Triple-task mutual consistency for semi-supervised 3D medical image segmentation.

Semi-supervised deep learning algorithm is an effective means of medical image segmentation. Among these methods, multi-task learning with consistency regularization has achieved outstanding results. However, most of the existing methods usually simply embed the Signed Distance Map (SDM) task into the network, which underestimates the potential ability of SDM in edge awareness and leads to excessive dependence between tasks. In this work, we propose a novel triple-task mutual consistency (TTMC) framework to enhance shape and edge awareness capabilities, and overcome the task dependence problem underestimated in previous work. Specifically, we innovatively construct the Signed Attention Map (SAM), a novel fusion image with attention mechanism, and use it as an auxiliary task for segmentation to enhance the edge awareness ability. Then we implement a triple-task deep network, which jointly predicts the voxel-wise classification map, the Signed Distance Map and the Signed Attention Map. In our proposed framework, an optimized differentiable transformation layer associates SDM with voxel-wise classification map and SAM prediction, while task-level consistency regularization utilizes unlabeled data in an unsupervised manner. Evaluated on the public Left Atrium dataset and NIH Pancreas dataset, our proposed framework achieves significant performance gains by effectively utilizing unlabeled data, outperforming recent state-of-the-art semi-supervised segmentation methods. Code is available at https://github.com/Saocent/TTMC.

Graded-Band-Gap Zinc-Tin Oxide Thin-Film Transistors with a Vertically Stacked Structure for Wavelength-Selective Photodetection.

Filter-free wavelength-selective photodetectors have garnered significant attention due to the growing demand for smart sensors, artificial intelligence, the Internet of Everything, and so forth. However, the challenges associated with large-scale preparation and compatibility with complementary metal-oxide-semiconductor (CMOS) technology limit their wide-ranging applications. In this work, we address the challenges by constructing vertically stacked graded-band-gap zinc-tin oxide (ZTO) thin-film transistors (TFTs) specifically designed for wavelength-selective photodetection. The ZTO thin films with various band gaps are fabricated via atomic layer deposition (ALD) by varying the ALD cycle ratios of zinc oxide (ZnO) and SnO2. The ZTO film with a small Sn ratio exhibits a decreased band gap, and the resultant TFT shows a degraded performance, which can be attributed to the Sn4+ dopant introducing a series of deep-state energy levels in the ZnO band gap. As the ratio of Sn increases further, the band gap of the ZTO also increases, and the mobility of the ZTO TFT increases up to 30 cm2/V s, with a positive shift of the threshold voltage. The photodetectors employing ZTO thin films with distinct band gaps show different spectral responsivities. Then, vertically stacked ZTO (S-ZTO) thin films, with gradient band gaps increasing from the bottom to the top, have been successfully deposited using consecutive ALD technology. The S-ZTO TFT shows decent performance with a mobility of 18.4 cm2/V s, a threshold voltage of 0.5 V, an on-off current ratio higher than 107, and excellent stability under ambient conditions. The resultant S-ZTO TFT also exhibits obviously distinct photoresponses to light at different wavelength ranges. Furthermore, a device array of S-ZTO TFTs demonstrates color imaging by precisely reconstructing patterned illuminations with different wavelengths. Therefore, this work provides CMOS-compatible and structure-compact wavelength-selective photodetectors for advanced and integrable optoelectronic applications.

Acute stress selectively blunts reward anticipation but not consumption: An ERP study.

Stress-induced dysfunction of reward processing is documented to be a critical factor associated with mental illness. Although many studies have attempted to clarify the relationship between stress and reward, few studies have investigated the effect of acute stress on the temporal dynamics of reward processing. The present study applied event-related potentials (ERP) to examine how acute stress differently influences reward anticipation and consumption. In this study, seventy-eight undergraduates completed a two-door reward task following a Trier Social Stress Task (TSST) or a placebo task. The TSST group showed higher cortisol levels, perceived stress, anxiety, and negative affect than the control group. For the control group, a higher magnitude of reward elicited a reduced cue-N2 but increased stimulus-preceding negativity (SPN), suggesting that controls were sensitive to reward magnitude. In contrast, these effects were absent in the stress group, suggesting that acute stress reduces sensitivity to reward magnitude during the anticipatory phase. However, the reward positivity (RewP) and P3 of both groups showed similar patterns, which suggests that acute stress has no impact on reward responsiveness during the consummatory phase. These findings suggest that acute stress selectively blunts sensitivity to reward magnitude during the anticipatory rather than the consummatory phase.

