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Purpose: The incomplete resection of non-muscle invasive bladder cancer (NMIBC) augments the risk of disease recurrence. Imaging-guided surgery by molecular probes represents a pivotal strategy for mitigating postoperative recurrence. Traditional optical molecular probes, primarily composed of antibodies/peptides targeting tumour cells and fluorescent groups, are challenged by the high heterogeneity of NMIBC cells, leading to inadequate probe sensitivity. We have developed a collagen-adhesive probe (CA-P) to target the collagen within the tumour microenvironment, aiming to address the issue of insufficient imaging sensitivity., Methods: The distribution characteristics of collagen in animal bladder cancer models and human bladder cancer tissues were explored. The synthesis and properties of CA-P were validated. In animal models, the imaging performance of CA-P was tested and compared with our previously reported near-infrared probe PLSWT7-DMI. The clinical translational potential of CA-P was assessed using human ex vivo bladder tissues., Results: The distribution of collagen on the surface of tumour cells is distinct from its expression in normal urothelium. In vitro studies have demonstrated the ability of the CA-P to undergo a "sol-gel" transition upon interaction with collagen. In animal models and human ex vivo bladder specimens, CA-P exhibits superior imaging performance compared to PLSWT7-DMI. The sensitivity of this probe is 94.1%, with a specificity of 81%., Conclusion: CA-P demonstrates the capability to overcome tumour cell heterogeneity and enhance imaging sensitivity, exhibiting favorable imaging outcomes in preclinical models. These findings provide a theoretical basis for the application of CA-P in intraoperative navigation for NMIBC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Adult skeletal muscle stem cells, also known satellite cells (SCs), are quiescent and activate in response to injury. However, the activation mechanisms of quiescent SCs (QSCs) remain largely unknown. Here, we investigated the metabolic regulation of SC activation by identifying regulatory metabolites that promote SC activation. Using targeted metabolomics, we found that spermidine acts as a regulatory metabolite to promote SC activation and muscle regeneration in mice. Mechanistically, spermidine activates SCs via generating hypusinated eIF5A. Using SC-specific eIF5A-knockout (KO) and Myod-KO mice, we further found that eIF5A is required for spermidine-mediated SC activation by controlling MyoD translation. More significantly, depletion of eIF5A in SCs results in impaired muscle regeneration in mice. Together, the findings of our study define a novel mechanism that is essential for SC activation and acts via spermidine-eIF5A-mediated MyoD translation. Our findings suggest that the spermidine-eIF5A axis represents a promising pharmacological target in efforts to activate endogenous SCs for the treatment of muscular disease., (© 2024. The Author(s).)

Background and Objectives: We aim to establish deep learning models to optimize the individualized energy delivery for septic patients., Methods and Study Design: We conducted a study of adult septic patients in ICU, collecting 47 indicators for 14 days. We filtered out nutrition-related features and divided the data into datasets according to the three metabolic phases proposed by ESPEN: acute early, acute late, and rehabilitation. We then established optimal energy target models for each phase using deep learning and conducted external validation., Results: A total of 179 patients in training dataset and 98 patients in external validation dataset were included in this study, and total data size was 3115 elements. The age, weight and BMI of the patients were 63.05 (95%CI 60.42-65.68), 61.31(95%CI 59.62-63.00) and 22.70 (95%CI 22.21-23.19), respectively. And 26.0% (72) of the patients were female. The models indicated that the optimal energy targets in the three phases were 900kcal/d, 2300kcal/d, and 2000kcal/d, respectively. Excessive energy intake increased mortality rapidly in the early period of the acute phase. Insufficient energy in the late period of the acute phase significantly raised the mortality as well. For the rehabilitation phase, too much or too little energy delivery were both associated with elevated death risk., Conclusions: Our study established time-series prediction models for septic patients to optimize energy delivery in the ICU. We recommended permissive underfeeding only in the early acute phase. Later, increased energy intake may improve survival and settle energy debts caused by underfeeding., Competing Interests: The authors declare that they have no competing interests

GPCR-G protein signaling from endosomes plays a crucial role in various physiological and pathological processes. However, the mechanism by which endosomal G protein signaling is terminated remains largely unknown. In this study, we aimed to investigate the regulatory mechanisms involved in terminating the signaling of Gα subunits from endosomes. Through structural analysis and cell-based assays, we have discovered that SNX25, a protein that targets endosomes via its PXA or PXC domain, interacts with regulator of G protein signaling (RGS) proteins (including RGS2, RGS4, RGS8, and RGS17) in a redox-regulated manner. The interaction between SNX25 and these RGS proteins enhances their GTPase-accelerating activity towards Gα i/q and their ability to bind GDP-bound (inactive form) Gα i/q . As a result, SNX25 recruits these RGS proteins to endosomes, leading to the termination of endosomal Gα i/q signaling. Furthermore, we have found that the SNX25/RGS complex also exerts a negative regulatory effect on Gα i/q signaling from the plasma membrane. This is achieved by recruiting Gα i/q to endosomes and preventing its activation on the plasma membrane. Our findings shed light on the previously unknown role of redox-modulated SNX25 in inhibiting Gα i/q signaling, thereby uncovering a novel mechanism for terminating Gα i/q signaling from endosomes. Importantly, this study expands our understanding of the regulation of GPCR-Gα i/q signaling beyond the plasma membrane., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Small ubiquitin-like modifier (SUMO) modification regulates various eukaryotic cellular processes and plays a pivotal role in interferon (IFN)-mediated antiviral defense. While immunoprecipitation enrichment method is widely used for proteome-wide analysis of endogenous SUMOylation, the inability to target all SUMO forms and high cost of antibodies limited its further application. Herein, we proposed an antibody-free enrichment method based on SUMO-specific protease and strong anion exchange chromatography (SPAX) to globally profile the endogenous SUMOylation. The SUMO1/2/3-modified peptides could be simultaneously enriched by SAX chromatography by utilizing its electrostatic interaction with SUMO1/2/3 remnants, which contained multiple aspartic acids (D) and glutamic acids (E). To remove the co-enriched D/E-containing peptides which might interfere with the detection of low-abundance SUMOylated peptides, SUMO-specific protease was used to cleave the SUMO1/2/3 remnants from enriched SUMOylated peptides. As the deSUMOylated peptides lost SUMO remnants, their interaction with SAX materials became weaker, and the D/E-containing peptides could thus be depleted through the second SAX separation. The SPAX method identified over twice the SUMOylated sites than using SAX method only, greatly improving the identification coverage of endogenous SUMOylated sites. Our strategy was then applied to the site-specific identification and quantification of endogenous SUMOylation in A549 cells stimulated by IFN-γ for the first time. A total of 226 SUMOylated sites on 146 proteins were confidently identified, among which multiple up-regulated sites were involved in IFN-mediated antiviral defense, demonstrating the great promise of SPAX to globally profile and discover endogenous SUMOylation with significant biological functions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The CoSn(OH) 6 perovskite hydroxide is a structure stable and inexpensive electrocatalyst for the oxygen evolution reaction (OER). However, the OER activity of CoSn(OH) 6 is still unfavorable due to its limited active sites. In this work, an Fe 3+ doping strategy is used to optimize the d-band state of the CoSn(OH) 6 perovskite hydroxide. The CoSn(OH) 6 catalyst with slightly Fe 3+ doped nanocubes is synthesized by a facile hydrothermal method. Structure characterization shows that Fe 3+ ions are incorporated into the crystal structure of CoSn(OH) 6 . Owing to the regulation of the electronic structure, CoSn(OH) 6 -Fe1.8% exhibits an OER overpotential of 289 mV at a current density of 10 mA cm -2 in OER electrochemical tests. In situ Raman spectroscopy shows that no obvious re-construction occurred during the OER for both CoSn(OH) 6 and CoSn(OH) 6 -Fe1.8%. DFT calculations show that the introduction of Fe 3+ into CoSn(OH) 6 can shift the d-band center to a relatively high position, thus promoting the OER intermediates' adsorption ability. Further DFT calculations suggest that incorporation of an appropriate amount of Fe 3+ into CoSn(OH) 6 significantly reduces the rate-determining Gibbs free energy during the OER. This work offers valuable insights into tuning the d-band center of perovskite hydroxide materials for efficient OER applications.

