Decreased consumption of natural rewards in rhesus monkeys with prolonged methamphetamine abstinence.

Rationale: Relapse to drug use is a major clinical challenge in the treatment of addictive disorders, including psychostimulant use and may be exacerbated by reduced sensitivity to natural, non-drug reward. Given the relatively limited set of outcomes, and short withdrawal time in rodent studies, we conducted a more detailed assessment of the response to natural rewards in methamphetamine (METH) naive versus exposed monkeys during long-term abstinence. Methods: This study introduced an improved sucrose preference test (iSPT) to assess natural reward seeking and consumption in monkeys with long-term abstinence after methamphetamine (METH) use. The test was administered to sixteen naive monkeys and five METH exposed monkeys that had been abstinent for at least 3 months. Results: METH exposed monkeys showed a lower sucrose preference score in both the iSPT (z = -2.10, p = 0.036) and the sucrose preference test (z = -2.61, p = 0.009). The sucrose preference score was significantly correlated with the latency of the establishment of stable sucrose-preference (r = -0.76, df = 46, p < 0.001) but not with the other variables. Furthermore, water-sucrose switch latency and switch times were significantly negatively correlated (r = -0.50, df = 20, p = 0.02). Conclusion: These results show reductions in natural reward consumption during long-term methamphetamine abstinence.

A 3D-Printed helmet for precise and repeatable neuromodulation targeting in awake non-human primates.

The application of non-invasive brain stimulation (NIBS) in non-human primates (NHPs) is critical for advancing understanding of brain networks and developing treatments for neurological diseases. Improving the precision of targeting can significantly enhance the efficacy of these interventions. Here, we introduce a 3D-printed helmet designed to achieve repeatable and precise neuromodulation targeting in awake rhesus monkeys, eliminating the need of head fixation. Imaging studies confirmed that the helmet consistently targets the primary motor cortex (M1) with a margin of error less than 1 mm. Evaluations of stimulation efficacy revealed high resolution and stability. Additionally, physiological evaluations under propofol anesthesia showed that the helmet effectively facilitated the generation of recruitment curves for motor area, confirming successful neuromodulation. Collectively, our findings present a straightforward and effective method for achieving consistent and precise NIBS targeting in awake NHPs, potentially advancing both basic neuroscience research and the development of clinical neuromodulation therapies.

Effects of IL-6R Expression on IL-6/STAT3/HIF-1α Signaling Pathway in a Mouse Model of Parkinson's Disease with Type 2 Diabetes Co-Morbidity.

BACKGROUND: More and more evidence has shown the process of Parkinson's disease (PD). Probably, inflammation exerts a crucial role between them. Therefore, the aim of this study was to analyze the impact of interleukin-6 receptor (IL-6R) expression on the IL-6/signal transducer and activator of transcription 3 (STAT3)/hypoxia-inducible factor-1α (HIF-1α) inflammatory signaling pathway within a mouse model of PD with type 2 diabetes mellitus (T2DM) as co-morbidity. METHODS: We chose healthy wild-type C57BL/6J male mice at the age of 10 weeks to prepare a mouse model of PD with T2DM co-morbidity. Adeno-associated virus (AAV) overexpressing IL-6R or AAV IL-6R-shRNA genes were injected into the substantia nigra (SN) of the mice. The behavioral indices of the pole test were used for examining the motor function of the mice. Using immunofluorescence analysis, the impacts of IL-6R on the level of tyrosine hydroxylase (TH) and anti-ionized calcium-binding adaptor molecule 1 (IBA-1) on dopaminergic neurons and microglia were examined. Additionally, enzyme-linked immunosorbent assay (ELISA) was adopted for determining the expressions of HIF-1α and inflammatory cytokines like tumor necrosis factor-α (TNF-α), IL-1ß, IL-6, and IL-4 in the serum. In this study, the protein expression levels of TH, α-Synuclein (α-Syn), IBA-1, IL-6, IL-6R, phosphorylated and total signal transducer and activator of transcription 3 (p-STAT3 (Tyr705) and STAT3) and HIF-1α in the SN were tested via western blotting. To ascertain the mRNA expressions of TNF-α, IL-1ß, IL-6, IL-4, and HIF-1α, we used quantitative Real-Time Polymerase Chain Reaction (RT-qPCR). RESULTS: IL-6R-shRNA treatment could markedly shorten the total time of PD in the T2DM co-morbidity mouse model based on the pole test results, reverse the decrease in TH-positive neurons stimulated by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), and lower the activation of microglia (all p < 0.05). Further, IL-6R-shRNA treatment hindered the expression of IL-6, p-STAT3 (Tyr705), and HIF-1α in the SN, lowered the levels of TNF-α, IL-1ß, IL-6, IL-4, and HIF-1α in the serum, and mRNA expressions of TNF-α, IL-1ß, IL-6, and HIF-1α in the SN (all p < 0.05). In contrast, IL-6R overexpression reduced TH levels, upregulated the level of IBA-1, IL-6, p-STAT3 (Tyr705), and HIF-1α, increased the level of IL-1ß, TNF-α, IL-6, IL-4, and HIF-1α (all p < 0.05) in the serum and SN in the PD mouse model with T2DM as a co-morbidity. CONCLUSIONS: PD progression with T2DM as a co-morbidity can be boosted by AAV IL-6R-overexpression through upregulation of the IL-6/STAT3/HIF-1α axis. Conversely, AAV IL-6R-shRNA treatment suppressed the IL-6/STAT3/HIF-1α pathway and alleviated neuroinflammation, thus weakening the development of PD with T2DM as a co-morbidity.

