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Menglan Zhou,1–3 Yao Wang,1,3 Chang Liu,1–3 Timothy Kudinha,4 Xiaolin Liu,5,6 Yanping Luo,7 Qiwen Yang,1,3,6 Hongli Sun,1,3,6 Jihong Hu,8 Ying-Chun Xu1,3,6 1Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China; 2Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China; 3Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, China; 4Department of Clinical Laboratory, Charles Sturt University, Leeds Parade, Orange, New South Wales, Australia; 5National Health and Family Planning Commission Expert Committee for Clinical Use of Antibiotics and Assessment of Bacterial Resistance, Beijing, China; 6Quality Management Center of China Antimicrobial Resistance Surveillance System (CARSS), Beijing, China; 7Department of Clinical Laboratory, Chinese PLA General Hospital, Beijing, China; 8National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, China Objective: The objective of this study was to evaluate the performance of five commonly used automated antimicrobial susceptibility testing (AST) systems in China (Vitek 2, Phoenix, Microscan, TDR, and DL). Materials and methods: Two “unknown” isolates, S1 (ESBL-producing Escherichia coli) and S2 (KPC-producing Klebsiella pneumoniae), were sent to 886 hospitals in China for identification and AST. Using broth microdilution method (BMD) as gold standard, minimum inhibitory concentrations (MICs) were determined. Results: Most hospitals (392, 46.1%) used Vitek 2, followed by 16% each for Phoenix, Microscan, and DL systems, and 5.9% (50) used TDR system. MICs of 22 antimicrobials were evaluated for two study isolates plus three ATCC strains. Individual susceptibility results for three ATCC strains (n=1581) were submitted by 780 (91.2%) hospitals. For each AST system, 8.7% (6/69) to 13.0% (33/253) reported MICs outside the expected range for several drugs. For the two study isolates, TDR and DL systems performed the worst in MIC determination and susceptibility categorization of cefazolin and cefepime, while the Microscan system had difficulties in susceptibility categorization for aztreonam and ertapenem. Categorical agreements were >90% for most antimicrobials tested for both the isolates, among which, using BMD, no essential agreements were noted for ampicillin, piperacillin, cefazolin, cefuroxime, ceftriaxone, and trimethoprim/sulfamethoxazole. All AST systems except Vitek 2 showed unacceptable VMEs for cefazolin (S1 and S2) and major errors for ceftazidime, cefepime, and aztreonam (isolate S1), while Vitek 2 showed a high VME rate for cefepime (10.0%) and meropenem (6.2%) for S2. Conclusion: None of the five automated systems met the criteria for acceptable AST performance, but Vitek 2 provided a relatively accurate and conservative performance for most of the antimicrobials. Keywords: automated susceptibility testing, accuracy, evaluation, CARSS

Ye Wang,1,* Qi-Wei Yang,1,2,* Qing Yang,2,* Tie Zhou,1 Min-Feng Shi,1,3 Chen-Xia Sun,4 Xiu-Xia Gao,4 Yan-Qiong Cheng,1 Xin-Gang Cui,2 Ying-Hao Sun1 1Department of Urology, Changhai Hospital, 2Department of Urology, The Third Affiliated Hospital, 3Reproductive Center, Changhai Hospital, Second Military Medical University, Shanghai, 4The Reproductive Center, Institute for Nutritional Sciences, Shanghai Institute for Biological Science, Chinese Academy of Science, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Disordered copper metabolism plays a critical role in the development of various cancers. As a nanomedicine containing copper, cuprous oxide nanoparticles (CONPs) exert ideal antitumor pharmacological effects in vitro and in vivo. Prostate cancer is a frequently diagnosed male malignancy prone to relapse, and castration resistance is the main reason for endocrine therapy failure. However, whether CONPs have the potential to treat castration-resistant prostate cancer is still unknown. Here, using the castration-resistant PC-3 human prostate cancer cell line as a model, we report that CONPs can selectively induce apoptosis and inhibit the proliferation of cancer cells in vitro and in vivo without affecting normal prostate epithelial cells. CONPs can also attenuate the stemness of cancer cells and inhibit the Wnt signaling pathway, both of which highlight the great potential of CONPs as a new clinical castration-resistant prostate cancer therapy. Keywords: cuprous oxide nanoparticle, prostate cancer, CRPC, nanomedicine, Wnt signaling pathway

The mission of HL-2A is to explore the key physical topics relevant to ITER and to the advanced tokamak operation (e.g. the operation of future HL-2M), such as the access of H-mode, energetic particle physics, edge-localized mode (ELM) mitigation/suppression and disruption mitigation. Since the 2016 Fusion Energy Conference, the HL-2A team has focused on the investigations on the following areas: (i) pedestal dynamics and L-H transition, (ii) techniques of ELM control, (iii) turbulence and transport, (iv) energetic particle physics. The HL-2A results demonstrated that the increase of mean shear flow plays a key role in triggering L-I and I-H transitions, while the change of flow is mainly induced by the ion pressure gradient. Both mitigation and suppression of ELMs were realized by laser blow-off seeded impurity (Al, Fe, W). The 30% Ne mixture supersonic molecular beam injection seeding also robustly induced ELM mitigation. The ELMs were mitigated by low-hybrid current drive. The stabilization of m/n = 1/1 ion fishbone activities by electron cyclotron resonance heating was found on the HL-2A. A new m/n = 2/1 ion fishbone activity was observed recently, and the modelling indicated that passing fast ions dominantly contribute to the driving of 2/1 fishbone. The non-linear coupling between the toroidal Alfven eigenmode and tearing mode (TM) led to the generation of a high frequency mode with the toroidal mode number n = 0. The turbulence was modulated by TM when the island width exceeds a threshold and the modulation is localized merely in the inner area of the islands. Meanwhile, turbulence radial spread took place across the island region.

The synchronization of geodesic acoustic modes (GAMs) and magnetic fluctuations is identified in the edge plasmas of the HL-2A tokamak. Mesoscale electric fluctuations (MSEFs) having components of a dominant GAM, and m/n=6/2 potential fluctuations are found at the same frequency as that of the magnetic fluctuations of m/n=6/2 (m and n are poloidal and toroidal mode numbers, respectively). The temporal evolutions of the MSEFs and the magnetic fluctuations clearly show the frequency entrainment and the phase lock between the GAM and the m/n=6/2 magnetic fluctuations. The results indicate that GAMs and magnetic fluctuations can transfer energy through nonlinear synchronization. Such nonlinear synchronization may also contribute to low-frequency zonal flow formation, reduction of turbulence level, and thus confinement regime transitions.

