A modified drag coefficient model for calculating the terminal settling velocity and horizontal diffusion distance of irregular plume particles in deep-sea mining.

Deep-sea mining inevitably produces plumes, which will pose a serious threat to the marine environment with the continuous movement and diffusion of plumes along with ocean currents. The terminal settling velocity (wt) of irregular particles is one of the crucial factors for determining the plumes' diffusion range. It is generally calculated by drag coefficient (CD), while most existing CD models only consider single shape characteristic parameter or have a smaller range of Reynolds number (Re). In this study, a new shape factor (γ) of irregular particles is proposed by considering the thickness (one-dimension), the projected area (two-dimension), and the surface area (three-dimension) of irregular particles as well as their coupling effect to establish a modified CD model for calculating the wt. A modified Gaussian plume model is proposed to predict the horizontal diffusion distance of the plume particles by considering the settling velocity and diffusion effect of irregular particles. Research results show that the wt increases nearly linearly, with a gradually decreased slope and slightly then greatly with the increasing of γ, dp (diameter) and ρp (density), respectively. The modified CD model is verified to be more valid with a wider application range (Re < 3×105) than five existing CD models by the test results. The larger the ρp or dp, the larger the wt and thus the smaller the Sh. This study could provide a theoretical basis for calculating the plume diffusion range to further study the impact of deep-sea mining on the ocean environment.

Longitudinal Trajectories of Social Mobility Beliefs among Chinese Adolescents: The Protective Roles of Parental Academic Involvement and Adolescent Future Orientation.

Social mobility beliefs play a significant role in shaping adolescents' adaptive developmental outcomes, including well-being and academic functioning. Nevertheless, existing research may not cast light on the distinct trajectories and potential protective factors of social mobility beliefs. The present study aims to identify heterogeneity in trajectory patterns of social mobility beliefs among Chinese adolescents (Mage = 12.45, SDage = 2.60; 55.1% boys; 40.0% rural adolescents) in a four-wave (i.e., fall 2017, fall 2018, spring 2019, and fall 2019) longitudinal design, and examines the protective roles of parental academic involvement and adolescent future orientation. Three distinct trajectories of social mobility beliefs were identified: high-increasing (35.1%; a positive trajectory with the best developmental outcomes, including the lowest problem behaviors and depression symptoms, and the highest life satisfaction and academic competence), moderate-stable (49.8%), and low-decreasing (15.1%; a negative trajectory with the worst developmental outcomes, including the highest problem behaviors and depression symptoms, and the lowest life satisfaction and academic competence). Apart from the main effects of parental academic involvement and future orientation, a significant interaction effect of these two protective factors and adolescent group was detected, and only rural adolescents who reported both high levels of parental academic involvement and future orientation have a greater chance of being placed in the high-increasing trajectory than the low-decreasing trajectory. These findings highlight the significance of clarifying individual differences in the dynamic process of social mobility beliefs during adolescence, and elucidate rural-urban disparities in the influences of protective factors on social mobility beliefs trajectories, and inform individualized intervention strategies.

Comparison of the Efficacy Among Nilotinib, Dasatinib, Flumatinib and Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia Patients: A Real-World Multi-Center Retrospective Study.

BACKGROUND: There are limited data comprehensively comparing therapy responses and outcomes among nilotinib, dasatinib, flumatinib and imatinib for newly diagnosed chronic-phase chronic myeloid leukemia in a real-world setting. PATIENTS AND METHODS: Data from patients with chronic-phase CML receiving initial a second-generation tyrosine-kinase inhibitor (2G-TKI, nilotinib, dasatinib or flumatinib) or imatinib therapy from 77 Chinese centers were retrospectively interrogated. Propensity-score matching (PSM) analyses were performed to to compare therapy responses and outcomes among these 4 TKIs. RESULTS: 2,496 patients receiving initial nilotinib (n = 512), dasatinib (n = 134), flumatinib (n = 411) or imatinib (n = 1,439) therapy were retrospectively interrogated in this study. PSM analyses indicated that patients receiving initial nilotinib, dasatinib or flumatinib therapy had comparable cytogenetic and molecular responses (p = .28-.91) and survival outcomes including failure-free survival (FFS, p = .28-.43), progression-free survival (PFS, p = .19-.93) and overall survival (OS) (p values = .76-.78) but had significantly higher cumulative incidences of cytogenetic and molecular responses (all p values < .001) and higher probabilities of FFS (p < .001-.01) than those receiving imatinib therapy, despite comparable PFS (p = .18-.89) and OS (p = .23-.30). CONCLUSION: Nilotinib, dasatinib and flumatinib had comparable efficacy, and significantly higher therapy responses and higher FFS rates than imatinib in newly diagnosed CML patients. However, there were no significant differences in PFS and OS among these 4 TKIs. These real-world data may provide additional evidence for routine clinical assessments to identify more appropriate therapies.

