Cancer on motors: How kinesins drive prostate cancer progression?

Prostate cancer causes numerous male deaths annually. Although great progress has been made in the diagnosis and treatment of prostate cancer during the past several decades, much about this disease remains unknown, especially its pathobiology. The kinesin superfamily is a pivotal group of motor proteins, that contains a microtubule-based motor domain and features an adenosine triphosphatase activity and motility characteristics. Large-scale sequencing analyses based on clinical samples and animal models have shown that several members of the kinesin family are dysregulated in prostate cancer. Abnormal expression of kinesins could be linked to uncontrolled cell growth, inhibited apoptosis and increased metastasis ability. Additionally, kinesins may be implicated in chemotherapy resistance and escape immunologic cytotoxicity, which creates a barrier to cancer treatment. Here we cover the recent advances in understanding how kinesins may drive prostate cancer progression and how targeting their function may be a therapeutic strategy. A better understanding of kinesins in prostate cancer tumorigenesis may be pivotal for improving disease outcomes in prostate cancer patients.

Effect of inflammatory response on joint function after hip fracture in elderly patients: A clinical study.

BACKGROUND: Excellent hip joint function facilitates limb recovery and improves the quality of survival. This study aimed to investigate the potential risk factors affecting postoperative joint functional activity and outcomes in elderly hip fractures patients and to provide evidence for patient rehabilitation and clinical management. AIM: To explore the relationship between inflammatory factors and hip function and the interaction between inflammation and health after hip fracture in elderly patients. METHODS: The elderly patients who had hip fracture surgery at our hospital between January 1, 2021, and December 31, 2022 were chosen for this retrospective clinical investigation. Patients with excellent and fair postoperative hip function had their clinical information and characteristics gathered and compared. Age, gender, fracture site, surgical technique, laboratory indices, and other variables that could have an impact on postoperative joint function were all included in a univariate study. To further identify independent risk factors affecting postoperative joint function in hip fractures, risk factors that showed statistical significance in the univariate analysis were then included in a multiple logistic regression analysis. In addition to this, we also compared other outcome variables such as visual analogue scale and length of hospital stay between the two groups. RESULTS: A total of 119 elderly patients with hip fractures were included in this study, of whom 37 were male and 82 were female. The results of univariate logistic regression analysis after excluding the interaction of various factors showed that there was a statistically significant difference in interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP), and complement C1q (C1q) between the fair and excellent joint function groups (P < 0.05). The results of multiple logistic regression analysis showed that IL-6 > 20 pg/mL [(Odds ratio (OR) 3.070, 95%CI: 1.243-7.579], IL-8 > 21.4 pg/ mL (OR 3.827, 95%CI: 1.498-9.773), CRP > 10 mg/L (OR 2.142, 95%CI: 1.020-4.498) and C1q > 233 mg/L (OR 2.339, 95%CI: 1.094-5.004) were independent risk factors for poor joint function after hip fracture surgery (all P < 0.05). CONCLUSION: After hip fractures in older patients, inflammatory variables are risk factors for fair joint function; therefore, early intervention to address these markers is essential to enhance joint function and avoid consequences.

Dialysis bag-microalgae photobioreactor: Novel strategy for enhanced bioresource production and wastewater purification.

Cultivating microalgae in wastewater offers various advantages, but it still faces limitations such as bacteria and other impurities in wastewater affecting the growth and purity of microalgae, difficulty in microalgae harvesting, and extracellular products of microalgae affecting effluent quality. In this study, a novel dialysis bag-microalgae photobioreactor (Db-PBR) was developed to achieve wastewater purification and purer bioresource recovery by culturing microalgae in a dialysis bag. The dialysis bag in the Db-PBR effectively captured the microalgae cells and promoted their lipid accumulation, leading to higher biomass (1.53 times of the control) and lipid production (2.50 times of the control). During the stable operation stage of Db-PBR, the average soluble microbial products (SMP) content outside the dialysis bag was 25.83 mg L-1, which was significantly lower than that inside the dialysis bag (185.63 mg L-1), indicating that the dialysis bag effectively intercepted the SMP secreted by microalgae. As a result, the concentration of dissolved organic carbon (DOC) in Db-PBR effluent was significantly lower than that of traditional photobioreactor. Furthermore, benefiting from the dialysis bag in the reactor effectively intercepted the microorganisms in wastewater, significantly improving the purity of the cultured microalgae biomass, which is beneficial for the development of high-value microalgae products.