Risk factors analysis and prediction model construction for severe pneumonia in older adult patients.

Objective: Pneumonia is a common and serious infectious disease that affects the older adult population. Severe pneumonia can lead to high mortality and morbidity in this group. Therefore, it is important to identify the risk factors and develop a prediction model for severe pneumonia in older adult patients. Method: In this study, we collected data from 1,000 older adult patients who were diagnosed with pneumonia and admitted to the intensive care unit (ICU) in a tertiary hospital. We used logistic regression and machine learning methods to analyze the risk factors and construct a prediction model for severe pneumonia in older adult patients. We evaluated the performance of the model using accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and calibration plot. Result: We found that age, comorbidities, vital signs, laboratory tests, and radiological findings were associated with severe pneumonia in older adult patients. The prediction model had an accuracy of 0.85, a sensitivity of 0.80, a specificity of 0.88, and an AUC of 0.90. The calibration plot showed good agreement between the predicted and observed probabilities of severe pneumonia. Conclusion: The prediction model can help clinicians to stratify the risk of severe pneumonia in older adult patients and provide timely and appropriate interventions.

Characterization of Gut Microbiota in Rats and Rhesus Monkeys After Methamphetamine Self-administration.

Methamphetamine (MA) is one of the most abused drugs globally, but the mechanism of its addiction remains unclear. Several animal studies have shown that the gut microbiota (GM) influences addictive behaviors, but the pattern of GM changes during addiction in animals of different species remains unclear. The aim of this study was to explore the association between dynamic changes in GM and MA self-administration acquisition among two classical mammals, rhesus monkeys (Macaca mulatta) and rats, MA self-administration models. Male Sprague-Dawley rats and male rhesus monkeys were subjected to classical MA self-administration training, and fecal samples were collected before and after MA self-administration training, respectively. 16S rRNA sequencing was used for GM analyses. We found that GM changes were more pronounced in rats than in rhesus monkeys, as evidenced by more GM taxa producing significant differences before and after MA self-administration training in rats than in monkeys. We also found that the expression of the genus Clostridia_vadinBB60_group significantly decreased after MA self-administration training in both rats and rhesus monkeys. Lactobacillus changes were significantly negatively correlated with total MA uptake in rats (Pearson R = - 0.666, p = 0.035; Spearman R = - 0.721, p = 0.023), whereas its change was also highly negatively correlated with total MA uptake in rhesus monkeys (Pearson R = - 0.882, p = 0.118; Spearman R = - 1.000, p = 0.083), although this was not significant. These findings suggest that MA causes significant alterations in GM in both rhesus monkeys and rats and that the genus Lactobacillus might be a common therapeutic target for MA uptake prevention across the species.