Phenolic compounds weaken the impact of drought on soil enzyme activity in global wetlands.

Soil enzymes play a central role in carbon and nutrient cycling, and their activities can be affected by drought-induced oxygen exposure. However, a systematic global estimate of enzyme sensitivity to drought in wetlands is still lacking. Through a meta-analysis of 55 studies comprising 761 paired observations, this study found that phosphorus-related enzyme activity increased by 38% as result of drought in wetlands, while the majority of other soil enzyme activities remained stable. The expansion of vascular plants under long-term drought significantly promoted the accumulation of phenolic compounds. Using a 2-week incubation experiment with phenol supplementation, we found that phosphorus-related enzyme could tolerate higher biotoxicity of phenolic compounds than other enzymes. Moreover, a long-term (35 years) drainage experiment in a northern peatland in China confirmed that the increased phenolic concentration in surface layer resulting from a shift in vegetation composition inhibited the increase in enzyme activities caused by rising oxygen availability, except for phosphorus-related enzyme. Overall, these results demonstrate the complex and resilient nature of wetland ecosystems, with soil enzymes showing a high degree of adaptation to drought conditions. These new insights could help evaluate the impact of drought on future wetland ecosystem services and provide a theoretical foundation for the remediation of degraded wetlands.

Exploring the symptom patterns of depression and anxiety among teachers during COVID-19: A latent profile analysis.

OBJECTIVE: The present study used the latent profile analysis (LPA) approach to explore the symptom patterns of depression and anxiety among Chinese teachers during COVID-19 and its relationship with fear of COVID-19 and suicidal ideation. METHOD: A sample of 6,121 teachers from primary and secondary schools in a district-level administrative unit in southern China was used. The LPA was employed to identify different symptom patterns of depression and anxiety. We subsequently used logistic regression to analyze the effects of demographic variables on the different profiles. The Bolck-Croon-Hagenaars method assessed the relationships between each profile and fear of COVID-19 and suicidal ideation. RESULTS: The study identified five significant latent profiles and two subtypes in the moderate psychological disorder group. We also found that gender, professional title, and age significantly influenced the distribution of the profiles. The risk for both fear of COVID-19 and suicidal ideation was highest in the severe psychological disorder group. The high anxiety subtype had a significantly greater fear of the new coronavirus epidemic than the high depression subtype, which had a significantly higher level of suicidal ideation than the high anxiety subtype. CONCLUSION: The profiles we identified have distinct features that confirm their unique patterns of symptom endorsement. Our study may have important implications for early warning and intervention in teacher mental health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Preparation of High-Performance Mn-Doped SnTe Materials at High Pressure and High Temperature.

SnTe is an environmentally friendly medium-temperature thermoelectric material, but its inherent low power factor (PF) and high lattice thermal conductivity severely limit its application. In this study, based on the fact that Mn doping can induce band convergence, the high-pressure and high-temperature (HPHT) synthesis method was used to optimize the sample preparation and shorten the synthesis cycle to 30 min. The results show that the Sn0.93Mn0.10Te sample achieves the maximum PF value of 34.00 µW cm-1 K-2 at 775 K and PFave value of 21.36 µW cm-1 K-2 between 300-875 K. Microstructure analysis shows that the high-pressure synthesis method introduces abundant grain boundaries, various grain sizes, multiple defects, and pore structures into the sample. These microscopic crystal structures can effectively scatter phonons and lower the lattice thermal conductivity. The modification of these micromorphologies results in the Sn0.92Mn0.11Te sample attaining a minimum lattice thermal conductivity of 0.45 W m-1 K-1 at 625 K. The thermoelectric figure of merit (zT) of sample Sn0.92Mn0.11Te reaches a maximum value of 1.1 at 775 K, and the zTave reaches 0.63 in the range of 300-875 K. This study indicates that the synergistic effect of Mn element doping and microstructure modification can effectively optimize the thermoelectric transport performance of SnTe materials.

