The OsMOB1A-OsSTK38 kinase complex phosphorylates CYCLIN C, controlling grain size and weight in rice.

Grain size and weight are crucial yield-related traits in rice (Oryza sativa). Although certain key genes associated with rice grain size and weight have been successfully cloned, the molecular mechanisms underlying grain size and weight regulation remain elusive. Here, we identified a molecular pathway regulating grain size and weight in rice involving the MPS ONE BINDER KINASE ACTIVATOR-LIKE 1A-SERINE/THREONINE-PROTEIN KINASE 38-CYCLIN C (OsMOB1A-OsSTK38-OsCycC) module. OsSTK38 is a nuclear Dbf2-related kinase that positively regulates grain size and weight by coordinating cell proliferation and expansion in the spikelet hull. OsMOB1A interacts with and enhances the autophosphorylation of OsSTK38. Specifically, the critical role of the OsSTK38 S322 site in its kinase activity is highlighted. Furthermore, OsCycC, a component of the Mediator complex, was identified as a substrate of OsSTK38, with enhancement by OsMOB1A. Notably, OsSTK38 phosphorylates the T33 site of OsCycC. The phosphorylation of OsCycC by OsSTK38 influenced its interaction with the transcription factor KNOTTED-LIKE HOMEOBOX OF ARABIDOPSIS THALIANA 7 (OsKNAT7). Genetic analysis confirmed that OsMOB1A, OsSTK38 and OsCycC function in a common pathway to regulate grain size and weight. Taken together, our findings revealed a connection between the Hippo signalling pathway and the Cyclin-Dependent Kinase (CDK) module in eukaryotes. Moreover, they provide insights into the molecular mechanisms linked to yield-related traits and propose innovative breeding strategies for high-yielding varieties.

Microsatellite instability in mismatch repair proficient colorectal cancer: clinical features and underlying molecular mechanisms.

BACKGROUND: Both defects in mismatch repair (dMMR) and high microsatellite instability (MSI-H) have been recognised as crucial biomarkers that guide treatment strategies and disease management in colorectal cancer (CRC). As MMR and MSI tests are being widely conducted, an increasing number of MSI-H tumours have been identified in CRCs with mismatch repair proficiency (pMMR). The objective of this study was to assess the clinical features of patients with pMMR/MSI-H CRC and elucidate the underlying molecular mechanism in these cases. METHODS: From January 2015 to December 2018, 1684 cases of pMMR and 401 dMMR CRCs were enrolled. Of those patients, 93 pMMR/MSI-H were identified. The clinical phenotypes and prognosis were analysed. Frozen and paraffin-embedded tissue were available in 35 patients with pMMR/MSI-H, for which comprehensive genomic and transcriptomic analyses were performed. FINDINGS: In comparison to pMMR/MSS CRCs, pMMR/MSI-H CRCs exhibited significantly less tumour progression and better long-term prognosis. The pMMR/MSI-H cohorts displayed a higher presence of CD8+ T cells and NK cells when compared to the pMMR/MSS group. Mutational signature analysis revealed that nearly all samples exhibited deficiencies in MMR genes, and we also identified deleterious mutations in MSH3-K383fs. INTERPRETATION: This study revealed pMMR/MSI-H CRC as a distinct subgroup within CRC, which manifests diverse clinicopathological features and long-term prognostic outcomes. Distinct features in the tumour immune-microenvironment were observed in pMMR/MSI-H CRCs. Pathogenic deleterious mutations in MSH3-K383fs were frequently detected, suggesting another potential biomarker for identifying MSI-H. FUNDING: This work was supported by the Science and Technology Commission of Shanghai Municipality (20DZ1100101).

Molybdesum selenide-based platelet-rich plasma containing carboxymethyl chitosan/polyvinyl pyrrolidone composite antioxidant hydrogels dressing promotes the wound healing.

