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1.
Br J Haematol ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38955502

ABSTRACT

This open-label, prospective trial evaluated the combination of ixazomib, cyclophosphamide and dexamethasone (ICD) in 12 newly diagnosed POEMS syndrome patients. The study is registered with the Chinese Clinical Trials Registry (ChiCTR2000030072). The treatment protocol consisted of 12 cycles of the ICD regimen compromising ixazomib (4 mg on Days 1, 8 and 15), oral cyclophosphamide (300 mg on Days 1, 8 and 15) and dexamethasone (20 mg weekly). A total of 12 patients received a median of 10 (range: 3-23) cycles of the ICD regimen. The haematological response could be evaluated in 10 patients. The overall haematological response rate was 80% (8/10), with 30% (3/10) achieving complete haematological response, and the overall serum VEGF response rate and neurological response were 100% and 83.3% respectively. Two patients experienced grade 3/4 AEs, including diarrhoea (n = 1) and leukopenia (n = 1). The combination of ixazomib, cyclophosphamide and dexamethasone demonstrated both efficacy and safety in newly diagnosed POEMS syndrome, making it a viable treatment option.

2.
Eur J Oncol Nurs ; 71: 102617, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38865852

ABSTRACT

PURPOSE: This study aims to explore heterogeneous trajectories of psychosocial adjustment among young to middle-aged women with breast cancer and determine the predictive factors influencing these trajectories. METHODS: This study was conducted from October 2019 to October 2022 across two hospitals in Guangzhou. Demographic and disease characteristics, psychosocial adjustment, self-efficacy, social support, and coping modes were collected at baseline. Follow-up evaluations of psychosocial adjustment occurred at 1, 3, and 6 months post-surgery. Latent class growth modeling identified distinct patterns of psychosocial adjustment trajectories. Logistic regression analysis determined the predictive factors. RESULTS: A total of 377 young to middle-aged women with breast cancer participated in this study, with 289 participants completing the 6-month follow-up. Three distinct trajectories of psychosocial adjustment were identified including a "sustained severe maladjustment" trajectory, comprising 22.5% of participants, a "sustained moderate maladjustment" trajectory, comprising 50.4% of participants, and a "well-adjusted class" trajectory, comprising 27.1% of participants. Predictors of psychosocial adjustment trajectories included affected side, surgical type, chemotherapy, self-efficacy, social support, and coping modes. CONCLUSIONS: This study revealed three distinct trajectories of psychosocial adjustment among young to middle-aged women with breast cancer. Those with right-sided breast cancer, undergoing total mastectomy, receiving chemotherapy, low self-efficacy, limited social support, and relying on confrontation or avoidance coping modes may experience sustained maladjustment.

3.
Clin Cancer Res ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38869658

ABSTRACT

PURPOSE: This study aimed to report the five-year clinical outcomes of anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell (HDS269B) therapy in relapsed/refractory multiple myeloma (RRMM) patients, including those with poor performance status (Eastern Cooperative Oncology Group [ECOG] 3-4), and to identify factors influencing long-term outcomes. METHODS: Forty-nine RRMM patients enrolled from 2016 to 2020 received HDS269B (9×106 cells/kg) after receiving a conditioning chemotherapy consisting of cyclophosphamide and fludarabine. The overall response, long-term outcomes, and safety were assessed, as were their associations with clinical and disease characteristics. RESULTS: With a median follow-up of 59.0 months, the overall response rate was 77.55%. The median progression-free survival (PFS) and overall survival (OS) were 9.5 months (95% confidence interval [CI], 5.01-13.99) and 20.0 months (95% CI, 11.26-28.74), respectively. The 5-year PFS and OS rates were 21.3% (95% CI, 12.3%-36.7%) and 34.1% (95% CI, 22.7%-51.3%), respectively. Patients with ECOG 0-2 had marked longer survival, with a median PFS of 11.0 months and median OS of 41.8 months. Early minimal residual disease negativity, and higher and persistent CAR-T cell expansion and absence of extramedullary disease were associated with better survival outcomes. No new CAR-T cell therapy associated toxicities were observed. Importantly, ECOG 0-2, prior therapy lines <4, and CAR-T cell persistence at ≥6 months were independently associated with longer OS. CONCLUSIONS: HDS269B is effective and safe, especially for patients with ECOG 0-2. Early CAR-T cell intervention may improve prognosis in patients with RRMM.

