Endovascular treatment of aorta-iliac arterial pseudoaneurysm caused by Brucella.

We aimed to analyze the feasibility of endovascular treatment for brucellosis-related aorta-iliac artery pseudoaneurysm. We did a statistical analysis that among the 11 cases, the thoracic aorta was involved in 3 cases, the abdominal aorta was involved in 6 cases, and the iliac artery was involved in 2 cases. Five patients had a history of contact with cattle and sheep, 3 had a history of drinking raw milk, 10 patients had a fever before the operation, and 11 patients had positive serum agglutination test. Blood culture was positive in 2 patients. All patients were given anti-brucellosis treatment immediately after diagnosis. One died of aortic rupture 5 days after emergency endovascular gastrointestinal bleeding. Endovascular-covered stent implantation and active anti-brucellosis therapy were used to treat 10 patients. The follow-up period was 8 years without aortic complications or death for all patients. We think early diagnosis and a combination of anti-brucellosis drugs and endovascular therapy may be the first choice for treating the pseudoaneurysm caused by Brucella.

Adherence to guidelines and central line-associated bloodstream infection occurrence during insertion and maintenance of intravascular catheters: evidence from 20 tertiary hospitals.

OBJECTIVE: To investigate adherence to intravascular catheter (IVC) insertion and maintenance guidelines in Chinese tertiary hospitals. METHODS: A cross-sectional questionnaire survey of adult inpatients with IVC placements was conducted from July to September 2022 in 20 tertiary hospitals in China. One clinical staff member from each department in each hospital was assigned to participate in the survey. Questionnaires were uniformly collected and reviewed after 3 months. RESULTS: This study included 1815 cases (62.69%) of central venous catheter, 471 cases (16.27%) of peripherally inserted central catheter, 461 cases (15.92%) of PORT, and 147 cases (5.08%) of haemodialysis catheter insertions. Statistically significant differences in compliance were observed across the four IVC types, specifically in relation to the insertion checklist, standard operating procedure, and insertion environment (P<0.05). Practice adherence during IVC maintenance differed significantly across the four IVC types in aspects such as availability of IVC maintenance verification forms, daily scrubbing of the catheterised patients, and catheter connection methods (P<0.05). A total of 386 (13.34%) patients developed fever, 1086 (37.53%) were treated with therapeutic antibiotics, 16 (0.55%) developed central line-associated bloodstream infections, two (0.07%) developed local skin infections, and six (0.21%) developed deep vein thrombosis. CONCLUSIONS: Adherence to guidelines regarding insertion and maintenance differed across the four IVC types; there is a gap between the recommended measures and the actual operation of the guideline. Therefore, it is necessary to further enhance training and develop checklists to prevent CLABSIs.

Abnormal sleep patterns are associated with depressive symptoms in Chinese community-dwelling older adults.

OBJECTIVE: Depression is an important public health issue among older adults, often associated with their sleep-related problems. We aimed to investigate the association between sleep-related problems and depressive symptoms among Chinese community-dwelling older adults. METHODS: This cross-sectional study utilized self-reported data from 2896 participants (aged ≥60 years) from Shanghai, China. Nocturnal sleep duration and difficulty initiating sleep (DIS) symptoms were obtained through face-to-face questionnaires. Nocturnal sleep duration was categorized as 'short' (<7 h), 'normal' (7-8 h), and 'long' (>8 h). Subsequently, the 3 groups were further divided into 6 groups based on the presence of DIS, and the combined sleep behaviors were termed 'sleep patterns'. Logistic regression was conducted to assess the association of sleep variables and sleep patterns with the risk of depressive symptoms. RESULTS: Compared to the reference group, 'short sleep duration' and DIS symptoms were associated with depressive symptoms (with odds ratios (OR) of 1.50 and 1.79, respectively, with 95% confidence intervals (CI) of 1.14-1.97 and 1.39-2.31). When compared to 'normal sleep duration without DIS', both 'short sleep duration with DIS' (OR = 2.60, 95% CI: 1.81-3.72) and 'normal sleep duration with DIS' (OR = 1.60, 95% CI: 1.03-2.49) were statistically associated with depressive symptoms in adjusted regression models. CONCLUSION: Short sleep duration and DIS symptoms were found to be associated with depressive symptoms. Combining DIS symptoms with sleep duration, DIS was identified as a risk factor for elevated depressive symptoms in individuals with short and normal sleep durations. In managing depressive symptoms, it is imperative to thoroughly evaluate insomnia and nighttime sleep, which can provide valuable insights for nursing and medical policy.