Excess free radicals at the wound site can cause an inflammatory response, which is not conducive to wound healing. Hydrogels with antioxidant properties can prevent inflammatory storms by scavenging free radicals from the wound site and inhibiting the release of inflammatory factors. In this study, we prepared the carboxymethyl chitosan (CMCS)/polyvinyl pyrrolidone (PVP)/Molybdenum (IV) Selenide (MoSe2), and platelet-rich plasma (PRP) (CMCS/PVP/MoSe2/PRP) hydrogels for accelerating the repair of wounds. In the hydrogels, the MoSe2 can scavenge various free radicals to reduce oxidative stress at the site of inflammation, endowed the hydrogels with antioxidant properties. Interestingly, growth factors released by PRP assisted the tissue repair by promoting the formation of new capillaries. CMCS as a backbone not only showed good biocompatibility and biodegradability but also played a significant role in maintaining the sustained release of growth factors. In addition, incorporating PVP enhanced the tissue adhesion and mechanical properties. The multifunctional composite antioxidant hydrogels have good swelling properties and biodegradability, which is completely degraded within 28 days. Thus, the antioxidant CMCS/PVP/MoSe2/PRP hydrogels provide a new idea for designing ideal multifunctional wound dressings.

Development of erythrina-based PARP-1/FTase dual-target inhibitors against lung cancer epithelial-mesenchymal transition (EMT) in vivo and in vitro.

A novel series of erythrina derivatives as PARP-1/FTase inhibitors were synthesized, and evaluated for their biological activities. Compound T9 had excellent inhibitory effects on cell viability (A549: IC50 = 1.74 µM; A549/5-Fu: IC50 = 1.03 µM) and in vitro enzyme activities (PARP-1: IC50 = 0.40 µM; FTase: IC50 = 0.067 µM). Molecular docking and point mutation assays demonstrated the interaction of compound T9 with key amino acid residues. The compound T9 exhibited potent anti-proliferation and anti-migration capabilities against A549 and A549/5-Fu cells. PCR array and western blot results showed that compound T9 could effectively inhibit EMT-related proteins in A549 and A549/5-Fu cells, thereby inhibiting the development of lung cancer. Importantly, compound T9 could significantly inhibit tumor growth in the A549 xenograft tumor model (TGI = 65.3 %). In conclusion, this study was the first presentation of the concept of dual-target inhibitors of the PARP-1/FTase enzymes. It also provides the basis for further research and development of novel PARP-1/FTase inhibitors.

Reducing blood product wastage through the inter-hospital redistribution of near-outdate inventory.

BACKGROUND: Hospital transfusion services order blood products to satisfy orders and maintain inventory levels during unexpected periods of increased blood demand. Surplus inventory may outdate before being allocated to a recipient. Blood product outdating is the largest contributor to blood wastage. STUDY DESIGN: A province-wide redistribution program was designed and implemented to redistribute near-outdate plasma protein and related blood products from low-usage to high-usage hospitals. Program operations and details are described in this paper. Two transport container configurations were designed and validated for transport of all blood products. A cost-analysis was performed to determine the effectiveness of this redistribution program. RESULTS: A total of 130 hospital transfusion services contributed at least one near-outdate blood product for redistribution between January 2012 and March 2020. These services redistributed 15,499 products through 3412 shipments, preventing the outdating of $17,570,700 CAD worth of product. Program costs were $14,900 for shipping and $30,000 for staffing. Failed time limits or non-compliance with packing configurations resulted in $388,200 worth of blood products (97 shipments containing 816 products) being discarded. Courier transport delays was the most common reason (42/97; 43%) for transport failure. CONCLUSION: Redistributing near-outdate blood products between hospitals is a feasible solution to minimize outdating. Despite heterogeneity of Canadian blood product inventory, all products (each with unique storage and transport requirements) were successfully redistributed in one of two validated and simple containers. Total operation costs of this program were small in comparison to the $17.6 million in savings associated with preventing the discard of outdated products.

Sarcopenia predicts postoperative complications in head and neck cancer: a systematic review and meta-analysis.