FMRP phosphorylation modulates neuronal translation through YTHDF1.

RNA-binding proteins (RBPs) control messenger RNA fate in neurons. Here, we report a mechanism that the stimuli-induced neuronal translation is mediated by phosphorylation of a YTHDF1-binding protein FMRP. Mechanistically, YTHDF1 can condense with ribosomal proteins to promote the translation of its mRNA targets. FMRP regulates this process by sequestering YTHDF1 away from the ribosome; upon neuronal stimulation, FMRP becomes phosphorylated and releases YTHDF1 for translation upregulation. We show that a new small molecule inhibitor of YTHDF1 can reverse fragile X syndrome (FXS) developmental defects associated with FMRP deficiency in an organoid model. Our study thus reveals that FMRP and its phosphorylation are important regulators of activity-dependent translation during neuronal development and stimulation and identifies YTHDF1 as a potential therapeutic target for FXS in which developmental defects caused by FMRP depletion could be reversed through YTHDF1 inhibition.

Hierarchical MoN@NiFe-LDH Heterostructure Nanowire Array for Highly Efficient Electrocatalytic Hydrogen Evolution.

The slow charge transfer and high energy barrier are the key restrictions of cost-effective electrocatalysts for hydrogen production. A hierarchical heterostructure of MoN@NiFe-layered double hydroxides (LDH) is developed, with NiFe-LDH nanosheets supported on MoN nanowire arrays. The as-prepared MoN@NiFe-LDH exhibits a remarkably high performance on hydrogen production in alkaline medium, which is close to the benchmark Pt/C. The theoretical computations indicate that MoN@NiFe-LDH has a metallic character inherited from MoN, which gives rise to the promoted charge transfer. Furthermore, the adsorption intensity of intermediates on MoN@NiFe-LDH is optimized and thereby the energy barrier is diminished. This work demonstrates the significance of constructing heterostructure for boosting the charge transfer and reducing the energy barrier, which can shed light on the development of highly efficient and low-cost electrocatalyst for hydrogen production.

Development and validation of a novel nomogram of 1-year mortality in the elderly with hip fracture: a study of the MIMIC-III database.

OBJECTIVE: Hip fracture is a prevalent condition with a significant death rate among the elderly. We sought to develop a nomogram-based survival prediction model for older patients with hip fracture. DESIGN: A retrospective case-control study. SETTING: The data from Medical Information Mart for Intensive Care III (MIMIC-III V.1.4). PARTICIPANTS: The clinical features of elderly patients with hip fracture, including basic information, comorbidities, severity score, laboratory tests and therapy, were filtered out based on the MIMIC-III V.1.4. METHODS AND MAIN OUTCOME MEASURES: All patients included in the study were from critical care and randomly divided into training and validation sets (7:3). On the basis of retrieved data, the least absolute shrinkage and selection operator (LASSO) regression and multiple logistic regression analysis were used to identify independent predictive variables of 1-year mortality, and then constructed a risk prediction nomogram. The predictive values of the nomogram model were evaluated by the concordance indexes (C-indexes), receiver operating characteristic curve, decision curve analysis (DCA) and calibration curve. RESULTS: A total of 341 elderly patients with hip fracture were included in this study; 121 cases died within 1 year. After LASSO regression and multiple logistic regression analysis, a novel nomogram contained the predictive variables of age, weight, the proportion of lymphocyte count, liver disease, malignant tumour and congestive heart failure. The constructed model proved satisfactory discrimination with C-indexes of 0.738 (95% CI 0.674 to 0.802) in the training set and 0.713 (95% CI 0.608 to 0.819) in the validation set. The calibration curve shows a good degree of fitting between the predicted and observed probabilities and the DCA confirms the model's clinical practicability. CONCLUSIONS: The novel prediction model provides personalised predictions for 1-year mortality in elderly patients with hip fractures. Compared with other hip fracture models, our nomogram is particularly suitable for predicting long-term mortality in critical patients.