Non-Line-of-Sight Imaging and Vibrometry Using a Comb-Calibrated Coherent Sensor.

Non-line-of-sight (NLOS) imaging has the ability to reconstruct hidden objects, allowing a wide range of applications. Existing NLOS systems rely on pulsed lasers and time-resolved single-photon detectors to capture the information encoded in the time of flight of scattered photons. Despite remarkable advances, the pulsed time-of-flight LIDAR approach has limited temporal resolution and struggles to detect the frequency-associated information directly. Here, we propose and demonstrate the coherent scheme-frequency-modulated continuous wave calibrated by optical frequency comb-for high-resolution NLOS imaging, velocimetry, and vibrometry. Our comb-calibrated coherent sensor presents a system temporal resolution at subpicosecond and its superior signal-to-noise ratio permits NLOS imaging of complex scenes under strong ambient light. We show the capability of NLOS localization and 3D imaging at submillimeter scale and demonstrate NLOS vibrometry sensing at an accuracy of dozen Hertz. Our approach unlocks the coherent LIDAR techniques for widespread use in imaging science and optical sensing.

The effect of city reputation on Chinese corporate risk-taking.

City reputation is a valuable asset for the local economy and firms in the contemporary society. However, the impact of city reputation on micro-level firms has been largely overlooked by the literature. This paper uses the National Civilized City (NCC) policy in China as a quasi-natural experiment to enhance city reputation. We employ the DID approach to investigate the relationship between city reputation and corporate risk-taking. The result shows that corporate risk-taking significantly increases following the NCC policy adoption. Moreover, information asymmetry can strengthen the positive impact of city reputation on corporate risk-taking. Channel tests show that city reputation improves financial condition and decreases default risk, leading to improved risk-taking tolerance. Overall, our paper indicates that city reputation is an important mechanism to improve corporate financial performance, providing empirical evidence for local governments to pursue the NCC title.

Comparative transcriptomic evidence of physiological changes and potential relationships in vertebrates under different dormancy states.

Dormancy represents a fascinating adaptive strategy for organisms to survive in unforgiving environments. After a period of dormancy, organisms often exhibit exceptional resilience. This period is typically divided into hibernation and aestivation based on seasonal patterns. However, the mechanisms by which organisms adapt to their environments during dormancy, as well as the potential relationships between different states of dormancy, deserve further exploration. Here, we selected Perccottus glenii and Protopterus annectens as the primary subjects to study hibernation and aestivation, respectively. Based on histological and transcriptomic analysis of multiple organs, we discovered that dormancy involved a coordinated functional response across organs. Enrichment analyses revealed noteworthy disparities between the two dormant species in their responses to extreme temperatures. Notably, similarities in gene expression patterns pertaining to energy metabolism, neural activity, and biosynthesis were noted during hibernation, suggesting a potential correlation between hibernation and aestivation. To further explore the relationship between these two phenomena, we analyzed other dormancy-capable species using data from publicly available databases. This comparative analysis revealed that most orthologous genes involved in metabolism, cell proliferation, and neural function exhibited consistent expression patterns during dormancy, indicating that the observed similarity between hibernation and aestivation may be attributable to convergent evolution. In conclusion, this study enhances our comprehension of the dormancy phenomenon and offers new insights into the molecular mechanisms underpinning vertebrate dormancy.

DPY30 knockdown suppresses colorectal carcinoma progression via inducing Raf1/MST2-mediated apoptosis.