A Novel Photosensitizer Based 450-nm Blue Laser-Mediated Photodynamic Therapy Induces Apoptosis in Colorectal Cancer - in Vitro and in Vivo Study.

BACKGROUND: Due to its non-invasive and widely applicable features, photodynamic therapy (PDT) has been a prominent treatment approach against cancer in recent years. However, its widespread application in clinical practice is limited by the dark toxicity of photosensitizers and insufficient penetration of light sources. This study assessed the anticancer effects of a novel photosensitizer 5-(4-amino-phenyl)-10,15,20-triphenylporphyrin with diethylene-triaminopentaacetic acid (ATPP-DTPA)-mediated PDT (hereinafter referred to as ATPP-PDT) under the irradiation of a 450-nm blue laser on colorectal cancer (CRC) in vivo and in vitro. METHODS: After 450-nm blue laser-mediated ATPP-PDT and the traditional photosensitizer 5-aminolevulinic acid (5-ALA)-PDT treatment, cell viability was detected through Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. Reactive oxygen species (ROS) generation was quantified by flow cytometry and fluorescence microscopy. Western blotting and transcriptome RNA sequencing and functional experiments were used to evaluate cell apoptosis and its potential mechanism. Anti-tumor experiment in vivo was performed in nude mice with subcutaneous tumors. RESULTS: ATPP-DTPA had a marvelous absorption in the blue spectrum. Compared with 5-ALA, ATPP-DTPA could achieve significant killing effects at a lower dose. Owing to generating an excessive amount of ROS, 450-nm blue laser-mediated PDT based on ATPP-DTPA resulted in evident growth inhibition and apoptosis in CRC cells in vitro. After transcriptome RNA sequencing and functional experiments, p38 MAPK signaling pathway was confirmed to be involved in the regulation of apoptosis induced by 450-nm blue laser-mediated ATPP-PDT. Additionally, animal studies using xenograft model confirmed that ATPP-PDT had excellent anti-tumor effect and reasonable biosafety in vivo. CONCLUSIONS: PDT mediated by 450-nm blue laser combined with ATPP-DTPA may be a novel and effective method for the treatment of CRC.

Tartaric Acid Cross-Linking Polyvinyl Alcohol as Degradable Separators for Rechargeable Lithium Ion Batteries.

The escalating focus on environmental concerns and the swift advancement of eco-friendly biodegradable batteries raises a pressing demand for enhanced material design in the battery field. The traditional polypropylene (PP) that is monopolistically utilized in the commercial LIBs is hard to recycle. In this work, we prepare a novel water degradable separators via the cross-linking of polyvinyl alcohol (PVA) and dibasic acid (tartaric acid, TA). Through the integration of non-solvent liquid-phase separation, we successfully produced a thermally stable PVA-TA membrane with tunable thickness and a high level of porosity. These specially engineered PVA-TA separators were implemented in LiFePO4 (LFP)|separator|Li cells, resulting in superior multiplicative performance and achieving a capacity of 88 mAh g-1 under 5 C. Additionally, the straightforward small molecule cross-linking technique significantly reduced the crystalline region of the polymer, thereby enhancing ionic conductivity. Notably, after cycling, the PVA-TA separators can be easily dissolved in 95 °C hot water, enabling its reutilization for the production of new PVA-TA separators. Therefore, this work introduces a novel concept to design green and sustainable separators for recyclable lithium batteries.

Surface defect detection method for discarded mechanical parts under heavy rust coverage.