PURPOSE: We performed this systematic review and meta-analysis to explore the impact of preoperative sarcopenia on postoperative complication risks after head and neck cancer (HNC) surgery. METHODS: We identified eligible studies by searching Ovid-MEDLINE, Ovid-Embase, EBM Reviews-Cochrane Central Register of Controlled Trials, Web of Science Core Collection, and Scopus. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. RESULTS: Twenty-one studies with a total of 3480 patients met our inclusion criteria. The presence of sarcopenia significantly increased the incidence of overall postoperative complications (OR = 1.72, 95% CI 1.23, 2.41; P = 0.002; I2 = 59%). Subgroup analyses showed a higher risk of postoperative complications in the populations in which sarcopenia was diagnosed with low L3-skeletal muscle index (L3-SMI) or low cross-sectional area of the rectus femoris, but not in the group that sarcopenia was diagnosed with low C3-SMI. Preoperative sarcopenia also substantially increased the risk of severe postoperative complications (OR = 2.26), pharyngocutaneous fistulas (OR = 2.15), free flap-related complications (OR = 1.63), and surgical site infections (OR = 1.84). We also found a tendency toward a higher incidence of wound complications and 30-day mortality in patients with sarcopenia. CONCLUSION: Preoperative sarcopenia is a negative prognostic indicator for postoperative complications in patients with HNC after surgery. To reduce the incidence of postoperative complications and improve poor prognosis, further attention needs to be paid to the evaluation and management of preoperative sarcopenia.

Improving appropriate use of intravenous albumin: results of a single-centre audit and multifaceted intervention.

BACKGROUND: Intravenous albumin has limited indications supported by randomised controlled trials, yet it is often prescribed for indications not supported by evidence. AIM: To reduce unnecessary transfusion of albumin. INTERVENTIONS: Under the leadership of a multidisciplinary quality improvement team, evidence-based recommendations were disseminated in tandem with a new electronic order set, an educational strategy, qualitative interviews with prescribers and a return policy change to reduce wastage. IMPLEMENTATION AND EVALUATION: Interventions were introduced in a staggered fashion. The primary outcome, appropriate use of albumin, was monitored and quantified using pre-intervention and post-intervention audits. Process measures included statistical process run charts of monthly usage of 5% and 25% albumin and wastage. Data on length of stay (hospital and intensive care), new inpatient starts on kidney replacement and mortality were collected as balancing measures. RESULTS: Appropriate albumin usage based on indication increased from 30% to 50% (p<0.0001). There was significantly less overall albumin usage in the post-intervention period compared with the pre-intervention period (negative coefficient, p<0.0001), driven by a major reduction in the utilisation of the 5% formulation (p<0.0001). Overall albumin usage was significantly lower in the post-intervention period, decreasing from 800 to 450 vials per month. The intervention resulted in significantly less wastage (negative coefficient, p=0.017). Mortality, length of stay and new starts on kidney replacement therapy remained constant throughout the study period. CONCLUSION: Improved prescribing of albumin was achieved with a multifaceted approach. Substantial and sustained reductions in usage were achieved without negatively impacting patient-important outcomes. The estimated annual savings for the purchase cost of albumin was CAN $300 000. We provide a structured process for other organisations to optimise their use of albumin.

N6022 attenuates cerebral ischemia/reperfusion injury-induced microglia ferroptosis by promoting Nrf2 nuclear translocation and inhibiting the GSNOR/GSTP1 axis.

Stroke poses a significant risk of mortality, particularly among the elderly population. The pathophysiological process of ischemic stroke is complex, and it is crucial to elucidate its molecular mechanisms and explore potential protective drugs. Ferroptosis, a newly recognized form of programmed cell death distinct from necrosis, apoptosis, and autophagy, is closely associated with the pathophysiology of ischemic stroke. N6022, a selective inhibitor of S-nitrosoglutathione reductase (GSNOR), is a "first-in-class" drug for asthma with potential therapeutic applications. However, it remains unclear whether N6022 exerts protective effects in ischemic stroke, and the precise mechanisms of its action are unknown. This study aimed to investigate whether N6022 mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis and to elucidate the underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) cell model and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to mimic cerebral I/R injury. Our data, both in vitro and in vivo, demonstrated that N6022 effectively protected against I/R-induced brain damage and neurological deficits in mice, as well as OGD/R-induced BV2 cell damage. Mechanistically, N6022 promoted Nrf2 nuclear translocation, enhancing intracellular antioxidant capacity of SLC7A11-GPX4 system. Furthermore, N6022 interfered with the interaction of GSNOR with GSTP1, thereby boosting the antioxidant capacity of GSTP1 and attenuating ferroptosis. These findings provide novel insights, showing that N6022 attenuates microglial ferroptosis induced by cerebral I/R injury through the promotion of Nrf2 nuclear translocation and inhibition of the GSNOR/GSTP1 axis.

