Exploring the role of spinal astrocytes in the onset of hyperalgesic priming signals in acid-induced chronic muscle pain.

Hyperalgesic priming, a form of pain plasticity initiated by initial injury, leads to heightened sensitivity to subsequent noxious stimuli, contributing to chronic pain development in animals. While astrocytes play active roles in modulating synaptic transmission in various pain models, their specific involvement in hyperalgesic priming remains elusive. Here, we show that spinal astrocytes are essential for hyperalgesic priming formation in a mouse model of acid-induced muscle pain. We observed spinal astrocyte activation 4 h after initial acid injection, and inhibition of this activation prevented chronic pain development upon subsequent acid injection. Chemogenetic activation of spinal astrocytes mimicked the first acid-induced hyperalgesic priming. We also demonstrated that spinal phosphorylated extracellular regulated kinase (pERK)-positive neurons were mainly vesicular glutamate transporter-2 positive (Vglut2+) neurons after the first acid injection, and inhibition of spinal pERK prevented astrocyte activation. Furthermore, pharmacological inhibition of astrocytic glutamate transporters glutamate transporter-1 and glutamate-aspartate transporter abolished the hyperalgesic priming. Collectively, our results suggest that pERK activation in Vglut2+ neurons activate astrocytes through astrocytic glutamate transporters. This process eventually establishes hyperalgesic priming through spinal D-serine. We conclude that spinal astrocytes play a crucial role in the transition from acute to chronic pain.

HEMATOLOGY AND BIOCHEMISTRY REFERENCE VALUES IN NESTLING RED KITES (MILVUS MILVUS) IN SHORT-TERM HUMAN CARE IN ENGLAND.

Between the years 2022 and 2023, 62 red kite (Milvus milvus) nestlings were translocated from England to Spain to bolster declining populations in mainland Europe as part of a wider conservation initiative. Health examinations were undertaken by veterinarians ahead of translocation, including examination of hematology and biochemistry parameters from blood samples. This study aimed to establish reference values for these parameters in nestling red kites for use in future translocations or for other clinical purposes. All individuals included in the analysis were clinically healthy at the time of sampling. Biochemical reference intervals were comparable to published values for other Accipitridae, although differences in hematology were noted: PCV was generally lower; and WBC counts higher than (up to triple) those reported for related species of a similar age. It is hypothesized that these differences reflect species variations or the effects of the stress of recent capture on the immune system of the red kites. A Leucocytozoon species was identified on blood smears of six of the red kites. The reference intervals presented in this study are representative of free-living red kite nestlings in England that have recently been captured for conservation translocation purposes.

Beta-Blockers for Secondary Prevention following Myocardial Infarction in Patients Without Reduced Ejection Fraction or Heart Failure: An Updated Meta-Analysis.

AIM: The 2023 ESC guidelines for acute coronary syndrome note that contemporary data are heterogenous regarding beta-blockers (BB) use post-myocardial infarction (MI) in patients without reduced ejection fraction (EF) or heart failure (HF). We aimed to address the heterogeneity in contemporary data around BB post-MI in this population. METHODS: We searched 6 databases from Jan 1, 2000 to Sep 1, 2024 to identify contemporary studies enrolling MI patients without reduced EF (≤40%) or history of HF receiving BB at index MI, and comparing outcomes between BB users and non-users. The primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiac and cerebrovascular events (MACCE) and cardiovascular (CV) mortality. Random-effects meta-analysis was conducted using the restricted maximum likelihood method. RESULTS: There were 24 studies including 290,349 patients enrolled in the contemporary era. Overall, BB use was associated with a significant 11% reduction in all-cause mortality (HR, 0.89; 95% CI, 0.81 to 0.97; I2 = 40%; Figure 1), however with moderate-to-high statistical heterogeneity. Prespecified subgroup analyses demonstrate comparable all-cause mortality (HR, 0.99; 95% CI, 0.94 to 1.06; I2 = 0%), CV mortality (HR, 0.99; 95% CI, 0.85 to 1.15; I2 = 0%), and MACCE (HR, 1.24; 95% CI, 1.01 to 1.52; I2 = 0%) in patients with a 1-year event-free period, defined as no death, recurrent MI, or HF while on BB following index MI. In patients with no event-free period, meta-regression revealed that BB mortality benefits were modified by the study inclusion period (P = 0.01), reflecting a temporal trend of decreasing BB mortality benefits over time. Based on the temporal trend, in patients with preserved EF post-2010, BB exhibited no reduction in all-cause mortality (HR, 0.97; 95% CI, 0.90 to 1.04; I2 = 0%), but a non-significant trend towards increased CV mortality (HR, 1.29; 95% CI, 0.96 to 1.72; I2 = 0%) and a significant increase in MACCE (HR, 1.24; 95% CI, 1.01 to 1.52; I2 = 0%). CONCLUSION: In the contemporary reperfusion era, BB may not confer additional mortality benefits beyond a 1-year event-free period post-MI in patients without reduced EF. Moreover, post-MI BB use was associated with detrimental effects in patients with preserved EF.