Ferroptosis, a novel form of nonapoptotic cell death, can effectively enhance photodynamic therapy (PDT) performance by disrupting intracellular redox homeostasis and promoting apoptosis. However, the extremely hypoxic tumor microenvironment (TME) together with highly expressed hypoxia-inducible factor-1α (HIF-1α) presents a considerable challenge for clinical PDT against osteosarcoma (OS). Hence, an innovative nanoplatform that enhances antitumor PDT by inducing ferroptosis and alleviating hypoxia is fabricated. Capsaicin (CAP) is widely reported to specifically activate transient receptor potential vanilloid 1 (TRPV1) channel, trigger an increase in intracellular Ca 2+ concentration, which is closely linked with ferroptosis, and participate in decreased oxygen consumption by inhibiting HIF-1α in tumor cells, potentiating PDT antitumor efficiency. Thus, CAP and the photosensitizer IR780 are coencapsulated into highly biocompatible human serum albumin (HSA) to construct a nanoplatform (CI@HSA NPs) for synergistic tumor treatment under near-infrared (NIR) irradiation. Furthermore, the potential underlying signaling pathways of the combination therapy are investigated. CI@HSA NPs achieve real-time dynamic distribution monitoring and exhibit excellent antitumor efficacy with superior biosafety in vivo. Overall, this work highlights a promising NIR imaging-guided "pro-death" strategy to overcome the limitations of PDT for OS by promoting ferroptosis and alleviating hypoxia, providing inspiration and support for future innovative tumor therapy approaches., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Background: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain., Methods: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event., Results: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60)., Conclusions: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.)., (Copyright © 2024 Massachusetts Medical Society.)

The distillation process plays an essential role in the petrochemical industry. However, the high-purity distillation column has complicated dynamic characteristics such as strong coupling and large time delay. To control the distillation column accurately, we proposed an extended generalized predictive control (EGPC) method inspired by the principles of extended state observer and proportional-integral-type generalized predictive control method; the proposed EGPC can adaptively compensate the system for the effects of coupling and model mismatch online and performs well in controlling time-delay systems. The strong coupling of the distillation column needs fast control, and the large time delay requires soft control. To balance the requirement for fast and soft control at the same time, a grey wolf optimizer with reverse learning and adaptive leaders number strategies (RAGWO) was proposed to tune the parameters of EGPC, and these strategies enable RAGWO to have a better initial population and improve its exploitation and exploration ability. The benchmark test results indicate that the RAGWO outperforms the existing optimizers for most of the selected benchmark functions. Extensive simulations show that the proposed method in terms of fluctuation and response time is superior to other methods for controlling the distillation process.

Novel evanescently coupled waveguide modified uni-traveling carrier photodiodes (MUTC-PDs) employing a thick multi-layer coupling waveguide are reported. To improve the optical-to-electrical (O/E) conversion efficiency, a thick multi-layer coupling waveguide with a gradually increased refractive index from the bottom layer to the absorption layer is utilized. The refractive index profile facilitates the upward transmission of incident light into the absorption region, thereby enhancing the evanescent coupling efficiency. Meanwhile, the coupling waveguide, with a total thickness of 1.75 µm, expands the mode field diameter, thereby reducing the input coupling loss. Additionally, the top layer of the coupling waveguide also serves as the drift layer. This configuration facilitates efficient light absorption within a short PD length, thus ensuring ultrawide bandwidth and high O/E conversion efficiency simultaneously. Without an additional spot size coupler or anti-reflection coating, the measured responsivity is as high as 0.38 A/W for the PD with an active area of 5 × 6 µm 2 . Meanwhile, an ultrawide 3-dB bandwidth of 153 GHz has been demonstrated.

Infantile hemangioma (IH) is the most common tumor in children and a paradigm for pathological vasculogenesis, angiogenesis and regression. Propranolol is the mainstay of treatment for IH. It inhibits hemangioma vessel formation via a β-adrenergic receptor independent off-target effect of its R(+) enantiomer on the endothelial specific transcription factor sex-determining region Y (SRY) box transcription factor 18 (SOX18). Transcriptomic profiling of patient-derived hemangioma stem cells uncovered the mevalonate pathway (MVP) as a target of R(+) propranolol. Loss of SOX18 function confirmed R(+) propranolol mode of action on the MVP. Functional validation in preclinical IH models revealed that statins - targeting the MVP - are potent inhibitors of hemangioma vessel formation. We propose a novel SOX18-MVP-axis as a central regulator of IH pathogenesis and suggest statin repurposing to treat IH. Our findings reveal novel pleiotropic effects of beta-blockers and statins acting on the SOX18-MVP axis to disable an endothelial specific program in IH, which may impact other scenarios involving pathological vasculogenesis and angiogenesis.

Background: Previous studies have shown that TREM2 plays a protective role in acute lung injury (ALI). This prospective study aimed to investigate the role of sTREM2 as a forecasting factor for ALI in infants after pediatric cardiac surgery undergoing cardiopulmonary bypass (CPB)., Methods: Seventy-five consecutive patients younger than 1 year who underwent cardiac surgery were enrolled in this study. Sixty-one fulfilled the inclusion criteria and had been divided into ALI and non-ALI groups. Children's demographic characteristics and clinical data were collected. Perioperative sTREM2 levels were analyzed at five timepoints., Results: In this study, children in the ALI group were younger, lighter, with higher RACHS-1 scores and underwent significantly longer CPB time. Post-CPB ALI had an impact on clinical outcomes, which contributed to a longer duration of mechanical ventilation, ICU and hospital stay than non-ALI group. Significant differences were manifested off-CPB, 1 h/6 h after CPB, and day 1 after surgery between the two groups. Binary logistic models revealed that off-CPB sTREM2 was significantly associated with the incidence of post-CPB ALI after adjustment. ROC analysis showed that the AUC of off-CPB sTREM2 level was 0.791, and the optimal cutoff value was 788.6 pg/ml., Conclusions: The off-CPB sTREM2 level was an independent prognostic factor for post-CPB ALI in infants., Impact: Plasma sTREM2 works together with downstream TREM2 to regulate inflammation response by binding the receptor to other cells. Previous studies have shown that TREM2 plays a protective role in ischemia-reperfusion and has anti-inflammatory effects on acute lung injury (ALI). This study analyzed the risk factors of post-cardiopulmonary bypass (CPB) ALI. We found that weight and off-CPB sTREM2 level were independent prognostic factors for post-CPB ALI. Plasma sTREM2 may serve as an early biomarker in the prognostic evaluation of acute lung injury after cardiac surgery in infants., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Purpose: We sought to establish whether nucleated red blood cells (NRBCs) are predictive of disposition, morbidity, and mortality for pediatric patients presenting to the emergency department (ED)., Methods: A single-center retrospective cohort study examining all ED encounters from patients aged younger than 19 years between January 2016 and March 2020, during which a complete blood count was obtained. Univariate analysis and multivariable logistic regression were used to test the presence of NRBCs as an independent predictor of patient-related outcomes., Results: The prevalence of NRBCs was 8.9% (4195/46,991 patient encounters). Patient with NRBCs were younger (median age 4.58 vs 8.23 years; P < 0.001). Those with NRBCs had higher rates of in-hospital mortality (30/2465 [1.22%] vs 65/21,741 [0.30%]; P < 0.001), sepsis (19% vs 12%; P < 0.001), shock (7% vs 4%; P < 0.001), and cardiopulmonary resuscitation (CPR) (0.62% vs 0.09%; P < 0.001). They were more likely to be admitted (59% vs 51%; P < 0.001), have longer median hospital length of stay {1.3 (interquartile range [IQR], 0.22-4.14) vs 0.8 days (IQR, 0.23-2.64); P < 0.001}, and median intensive care unit (ICU) length of stay (3.9 [IQR, 1.87-8.72] vs 2.6 days [IQR, 1.27-5.83]; P < 0.001). Multivariable regression revealed presence of NRBCs as an independent predictor for in-hospital mortality (adjusted odds ratio [aOR], 2.21; 95% confidence interval [CI], 1.38-3.53; P < 0.001), ICU admission (aOR, 1.30; 95% CI, 1.11-1.51; P < 0.001), CPR (aOR, 3.83; 95% CI, 2.33-6.30; P < 0.001), and 30-day return to the ED (aOR, 1.15; 95% CI, 1.15-1.26; P < 0.001)., Conclusions: The presence of NRBCs is an independent predictor for mortality, including in-hospital mortality, ICU admission, CPR, and readmission within 30 days for children presenting to the ED., Competing Interests: Disclosure: K.A.M. received funding through award K08HS026503 from the Agency for Healthcare Research and Quality. C.V. received funding through a grant supported by the Georgia Claire Bowen Foundation. A.G. received funding through 5T32HL007572-38 from the National Institute of Health Research Methods in Pediatric Cardiovascular Disease. The other authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