With a significant number of mechanical products approaching the retirement phase, the batch recycling of discarded mechanical parts necessitates a preliminary assessment of their surface condition. However, the presence of surface rust poses a challenge to defect identification. Therefore, this paper proposes a method for detecting heavily rusted surface defects based on an improved YOLOv8n network. In the Backbone, the C2f-DBB module of re-parameterized deep feature extraction was introduced, and the attention module was designed to improve the accuracy of information extraction. In the Neck part, a Bi-Afpn multiscale feature fusion strategy is designed to facilitate information exchange between features at different scales. Finally, Focal-CIoU is employed as the bounding box loss function to enhance the network's localization performance and accuracy for defects. Experimentally, it is proved that the improved network in this paper improves the Recall, Precision, and mAP0.5 by 1.2%, 2.1%, and 1.9%, respectively, on the original basis, which is better than other network models.

Curcumin Inhibits Vasculogenic Mimicry Via Regulating ETS-1 in Renal Cell Carcinoma.

BACKGROUND: Metastatic renal cell carcinoma (RCC) poses a huge challenge once it has become resistant to targeted therapy. Vasculogenic mimicry (VM) is a novel blood supply system formed by tumor cells that can circumvent molecular targeted therapies. As one of the herbal remedies, curcumin has been demonstrated to play antineoplastic effects in many different types of human cancers; however, its function and mechanism of targeting VM in RCC remains unknown. OBJECTIVE: Here, in the work, we explored the role of curcumin and its molecular mechanism in the regulation of VM formation in RCC. METHODS: RNA-sequencing analysis, immunoblotting, and immunohistochemistry were used to detect E Twenty Six-1(ETS-1), vascular endothelial Cadherin (VE-Cadherin), and matrix metallopeptidase 9 (MMP9) expressions in RCC cells and tissues. RNA sequencing was used to screen the differential expressed genes. Plasmid transfections were used to transiently knock down or overexpress ETS-1. VM formation was determined by tube formation assay and animal experiments. CD31-PAS double staining was used to label the VM channels in patients and xenograft samples. RESULTS: Our results demonstrated that VM was positively correlated with RCC grades and stages using clinical patient samples. Curcumin inhibited VM formation in dose and time-dependent manner in vitro. Using RNA-sequencing analysis, we discovered ETS-1 as a potential transcriptional factor regulating VM formation. Knocking down or overexpression of ETS-1 decreased or increased the VM formation, respectively and regulated the expression of VE-Cadherin and MMP9. Curcumin could inhibit VM formation by suppressing ETS-1, VE-Cadherin, and MMP9 expression both in vitro and in vivo. CONCLUSION: Our finding might indicate that curcumin could inhibit VM by regulating ETS-1, VE-Cadherin, and MMP9 expression in RCC cell lines. Curcumin could be considered as a potential anti-cancer compound by inhibiting VM in RCC progression.

Association with the plasma atherogenic index with hepatic steatosis and fibrosis in the US population.

Plasma atherogenic index (AIP) reflects a novel intricate biochemical indicator of lipids' metabolism. The involvement of lipid metabolism for pathogenesis concerning nonalcoholic fatty liver disease (NAFLD) has been established. However, the precise association across AIP and hepatic steatosis and fibrosis remains unclear. This present investigation explored the potential correlation across AIP, hepatic steatosis and fibrosis. Data were acquired through National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Hepatic steatosis was detected through the controlled attenuation parameter (CAP), while hepatic fibrosis was examined via liver stiffness measurement (LSM). The study employed multiple linear, Fitted smoothed curves and subgroup analyses were used for investigating relationships between the AIP, CAP, and LSM. The study recruited 6239 participants. In multivariate linear regression analysis, findings indicated a remarkable correlation between AIP and exacerbated NAFLD risk [odds ratio (95% confidence interval), 1.17 (1.12, 1.21)]. Analysis further revealed a positive link across AIP and hepatic steatosis, as indicated through the CAP [ß (95% CI), 4.07 (3.32, 4.82)]. Tests for non-linearity, revealed a non-linear correlation between AIP and CAP (inflection point = 0.22). Subgroup analyses assessed the consistency of the link across AIP and CAP, indicating that the association remained comparable across all subgroups. Following the adjustment for all relevant variables, the linear regression analysis revealed a lack of statistical significance across the AIP and hepatic fibrosis. [LSM, ß (95% CI), -0.39 (-1.06, 0.28), P = .2501]. Smooth-fitting curves examined the link across AIP and LSM and showed a U-shaped pattern, indicating their positive correlation with AIP less than 0.48. However, no significant correlation was observed with AIP more than 0.48. This study highlighted a substantial positive relationship across AIP and hepatic steatosis, as measured through CAP, and suggests that it may be used as an efficient and rapid measure for clinical prediction of hepatic steatosis.