Transitions between low (L-mode) and intermediate (I-phase) confinement regimes triggered by sawteeth are investigated using multiple Langmuir probe arrays in the edge plasmas of the HL-2A tokamak. The I-phase is characterized by limit-cycle oscillations (LCOs). Repeated L-I-L transitions induced by sawtooth heat pulses are also observed. Statistical analyses show that the delay time of the L-I transition relative to sawtooth crashes is less than ∼1 ms. The intensity of turbulence bursts in the I-phase is stronger than those observed in L-mode plasmas. Measurements are consistent with zonal flow reducing turbulence intensity in the frequency band ∼20-100 kHz, while the LCO turbulence of frequency higher than 100 kHz has more power than that in the L-mode. The analyses of time-resolved power transfers between turbulence and zonal flows suggest that power transfers exist between turbulence and zonal flows. The direction of the power transfers is from turbulence into geodesic acoustic modes in ohmic plasmas. © 2013 IAEA, Vienna.

For the first time supersonic molecular beam injection (SMBI) and cluster jet injection (CJI) were applied to mitigate edge-localized modes (ELMs) in HL-2A successfully. The ELM frequency increased by a factor of 2-3 and the heat flux on the divertor target plates decreased by 50% on average after SMBI or CJI. Energetic particle induced modes were observed in different frequency ranges with high-power electron cyclotron resonance heating (ECRH). The high frequency (200-350 kHz) of the modes with a relatively small amplitude was close to the gap frequency of the toroidicity-induced Alfvén eigenmode. The coexistent multi-mode magnetic structures in the high-temperature and low-collision plasma could affect the plasma transport dramatically. Long-lived saturated ideal magnetohydrodynamic instabilities during strong neutral beam injection heating could be suppressed by high-power ECRH. The absolute rate of nonlinear energy transfer between turbulence and zonal flows was measured and the secondary mode competition between low-frequency (LF) zonal flows (ZFs) and geodesic acoustic modes (GAMs) was identified, which demonstrated that ZFs played an important role in the L-H transition. The spontaneously generated E × B shear flow was identified to be responsible for the generation of a large-scale coherent structure (LSCS), which provided unambiguous experimental evidence for the LSCS generation mechanism. New meso-scale electric potential fluctuations (MSEFs) at frequency f ∼ 10.5 kHz with two components of n = 0 and m/n = 6/2 were also identified in the edge plasmas for the first time. The MSEFs coexisted and interacted with magnetic islands of m/n = 6/2, turbulence and LF ZFs. © 2013 IAEA, Vienna.

The radial structures of multiple sheared flow populations and fluctuations are simultaneously measured using combinations of Langmuir probe arrays in the edge plasmas of the HL-2A tokamak with ohmic and electron cyclotron resonance heating (ECRH). The maximum of geodesic acoustic mode (GAM) amplitude locates at ∼2-3 cm inside the last close flux surface (LCFS). The low-frequency zonal flow (LFZF) and GAM tend to coexist in the inner region. The dependences of the amplitudes of the multiple sheared flows and turbulence on ECRH heating power are also investigated. The measured turbulent Reynolds stresses are shown to be strongly correlated with the sheared flows, as predicted by theory. The turbulence is modulated at the each frequency of the multiple sheared flows simultaneously, and the particle fluxes induced by the turbulence are significantly reduced near the LCFS and in the GAM peaking region. The analyses also show that the spatial structures of the turbulent envelopes at the LFZF and GAM frequencies are similar to those observed in LFZF and GAM. © 2013 IAEA, Vienna.

Abstract Density profiles in the pedestal region (H-mode) are measured in HL-2A and the characteristics of the density pedestal are described. Cold particle deposition by supersonic molecular beam injection (SMBI) within the pedestal is verified. Edge-localized mode (ELM) mitigation by SMBI into the H-mode pedestal is demonstrated and the relevant physics is elucidated. The sensitivity of the effect to SMBI pressure and duration is studied. Following SMBI, the ELM frequency increases and the ELM amplitude decreases for a finite duration. Increases in ELM frequency of are achieved. This experiment argues that the ELM mitigation results from an increase in higher frequency fluctuations and transport events in the pedestal, which are caused by SMBI. These inhibit the occurrence of large transport events which span the entire pedestal width. The observed change in the density pedestal profiles and edge particle flux spectrum with and without SMBI supports this interpretation. An analysis of the experiment and a model shows that ELMs can be mitigated by SMBI with shallow particle penetration into the pedestal.

The absolute rate of nonlinear energy transfer among broadband turbulence, low-frequency zonal flows (ZFs) and geodesic acoustic modes (GAMs) was measured for the first time in fusion-grade plasmas using two independent methods across a range of heating powers. The results show that turbulent kinetic energy from intermediate frequencies (20-80 kHz) was transferred into ZFs and GAMs, as well as into fluctuations at higher frequencies (>80  kHz). As the heating power was increased, the energy transfer from turbulence into GAMs and the GAM amplitudes increased, peaked and then decreased, while the energy transfer into the ZFs and the ZFs themselves increased monotonically with heating power. Thus there exists a competition between ZFs and GAMs for the transfer of turbulent energy, and the transfer into ZFs becomes dominant as the heating power is increased. The poloidal-radial Reynolds stress and the mean radial electric field profiles were also measured at different heating powers and found to be consistent with the energy transfer measurement. The results suggest that ZFs play an important role in the low-to-high (L-H) plasma confinement transition.

A static-based detection method is proposed in this study to provide an insight to the location and extent of structural damage. The proposed method makes use of the new flexibility disassembly technique and approaches the damage location and extent problem in a decoupled fashion. First, a scheme is developed to determine the damage location by calculating a damage localization vector, which is derived from the static response equation. With location determined, the corresponding damage extent can be easily calculated only by simple arithmetic operations. For selecting the loading location, a simple approach is presented to determine the static load that can activate all parts of a structure to have deformations. The efficiency of the proposed method is demonstrated by three numerical examples. Results show that the method is simple and effective for structural damage detection. [ABSTRACT FROM AUTHOR]

This paper presented a new method for structural damage identification based on flexibility disassembly. The basic idea of the developed theory is to decompose a structural flexibility matrix into a matrix representation of the connectivity between degrees-of-freedom and a diagonal matrix containing the magnitude information. Using the flexibility disassembly, a new damage detection scheme is presented to approach the damage identification problem in three steps. The scheme has a unique advantage that it can accurately compute the stiffness perturbation parameter without any higher-order sensitivity analysis or iteration. The efficiency of the proposed method is demonstrated by five numerical examples. [ABSTRACT FROM PUBLISHER]

Diclazuril (DIC) is a broad-spectrum anti-coccidiosis drug of the triazine class, widely used in poultry farming. The overuse of DIC may lead to its accumulation in animal bodies, which may enter the food chain and threaten human health. In this work, we fabricated a stable Eu 3+ -doped UiO-66 fluorescence sensor (EuUHIPA-30) for the sensitive detection of DIC. Among 20 veterinary drugs, the fluorescence of EuUHIPA-30 selectively responds to DIC, with a low detection limit (0.19 μM) and fast response (10 s). EuUHIPA-30 is recyclable and can detect DIC in chicken and eggs with good recoveries. Moreover, a smartphone-integrated paper-based sensor enables the instrument-free, rapid, visual, and intelligent detection of DIC in chickens and eggs. This work provides a promising candidate for practical fluorescent DIC sensing in animal-derived food to promote food safety., 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 Ltd. All rights reserved.)