4.
Article in English | MEDLINE | ID: mdl-38913604

ABSTRACT

The depletion of lithium resources has prompted exploration into alternative rechargeable energy storage systems, and potassium-ion batteries (PIBs) have emerged as promising candidates. As an active cathode material for PIBs, potassium vanadate (KxV2O5) usually suffers from structural damage during electrochemical K-ion insertion/extraction and hence leading to unsatisfactory cycling performance. Here, we introduce Ca2+ ions as pillars into the potassium vanadate to enhance its structural stability and smooth its phase transition behavior. The additional Ca2+ not only stabilizes the layered structure but also promotes the rearrangement of interlayer ions and leads to a smooth solid-solution phase transition. The optimal composition K0.36Ca0.05V2O5 (KCVO) exhibits outstanding cyclic stability, delivering a capacity of ∼90 mA h g-1 at 20 mA g-1 with negligible capacity decay even after 700 cycles at 500 mA g-1. Theoretical calculations indicate lower energy barriers for K+ diffusion, promoting rapid reaction kinetics. The excellent performances and detailed investigations offer insights into the structural regulation of layered vanadium cathodes.

5.
J Microbiol Biotechnol ; 34(6): 1249-1259, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38938004

ABSTRACT

It remains to be determined whether there is a geographical distribution pattern and phylogenetic signals for the Mycena strains with seed germination of the orchid plant Gastrodia elata. This study analyzed the community composition and phylogenetics of 72 Mycena strains associated with G. elata varieties (G. elata. f. glauca and G. elata. f. viridis) using multiple gene fragments (ITS+nLSU+SSU). We found that (1) these diverse Mycena phylogenetically belong to the Basidiospore amyloid group. (2) There is a phylogenetic signal of Mycena for germination of G. elata. Those strains phylogenetically close to M. abramsii, M. polygramma, and an unclassified Mycena had significantly higher germination rates than those to M. citrinomarginata. (3) The Mycena distribution depends on geographic site and G. elata variety. Both unclassified Mycena group 1 and the M. abramsii group were dominant for the two varieties of G. elata; in contrast, the M. citrinomarginata group was dominant in G. elata f. glauca but absent in G. elata f. viridis. Our results indicate that the community composition of numerous Mycena resources in the Zhaotong area varies by geographical location and G. elata variety. Importantly, our results also indicate that Mycena's phylogenetic status is correlated with its germination rate.


Subject(s)
Gastrodia , Germination , Phylogeny , Gastrodia/microbiology , Gastrodia/genetics , DNA, Fungal/genetics , Seeds/microbiology , Seeds/growth & development , Basidiomycota/genetics , Basidiomycota/classification , Basidiomycota/physiology
6.
RSC Adv ; 14(28): 20191-20198, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38915332

ABSTRACT

Advances in high-efficiency solar cells introduce photon management challenges, including the difficult texturization of flat surfaces and low photon utilization at short wavelengths. While bifacial crystalline silicon solar cells have a front pyramid structure and SiN x layers reduce reflections, managing photons on the flat backside remains a challenge. To enhance light utilization, a soft nanoimprint technique was utilized to create pyramid micro-structured polyurethane films doped with europium (Eu3+) complex. These films, which possess anti-reflection and down-conversion properties, can be applied externally to various high-efficiency solar cells without compromising electrical performance. Research on the backside of bifacial PERC solar cells revealed that the optimal composite functional film increases the integrated current by 5.70%, with a 1.27% gain from down-conversion effects. This specialized film presents a novel approach to interface matching for different types of solar cells.