MYC induces CDK4/6 inhibitors resistance by promoting pRB1 degradation.

CDK4/6 inhibitors (CDK4/6i) show anticancer activity in certain human malignancies, such as breast cancer. However, their application to other tumor types and intrinsic resistance mechanisms are still unclear. Here, we demonstrate that MYC amplification confers resistance to CDK4/6i in bladder, prostate and breast cancer cells. Mechanistically, MYC binds to the promoter of the E3 ubiquitin ligase KLHL42 and enhances its transcription, leading to RB1 deficiency by inducing both phosphorylated and total pRB1 ubiquitination and degradation. We identify a compound that degrades MYC, A80.2HCl, which induces MYC degradation at nanomolar concentrations, restores pRB1 protein levels and re-establish sensitivity of MYC high-expressing cancer cells to CDK4/6i. The combination of CDK4/6i and A80.2HCl result in marked regression in tumor growth in vivo. Altogether, these results reveal the molecular mechanisms underlying MYC-induced resistance to CDK4/6i and suggest the utilization of the MYC degrading molecule A80.2HCl to potentiate the therapeutic efficacy of CDK4/6i.

A Time-Varying Mixture Integer-Valued Threshold Autoregressive Process Driven by Explanatory Variables.

In this paper, a time-varying first-order mixture integer-valued threshold autoregressive process driven by explanatory variables is introduced. The basic probabilistic and statistical properties of this model are studied in depth. We proceed to derive estimators using the conditional least squares (CLS) and conditional maximum likelihood (CML) methods, while also establishing the asymptotic properties of the CLS estimator. Furthermore, we employed the CLS and CML score functions to infer the threshold parameter. Additionally, three test statistics to detect the existence of the piecewise structure and explanatory variables were utilized. To support our findings, we conducted simulation studies and applied our model to two applications concerning the daily stock trading volumes of VOW.

CYLD regulates cell ferroptosis through Hippo/YAP signaling in prostate cancer progression.

Prostate cancer (PCa) is one of the most common malignancy in men. However, the molecular mechanism of its pathogenesis has not yet been elucidated. In this study, we demonstrated that CYLD, a novel deubiquitinating enzyme, impeded PCa development and progression via tumor suppression. First, we found that CYLD was downregulated in PCa tissues, and its expression was inversely correlated with pathological grade and clinical stage. Moreover, we discovered that CYLD inhibited tumor cell proliferation and enhanced the sensitivity to cell ferroptosis in PCa in vitro and in vivo, respectively. Mechanistically, we demonstrated that CYLD suppressed the ubiquitination of YAP protein, then promoted ACSL4 and TFRC mRNA transcription. Then, we demonstrated that CYLD could enhance the sensitivity of PCa xenografts to ferroptosis in vivo. Furthermore, we discovered for the first time that there was a positive correlation between CYLD expression and ACSL4 or TFRC expression in human PCa specimens. The results of this study suggested that CYLD acted as a tumor suppressor gene in PCa and promoted cell ferroptosis through Hippo/YAP signaling.

A Dynamically Stable Sulfide Electrolyte Architecture for High-Performance All-Solid-State Lithium Metal Batteries.