Metabolomics of Mice with Type 2 Diabetes and Nonalcoholic Fatty Liver Treated by Acupuncture.

Introduction: To investigate the effects of acupuncture on endogenous metabolites in the liver of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD) mice-based metabolomics. Methods: Proton nuclear magnetic resonance (1H-NMR) metabolomics combined with multivariate statistical analysis and univariate analysis were used to analyze the changes of endogenous metabolites in the liver of mice in each group and to provide new clinical ideas for acupuncture in the treatment of glycolipid metabolism disorders caused by T2DM and NAFLD. Results: After 4 weeks of continuous treatment, fasting blood glucose (FBG), insulin (INS), total cholesterol (TC), and triglyceride (TG) decreased significantly in mice in the acupuncture treatment group (ATG), and the content of liver glycogen increased significantly. Based on 1H-NMR metabolomic analysis, a total of 47 metabolites were identified in the liver of T2DM with NAFLD mice, of which eight metabolites: UDP-N-acetylglucosamine, adenosine, glutamate, isoleucine, ATP, 3-hydroxybutyric acid, NADP+, and leucine were significantly altered by acupuncture treatment. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it is found that acupuncture has an intervention effect on five metabolic pathways, mainly involving amino acid metabolism, energy metabolism, and oxidative stress. Conclusion: Our study shows that acupuncture can regulate the liver metabolism mode of T2DM in NAFLD mice. It can reduce blood glucose and lipid accumulation in the liver, and these findings provide a new idea and theoretical basis for acupuncture in the treatment of diseases related to glucose and lipid metabolism.

Biological Self-Assembled Transmembrane Electron Conduits for High-Efficiency Ammonia Production in Microbial Electrosynthesis.

Usually, CymA is irreplaceable as the electron transport hub in Shewanella oneidensis MR-1 bidirectional electron transfer. In this work, biologically self-assembled FeS nanoparticles construct an artificial electron transfer route and implement electron transfer from extracellular into periplasmic space without CymA involvement, which present similar properties to type IV pili. Bacteria are wired up into a network, and more electron transfer conduits are activated by self-assembled transmembrane FeS nanoparticles (electron conduits), thereby substantially enhancing the ammonia production. In this study, we achieved an average NH4+-N production rate of 391.8 µg·h-1·L reactor-1 with the selectivity of 98.0% and cathode efficiency of 65.4%. Additionally, the amide group in the protein-like substances located in the outer membrane was first found to be able to transfer electrons from extracellular into intracellular with c-type cytochromes. Our work provides a new viewpoint that contributes to a better understanding of the interconnections between semiconductor materials and bacteria and inspires the exploration of new electron transfer chain components.

Voluntary wheel exercise improves glymphatic clearance and ameliorates colitis-associated cognitive impairment in aged mice by inhibiting TRPV4-induced astrocytic calcium activity.