MyoD is a skeletal muscle-specifically expressed transcription factor and plays a critical role in regulating myogenesis during muscle development and regeneration. However, whether myofibers-expressed MyoD exerts its metabolic function in regulating whole body energy homeostasis in vivo remains largely unknown. Here, we report that genetic deletion of Myod in male mice enhances the oxidative metabolism of muscle and, intriguingly, renders the male mice resistant to high fat diet-induced obesity. By performing lipidomic analysis in muscle-conditioned medium and serum, we identify 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) as a muscle-released lipid that is responsible for MyoD-orchestrated body energy homeostasis in male Myod KO mice. Functionally, the administration of DLPC significantly ameliorates HFD-induced obesity in male mice. Mechanistically, DLPC is found to induce white adipose browning via lipid peroxidation-mediated p38 signaling in male mice. Collectively, our findings not only uncover a novel function of MyoD in controlling systemic energy homeostasis through the muscle-derived lipokine DLPC but also suggest that the DLPC might have clinical potential for treating obesity in humans., (© 2023. The Author(s).)

Background: N6, 2'-O-dimethyladenosine (m 6 Am) is an abundant RNA methylation modification on vertebrate mRNAs and is present in the transcription initiation region of mRNAs. It has recently been experimentally shown to be associated with several human disorders, including obesity genes, and stomach cancer, among others. As a result, N6,2'-O-dimethyladenosine (m 6 Am) site will play a crucial part in the regulation of RNA if it can be correctly identified., Results: This study proposes a novel deep learning-based m 6 Am prediction model, EMDL&#95;m6Am, which employs one-hot encoding to expressthe feature map of the RNA sequence and recognizes m 6 Am sites by integrating different CNN models via stacking. Including DenseNet, Inflated Convolutional Network (DCNN) and Deep Multiscale Residual Network (MSRN), the sensitivity (Sn), specificity (Sp), accuracy (ACC), Mathews correlation coefficient (MCC) and area under the curve (AUC) of our model on the training data set reach 86.62%, 88.94%, 87.78%, 0.7590 and 0.8778, respectively, and the prediction results on the independent test set are as high as 82.25%, 79.72%, 80.98%, 0.6199, and 0.8211., Conclusions: In conclusion, the experimental results demonstrated that EMDL&#95;m6Am greatly improved the predictive performance of the m 6 Am sites and could provide a valuable reference for the next part of the study. The source code and experimental data are available at: https://github.com/13133989982/EMDL-m6Am ., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Anticancer peptides (ACPs) have been proven to possess potent anticancer activities. Although computational methods have emerged for rapid ACPs identification, their accuracy still needs improvement. In this study, we propose a model called ACP-BC, a three-channel end-to-end model that utilizes various combinations of data augmentation techniques. In the first channel, features are extracted from the raw sequence using a bidirectional long short-term memory network. In the second channel, the entire sequence is converted into a chemical molecular formula, which is further simplified using Simplified Molecular Input Line Entry System notation to obtain deep abstract features through a bidirectional encoder representation transformer (BERT). In the third channel, we manually selected four effective features according to dipeptide composition, binary profile feature, k-mer sparse matrix, and pseudo amino acid composition. Notably, the application of chemical BERT in predicting ACPs is novel and successfully integrated into our model. To validate the performance of our model, we selected two benchmark datasets, ACPs740 and ACPs240. ACP-BC achieved prediction accuracy with 87% and 90% on these two datasets, respectively, representing improvements of 1.3% and 7% compared to existing state-of-the-art methods on these datasets. Therefore, systematic comparative experiments have shown that the ACP-BC can effectively identify anticancer peptides.

Hydroquinone (HQ) is an important metabolites of benzene in the body, and it has been found to result in cellular DNA damage, mutation, cell cycle imbalance, and malignant transformation. The JNK1 signaling pathway plays an important role in DNA damage repair. In this study, we focused on whether the JNK1 signaling pathway is involved in the HQ-induced cell cycle abnormalities and the underlying mechanism. The results showed that HQ induced abnormal progression of the cell cycle and initiated the JNK1 signaling pathway. We further confirmed that JNK1 suppression decelerated the cell cycle progression through inhibiting pRb/E2F1 signaling pathway and triggering p53/p21 pathway. Therefore, we concluded that JNK1 might be involved in HQ-induced malignant transformation associated with activating pRb/E2F1 and inhibiting p53/p21 signaling pathway which resulting in accelerating the cell cycle progression., (© 2023 Wiley Periodicals LLC.)

Lymphangiogenesis in tumors provides an auxiliary route for cancer cell invasion to drainage lymph nodes, facilitating the development of lymphatic metastasis (LM). However, the mechanisms governing tumor lymphangiogenesis and lymphatic permeability in gastric cancer (GC) remain largely unknown. Here, the unprecedented role and mechanism of cysteine-rich intestinal protein-1 (CRIP1) in mediating the development of GC LM is uncovered. A series of assays are performed to identify downstream targets of CRIP1, and rescue experiments are performed to confirm the effects of this regulatory axis on LM. CRIP1 overexpression facilitates LM in GC by promoting lymphangiogenesis and lymphatic vessel permeability. CRIP1 promotes phosphorylation of cAMP responsive element binding protein 1(CREB1), which then mediates vascular endothelial growth factor C (VEGFC) expression necessary for CRIP1-induced lymphangiogenesis and transcriptionally promotes C-C motif chemokine ligand 5 (CCL5) expression. CCL5 recruits macrophages to promote tumor necrosis factor alpha (TNF-α) secretion, eventually enhancing lymphatic permeability. The study highlights CRIP1 regulates the tumor microenvironment to promote lymphangiogenesis and LM in GC. Considering the current limited understanding of LM development in GC, these pathways provide potential targets for future therapeutics., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Area-based sociodemographic markers, such as census tract foreign-born population, have been used to identify individuals and communities with a high risk for tuberculosis (TB) infection in the United States. However, these markers have not been evaluated as independent risk factors for TB infection in children. We evaluated associations between census tract poverty, crowding, foreign-born population, and the CDC's Social Vulnerability Index (CDC-SVI) ranking and TB infection in a population of children tested for TB infection in Boston, Massachusetts. After adjustment for age, crowding, and foreign-born percentage, increasing census tract poverty was associated with increased odds of TB infection (adjusted odds ratio [aOR] per 10% increase in population proportion living in poverty: 1.20 [95% CI, 1.04-1.40]; P = 0.01), although this association was attenuated after further adjustment for preferred language. In separate models, increasing CDC-SVI ranking was associated with increased odds of TB infection, including after adjustment for age and language preference (aOR per 10-point increase in CDC-SVI rank: 1.08 [95% CI, 1.02-1.15]; P = 0.01). Our findings suggest area-based sociodemographic factors may be valuable for characterizing TB infection risk and defining the social ecology of pediatric TB infection in low-burden settings.

