Mitophagy in mammalian follicle development and health.

Mitophagy, the cellular process that removes damaged mitochondria, plays a crucial role in maintaining normal cell functions. It is deeply involved in the entire process of follicle development and is associated with various ovarian diseases. This review aims to provide a comprehensive overview of mitophagy regulation, emphasizing its role at different stages of follicular development. Additionally, the study illuminates the relationship between mitophagy and ovarian diseases, including ovary aging (OA), primary ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS). A detailed understanding of mitophagy could reveal valuable insights and novel strategies for managing female ovarian reproductive health.

Discovery of Sovleplenib, a Selective Inhibitor of Syk in Clinical Development for Autoimmune Diseases and Cancers.

Herein we describe the medicinal chemistry efforts that led to the discovery of the clinical-staged Syk inhibitor sovleplenib (41) via a structure-activity relationship investigation and pharmacokinetics (PK) optimization of a pyrido[3,4-b]pyrazine scaffold. Sovleplenib is a potent and selective Syk inhibitor with favorable preclinical PK profiles and robust anti-inflammation efficacy in a preclinical collagen-induced arthritis model. Sovleplenib is now being developed for treating autoimmune diseases such as immune thrombocytopenic purpura and warm antibody hemolytic anemia as well as hematological malignancies.

The Value of Chemokine and Chemokine Receptors in Diagnosis, Prognosis, and Immunotherapy of Hepatocellular Carcinoma.

Background: Chemokines and chemokine receptors (CCRs) are involved in a variety of anti-tumour and pro-tumour immune processes in vivo, such as angiogenesis, metastasis, proliferation and invasiveness, and influence patient prognosis and response to therapy. Methods: CCRs differentially expressed in HCC and associated with prognosis were extracted from TCGA and GEO databases, and the obtained CCRs were then used to construct signature genes, and the signature gene were selected for expression validation as well as functional experiments to explore the role of CCRs in the treatment and prognosis of HCC. Results: We constructed a prognostic model including five CCRs (CCL20, CCL23, CCR3, CCR10, and CXCR3) and validated the expression of signature genes. The model's risk score is an independent prognostic factor for HCC. We have also developed prognostic model nomograms for clinical use. In addition, we validated that CCR3 expression is associated with poor prognosis in HCC, and the proliferation and migration ability of HCC cells was significantly inhibited after interfering with the expression of CCR3 in MHCC-LM3. We also looked at differences in pathway enrichment, immune infiltration and immune checkpoints. Finally, we found that risk scores were also correlated with drug sensitivity, the high-risk group had a better sensitivity to sorafenib. Conclusion: The CCRs-related gene signature may better assess HCC prognosis and response to immunotherapy and tyrosine kinase inhibitors such as sorafenib in HCC, providing prospective solutions for diagnosis and treatment.

PAFAH1B3 is a KLF9 target gene that promotes proliferation and metastasis in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. Uncontrolled cell proliferation, invasion and migration of pancreatic cancer cells are the fundamental causes of death in PDAC patients. Our previous studies showed that KLF9 inhibits the proliferation, invasion and migration of pancreatic cancer cells. However, the underlying mechanisms are not fully understood. In this study, we found that platelet-activating factor acetylhydrolase IB3 (PAFAH1B3) is highly expressed in pancreatic cancer tissues and cells. In vitro and in vivo studies showed that overexpression of PAFAH1B3 promoted the proliferation and invasion of pancreatic cancer cells, while downregulation of PAFAH1B3 inhibited these processes. We found that KLF9 expression is negatively correlated with PAFAH1B3 expression in pancreatic cancer tissues and cells. Western blotting revealed that KLF9 negatively regulates the expression of PAFAH1B3 in pancreatic cancer tissues and cells. Rescue experiments showed that overexpression of PAFAH1B3 could partially attenuate the suppression of pancreatic cancer cell proliferation, invasion and migration induced by KLF9 overexpression. Finally, chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were carried out, and the results showed that KLF9 directly binds to the promoter of PAFAH1B3 and inhibits its transcriptional activity. In conclusion, our study indicated that KLF9 can inhibit the proliferation, invasion, migration and metastasis of pancreatic cancer cells by inhibiting PAFAH1B3.

Ice sheet and precession controlled subarctic Pacific productivity and upwelling over the last 550,000 years.