Three undescribed compounds from Diaporthe biguttusis T-24, an endophytic fungus isolated from Ligularia fischeri.

Diaporthpyran A (1), diaporthester E (2) and diaporthester F (3), three new compounds along with four known compounds (4-7) were isolated from the crude extract of Diaporthe biguttusis T-24, an endophytic fungus isolated from Ligularia fischeri. The planar structures of compounds 1-3 including the relative and absolute configurations were elucidated on the basis of HRMS, NMR, J-based coupling constant analysis, CD, and calculated ECD analysis. In addition, compounds 1 and 3 were evaluated for their cytotoxic activities against four human cancer cell lines.

Myosin VI stabilizes intercellular junctions in the testis through the LHR and MAPK signalling pathway during spermatogenesis in Eriocheir sinensis.

The myosin motor protein myosin VI plays an essential role in mammalian spermatogenesis, however, the effects of myosin VI on male reproduction in Crustacea remain obscure. We identified the macromolecule es-Myosin VI in Eriocheir sinensis, and studied it by multiple methods. It co-localized with F-actin and was highly expressed in the testis. We interfered es-Myosin VI using dsRNA in vivo, an apparent decrease in spermatozoa count was detected. We also found that the MAPK signalling pathway was changed, subsequently causing disruption of intercellular junctions and damage to the functional hemolymph-testis barrier. We observed that luteinizing hormone receptor es-LHR was located within seminiferous tubules, which was different from the expression in mammals. Es-LHR could bind with es-Myosin VI in testis of E. sinensis, its localization was significantly altered when es-Myosin VI was deleted. Moreover, we obtained consistent results for the MAPK signalling pathway and spermatogenesis defects between the es-LHR and es-Myosin VI knockdown groups. In summary, our research demonstrated that knockdown of es-Myosin VI disturbed the intercellular junction and HTB function via the MAPK signalling pathway by changing the localization of es-LHR in the testis of E. sinensis, which was the potential reason for its negative impact on spermatogenesis.

mTORC1/rpS6 and mTORC2/PKC regulate spermatogenesis through Arp3-mediated actin microfilament organization in Eriocheir sinensis.

Mammalian target of rapamycin (mTOR) is a crucial signaling protein regulating a range of cellular events. Numerous studies have reported that the mTOR pathway is related to spermatogenesis in mammals. However, its functions and underlying mechanisms in crustaceans remain largely unknown. mTOR exists as two multimeric functional complexes termed mTOR complex 1 (mTORC1) and mTORC2. Herein, we first cloned ribosomal protein S6 (rpS6, a downstream molecule of mTORC1) and protein kinase C (PKC, a downstream effector of mTORC2) from the testis of Eriocheir sinensis. The dynamic localization of rpS6 and PKC suggested that both proteins may be essential for spermatogenesis. rpS6/PKC knockdown and Torin1 treatment led to defects in spermatogenesis, including germ cell loss, retention of mature sperm and empty lumen formation. In addition, the integrity of the testis barrier (similar to the blood-testis barrier in mammals) was disrupted in the rpS6/PKC knockdown and Torin1 treatment groups, accompanied by changing in expression and distribution of junction proteins. Further study demonstrated that these findings may result from the disorganization of filamentous actin (F-actin) networks, which were mediated by the expression of actin-related protein 3 (Arp3) rather than epidermal growth factor receptor pathway substrate 8 (Eps8). In summary, our study illustrated that mTORC1/rpS6 and mTORC2/PKC regulated spermatogenesis via Arp3-mediated actin microfilament organization in E. sinensis.

The Characteristics of the Metal-Free and Non-Conjugated Polymer Film with Self-Assembled Nanoparticles.

It is shown in this paper that a polymer, MA-PEG 1000-DGEBA (MP1D), exhibits antireflection, substrate-dependent photoluminescence (SDP), wide band-gap, and photoconduction characterization. MP1D was synthesized from maleic anhydride, polyethylene glycol 1000, and bisphenol-A diglycidyl ether. Self-assembled nanoparticles embedded in MP1D film and ranging from 2.5 to 31.6 nm are observed, which could be expected as scatterers to enhance light trapping and extraction. The size of the nanoparticle increases with the concentration of the MP1D solution. Besides solution concentration, the nanoparticle dimension could be modified by the chain length of polyethylene glycol in the polymer synthesis. The effects of solution concentration, annealing temperature, annealing period, and substrate on the photoluminescence (PL) of MP1D films are examined. Increasing solution concentration increases PL intensity. However, aggregation-caused quenching is explicit as the solution concentration exceeds 100 mM. PL intensity increases with annealing temperature, which could be attributed to crystallinity improvement. PL intensity increases with increasing the annealing period from 0.5 to 2 h. Nonetheless, as the annealing period exceeds 2 h, PL quenching is emerging, which could be due to aggregation. It is expected that MP1D could be a promising candidate for host materials and MP1D film could play a multifunctional role (antireflective and light-trapping functions) in optoelectronics.

es-Arp3 and es-Eps8 regulate spermatogenesis via microfilaments in the seminiferous tubule of Eriocheir sinensis.