What Is Already Known About This Topic?: Allergic diseases have affected an estimated 40% of the population in China. However, our understanding of the full spectrum of these diseases remains insufficient., What Is Added by This Report?: Between 2018 and 2021, Yichang City documented 625,929 outpatient visits mainly related to skin and mucous membrane allergies (77.90%) and allergic respiratory conditions (19.64%). In 2021, the occurrence of outpatient visits for conditions such as allergic rhinitis, acute atopic conjunctivitis, and atopic dermatitis increased. The demographic analysis revealed that male patients comprised the majority of the under 18 age bracket (56.05%), while female patients were predominantly represented in the 18 to 65 age bracket (61.79%)., What Are the Implications for Public Health Practice?: This constitutes the first analysis of the spectrum of allergic diseases, utilizing regional outpatient data, which has substantial implications for understanding the disease burden., Competing Interests: No conflicts of interest., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2023.)

Background: Acute kidney injury (AKI) is a potential complication after cardiopulmonary bypass (CPB) of pediatric cardiac surgery and contributes to a certain amount of perioperative mortality. Serum soluble triggering receptor expressed on myeloid cells2 (sTREM2) is an inflammation-associated cytokine in circulation. Alterations of sTREM2 level have been reported in Alzheimer's disease, sepsis, and some other pathologic conditions. This study aimed to investigate the role of sTREM2 as a forecasting factor for AKI in infants and young children and other factors associated with early renal injury after pediatric CPB., Methods: A prospective cohort study with consecutive infants and young children ≤ 3 years old undergoing CPB from September 2021 to August 2022 was conducted in an affiliated university children's hospital. These patients were divided into an AKI group ( n  = 10) and a non-AKI group ( n  = 60). Children's characteristics and clinical data were measured. Perioperative sTREM2 levels were analyzed with enzyme-linked immunosorbent assay (ELISA)., Results: In children developing AKI, the sTREM2 levels significantly decreased at the beginning of CPB compared to the non-AKI group. Based on binary logistic regression analysis and multivariable regression analysis, risk-adjusted classification for congenital heart surgery (RACHS-1), operation time, and the s-TREM2 level at the beginning of CPB (AUC = 0.839, p  = 0.001, optimal cut-off value: 716.0 pg/ml) had predictive value for post-CPB AKI. When combining the sTREM2 level at the beginning of CPB and other indicators together, the area under the ROC curve enlarged., Conclusions: Operation time, RACHS-1 score, and sTREM2 level at the beginning of CPB were independent prognosis factors of post-CPB AKI in infants and young children ≤ 3 years old. Decreased sTREM2 identified post-CPB AKI, and ultimately hampered the outcomes. Our findings indicated that sTREM2 may be a protective factor for AKI after CPB in infants and young children ≤ 3 years old., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Sun, Yang, Zong, Ying, Liu, and Lin.)

Whether early or late drain removal (EDR/LDR) is better for patients after pancreatic resection remains controversial. We aim to systematically evaluate the safety and efficacy of early or late drain removal in patients who undergo pancreatic resection. We searched seven databases from January 1, 2000, through September 2021, and included randomized controlled trials (RCTs) or observational studies comparing EDR vs. LDR in patients after pancreatic resection. We separately pooled effect estimates across RCTs and observational studies. Finally, we included 4 RCTs with 711 patients and 8 nonRCTs with 7207 patients. Based on the pooled RCT data, compared to LDR, EDR reduced hospital length of stay (LOS) (RR: -2.59, 95% CI: -4.13 to -1.06) and hospital cost (RR: -1022.27, 95% CI: -1990.39 to -54.19). Based on the pooled nonRCT data, EDR may reduce the incidence of all complications (OR: 0.45, 95% CI: 0.32 to 0.63), pancreatic fistula (OR: 0.26, 95% CI: 0.15 to 0.45), wound infection (RR: 0.59, 95% CI: 0.06 to 5.45)), reoperation (OR: 0.62, 95% CI: 0.40 to 0.96) and hospital readmission (OR: 0.57, 95% CI: 0.47 to 0.69). There was an uncertain effect on mortality (OR from pooled nonRCTs: 1.02, 95% CI: 0.41 to 2.53) and delayed gastric emptying (RR from pooled RCTs: 0.76, 95% CI: 0.41 to 1.41). The findings of this meta-analysis suggest that early drain removal is associated with lower hospital cost, is safe and may reduce the incidence of complications compared to late drain removal in patients after pancreaticoduodenectomy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

The prediction of damage and failure to fiber-reinforced polymer composites in extreme environments, particularly when subjected to impact loading, is a crucial issue for the application and design of protective structures. In this paper, based on the prototype microelastic brittle (PMB) model and the LaRC05 composite materials failure model, we proposed a bond-based peridynamic (BB-PD) model with the introduction of plastic hardening of the resin matrix for fiber-reinforced polymer composites. The PD constitutive relationships of the matrix bond and interlayer bond under compressive loading are considered to include two stages of linear elasticity and plastic hardening, according to the stress-strain relationship of the resin matrix in the LaRC05 failure model. The proposed PD model is employed to simulate the damage behaviors of laminated composites subjected to impact loading. The corresponding ballistic impact tests of composite laminates were carried out to observe their damage behaviors. The PD prediction results are in good agreement with the ballistic experimental results, which can verify the correctness and accuracy of the PD model developed in this study in describing the impact damage behaviors of composite materials. In addition, the characteristics and degree of damage in composite laminates are analyzed and discussed based on this PD model. The difference in the impact resistance of composite laminates with different stacking sequences is also studied using the numerical simulation results.

Ubiquitination is a reversible post-translational modification that plays a pivotal role in numerous biological processes. Antibody-based approaches, as the most used methods for identifying ubiquitination sites, exist sequence recognition bias, high cost, and ubiquitin-like protein modification interference, limiting their widespread application. Here, we proposed an Antibody-Free approach for Ubiquitination Profiling, termed AFUP, by selectively clicking the ubiquitinated lysine to enrich and profile endogenous ubiquitinated peptides using mass spectrometry. Briefly, protein amines were blocked with formaldehyde, and then the ubiquitin molecules were hydrolyzed from the ubiquitinated proteins by non-specific deubiquitinases USP2 and USP21 to release the free ε-amine of lysine. Peptides containing free ε-amines were selectively enriched with streptavidin beads upon NHS-SS-biotin labeling. Finally, the enriched peptides were eluted by DTT and analyzed by LC-MS/MS, resulting in ubiquitination profiling. Preliminary experiment showed that 349 ± 7 ubiquitination sites were identified in 0.8 mg HeLa lysates with excellent reproducibility (CV = 2%) and high quantitative stability (Pearson, r ≥ 0.91) using our method. With the combination of AFUP and simple basic C18 pre-fractionation, approximately 4000 ubiquitination sites were identified in a single run of 293T cells. In addition, we showed that 209 ubiquitination sites were significantly regulated in UBE2O knockdown cells after normalized to protein abundance. In conclusion, our results demonstrated that AFUP is a robust alternative strategy for ubiquitomics research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Interferon-gamma release assays (IGRAs) are approved for children ≥2 years old to aid in diagnosis of Mycobacterium tuberculosis (TB) infection and disease. Tuberculin skin tests (TSTs) continue to be the recommended method for diagnosis of TB infection in children <2 years, in part due to limited data and concern for high rates of uninterpretable results., Methods: We performed a retrospective cohort study of IGRA use in patients <2 years old in 2 large Boston healthcare systems. The primary outcome was the proportion of valid versus invalid/indeterminate IGRA results. Secondary outcomes included concordance of IGRAs with paired TSTs and trends in IGRA usage over time., Results: A total of 321 IGRA results were analyzed; 308 tests (96%) were valid and 13 (4%) were invalid/indeterminate. Thirty-seven IGRAs were obtained in immunocompromised patients; the proportion of invalid/indeterminate results was significantly higher among immunocompromised (27%) compared with immunocompetent (1%) patients ( P < 0.001). Paired IGRAs and TSTs had a concordance rate of 64%, with most discordant results in bacille Calmette-Guérin-vaccinated patients. The proportion of total TB tests that were IGRAs increased over the study period (Pearson correlation coefficient 0.85, P < 0.001)., Conclusions: The high proportion of valid IGRA test results in patients <2 years of age in a low TB prevalence setting in combination with the known logistical and interpretation challenges associated with TSTs support the adoption of IGRAs for this age group in certain clinical scenarios. Interpretation of IGRAs, particularly in immunocompromised patients, should involve consideration of the broader clinical context., Competing Interests: J.E.H. reports consulting fees from Merck and owns stock in Natera. The other authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To characterize losses from the pediatric tuberculosis (TB) infection care cascade to identify ways to improve TB infection care delivery., Study Design: We conducted a retrospective cohort study of children (age <18 years) screened for TB within 2 Boston-area health systems between January 2017 and May 2019. Patients who received a tuberculin skin test (TST) and/or an interferon gamma release assay (IGRA) were included., Results: We included 13 353 tests among 11 622 patients; 93.9% of the tests were completed. Of 199 patients with positive tests for whom TB infection evaluation was clinically appropriate, 59.3% completed treatment or were recommended to not start treatment. Age 12-17 years (vs < 5 years; aOR 1.59; 95% CI, 1.32-1.92), non-English/non-Spanish language preference (vs English; aOR, 1.34; 95% CI, 1.02-1.76), and receipt of an IGRA (vs TST, aOR, 30.82; 95% CI, 21.92-43.34) were associated with increased odds of testing completion. Odds of testing completion decreased as census tract social vulnerability index quartile increased (ie, social vulnerability worsened; most vulnerable quartile vs least vulnerable quartile, aOR, 0.77; 95% CI, 0.60-0.99). Odds of completing treatment after starting treatment were higher in females (vs males; aOR, 2.35; 95% CI, 1.14-4.85) and were lower in patients starting treatment in a primary care clinic (vs TB/infectious diseases clinic; aOR, 0.44; 95% CI, 0.27-0.71)., Conclusions: Among children with a high proportion of negative TB infection tests, completion of testing was high, but completion of evaluation and treatment was moderate. Transitions toward IGRA testing will improve testing completion; interventions addressing social determinants of health are important to improve treatment completion., (Copyright © 2022 Elsevier Inc. All rights reserved.)