Colorectal Carcinoma (CRC) is one of the most common malignant tumors of the digestive tract, with a high mortality rate. DPY30 is one of the core subunits of the histone methyltransferase complex, which was involved in many cancer processes. However, the role of DPY30 in the occurrence and progression of CRC remains unclear. In this study, we sought to evaluate the role and mechanism of DPY30 in CRC cells apoptosis. Here, we identified that knockdown of DPY30 significantly inhibited the HT29 and HCT116 cells proliferation in vitro. Moreover, the knockdown of DPY30 significantly increased the apoptosis rate and promoted the expression of apoptosis-related proteins in CRC cells. Meanwhile, DPY30 knockdown promoted CRC cells apoptosis through endogenous programmed death and in a caspase activation-dependent manner. Furthermore, RNA-seq analysis revealed that the action of DPY30 is closely related to the apoptosis biological processes, and screened its potential effectors Raf1. Mechanistically, DPY30 downregulation promotes MST2-induced apoptosis by inhibiting Raf1 transcriptional activity through histone H3 lysine 4 trimethylation (H3K4me3). In vivo experiments showed that DPY30 was correlated with Raf1 in nude mouse subcutaneous xenografts tissues significantly. Clinical colorectal specimens further confirmed that overexpression of DPY30 in malignant tissues was significantly correlated with Raf1 level. The vital role of the DPY30/Raf1/MST2 signaling axis in the cell death and survival rate of CRC cells was disclosed, which provides potential new targets for early diagnosis and clinical treatment of CRC.

GPR39 regulated spinal glycinergic inhibition and mechanical inflammatory pain.

G protein-coupled receptor 39 (GPR39) senses the change of extracellular divalent zinc ion and signals through multiple G proteins to a broad spectrum of downstream effectors. Here, we found that GPR39 was prevalent at inhibitory synapses of spinal cord somatostatin-positive (SOM+) interneurons, a mechanosensitive subpopulation that is critical for the conveyance of mechanical pain. GPR39 complexed specifically with inhibitory glycine receptors (GlyRs) and helped maintain glycinergic transmission in a manner independent of G protein signalings. Targeted knockdown of GPR39 in SOM+ interneurons reduced the glycinergic inhibition and facilitated the excitatory output from SOM+ interneurons to spinoparabrachial neurons that engaged superspinal neural circuits encoding both the sensory discriminative and affective motivational domains of pain experience. Our data showed that pharmacological activation of GPR39 or augmenting GPR39 interaction with GlyRs at the spinal level effectively alleviated the sensory and affective pain induced by complete Freund's adjuvant and implicated GPR39 as a promising therapeutic target for the treatment of inflammatory mechanical pain.

Disrupted inter-brain synchronization in the prefrontal cortex between adolescents and young adults with gaming disorders during the real-world cooperating video games.

BACKGROUND: Gaming disorder (GD) and hazardous gaming (HG) have a high incidence among adolescents and young adults and have caused various negative consequences. Interpersonal interaction deficits are closely related to GD and HG, however, the underlying brain mechanisms are still unclear. METHODS: The current study recruited 46 healthy subjects and 32 subjects with GD/HG. Gaming time and frequency, gaming disorder risks, life events, strengths, and difficulties were measured with scales. Subjects were randomly paired into 12 HC-HC dyads, 15 GD/HG-HC dyads, and 7 GD/HG-GD/HG dyads and in pairs completed a real-world cooperating video game - "Tied Together" with functional near-infrared spectroscopy hyperscanning recording in the prefrontal cortex. The inter-brain synchronization in each region of the PFC between dyads was calculated by wavelet to transform coherence to measure brain-to-brain synchronization. RESULTS: We found subjects with GD/HG reported higher risks of gaming. The highest IBS in the left dorsolateral prefrontal cortex significantly decreased in the GD/HG-HC and GD/HG-GD/HG dyads compared with healthy controls. A decreasing highest IBS of the left dlPFC was related to a decreasing level of peer problems. LIMITATIONS: We declare limitations of age gaps of samples, undistinguishing GD from HG, use of sub-samples, and the broad concept of interpersonal interaction. CONCLUSIONS: The current study found a decreased highest IBS in the left dlPFC among adolescents and young adults with gaming diseases. It may provide new prevention and treatment insights into gaming disorders targeting disrupted interpersonal interaction.

Virtual agents among participants with methamphetamine use disorders: Acceptability and usability study.