The polar oceans play a vital role in regulating atmospheric CO2 concentrations (pCO2) during the Pleistocene glacial cycles. However, despite being the largest modern reservoir of respired carbon, the impact of the subarctic Pacific remains poorly understood due to limited records. Here, we present high-resolution, 230Th-normalized export productivity records from the subarctic northwestern Pacific covering the last five glacial cycles. Our records display pronounced, glacial-interglacial cyclicity superimposed with precessional-driven variability, with warm interglacial climate and high boreal summer insolation providing favorable conditions to sustain upwelling of nutrient-rich subsurface waters and hence increased export productivity. Our transient model simulations consistently show that ice sheets and to a lesser degree, precession are the main drivers that control the strength and latitudinal position of the westerlies. Enhanced upwelling of nutrient/carbon-rich water caused by the intensification and poleward migration of the northern westerlies during warmer climate intervals would have led to the release of previously sequestered CO2 from the subarctic Pacific to the atmosphere. Our results also highlight the significant role of the subarctic Pacific in modulating pCO2 changes during the Pleistocene climate cycles, especially on precession timescale ( ~ 20 kyr).

An O/N/S-rich porous Fe-based metal-organic framework (MOF) for gold recovery from the aqueous phase with excellent performance.

Recovering gold from wastewater has both economic and environmental benefits. However, how to effectively recover it is challenging. In this work, a novel Fe-based metal-organic framework (MOF) was synthesized and decorated with 2,5-thiophenedicarboxylic acid to have a well-developed porous architecture to effectively recover Au(III) from water. The maximum Au(III) sorption capacity by the finally-synthesized porous material MIL-101(Fe)-TDCA reached 2350 mg/g at pH = 6.00 ± 0.15, which is one of the highest among all literature-reported relevant materials including MOFs, and high sorption strength can be maintained within a wide pH range from 2.0 to 10.0. Besides, Au(III) sorption efficiency at low concentrations (i.e., 3.5 × 104 mg/mL) reached over 99%. Mechanically, outstanding Au(III) sorption by MIL-101(Fe)-TDCA resulted from the O/N/S-containing moieties on its surface, large surface area and porosity. The N- and S-containing functionalities (CS, CONH) served as electron donors to chelate Au(III). The O-containing (FeOFe, COFe, COOH, and coordinated H2O) and N-containing (CONH) moieties on MIL-101(Fe)-TDCA interacted with OH groups on the hydrolyzed species of Au(III) (AuCl3(OH)-, AuCl2(OH)2-, and AuCl(OH)3-) by hydrogen bond, which further increased Au(III) sorption. Furthermore, about 45.71% of Au(III) was reduced to gold nanoparticles by CS groups on the decorated 2,5-dithiophene dicarboxylic acid during sorption on MIL-101(Fe)-TDCA. Over 98.35% of Au(III) was selectively sorbed on MIL-101(Fe)-TDCA at pH 4.0, much higher than that of the coexisting heavy metal ions including Cu(II), Zn(II), Pb(II), and Ni(II) (< 5%), despite their same concentration at 0.01 mg/mL. Although sorption selectivity of a noble metal Pt(IV) by MIL-101(Fe)-TDCA is relatively poor (68.23%), it could be acceptable. Moreover, reusability of MIL-101(Fe)-TDCA is also excellent, since above 90.5% Au(III) still can be sorbed after two sorption-desorption cycles. Overall, excellent sorption performance and the roughly-calculated gold recycling benefits (26.30%) highlight that MIL-101(Fe)-TDCA is a promising porous material for gold recovery from the aqueous phase.

Presepsin as a prognostic biomarker in COVID-19 patients: combining clinical scoring systems and laboratory inflammatory markers for outcome prediction.