Accumulation of circulating myeloid-derived suppressor cell subsets: predicting poor clinical efficacy and prognosis through T cell suppression in non-Hodgkin's lymphoma.

Myeloid-derived suppressor cells (MDSC) are implicated in the regulation of immune responses closely associated with poor clinical outcomes in cancer. However, the MDSC subtypes in non-Hodgkin's Lymphoma (NHL) has not been systematically investigated. So we investigated the percentage of MDSC subsets in 78 newly diagnosed NHL patients by flow cytometry. The results showed that all MDSC subsets increased in NHL patients compared to healthy donors. Notably, MDSC, M-MDSC, and CD14+CD66b+MDSC significantly increased in NHL patients compared to those with lymphadenitis. PMN-MDSC, e-MDSC and IPI were independent risk factors for poor clinical efficacy and were involved in constructing the nomogram for predicting clinical efficacy. Progression-free survival (PFS) was significantly shorter in patients with high level of MDSC subsets, and PMN-MDSC emerged as an independent prognostic factor for PFS. PMN-MDSC, e-MDSC and IPI were involved in constructing the nomogram for predicting PFS. Patients with a higher percentage of MDSC, PMN-MDSC, e-MDSC, and CD14+CD66b+MDSC experienced a shorter OS compared to those with lower percentages. In addition, research on mechanisms found that T cell function was suppressed and mediated by the expansion of MDSC via involving Arg-1 and IL-10 in vitro and in vivo. In conclusion, our study demonstrates that the increased circulating MDSC subsets predict poor clinical efficacy and prognosis in NHL, potentially involving T cell suppression through MDSC subsets expansion. These findings indicate the potential of MDSC subsets as comprehensive diagnostic, prognostic biomarkers, and therapeutic targets for NHL.

Patient Versus Physician Perspective in the Management of Chronic Myeloid Leukemia During Treatment with Tyrosine Kinase Inhibitors.

INTRODUCTION: Chronic myeloid leukemia (CML) is a chronic disease with treatment-free remission (TFR) increasingly regarded as a feasible goal of treatment. However, various factors may influence adherence to international guidelines for CML management. This study aimed to compare the reporting of care between patients with CML and their treating doctors. METHODS: Parallel patient and physician online surveys were conducted between September 22, 2021, and March 15, 2022, which focused on the perceptions of 1882 adult patients with CML and 305 physicians regarding tyrosine kinase inhibitor (TKI) treatment options, monitoring and toxicities, TFR, and challenges faced. RESULTS: Among the enrolled patients, 69.9% received first-line imatinib treatment, 18.6% received nilotinib, and 4.7% received dasatinib. Among the patients treated with imatinib, 36.7% switched to other TKIs due to imatinib resistance/intolerance (71.1%), exploration of more potent TKIs to achieve TFR (8.9%), and treating physicians' recommendation (14.0%), with a median duration of initial treatment of 14 months [interquartile range (IQR) 6-36]. Most (91.8%) physicians agreed that the breakpoint cluster region-Abelson 1 (BCR::ABL1) transcript level should be assessed every 3 months, but only 42.7% of individuals committed to 3-monthly testing and only 17.8% strictly followed their treating physicians' recommendation. Half of the patients aimed for TFR; however, just 45.2% of physicians considered TFR as one of the top three goals for their patients. The major concern in obtaining TFR was patients' adherence. Fatigue was often distressing for patients with TKIs, while physicians were more concerned about platelet and neutrophil counts. A total of 12% and 20.8% of patients reported moderate/severe anxiety and depression, respectively, while only 53.7% of physicians had concerns about their patients' mental health. During the coronavirus disease 2019 (COVID-19) pandemic, 69.2% of patients reported a reduction in their income. Among these patients, 61.8% maintained their current treatment, while 7.3% switched to cheaper alternatives or discontinued treatment, with over 80% of these patients belonging to the low-income group. CONCLUSIONS: Overcoming challenges in patient-physician communication and treatment access is key to improving disease management and quality of life, especially for patients with low income. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05092048.