YTHDF2 inhibition potentiates radiotherapy antitumor efficacy.

RNA N6-methyladenosine (m6A) modification is implicated in cancer progression. However, the impact of m6A on the antitumor effects of radiotherapy and the related mechanisms are unknown. Here we show that ionizing radiation (IR) induces immunosuppressive myeloid-derived suppressor cell (MDSC) expansion and YTHDF2 expression in both murine models and humans. Following IR, loss of Ythdf2 in myeloid cells augments antitumor immunity and overcomes tumor radioresistance by altering MDSC differentiation and inhibiting MDSC infiltration and suppressive function. The remodeling of the landscape of MDSC populations by local IR is reversed by Ythdf2 deficiency. IR-induced YTHDF2 expression relies on NF-κB signaling; YTHDF2 in turn leads to NF-κB activation by directly binding and degrading transcripts encoding negative regulators of NF-κB signaling, resulting in an IR-YTHDF2-NF-κB circuit. Pharmacological inhibition of YTHDF2 overcomes MDSC-induced immunosuppression and improves combined IR and/or anti-PD-L1 treatment. Thus, YTHDF2 is a promising target to improve radiotherapy (RT) and RT/immunotherapy combinations.

Molecular Insights into the Improved Bioactivity of Interferon Conjugates Attached to a Helical Polyglutamate.

Attaching polymers, especially polyethylene glycol (PEG), to protein drugs has emerged as a successful strategy to prolong circulation time in the bloodstream. The hypothesis is that the flexible chain wobbles on the protein's surface, thus resisting potential nonspecific adsorption. Such a theoretical framework may be challenged when a helical polyglutamate is used to conjugate with target proteins. In this study, we investigated the structure-activity relationships of polyglutamate-interferon conjugates P(EG3Glu)-IFN using molecular simulations. Our results show that the local crowding effect induced by oligoethylene glycols (i.e., EG3) is the primary driving force for helix formation in P(EG3Glu), and its helicity can be effectively increased by reducing the free volume of the two termini. Furthermore, it was found that the steric hindrance induced by IFN is not conductive to the helicity of P(EG3Glu) but contributes to its dominant orientation relative to interferon. The orientation of IFN relative to the helical P(EG3Glu) can help to protect the protein drug from neutralizing antibodies while maintaining its bioactivity. These findings suggest that the helical structure and its orientation are critical factors to consider when updating the theoretical framework for protein-polymer conjugates.

Association between different MAP levels and 30-day mortality in sepsis patients: a propensity-score-matched, retrospective cohort study.

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by the infection-related host response disorder. Adequate mean arterial pressure is an important prerequisite of tissue and organ perfusion, which runs through the treatment of sepsis patients, and an appropriate mean arterial pressure titration in the early-stage correlates to the positive outcome of the treatment. Therefore, in the present study, we aimed to elucidate the relationship between early mean arterial pressure levels and short-term mortality in sepsis patients. METHODS: We included all suspected sepsis patients from MIMIC-III database with average mean arterial pressure ≥ 60 mmHg on the first day of intensive care unit stay. Those patients were then divided into a permissive low-mean arterial pressure group (60-65 mmHg) and a high-mean arterial pressure group (> 65 mmHg). Multivariate Cox regression analysis was conducted to analyze the relationship between MAP level and 30-day, 60-day, and 100-day mortality of suspected sepsis patients in the two groups. Propensity score matching, inverse probability of treatment weighing, standardized mortality ratio weighting, PA weighting, overlap weighting, and doubly robust analysis were used to verify our results. RESULTS: A total of 14,031 suspected sepsis patients were eligible for inclusion in our study, among which 1305 (9.3%) had an average first-day mean arterial pressure of 60-65 mmHg, and the remaining 12,726 patients had an average first-day mean arterial pressure of more than 65 mmHg. The risk of 30-day mortality was reduced in the high mean arterial pressure group compared with the permissive low-mean arterial pressure group (HR 0.67 (95% CI 0.60-0.75; p < 0.001)). The higher mean arterial pressure was also associated with lower 60-day and 100-day in-hospital mortality as well as with shorter duration of intensive care unit stay. Patients in the high-mean arterial pressure group also had more urine output on the first and second days of intensive care unit admission. CONCLUSIONS: After risk adjustment, the initial mean arterial pressure of above 65 mmHg was associated with reduced short-term mortality, shorter intensive care unit stay, and higher urine volume in the first two days among patients with sepsis.