As a key issue in orchestrating various biological processes and functions, protein post-translational modification (PTM) occurs widely in the mechanism of protein's function of animals and plants. Glutarylation is a type of protein-translational modification that occurs at active ε-amino groups of specific lysine residues in proteins, which is associated with various human diseases, including diabetes, cancer, and glutaric aciduria type I. Therefore, the issue of prediction for glutarylation sites is particularly important. This study developed a brand-new deep learning-based prediction model for glutarylation sites named DeepDN&#95;iGlu via adopting attention residual learning method and DenseNet. The focal loss function is utilized in this study in place of the traditional cross-entropy loss function to address the issue of a substantial imbalance in the number of positive and negative samples. It can be noted that DeepDN&#95;iGlu based on the deep learning model offers a greater potential for the glutarylation site prediction after employing the straightforward one hot encoding method, with Sensitivity (Sn), Specificity (Sp), Accuracy (ACC), Mathews Correlation Coefficient (MCC), and Area Under Curve (AUC) of 89.29%, 61.97%, 65.15%, 0.33 and 0.80 accordingly on the independent test set. To the best of the authors' knowledge, this is the first time that DenseNet has been used for the prediction of glutarylation sites. DeepDN&#95;iGlu has been deployed as a web server (https://bioinfo.wugenqiang.top/~smw/DeepDN&#95;iGlu/) that is available to make glutarylation site prediction data more accessible.

Foot-and-mouth disease virus (FMDV) poses a significant threat to the livestock industry. Through their recognition of the conserved epitopes presented by the swine leukocyte antigen (SLA), T cells play a pivotal role in the antiviral immunity of pigs. Herein, based on the peptide binding motif of SLA-2*HB01, from an original SLA-2 allele, a series of functional T-cell epitopes derived from the dominant antigen VP1 of FMDV with high binding capacity to SLA-2 were identified. Two parallel peptides, Hu64 and As64, from the O and Asia I serotypes, respectively, were both crystallized with SLA-2*HB01. Compared to SLA-1 and SLA-3, the SLA-2 structures showed the flexibility of residues in the P4, P6, and P8 positions and in their potential interface with TCR. Notably, the peptides Hu64 and As64 adopted quite similar overall conformation when bound to SLA-2*HB01. Hu64 has two different conformations, a more stable 'chair' conformation and an unstable 'boat' conformation observed in the two molecules of one asymmetric unit, whereas only a single 'chair' conformation was observed for As64. Both Hu64 and As64 could induce similar dominant T-cell activities. Our interdisciplinary study establishes a basis for the in-depth interpretation of the peptide presentation of SLA-I, which can be used toward the development of universal vaccines.

US guidelines recommend interferon gamma release assays (IGRAs) for diagnosis of tuberculosis infection in children. In this retrospective cohort study, IGRA use in children 2-17 years of age increased substantially between 2015 and 2021. Testing in inpatient/subspecialty settings (vs. primary care), public (vs. private) insurance, lower age and non-English preferred language were associated with increased odds of receiving an IGRA., Competing Interests: J.I.C. was supported by Agency for Healthcare Research and Quality grant number T32 HS000063 as part of the Harvard-wide Pediatric Health Services Research Fellowship Program. J.E.H. is a consultant for Merck. The other authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Rolling bearings are the core components of mechanical and electrical systems. A practical fault diagnosis scheme is the key to ensure operational safety. There are excessive characteristic parameters with remarkable randomness and severe signal coupling in the rolling bearing operation, which makes the fault diagnosis to be challenging. To deal with this problem, the Gramian angular field (GAF) and DenseNet are combined to perform feature extraction and fault diagnosis. The GAF can convert 1-dimensional time series into an image, which can guarantee the completeness of feature information without temporal dependence. The GAF images are then trained by using the DenseNet to generate a data set network. In this process, the transfer learning (TL), which can solve the problem of insufficient samples, is integrated to the DenseNet to enhance its extensibility. The comparative simulations are carried out to illustrate the effectiveness of the proposed method.

Background: Sepsis is an inflammatory syndrome with life-threatening organ dysfunction and high mortality. In the recent 10 years, high-dose intravenous injection of vitamin C, the first-line antioxidant of humans, has received highlighted attention in the field of critical care. The study aims to examine the efficacy and safety of high-dose intravenous injection of vitamin C in the treatment of sepsis., Methods and Design: Here, we are conducting a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study named High-Dose Vitamin C on Sepsis (HDVCOS). A total of 620 participants diagnosed with sepsis in four participating sites across China that satisfy the eligibility criteria will be randomized at a ratio of 1:1 to receive treatment with a high-dose intravenous injection of vitamin C (200 mg/kg/24 h) or placebo (saline) for 4 days. The primary outcome is 28 days of mortality. The secondary outcomes include the incidence of organ failure, Sequential Organ Failure Assessment (SOFA) score change, organ support, the relationship between plasma vitamin C concentration and outcomes, and adverse events., Conclusion: The findings of this study will provide potential evidence for high-dose intravenous injection of vitamin C in the treatment of sepsis., Clinical Trial Registration: [http://www.chictr.org.cn/showprojen.aspx?proj=29851], identifier [ChiCTR1800017633]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Li, Sun, Li, Liu, Wang, Sun, Xu, Qi, Xie, Zhou, Ni, Yao, Chen, Yu, Jiang, Ning, Sheng, Chen, Wang, Tong, Cao, Sun and Mao.)