7.
Small ; : e2402845, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38895955

ABSTRACT

Metal chalcogenides as an ideal family of anode materials demonstrate a high theoretical specific capacity for potassium ion batteries (PIBs), but the huge volume variance and poor cyclic stability hinder their practical applications. In this study, a design of a stress self-adaptive structure with ultrafine SnSe nanoparticles embedded in carbon nanofiber (SnSe@CNF) via the electrospinning technology is presented. Such an architecture delivers a record high specific capacity (272 mAh g-1 at 50 mA g-1) and high-rate performance (125 mAh g-1 at 1 A g-1) as a PIB anode. It is decoded that the fundamental understanding for this great performance is that the ultrafine SnSe particles enhance the full utilization of the active material and achieve stress relief as the stored strain energy from cycling is insufficient to drive crack propagation and thus alleviates the intrinsic chemo-mechanical degradation of metal chalcogenides.

8.
Nat Metab ; 6(6): 1092-1107, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38773347

ABSTRACT

Lipid droplet tethering with mitochondria for fatty acid oxidation is critical for tumor cells to counteract energy stress. However, the underlying mechanism remains unclear. Here, we demonstrate that glucose deprivation induces phosphorylation of the glycolytic enzyme phosphofructokinase, liver type (PFKL), reducing its activity and favoring its interaction with perilipin 2 (PLIN2). On lipid droplets, PFKL acts as a protein kinase and phosphorylates PLIN2 to promote the binding of PLIN2 to carnitine palmitoyltransferase 1A (CPT1A). This results in the tethering of lipid droplets and mitochondria and the recruitment of adipose triglyceride lipase to the lipid droplet-mitochondria tethering regions to engage lipid mobilization. Interfering with this cascade inhibits tumor cell proliferation, promotes apoptosis and blunts liver tumor growth in male mice. These results reveal that energy stress confers a moonlight function to PFKL as a protein kinase to tether lipid droplets with mitochondria and highlight the crucial role of PFKL in the integrated regulation of glycolysis, lipid metabolism and mitochondrial oxidation.


Subject(s)
Cell Proliferation , Glycolysis , Lipid Droplets , Lipolysis , Mitochondria , Oxidation-Reduction , Lipid Droplets/metabolism , Animals , Mitochondria/metabolism , Mice , Humans , Male , Lipid Metabolism , Perilipin-2/metabolism , Phosphorylation , Carnitine O-Palmitoyltransferase/metabolism , Cell Line, Tumor
9.
bioRxiv ; 2024 May 12.
Article in English | MEDLINE | ID: mdl-38766072

ABSTRACT

Protein retention expansion microscopy (ExM) retains genetically encoded fluorescent proteins or antibody-conjugated fluorescent probes in fixed tissue and isotropically expands the tissue through a swellable polymer network to allow nanoscale (<70 nm) resolution on diffraction-limited confocal microscopes. Despite numerous advantages ExM brings to biological studies, the full protocol is time-consuming and can take multiple days to complete. Here, we adapted the ExM protocol to the vibratome-sectioned brain tissue of Xenopus laevis tadpoles and implemented a microwave-assisted protocol to reduce the workflow from days to hours. In addition to the significantly accelerated processing time, our microwave-assisted ExM (M/WExM) protocol maintains the superior resolution and signal-to-noise ratio of the original ExM protocol. Furthermore, the M/WExM protocol yields higher magnitude of expansion, suggesting that in addition to accelerating the process through increased diffusion rate of reagents, microwave radiation may also facilitate the expansion process. To demonstrate the applicability of this method to other specimens and protocols, we adapted the microwave-accelerated protocol to whole mount adult brain tissue of Drosophila melanogaster fruit flies, and successfully reduced the total processing time of a widely-used Drosophila IHC-ExM protocol from 6 days to 2 days. Our results demonstrate that with appropriate adjustment of the microwave parameters (wattage, pulse duration, interval, and number of cycles), this protocol can be readily adapted to different model organisms and tissue types to greatly increase the efficiency of ExM experiments.