Spermatogenesis is a complicated process that includes spermatogonia differentiation, spermatocytes meiosis, spermatids spermiogenesis and final release of spermatozoa. Actin-related protein 3 (Arp3) and epidermal growth factor receptor pathway substrate 8 (Eps8) are two actin binding proteins that regulate cell adhesion in seminiferous tubules during mammalian spermatogenesis. However, the functions of these two proteins during spermatogenesis in nonmammalian species, especially Crustacea, are still unknown. Here, we cloned es-Arp3 and es-Eps8 from the testis of Chinese mitten crab Eriocheir sinensis. es-Arp3 and es-Eps8 were located in spermatocytes, spermatids and spermatozoa. Knockdown of es-Arp3 and es-Eps8 in vivo caused morphological changes to seminiferous tubules including delayed spermatozoa release, shedding of germ cells and vacuoles. Filamentous-actin (F-actin) filaments network was disorganized due to deficiency of es-Arp3 and es-Eps8. Accompanying this, four junctional proteins (α-catenin, ß-catenin, pinin and ZO1) displayed abnormal expression levels as well as penetrating biotin signals in seminiferous tubules. We also used the Arp2/3 complex inhibitor CK666 to block es-Arp3 activity and supported es-Arp3 knockdown results. In summary, our study demonstrated for the first time that es-Arp3 and es-Eps8 are important for spermatogenesis via regulating microfilament-mediated cell adhesion in Eriocheir sinensis.

mTORC1/C2 regulate spermatogenesis in Eriocheir sinensis via alterations in the actin filament network and cell junctions.

Spermatogenesis is a finely regulated process of germ cell proliferation and differentiation that leads to the production of sperm in seminiferous tubules. Although the mammalian target of rapamycin (mTOR) signaling pathway is crucial for spermatogenesis in mammals, its functions and molecular mechanisms in spermatogenesis remain largely unknown in nonmammalian species, particularly in Crustacea. In this study, we first identified es-Raptor (the core component of mTOR complex 1) and es-Rictor (the core component of mTOR complex 2) from the testis of Eriocheir sinensis. Dynamic localization of es-Raptor and es-Rictor implied that these proteins were indispensable for the spermatogenesis of E. sinensis. Furthermore, es-Raptor and es-Rictor knockdown results showed that the mature sperm failed to be released, causing almost empty lumens in the testis. We investigated the reasons for these effects and found that the actin-based cytoskeleton was disrupted in the knockdown groups. In addition, the integrity of the testis barrier (similar to the blood-testis barrier in mammals) was impaired and affected the expression of cell junction proteins. Further study revealed that es-Raptor and es-Rictor may regulate spermatogenesis via both mTORC1- and mTORC2-dependent mechanisms that involve es-rpS6 and es-Akt/es-PKC, respectively. Moreover, to explore the testis barrier in E. sinensis, we established a cadmium chloride (CdCl2)-induced testis barrier damage model as a positive control. Morphological and immunofluorescence results were similar to those of the es-Raptor and es-Rictor knockdown groups. Altogether, es-Raptor and es-Rictor were important for spermatogenesis through maintenance of the actin filament network and cell junctions in E. sinensis.

Follicle-stimulating hormone signaling in Sertoli cells: a licence to the early stages of spermatogenesis.

Follicle-stimulating hormone signaling is essential for the initiation and early stages of spermatogenesis. Follicle-stimulating hormone receptor is exclusively expressed in Sertoli cells. As the only type of somatic cell in the seminiferous tubule, Sertoli cells regulate spermatogenesis not only by controlling their own number and function but also through paracrine actions to nourish germ cells surrounded by Sertoli cells. After follicle-stimulating hormone binds to its receptor and activates the follicle-stimulating hormone signaling pathway, follicle-stimulating hormone signaling will establish a normal Sertoli cell number and promote their differentiation. Spermatogonia pool maintenance, spermatogonia differentiation and their entry into meiosis are also positively regulated by follicle-stimulating hormone signaling. In addition, follicle-stimulating hormone signaling regulates germ cell survival and limits their apoptosis. Our review summarizes the aforementioned functions of follicle-stimulating hormone signaling in Sertoli cells. We also describe the clinical potential of follicle-stimulating hormone treatment in male patients with infertility. Furthermore, our review may be helpful for developing better therapies for treating patients with dysfunctional follicle-stimulating hormone signaling in Sertoli cells.