BACKGROUND AND OBJECTIVES: Chronic colitis exacerbates neuroinflammation, contributing to cognitive impairment during aging, but the mechanism remains unclear. The polarity distribution of astrocytic aquaporin 4 (AQP4) is crucial for the glymphatic system, which is responsible for metabolite clearance in the brain. Physical exercise (PE) improves cognition in the aged. This study aims to investigate the protective mechanism of exercise in colitis-associated cognitive impairment. METHODS: To establish a chronic colitis model, 18-month-old C57BL/6 J female mice received periodic oral administration of 1% wt/vol dextran sodium sulfate (DSS) in drinking water. The mice in the exercise group received four weeks of voluntary wheel exercise. High-throughput sequencing was conducted to screen for differentially expressed genes. Two-photon imaging was performed to investigate the function of the astrocytic calcium activity and in vivo intervention with TRPV4 inhibitor HC-067047. Further, GSK1016790A (GSK1), a TRPV4 agonist, was daily intraperitoneally injected during the exercise period to study the involvement of TRPV4 in PE protection. Colitis pathology was confirmed by histopathology. The novel object recognition (NOR) test, Morris water maze test (MWM), and open field test were performed to measure colitis-induced cognition and anxiety-like behavior. In vivo two-photon imaging and ex vivo imaging of fluorescent CSF tracers to evaluate the function of the glymphatic system. Immunofluorescence staining was used to detect the Aß deposition, polarity distribution of astrocytic AQP4, and astrocytic phenotype. Serum and brain levels of the inflammatory cytokines were tested by Enzyme-linked immunosorbent assay (ELISA). The brain TUNEL assay was used to assess DNA damage. Expression of critical molecules was detected using Western blotting. RESULTS: Voluntary exercise alleviates cognitive impairment and anxiety-like behavior in aged mice with chronic colitis, providing neuroprotection against neuronal damage and apoptosis. Additionally, voluntary exercise promotes the brain clearance of Aß via increased glymphatic clearance. Mechanistically, exercise-induced beneficial effects may be attributed, in part, to the inhibition of TRPV4 expression and TRPV4-related calcium hyperactivity, subsequent promotion of AQP4 polarization, and modulation of astrocyte phenotype. CONCLUSION: The present study reveals a novel role of voluntary exercise in alleviating colitis-related cognitive impairment and anxiety disorder, which is mediated by the promotion of AQP4 polarization and glymphatic clearance of Aß via inhibition of TRPV4-induced astrocytic calcium hyperactivity.

A MOF nanoparticle@carbon aerogel integrated photothermal catalytic microreactor for CO2 utilization.

A practical carbon dioxide (CO2) conversion and utilization system shows great potential for ameliorating the greenhouse effect. Herein, an integrated carbon aerogel-based photothermal catalysis microreactor with photothermal conversion, enhanced mass transfer adsorption and a thermal catalytic reactor is designed. As a solar-powered CO2 utilization module, this microreactor can conveniently convert CO2 into economically valuable products without elaborate equipment and operation processes.

Stereotactic Body Radiotherapy for Extracranial Oligometastatic Disease from Head and Neck Primary Cancers: A Systematic Review and Meta-Analysis.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) is increasingly used to treat disease in the oligometastatic (OM) setting due to mounting evidence demonstrating its efficacy and safety. Given the low population representation in prospective studies, we performed a systematic review and meta-analysis of outcomes of HNC patients with extracranial OM disease treated with SBRT. METHODS: A systematic review was conducted with Cochrane, Medline, and Embase databases queried from inception to August 2022 for studies with extracranial OM HNC treated with stereotactic radiotherapy. Polymetastatic patients (>five lesions), mixed-primary cohorts failing to report HNC separately, lack of treatment to all lesions, nonquantitative endpoints, and other definitive treatments (surgery, conventional radiotherapy, and radioablation) were excluded. The meta-analysis examined the pooled effects of 12- and 24-month local control (LC) per lesion, progression-free survival (PFS), and overall survival (OS). Weighted random-effects were assessed using the DerSimonian and Laird method, with heterogeneity evaluated using the I2 statistic and Cochran Qtest. Forest plots were generated for each endpoint. RESULTS: Fifteen studies met the inclusion criteria (639 patients, 831 lesions), with twelve eligible for quantitative synthesis with common endpoints and sufficient reporting. Fourteen studies were retrospective, with a single prospective trial. Studies were small, with a median of 32 patients (range: 6-81) and 63 lesions (range: 6-126). The OM definition varied, with a maximum of two to five metastases, mixed synchronous and metachronous lesions, and a few studies including oligoprogressive lesions. The most common site of metastasis was the lung. Radiation was delivered in 1-10 fractions (20-70 Gy). The one-year LC (LC1), reported in 12 studies, was 86.9% (95% confidence interval [CI]: 79.3-91.9%). LC2 was 77.9% (95% CI: 66.4-86.3%), with heterogeneity across studies. PFS was reported in five studies, with a PFS1 of 43.0% (95% CI: 35.0-51.4%) and PFS2 of 23.9% (95% CI: 17.8-31.2%), with homogeneity across studies. OS was analyzed in nine studies, demonstrating an OS1 of 80.1% (95% CI: 74.2-85.0%) and OS2 of 60.7% (95% CI: 51.3-69.4%). Treatment was well tolerated with no reported grade 4 or 5 toxicities. Grade 3 toxicity rates were uniformly below 5% when reported. CONCLUSIONS: SBRT offers excellent LC and promising OS, with acceptable toxicities in OM HNC. Durable PFS remains rare, highlighting the need for effective local or systemic therapies in this population. Further investigations on concurrent and adjuvant therapies are warranted.