BACKGROUND: There is still limited research on the prognostic value of Presepsin as a biomarker for predicting the outcome of COVID-19 patients. Additionally, research on the combined predictive value of Presepsin with clinical scoring systems and inflammation markers for disease prognosis is lacking. METHODS: A total of 226 COVID-19 patients admitted to Beijing Youan Hospital's emergency department from May to November 2022 were screened. Demographic information, laboratory measurements, and blood samples for Presepsin levels were collected upon admission. The predictive value of Presepsin, clinical scoring systems, and inflammation markers for 28-day mortality was analyzed. RESULTS: A total of 190 patients were analyzed, 83 (43.7%) were mild, 61 (32.1%) were moderate, and 46 (24.2%) were severe/critically ill. 23 (12.1%) patients died within 28 days. The Presepsin levels in severe/critical patients were significantly higher compared to moderate and mild patients (p < 0.001). Presepsin showed significant predictive value for 28-day mortality in COVID-19 patients, with an area under the ROC curve of 0.828 (95% CI: 0.737-0.920). Clinical scoring systems and inflammation markers also played a significant role in predicting 28-day outcomes. After Cox regression adjustment, Presepsin, qSOFA, NEWS2, PSI, CURB-65, CRP, NLR, CAR, and LCR were identified as independent predictors of 28-day mortality in COVID-19 patients (all p-values < 0.05). Combining Presepsin with clinical scoring systems and inflammation markers further enhanced the predictive value for patient prognosis. CONCLUSION: Presepsin is a favorable indicator for the prognosis of COVID-19 patients, and its combination with clinical scoring systems and inflammation markers improved prognostic assessment.

Iron-enhanced microscale laboratory aerated filters in the treatment of artificial mariculture wastewater: A study on nitrogen removal performance and the impact on microbial community structure.

This study investigates the nitrogen removal efficacy and microbial community dynamics in seawater aquaculture effluent treatment using three different substrate combinations of microscale laboratory aerated filters (MFs) - MF1 (LECA), MF2 (LECA/Fe-C), and MF3 (LECA/Pyrite). The findings indicated that the COD removal exceeded 95% across all MFs, with higher removal efficiencies in MF2 and MF3. In terms of nitrogen removal performance, MF2 exhibited the highest average nitrogen removal of 93.17%, achieving a 12.35% and 3.56% increase compared to MF1 (80.82%) and MF3 (89.61%), respectively. High-throughput sequencing analysis revealed that the Fe-C substrate significantly enhanced the diversity of the microbial community. Notably, in MF2, the salinophilic denitrifying bacterium Halomonas was significantly enriched, accounting for 42.6% of the total microbial community, which was beneficial for nitrogen removal. Moreover, an in-depth analysis of nitrogen metabolic pathways and microbial enzymes indicated that MF2 and MF3 possessed a high abundance of nitrification and denitrification enzymes, related to the high removal rates of NH4+-N and NO3--N. Therefore, the combination of LECA with iron-based materials significantly enhances the nitrogen removal efficiency from mariculture wastewater.

[Determination of 35 prohibited pesticide residues in Saussurea costus by modified QuEChERS method based on multi-walled carbon nanotubes coupled with gas chromatography-tandem mass spectrometry].

Saussurea costus, a perennial herb belonging to the Asteraceae family, is a vital ingredient in traditional Chinese medicine. Increased demands for the herb have led to its widespread cultivation in China, but the corresponding increase in pesticide use has raised concerns about pesticide residues. Such residues would affect the safety and global market potential of Saussurea costus. Thus, a simple method is crucial to detect pesticide residues. The QuEChERS technique, in combination with gas chromatography-tandem mass spectrometry (GC-MS/MS), is commonly used for residue detection. However, traditional adsorbents may be unable to purify complex herbal mixtures well, affecting accuracy and instrument performance. Choosing suitable purification materials for Saussurea costus samples with complex matrices is of significant importance. This study focused on the detection of 35 prohibited pesticides in Saussurea costus. A rapid detection method was established by combining the QuEChERS technique with GC-MS/MS and utilizing a combination of multiwalled carbon nanotubes (MWCNTs), octadecylsilane-bonded silica gel (C18), and anhydrous magnesium sulfate (MgSO4) as the purification adsorbent. The samples were extracted with acetonitrile, purified by an improved QuEChERS process, subjected to GC-MS/MS analysis in multiple reaction monitoring (MRM) mode, and quantified using the internal standard method. The purification effects of four materials (C18, MWCNTs, N-propyl ethylenediamine (PSA), and graphitized carbon black (GCB)) and their optimal dosages were investigated by considering the matrix characteristics of the samples. An orthogonal experimental design was employed to optimize the ratio of adsorbent combinations, and the optimal adsorbent combination was determined to be 450 mg of MgSO4, 400 mg of C18, and 50 mg of MWCNTs. Matrix effect (ME) evaluation of the S. costus matrix showed that 31 target compounds strongly exhibited matrix-enhancement effects. Thus, matrix-matched calibration was employed in this study. Methodological investigation revealed that the standard curves for the 35 pesticides exhibited good linearity, with correlation coefficients (r2) greater than 0.9970. The average recoveries at three spiked levels ranged from 69.6% to 126.9%, and the relative standard deviations (RSDs) for parallel groups were all less than 10%. The limits of detection (LODs) and quantification (LOQs) ranged from 0.2 to 5.4 µg/kg and from 0.6 to 18.1 µg/kg, respectively. The developed method was used to screen and detect 35 pesticide residues in 20 batches of S. costus samples, and the target compounds were detected in six batches. The proposed method is simple, sensitive, and accurate. Thus, it is suitable for the rapid screening and detection of the 35 pesticide residues in S. costus and provides technical support for the cultivation, production, and quality control of the herb.