What Does Androgen Receptor Signaling Pathway in Sertoli Cells During Normal Spermatogenesis Tell Us?

Androgen receptor signaling pathway is necessary to complete spermatogenesis in testes. Difference between androgen binding location in Sertoli cell classifies androgen receptor signaling pathway into classical signaling pathway and non-classical signaling pathway. As the only somatic cell type in seminiferous tubule, Sertoli cells are under androgen receptor signaling pathway regulation via androgen receptor located in cytoplasm and plasma membrane. Androgen receptor signaling pathway is able to regulate biological processes in Sertoli cells as well as germ cells surrounded between Sertoli cells. Our review will summarize the major discoveries of androgen receptor signaling pathway in Sertoli cells and the paracrine action on germ cells. Androgen receptor signaling pathway regulates Sertoli cell proliferation and maturation, as well as maintain the integrity of blood-testis barrier formed between Sertoli cells. Also, Spermatogonia stem cells achieve a balance between self-renewal and differentiation under androgen receptor signaling regulation. Meiotic and post-meiotic processes including Sertoli cell - Spermatid attachment and Spermatid development are guaranteed by androgen receptor signaling until the final sperm release. This review also includes one disease related to androgen receptor signaling dysfunction named as androgen insensitivity syndrome. As a step further ahead, this review may be conducive to develop therapies which can cure impaired androgen receptor signaling in Sertoli cells.

One novel naphthalene derivative and other constituents with anti-complementary activities from the aerial parts of Dracocephalum moldavica.

One novel naphthalene derivative, 2-octa-2',4',6'-atriynenaphthalene (1), together with eighteen known compounds (2-19) were isolated from the aerial parts of Dracocephalum moldavica L. Compounds 2, 8, 10, 13, 15-17 and 19 were obtained from the family Lamiaceae for the first time, and compounds 11 and 18 were firstly identified from the genus of Dracocephalum. All the isolates were evaluated for anti-complementary activities through the classical and alternative pathways, and the targets of the most active compounds on the complement activation cascade were also investigated.

Two new phenolic glycosides from the fruits of Illicium verum.

Two new phenolic glycosides (1-2) and eleven known compounds (3-13) were isolated from the fruits of Illicium verum Hook.f. using silica-gel column and preparative middle pressure liquid chromatography (MPLC). The structures of the compounds were elucidated by NMR spectroscopic data. Among them, compounds 3, 5, and 10 were isolated from the family Magnoliaceae for the first time. Additionally, all the compounds were evaluated for their anti-complementary activities against the classical pathway (CP) and the alternative pathway (AP).

Four new fatty acid derivatives from Diaporthe sp. T24, an endophytic fungus isolated from Ligularia fischer.

The endophytic fungus Diaporthe sp. is known to contain many secondary metabolites, but fatty acid derivatives have rarely been found. In this study, four new fatty acid derivatives (1-4), together with four known compounds (5-8), were isolated from Diaporthe sp., which was obtained from the stem of Ligularia fischeri. The absolute configurations of the new compounds 1-4 were deduced based on spectroscopic technique and J-based coupling constant analysis. Moreover, compound 1 exhibited cytotoxic activities against HCT-8 and MCF-7 cancer cells, and compounds 3 and 4 showed modest selectivity for HCT-8 cells by MTT assay.

The Mediating Role of Job Competence between Safety Participation and Behavioral Compliance.

The effective improvement of employee behavioral compliance and safety performance is an important subject related to the sustainable development of the construction industry. Based on data from a Chinese company (n = 290), this study used a partial least squares-structural equation model to clarify the relationship among safety participation, job competence, and behavioral compliance. Empirical analysis found that: (1) safety participation had a significant positive impact on employees' behavioral compliance; and (2) job competence played a partial mediating role between safety participation and behavioral compliance. By selecting two new perspectives of safety participation and job competence, this study derived new factors affecting behavioral compliance, constructed a new theory about safety management, and conducted an in-depth discussion on improving behavioral compliance theoretically. Practically, the research put forward a new decision-making model, deconstructed the mechanism between safety participation and behavioral compliance, and provided new guiding strategies for improving employee behavioral compliance.