Selective PPARγ modulator diosmin improves insulin sensitivity and promotes browning of white fat.

Peroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of adipocyte differentiation, glucolipid metabolism, and inflammation. Thiazolidinediones are PPARγ full agonists with potent insulin-sensitizing effects, whereas their oral usage is restricted because of unwanted side effects, including obesity and cardiovascular risks. Here, via virtual screening, microscale thermophoresis analysis, and molecular confirmation, we demonstrate that diosmin, a natural compound of wide and long-term clinical use, is a selective PPARγ modulator that binds to PPARγ and blocks PPARγ phosphorylation with weak transcriptional activity. Local diosmin administration in subcutaneous fat (inguinal white adipose tissue [iWAT]) improved insulin sensitivity and attenuated obesity via enhancing browning of white fat and energy expenditure. Besides, diosmin ameliorated inflammation in WAT and liver and reduced hepatic steatosis. Of note, we determined that iWAT local administration of diosmin did not exhibit obvious side effects. Taken together, the present study demonstrated that iWAT local delivery of diosmin protected mice from diet-induced insulin resistance, obesity, and fatty liver by blocking PPARγ phosphorylation, without apparent side effects, making it a potential therapeutic agent for the treatment of metabolic diseases.

CoP@Ni core-shell heterostructure nanowire array: A highly efficient electrocatalyst for hydrogen evolution.

The inferior performance of non-precious metals on electrocatalytic hydrogen evolution can be mainly attributed to the inappropriate adsorption strength of intermediates. A core-shell heterostructure of CoP@Ni is developed by hydrothermal reaction, thermal phosphorization and subsequent electrodeposition, with metallic Ni supported by CoP nanowire array. The as-prepared CoP@Ni core-shell heterostructure nanowire array has a superior activity on hydrogen evolution in alkaline electrolyte, with an overpotential of 71 mV to drive 10 mA cm-2 and a Tafel slope of 66 mV dec-1. The electronic structure of CoP@Ni is tuned for modulating the adsorption strength of intermediates. The theoretical calculations reveal that CoP@Ni has metallic characteristics with a zero-bandgap, which leads to the promoted charge transfer. More importantly, the intrinsic activity of CoP@Ni is greatly increased, with a lower energy barrier in the reaction pathway. This work points out the importance of constructing the heterostructure for improving the intrinsic activity, which can pave the way to the exploration of high-performance and cost-effective electrocatalysts for hydrogen production.

Flexible Microspectrometers Based on Printed Perovskite Pixels with Graded Bandgaps.

Miniaturized spectrometers have attracted much attention due to their capability to detect spectral information within a small size. However, such technology still faces challenges including large-scale preparation and performance repeatability. In this work, we overcome these challenges by demonstrating a microspectrometer constructed with a series of pixelized graded-bandgap perovskite photodetectors fabricated with inkjet printing. High-quality perovskite films with minimal pinholes and large grains are deposited by optimizing printing conditions including substrate temperature and surface modification. The resulting perovskite photodetectors show decent photosensing performance, and the different photodetectors based on perovskite films with different bandgaps exhibit various spectral responsivities with different cutoff wavelength edges. Microspectrometers are then constructed with the array of the pixelized graded-bandgap perovskite photodetectors, and incident spectra are algorithmically reconstructed by combining their output currents. The reconstruction performance of the miniaturized spectrometer is evaluated by comparing the results to the spectral curve measured with a commercial bulky spectrometer, indicating a reliable spectral reconstruction with a resolution of around 10 nm. More significantly, the miniaturized spectrometers are successfully fabricated on polymer substrates, and they demonstrate excellent mechanical flexibility. Therefore, this work provides a flexible miniaturized spectrometer with large-scale fabricability, which is promising for emerging applications including wearable devices, hyperspectral imaging, and internet of things.