Artificial Intelligence-Assisted RFID Tag-Integrated Multi-Sensor for Quality Assessment and Sensing.

Radio frequency identification (RFID) is well known as an identification, track, and trace approach and is considered to be the key physical layer technology for the industrial internet of things (IIoT). However, IIoT systems have to introduce additional complex sensor networks for pervasive monitoring, and there are still challenges related to item-level sensing and data recording. To overcome the shortage, this work proposes an artificial intelligence (AI)-assisted RFID-based multi-sensing technology. Both passive and semi-passive RFID tag-integrated multi-sensors are developed. The main contributions and the novelty of this investigation are as follows. A UHF RFID tag-integrated multi-sensor with a boosted charge pump is proposed; it enables high RF signal sensitivity and a long operational range. The whole hardware design, including the antenna and energy harvester, are studied. Moreover, a demonstration with real-world ham product sensing data is conducted. This work also proposes and successfully demonstrates the integration of machine learning algorithms, specifically the NARX neural network, with RFID sensing data for food product quality assessment and sensing (QAS). This application of machine learning to RFID-generated data for quality assessment is also a novel aspect of the research. The deployment of an autoregressive model with an exogenous input (NARX) neural network model, tailored for nonlinear processes, emerges as the most effective, achieving a root mean square error (RMSE) of 0.007 and an R-squared value of 0.99 for ham product QAS. By deploying the technology, low-cost, timely, and flexible product QAS can be achieved in manufacturing industries, which helps product quality improvement and the optimization of the manufacturing line and supply chain.

TMEM160 promotes tumor immune evasion and radiotherapy resistance via PD-L1 binding in colorectal cancer.

BACKGROUND: The effectiveness of anti-programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1) therapy in treating certain types of cancer is associated with the level of PD-L1. However, this relationship has not been observed in colorectal cancer (CRC), and the underlying regulatory mechanism of PD-L1 in CRC remains unclear. METHODS: Binding of TMEM160 to PD-L1 was determined by co-immunoprecipitation (Co-IP) and GST pull-down assay.The ubiquitination levels of PD-L1 were verified using the ubiquitination assay. Phenotypic experiments were conducted to assess the role of TMEM160 in CRC cells. Animal models were employed to investigate how TMEM160 contributes to tumor growth.The expression and clinical significance of TMEM160 and PD-L1 in CRC tissues were evaluated by immunohistochemistry(IHC). RESULTS: In our study, we made a discovery that TMEM160 interacts with PD-L1 and plays a role in stabilizing its expression within a CRC model. Furthermore, we demonstrated that TMEM160 hinders the ubiquitination-dependent degradation of PD-L1 by competing with SPOP for binding to PD-L1 in CRC cells. Regarding functionality, the absence of TMEM160 significantly inhibited the proliferation, invasion, metastasis, clonogenicity, and radioresistance of CRC cells, while simultaneously enhancing the cytotoxic effect of CD8 + T cells on tumor cells. Conversely, the upregulation of TMEM160 substantially increased these capabilities. In severely immunodeficient mice, tumor growth derived from lentiviral vector shTMEM160 cells was lower compared with that derived from shNC control cells. Furthermore, the downregulation of TMEM160 significantly restricted tumor growth in immune-competent BALB/c mice. In clinical samples from patients with CRC, we observed a strong positive correlation between TMEM160 expression and PD-L1 expression, as well as a negative correlation with CD8A expression. Importantly, patients with high TMEM160 expression exhibited a worse prognosis compared with those with low or no TMEM160 expression. CONCLUSIONS: Our study reveals that TMEM160 inhibits the ubiquitination-dependent degradation of PD-L1 that is mediated by SPOP, thereby stabilizing PD-L1 expression to foster the malignant progress, radioresistance, and immune evasion of CRC cells. These findings suggest that TMEM160 holds potential as a target for the treatment of patients with CRC.