Prognostic index for estimating the survival benefit of postoperative radiotherapy in pathologic N2 non-small cell lung cancer: A real-world validation study.

OBJECTIVES: This study aimed to evaluate the effect of postoperative radiotherapy (PORT) in patients with resected pathologic N2 (pN2) non-small cell lung cancer (NSCLC) with different locoregional recurrence (LRR) risks. MATERIALS AND METHODS: The primary cohort and validation cohort were retrieved from two independent medical centres. Data for all consecutive patients with completely resected pathologic stage T1-3N2M0 NSCLC were analysed. Patients without PORT in the primary cohort were identified as a training set. Significant prognostic factors for LRR were identified by the Fine-Gray model to develop a prognostic index (PI) in the training set. RESULTS: The primary cohort consisted of 357 patients who met the eligibility criteria (training set, 287 patients without PORT). The external validation cohort consisted of 1044 patients who met the eligibility criteria (validation set, 711 patients without PORT). Heavy cigarette smoking history, clinical N2 status (cN2), and the number of positive lymph nodes >4 were identified as independent risk factors. The PI was computed as follows: PI＝0.8*smoking history＋0.5*cN2＋0.7*the number of involved lymph nodes (reference level was assigned the value 1 and risk level the value 2). In the low-risk group (PI score< = 3), PORT showed a trend towards decreased LRR rates but not significantly improved overall survival (OS). In the high-risk group (PI score>3), PORT significantly reduced the risk of LRR and improved OS. CONCLUSIONS: We constructed and validated a PI to predict individually the effect of PORT in patients with completely resected pN2 NSCLC. Patients with a higher PI score can benefit from PORT in terms of OS.

Intensity Modulated Radiation Therapy for Pleural Recurrence of Thymoma: A Prospective Phase 2 Study.

PURPOSE: This study aimed to evaluate the efficacy and safety of intensity modulated radiation therapy (IMRT) for pleural recurrence of thymoma that was not suitable for surgery and had progressed after chemotherapy. MATERIALS AND METHODS: From February 2012, consecutive patients with pleural recurrence of thymoma were prospectively enrolled. Due to dose restrictions to normal tissue (lung, liver, and kidney), 3 different levels of radiation doses (30 Gy, 40 Gy, and 50 Gy) were prescribed for pleural lesions of different sizes and locations, with a daily fraction dose of 2 Gy. The objective response rate, local control time (LCT), overall survival time, and toxicity were recorded, respectively. RESULTS: By August 2016, 31 patients had completed the IMRT treatment. There were 21 male and 10 female patients, with a median age of 49 (range, 22-70) years. B3 thymoma was the major (62%) tumor subtype observed. During the median follow-up of 48 (24-70) months, the objective response rate was 97%, and the median LCT was 49 (95% confidence interval, 40.4-58.1) months. However, 29 (93.5%) patients developed out-of-field recurrence, among whom 10 (32%; 30 Gy, n = 7; 40 Gy, n = 3) developed both out-of-field and in-field recurrence. The median progression-free survival was 19 months, and no in-field recurrence occurred in the 50 Gy group. Moreover, a higher dose was related to a longer LCT. No toxicities higher than a grade 4 occurred after IMRT within the normal-tissue dose limitation. The 5-year overall survival of the patients was 81%. CONCLUSIONS: IMRT for pleural recurrence may act as an alternative treatment when surgery is not feasible, with a higher dose resulting in a longer LCT. In this study, out-of-field recurrence was considerably common, but repeated IMRT for new recurrence should be cautiously carried out due to the high risk of radiation-induced pneumonitis.

Effective Radiotherapy in Tracheobronchial Adenoid Cystic Carcinoma With Positive Surgical Margin.