10.
Neurosurg Rev ; 47(1): 222, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758384

ABSTRACT

To assess whether monitoring brain tissue oxygen partial pressure (PbtO2) or employing intracranial pressure (ICP)/cerebral perfusion pressure (CCP)-guided management improves patient outcomes, including mortality, hospital length of stay (LOS), mean daily ICP and mean daily CCP during the intensive care unit(ICU)stay. We searched the Web of Science, EMBASE, PubMed, Cochrane Library, and MEDLINE databases until December 12, 2023. Prospective randomized controlled and cohort studies were included. A meta-analysis was performed for the primary outcome measure, mortality, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eleven studies with a total of 37,492 patients were included. The mortality in the group with PbtO2 was 29.0% (odds ratio: 0.73;95% confidence interval [CI]:0.56-0.96; P = 0.03; I = 55%), demonstrating a significant benefit. The overall hospital LOS was longer in the PbtO2 group than that in the ICP/CPP group (mean difference:2.03; 95% CI:1.03-3.02; P<0.0001; I = 39%). The mean daily ICP in the PbtO2 monitoring group was lower than that in the ICP/CPP group (mean difference:-1.93; 95% CI: -3.61 to -0.24; P = 0.03; I = 41%). Moreover, PbtO2 monitoring did not improve the mean daily CPP (mean difference:2.43; 95%CI: -1.39 to 6.25;P = 0.21; I = 56%).Compared with ICP/CPP monitoring, PbtO2 monitoring reduced the mortality and the mean daily ICP in patients with severe traumatic brain injury; however, no significant effect was noted on the mean daily CPP. In contrast, ICP/CPP monitoring alone was associated with a short hospital stay.


Subject(s)
Brain Injuries, Traumatic , Brain , Intracranial Pressure , Oxygen , Humans , Brain Injuries, Traumatic/mortality , Brain Injuries, Traumatic/diagnosis , Brain Injuries, Traumatic/therapy , Cerebrovascular Circulation/physiology , Intracranial Pressure/physiology , Length of Stay , Monitoring, Physiologic/methods , Oxygen/metabolism , Oxygen/blood , Partial Pressure , Prognosis
11.
Exp Cell Res ; 439(1): 114094, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38750718

ABSTRACT

Pirarubicin (THP) is a new generation of cell cycle non-specific anthracycline-based anticancer drug. In the clinic, THP and THP combination therapies have been shown to be effective in hepatocellular carcinoma (HCC) patients with transcatheter arterial chemoembolization (TACE) without serious side effects. However, drug resistance limits its therapeutic efficacy. Berberine (BBR), an isoquinoline alkaloid, has been shown to possess antitumour properties against various malignancies. However, the synergistic effect of BBR and THP in the treatment of HCC is unknown. In the present study, we demonstrated for the first time that BBR sensitized HCC cells to THP, including enhancing THP-induced growth inhibition and apoptosis of HCC cells. Moreover, we found that BBR sensitized THP by reducing the expression of autophagy-related 4B (ATG4B). Mechanistically, the inhibition of HIF1α-mediated ATG4B transcription by BBR ultimately led to attenuation of THP-induced cytoprotective autophagy, accompanied by enhanced growth inhibition and apoptosis in THP-treated HCC cells. Tumor-bearing experiments in nude mice showed that the combination treatment with BBR and THP significantly suppressed the growth of HCC xenografts. These results reveal that BBR is able to strengthen the killing effect of THP on HCC cells by repressing the ATG4B-autophagy pathway, which may provide novel insights into the improvement of chemotherapeutic efficacy of THP, and may be conducive to the further clinical application of THP in HCC treatment.