Our study aimed to synthesize current evidence around post-myocardial infarction (MI) beta-blocker (BB) use in patients without reduced ejection fraction (EF) or heart failure (HF). We reveal that the mortality benefits of BB are modified by 3 factors, namely an event-free period, study inclusion period, and EF.In patients on BB post-MI with 1 year free of death, recurrent MI, or HF, there may not be additional mortality benefit to continuing the BB.For patients included after 2010, BB did not offer mortality benefits and may even be harmful in those with preserved EF.In contrast to those with preserved EF, patients with mildly reduced EF derive mortality benefits from BB.

Climate Change Projections for Stroke Incidence in Taiwan: Impact of 2 °C and 4 °C Global Warming Level.

OBJECTIVES: This study aimed to establish the exposure-lag-response effect between daily maximum temperature and stroke-related emergency department visits and to project heat-induced stroke impacts under global warming levels (GWL) of 2 °C and 4 °C. METHODS: Stroke-related emergency department visits in Taiwan from 2001 to 2020 were identified using the National Health Insurance Research Database (NHIRD). The study population consisted of 1,100,074 initial stroke cases matched with 2,200,148 non-stroke controls. We employed Distributed Lag Nonlinear Models (DLNM) in a case-crossover study to investigate the association between temperature and stroke. Generalized Estimating Equations (GEE) models with a Poisson function were used to correlate high-temperature exposure with annual stroke incidence rates. Projections were made under two global warming scenarios, GWL 2.0 °C and 4.0 °C, using Coupled General Circulation Model (GCMs). Baseline data from 1995 to 2014 were transformed for spatial distribution at the township level. Geographic Information System (GIS) spatial analysis was performed using Quantum GIS 3.2.0 software. RESULTS: DLNM exposure-lag-response effect revealed that daily maximum temperature exceeding 34 °C significantly increased the risk of stroke-related emergency department visits, particularly for ischemic stroke. Under the 2 °C GWL scenario, the frequency of days with temperatures surpassing 34 °C is projected to rise substantially by the median year of 2042, with a further increase to 92.6 ± 18.0 days/year by 2065 under the 4 °C GWL scenario. Ischemic stroke showed the highest increase in temperature-related incidence rates, notably rising from 7.80% under the GWL 2 °C to 36.06% under the GWL 4 °C. Specifically, the annual temperature-related incidence rate for ischemic stroke is expected to increase significantly by 2065. Regions such as Taichung, Hsinchu, Yilan, and Taitung demonstrated pronounced changes in heat-related ischemic stroke incidence under the GWL 4 °C. CONCLUSIONS: The findings emphasize the importance of addressing temperature-related stroke risks, particularly in regions projected to experience significant temperature increases. Effective mitigation strategies are crucial to reduce the impact of rising temperatures on stroke incidence and safeguard public health.

Psychosocial Phenotypes of Older Adults With Pain and Their Associated Clinical Outcomes.