Objectives: To establish the epidemiology cut-off (ECOFF) values of eravacycline against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter baumannii and Staphylococcus aureus, from a multi-centre study in China., Methods: We collected 2500 clinical isolates from five hospitals in China from 2017 to 2020. The MICs of eravacycline were determined using broth microdilution. The ECOFF values of eravacycline against the five species commonly causing cIAIs were calculated using visual estimation and ECOFFinder following the EUCAST guideline., Results: The MICs of eravacycline against all the strains were in the range of 0.004-16 mg/L. The ECOFF values of eravacycline were 0.5 mg/L for E. coli, 2 mg/L for K. pneumonia and E. cloacae, and 0.25 mg/L for A. baumannii and S. aureus, consistent with the newest EUCAST publication of eravacycline ECOFF values for the populations. No discrepancy was found between the visually estimated and 99.00% ECOFF values calculated using ECOFFinder., Conclusions: The determined ECOFF values of eravacycline against the five species can assist in distinguishing wild-type from non-wild-type strains. Given its promising activity, eravacycline may represent a member of the tetracycline class in treating cIAIs caused by commonly encountered Gram-negative and Gram-positive pathogens., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Objective: The objective of this study was to investigate the correlation between serum levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels and their ratios with the severity of white matter hyperintensities (WMHs) in patients with cerebral small vessel disease (CSVD)., Methods: This cross-sectional study was done on a prospective cohort of patients with CSVD. Qualitative and quantitative analyses of WMHs were performed using Fazekas grading and lesion prediction algorithm (LPA) methods. Biomarkers MMP-2, MMP-9, and TIMP-1 were measured to explore their correlation with the severity of WMHs., Results: The sample consisted of 144 patients with CSVD. There were 63 male and 81 female patients, with an average age of 67.604 ± 8.727 years. Among these, 58.33% presented with white matter hyperintensities at Fazekas grading level 1, with an average total template volume of WMHs of 4.305 mL. MMP-2 (P = 0.025), MMP-9 (P = 0.008), TIMP-1 (P = 0.026), and age (P = 0.007) were identified as independent correlates of WMHs based on Fazekas grading. Independent correlates of the total template volume of WMHs included MMP-2 (P = 0.023), TIMP-1 (P = 0.046), age (P = 0.047), systolic blood pressure (P = 0.047), and homocysteine (Hcy) (P = 0.014). In addition, age (P = 0.003; P < 0.001), interleukin-6 (IL-6) (P < 0.001; P = 0.044), Hcy (P < 0.001; P < 0.001), glycated hemoglobin (HbA1c) (P = 0.016; P = 0.043), and chronic kidney disease (P < 0.001; P < 0.001) were associated with both WMHs Fazekas grading and the total template volume of WMHs., Conclusion: Serum levels of MMP-9, MMP-2, and TIMP-1 were independently associated with the Fazekas grading, while serum TIMP-1 and MMP-2 levels were independently related to the total template volume of WMHs. The association of TIMP-1 and MMP-2 with the severity of CSVD-related WMHs suggests their potential role as disease-related biomarkers. However, further research is required to uncover the specific mechanisms underlying these interactions., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: Although lactate supplementation at the reperfusion stage of ischemic stroke has been shown to offer neuroprotection, whether the role of accumulated lactate at the ischemia phase is neuroprotection or not remains largely unknown. Thus, in this study, we aimed to investigate the roles and mechanisms of accumulated brain lactate at the ischemia stage in regulating brain injury of ischemic stroke. Methods and Results: Pharmacological inhibition of lactate production by either inhibiting LDHA or glycolysis markedly attenuated the mouse brain injury of ischemic stroke. In contrast, additional lactate supplement further aggravates brain injury, which may be closely related to the induction of neuronal death and A1 astrocytes. The contributing roles of increased lactate at the ischemic stage may be related to the promotive formation of protein lysine lactylation (Kla), while the post-treatment of lactate at the reperfusion stage did not influence the brain protein Kla levels with neuroprotection. Increased protein Kla levels were found mainly in neurons by the HPLC-MS/MS analysis and immunofluorescent staining. Then, pharmacological inhibition of lactate production or blocking the lactate shuttle to neurons showed markedly decreased protein Kla levels in the ischemic brains. Additionally, Ldha specific knockout in astrocytes ( Aldh1l1 CreERT2 ; Ldha fl/fl mice, cKO) mice with MCAO were constructed and the results showed that the protein Kla level was decreased accompanied by a decrease in the volume of cerebral infarction in cKO mice compared to the control groups. Furthermore, blocking the protein Kla formation by inhibiting the writer p300 with its antagonist A-485 significantly alleviates neuronal death and glial activation of cerebral ischemia with a reduction in the protein Kla level, resulting in extending reperfusion window and improving functional recovery for ischemic stroke. Conclusion: Collectively, increased brain lactate derived from astrocytes aggravates ischemic brain injury by promoting the protein Kla formation, suggesting that inhibiting lactate production or the formation of protein Kla at the ischemia stage presents new therapeutic targets for the treatment of ischemic stroke., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

White matter injury (WMI) causes oligodendrocyte precursor cell (OPC) differentiation arrest and functional deficits, with no effective therapies to date. Here, we report increased expression of growth hormone (GH) in the hypoxic neonatal mouse brain, a model of WMI. GH treatment during or post hypoxic exposure rescues hypoxia-induced hypomyelination and promotes functional recovery in adolescent mice. Single-cell sequencing reveals that Ghr mRNA expression is highly enriched in vascular cells. Cell-lineage labeling and tracing identify the GHR-expressing vascular cells as a subpopulation of pericytes. These cells display tip-cell-like morphology with kinetic polarized filopodia revealed by two-photon live imaging and seemingly direct blood vessel branching and bridging. Gain-of-function and loss-of-function experiments indicate that GHR signaling in pericytes is sufficient to modulate angiogenesis in neonatal brains, which enhances OPC differentiation and myelination indirectly. These findings demonstrate that targeting GHR and/or downstream effectors may represent a promising therapeutic strategy for WMI., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Metagenomic next-generation sequencing (mNGS) has been increasingly applied in sepsis. We aimed to evaluate the diagnostic and therapeutic utility of mNGS of paired plasma and peritoneal drainage (PD) fluid samples in comparison to culture-based microbiological tests (CMTs) among critically ill patients with suspected acute intra-abdominal infections (IAIs)., Methods: We conducted a prospective study from October 2021 to December 2022 enrolling septic patients with suspected IAIs (n = 111). Pairwise CMTs and mNGS of plasma and PD fluid were sent for pathogen detection. The mNGS group underwent therapeutic regimen adjustment based on mNGS results for better treatment. The microbial community structure, clinical features, antibiotic use and prognoses of the patients were analyzed., Results: Higher positivity rates were observed with mNGS versus CMTs for both PD fluid (90.0% vs. 48.3%, p < 0.005) and plasma (76.7% vs. 1.6%, p < 0.005). 90% of enrolled patients had clues of suspected pathogens combining mNGS and CMT methods. Gram-negative pathogens consist of most intra-abdominal pathogens, including a great variety of anaerobes represented by Bacteroides and Clostridium. Patients with matched plasma- and PD-mNGS results had higher mortality and sepsis severity. Reduced usage of carbapenem (30.0% vs. 49.4%, p < 0.05) and duration of anti-MRSA treatment (5.1 ± 3.3 vs. 7.0 ± 8.4 days, p < 0.05) was shown in the mNGS group in our study., Conclusions: Pairwise plasma and PD fluid mNGS improves microbiological diagnosis compared to CMTs for acute IAI. Combining plasma and PD mNGS could predict poor prognosis. mNGS may enable optimize empirical antibiotic use., (© 2024. The Author(s).)