Stereotactic body radiotherapy for distant metastases to the head and neck.

PURPOSE: To report clinical outcomes for patients with metastatic disease to the head and neck (HN) treated with stereotactic body radiation therapy (SBRT). METHODS: A retrospective review of patients treated with SBRT to HN sites from 2012 to 2020 was conducted. Treatment indications included the following: oligometastases, oligoprogression, and control a dominant area of progression (DAP). Kaplan-Meier method was used to estimate local control (LC), regional control (RC), overall survival (OS), and progression-free survival (PFS). Univariable (UVA) and multivariable analyses (MVA) were performed. Grade 3-4 acute and late toxicities were reported by the Common Terminology Criteria for Adverse Events v5.0. RESULTS: Fifty-six patients (58 lesions) were analysed with a median follow-up of 16 months. Primary sites included lung (25.0%), kidney (19.6%), breast (19.6%) and other (35.8%). SBRT indications were as follows: oligometastases (42.9%), oligoprogression (19.6%) and local control of a dominant area of progression (37.5%). Most patients received SBRT to a single neck node (n = 47, 81.0%). Median SBRT dose was 40 Gy (range 25-50 Gy) in five fractions, with a median biologically effective dose (BED10) of 72 Gy (range 37.5-100 Gy). One- and 2-year LC and RC rates were 97.6% and 72.7% as well as 100% and 86.7%, respectively. Median OS was 19.2 months (95% [CI] 14.8-69.4), and median PFS was 7.4 months (95% [CI] 5.2-11.9). The 1-year OS and PFS rates for oligometastases, oligoprogression and DAP were 95.8%, 63.6% and 38.1% (p = 0.0039) as well as 56.5%, 27.3% and 19.1% (p = 0.0004), respectively. On MVA, treatment indication and histology were predictive for OS, while indication and prior systemic therapy were predictive for PFS. Cumulative late grade 3 + toxicity rate was 11.3%, without grade 5 events. CONCLUSION: The use of SBRT for metastatic disease to the HN provided excellent LC rates with low rates of regional failure and an acceptable toxicity profile, highlighting its utility in these patients. Patients with oligometastatic disease had better OS and PFS than others.

Cathepsin B: The dawn of tumor therapy.

Cathepsin B (CTSB) is a key lysosomal protease that plays a crucial role in the development of cancer. This article elucidates the relationship between CTSB and cancer from the perspectives of its structure, function, and role in tumor growth, migration, invasion, metastasis, angiogenesis and autophagy. Further, we summarized the research progress of cancer treatment related drugs targeting CTSB, as well as the potential and advantages of Traditional Chinese medicine in treating tumors by regulating the expression of CTSB.

Molecular imaging reveals the heterogeneous progression of tumor cells and tumor stroma: a practice of FDG PET and FAPI PET in diagnosing PSMA-negative bone metastases of progressive prostate cancer.