Subject(s)
Apoptosis , Autophagy-Related Proteins , Autophagy , Berberine , Carcinoma, Hepatocellular , Doxorubicin , Liver Neoplasms , Mice, Nude , Berberine/pharmacology , Berberine/analogs & derivatives , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Autophagy/drug effects , Animals , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Autophagy-Related Proteins/metabolism , Autophagy-Related Proteins/genetics , Mice , Apoptosis/drug effects , Doxorubicin/pharmacology , Doxorubicin/analogs & derivatives , Xenograft Model Antitumor Assays , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Synergism , Mice, Inbred BALB C , Antineoplastic Agents/pharmacology , Signal Transduction/drug effects , Cysteine Endopeptidases
12.
Front Plant Sci ; 15: 1381071, 2024.
Article in English | MEDLINE | ID: mdl-38699538

ABSTRACT

Introduction: The biosynthesis of secondary metabolites like anthocyanins is often governed by metabolic gene clusters (MGCs) in the plant ancestral genome. However, the existence of gene clusters specifically regulating anthocyanin accumulation in certain organs is not well understood. Methods and results: In this study, we identify MGCs linked to the coloration of cotton reproductive organs, such as petals, spots, and fibers. Through genetic analysis and map-based cloning, we pinpointed key genes on chromosome A07, such as PCC/GhTT19, which is involved in anthocyanin transport, and GbBM and GhTT2-3A, which are associated with the regulation of anthocyanin and proanthocyanidin biosynthesis. Our results demonstrate the coordinated control of anthocyanin and proanthocyanidin pathways, highlighting the evolutionary significance of MGCs in plant adaptation. The conservation of these clusters in cotton chromosome A07 across species underscores their importance in reproductive development and color variation. Our study sheds light on the complex biosynthesis and transport mechanisms for plant pigments, emphasizing the role of transcription factors and transport proteins in pigment accumulation. Discussion: This research offers insights into the genetic basis of color variation in cotton reproductive organs and the potential of MGCs to enhance our comprehension of plant secondary metabolism.

13.
Clin Exp Immunol ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38743453

ABSTRACT

Serum B-cell maturation antigen (sBCMA) levels can serve as a sensitive biomarker in multiple myeloma (MM). In the research setting, sBCMA levels can be accurately detected by enzyme-linked immunosorbent assay (ELISA), but the approach has not been approved for clinical use. Here, we used a novel chemiluminescence method to assess sBCMA levels in 759 serum samples from 17 healthy donors and 443 patients with plasma cell (PC) diseases including AL amyloidosis, POEMS syndrome and MM. Serum BCMA levels were elevated 16.1-fold in patients with newly diagnosed MM compared to healthy donors and rare PC diseases patients. Specifically, the sBCMA levels in patients with progressive disease were 64.6-fold higher than those who showed partial response or above to treatment. The sBCMA level also correlated negatively with the response depth of MM patients. In newly diagnosed and relapsed MM patients, survival was significantly longer among those subjects whose sBCMA levels are below the median levels compared with those above the median value. We optimized the accuracy of the survival prediction further by integrating sBCMA level into the Second Revised International Staging System (R2-ISS). Our findings provide evidence that the novel chemiluminescence method is sensitive and practical for measuring sBCMA levels in clinical samples and confirm that sBCMA might serve as an independent prognostic biomarker for MM.

14.
ACS Appl Mater Interfaces ; 16(19): 25422-25431, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38695314

ABSTRACT

Flexible piezoresistive pressure sensors are garnering substantial attention, in line with advancements in biointegrated and wearable electronics. However, a significant portion of piezoresistive pressure sensors suffer from the trade-off between sensitivity and pressure range. Moreover, the current piezoresistive sensors generally rely on a rigid metallic electrode, severely deteriorating their long-term durability. Herein, a fully flexible piezoresistive sensor coupling polyurethane (PU) based electrode and active sensing element is proposed to circumvent the aforementioned problems. By rationally regulating the double-permeable conductive networks within the PU matrix, an elastomeric electrode and sensing element are implemented, respectively. The assembled heterostructured configurations enable impressive sensitivity up to 7.023 kPa-1, broad pressure detection (up to 420 kPa), an ultralow pressure sensing limit (0.1 Pa), and extraordinary operation stability over 80000 cyclic pressings along with fast response/relaxation times (60 ms/80 ms). Additionally, the fully flexible sensor is capable of both real-time detection of physiological signals and mimicking keyboards, implying its viability as a high-performance pressure sensor.