Chinese expert consensus on the management of patients with hematologic malignancies infected with SARS-CoV-2.

In December 2022, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became dominant in China due to its high infectivity and lower mortality rate. The risk of critical illness and mortality among patients with hematologic malignancies who contracted SARS-CoV-2 was particularly high. The aim of this study was to draft a consensus to facilitate effective treatments for these patients based on the type and severity of the disease. Following the outbreak of the novel coronavirus in China, a steering committee consisting of experienced hematologists was formed by the Specialized Committee of Oncology and Microecology of the Chinese Anti-Cancer Association. The expert group drafted a consensus on the management and intervention measures for different types of hematologic malignancies based on the clinical characteristics of the Omicron variant of the SARS-CoV-2 infection, along with relevant guidelines and literature. The expert group drafted independent recommendations on several important aspects based on the epidemiology of the Omicron variant in China and the unique vulnerability of patients with hematologic malignancies. These included prophylactic vaccinations for those with hematologic malignancies, the use of plasma from blood donors who recovered from the novel coronavirus infection, the establishment of negative pressure wards, the use of steady-state mobilization of peripheral blood hematopoietic stem cells, the provision of psychological support for patients and medical staff, and a focus on maintaining a healthy intestinal microecology.

18 months follow-up of deep molecular response 4.5 (MR4.5) with nilotinib in patients with newly diagnosed chronic-phase chronic myeloid leukemia: a prospective, multi-center study in China.

Introduction: Early stable deep molecular response (DMR) to nilotinib is associated with goal of treatment-free remission (TFR) in patients with chronic-phase chronic myeloid leukemia (CML-CP). It is important to early distinguish between patients who can achieve a DMR and those who are fit for TFR. Methods: We performed a multicenter study to explore the early cumulative MR4.5 rate at 18 months with nilotinib in patients with newly diagnosed CML-CP (ND-CML-CP) in China. Of the 29 institutes, 106 patients with ND-CML-CP received nilotinib (300 mg BID). Results and discussion: The cumulative MR4.5 rate of nilotinib treatment at 18 months was 69.8% (74/106). The cumulative MMR and MR4.0 rates for nilotinib at 18 months were 94.3% (100/106) and 84.9% (90/106), respectively. Patients with an ultra-early molecular response (u-EMR) at 6 weeks were not significantly different in obtaining DMR or MMR by 24 months compared with those without u-EMR (p = 0.7584 and p = 0.9543, respectively). Our study demonstrated that nilotinib treatment in patients with ND-CML-CP contributed to obtain high early MR4.5.

Satellite monitoring reveals short-term cumulative and time-lag effect of drought and heat on autumn photosynthetic phenology in subtropical vegetation.

Comparing with the effect of the average climate change on vegetation phenology, the impacts of extreme climate events remain unclear, especially considering their characteristic cumulative and time-lag effects. Using solar-induced chlorophyll fluorescence (SIF) satellite records, we investigated the cumulative and time-lag effects of drought and heat events on photosynthesis, particularly for the end date of autumn photosynthesis (EOP), in subtropical vegetation in China. Our results showed a negative effect of drought on the delay of EOP, with the cumulative effect on 30.12% (maximum continuous dry days, CDD), 34.82% (dry days, DRD), and 26.14% (dry period, DSDI) of the study area and the general time-lag effect on 50.73% (maximum continuous dry days), 56.61% (dry days), and 47.55% (dry period) of the study area. The cumulative and lagged time were 1-3 months and 2-3 months, respectively. In contrast, the cumulative effect of heat on EOP was observed in 16.27% (warm nights, TN90P), 23.66% (moderate heat days, TX50P), and 19.19% (heavy heat days, TX90P) of the study area, with cumulative time of 1-3 months. The lagged time was 3-4 months, detected in 31.02% (warm nights), 45.86% (moderate heat days), and 36.52% (heavy heat days) of the study area. At the vegetation community level, drought and heat had relatively rapid impacts on EOP in the deciduous broadleaved forest, whereas evergreen forests and bushes responded to heat slowly and took a longer time. Our results revealed that drought and heat have short-term cumulative and time-lag effects on the EOP of subtropical vegetation in China, with varying effects among different vegetation types. These findings provide new insights into the effect of drought and heat on subtropical vegetation and confirm the need to consider these effects in the development of prediction models of autumn phenology for subtropical vegetation.