Tumors are often with complex and heterogeneous biological processes, such as glycometabolism and fibrosis, which are the main biochemical pathways that determine therapeutic effects. Specifically, this study aims to assess the diagnosing performance of 18F-FDG and 68Ga-FAPI-04 PET for different stages of progressive bone metastases with PSMA-negative pathology. Bone metastatic mouse model of prostate cancer was constructed via intra-bone injection of PSMA-negative prostate cancer PC3 cells. Cellular uptakes of 18F-FDG and 68Ga-FAPI-04 were separately performed on PC3, NIH-3T3 (FAP-positive) and a mixture. 68Ga-PSMA-11, 18F-FDG and 68Ga-FAPI-04 PET/CT imaging were performed at 2, 4 weeks after tumor cell transplantation. Furthermore, PSMA and FAP expression in bone metastases were assessed by immunohistochemistry, and then compared with the imageological findings. On the cellular level, the independent tracer uptake on the basis of glycometabolism and fibrosis was observed. For animal imaging, 68Ga-PSMA-11 imaging showed weak or absent tracer uptake in PSMA-negative bone metastatic lesions. In contrast, 68Ga-FAPI-04 PET of bone metastases had a higher uptake and tumor-to-muscle (T/M) ratio than 18F-FDG PET that was relative steady during the observation, but T/M ratio of fibrosis gradually decreased with increasing tumor growth, which ranged from 5.11 ± 1.26 at 2 weeks to 3.54 ± 0.23 at 4 weeks, revealing the delayed formation of tumor stroma in rapid proliferation. In addition, PET imaging results were corroborated by immunohistochemical assessment. In conclusion, molecular imaging approach revealed the heterogeneous progression of tumor cells and tumor stroma of bone metastasis of prostate cancer, and further confirming the necessity of multi-molecular imaging in cancer imaging.

A multi-scale attention residual-based U-Net network for stroke electrical impedance tomography.

Electrical impedance tomography (EIT), a non-invasive, radiation-free, and convenient imaging technique, has been widely used in the diagnosis of stroke. However, due to soft-field nonlinearity and the ill-posed inverse problem, EIT images always suffer from low spatial resolution. Therefore, a multi-scale convolutional attention residual-based U-Net (MARU-Net) network is proposed for stroke reconstruction. Based on the U-Net network, a residual module and a multi-scale convolutional attention module are added to the concatenation layer. The multi-scale module extracts feature information of different sizes, the attention module strengthens the useful information, and the residual module improves the performance of the network. Based on the above advantages, the network is used in the EIT system for stroke imaging. Compared with convolutional neural networks and one-dimensional convolutional neural networks, the MARU-Net network has fewer artifacts, and the reconstructed image is clear. At the same time, the reduction of noisy artifacts in the MARU-Net network is verified. The results show that the image correlation coefficient of the reconstructed image with noise is greater than 0.87. Finally, the practicability of the network is verified by a model physics experiment.

Ononin promotes radiosensitivity in lung cancer by inhibiting HIF-1α/VEGF pathway.

BACKGROUND: In our previous study, we provided evidence that Astragalus mongholicus Bunge(AM) and its extracts possess a protective capability against radiation-induced damage, potentially mediated through the reduction of reactive oxygen species (ROS) and nitric oxide (NO). However, we were pleasantly surprised to discover during our experimentation that AM not only offers protection against radiation damage but also exhibits a radiation sensitization effect. This effect may be attributed to a specific small molecule present in AM known as ononin. Currently, radiation sensitizers are predominantly found in nitrazole drugs and nanomaterials, with no existing reports on the radiation sensitization properties of ononin, nor its underlying mechanism. PURPOSE: This study aims to investigate the sensitization effect of the small molecule ononin derived from AM on lung cancer radiotherapy, elucidating its specific molecular mechanism of action. Additionally, the safety profile of combining astragalus small molecule ononin with radiation therapy will be evaluated. METHODS: The effective concentration of ononin was determined through cell survival experiments, and the impact of ononin combined with varying doses of radiation on lung cancer cells was observed using CCK-8 and cell cloning experiments. The apoptotic effect of ononin combined with radiation on lung cancer cells was assessed using Hochester staining, flow cytometry, and WB assay. Additionally, WB and immunofluorescence analysis were conducted to investigate the influence of ononin on HIF-1α/VEGF pathway. Furthermore, Molecular Dynamics Simulation was employed to validate the targeted binding ability of ononin and HIF-1α. A lung cancer cell line was established to investigate the effects of knockdown and overexpression of HIF-1α. Subsequently, the experiment was repeated using tumor bearing nude mice and C57BL/6 mouse models in an in vivo study. Tumor volume was measured using a vernier caliper, while HE, immunohistochemistry, and immunofluorescence techniques were employed to observe the effects of ononin combined with radiation on tumor morphology, proliferation, and apoptosis. Additionally, Immunofluorescence was employed to examine the impact of ononin on HIF-1α/VEGF pathway in vivo, and its effect on liver function in mice was assessed through biochemistry analysis. RESULTS: At a concentration of 25 µM, ononin did not affect the proliferation of lung epithelial cells but inhibited the survival of lung cancer cells. In vitro experiments demonstrated that the combination of ononin and radiation could effectively inhibit the growth of lung cancer cells, induce apoptosis, and suppress the excessive activation of the Hypoxia inducible factor 1 alpha/Vascular endothelial growth factor pathway. In vivo experiments showed that the combination of ononin and radiation reduced the size and proliferation of lung cancer tumors, promoted cancer cell apoptosis, mitigated abnormal activation of the Hypoxia inducible factor 1 alpha pathway, and protected against liver function damage. CONCLUSION: This study provides evidence that the combination of AM and its small molecule ononin can enhance the sensitivity of lung cancer to radiation. Additionally, it has been observed that this combination can specifically target HIF-1α and exert its effects. Notably, ononin exhibits the unique ability to protect liver function from damage while simultaneously enhancing the tumor-killing effects of radiation, thereby demonstrating a synergistic and detoxifying role in tumor radiotherapy. These findings contribute to the establishment of a solid basis for the development of novel radiation sensitizers derived from traditional Chinese medicine.