Introduction: Health literacy (HL) has been concerned a key factor for determining the use of health information and promoting health. The study aimed to explore the relationship between different health literacy types and health promoting lifestyle (HPL) in different health literacy population., Methods: The survey analyzed a sample of 16,921 community residents in Shenzhen. The Chinese Citizen Health Literacy Questionnaire and health-promoting lifestyle profile II (HPLP- II) were used to assess health literacy and health promoting lifestyle., Results: Participants were divided into different populations based on the correlation between HL and HPL. The low-HL and medium-HL populations were judged to lack health literacy, and demographic characteristics were significantly different between different HPL levels in low-HL and medium-HL populations. There were 6 types of HL, and health information literacy (β = 0.08, P < 0.001) and chronic disease literacy (β = 0.08, P < 0.001) positively predicted HPL in the low-HL population. In the medium-HL population, the results of reward and punishment analysis showed that health information was a basic factor, chronic disease was performance factor, medical care was a motivating factor for HPL; there were 6 dimensions of HPL, and health responsibility (HR), stress management (SM) and physical activity (PA) were not significantly different in medium-HL population. The results of regression analysis showed that HR and PA had a great impact on HPL (HR: β = 0.193, PA: β =0.179, β for other dimensions was 0.186, 0.176, 0.171, 0.164), but the HR and PA standardized scores were lowest in the HPL dimensions (HR: 69.42, PA: 68.5, lower than other dimensions), so it may be HR and PA that cause HPL unchanged between groups in the medium-HL population., Conclusions: Different HL levels have different relationships with HPL, and different HL types have different effects on HPL. Shenzhen community residents need to improve their HL, and they have great potentials for further progress to improve the population health. Public health policy makers need to consider formulating different policies for people with different HL levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Liao, Pan, Liang, Zeng, Sun, Luo, Ma, Yin and Ni.)

Ubiquitination is a versatile post-translational modification (PTM), which regulates diverse fundamental features of protein substrates, including stability, activity, and localization. Unsurprisingly, dysregulation of the complex interaction between ubiquitination and deubiquitination leads to many pathologies, such as cancer and neurodegenerative diseases. The versatility of ubiquitination is a result of the complexity of ubiquitin (Ub) conjugates, ranging from a single Ub monomer to Ub polymers with different length and linkage types. To further understand the molecular mechanism of ubiquitination signaling, innovative strategies are needed to characterize the ubiquitination sites, the linkage type, and the length of Ub chain. With advances in chemical biology tools, computational methodologies, and mass spectrometry, protein ubiquitination sites and their Ub chain architecture have been extensively revealed. The obtained information on protein ubiquitination helps to crack the molecular mechanism of ubiquitination in numerous pathologies. In this review, we summarize the recent advances in protein ubiquitination analysis to gain updated knowledge in this field. In addition, the current and future challenges and barriers are also reviewed and discussed., (© 2022. The Author(s).)

Scheduling lag time is the time between the date of an appointment and the date an appointment was created in the scheduling system. We sought to determine the scheduling lag time in a pediatric ophthalmology clinic for children <8 years of age, referred by a primary care provider for an abnormal red reflex (ARR), cataract, leukocoria, or retinoblastoma. The median scheduling lag time was 1.8 days (IQR, 0.8-5.0). Of the 106 total appointments, 89 (84%) were completed as scheduled, 12 (11%) were canceled, and 5 (5%) were no-shows. Ten patients (12%) were never seen. There was a shorter scheduling lag time for completed visits (median, 1.1 days; IQR, 0.2-4.0) than canceled visits (median, 12.0 days; IQR, 3.1-48.5; P < 0.001). Monitoring of the scheduling lag time for urgent referrals may be a metric for quality improvement in pediatric ophthalmology., (Copyright © 2022 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Dynamic miRNA alteration is known to occur in colitis-associated colon cancer (CAC), while the molecular mechanisms underpinning how miRNAs modulate the development from chronic inflammation to CAC is lacking. For the first time, we constructed knockout (KO) mice for individual miR-148/152 family members and entire miR-148/152 family. Based on these KO mice, we conduct the first comprehensive analysis of miR-148/152 family, demonstrating that deficiency of any member of miR-148/152 family aggravate colitis and CAC. Loss of individual miR-148/152 family members or full-family enhance MMP10 and MMP13 expression, causing disruption of intestinal barrier and cleaving pro-TNF-α into bioactive TNF-α fragments to activate NF-κB signaling, thereby aggravating colitis. Individual and full-family deletion also increase accumulation of IKKα and IKKβ, resulting in further hyperactivation of NF-κB signaling, exacerbating colitis and CAC. Moreover, blocking NF-κB signaling exerts a restorative effect on colitis and CAC models only in KO mice. Taken together, these findings demonstrate deleting the full miR-148/152 family or individual members exhibit similar effects in colitis and CAC. Mechanically, miR-148/152 family members deficiency in mice elevates MMP10 and MMP13 to accelerate colitis and CAC via disrupting intestinal barrier function and activating NF-κB signaling, suggesting a potential therapeutic strategy for colitis and CAC., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Phosphopeptides presented by major histocompatibility complex (MHC) class I have been regarded as a pivotal type of cancer neoantigens that are recognized by T cells. The structural basis of single-phosphorylated peptide presentation has been well studied. Diphosphorylation with one interval between two sites is one of the prevalent forms of multisite-phosphorylated peptides. Herein, we determined the molecular basis of presentation of two P4/P6 double pS-containing peptides by HLA-B27 and compared them with unmodified and single-phosphorylated peptide complexes. These data clarified not only the HLA allele-specific presentation of phosphopeptides by MHC class I molecules but also the cooperativity of peptide conformation within P4 and P6 phosphorylation sites. The phosphorylation of P6 site can influence the binding mode of P4 phosphorylated site to HLA-B27. And we found the diphospho-dependent attenuated effect of peptide binding affinity. This study provides insights into the MHC presentation features of diphosphopeptides, which is different from monophosphopeptides., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Cancer is one of the most dangerous threats to human health. One of the issues is drug resistance action, which leads to side effects after drug treatment. Numerous therapies have endeavored to relieve the drug resistance action. Recently, anticancer peptides could be a novel and promising anticancer candidate, which can inhibit tumor cell proliferation, migration, and suppress the formation of tumor blood vessels, with fewer side effects. However, it is costly, laborious and time consuming to identify anticancer peptides by biological experiments with a high throughput. Therefore, accurately identifying anti-cancer peptides becomes a key and indispensable step for anticancer peptides therapy. Although some existing computer methods have been developed to predict anticancer peptides, the accuracy still needs to be improved. Thus, in this study, we propose a deep learning-based model, called ACPNet, to distinguish anticancer peptides from non-anticancer peptides (non-ACPs). ACPNet employs three different types of peptide sequence information, peptide physicochemical properties and auto-encoding features linking the training process. ACPNet is a hybrid deep learning network, which fuses fully connected networks and recurrent neural networks. The comparison with other existing methods on ACPs82 datasets shows that ACPNet not only achieves the improvement of 1.2% Accuracy, 2.0% F1-score, and 7.2% Recall, but also gets balanced performance on the Matthews correlation coefficient. Meanwhile, ACPNet is verified on an independent dataset, with 20 proven anticancer peptides, and only one anticancer peptide is predicted as non-ACPs. The comparison and independent validation experiment indicate that ACPNet can accurately distinguish anticancer peptides from non-ACPs.

The fast advancement and deployment of sequencing technologies after the Human Genome Project have greatly increased our knowledge of the eukaryotic genome sequences. However, due to technological concerns, high-quality genomic data has been confined to a few key organisms. Moreover, our understanding of which portions of genomes make up genes and which transcript isoforms synthesize these genes is scarce. Therefore, the current study has been designed to explore the reliability of the tiger lily ( Lilium lancifolium Thunb ) transcriptome. The PacBio-SMRT was used for attaining the complete transcriptomic profile. We obtained a total of 815,624 CCS (Circular Consensus Sequence) reads with an average length of 1295 bp. The tiger lily transcriptome has been sequenced for the first time using third-generation long-read technology. Furthermore, unigenes (38,707), lncRNAs (6852), and TF members (768) were determined based on the transcriptome data, followed by evaluating SSRs (3319). It has also been revealed that 105 out of 128 primer pairs effectively amplified PCR products. Around 15,608 transcripts were allocated to 25 distinct KOG Clusters, and 10,706 unigenes were grouped into 52 functional categories in the annotated transcripts. Until now, no tiger lily lncRNAs have been discovered. Results of this study may serve as an extensive set of reference transcripts and help us learn more about the transcriptomes of tiger lilies and pave the path for further research., Competing Interests: Each author declares that their interests are not contradictory., (Copyright © 2022 Mingwei Sun et al.)