15.
ACS Nano ; 18(15): 10341-10373, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38572836

ABSTRACT

Noble-metal nanocrystals have emerged as essential electrode materials for catalytic oxidation of organic small molecule fuels in direct liquid fuel cells (DLFCs). However, for large-scale commercialization of DLFCs, adopting cost-effective techniques and optimizing their structures using advanced matrices are crucial. Notably, noble metal-decorated porous carbon nanoarchitectures exhibit exceptional electrocatalytic performances owing to their three-dimensional cross-linked porous networks, large accessible surface areas, homogeneous dispersion (of noble metals), reliable structural stability, and outstanding electrical conductivity. Consequently, they can be utilized to develop next-generation anode catalysts for DLFCs. Considering the recent expeditious advancements in this field, this comprehensive review provides an overview of the current progress in noble metal-decorated porous carbon nanoarchitectures. This paper meticulously outlines the associated synthetic strategies, precise microstructure regulation techniques, and their application in electrooxidation of small organic molecules. Furthermore, the review highlights the research challenges and future opportunities in this prospective research field, offering valuable insights for both researchers and industry experts.

17.
Int J Nurs Stud ; 154: 104735, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38521005

ABSTRACT

BACKGROUND: Frailty is commonly observed in stroke patients and it is associated with adverse outcomes. However, there remains a gap in longitudinal studies investigating the causal relationship between baseline frailty and short-term prognosis in discharged adult stroke patients. OBJECTIVE: To examine the causal impact of frailty on non-elective readmission and major adverse cardiac and cerebral events, and investigate its associations with cognitive impairment and post-stroke disability. DESIGN: A multicenter prospective cohort study. SETTING: Two tertiary hospitals in Central and Northwest China. PARTICIPANTS: 667 adult stroke patients in stroke units were included from January 2022 to June 2022. METHODS: Baseline frailty was assessed by the Frailty Scale. Custom-designed questions were utilized to assess non-elective readmission and major adverse cardiac and cerebral events as primary outcomes. Cognitive impairment, assessed using the Mini-Mental State Examination Scale (MMSE), and post-stroke disability, measured with the Modified Rankin Scale (mRS), were considered secondary outcomes at a 3-month follow-up. The impact of baseline frailty on non-elective readmission and major adverse cardiac and cerebral events was examined using bivariate and multiple Cox regression analyses. Furthermore, associations between baseline frailty and cognitive impairment, or post-stroke disability, were investigated through generalized linear models. RESULTS: A total of 5 participants died, 12 had major adverse cardiac and cerebral events, and 57 had non-selective readmission among 667 adult stroke patients. Frailty was an independent risk factor for non-selective readmission (hazard ratio [HR]: 2.71, 95 % confidence interval [CI]: 1.59, 4.62) and major adverse cardiac and cerebral events (HR: 3.77, 95 % CI: 1.07, 13.22) for stroke patients. Baseline frailty was correlated with cognitive impairment (regression coefficient [ß]: -2.68, 95 % CI: -3.78, -1.58) adjusting for socio-demographic and clinical factors and follow-up interval. However, the relationship between frailty and cognitive impairment did not reach statistical significance when further adjusting for baseline MMSE (ß: -0.39, 95 % CI: -1.43, 0.64). Moreover, baseline frailty was associated with post-stroke disability (ß: 0.36, 95 % CI: 0.08, 0.65) adjusting for socio-demographic and clinical variables, follow-up interval, and baseline mRS. CONCLUSIONS: The finding highlights the importance of assessing baseline frailty in discharged adult stroke patients, as it is significantly associated with non-elective readmission, major adverse cardiac and cerebral events, and post-stroke disability at 3 months. These results highlight the crucial role of screening and evaluating frailty status in improving short-term prognosis for adult stroke patients. Interventions should be developed to address baseline frailty and mitigate the short-term prognosis of stroke. TWEETABLE ABSTRACT: Baseline frailty predicts non-elective readmission, major adverse cardiac and cerebral events, and post-stroke disability in adult stroke patients. @haiyanhexyyy.