Analyzing roles of small nucleolar RNA host gene 25 from clinical, molecular target and tumor formation in prostate cancer.

BACKGROUND: Prostate cancer (PCa) is one of the most deadly and metastatic cancers of the urinary tract. Latest studies have confirmed that long non-coding RNAs (lncRNAs) play a crucial role in a variety of cancers. Some of these lncRNAs code for small nucleolar RNAs (snoRNAs), called small nucleolar RNA host genes (SNHGs), which exert some value in predicting the prognosis of certain cancer patients, but little is known regarding the function of SNHGs within the PCa. AIM OF THE STUDY: To explore the expression distribution and differential analysis of SNHGs in different tumors using RNA-seq and survival data from TCGA and GTEx, and to assess the potential impacts of the lncRNA SNHG25 on human PCa. To validate the expression of SNHG25 using experimental data and to investigate in detail its particular molecular biological function on PCa both in vivo and in vitro. METHODS: LncRNA SNHG25 expression was analyzed by bioinformatic prediction and qPCR. CCK-8, EdU, transwell, wound healing, and western blotting assays were conducted to investigate the main role of lncRNA SNHG25 in PCa. Xenograft tumour growth model in nude mice was surveyed by in vivo imaging and Ki-67 staining. AKT pathway activator (SC79) was used to verify the interaction among SNHG25 and PI3K/AKT signaling pathway. RESULTS: Bioinformatics analysis and experimental research illuminated that the expression of lncRNA SNHG25 was observably up-regulated in PCa tissues and cells. Moreover, SNHG25 knockdown restrained PCa cell proliferation, invasion and migration, while promoting apoptosis. Xenografts model confirmed that the si-SNHG25 group had a significant inhibitory effect on PCa tumour growth in vivo. Additionally, a series of gain-of-function analyses suggested that SNHG25 could activate the PI3K/AKT pathway to accelerate PCa progression. CONCLUSIONS: These in vitro and in vivo findings demonstrate that SNHG25 is highly expressed in PCa and facilitates PCa development through regulation of PI3K/AKT signaling pathway. SNHG25 acts as an oncogene to predict tumour malignancy and survival in PCa patients and may therefore become a promising potential molecular target for early detection and therapy of lethal PCa.

A transcription-independent mechanism determines rapid periodic fluctuations of BRCA1 expression.

BRCA1 expression is highly regulated to prevent genomic instability and tumorigenesis. Dysregulation of BRCA1 expression correlates closely with sporadic basal-like breast cancer and ovarian cancer. The most significant characteristic of BRCA1 regulation is periodic expression fluctuation throughout the cell cycle, which is important for the orderly progression of different DNA repair pathways throughout the various cell cycle phases and for further genomic stability. However, the underlying mechanism driving this phenomenon is poorly understood. Here, we demonstrate that RBM10-mediated RNA alternative splicing coupled to nonsense-mediated mRNA decay (AS-NMD), rather than transcription, determines the periodic fluctuations in G1/S-phase BRCA1 expression. Furthermore, AS-NMD broadly regulates the expression of period genes, such as DNA replication-related genes, in an uneconomical but more rapid manner. In summary, we identified an unexpected posttranscriptional mechanism distinct from canonical processes that mediates the rapid regulation of BRCA1 as well as other period gene expression during the G1/S-phase transition and provided insights into potential targets for cancer therapy.

Prognostic value of combined WT1 and multiparameter flow cytometry assessment for measurable residual disease after induction in non-APL acute myeloid leukemia.