Drawing upon a dataset of cross-border mergers and acquisitions (M&A) events of Chinese enterprises from 2010 to 2017, this study investigates the impact of corporate social responsibility (CSR) on the completion of cross-border M&A with a focus on the moderating role of institutional distance. The results highlight the significance of CSR on the completion of cross-border M&A. The robustness tests including changing estimation model, new measurements, propensity score matching, and instrumental variable tests show that the main results are consistent. Second, both formal and informal institutional distance have positive moderating effects of CSR on the completion of cross-border M&A., Competing Interests: The authors have declared that no competing interests exist.

Background: Pediatric acute fulminant myocarditis (AFM) is a very dangerous disease that may lead to acute heart failure or even sudden death. Previous reports have identified some prognostic factors in adult AFM; however, there is no such research on children with AFM on venoarterial extracorporeal membrane oxygenation (VA-ECMO). This study aimed to find relevant prognostic factors for predicting adverse clinical outcomes., Methods: A retrospective analysis was performed in an affiliated university children's hospital with consecutive patients receiving VA-ECMO for AFM from July 2010 to November 2020. These children were classified into a survivor group (n=33) and a non-survivor group (n=8). Patient demographics, clinical events, laboratory findings, and electrocardiographic and echocardiographic parameters were analyzed., Results: Peak serum creatinine (SCr) and peak creatine kinase isoenzyme MB during ECMO had joint predictive value for in-hospital mortality (p=0.011, AUC=0.962). Based on multivariable logistic regression analysis, peak SCr level during ECMO support was an independent predictor of in-hospital mortality (OR=1.035, 95% CI 1.006 to 1.064, p=0.017, AUC=0.936, with optimal cut-off value of 78 μmol/L)., Conclusion: Tissue hypoperfusion and consequent end-organ damage ultimately hampered the outcomes. The need for left atrial decompression indicated a sicker patient on ECMO and introduced additional risk for complications. Earlier and more cautious deployment would likely be associated with decreased risk of complications and mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To investigate the current use status of official WeChat accounts for the Centers for Disease Control and Prevention in public health education and relevant factors that can impact the effectiveness of message delivery., Methods: A retrospective survey was conducted to evaluate the effectiveness of official WeChat accounts. About 531 official WeChat accounts and 50 939 articles were analyzed using a cluster sampling survey design. The Kruskal-Wallis test and multivariate logistic regression were used to explore factors associated with the usefulness of the number of views and "Likes" of the articles., Results: The study identified a total of 531 public WeChat accounts, including 19 province-level accounts, 179 municipal-level accounts and 333 county-level accounts. In the univariable analysis, the administrative level of the account, article order, time segment, article originality and thematic category were associated with the number of views and "Likes." Province-level accounts, first articles, the 5:00-6:00 time segment, original articles and theme 3 (emergencies) had higher numbers of views and "Likes" than the others (P < 0.05)., Conclusions: Promoting health education through Official WeChat account is an effective, sustainable and feasible strategy. Potential indicators of the impact of public health education suggest that administrators should effectively use official WeChat accounts for public health education., (© The Author(s) 2020. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Mycobacterium tuberculosis, the causative agent of human tuberculosis, harbors a branched electron transport chain, preventing the bactericidal action of cytochrome bc 1 inhibitors (e.g., TB47). Here, we investigated, using luminescent mycobacterial strains, the in vitro combination activity of cytochrome bc 1 inhibitors and nitric oxide (NO) donors including pretomanid (PMD) and explored the mechanisms of combination activity. The TB47 and PMD combination quickly abolished the light emission of luminescent bacilli, as was the case for the combination of TB47 and aurachin D, a putative cytochrome bd inhibitor. The TB47 and PMD combination inhibited M. tuberculosis oxygen consumption, decreased ATP levels, and had a delayed bactericidal effect. The NO scavenger carboxy-PTIO prevented the bactericidal activity of the drug combination, suggesting the requirement for NO. In addition, cytochrome bc 1 inhibitors were largely bactericidal when administered with DETA NONOate, another NO donor. Proteomic analysis revealed that the cotreated bacilli had a compromised expression of the dormancy regulon proteins, PE/PPE proteins, and proteins required for the biosynthesis of several cofactors, including mycofactocin. Some of these proteomic changes, e.g., the impaired dormancy regulon induction, were attributed to PMD. In conclusion, combination of cytochrome bc 1 inhibitors with PMD inhibited M. tuberculosis respiration and killed the bacilli. The activity of cytochrome bc 1 inhibitors can be greatly enhanced by NO donors. Monitoring of luminescence may be further exploited to screen cytochrome bd inhibitors.

Poly(ADP-ribose)polymerase-1 (PARP-1) plays a crucial role in DNA damage repair and could be viewed as both a tumor promoter and tumor-suppressor gene. However, the effects of PARP-1 in hydroquinone-induced malignant transformation of TK6 cells remain to be further elucidated. The present research evaluated the potential mechanism of PARP-1 in hydroquinone-induced malignant transformation of TK6 cells. The results indicated that high PARP-1 inhibited TK6 cells malignant transformation after chronic exposure to HQ. We further confirmed that PARP-1 overexpression blocked cell proliferation, and decelerated cell cycle progression in vitro and in vivo. The immunoblotting analysis indicated that PARP-1 regulated cell cycle progression via p16/Rb and p53. Therefore, we conclude that PARP-1 is involved in HQ-induced malignant transformation associated with increasing p16/Rb and p53 which resulting in decelerating the cell cycle progression., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The proportion of aging in China is increasing, which needs more healthcare recourses. To analyze the risk factors of the direct medical economic burden of aging in China and provide the strategies to control the cost of treatment, the information was collected based on Guangdong Province's regular health expenditure accounting data collection plan., Methods: The multiple linear regression models were used to explore the risk factors of inpatient expenses of the elderly in Guangdong province., Results: The results revealed that hospital day, age, male patients, and patients who suffer from malignant tumors are key factors to increase the direct medical economic burden of aging. Moreover, the medical insurance for urban employees can reduce the medical economic burden, comparing with the medical insurance for urban residents., Conclusions: The basic medical insurance system and the serious illness insurance system should be improved. While striving to speed up the development of regional economy, the government should pay attention to the construction of basic medical institutions in economically backward areas, increase the allocation of health human resources, and facilitate the masses to seek medical treatment nearby., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Jialong Chen et al.)

The endocrine disruption potency of BPA was reported elsewhere, but the mechanisms of its analogues have not been fully resolved. In this study, endocrine disruption potentials of nine alternative bisphenol analogues, namely 2,2-bis(4-hydroxyphenyl)butane (BPB), 2,2-Bis(4-hydroxy-3-methylphenyl)propane (BPC), 4,4'-dihydroxydiphenylmethane (BPF), 4,4'-(1,3-Phenylene diisopropylidene)bisphenol (BPM), 4,4'-(1,4-phenylenediisopropylidene)bisphenol (BPP), 4,4'- sulfonyldiphenol (BPS), 4,4' cyclohexylidenebisphenol (BPZ), 4,4' (hexafluoroisopropylidene)-diphenol (BPAF) and 4,4'-(1-phenylethylidene)bisphenol (BPAP), plus 2,2-bis(4-hydroxyphenyl)propane (BPA) were investigated by H295R cell and MVLN cell bioassays. In the H295R cell assay, the endpoints included hormone production and key genes for steroidogenesis (CYP11A, CYP17, CYP19 and 3βHSD2) or metabolism sulfotransferase (SULT1A1, SULT2A1 and SULT2B1) at the molecular level. The results indicated that except for BPP or BPAF, the eight other bisphenols significantly increased the E2/T ratio. In addition, BPB, BPF and BPS significantly up-regulate CYP19 gene expression, and only BPB significantly reduced sulfotransferase gene expression. In the MVLN luciferase gene reporter assay, seven bisphenols induced luciferase activity alone, and are 10 4 to 10 8 -fold less potent than E2. Their nuclear ERα binding activity is in the order of BPAF > BPZ > BPP > BPB > BPA > BPF > BPS. In summary, all nine tested bisphenols showed endocrine toxicity through different mechanisms. Some had similar potency as BPA, but some had even higher potency. Further research is necessary to evaluate the toxicity of these potential BPA substitutes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