Introduction: The impact of immunosuppression on prognosis of carbapenem-resistant organism (CRO) bloodstream infection (BSI) remains unclear. The aim of this study was to clarify the relationship between immunosuppression and mortality of CRO-BSI and to identify the risk factors associated with mortality in immunosuppressed patients., Methods: This retrospective study included 279 patients with CRO-BSI from January 2018 to March 2023. Clinical characteristics and outcomes were compared between the immunosuppressed and immunocompetent patients. The relationship between immunosuppression and 30-day mortality after BSI onset was assessed through logistic-regression analysis, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Factors associated with mortality in immunosuppressed patients were analyzed using multivariable logistic regression analysis., Results: A total of 88 immunocompetent and 191 immunosuppressed patients were included, with 30-day all-cause mortality of 58.8%. Although the 30-day mortality in immunosuppressed patients was significantly higher than in immunocompetent patients (46.6% vs. 64.4%, P = 0.007), immunosuppression was not an independent risk factor for mortality in multivariate logistic regression analysis (odds ratio [OR] 3.53, 95% confidence interval [CI] 0.74-18.89; P = 0.123), PSM (OR 1.38, 95% CI 0.60-3.18; P = 0.449,) or IPTW (OR 1.40, 95% CI 0.58-3.36; P = 0.447). For patients with CRO-BSI, regardless of immune status, appropriate antibiotic therapy was associated with decreased 30-day mortality, while Charlson comorbidity index (CCI), intensive care unit (ICU)-acquired infection and thrombocytopenia at CRO-BSI onset were associated with increased mortality., Conclusion: Despite the high mortality rate of CRO-BSI, immunosuppression did not affect the mortality. Appropriate antibiotic therapy is crucial for improving the prognosis of CRO-BSI, regardless of the immune status., (© 2024. The Author(s).)

The photo-Fenton process provides a sustainable and cost-effective strategy for removing refractory organic contaminants in wastewater. Herein, a high-efficient Fe-doped g-C 3 N 4 photocatalyst (Fe@CN 10 ) with a unique 3D porous mesh structure was prepared by one-pot thermal polymerization for ultrafast degradation of azo dyes, antibiotics, and phenolic acids in heterogeneous photo-Fenton systems under visible light irradiation. Fe@CN 10 exhibited a synergy between adsorption-degradation processes due to the co-existence of Fe 3 C and Fe 3 N active sites. Specifically, Fe 3 C acted as an adsorption site for pollutant and H 2 O 2 molecules, while Fe 3 N acted as a photocatalytic active site for the high-efficient degradation of MO. Resultingly, Fe@CN 10 showed a photocatalytic degradation rate of MO up to 140.32 mg/L min -1 . The dominant ROS contributed to the removal of MO in the photo-Fenton pathway was hydroxyl radical (•OH). Surprisingly, as the key reactive species, singlet oxygen ( 1 O 2 ) generated from superoxide radical (•O 2 - ) also efficiently attacked MO in a photo-self-Fenton pathway. Additionally, sponge/Fe@CN 10 was prepared and filled in the continuous flow reactors for nearly 100% degradation of MO over 150 h when treating artificial organic wastewater. This work provided a facile route to prepare highly-active Fe-doped photocatalysts and develop a green photocatalytic system for wastewater treatment in the future., 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 Ltd. All rights reserved.)

Major facilitator superfamily domain-containing 2a (Mfsd2a) is a sodium-dependent lysophosphatidylcholine cotransporter that plays an important role in maintaining the integrity of the blood-brain barrier and neurological function. Abnormal degradation of Mfsd2a often leads to dysfunction of the blood-brain barrier, while upregulation of Mfsd2a can retrieve neurological damage. It has been reported that Mfsd2a can be specifically recognized and ubiquitinated by neural precursor cell-expressed developmentally downregulated gene 4 type 2 (NEDD4-2) ubiquitin ligase and finally degraded through the proteasome pathway. However, the structural basis for the specific binding of Mfsd2a to NEDD4-2 is unclear. In this work, we combined deep learning and molecular dynamics simulations to obtain a Mfsd2a structure with high quality and a stable Mfsd2a/NEDD4-2-WW3 interaction model. Moreover, molecular mechanics generalized Born surface area (MM-GBSA) methods coupled with per-residue energy decomposition studies were carried out to analyze the key residues that dominate the binding interaction. Based on these results, we designed three peptides containing the key residues by truncating the Mfsd2a sequences. One of them was found to significantly inhibit Mfsd2a ubiquitination, which was further validated in an oxygen-glucose deprivation (OGD) model in a human microvascular endothelial cell line. This work provides some new insights into the understanding of Mfsd2a and NEDD4-2 interaction and might promote further development of drugs targeting Mfsd2a ubiquitination.