The objective of this study was to investigate the expression pattern of Wilms tumor 1 (WT1) gene at diagnosis, complete remission (CR) and relapse status in non-acute promyelocytic leukemia (non-APL) acute myeloid leukemia (AML) patients, and further explore the prognostic value of measurable residual disease (MRD) assessment by WT1 gene and multiparameter flow cytometry (MFC). Our results showed that the average expression level of WT1 was 4026 ± 616.1 copies/104 ABL at diagnosis, 155.3 ± 36.03 copies/104 ABL at CR, and 1766 ± 238.8 copies/104 ABL at relapse, with statistically significant differences (p = .000). ROC analysis showed that WT1 expression levels were 118.1 copies/104 ABL and MFC-MRD was 0.155%, which had good predictive efficacy for relapse of patients during consolidation therapy. Both WT1-MRD and MFC-MRD had a significant impact on relapse-free survival (RFS) and overall survival (OS). Patients with WT1-MRD positive or MFC-MRD positive were associated with worse RFS (HR 3.840, 95% CI 1.582-9.320, p = .003), (HR 4.464, 95% CI 1.841-10.984, p = .001) and worse OS (HR 2.963, 95% CI 1.058-8.295, p = .039), (HR 3.590, 95% CI 1.254-10.280, p = .017). Besides, compared with patients who were negative for both WT1-MRD and MFC-MRD, patients who were positive both WT1-MRD and MFC-MRD were associated with worse RFS (HR 6.200, 95% CI 2.206-17.430, p = .001) and worse OS (HR 4.886, 95% CI 1.388-17.197, p = .013). This study demonstrates that combined assessment of MRD by WT1 and MFC improves relapse and prognosis prediction in non-APL AML patients, and may help guide interventions for disease relapse.

Japanese encephalitis virus induces apoptosis by activating the RIG-1 signaling pathway.

Japanese encephalitis virus (JEV) infection can cause brain tissue lesions characterized by neuronal death, and apoptosis is involved in JEV-induced neuronopathy. In the present study, mouse microglia were infected with JEV, and pyknosis with dark-staining nuclei of infected cells was detected using Hoechst 33342 staining. TUNEL staining showed that JEV infection promoted the apoptosis of BV2 cells, and the apoptosis rate was significantly increased at 24-60 hours postinfection (hpi) (P < 0.01) and was the highest at 36 h (P < 0.0001). Western blot results showed that the expression of the Bcl-2 protein in JEV-infected cells was downregulated significantly at 60 hpi (P < 0.001), whereas that of the Bax protein was observably upregulated at 60 hpi (P < 0.001). At the same time, the level of cytochrome c (Cyt c) was significantly increased (P < 0.001), and the expression levels of two apoptosis-related proteins, namely, cleaved caspase-3 (P < 0.01) and caspase-9 (P < 0.001), were elevated significantly. Immunofluorescence staining showed that the amount of Cyt c increased with time after infection. After BV2 cells were infected with JEV, the expression of RIG-1 increased significantly from 24 hpi to 60 h (P < 0.001). The expression of MAVS increased significantly at 24 h (P < 0.001) and decreased gradually from 24 h to 60 hpi. The expression of TBK1 and NF-κB (p65) was not significantly changed. The expression of p-TBK1 and p-NF-κB (p-p65) increased significantly within 24 h (P < 0.001) and decreased from 24 to 60 hpi. The expression levels of IRF3 and p-IRF3 peaked at 24 hpi (P < 0.001) and decreased gradually from 24 to 60 hpi. However, the expression levels of JEV proteins showed no significant change at 24 and 36 hpi but were markedly elevated at 48 and 60 hpi. Interference with the expression of the RIG-1 protein in BV2 cells resulted in a dramatic increase in the expression of the anti-apoptotic protein Bcl-2 (P < 0.05), whereas the pro-apoptotic protein Bax, cleaved caspase-9, and especially cleaved caspase-3 were downregulated (P < 0.05), and viral protein expression was notably reduced (P < 0.05). These results indicate that JEV induces apoptosis through mitochondrial-dependent apoptosis pathways, interfering with the expression of RIG-1 in BV2 cells can inhibit viral replication and inhibit apoptosis.

Vegetation browning: global drivers, impacts, and feedbacks.

As global climate conditions continue to change, disturbance regimes and environmental drivers will continue to shift, impacting global vegetation dynamics. Following a period of vegetation greening, there has been a progressive increase in remotely sensed vegetation browning globally. Given the many societal benefits that forests provide, it is critical that we understand vegetation dynamic alterations. Here, we review associative drivers, impacts, and feedbacks, revealing the complexity of browning. Concomitant increases in browning include the weakening of ecosystem services and functions and alterations to vegetation structure and species composition, as well as the development of potential positive climate change feedbacks. Also discussed are the current challenges in browning detection and understanding associated impacts and feedbacks. Finally, we outline recommended strategies.

HSPA5 Promotes the Proliferation, Metastasis and Regulates Ferroptosis of Bladder Cancer.