A comprehensive understanding of the patterns of psychosocial characteristics in older adults with pain is needed. Our objectives were to (1) identify psychosocial phenotypes (comprising depression, anxiety, affect, self-realization, resilience, and social participation) among older adults with pain and (2) compare pain characteristics, physical health, and cognition among the identified phenotypes. Using cross-sectional 2021 data from the National Health and Aging Trends Study, we performed latent class analysis to identify four psychosocial phenotypes of older adults with pain (N = 1903): Favorable (best psychosocial characteristics, 67.7%), Adverse (worst psychosocial characteristics, 4.9%), Intermediate (moderate scores on psychosocial variables, 12.6%), and Compensated (moderate scores with relatively high self-realization and resilience, 14.9%). Phenotypes with less psychosocial adversity had generally better clinical outcomes. Future research should explore precision pain management interventions in older adults based on their psychosocial phenotypes, longitudinal trajectories of phenotypes, and technology-based, point-of-care clinical insights for pain management.

MRI Indices of Glymphatic Function Correlate With Disease Duration in Idiopathic Intracranial Hypertension.

BACKGROUND: The glymphatic system represents an extravascular network of astrocytic channels responsible for interstitial fluid and solute transit through the brain parenchyma. Its dysfunction has been considered as a possible cause of idiopathic intracranial hypertension (IIH). METHODS: We enrolled participants with active IIH, treated or cured IIH, and controls. The active IIH group was divided into untreated participants with recently developed (<6 mo) and chronic (6+ mo) disease. Glymphatic function was assessed using diffusion tensor imaging along the paravascular space (DTI-ALPS) to generate an ALPS-index, hypothesized to measure glymphatic function. Participants were imaged before lumbar puncture (LP) if IIH was suspected and following LP when possible. RESULTS: ALPS indices were higher in participants with chronically present, active IIH than in those either with recently developed IIH or control participants. ALPS-indices correlated with papilledema but did not correlate significantly with age, BMI, or intracranial pressure (ICP). CONCLUSIONS: Our findings suggest that DTI-ALPS-indices of glymphatic function may be influenced by the chronicity of intracranial hypertension but do not support the hypothesis that glymphatic dysfunction causes IIH. Though these findings are preliminary, glymphatic imaging may be a useful radiographic biomarker in IIH.

Long-term exposure to NO2 and PM2.5 and the occurrence of chronic kidney disease among patients with type 2 diabetes in Taiwan.

BACKGROUND: Individuals diagnosed with type 2 diabetes (T2D) frequently exhibit chronic kidney disease (CKD) which may be caused by environmental hazards such as exposure to air pollutants. However, limited research has explored the effects of prolonged exposure to air pollutants on CKD development in this population. This study examines the relationship between long-term exposure to air pollutants and CKD incidence in a longitudinal cohort of individuals with type 2 diabetes in Taiwan METHODS: Between 2003 and 2005, we recruited 1316 T2D patients (693 females [52.66 %]; mean age 56.16 ± 8.97 years). Patients were followed until December 31, 2012, with at least two clinical visits. Baseline demographics, medical history, and biomarker levels were collected. The development of CKD was determined by eGFR level < 60 mL/min/1.73 m2. Monthly averages of nitrogen dioxide (NO2) and fine particulate matter [PM ≤ 2.5 µm in aerodynamic diameter (PM2.5)] were acquired from 72 ambient air monitoring stations. The kriging method was employed to estimate the exposure levels to PM2.5, NO2, temperature, and relative humidity in the participants' residential areas. Cox regression with time-dependent covariates regression was applied to assess the impact of long-term exposure to air pollutants and CKD risk. RESULTS: Of 992 patients with normal renal function at baseline, 411 (41.43 %) experienced CKD occurrence over a median follow-up period of 5.45 years. The incidence of CKD was 93.96 cases per 1000 person-years. In multivariable adjusted models, patients exposed to PM2.5 levels above the third quartile of (>33.44 µg/m3) and NO2 levels above the fourth quartile (>22.55 ppb) were found to have an increased risk of CKD occurrence compared to lower exposure levels. CONCLUSIONS: This longitudinal study highlights the increased risk of CKD in individuals with type 2 diabetes due to prolonged exposure to NO2 and PM2.5, emphasizing the need for tailored air quality management strategies for this high-risk population.