The Variation Patterns of the Martensitic Hierarchical Microstructure and Mechanical Properties of 35Si2MnCr2Ni3MoV Steel at Different Austenitizing Temperatures.

This study investigates the influence of varying austenitizing temperatures on the microstructure and mechanical properties of 35Si2MnCr2Ni3MoV steel, utilizing Charpy impact testing and microscopic analysis techniques such as scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD). The findings reveal that optimal combination of strength and toughness is achieved at an austenitizing temperature of 980 °C, resulting in an impact toughness of 67.2 J and a tensile strength of 2032 MPa. The prior austenite grain size initially decreases slightly with increasing temperature, then enlarges significantly beyond 1100 °C. The martensite blocks' and packets' structures exhibit a similar trend. The proportion of high-angle grain boundaries, determined by the density of the packets, peaks at 980 °C, providing maximal resistance to crack propagation. The amount of retained austenite increases noticeably after 980 °C; beyond 1200 °C, the coarsening of packets and a decrease in density reduce the likelihood of trapping retained austenite. Across different austenitizing temperatures, the steel demonstrates superior crack initiation resistance compared to crack propagation resistance, with the fracture mode transitioning from ductile dimple fracture to quasi-cleavage fracture as the austenitizing temperature increases.

PARVB promotes malignant melanoma progression and is enhanced by hypoxic conditions.

Beta-Parvin (PARVB) is an actin-binding protein with functionality in extracellular matrix binding. Recent studies suggest its potential as a biomarker for various cancers, given its role in governing several malignancies. Yet, its involvement and modulatory mechanisms in malignant melanoma remain under-explored.  In this research, we undertook a comprehensive pan-cancer analysis centered on PARVB. We probed its aberrant expression and prognostic implications, and assessed correlations between PARVB expression and immunocyte infiltration. This expression was subsequently corroborated using clinical samples. Both in vitro and in vivo, we discerned the functional ramifications of PARVB on melanoma. Furthermore, we scrutinized how HIF-1α/2α modulates PARVB and initiated a preliminary investigation into potential downstream pathways influenced by PARVB. Our results illuminate that elevated PARVB expression manifests across various tumors and significantly influences the prognosis of multiple cancers, emphasizing its peculiar expression and prognostic relevance in melanoma. Augmented PARVB levels were inversely proportional to immunocyte penetration in melanoma. Silencing PARVB curtailed cellular proliferation, migration, and invasion in vitro and decelerated tumor expansion in vivo. Notably, hypoxic conditions, triggering HIF-1α/2α activation, appear to elevate PARVB expression by anchoring to the hypoxia-specific responsive element within the PARVB promoter. Enhanced PARVB levels seem intertwined with the activation of cellular proliferation circuits and the damping of inflammatory trajectories. Collectively, these revelations posit PARVB as a potential prognostic indicator and therapeutic linchpin for malignant melanoma.

Morphology and Distribution of Primary Carbides in Forged Cr-Ni-Mo-V/Nb Steel.

This study aims to investigate in situ the three-dimensional (3D) morphology and distribution of primary carbides (PCs) in electro-slag remelting (ESR) forged 30Cr3Ni3Mo2V steel. A facile non-aqueous electrolytic etching method was applied to prepare 3D PCs on the matrix. The morphology, composition, and element concentrations of PCs were characterized using a combination of optical microscopy (OM), scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS), and electron back-scattered diffusion (EBSD). The precipitation, type, and composition of PCs in the same steel were also simulated using Thermo-Calc software Version 2015a. The results indicate that PC is rich in Nb, which is a potential heterogeneous nucleating agent. Both the size and number of PCs increase from the edge to the center of the ingot. The large-sized PCs present three dominant types of morphology, which vary in different regions, i.e., a bulky type dominates in the edge region, a lamellar type dominates in the middle region, and a stripy type dominates in the core region. The results of EBSD analysis show that the orientation of PCs with different morphologies is different and that more nanosized V-rich type carbides are precipitated on the matrix. The thermodynamic calculations show that MC precipitates from the liquid phase when the solid phase fraction is greater than 0.985 and that the MC-type carbides are rich in Nb, which agrees well with the experimental results.

Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src.

Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for ∼35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity. Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp-10) causes Dusp18 to dephosphorylate Src at Tyr 416. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase at its proline/arginine-rich motif in its C terminus. We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18. Kiss1, Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation.

Long-term postoperative outcomes of spinal cellular schwannoma: study of 93 consecutive cases.

BACKGROUND CONTEXT: Cellular schwannoma (CS) is a rare tumor that accounts for 2.8%-5.2% of all benign schwannomas. There is a dearth of up-to-date information on spinal CS in the literature. PURPOSE: The aims of this study were to identify the proportion of CS cases amongst spinal benign schwannoma, describe the clinical features of spinal CS, and identify prognostic factors for local recurrence by analyzing data from 93 consecutive CS cases. STUDY DESIGN: Retrospective review. PATIENT SAMPLE: We analyzed 93 PSGCT screened from 1,706 patients with spine CS who were treated at our institute between 2008 and 2021. OUTCOME MEASURES: Demographic, radiographic, operative and postoperative data were recorded and analyzed. METHODS: We compared the clinical features of spinal CS from the cervical, thoracic, lumbar and sacral segments. Prognostic factors for local recurrence-free survival (RFS) were identified by the Kaplan-Meier method. Factors with p≤.05 in univariate analysis were subjected to multivariate analysis by Cox regression analysis. RESULTS: The proportion of spinal CS in all benign schwannomas was 6.7%. The mean and median follow-up times for the 93 patients in this study were 92.2 and 91.0 months respectively (range 36-182 months). Local recurrence was detected in 11 cases, giving an overall recurrence rate of 11.7%, with one patient death. Statistical analysis revealed that tumor size ≥5 cm, intralesional resection, and Ki-67 ≥5% were independent negative prognostic factors for RFS in spinal CS. CONCLUSIONS: Whenever possible, en bloc resection is recommended for spinal CS. Long-term follow-up should be carried out for patients with tumor size ≥5 cm and postoperative pathological Ki-67 ≥5%.

Enhanced Antipediatric Sarcoma Effect of Everolimus with Secukinumab by Targeting IL17A.

In this study, we explored the therapeutic potential of everolimus, an mTOR inhibitor, in a patient-derived xenograft (PDX) of rhabdomyosarcoma, the most prevalent malignant pediatric sarcoma. In addition, rhabdoid tumor cell line A-204 and Ewings sarcoma cell line A-673 were cultured to assess the in vitro effect of everolimus. Furthermore, the cell-derived xenograft (CDX) of A-673 was established and treated with everolimus in vivo. IHC and Western blotting were performed to detect the expressions of pertinent proteins. Results showed that everolimus intervention had limited inhibitory effect on PDX tumor growth compared with cyclophosphamide. Nevertheless, everolimus treatment significantly influenced the phosphorylation levels of S6 kinase beta 1 (S6K1) and eIF4E-binding protein 1 (p-4E-BP1), resulting in the inhibition of angiogenesis in vitro and in vivo. Interestingly, everolimus led to an upregulation in the level of IL17A in sarcoma cells. Notably, when secukinumab, a mAb of IL17A, was combined with everolimus, it synergistically enhanced the inhibitory effect of everolimus on sarcoma cell proliferation in vitro and on the growth of PDX or CDX xenograft tumors in vivo. Importantly, this combination therapy did not affect the mTOR signaling. These results indicate that everolimus exerts an antipediatric sarcoma effect by inhibiting mTOR signal. However, everolimus induces sarcoma cells to produce IL17A, which promotes tumor cell survival and counteracts its antipediatric sarcoma effect. The combination of secukinumab effectively eliminates the effects of IL17A, thereby improving the therapeutic efficacy of everolimus in the context of pediatric sarcomas.

Comparison of efficacy between endoscope-assisted anterior cervical discectomy and fusion (ACDF) and open ACDF in the treatment of single-segment cervical spondylotic myelopathy.