INTRODUCTION: While the potential future role of virtual agents (VAs) in treating addiction is promising, participants' attitudes toward the use of VAs in psychotherapy remain insufficiently investigated. This lack of investigation could pose barriers to the adoption of VA-led psychotherapy for people with substance use disorders (SUD). This research aims to explore the acceptability and usability of VAs for people with methamphetamine use disorder. METHODS: Following a single session of psychotherapy led by VAs through the Echo-app, a group of 49 individuals actively seeking treatment for current DSM-V substance dependence (with a mean age of 39.06 ± 8.02) completed self-administered questionnaires and participated in focus group interviews. These questionnaires aimed to investigate participants' preference regarding the type of psychotherapy and their willingness to engage in VA-led psychotherapy, taking into account their diverse psychological needs. RESULTS: Quantitative data were subjected to analysis through both descriptive and inferential statistical methods. Interestingly, participants exhibited a significantly higher acceptability for traditional face-to-face psychotherapy compared to email-based psychotherapy (p = 0.042), but there was no statistically significant difference between their acceptance of traditional psychotherapy and VA-led psychotherapy (p = 0.059). The questionnaire outcomes indicated participants' willingness to engage in VA-led psychotherapy for purposes such as relapse prevention intervention, addressing emotional issues, managing somatic experiences, and facilitating social and family functional recovery. Furthermore, the participants' attitudes toward VA-led psychotherapy were predicted by factors including the need for anxiety-focused psychotherapy (p = 0.027; OR [95%CI] = 0.14[0.03,0.80]), the presence of chronic somatic diseases (p = 0.017; OR [95%CI] = 13.58[1.59,116.03]), and marital status (p = 0.031; OR [95%CI] = 5.02[1.16,21.79]). DISCUSSION: Through the interviews, the study uncovered the factors that either supported or hindered participants' experiences with VA-led psychotherapy, while also gathering suggestions for future improvements. This research highlights the willingness and practicality of individuals with SUD in embracing VA-led psychotherapy. The findings are anticipated to contribute to the refinement of VA-led tools to better align with the preferences and needs of the users.

Progress in advanced electrospun membranes for CO2 capture: Feedstock, design, and trend.

The emission of large amounts of carbon dioxide has caused serious environmental problems and hindered the construction of a green and low-carbon society. Efficient carbon dioxide capture has become an important means to slow down global climate warming and achieve effective utilization of carbon dioxide. Membranes synthesized by electrospinning technology are becoming promising carbon capture materials due to their unique characteristics. This review describes the features of membranes prepared from available raw materials and presents their application performances in carbon capture. The preparation methods of various types of membrane materials with excellent capture performance are summarized, and the effects of electrospinning parameters on electrospun fibers are systematically analyzed. Furthermore, recommendations and expectations for further development of electrospun membranes for carbon capture applications are given. These works provide important references for an in-depth understanding of the development status of electrospun membranes in the field of carbon capture and for expanding future research.

Serine/Threonine Kinase (STK) 33 promotes the proliferation and metastasis of human esophageal squamous cell carcinoma via inflammation-related pathway.

The serine/threonine kinase (STK) 33 plays a key role in cancer cell proliferation and metastasis. Abnormal STK33 expression is closely related to malignancy of numerous cancers. This study suggests the important role of STK33 in the pathogenesis and metastatic progression of esophageal squamous cell carcinoma (ESCC). STK33 expression in human ESCC tissues was detected by immunohistochemical technique. Further, we analyzed the relationship between STK33 and clinical and pathological factors as well as the prognosis of patients. ECa109 cell line was cultured and transfected with STK33-RNAi lentiviral vector to perform Hochest33342 & PI and metastasis experiments. The TCGA database was used to analyze the STK33 expression level in ESCC. All statistical analyses were performed in SPSS 23.0 software. Differences with P < 0.05 were considered statistically significant. In human ESCC specimens, STK33 was overexpressed and associated with poor prognosis. Silencing STK33 expression suppressed ESCC proliferation, migration, invasion, and tumor growth. STK33 also mediated angiogenesis, TGFß, and inflammatory response in ESCC. Mechanistic investigations revealed that STK33 regulates ESCC through multiple complex pathways. Dysregulated STK33 signaling promotes ESCC growth and progression. Thus, our findings identified STK33 as a candidate treatment target that improves ESCC therapy.