All-solid-state batteries employing sulfide solid electrolyte and Li metal anode are promising because of their high safety and energy densities. However, the interface between Li metal and sulfides suffers from catastrophic instability which stems the practical use. Here, a dynamically stable sulfide electrolyte architecture to construct the hierarchy of interface stability is reported. By rationally designing the multilayer structures of sulfide electrolytes, the dynamic decomposing-alloying process from MS4 (M = Ge or Sn) unit in sulfide interlayer can significantly prohibit Li dendrite penetration is revealed. The abundance of highly electronic insulating decompositions, such as Li2 S, at the sulfide interlayer interface helps to well constrain the dynamic decomposition process and preserve the long-term polarization stability is also highlighted. By using Li6 PS5 Cl||Li10 SnP2 S12 ||Li6 PS5 Cl electrolyte architecture, Li metal anode shows an unprecedented critical current density over 3 mA cm-2 and achieves the steady over-potential for ≈900 hours. Based upon the merits, the Li||LiNi0.8 Co0.1 Mn0.1 O2 battery delivers a remarkable 75.3% retention even after 600 cycles at 1 C (1C-0.95 mA cm-2 ) under a low stack pressure of 15 MPa.

The Association between Four Common Polymorphisms in microRNA and Risk of Hepatocellular Carcinoma: An Updated Meta-Analysis.

Background: Many epidemiological studies have explored the relationship between single-nucleotide polymorphism and hepatocellular carcinoma (HCC). However, the results remain controversial. We performed a large-scale meta-analysis to draw a more precise estimation of the aforementioned association. Methods: Studies on the association between microRNA (MIR) polymorphisms and HCC risk that had been published up to Sep 30, 2021 were identified by searching the PubMed, Cochrane Library, Google Scholar, Web of Science, and Chinese Biomedical Literature electronic databases and the Excerpta Medical Database. The association between MIR polymorphisms and HCC risk was assessed using odds ratios (ORs) and their 95% confidence intervals (CIs). Results: Overall, 29 studies, with a total of 9,263 cases and 10,875 controls, were included in our meta-analysis. MicroRNA149 (MIR149) significantly decreased the risk of developing HCC on the overall population (homozygous model CC vs. TT: OR = 0.703, 95% CI = 0.549-0.899, P = 0.005), and microRNA 196 (MIR196) significantly decreased the risk of developing HCC on the overall population (recessive model TT vs. CT+CC: OR = 0.864, 95% CI = 0.751-0.993, P = 0.04) and on Caucasians (OR = 0.613, 95% CI = 0.414-0.907, P = 0.014). Conclusion: The MIR149 and MIR196 polymorphisms are the protect factors of developing HCC. The conduct of multi-center and multi-region studies with gene-gene, gene-environment should be considered.

Knocking down AR promotes osteoblasts to recruit prostate cancer cells by altering exosomal circ-DHPS/miR-214-3p/CCL5 pathway.

ABSTRACT: Tumor-derived exosomes have been shown to play a key role in organ-specific metastasis, and the androgen receptor regulates prostate cancer (PCa) progression. It is unclear whether the androgen receptor regulates the recruitment of prostate cancer cells to the bone microenvironment, even bone metastases, through exosomes. Here, we found that exosomes isolated from PCa cells after knocking down androgen receptor (AR) or enzalutamide treatment can facilitate the migration of prostate cancer cells to osteoblasts. In addition, AR silencing or treatment with the AR antagonist enzalutamide may increase the expression of circular RNA-deoxyhypusine synthase (circ-DHPS) in PCa cells, which can be transported to osteoblasts by exosomes. Circ-DHPS acts as a competitive endogenous RNA (ceRNA) against endogenous miR-214-3p to promote C-C chemokine ligand 5 (CCL5) levels in osteoblasts. Increasing the level of CCL5 in osteoblasts could recruit more PCa cells into the bone microenvironment. Thus, blocking the circ-DHPS/miR-214-3p/CCL5 signal may decrease exosome-mediated migration of prostate cancer cells to osteoblasts.

Structures and Biological Activities of Secondary Metabolites from the Trichoderma genus (Covering 2018-2022).