Neurological disorders affect a large population, often leading to different levels of disability and resulting in decreased quality of life. Due to the limited recovery obtained from surgical procedures and other medical approaches, a large number of patients with prolonged dysfunction receive neurorehabilitation protocols to improve their neural plasticity and regeneration. However, the poor neural regeneration ability cannot effectively rebuild the tissue integrity and neural functional networks; consequently, the prognoses of neurorehabilitation remain undetermined. To increase the chances of neural regeneration and functional recovery for patients with neurological disorders, regenerative rehabilitation was introduced with combined regenerative medicine and neurorehabilitation protocols to repair neural tissue damage and create an optimized biophysical microenvironment for neural regeneration potential. With the deepening of exosome research, an increasing number of studies have found that the systemic therapeutic effects of neurorehabilitation approaches are mediated by exosomes released by physically stimulated cells, which provides new insight into rehabilitative mechanisms. Meanwhile, exosome therapy also serves as an alternative cell-free therapy of regenerative medicine that is applied in partnership with neurorehabilitation approaches and formulates exosome-based neurological regenerative rehabilitation. In this study, we review the current state of exosome-associated neurorehabilitation. On the one hand, we focus on presenting the varied mediating effects of exosomes in neurorehabilitation protocols of specific neurological pathologies; on the other hand, we discuss the diverse combinations of exosome therapies and neurorehabilitation approaches in the field of neurological regenerative rehabilitation, aiming to increase the awareness of exosome research and applications in the rehabilitation of neurological disorders., 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: The identification of Aspergillus by metagenomic next-generation sequencing (mNGS) remains a challenging task due to the difficulty of nucleic acid extraction. The objective of this study was to determine whether mNGS could provide an accurate and efficient method for detecting invasive pulmonary aspergillosis (IPA) in immunocompromised patients (ICP)., Methods: A total of 133 ICP admitted to the ICU between January 2020 and September 2022 were enrolled in the study, of which 46 were diagnosed with IPA and 87 were non-IPA cases. The bronchoalveolar lavage fluid (BALF) was analyzed for the presence of Aspergillosis and other co-pathogens using mNGS, and its diagnostic performance was compared to conventional microbial tests (CMTs) that included smear, cultures, serum and BALF galactomannan (GM) test. Clinical composite diagnosis was used as the reference standard., Results: mNGS had a sensitivity, specificity, and accuracy of 82.6%, 97.7%, and 92.5%, respectively, in diagnosing IPA. These findings were comparable to those of the combination of multiple CMTs. Interestingly, the sensitivity of mNGS was superior to that of any single CMT method, as demonstrated by comparisons with smears (8.7%, P < 0.001), culture (39.1%, P < 0.001), serum GM (23.9%, P < 0.001) and BALF GM (69.6%, P = 0.031). mNGS was capable of accurately distinguish strains of Aspergillus genus, with a consistency of 77.8% with culture. Furthermore, mNGS also identified A. fumigatus , A. flavus , A. terrestris , A. oryzae and Mucor spp. in culture-negative cases. The sequencing reads of Aspergillus by mNGS exhibited extensive variation, ranging from 11 to1702. A positive correlation was observed between the optical density index of BALF GM and unique reads by mNGS (r = 0.607, P = 0.001) in BALF-GM positive patients. Notably, mNGS was able to diagnose 35 out of 37 cases with mixed infection, with P. jirovecii and cytomegalovirus being the most common co-pathogens., Conclusions: mNGS presents a feasible and remarkably sensitive approach for detecting Aspergillus in ICP, thereby serving as a valuable adjunctive tool to CMT. Furthermore, mNGS's ability to accurately identify fungal species and co-pathogens can assist in guiding appropriate antimicrobial therapy., 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 © 2023 Shi, Peng, Hu, Yang and Wang.)

Although the cell atlas of the human ocular anterior segment of the human eye was revealed by single-nucleus RNA sequencing, whether subtypes of lens stem/progenitor cells exist among epithelial cells and the molecular characteristics of cell differentiation of the human lens remain unclear. Single-cell RNA sequencing is a powerful tool to analyse the heterogeneity of tissues at the single cell level, leading to a better understanding of the processes of cell differentiation. By profiling 18,596 cells in human lens superficial tissue through single-cell sequencing, we identified two subtypes of lens epithelial cells that specifically expressed C8orf4 and ADAMTSL4 with distinct spatial localization, a new type of fibre cells located directly adjacent to the epithelium, and a subpopulation of ADAMTSL4 + cells that might be lens epithelial stem/progenitor cells. We also found two trajectories of lens epithelial cell differentiation and changes of some important genes during differentiation., (© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Background: APROPOS was a multicentre, randomized, blinded trial focus on investigating the perineal nerve block versus the periprostatic block in pain control for men undergoing a transperineal prostate biopsy. In the analysis reported here, the authors aimed to evaluate the association of biopsy core count and location with pain outcomes in patients undergoing a transperineal prostate biopsy under local anesthesia., Methods: APROPOS was performed at six medical centers in China. Patients with suspected prostate cancer were randomized to receive either a perineal nerve block or a periprostatic block (1:1), followed by a transperineal prostate biopsy. The secondary analysis outcomes were the worst pain experienced during the prostate biopsy and postbiopsy pain at 1,6, and 24 h., Results: Between 12 August 2020 and 20 July 2022, a total of 192 patients were randomized in the original trial, and 188 were involved in this analysis, with 94 patients per group. Participants had a median (IQR) age of 68 (63-72) and a median (IQR) prostate volume of 42.51 (30.04-62.84). The patient population had a median (IQR) number of biopsy cores of 15 (12-17.50), and 26.06% of patients had a biopsy cores count of more than 15. After adjusting the baseline characteristics, the number of biopsy cores was associated with the worst pain during the biopsy procedure in both the perineal nerve block group ( β 0.19, 95% CI: 0.12-0.26, P <0.001) and the periprostatic block group ( β 0.16, 95% CI: 0.07-0.24, P <0.001). A similar association was also evident for the postbiopsy pain at 1, 6, and 24 h. A lesser degree of pain in both groups at any time (r range -0.57 to -0.01 for both groups) was associated with biopsy cores from the peripheral zone of the middle gland, while other locations were associated with a higher degree of pain. In addition, the location of the biopsy core had less of an effect on pain during the biopsy (r range -0.01-0.25 for both groups) than it did on postbiopsy pain (r range -0.57-0.60 for both groups)., Conclusions: In this secondary analysis of a randomized trial, biopsy core count and location were associated with pain in patients undergoing a transperineal prostate biopsy under local anesthesia. These results may be helpful for making clinical decisions about the anesthetic approach for scheduled transperineal prostate biopsies., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The effective regeneration and functional restoration of damaged spinal cord tissue have been a long-standing concern in regenerative medicine. Treatment of spinal cord injury (SCI) is challenging due to the obstruction of the blood-spinal cord barrier (BSCB), the lack of targeting of drugs, and the complex pathophysiology of injury sites. Lipid nanovesicles, including cell-derived nanovesicles and synthetic lipid nanovesicles, are highly biocompatible and can penetrate BSCB, and are therefore effective delivery systems for targeted treatment of SCI. We summarize the progress of lipid nanovesicles for the targeted treatment of SCI, discuss their advantages and challenges, and provide a perspective on the application of lipid nanovesicles for SCI treatment. Although most of the lipid nanovesicle-based therapy of SCI is still in preclinical studies, this low immunogenicity, low toxicity, and highly engineerable nanovesicles will hold great promise for future spinal cord injury treatments., 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 © 2023 Lu, Wu, Yang, Wang, Yang, Zhang, Wang, Yang, Zhu and Sun.)