Heat shock protein family A (HSP70) member 5 (HSPA5) is aberrantly expressed in various tumors and closely associated with the progression and prognosis of cancer. Nevertheless, its role in bladder cancer (BCa) remains elusive. The results of our study demonstrated that HSPA5 was upregulated in BCa and correlated with patient prognosis. Cell lines with low expression level of HSPA5 were constructed to explore the role of this protein in BCa. HSPA5 knockdown promoted apoptosis and retarded the proliferation, migration and invasion of BCa cells by regulating the VEGFA/VEGFR2 signaling pathway. In addition, overexpression of VEGFA alleviated the negative effect of HSPA5 downregulation. Moreover, we found that HSPA5 could inhibit the process of ferroptosis through the P53/SLC7A11/GPX4 pathway. Hence, HSPA5 can facilitate the progression of BCa and may be used as a novel biomarker and latent therapeutic target in the clinic.

SESN2 Could Be a Potential Marker for Diagnosis and Prognosis in Glioma.

(1) Background: Glioma is among the most common brain tumors, and is difficult to eradicate with current therapeutic strategies due to its highly invasive and aggressive characteristics. Sestrin2 (SESN2) is an autophagy inducer. The effect of SESN2 on glioma is controversial and unclear. (2) Methods: We downloaded related RNA-seq data from the TCGA and GTEx databases. Bioinformatic analyses including differential gene expression analysis, KM survival curve analysis, univariate and multivariate Cox regression analyses, nomogram analysis, ROC curve analysis, gene function enrichment analysis, and immune cell infiltration analysis were conducted. In addition, data from the Human Protein Atlas (HPA) database were collected to validate SESN2 expression in glioma. (3) Results: In comparison with normal tissue, expression of SESN2 in glioma tissue was higher, and those with higher expressions had significantly lower overall survival rates. The results of univariate Cox regression analyses showed that SESN2 can be a disadvantageous factor in poor glioma prognosis. Both nomograms and ROC curves confirmed these findings. Meanwhile, according to gene function analysis, SESN2 may be involved in immune responses and the tumor microenvironment (TME). Based on the HPA database results, SESN2 is localized in the cytosol and shows high expression in glioma. (4) Conclusions: The expression of SESN2 in gliomas was positively relevant to a poorer prognosis, suggesting that SESN2 could be used as a prognostic gene.

MicroRNA-27a-3p targeting Vangl1 and Vangl2 inhibits cell proliferation in mouse granulosa cells.

BACKGROUND: Mammalian folliculogenesis is the complex process through which primordial follicles develop into preovulatory follicles. The chief function of ovarian follicle granulosa cells is to play a vital role in the growth, development and atresia of ovarian follicles via gap junctions. Increasing evidence suggests that microRNAs (miRNAs) are essential regulators of granulosa cell apoptosis or proliferation. METHODS: The expression level of miR-27a-3p, myogenic differentiation (MyoD), Vangl1 and Vangl2 was investigated by Real-time quantitative PCR (RT-qPCR) and Western blot. Luciferase reporter assay, bioinformatics analysis and ChIP-PCR was used to detect the binding sites between miR-27a-3p, transcription factor and target genes. KEGG pathway analyses were performed to reveal the predicted targets of miR-27a-3p. Ethynyl deoxyuridine (EdU) proliferation assay was used to measure cell proliferation. RESULTS: To explore the underlying mechanisms of the miR-27a-3p function in the development of mouse granulosa cells (mGCs), we screened for the target genes of miR-27a-3p, confirmed its interaction with Vangl1 and Vangl2 and elucidated their roles in mGCs. MiR-27a-3p inhibited the proliferation of mGCs, whereas target genes Vangl1 and Vangl2 had the opposite effect. In addition, the transcription factor MYOD bound to and activated the promoter of miR-27a-3p. MiR-27a-3p suppressed Vangl1 and Vangl2 expression by targeting their 3'-untranslated region (3'-UTR). Furthermore, Vangl1 and Vangl2 suppressed the Wnt pathway by reducing the expression of ß-catenin and B-cell lymphoma/leukemia-2 (Bcl-2). CONCLUSION: These findings indicate a pro-survival mechanism of the MyoD/miR-27a-3p/Vangl1/Vangl2 axis for granulosa cell proliferation and suggest a novel target for the improvement of female fertility.