Jing-Si Herbal Tea Suppresses H2O2-Instigated Inflammation and Apoptosis by Inhibiting Bax and Mitochondrial Cytochrome C Release in HIG-82 Synoviocytes.

Inflammation is an intrinsic protective mechanism against various forms of cellular injuries in humans; however, its undesired activation results in tissue damage and cell death. The onset of chronic inflammation and oxidative stress are the key characteristics of autoimmune inflammatory diseases such as rheumatoid arthritis (RA), for which an effective treatment is yet to be developed. Therefore, in this study, we investigated the protective effects and molecular mechanisms of a novel herbal preparation, Jing-Si herbal tea (JS), against H2O2-induced inflammation and cellular damage in HIG-82 synoviocytes. We found that JS did not show any significant alterations in cell viability at <188 µg/mL; however, a cytotoxic effect was observed at 188-1883 µg/mL concentrations tested. We found that expressions of inflammation associated extracellular matrix (ECM)-degrading proteases MMP-13, ADAMTS-2, -8, and -17 were abnormally enhanced under H2O2-induced pathological oxidative stress (ROS) in HIG-82 cells. Interestingly, JS treatment not only reduced the ROS levels but also significantly repressed the protein expressions of collagen degrading proteases in a dose-dependent manner. Treatment with JS showed enhanced cell viability against H2O2-induced toxic ROS levels. The expressions of cell protective aggrecan, Collagen II, and Bcl-2 were increased, whereas MMP-13, ADAMTS-2, Cytochrome C, and cleaved Caspase 3 were decreased by JS under inflammatory agents H2O2, MIA, LPS, and TNF-α treatment, respectively, in HIG-82 cells. Interestingly, the cytoprotective effect of JS treatment was attributed to a decreased mitochondrial localization of Bax and a reduction of Cytochrome C release into the cytoplasm of H2O2-treated HIG-82 cells. Collectively, our results suggest a novel protective mechanism of JS for RA treatment, which could be potentially applied as a complementary treatment or as an alternative therapeutic approach to mitigate inflammatory diseases.

PROTAC-DB 3.0: an updated database of PROTACs with extended pharmacokinetic parameters.

Proteolysis-targeting chimera (PROTAC) is an emerging therapeutic technology that leverages the ubiquitin-proteasome system to target protein degradation. Due to its event-driven mechanistic characteristics, PROTAC has the potential to regulate traditionally non-druggable targets. Recently, AI-aided drug design has accelerated the development of PROTAC drugs. However, the rational design of PROTACs remains a considerable challenge. Here, we present an updated online database, PROTAC-DB 3.0. In this third version, we have expanded the database to include 6111 PROTACs (87% increase compared to the 2.0 version). Additionally, the database now contains 569 warheads (small molecules targeting the protein), 2753 linkers, and 107 E3 ligands (small molecules recruiting E3 ligases). The number of target-PROTAC-E3 ternary complex structures has also increased to 959. Recognizing the importance of druggability in PROTAC design, we have incorporated pharmacokinetic data to PROTAC-DB 3.0. To enhance user experience, we have added features for sorting based on molecular similarity and literature publication date. PROTAC-DB 3.0 is accessible at http://cadd.zju.edu.cn/protacdb/.

Interactive effect between transcranial focused ultrasound and transcranial magnetic stimulation on human motor cortex.