Objective: To analyze the related factors of futile recanalization (FR) after emergency endovascular treatment of large artery occlusion in anterior circulation. Methods: Three studies on endovascular treatment of acute anterior circulation large vessels occlusion stroke were selected, and their data were merged for retrospective analysis. Patients were divided into the FR group and favorable prognosis group according to the functional prognosis. Risk factor analysis was conducted using multivariate logistic regression. Results: A total of 1 581 patients were finally included, with 858 (48.9%) patients in favorable prognosis group and 926 (51.91%) patients in FR group. Among them, there were 939 males and 642 females, with a mean age of (65±12) years. Multivariate logistic regression analysis showed that National Institute of Health Stroke Scale (NIHSS) score ( OR =1.089,95% CI :1.066-1.113), puncture to recanalization time ( OR =0.756, 95% CI :0.586-0.971), age ( OR =1.04,95% CI :1.029-1.051), serum glucose ( OR =1.101,95% CI :1.062-1.143), systolic blood pressure ( OR =1.005,95% CI :1.001-1.010), passes≥3( OR =1.941,95% CI :1.294-2.941)Alberta stroke program early CT (ASPECT) score ( OR =0.919,95% CI :0.847-0.996), occlusion site (M1 segment of middle cerebral artery, OR =0.744,95% CI :0.565-0.980) and collateral circulation [(2 points, OR =0.757, 95% CI :0.581-0.985); (3-4 points, adjusted OR =0.640, 95% CI : 0.472-0.866)] were independent factors of FR. Conclusion: The incidence of FR in patients with large artery occlusion in anterior circulation who achieve satisfied reperfusion after endovascular treatment is high. Higher NIHSS score, longer puncture to recanalization time, older age, higher serum glucose and systolic blood pressure are risk factors, while lower ASPECTS, occlusion in cerebral middle M1 segment, better collateral circulation are protective factors.

Vascular recanalization therapy has been proven to be one of the most effective treatments for acute ischemic stroke (AIS) worldwide. Recently, the neurological functions have dramatically improved for AIS patients receiving endovascular thrombectomy, especially after the issue and promotion of evidence from different clinical studies. But nearly 50% of the patients had unfavorable clinical outcome even after successful recanalization [modified thrombolysis in cerebral infarction (mTICI)≥2b/3], which was termed as"futile recanalization". The mechanisms are complex, which may be related to poor collateral circulation, microthrombus and small artery reocclusion. The most significant pathophysiological change is brain tissue hypoperfusion although complete opening of the large artery, known as"no-reflow phenomenon". Therefore, it is urgent to manage the complications after vascular recanalization, such as hemorrhagic transformation, hyperperfusion syndrome, vascular re-occlusion, and even surgery-related complications (arterial dissection, contrast-induced encephalopathy), and future research is warranted to focus on the strategy of drugs with multi-target protection combined with vascular recanalization treatment. The current article covers the review, original research and case report focusing on this topic, aiming to raise clinical questions and call for more contribution to explore the mechanism and potential therapeutic strategy of futile recanalization, and thus provides more selections on the improvement of clinical outcome for AIS patients.

Background: Flavivirus causes many serious public health problems worldwide. However, licensed DENV vaccine has restrictions on its use, and there is currently no approved ZIKV vaccine. Development of a potent and safe flavivirus vaccine is urgently needed. As a previous study revealed the epitope, RCPTQGE, located on the bc loop in the E protein domain II of DENV, in this study, we rationally designed and synthesized a series of peptides based on the sequence of JEV epitope RCPTTGE and DENV/ZIKV epitope RCPTQGE., Methods: Immune sera were generated by immunization with the peptides which were synthesized by using five copies of RCPTTGE or RCPTQGE and named as JEV-NTE and DV/ZV-NTE . Immunogenicity and neutralizing abilities of JEV-NTE or DV/ZV-NTE-immune sera against flavivirus were evaluated by ELISA and neutralization tests, respectively. Protective efficacy in vivo were determined by passive transfer the immune sera into JEV-infected ICR or DENV- and ZIKV-challenged AG129 mice. In vitro and in vivo ADE assays were used to examine whether JEV-NTE or DV/ZV-NTE-immune sera would induce ADE., Results: Passive immunization with JEV-NTE-immunized sera or DV/ZV-NTE-immunized sera could increase the survival rate or prolong the survival time in JEV-challenged ICR mice and reduce the viremia levels significantly in DENV- or ZIKV-infected AG129 mice. Furthermore, neither JEV -NTE- nor DV/ZV-NTE-immune sera induced antibody-dependent enhancement (ADE) as compared with the control mAb 4G2 both in vitro and in vivo., Conclusions: We showed for the first time that novel bc loop epitope RCPTQGE located on the amino acids 73 to 79 of DENV/ZIKV E protein could elicit cross-neutralizing antibodies and reduced the viremia level in DENV- and ZIKV-challenged AG129 mice. Our results highlighted that the bc loop epitope could be a promising target for flavivirus vaccine development., (© 2023. The Author(s).)

Objectives: To evaluate the efficacy and safety of immune checkpoint inhibitor (ICI) combination therapy in the first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN)., Methods: We conducted a meta-analysis between ICI combination therapy and standard of care (SOC) treatment (chemotherapy with or without cetuximab) in R/M-SCCHN based on randomized controlled trials (RCTs). The outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs)., Results: Five RCTs involving 2576 patients were included in the analysis. Compared with SOC, PD-1 inhibitor plus chemotherapy significantly improved OS (hazard ratio [HR], 0.73, 95 % CI 0.62-0.87, p = 0.0004), PFS (HR, 0.65, 95 % CI 0.43-0.99, p = 0.04) and ORR (risk ratio [RR], 1.10; 95 % CI 1.01-1.19, p = 0.02) of patients, while double-agent immunotherapy could not improve either the outcome of OS, PFS, or ORR (all p > 0.05). In safety analyses, combination immunotherapy showed similar risks of grade 3 or higher treatment-related AEs (RR, 0.79, 95 % CI 0.56-1.11, P = 0.17) and treatment-related deaths (RR, 1.16, 95 % CI 0.65-2.07, P = 0.63) compared to SOC., Conclusions: Compared with SOC, PD-1 inhibitor plus chemotherapy enhanced OS, PFS, and ORR in the first-line treatment for patients with R/M-SCCHN, but double-agent immunotherapy showed no more benefit for these patients., 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.)

Eugenol is widely used as an analgesic in the dental treatment. The underlying mechanisms may involve its modulation of various ion channels. Acid-sensing ion channels (ASICs) are pH sensors and expressed in trigeminal ganglion (TG) neurons. In the present study, we found that eugenol concentration-dependently inhibited ASIC currents in TG neurons with an IC 50 of 98.8 ± 7.4 μM. Eugenol decreased the maximum response to acidic pH and did not alter pH 0.5 in the concentration-response curve of acidic pH, suggesting a noncompetitive inhibition of ASICs by eugenol. G-proteins were not involved in eugenol-induced inhibition, since pre-application of eugenol also decreased ASIC currents in the presence of the G-protein blocker GDP-β-S. In addition, eugenol also partly inhibited ASIC3 currents in Chinese hamster ovary cells transfected with ASIC3. In conclusion, eugenol partly inhibited ASIC currents in TG neurons in a concentration-dependent, non-competitive and G-protein independent manner. These results suggested that the ASICs could be a molecular target for eugenol in TG neurons, which contributed to its analgesic effect., 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.)