BACKGROUND: The study aimed to evaluate the role of postoperative radiotherapy (PORT) in the treatment of trachea and main bronchus adenoid cystic carcinoma (ACC) with a positive surgical margin. METHODS: Patients with pathologically confirmed trachea or main bronchus ACC operated on at Shanghai Chest Hospital were enrolled. Survival, univariate, and multivariate analyses were performed. The χ2 test was applied to analyze the failure patterns among different groups (R0/0: negative margin resection without PORT; R1/0: positive margin resection without PORT; R1/1: positive margin resection with PORT). RESULTS: From January 2001 to December 2014, 77 patients were deemed eligible for the study. Pairwise comparisons showed that the overall survival rate of group R1/1 was comparable to that of group R0/0 (P = .438), and significantly longer than the rate of group R1/0 (P = .032). Additionally, the local disease-free survival rate of group R1/1 was much higher than that of group R0/0 (P = .023) and R1/0 (P = .001). Cox multivariate analysis identified the radiologic feature (P = .012) and PORT (P = .006) as significantly favorable prognostic factors for locoregional disease-free survival. By contrast, for overall survival, PORT (P = .032) was the only corresponding variable identified by univariate analysis. Furthermore, PORT significantly decreased the locoregional recurrence rate (P = .002) but not distant metastases (P > .999). CONCLUSIONS: PORT helped patients with tracheobronchial ACC and microscopic positive surgical margins to achieve a similar outcome as patients with complete resection. R0 resection may not be necessary for tracheobronchial ACC if it is difficult to be completely resected.

Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio associations with heart and body dose and their effects on patient outcomes in locally advanced non-small cell lung cancer treated with definitive radiotherapy.

BACKGROUND: Inflammation plays a vital role in tumor growth and progression and can be affected by radiotherapy (RT) and chemotherapy. We sought to investigate the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and their associations with dosimetric factors in locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: In this retrospective study, subjects consisted of 244 patients who had received definitive RT ± chemotherapy for LA-NSCLC between 2012 and 2016. Absolute lymphocyte count (ALC), NLR and PLR recorded at pretreatment, during RT and post-RT were analyzed. Multivariable analysis (MVA) was performed to correlate clinical factors and inflammatory biomarkers with progression-free survival (PFS) and overall survival (OS) using a Cox regression model. Relationships between NLR or PLR with OS and PFS were evaluated with Kaplan-Meier analysis and compared with log-rank test results. Multiple stepwise linear regression was used to assess the associations between dosimetric factors and NLR or PLR. RESULTS: The median PFS and OS for all patients were 8.6 and 15.8 months, respectively. On MVA for PFS and OS, higher 1-month post-RT start NLR [hazard ratio (HR) 1.049; 95% CI: 1.018-1.080; P=0.001] or higher 1-month post-RT start PLR (HR 1.001; 95% CI: 1.000-1.002; P<0.001) was associated with inferior PFS. Higher 1-month post-RT start NLR (HR 1.040; 95% CI: 1.013-1.069; P=0.004) or PLR (HR 1.001; 95% CI: 1.001-1.002; P<0.001) was also an independent predictor of OS. ALCmin, baseline NLR and PLR were not associated with treatment outcomes. Multiple stepwise linear regression analysis confirmed that baseline NLR (P<0.001), heart V20 (P<0.001), heart V40 (P<0.001), and mean body dose (MBD) were significantly associated with 1-month post-RT start NLR. Also, baseline PLR (P<0.001) and MBD (P<0.001) were significantly associated with 1-month post-RT start PLR. CONCLUSIONS: Higher NLR and PLR during treatment were associated with worse patient outcomes, and heart dose or body dose was correlated with NLR or PLR in advanced NSCLC patients treated with definitive RT.

Unveiling the Pharmacological Mechanisms of Eleutheroside E Against Postmenopausal Osteoporosis Through UPLC-Q/TOF-MS-Based Metabolomics.

Postmenopausal osteoporosis (PMOP) is a common metabolic bone disease in postmenopausal women in the Worldwide, and seriously affects the quality of life of middle-aged and elderly women. Therefore, there is an urgent need to discover a highly effective drug for PMOP treatment. In this study, ultra-high performance liquid tandem quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was used to analyze the urine metabolic profiling and potential biomarkers, the relevant metabolic network of PMOP rats, and further to evaluate the intervention effect of Eleutheroside E (EE) against PMOP. Using multivariate statistical analysis combined with UPLC-Q/TOF-MS, a total of 27 biomarkers were identified, which related with 16 metabolic pathways, mainly involving steroidogenesis, beta oxidation of very long chain fatty acids, glutathione metabolism, carnitine synthesis, estrone metabolism, oxidation of branched chain fatty acids, etc. After treatment of EE, these biomarkers were markedly regulated, mainly involving steroid hormone biosynthesis, arachidonic acid metabolism, primary bile acid biosynthesis, indicating that EE had the therapeutic effect on PMOP. This study identified the potential urine metabolic markers and related metabolic pathways of the PMOP, explained the metabolic effect and pharmacological mechanisms of EE against PMOP, and provided a basis for the pharmacological study of EE.