Four case reports of left anterior descending restenosis treated via the internal mammary artery: A literature review.

Objective: To analyse four cases of intervention via the internal mammary artery-anterior descending branch and provide and summarise the clinical treatment experience. Methods: The clinical data of four patients with distal restenosis of a left anterior descending artery (LAD) anastomosis after left internal mammary artery (LIMA)-LAD bypass surgery, who were admitted to the Gansu Institute of Cardiovascular Diseases between March 2013 and April 2022, were retrospectively analysed and reviewed together with the relevant literature. Results: Among the four patients, one was treated with intracoronary stenting via the internal mammary artery route, two were treated with intracoronary drug-coated balloon dilation (one of whom underwent fractional flow reserve [FFR] testing), and two underwent FFR testing (one of whom had a negative test result until the end of the procedure and continued to take medication during follow-up; the other patient had a positive result and further interventions). There were no deaths or postoperative complications in the group, and the patients were followed up for 4 months to 9 years, with good long-term outcomes. Conclusion: Percutaneous coronary intervention (PCI) via the internal mammary artery route is safe and effective, and patients with anastomotic distal stenosis or anastomotic stenosis of LAD bypass anastomosis may be considered for PCI via the internal mammary artery route.

Novel KMT2B gene mutation in MUC4 positive low-grade fibromyxoid sarcoma.

BACKGROUND: Low-grade Fibromyxoid Sarcoma(LGFM)is a rare fibrosarcoma, which mainly occurs in young people and is mostly seen in the trunk and limbs. The tumor is usually FUS-CREB3L2 fusion caused by t(7;16)(q32-34;p11)chromosome translocation, and rarely FUS-CREB3L1 and EWSR1-CREB3L1 fusion. MUC4 diffuse strong positive can be used as a specific index of LGFM. LGFM is similar to Sclerosing Epithelioid Fibrosarcoma(SEF) and may have the same origin. CASE PRESENTATION: We report a case of LGFM in the chest wall. A female who is 59 years old. In 2016, CT showed dense nodule shadow and focal thickening of the left pleura, the patient underwent surgery, Pathological report that low to moderate malignant fibrosarcoma(fibromyxoid type). The CT re-examination in 2021 showed that the tumors on the left chest wall were significantly larger than before. Pathological examination showed the disease is composed of alternating collagen like and mucinous areas. Under high-power microscope, the tumor cells are consistent in shape, spindle or short spindle, and the tumor cells are arranged in bundles. In local areas, the density of tumor cells is significantly increased, mixed with collagen fibers, and small focal SEF appear. The result of immunohistochemistry showed that SMA, Desmin, CD34, STAT6, S100, SOX10, HMB45 and Melan A were negative, EMA was weakly positive, MUC4 was diffuse and strongly positive, and Ki67 index was low (3%). CONCLUSION: Sequencing results showed that MET, EGFR, KMT2B and RET gene were mutated in LGFM, and KMT2B gene had cancer promoting effect, but there was no literature report in LGFM, which may be of certain significance for the diagnosis and treatment of LGFM.