Early diagnosis remains the key to prevent and control infectious diseases. In recent years, metagenomic next-generation sequencing (mNGS) technology breaks through the limitations of conventional culture methods or targeted molecular detection methods. It improves the diagnosis and treatment level of difficult and rare infectious pathogens through the shotgun high-throughput sequencing to conduct unbiased and rapid detection of microorganisms in clinical samples, which has been widely recognized in clinical practice. Due to the complex detection process of mNGS, there are no uniform specifications and requirements at present. Meanwhile, most laboratories lack of relevant talents at the initial stage of platform establishment, which poses severe challenges to the construction and quality control of the mNGS platform. Based on the practical experience in the construction and operation of the mNGS laboratory of Peking Union Medical College Hospital, the current article summarizes the hardware requirements for the establishment of the mNGS laboratory, the establishment and evaluation methods of the mNGS testing system and the quality assurance after the clinical application, and comprehensively introduces the suggestions for the standardized construction and operation of the mNGS testing platform and quality management system.

Background: We aimed to investigate perineal nerve block versus periprostatic block in pain control for men undergoing a transperineal prostate biopsy., Methods: In this prospective, randomised, blinded and parallel-group trial, men in six Chinese hospitals with suspected prostate cancer were randomly assigned (1:1) at the point of local anaesthesia to receive a perineal nerve block or periprostatic block and followed by a transperineal prostate biopsy. Centres used their usual biopsy procedure. Operators who performed anaesthesia were trained in both techniques before the trial and were masked to the randomised allocation until the time of anaesthesia and were not involved in the subsequent biopsy procedure and any assessment or analysis. Other investigators and the patients were masked until trial completion. The primary outcome was the level of the worst pain experienced during the prostate biopsy procedure. Secondary outcomes included pain (post-biopsy at 1, 6 and 24 h), changes in blood pressure, heart rate and breathing rate during the biopsy procedure, external manifestations of pain during biopsy, anaesthesia satisfaction, the detection rate of PCa and clinically significant PCa. This trial is registered on ClinicalTrials.gov, NCT04501055., Findings: Between August 13, 2020, and July 20, 2022, 192 men were randomly assigned to perineal nerve block or periprostatic block, 96 per study group. Perineal nerve block was superior for the relief of pain during the biopsy procedure (mean 2.80 for perineal nerve block and 3.98 for periprostatic block; adjusted difference in means -1.17, P < 0.001). Although the perineal nerve block had a lower mean pain score at 1 h post-biopsy compared with the periprostatic block (0.23 vs 0.43, P = 0.042), they were equivalent at 6 h (0.16 vs 0.25, P = 0.389) and 24 h (0.10 vs 0.26, P = 0.184) respectively. For the change in vital signs during biopsy procedure, perineal nerve block was significantly superior to periprostatic block in terms of maximum value of systolic blood pressure, maximum value of mean arterial pressure and maximum value of heart rate. There are no statistical differences in average value of systolic blood pressure, average value of mean, average value of heart rate, diastolic blood pressure and breathing rate. Perineal nerve block was also superior to periprostatic block in external manifestations of pain (1.88 vs 3.00, P < 0.001) and anaesthesia satisfaction (8.93 vs 11.90, P < 0.001). Equivalence was shown for the detection rate of PCa (31.25% for perineal nerve block and 29.17% for periprostatic block, P = 0.753) or csPCa (23.96% for perineal nerve block and 20.83% for periprostatic block, P = 0.604). 33 (34.8%) of 96 patients in the perineal nerve block group and 40 (41.67%) of 96 patients in the periprostatic block group had at least one complication., Interpretation: Perineal nerve block was superior to periprostatic block in pain control for men undergoing a transperineal prostate biopsy., Funding: Grant 2019YFC0119100 from the National Key Research and Development Program of China., Competing Interests: None of the authors have any conflicts of interest to declare., (© 2023 The Authors.)

Microbial fuel cells (MFCs) have been demonstrated as a renewable energy strategy to efficiently recover chemical energy stored in wastewater into clean electricity, yet the limited power density limits their practical application. Here, Fe-doped carbon and nitrogen (Fe@CN) nanoparticles were synthesized by a direct pyrolysis process, which was further decorated to fabricate Fe@CN carbon paper anode. The modified Fe@CN anode with a higher electrochemically active surface area was not only benefit for the adhesion of electrochemically active microorganisms (EAMs) and extracellular electron transfer (EET) between the anode and EAMs but also selectively enriched Geobacter, a typical EAMs species. Accordingly, the MFCs with Fe@CN anode successfully achieved a highest voltage output of 792.76 mV and a prolonged stable voltage output of 300 h based on the mixed culture feeding with acetate. Most importantly, the electroactive biofilms on Fe@CN anode achieved more content ratio of proteins to polysaccharides (1.40) in extracellular polymeric substances for the balance between EET and cell protection under a harsh environment. This work demonstrated the feasibility of development on anode catalysts for the elaboration of the catalytic principle about interface modification, which may contribute to the practical application of MFC in energy generation and wastewater treatment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cerebral ischemia, resulting from compromised blood flow, is one of the leading causes of death worldwide with limited therapeutic options. Potential deleterious injuries resulting from reperfusion therapies remain a clinical challenge for physicians. This study aimed to explore the metabolomic alterations during ischemia-reperfusion injury by employing metabolomic analysis coupled with gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and ultraperformance liquid chromatography quadrupole (UPLC/Q)-TOF-MS. Metabolomic data from mice subjected to middle cerebral artery occlusion (MCAO) followed by reperfusion (MCAO/R) were compared to those of the sham and MCAO groups. A total of 82 simultaneously differentially expressed metabolites were identified among each group. The top three major classifications of these differentially expressed metabolites were organic acids, lipids, and organooxygen compounds. Metabolomics pathway analysis was conducted to identify the underlying pathways implicated in MCAO/R. Based on impactor scores, the most significant pathways involved in the response to the reperfusion after cerebral ischemia were glycerophospholipid metabolism, linoleic acid metabolism, pyrimidine metabolism, and galactose metabolism. 17 of those 82 metabolites were greatly elevated in the MCAO/Reperfusion group, when compared to those in the sham and MCAO groups. Among those metabolites, glucose-6-phosphate 1, fructose-6-phosphate, cellobiose 2, o-phosphonothreonine 1, and salicin were the top five elevated metabolites in MCAO/R group, compared with the MCAO group. Glycolysis, the pentose phosphate pathway, starch and sucrose metabolism, and fructose and mannose degradation were the top four ranked pathways according to metabolite set enrichment analysis (MSEA). The present study not only advances our understanding of metabolomic changes among animals in the sham and cerebral ischemia groups with or without reperfusion via metabolomic profiling, but also paves the way to explore potential molecular mechanisms underlying metabolic alteration induced by cerebral ischemia-reperfusion., 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 © 2023 Chen, Zhou, Yuan, Xiong, Liu, Qiu, Hu, Lu, He, Liu and Yang.)