DPY30 promotes colorectal carcinoma metastasis by upregulating ZEB1 transcriptional expression.

DPY30 belongs to the core subunit of components of the histone lysine methyltransferase complex, which is implicated in tumorigenesis, cell senescence, and other biological events. However, its contribution to colorectal carcinoma (CRC) progression and metastasis has yet to be elucidated. Therefore, this study aimed to investigate the biological function of DPY30 in CRC metastasis both in vitro and in vivo. Herein, our results revealed that DPY30 overexpression is significantly positively correlated with positive lymph nodes, epithelial-mesenchymal transition (EMT), and CRC metastasis. Moreover, DPY30 knockdown in HT29 and SW480 cells markedly decreased EMT progression, as well as the migratory and invasive abilities of CRC cells in vitro and lung tumor metastasis in vivo. Mechanistically, DPY30 increased histone H3K4me3 level and promoted EMT and CRC metastasis by upregulating the transcriptional expression of ZEB1. Taken together, our findings indicate that DPY30 may serve as a therapeutic target and prognostic marker for CRC.

Repeated methamphetamine exposure decreases plasma brain-derived neurotrophic factor levels in rhesus monkeys.

Background: Brain-derived neurotrophic factor (BDNF) is known to prevent methamphetamine (METH)-induced neurotoxicity and plays a role in various stages of METH addiction. However, there is a lack of research with longitudinal design on changes in plasma BDNF levels in active METH-dependent individuals. Aims: The aim of the study was to investigate changes in BDNF levels during METH self-administration in monkeys. Methods: This study measured plasma BDNF levels in three male rhesus monkeys with continuous METH exposure and four male control rhesus monkeys without METH exposure. Changes in plasma BDNF levels were then assessed longitudinally during 40 sessions of METH self-administration in the three monkeys. Results: Repeated METH exposure decreased plasma BDNF levels. Additionally, plasma BDNF decreased with long-term rather than short-term accumulation of METH during METH self-administration. Conclusions: These findings may indicate that the changes in peripheral BDNF may reflect the quantity of accumulative METH intake during a frequent drug use period.

Metabolic and functional substrates of impulsive decision-making in individuals with heroin addiction after prolonged methadone maintenance treatment.

Elevated impulsivity has been frequently reported in individuals with opioid addiction receiving methadone maintenance therapy (MMT), but the underlying neural mechanisms and cognitive subprocesses are not fully understood. We acquired functional magnetic resonance imaging (fMRI) data from 37 subjects with heroin addiction receiving long-term MMT and 33 healthy controls who performed a probabilistic reversal learning task, and measured their resting-state brain glucose using fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET). Subjects receiving MMT exhibited significantly elevated self-reported impulsivity, and computational modeling revealed a marked impulsive decision bias manifested as switching more frequently without available evidence. Moreover, this impulsive decision bias was associated with the dose and duration of methadone use, irrelevant to the duration of heroin use. During the task, the switch-related hypoactivation in the left rostral middle frontal gyrus was correlated with the impulsive decision bias while the function of reward sensitivity was intact in subjects receiving MMT. Using prior brain-wide receptor density data, we found that the highest variance of regional metabolic abnormalities was explained by the spatial distribution of µ-opioid receptors among 10 types of neurotransmitter receptors. Heightened impulsivity in individuals receiving prolonged MMT is manifested as atypical choice bias and noise in decision-making processes, which is further driven by deficits in top-down cognitive control, other than reward sensitivity. Our findings uncover multifaceted mechanisms underlying elevated impulsivity in subjects receiving MMT, which might provide insights for developing complementary therapies to improve retention during MMT.

Antiviral, antioxidant, and anti-inflammatory activities of rhein against white spot syndrome virus infection in red swamp crayfish (Procambarus clarkii).