BACKGROUND: In this study, we compared the clinical efficacy of endoscope-assisted anterior cervical discectomy and fusion (ACDF) with open ACDF in the treatment of single-segment cervical spondylotic myelopathy. METHODS: A retrospective analysis was performed on 52 patients with single-segment cervical spondylotic myelopathy between June 2021 and February 2022, including 33 males and 19 females, with a mean age of 58.42 ± 9.26) years. Among them, 28 patients were treated with endoscope-assisted ACDF (Group A), including 2 cases of C4/5 segment, 16 cases of C5/6 segment, and 10 cases of C6/7 segment; 24 patients were treated with open ACDF (Group B), including 4 cases of C4/5 segment, 11 cases of C5/6 segment, and 9 cases of C6/7 segment. The operation time, intraoperative blood loss, hospital stay, and complications were recorded and compared between the two groups. The Visual Analogue Scale (VAS) and the Japanese Orthopaedic Association (JOA) score were used for clinical evaluation during the follow-up in the 1st month and 3rd month after surgery, and at the final follow-up. RESULTS: The 52 patients were followed up on average for 13.04 months (12-17 months). The operation time in Group A and Group B was (105.18 + 8.66) minutes and (81.88 + 6.05) minutes, the intraoperative blood loss was (84.29 + 13.45) mL and (112.92 + 17.81) mL, and the hospital stay was (6.75 + 1.29) days and (7.63 + 1.41) days, respectively. The difference between the two groups was statistically significant (P < 0.05). The VAS and JOA scores in the 1st month and the 3rd month after surgery and the last follow-up significantly improved in both groups compared with those before surgery (P < 0.05). The VAS and JOA scores of Group A in the 1st month, 3rd month after surgery, and the last follow-up were better than those in Group B (P < 0.05). The complication rate in Group A was 7% (2/28), which was not significantly different from the 17% (4/24) in Group B (P > 0.05). CONCLUSION: Both endoscope-assisted ACDF and open ACDF can achieve satisfactory clinical efficacy in the treatment of single-segment cervical spondylotic myelopathy. Although the operation time of endoscope-assisted ACDF is prolonged, it has the advantages of clear vision, thorough decompression, less blood loss, and reduced risk of nerve damage, and is worthy of clinical promotion and application.

Tracing sediment sources in a plain river network area by using optimized experimental design and reflectance spectroscopy.

Soil erosion in a plain river network area with dense rivers, fertile land, and agricultural development is easily causes river siltation, agricultural non-point source pollution, and water eutrophication. Therefore, the negative impact of the sediment on the environment cannot be underestimated. Most traditional sediment fingerprint tracing studies have focused on mountain basins and lack a scheme suitable for plain river network sediment tracing. Here, a typical plain river network in the Taihu Basin was selected as the study area. The flow structure and characteristics were analysed, and a sampling scheme for the stream segment and a two-step model of sediment tracing in a plain river network were proposed to quantitatively distinguish the types of sediment sources. The results indicated that the traditional discriminant function analysis adequately distinguishes the contribution rate of basin soil and has a good validation accuracy (R2 = 0.96, root mean square error of calibration = 5.91 %), whereas Random Forest obtains better discrimination results by mining non-linear information in the soil spectra of different land types, with R2 values of 0.89, 0.83, and 0.80 for farmland, forest, and grassland, respectively. The average proportion of soil in the sediment in the watershed was 23 %, and the proportion of soil in the watershed increased from upstream to downstream. The sediment sources of the Caoqiao, Yincun, and Shaoxiang Rivers mainly came from grassland (44 %), forest (39 %), and farmland (42 %), respectively. Land-use distribution, water conservation facilities, and soil particle size were the main factors affecting these sources. Each river adopts measures to remove the corresponding pollutants, optimise water and soil conservation measures for riverbank green belts and forest, and regularly clean up silt in water conservancy ditches and rivers, which can reduce the pollution impact caused by sediment.

Boosted hydrogen evolution kinetics of heteroatom-doped carbons with isolated Zn as an accelerant.

Carbon-based single-atom catalysts, a promising candidate in electrocatalysis, offer insights into electron-donating effects of metal center on adjacent atoms. Herein, we present a practical strategy to rationally design a model catalyst with a single zinc (Zn) atom coordinated with nitrogen and sulfur atoms in a multilevel carbon matrix. The Zn site exhibits an atomic interface configuration of ZnN4S1, where Zn's electron injection effect enables thermal-neutral hydrogen adsorption on neighboring atoms, pushing the activity boundaries of carbon electrocatalysts toward electrochemical hydrogen evolution to an unprecedented level. Experimental and theoretical analyses confirm the low-barrier Volmer-Tafel mechanism of proton reduction, while the multishell hollow structures facilitate the hydrogen evolution even at high current intensities. This work provides insights for understanding the actual active species during hydrogen evolution reaction and paves the way for designing high-performance electrocatalysts.