Trichoderma, a genus with more than 400 species, has a long history of use as an industrial bioreactor, biofertilizer, and biocontrol agent. It is considered a significant source of secondary metabolites (SMs) that possess unique structural features and a wide range of bioactivities. In recent years, numerous secondary metabolites of Trichoderma, including terpenoids, polyketides, peptides, alkaloids, and steroids, have been identified. Most of these SMs displayed antimicrobial, cytotoxic, and antifungal effects. This review focuses on the structural diversity, biological activities, and structure-activity relationships (SARs) of the SMs isolated from Trichoderma covered from 2018 to 2022. This study provides insights into the exploration and utilization of bioactive compounds from Trichoderma species in the agriculture or pharmaceutical industry.

A photoelectrochemical aptasensor for tetracycline based on the self-assembly of 2D MoS2 on a 3D ZnO/Au/ITO electrode.

Two-dimensional (2D) layered MoS2 has good dispersion and adsorption properties, but being a narrow bandgap semiconductor limits its application in photoelectric sensing. In this study, a homogeneous photoelectrochemical sensor based on three-dimensional (3D) ZnO/Au/2D MoS2 is proposed for the ultrasensitive detection of tetracycline (TET). MoS2 is uniformly embedded on the 3D ZnO/Au surface by ordered self-assembly. The physical method of π-π interaction of MoS2 replaces the conventional use of chemically modifying aptamers on the electrode material surface. Under optimal conditions, this method has been successfully applied to the detection of TET in milk, honey, pig kidney and pork samples with reliable results. We believe that this study presents a method for the preparation of sensing carriers and target detection with great potential for application.

Inhibition of autophagy can promote the apoptosis of bladder cancer cells induced by SC66 through the endoplasmic reticulum stress pathway.

Bladder cancer is among the ten most prevalent cancer types worldwide, and its prognosis has not improved significantly in the past three decades because of cognitive limitations in the molecular mechanisms that drive the malignant progression of bladder cancer. Therefore, there is an urgent need to identify new therapeutic drugs or molecular targets to improve the prognosis of patients with bladder cancer. SC66, a novel allosteric inhibitor of AKT, has recently been reported to exert potent anticancer effects on various cancer cells. However, the mechanisms underlying its anticancer effects in bladder cancer remain largely unknown. Consequently, this study aimed to conduct a series of molecular and cellular biology experiments to verify the anticancer effect and potential mechanism of action of SC66 in bladder cancer in vitro. A xenograft tumor model was established to confirm its anticancer role in vivo. Our results showed that SC66 inhibited cell proliferation, triggered mitochondria-mediated apoptosis, and initiated autophagy in bladder cancer cells dose-dependently. In addition, our results suggested that SC66-caused apoptosis and autophagy were endoplasmic reticulum stress-dependent. Interestingly, the activation of autophagy can partially protect bladder cancer cells from apoptosis under endoplasmic reticulum stress induced by SC66 treatment. This study shows that SC66 exerts its anticancer impact on bladder cancer by inhibiting cell proliferation and inducing apoptosis. It also reveals that inhibiting autophagy can increase the cytotoxic effects of SC66 in bladder cancer. Overall, this is the first study on the anticancer effect of SC66 mediated by the endoplasmic reticulum stress pathway and the first report on the AKT-independent anticancer mechanism of SC66 in bladder cancer. Conclusively, exploring the relationship between apoptosis, autophagy, and endoplasmic reticulum stress induced by SC66 indicates that SC66 is a promising novel agent for patients with bladder cancer.

Novel dual: rod plate system for EOS improves vertebral wedging and permits spinal growth.