IMPORTANCE: Aquaculture is essential for ensuring global food security by providing a significant source of animal protein. However, the spread of the white spot syndrome virus (WSSV) has resulted in considerable economic losses in crustacean industries. In this study, we evaluated the antiviral activity of rhein, the primary bioactive component of Rheum palmatum L., against WSSV infection, and many pathological aspects of WSSV were also described for the first time. Our mechanistic studies indicated that rhein effectively arrested the replication of WSSV in crayfish by modulating innate immunity to inhibit viral gene transcription. Furthermore, we observed that rhein attenuated WSSV-induced oxidative and inflammatory stresses by regulating the expression of antioxidant and anti-inflammatory-related genes while enhancing innate immunity by reducing total protein levels and increasing phosphatase activity. Our findings suggest that rhein holds great promise as a potent antiviral agent for the prevention and treatment of WSSV in aquaculture.

Predictive value of radiomics-based machine learning for the disease-free survival in breast cancer: a systematic review and meta-analysis.

Purpose: This study summarized the previously-published studies regarding the use of radiomics-based predictive models for the identification of breast cancer-associated prognostic factors, which can help clinical decision-making and follow-up strategy. Materials and methods: This study has been pre-registered on PROSPERO. PubMed, Embase, Cochrane Library, and Web of Science were searched, from inception to April 23, 2022, for studies that used radiomics for prognostic prediction of breast cancer patients. Then the search was updated on July 18, 2023. Quality assessment was conducted using the Radiomics Quality Score, and meta-analysis was performed using R software. Results: A total of 975 articles were retrieved, and 13 studies were included, involving 5014 participants and 35 prognostic models. Among the models, 20 models were radiomics-based and the other 15 were based on clinical or pathological information. The primary outcome was Disease-free Survival (DFS). The retrieved studies were screened using LASSO, and Cox Regression was applied for modeling. The mean RQS was 18. The c-index of radiomics-based models for DFS prediction was 0.763 (95%CI 0.718-0.810) in the training set and 0.702 (95%CI 0.637-0.774) in the validation set. The c-index of combination models was 0.807 (95%CI0.736-0.885) in the training set and 0.840 (95%CI 0.794-0.888) in the validation set. There was no significant change in the c-index of DFS at 1, 2, 3, and over 5 years of follow-up. Conclusion: This study has proved that radiomics-based prognostic models are of great predictive performance for the prognosis of breast cancer patients. combination model shows significantly enhanced predictive performance. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022332392.

Metformin alleviates cerebral ischemia/reperfusion injury aggravated by hyperglycemia via regulating AMPK/ULK1/PINK1/Parkin pathway-mediated mitophagy and apoptosis.

Stroke remains the main leading cause of death and disabilities worldwide, with diabetes mellitus being a significant independent risk factor for it. Metformin, as an efficient hypoglycemic drug in treating type 2 diabetes, has been reported to alleviate the risk of diabetes-related stroke. However, its underlying mechanisms remain unclear. This study aimed to investigate the role of mitophagy and its regulatory pathway in the neuroprotective mechanism of metformin against cerebral ischemia/reperfusion (I/R) injury aggravated by hyperglycemia. A hyperglycemic cerebral I/R animal model and a high glucose cultured oxygen-glucose deprivation/reperfusion (OGD/R) cell model were used in the experiment. The indexes of brain injury, cell activity, mitochondrial morphology and function, mitophagy, mitochondrial pathway apoptosis and the AMPK pathway were observed. In diabetic rats, metformin treatment decreased cerebral infarction volume and neuronal apoptosis, and improved neurological symptoms following I/R injury. Additionally, metformin induced activation of the AMPK/ULK1/PINK1/Parkin mitophagy pathway to have neuroprotective effects. In vitro, high glucose culture and OGD/R treatment impaired mitochondrial morphology and function, mitochondrial membrane potential, and induced apoptosis. However, metformin activated AMPK/ULK1/PINK1/Parkin mitophagy pathway, normalized mitochondrial injury. This protection was reversed by autophagy inhibitor 3-methyladenine (3MA) and AMPK inhibitor compound C. In conclusion, our present study validates the potential mechanism of metformin in alleviating hyperglycemia aggravated cerebral I/R injury by the activation of AMPK/ULK1/PINK1/Parkin mitophagy pathway.