Subject(s)
Frailty , Patient Discharge , Stroke , Humans , Prospective Studies , Frailty/complications , Female , Male , Prognosis , Middle Aged , Aged , Stroke/complications , China/epidemiology , Cohort Studies , Adult
18.
Nat Chem Biol ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38538923

ABSTRACT

Telomere dysfunction is intricately linked to the aging process and stands out as a prominent cancer hallmark. Here we demonstrate that telomerase activity is differentially regulated in cancer and normal cells depending on the expression status of fructose-1,6-bisphosphatase 1 (FBP1). In FBP1-expressing cells, FBP1 directly interacts with and dephosphorylates telomerase reverse transcriptase (TERT) at Ser227. Dephosphorylated TERT fails to translocate into the nucleus, leading to the inhibition of telomerase activity, reduction in telomere lengths, enhanced senescence and suppressed tumor cell proliferation and growth in mice. Lipid nanoparticle-mediated delivery of FBP1 mRNA inhibits liver tumor growth. Additionally, FBP1 expression levels inversely correlate with TERT pSer227 levels in renal and hepatocellular carcinoma specimens and with poor prognosis of the patients. These findings demonstrate that FBP1 governs cell immortality through its protein phosphatase activity and uncover a unique telomerase regulation in tumor cells attributed to the downregulation or deficiency of FBP1 expression.

19.
iScience ; 27(4): 109332, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38500832

ABSTRACT

Identification and differentiation of appropriate indications on hip preserving with bone grafting therapy remains a crucial challenge in the treatment of osteonecrosis of the femoral head (ONFH). A prospective cohort study on bone grafting therapy for ONFH aimed to evaluate hip survival rates, and to establish a risk scoring derived from potential risk factors (multivariable model) for hip preservation. Eight variables were identified to be strongly correlated with a decreased rate of hip survival post-therapy, and a comprehensive risk scoring was developed for predicting hip-preservation outcomes. The C-index stood at 0.72, and the areas under the receiver operating characteristics for the risk score's 5- and 10-year hip failure event predictions were 0.74 and 0.72, respectively. This risk score outperforms conventional methods in forecasting hip preservation. Bone grafting shows sustained benefits in treating ONFH when applied under the right indications. Furthermore, the risk scoring proves valuable as a decision-making tool, facilitating risk stratification for ONFH treatments in future.

20.
Ecol Evol ; 14(2): e11004, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38389997

ABSTRACT

Full myco-heterotrophic orchid Gastrodia elata Bl. is widely distributed in Northeast Asia, and previous research has not fully investigated the symbiotic fungal community of its early immature tubers. This study utilized Illumina sequencing to compare symbiotic fungal communities in natural G. elata immature tubers and their habitats. LEfSe (Linear Discriminant Analysis Effect Size) was used to screen for Biomarkers that could explain variations among different fungal communities, and correlation analyses were performed among Biomarkers and other common orchid mycorrhizal fungi. Our results illustrate that the symbiotic fungal communities of immature G. elata tubers cannot be simply interpreted as subsets of the environmental fungal communities because some key members cannot be traced back to the environment. The early growth of G. elata was related to a small group of fungi, such as Sebacina, Thelephora, and Inocybe, which were also common mycorrhizal fungi from other orchids. In addition, Mycena, Auricularia, and Cryptococcus were unique fungal partners of G. elata, and many new species have yet to be discovered. Possible symbiotic Mycena should be M. plumipes and its sibling species in this case. Our results provide insight into the symbiotic partner switch and trophic pattern change during the development and maturation of G. elata.

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