Objective: To investigate if there is a correlation between lipid-lowering treatment with statins and the occurrence, number, and location of cerebral microbleeds (CMBs) among patients with ischemic cerebrovascular disease (ICVD), and also to compare treatment with atorvastatin and rosuvastatin in terms of the occurrence of CMBs and their differences., Methods: In this retrospective study, we included patients who were diagnosed with ICVD and underwent susceptibility weighted imaging (SWI) in a grade A tertiary hospital from October 1, 2014 to October 1, 2022. We collected information on previous statin use, past medical history, clinical test indicators, and imaging data., Results: We found that out of 522 patients, 310 patients (59.4%) had no CMB and 212 patients (40.6%) had CMBs. There was no statistically significant correlation between prior statin use, the occurrence, and number of CMBs in patients diagnosed with ICVD (P < 0.05). As for the location of CMB, there was a statistically significant correlation between prior statin use and lobar CMBs (P < 0.048). However, there was no statistically significant correlation between the use of atorvastatin and rosuvastatin and the occurrence of CMBs (P > 0.05)., Conclusion: There was no independent correlation between previous statin use, and the occurrence, and number of CMBs in patients with ICVD. As for CMBs in different locations, there was a correlation between previous use of statin and lobar CMBs. There was no significant difference between atorvastatin and rosuvastatin in the occurrence of CMBs in patients with ICVD.

Background: Cisplatin-based concurrent chemoradiotherapy is a standard of care for locally advanced nasopharyngeal carcinoma (NPC), and weekly and triweekly cisplatin are both alternative regimens based on the results of squamous cell carcinoma of the head and neck. However, there is a lack of direct evidence on the efficacy and safety of weekly versus triweekly cisplatin concurrent with radiotherapy in NPC alone. This meta-analysis aimed to identify which regimen is more superior between weekly and triweekly cisplatin in patients with NPC treated with concurrent chemoradiotherapy., Methods: The PubMed, Embase, and Cochrane Library were searched for eligible literatures. Clinical outcome measures including 1-year overall survival (OS), 3-year OS, 5-year OS, 5-year loco-regional failure-free survival, 5-year distant metastasis-free survial and the most common 3 grade or higher acute toxicities (hematological toxicity, mucositis and nausea and vomiting) were analyzed by RevMan 5.4 software; significance level was 0.05., Results: Seven clinical controlled studies with 1795 patients were included in the meta-analysis. There were no significant differences between weekly and triweekly cisplatin in 1-year OS, 3-year OS, 5-year OS, 5-year loco-regional failure-free survival, and 5-year distant metastasis-free survial) (all P > .05). Grade 3 or higher mucositis and nausea and vomiting showed similar between the 2 arms. However, grade 3 or higher hematological toxicity of weekly cisplatin was significantly higher than that of triweekly cisplatin (1.55; 95% CI, 1.22-1.98, P = .0004)., Conclusions: Weekly cisplatin resulted in similar survival benifit as triweekly cisplatin, but with higher hematological toxicity., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

A new visible imaging system characterizing a flexible optical design and delivering high resolution frames is established on the HL-2A tokamak. It features a modular configuration, consisting of a front-end imaging lens, a set of bilateral telecentric relay lenses, and a camera. To avoid the effects of plasma radiation (x and gamma-rays) and magnetic field variation on the camera, it should be away from the coils. Therefore, the length of the relay lenses determines the total size of the imaging system. The main feature of this imaging system is to realize the variation of field of view (FOV) by interchanging the front-end prime lenses or by using a zoom lens directly rather than designing the optical system afresh, which lowers the cost drastically. The primary purpose of varying FOV is to enrich the versatility of this system, i.e., focusing on a narrow FOV such as gas puff imaging or a wide FOV such as the plasma cross sections. During the HL-2A experiments, this visible imaging system is used to provide high quality pictures of the plasma-wall interaction, divertor detachment, pellet injections, and so on. The frames confirmed that a strong radiation close to the X point is correlated with the completely detached inner target.

Neurons in the penumbra (the area surrounding ischemic tissue that consists of still viable tissue but with reduced blood flow and oxygen transport) may be rescued following stroke if adequate perfusion is restored in time. It has been speculated that post-stroke angiogenesis in the penumbra can reduce damage caused by ischemia. However, the mechanism for neovasculature formation in the brain remains unclear and vascular-targeted therapies for brain ischemia remain suboptimal. Here, we show that VEGFR1 was highly upregulated in pericytes after stroke. Knockdown of VEGFR1 in pericytes led to increased infarct area and compromised post-ischemia vessel formation. Furthermore, in vitro studies confirmed a critical role for pericyte-derived VEGFR1 in both endothelial tube formation and pericyte migration. Interestingly, our results show that pericyte-derived VEGFR1 has opposite effects on Akt activity in endothelial cells and pericytes. Collectively, these results indicate that pericyte-specific expression of VEGFR1 modulates ischemia-induced vessel formation and vascular integrity in the brain., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Tex264 is an endoplasmic reticulum (ER) membrane protein that was recently demonstrated to act as an ER-phagy receptor under starvation conditions to mediate endoplasmic reticulum autophagy. However, how Tex264 functions in the central nervous system (CNS) and tumors is unclear. Here, we identified 89 proteins from the rat brain that may specifically interact with Tex264 and confirmed the interaction between sorting nexin 27 (SNX27) and Tex264 by coimmunoprecipitation and immunofluorescence. Our results indicated that Tex264 may promote recycling of membrane proteins from endosomes to the cell plasma membrane by recruiting SNX27 retromer vesicles. siRNA-mediated knockdown of TEX264 in HeLa cells did not affect cell proliferation but did significantly inhibit cell migration through a mechanism that may involve a reduction in SNX27-mediated Itg α 5 receptor membrane recycling. Results of this study helped identify potential binding Tex264 partners and provide insights into Tex264 functions in the CNS and in tumors., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 Xiao-hui Xu et al.)

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis, closely associated with the immune system. Its pathogenesis is currently not clear. The lack of specificity in the clinical manifestations and histopathological changes of PG leads to a long clinical diagnosis cycle and even misdiagnosis, which is easy to delay treatment or promote the deterioration of ulcer wound. The diagnosis of this disease is still very difficult, which poses a great challenge to wound repair practitioners. This article reviews the research advances on the pathophysiology, clinical features, and diagnosis of PG in recent years, with the aim of providing reference for relevant clinical practitioners.