OBJECTIVE: Transcranial focused ultrasound (TUS) can suppress human motor cortical excitability. However, it is unclear whether the TUS may interact with transcranial magnetic stimulation (TMS) when they co-delivered in multiple trials. METHODS: Nineteen subjects received three different TUS-TMS co-stimulation protocols to the motor cortex including concurrent stimulation (TUS-TMS-C), separated stimulation (TUS-TMS-S), and TMS only. In each condition, two runs of 30 stimulation trials were conducted with a five-minute rest between runs. Motor-evoked potentials (MEP) were recorded during stimulation and at 0, 10, 20, and 30 min after stimulation. The MEP amplitudes after intervention were normalized to the mean pre-intervention MEP amplitude and expressed as MEP ratios. An additional test with TUS alone was applied to all participants to assess whether TUS itself can elicit after-effects. RESULTS: There were no significant after-effects of all three interventions on MEP ratios. However, 11 subjects who showed online inhibition (OI + ) during the TUS-TMS-C protocol, defined as having MEP ratio less than 1 during TUS-TMS-C, showed significant MEP suppression at 10, 20 and 30 min after TUS-TMS-C. In 8 subjects did not show online inhibition (OI-), defined as having MEP ratios greater than 1 during TUS-TMS-C, showed no significant inhibitory after-effects. OI + and OI- status did not change in a follow-up repeat TUS-TMS-C test. TUS alone did not generate inhibitory after-effects in either OI + or OI- participants. CONCLUSIONS: Our results showed that co-delivery of TUS and TMS can elicit inhibitory after-effect in subjects who showed online inhibition, suggesting that TUS and TMS may interact with each other to produce plasticity effects. SIGNIFICANCE: TUS and TMS may interact with each other to modulate cortical excitability.

A wearable adaptive penile rigidity monitoring system for assessment of erectile dysfunction.

Erectile dysfunction (ED) is a prevalent type of sexual dysfunction, and continuous monitoring of penile tumescence and rigidity during spontaneous nocturnal erections is crucial for its diagnosis and classification. However, the current clinical standard device, limited by its active mechanical load, is bulky and nonwearable and strongly interferes with erections, which compromises both monitoring reliability and patient compliance. Here, we report a wearable adaptive rigidity monitoring (WARM) system that employs a measurement principle without active loads, allowing for the assessment of penile tumescence and rigidity through a specifically designed elastic dual-ring sensor. The dual-ring sensor, comprising two strain-sensing rings with distinct elastic moduli, provides high resolution (0.1%), robust mechanical and electrical stability (sustaining over 1000 cycles), and strong interference resistance. An integrated flexible printed circuit (FPC) collects and processes sensing signals, which are then transmitted to the host computer via Bluetooth for ED assessment. Additionally, we validated the WARM system against the clinical standard device using both a penile model and healthy volunteers, achieving high consistency. Furthermore, the system facilitates the continuous evaluation of penile erections during nocturnal tumescence tests with concurrent sleep monitoring, demonstrating its ability to minimize interference with nocturnal erections. In conclusion, the WARM system offers a fully integrated, wearable solution for continuous, precise, and patient-friendly measurement of penile tumescence and rigidity, potentially providing more reliable and accessible outcomes than existing technologies. Erectile dysfunction (ED) is a prevalent sexual dysfunction, and continuous monitoring of penile tumescence and rigidity during spontaneous nocturnal erections is crucial for its diagnosis and classification. However, the current clinical standard device, limited by its active mechanical load, is bulky, nonwearable, and creates pronounced interference with erections, which compromises both monitoring reliability and patient compliance. Here, we report a wearable adaptive rigidity monitoring (WARM) system (Fig. 1a) that employs a measurement principle without active loads (Fig. 1b), allowing for the assessment of penile tumescence and rigidity through a specifically designed elastic dual-ring sensor. The dual-ring sensor, comprising two strain-sensing rings with distinct elastic moduli, provides high resolution (0.1%), robust mechanical and electrical stability (sustaining over 1000 cycles), and strong interference resistance. Additionally, we validate the WARM system against the clinical standard device using both a penile model and healthy volunteers, achieving high consistency. Furthermore, the system facilitates the continuous evaluation of penile erections during nocturnal tumescence tests, with concurrent sleep monitoring, demonstrating its ability to minimize interference with nocturnal erections (Fig. 1c). In conclusion, the WARM system offers a fully integrated, wearable solution for continuous, precise, and patient-friendly measurement of penile tumescence and rigidity, potentially providing more reliable and accessible outcomes than those from existing technologies.

Differential utilization of thyroid lobectomy after the 2015 American Thyroid Association guideline update.