SUMOylation is a reversible post-translational modification that plays crucial roles in numerous cellular processes. Although anti-SUMO antibodies have been applied to analyze exogenous and endogenous SUMOylation, such immunoprecipitation enrichment strategy is applicable only for the enrichment of one specific SUMO type in mammalian cells, unable to map the global landscape of all endogenous SUMOylation simultaneously. To address this issue, we proposed an antibody-free strategy to enrich and profile endogenous SUMO1/2/3-modified peptides simultaneously. Upon trypsin digestion, the SUMO1- and SUMO2/3-modified peptides contained SUMO remnants with 7 and 9 acidic amino acids respectively, which carried more negative charges at high pH and could interact with strong anion exchange (SAX) materials more strongly than non-SUMOylated peptides, thus enabling the specific enrichment of endogenous SUMOylated peptides. Followed by the secondary digestion with Asp-N/Glu-C to generate smaller SUMOylated peptides with proper length for MS identification, off-line high-pH C18 pre-fractionation and low pH nanoRPLC-ESI-MS/MS analysis, 177 SUMO1-modified sites and 74 SUMO2/3-modified sites were unbiasedly identified in HeLa cell lysate. To the best of our knowledge, this was the first antibody-free strategy to comprehensively profile various endogenous SUMOylation sites, demonstrating the great potential in the comprehensive analysis of endogenous SUMOylation across various species and organs, which might further facilitate the understanding of SUMO's function in physiology and pathology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: This study compares and analyzes the differences of residents' medical economic burden in different economic levels, explores the factors for improving the equity of health services in Guangdong, China., Methods: Cluster analysis was carried out in 20 cities of Guangdong Province by taking 7 key factors on the equity of health services as indicators. Seven key factors were collected from Guangdong Statistical Yearbook 2017 and the Sixth National Population Census. R-type clustering was used to reduce the dimensionality of 7 candidate variables through similarity index. Q-type clustering was used to classify 20 cities in Guangdong Province., Results: The cluster analysis divided Guangdong Province into three regions with different medical economic burden. The greater the proportion of the elderly over 65 years old, the greater the proportion of health care expenditure to per capita consumer expenditure of residents, and the heavier the medical economic burden. On average, 10.75% of the general budget expenditure of each city in Guangdong Province is spent on health care., Conclusions: The lower per capita GDP, the higher proportion of the elderly over 65 years old and the lack of medical technicians are risk factors for the heavier medical burden of the residents and the fairness of health services. While increasing the health expenditure, the government needs to further complete the reform of the medical and health system, improve the efficiency of the medical system and curb the rapid rise of absolute health expenditures of individuals, which can reduce the economic burden of residents' medical care.

Background: Glucocorticoid receptor (GR) signaling pathway has been shown to involve epithelial -to- mesenchymal transition which was implicated in the regulation of bladder cancer stem cells (CSCs) in our previous study. Herein, we aim to figure out how GR affects the stem-like properties of bladder cancer cells. Methods: We used dexamethasone (DEX) treatment or gene-knockdown/-knockout techniques to activate or silence the GR pathway, respectively. Then we applied immunohistochemical staining and flow cytometry to assess the associations between the expression levels of GR and a stem cell surface marker CD44. Stem-like properties were assessed by reactive oxygen species (ROS), sphere-formation and side population assays. The expression levels of cancer stem cell-associated molecules were assessed by quantitative PCR and Western blotting. Tumor growth was compared using mouse xenograft models. Results: In GR-positive bladder cancer cells, DEX significantly reduced the expression of CD44 as well as pluripotency transcription factors including β-catenin and its downstream target (C-MYC, Snail, and OCT-4), the rate of sphere formation, and the proportion of side populations, and induced the intracellular levels of ROS. By contrast, GR silencing in bladder cancer cells showed the opposite effects. In xenograft-bearing mice, GR silencing resulted in the enhancement of tumor growth. Conclusions: These data suggested that GR activity was inversely associated with the stem-like properties of bladder cancer cells, potentially via inactivating the β-catenin pathway., (Copyright © 2020 Xu, Sun, Zhang, Xu, Miyamoto and Zheng.)

Streptococcus agalactiae is one of the causative agents of subclinical mastitis, a common disease of dairy cows that causes great economic losses in the industry worldwide. It is thought that pathology is mainly due to inflammatory damage of bovine mammary epithelial cells (bMECs); however, the mechanism by which S. agalactiae damages the bMECs is not clear. The aim of this study was to evaluate the inflammatory effects of S. agalactiae on bMECs and the resulting changes in protein profiles. The bMECs were incubated with S. agalactiae for different times and assayed for cell viability by MTT assay, apoptosis by annexin V and propidium iodide dual staining, and morphological and ultrastructural changes by scanning and transmission electron microscopy. Quantitative real-time PCR was used to determine the effect of S. agalactiae on expression of mRNA of inflammatory factors in bMECs and protein levels were quantitated by liquid chromatography/mass spectrometry. Exposure to S. agalactiae significantly decreased the cell viability and triggered apoptosis, as well as up-regulating TNF-α, IL-1β and IL-6 mRNA, and inhibiting IL-8 expression. S. agalactiae also induced morphological and ultrastructural changes. Furthermore, we identified 325 up-regulated and 704 down-regulated proteins in the treated vs control group. All significant differentially expressed proteins (DSEPs) were classified into three major areas by function: biological processes, cellular components and molecular functions. These differentially expressed proteins included enzymes and proteins associated with various metabolic processes and cellular immunity. Pathway enrichment analysis showed that eight down-regulated signaling pathways were significantly enriched. Exposure to even subclinical levels of S. agalactiae can lead to inflammation and bMEC damage. Our data suggest some possible molecular mechanisms for the harmful effects of subclinical mastitis in dairy cows.

Protein phosphorylation is one of the most important post-translational modifications (PTM) and plays critical roles in maintaining many biological processes of plant species, such as being a significant signal related to resistance to tobacco mosaic virus (TMV) infection in tobacco. Compared to other organisms, in-depth profiling of plant phosphoproteome remains challenging due to the harsh extraction environment of plant proteins and low abundance of plant phosphorylation, generally requiring large amount of plant materials. Herein, we developed an integrated strategy for efficient sample preparation of amounts of plant tissues, by integrating ionic liquid (IL)-assisted protein extraction, in-solution digestion, precipitation-assisted IL removal, as well as immobilized metal ion affinity chromatography (IMAC) enrichment of phosphopeptides together. In this strategy, to improve the efficiency of protein extraction and enzymatic digestion, IL of 1-dodecyl-3-methylimidazolium chloride (C12Im-Cl) was used as the solubilizer due to its excellent solubilizing ability and enzyme compatibility demonstrated in our previous work. Briefly, the extraction capability of C12Im-Cl for protein amount from tobacco leaves was improved 1.9-fold compared to the commonly used urea-assisted method. Notably, to avoid its interference with subsequent LC-MS analysis, the IL was easily removed from the peptide solution by our proposed ion substitution-mediated C12Im + precipitation strategy with high efficiency. By handling 10 mg of starting protein materials of tobacco leaves, 14,441 unique phosphopeptides, assigned to 5153 unique phosphoproteins were confidently identified. To the best of our knowledge, this was the most comprehensive phosphorylation dataset for tobacco so far. All the results demonstrated our strategy was of great potential to promote the large-scale analysis of plant phosphoproteome., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2020. Published by Elsevier B.V.)