ERRα contributes to HDAC6-induced chemoresistance of osteosarcoma cells.

Chemotherapy resistance is an important problem for clinical therapy of osteosarcoma (OS). The potential effects of histone deacetylases (HDACs) on OS chemoresistance are studied. The expression of HDACs in OS cells resistance to doxorubicin (Dox) and cisplatin (CDDP) is checked. Among 11 members of HDACs, levels of HDAC6 are significantly upregulated in OS cells resistance to Dox and CDDP. Inhibition of HDAC6 via its specific inhibitor ACY1215 restores chemosensitivity of OS-resistant cells. Further, HDAC6 directly binds with estrogen-related receptors alpha (ERRα) to regulate its acetylation and protein stability. Inhibition of ERRα further strengthens ACY1215-increased chemosensitivity of OS-resistant cells. Mechanistically, K129 acetylation is the key residue for HDAC6-regulated protein levels of ERRα. Collectively, we find that ERRα contributes to HDAC6-induced chemoresistance of OS cells. Inhibition of HDAC6/ERRα axis might be a potential approach to overcome chemoresistance and improve therapy efficiency for OS treatment. 1. HDAC6 was significantly upregulated in Dox and CDDP resistant OS cells; 2. Inhibition of HDAC6 can restore chemosensitivity of OS cells; 3. HDAC6 binds with ERRα at K129 to decrease its acetylation and increase protein stability; 4. ERRα contributes to HDAC6-induced chemoresistance of OS cells.

Adaption and validation of the Perceived Control of Internal States Scale (PCOISS) in Chinese adults: a cross-sectional study.

BACKGROUND: Perceived control of internal states is important for disease prevention, stress buffering and life adaptability. However, there is no psychometric scale to measure control beliefs over internal states in China. This study aimed to adapt and validate the Perceived Control of Internal States Scale (PCOISS) in a large sample of Chinese adults. METHODS: Data was collected through a big project, in which a cross-sectional online survey was conducted nationwide in China using a powerful Chinese online survey platform named WenJuanXing ( https://www.wjx.cn/ ). We translated the PCOISS into Chinese (C-PCOISS) with the forward-backward translation procedure. For the first time of the survey, a sample of 2709 participants (Sample 1) was valid for final analysis. Sample 1 was split into two datasets for principal component analysis (PCA) (nA = 1355) and confirmatory factor analyses (CFA) (nB = 1354) to determine potential factor structure. The scale's validity (i.e., discriminant validity, convergent validity, criterion validity) and internal consistency reliability were evaluated. Among the 1354 respondents (nB), 761 (nC = 761) participated in the follow-up second wave of the survey to assess a cross-sectional test-retest reliability. RESULTS: The C-PCOISS retained 14 items. PCA yielded a three-factor model which was supported with the best fit indices in CFA. The C-PCOISS had satisfactory internal consistency with Cronbach's alpha coefficients of 0.86, 0.78 and 0.72 for three subscales, respectively. The scale also showed adequate test-retest reliability (Pearson correlations coefficient of 0.64, 0.62 and 0.54 with p < 0.001 for three subscales, respectively). Three factors of the C-PCOISS were positively associated with positive affect, and negatively associated with negative affect, depression, compulsion-anxiety and perceived stress. CONCLUSIONS: The C-PCOISS is reliable and valid for measuring control beliefs over internal states in Chinese adults.

State Estimation via Designing Controller and State Estimation-Based Stabilization for Boolean Control Networks.