Background: The 2015 American Thyroid Association (ATA) guidelines added thyroid lobectomy (TL) as the appropriate treatment for low-risk differentiated thyroid cancer (DTC). We aimed to investigate the population-level factors that influence the utilization of TL. Methods: The Surveillance, Epidemiology and End Results (SEER) database was queried for all DTC patients fitting low-risk criteria as defined by the ATA. Trends in total thyroidectomy (TT) and TL were identified using a Cochrane-Armitage test. Multivariable logistic regression identified patient and socioeconomic characteristics associated with TL, and difference-in-difference analysis was used to control for secular trends over time. Results: A total of 43,526 patients with low-risk DTC were identified in the SEER database; 39,411 pre-2015 and 4115 post-2015. After 2015, TT continued to outnumber TL (76.2% vs 23.8%), although the rate of TL increased significantly (11.6% to 23.8%, P < 0.001). However, difference-in-difference analysis found that age > 55 (OR 1.11, 95% CI 1.01-1.19, P < 0.001) and rurality (OR 1.16, 95% CI 1.05-1.28, P < 0.001) were independently associated with TT. TL was associated with T1 disease (OR 1.11, 95% CI 1.04-1.19, P = 0.001). Conclusion: Although the 2015 ATA guideline update led to an increase in TL for low-risk DTC, most patients still underwent TT. Age and neighborhood significantly impact the odds of receiving guideline-appropriate TL for low-risk DTC, especially for T2 disease.

B4GALT1-dependent galectin-8 binding with TGF-ß receptor suppresses colorectal cancer progression and metastasis.

Transforming growth factor (TGF)-ß signaling is critical for epithelial-mesenchymal transition (EMT) and colorectal cancer (CRC) metastasis. Disruption of Smad-depednent TGF-ß signaling has been shown in CRC cells. However, TGF-ß receptor remains expressed on CRC cells. Here, we investigated whether the cooperation between tumor-associated N-glycosylation and a glycan-binding protein modulated the TGF-ß-driven signaling and metastasis of CRC. We showed that galectin-8, a galactose-binding lectin, hampered TGF-ß-induced EMT by interacting with the type II TGF-ß receptor and competing with TGF-ß binding. Depletion of galectin-8 promoted the migration of CRC cells by increasing TGF-ß-receptor-mediated RAS and Src signaling, which was attenuated after recombinant galectin-8 treatment. Treatment with recombinant galectin-8 also induces JNK-dependent apoptosis in CRC cells. The anti-migratory effect of galectin-8 depended on ß4-galactosyltransferase-I (B4GALT1), an enzyme involved in N-glycan synthesis. Increased B4GALT1 expression was observed in clinical CRC samples. Depletion of B4GALT1 reduced the metastatic potential of CRC cells. Furthermore, inducible expression of galectin-8 attenuated tumor development and metastasis of CRC cells in an intra-splenic injection model. Our results thus demonstrate that galectin-8 alters non-canonical TGF-ß response in CRC cells and suppresses CRC progression.

Evaluation of the protective effects of chondroitin sulfate oligosaccharide against osteoarthritis via inactivation of NLRP3 inflammasome by in vivo and in vitro studies.

Osteoarthritis (OA) is the most prevalent degenerative arthritis disease linked to aging, obesity, diet, and accumulation of octacalcium phosphate (OCP) crystals in joints. Current research has focused on inflammation and chondrocytes apoptosis as underlying OA mechanisms. Inflammatory cytokines like IL-1ß activate matrix metalloproteinase-13 (MMP-13) and aggrecanase (the member of A Disintegrin and Metalloproteinase with Thrombospondin motifs family, ADAMTS), leading to cartilage matrix degradation. The NLRP3 inflammasome also contributes to OA pathogenesis by maturing IL-1ß. Natural products like chondroitin sulfate oligosaccharides (oligo-CS) show promise in OA treatment by inhibiting inflammation. Our study evaluates the protective effects of oligo-CS against OA by targeting NLRP3 inflammation. Stimulating human SW1353 chondrocytes and human mononuclear macrophage THP-1 cells with OCP showed increased NLRP3 inflammation initiation, NF-κB pathway activation, and the production of inflammatory cytokines (IL-1ß, IL-6) and the metabolic index (MMP-13, ADAMTS-5), leading to cartilage matrix degradation. However, oligo-CS treatment significantly reduced inflammation. In a 28-day in vivo study with C57BL/6 female mice, OCP was injected into their right knee and oligo-CS was orally administered. The OCP group exhibited significant joint space narrowing and chondrocyte loss, while the oligo-CS group maintained cartilage integrity. Oligo-CS groups also regulated gut microbiota composition to a healthier state. Taken together, our findings suggest that oligo-CS can be considered as a protective compound against OA.