BACKGROUND: To determine whether single-stage, growth-friendly instrumentation with a plate-rod spinal system (PRSS) can substantially correct the deformity of EOS at surgery and continue to rectify the deformity throughout the growth period. METHODS: An observational study of 35 children with EOS treated by PRSS between February 2000 and October 2010 during a mean follow-up of 72 months. The mean age at surgery was 7 years. X-rays were taken preoperatively and postoperatively and at each follow-up. The Cobb angle, the apical vertebral wedge angle (AVWA), remaining rod lengths, maximal thoracic kyphosis and total T1-S1 heights were measured and compared. RESULTS: Thirty-one patients, 9 boys and 22 girls, with a mean age of 7 years were completed follow-up. The Cobb angle changed from 64° to 36° after initial surgery and 26° at the last follow-up. The mean AVWA was 15° postoperatively and 5° at the last follow-up. The mean rod tail reserve length decreased from 53 mm immediately after surgery to 12 mm at the last follow-up. The mean preoperative maximum thoracic kyphosis was 41° and changed to 35° and 30° postoperatively and at latest follow-up, respectively. The mean preoperative T1-S1 height for all 32 patients was 52 mm acute lengthening and 122 mm of lengthening by the end of follow-up, respectively. CONCLUSION: The PRSS provided immediate correction of most of the deformity at surgery and continued to rectify remaining scoliosis during the growth period. AVWA may be a useful method for monitoring the function of the PRSS in EOS.

Melatonin suppresses Akt/mTOR/S6K activity, induces cell apoptosis, and synergistically inhibits cell growth with sunitinib in renal carcinoma cells via reversing Warburg effect.

BACKGROUND: Metabolic alteration drives renal cell carcinoma (RCC) development, while the impact of melatonin (MLT), a neurohormone secreted during darkness, on RCC cell growth and underlying mechanisms remains unclear. METHODS: We detected concentration of metabolites through metabolomic analyses using UPLC-MS/MS, and the oxygen consumption rate was determined using the Seahorse Extracellular Flux analyzer. RESULTS: We observed that MLT effectively inhibited RCC cell growth both in vitro and in vivo. Additionally, MLT increased ROS levels, suppressed antioxidant enzyme activity, and induced apoptosis. Furthermore, MLT treatment upregulated key TCA cycle metabolites while reducing aerobic glycolysis products, leading to higher oxygen consumption rate, ATP production, and membrane potential. Moreover, MLT treatment suppressed phosphorylation of Akt, mTOR, and p70 S6 Kinase as well as the expression of HIF-1α/VEGFA in RCC cells; these effects were reversed by NAC (ROS inhibitors). Conversely, MLT synergistically inhibited cell growth with sunitinib and counteracted the Warburg effect induced by sunitinib in RCC cells. CONCLUSIONS: In conclusion, our results indicate that MLT treatment reverses the Warburg effect and promotes intracellular ROS production, which leads to the suppression of Akt/mTOR/S6K signaling pathway, induction of cell apoptosis, and synergistically inhibition of cell growth with sunitinib in RCC cells. Overall, this study provides new insights into the mechanisms underlying anti-tumor effect of MLT in RCC cells, and suggests that MLT might be a promising therapeutic for RCC.

Geographical patterns and determinants in plant reproductive phenology duration.

Biodiversity is and always has been an important issue in ecological research. Biodiversity can reflect niche partitioning among species at several spatial and temporal scales and is generally highest in the tropics. One theory to explain it is that low-latitude tropical ecosystems are dominated by species that are generally only distributed over a narrow area. This principle is known as Rapoport's rule. One previously unconsidered extension of Rapoport's rule may be reproductive phenology, where variation in flowering and fruiting length may reflect a temporal range. Herein, we collected reproductive phenology data for more than 20,000 species covering almost all angiosperm species in China. We used a random forest model to quantify the relative role of seven environmental factors on the duration of reproductive phenology. Our results showed that the duration of reproductive phenology decreased with latitude, although there was no obvious change across longitudes. Latitude explained more of the variation in the duration of flowering and fruiting phases in woody plants than in herbaceous plants. Mean annual temperature and the length of the growing season strongly influenced the phenology of herbaceous plants, and average winter temperature and temperature seasonality were important drivers of woody plant phenology. Our result suggests the flowering period of woody plants is sensitive to temperature seasonality, while it does not influence herbaceous plants. By extending Rapoport's rule to consider the distribution of species in time as well as space, we have provided a novel insight into the mechanisms of maintaining high levels of diversity in low-latitude forests.