strongly reduced by derivative 14, with an IC50 of 2.96 µM. Western blot research revealed that 14 decreased the concentration-dependent expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS). Molecular docking was used to predict the binding of the inflammation-associated proteins COX-2 and INOS to compound 14.

Structurally Diverse Coumarins from Peucedanum praeruptorum and their Anti-Inflammatory Activities via NF-κB Signaling Pathway.

The phytochemical study of Peucedanum praeruptorum led to the isolation of twenty-five coumarins (1-25). Of which, (±) praeruptol A (±1), one pair of previous undescribed seco-coumarin enantiomers were obtained. Their structures were established according to HR-ESI-MS, NMR, X-ray single crystal diffraction analysis, as well as ECD calculation. All compounds were tested for anti-inflammatory activity in the RAW264.7 macrophage model, and eight compounds (7-10, and 13-16) exhibited significant inhibitory effects with IC50 values ranging from 9.48 to 34.66 µM. Among them, compound 7 showed the strongest inhibitory effect, which significantly suppressed the production of IL-6, IL-1ß, and TNF-α, as well as iNOS and COX-2 in a concentration-dependent manner. Further investigated results showed that compound 7 exerted an anti-inflammatory effect via the NF-κB signaling pathway.

New clerodane diterpenoids from Callicarpa pseudorubella and their antitumor proliferative activity.

Six previously undescribed clerodane diterpenes, cardorubellas A-F (1-6), along with seven known ones (7-13), were isolated from the aerial parts of Callicarpa pseudorubella. Their chemical structures were established by analysis of 1D and 2D NMR, HR-ESI-MS, X-ray diffraction, and electronic circular dichroism (ECD) data. Notably, cardorubella B (2) represented the first examples of naturally occurring succinic anhydride-containing clerodane diterpenes derivatives. The anti-proliferative activities of these compounds were assessed. Remarkably, compound 2 exhibited comparable inhibitory activity against HEL cell lines, surpassing the positive control with an IC50 value of 14.01 ± 0.77 µM, compared to 17.02 ± 4.70 µM for 5-fluorouracil.

Short sleep duration is associated with worse quality of life in Parkinson's disease: A multicenter cross-sectional study.

OBJECTIVE: To characterize sleep duration and investigate its association with quality of life among Parkinson's Disease (PD) patients. METHODS: In this multicenter cross-sectional study, 970 PD patients were divided into five groups based on self-reported sleep duration: <5, ≥5 to <6, ≥6 to <7, ≥7 to ≤8, and >8 h. The quality of life was evaluated using the 39-Item Parkinson's Disease Questionnaire (PDQ-39). Multivariable linear regression analysis, subgroup analysis, and mediation analysis were conducted to examine the association between sleep duration and quality of life. RESULTS: In multivariable linear regression model, patients with sleep duration (<5 h) had significantly higher PDQ-39 scores (ß = 8.132, 95 % CI: 3.99 to 12.266), especially in mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort (p < 0.05). The association between sleep duration (<5 h) and worse quality of life was more pronounced in patients with higher HY stage, longer disease duration, and sleep disorders. Moreover, a significant indirect effect of sleep duration (<5 h) on quality of life was observed, with UPDRS I, UPDRS II, and UPDRS IV scores acting as mediators. CONCLUSIONS: Short sleep duration (<5 h) is associated with worse quality of life among PD patients. This association was stronger among patients with advanced PD and sleep disorders, while non-motor symptoms and motor complications were identified as significant mediators in this association. These findings highlight the significance of adequate sleep duration and suitable interventions for sleep may help improve quality of life.

Discovery of tricyclic PARP7 inhibitors with high potency, selectivity, and oral bioavailability.

PARP7 has been recently identified as an effective drug target due to its specific role in tumor generation and immune function recovery. Herin, we report the discovery of compound 8, which contained a tricyclic fused ring, as a highly selective PARP7 inhibitor against other PARPs. In particular, compound 8 strongly inhibits PARP7 with an IC50 of 0.11 nM, and suppresses the proliferation of NCI-H1373 lung cancer cells with an IC50 of 2.5 nM. Compound 8 exhibits a favorable pharmacokinetic profile with a bioavailability of 104 % in mice, and 78 % in dogs. Importantly, daily treatment of 30 mg/kg of 8 induced 81.6 % tumor suppression in NCI-H1373 lung xenograft mice tumor models, which is significantly better than the clinical candidate, RBN-2397. These intriguing features highlight the promising advantages of 8 as an antitumor agent.

Detection of chlorophyll content based on optical properties of maize leaves.

The chlorophyll content reflects plants' photosynthetic capacity, growth stage, and nitrogen status. Maize is one of the three widely planted gain crops in the world. In order to offer useful information for the development of chlorophyll content detectors of maize leaves, a single integrating sphere system was used to measure the transmittance and reflectance spectra of maize leaves over the wavelength range of 500-950 nm. The linear relationships of transmittance and reflectance with chlorophyll content were investigated. The feature wavelengths (FWs) sensitive to chlorophyll content were extracted from the full transmittance and reflectance spectra using the successive projections algorithm (SPA). The partial least squares regression (PLSR) models for predicting the chlorophyll content were established using the full spectra and extracted FWs. The results showed that there were obvious linear relationships between transmittance and reflectance with chlorophyll content of maize leaves and the best linear relationships were found at 709 nm and 714 nm, respectively, with the linear correlation coefficients of 0.801 and 0.696, and the root-mean-squares error (RMSEP) of 0.321 mg·g-1 and 0.405 mg·g-1, respectively. Eight and 6 FWs were extracted from the transmittance and reflectance spectra, respectively. The PLSR model established using the selected FWs from transmittance spectra had better prediction performance with RMSEP of 0.208 mg·g-1 than using full transmittance spectra. The built PLSR models using the full reflectance spectra and extracted FWs had poor robustness. This research offers some theoretical basis for developing a maize leaf chlorophyll content detector based on transmittance or reflectance.

Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 1: Biogenic components and identification of targets and signaling pathways in amyotrophic lateral sclerosis patients.

BACKGROUND: There is evidence that Bu-Shen-Jian-Pi (BSJP), a traditional Chinese medicine, has curative effects in patients suffering from amyotrophic lateral sclerosis (ALS), a progressive and potentially fatal hypoxic condition. OBJECTIVE: To identify biogenic components in BSJP extracts having potential pharmacological efficacy in ALS. MATERIALS AND METHODS: Biogenic components in BSJP and their potential pharmacological targets and signaling pathways in ALS were identified and assessed using network pharmacology/hub node analysis. RESULTS: Network pharmacology analysis identified icariin, naringenin, kaempferol, quercetin, and formononetin as core components in BSJP with potential activity involving mitochondrial protection in patients with ALS. CONCLUSION: Network pharmacology analysis proved to be a successful screening tool for obtaining information from scientific databases on the pharmacology of biogenic components in BSJP showing potential therapeutic activity in ALS.