HDAC7 is a potential therapeutic target in acute erythroid leukemia.

Acute erythroleukemia (AEL) is a rare subtype of acute myeloid leukemia with a poor prognosis. In this study, we established a novel murine AEL model with Trp53 depletion and ERG overexpression. ERG overexpression in Trp53-deficient mouse bone marrow cells, but not in wild-type bone marrow cells, leads to AEL development within two months after transplantation with 100% penetrance. The established mouse AEL cells expressing Cas9 can be cultured in vitro, induce AEL in vivo even in unirradiated recipient mice, and enable efficient gene ablation using the CRISPR/Cas9 system. We also confirmed the cooperation between ERG overexpression and TP53 inactivation in promoting the growth of immature erythroid cells in human cord blood cells. Mechanistically, ERG antagonizes KLF1 and inhibits erythroid maturation, whereas TP53 deficiency promotes proliferation of erythroid progenitors. Furthermore, we identified HDAC7 as a specific susceptibility in AEL by the DepMap-based two-group comparison analysis. HDAC7 promotes the growth of human and mouse AEL cells both in vitro and in vivo through its non-enzymatic functions. Our study provides experimental evidence that TP53 deficiency and ERG overexpression are necessary and sufficient for the development of AEL and highlights HDAC7 as a promising therapeutic target for this disease.

Synergistic effect of GN-Ag NPs enhancing the efficient catalytic degradation of MB and CR by PDA@MMT composite hydrogel.

A novel composite hydrogel prepared from polyacrylamide (PAM), polydopamine-modified montmorillonite (PDA@MMT), graphene and hydroxypropyl cellulose (HPC), loaded with Ag NPs, was prepared for the catalytic degradation of methylene blue (MB) and Congo red (CR) using in situ reduction. HPC significantly enhanced the dispersion of PDA@MMT within the hydrogel, endowing the hydrogel with excellent mechanical properties, with stress and strain of 1773 kPa and 4005 %, and elastic modulus and toughness of 43.4 kPa and 29.54 MJ/m3, respectively. The introduction of graphene (GN) increased the rate of electron transfer during the catalytic process and significantly improved the catalytic efficiency, with catalytic rate constants of 1.360 and 0.803 min-1 for MB and CR at 20 °C, respectively. The hydrogels were endowed with excellent antimicrobial properties due to the introduction of Ag NPs. In the future, this hydrogel is expected to play an important role in environmental pollution control.

Outcome and Survival Analysis of Multicenter Lung Metastasectomy for Primary Liver Tumor with Pulmonary Metastasis.

Oligopulmonary metastases from primary liver tumors are typically treated surgically. We evaluated the clinical outcomes after lung metastasectomy in patients with pulmonary metastases from primary liver tumors. We retrospectively enrolled 147 consecutive patients with lung metastases from liver cancer who had undergone pulmonary metastasectomies at three medical centers between February 2007 and December 2020. All patients were pathologically confirmed to have lung metastases from liver cancer. Among the 147 patients, 110, 17, and 20 initially underwent surgical resection, radiofrequency ablation, and transcatheter arterial embolization, respectively. The 5-year overall survival (OS) in the study cohort was 22%. Univariate analysis revealed four factors associated with better OS: surgical resection as the initial primary liver tumor treatment (p = 0.004), a disease-free interval exceeding 12 months after the initial liver surgery (p = 0.036), a lower Model for End-Stage Liver Disease (MELD)-Na score (≤20) for liver cirrhosis (p = 0.044), and the absence of local liver tumor recurrence at the time of pulmonary metastasectomy (p = 0.004). Multivariate analysis demonstrated that surgical resection as the initial primary liver tumor treatment and lower MELD-Na scores significantly correlated with better OS. Our findings can assist thoracic surgeons in selecting suitable patients for surgery and predicting surgical outcomes.