This article investigates the issues of state estimation and state estimation-based stabilization for Boolean control networks (BCNs). Unlike previous state observers, this article proposes an optimal state estimator by designing a particular input sequence for the first time, where the maximum-minimum method is employed such that the state of BCNs can be uniquely estimated in short time steps. A minimum reconstructible state set (MRSS) is constructed to determine this input sequence. Next, based on the estimated state, a finite-time stabilization scheme is proposed by constructing a switching controller consisting of three stages. A controller is first developed to estimate the state of BCNs in finite-time steps, and a state reachable controller is also provided to make the state of BCNs reachable to a given equilibrium point. Subsequently, a constant controller is further developed to stabilize the state of BCNs to the equilibrium point. Finally, an oxidative stress response model is used to illustrate the effectiveness of the proposed results.

Incidence of postoperative symptomatic spinal epidural hematoma requiring surgical evacuation: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to determine the incidence of symptomatic spinal epidural hematoma (SSEH) following spine surgery. METHODS: We systematically searched for all relevant articles that mentioned the incidence of SSEH following the spine surgery published in the PubMed, Embase, and Cochrane Library databases through March 2022 and manually searched the reference lists of included studies. The Newcastle-Ottawa quality assessment scale (NOS) was used to assess the quality of the included studies. A fixed-effects or random-effects model was performed to calculate the pooled incidence of the totality and subgroups based on the heterogeneity. The potential publication bias was assessed by Egger's linear regression and a funnel plot. Sensitivity analysis was also conducted. RESULTS: A total of 40 studies were included in our meta-analysis based on our inclusion and exclusion criteria. The overall pooled incidence of SSEH was 0.52% (95% CI 0.004-0.007). In the subgroup analysis, the pooled incidence of SSEH in males and females was 0.86% (95% CI 0.004-0.023) and 0.68% (95% CI 0.003-0.017). Among the different indications, a higher incidence (2.9%, 95% CI 0.006-0.084) was found in patients with deformity than degeneration (1.12%, 95% CI 0.006-0.020) and tumor (0.30%, 95% CI 0.006-0.084). For different surgical sites, the incidences of SSEH in cervical, thoracic and lumbar spine were 0.32% (95% CI 0.002-0.005), 0.84% (95% CI 0.004-0.017) and 0.63% (95% CI 0.004-0.010), respectively. The incidences of SSEH in anterior and posterior approach were 0.24% (95% CI 0.001-0.006) and 0.70% (95% CI 0.004-0.011), respectively. The pooled incidence of SSEH was five times higher with minimally invasive surgery (1.94%, 95% CI 0.009-0.043) than with open surgery (0.42%, 95% CI 0.003-0.006). Delayed onset of SSEH had a lower incidence of 0.16% (95% CI 0.001-0.002) than early onset. There were no significant variations in the incidence of SSEH between patients who received perioperative anticoagulation therapy and those who did not or did not report getting chemopreventive therapy (0.44%, 95% CI 0.006-0.084 versus 0.42%, 95% CI 0.003-0.006). CONCLUSION: We evaluated the overall incidence proportion of SSEH after spine surgery and performed stratified analysis, including sex, surgical indication, site, approach, minimally invasive surgery, and delayed onset of SSEH. Our research would be helpful for patients to be accurately informed of their risk and for spinal surgeons to estimate the probability of SSEH after spine surgery.

Non-linear relationship between baseline mean arterial pressure and 30-day mortality in patients with sepsis: a retrospective cohort study based on the MIMIC-III database.

Background: Sepsis is a life-threatening organ dysfunction due to disturbance of the host's response to infection, and is often accompanied by shock. Timely and standardized hemodynamic management can effectively control disease progression. Mean arterial pressure (MAP) refers to tissue and organ perfusion and is one of the key factors for patient recovery. In this study, we focused on the relationship between MAP levels and 30-day mortality in patients with sepsis. Methods: This cohort study included 14,607 sepsis patients out of 38,597 adults admitted to Beth Israel Deaconess Medical Center in Boston between 2001 and 2012, according to the Sepsis 3.0 diagnostic criteria. According to the MAP value of the sepsis patients on the first day of intensive care unit (ICU) admission, they were divided into 5 groups (Q1 ≤67.4 mmHg, Q2 67.4-72.5 mmHg, Q3 72.5-77.6 mmHg, Q4 77.6-84.6 mmHg, Q5 ≥84.6 mmHg). At the same time, the baseline data of vital signs, critical illness score, comorbidities and laboratory examination were collected on the first day of admission to ICU. The 30-day mortality of the 5 groups of patients and the overall sepsis patients were recorded. Multivariate Cox regression analysis and smooth curve fitting were used to assess the independent association between MAP and 30-day mortality. Results: A total of 14,607 sepsis patients were screened. The mean age of participants was 67.2±16.3 years, approximately 46.9% were women, and the overall 30-day mortality rate was 21.0%. Multivariate Cox regression models and smooth curve fitting revealed a non-linear association between MAP and 30-day mortality. The inflection point occurred at 68.6 mmHg. The left side effect size of each 10-unit change in the exposure factor was [hazard ratio (HR): 0.479, 95% confidence interval (CI): 0.403-0.569, P<0.001]. To the right of the inflection point, the effect size was (HR: 0.996, 95% CI: 0.931-1.065, P<0.9018). Conclusions: Our study demonstrated a non-linear relationship between MAP and 30-day mortality in patients with sepsis. When MAP was less than 68.6 mmHg, it was a strong predictor of the potential risk of sepsis death, which declined by 52.1% for every 10 mmHg growth in MAP.

IGF2BP1-regulated expression of ERRα is involved in metabolic reprogramming of chemotherapy resistant osteosarcoma cells.

Doxorubicin (Dox) is the standard treatment approach for osteosarcoma (OS), while acquired drug resistance seriously attenuates its treatment efficiency. The present study aimed to investigate the potential roles of metabolic reprogramming and the related regulatory mechanism in Dox-resistant OS cells. The results showed that the ATP levels, lactate generation, glucose consumption and oxygen consumption rate were significantly increased in Dox-resistant OS cells compared with parental cells. Furthermore, the results revealed that the increased expression of estrogen-related receptor alpha (ERRα) was involved in metabolic reprogramming in chemotherapy resistant OS cells, since targeted inhibition of ERRα restored the shifting of metabolic profiles. Mechanistic analysis indicated that the mRNA stability, rather than ERRα transcription was markedly increased in chemoresistant OS cells. Therefore, it was hypothesized that the 3'-untranslated region of ERRα mRNA was methylated by N6-methyladenine, which could further recruit insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress mRNA decay and increase mRNA stability. IGF2BP1 knockdown downregulated ERRα and reversed the metabolic alteration of resistant OS cells. Additionally, the oncogenic effect of the IGF2BP1/ERRα axis on Dox-resistant OS cells was verified by in vitro and in vivo experiments. Clinical analysis also revealed that the expression levels of IGF2BP1 and ERRα were associated with the clinical progression of OS. Collectively, the current study suggested that the IGF2BP1/ERRα axis could regulate metabolic reprogramming to contribute to the chemoresistance of OS cells.

Phenoxyl mediators improve enzymatic degradation of organic pollutants: Effect and mechanism.

A mediation strategy can effectively overcome the low reaction activity of enzymes with nonspecific substrates. In this study, we demonstrated how phenol compounds can mitigate the substrate limitation of HRP in catalytic degradation of various organic pollutants. In a classical HRP/H2O2 system, phenol and natural phenolic compounds (4-HBA & pHBA), exhibited up to over 100-fold enhancement in eliminating organic dyes and persistent antibiotics while the loading is only 2-5 wt%. A combination of molecular modelling, docking and frontier orbital energy analysis was employed to elucidate the catalytic performance and mechanism. We revealed that (1) generating phenoxyl radicals required the proximity of mediators to the HRP active centre, and (2) the subsequent efficient radical transfer to pollutants was determined by the large energy gap between the SOMO energy of phenoxyl radicals and the HOMO energy of phenols. When considering phenols as pollutants, we showed a synergistic effect on catalytic degradation of phenols, dyes, and tetracycline with a removal efficiency of 71-92 %. Overall, this work not only demonstrates that phenoxyl mediators can overcome the lower efficiency and substrate-specificity limitations of the HRP/H2O2 system but also revealed their structure-mediation relationship, implying great potential in the biodegradation of diverse pollutants and their mixtures.