An integrated RNA-Seq and network pharmacology approach for exploring the preventive effect of Corydalis bungeana Turcz. Extract and Acetylcorynoline on LPS-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis bungeana Turcz. (KDD) is a Chinese herbal medicine with anti-inflammatory, lung cleansing, detoxification and other functions. Clinically, it is commonly used to treat respiratory infections. This study uses ALI as the research model, which is consistent with the clinical use of KDD. Acetylcorynoline (AC) is the main alkaloid component of the KDD extracts, and network pharmacology studies suggest that it may be the main active ingredient in the prevention of ALI. AIM OF THE STUDY: The aim of this study is to explore the underlying mechanisms and to study the efficacy material basis of KDD in anti-ALI effect by LPS-induced mice and using a combination of RNA sequencing (RNA-Seq) technology and network pharmacology. MATERIALS AND METHODS: Establish a mouse model of ALI by intraperitoneal injection of LPS (5 mg/kg). The main active ingredients of KDD were identified and analyzed by high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) and network pharmacology. IL-18, IL-1ß, and IL-6 levels in serum and bronchoalveolar lavage fluid (BALF), lung histopathological changes, and lung myeloperoxidase (MPO) activity were assessed. We investigated the possible molecular mechanisms of KDD and AC in an LPS-induced mouse ALI models with RNA-Seq technology. In addition, the anti-inflammatory effect of AC was verified in vitro by establishing an LPS-stimulated RAW264.7 inflammation model. Molecular docking further validated AC as the efficacy material basis of KDD in anti-ALI. RESULTS: Based on HPLC-QTOF-MS technology and network pharmacology, KDD is more strongly associated with lung tissue, and that AC may be the main active ingredient of KDD. Subsequently, in vivo experiments results showed that KDD and AC reduced the levels of pro-inflammatory cytokines in serum and BALF, reduced MPO levels and reduced inflammatory damage in the lungs. To elucidate its underlying mechanism, based on RNA-Seq analysis techniques performed in lung tissue, enrichment analysis showed that KDD and AC intervened through the NLR signaling pathway, thereby mitigating LPS-induced ALI. Then, RT-qPCR, IF, WB and other technologies were used to verify the anti-ALI core difference genes of KDD and AC from the gene transcription and protein expression levels of the NLR signaling pathway, and confirmed the anti-ALI. In vitro experimental results also showed that AC has anti-inflammatory effects in RAW264.7. Finally, the biotransformation and molecular docking results also further indicated that AC is the active ingredient of KDD in anti-ALI. CONCLUSIONS: Studies have shown that KDD has a good therapeutic effect on ALI, and AC is the main pharmacodynamic material basis for its therapeutic effect in ALI.

Computer Vision-Based Bridge Inspection and Monitoring: A Review.

Bridge inspection and monitoring are usually used to evaluate the status and integrity of bridge structures to ensure their safety and reliability. Computer vision (CV)-based methods have the advantages of being low cost, simple to operate, remote, and non-contact, and have been widely used in bridge inspection and monitoring in recent years. Therefore, this paper reviews three significant aspects of CV-based methods, including surface defect detection, vibration measurement, and vehicle parameter identification. Firstly, the general procedure for CV-based surface defect detection is introduced, and its application for the detection of cracks, concrete spalling, steel corrosion, and multi-defects is reviewed, followed by the robot platforms for surface defect detection. Secondly, the basic principle of CV-based vibration measurement is introduced, followed by the application of displacement measurement, modal identification, and damage identification. Finally, the CV-based vehicle parameter identification methods are introduced and their application for the identification of temporal and spatial parameters, weight parameters, and multi-parameters are summarized. This comprehensive literature review aims to provide guidance for selecting appropriate CV-based methods for bridge inspection and monitoring.

A 3D tetrathiafulvalene-based metal-organic framework with intramolecular charge transfer for efficient near-infrared photothermal conversion.

The selection of metal centers can endow donor-metal-accepter (D-M-A) type MOFs with progressive framework dimensions. 3D Cd-based MOFs with intramolecular charge transfer caused by D-M-A exhibit a satisfactory photothermal conversion efficiency of 35.7%, with the temperature rapidly rising from 25 °C to 201 °C in 7 s under 808 nm laser irradiation.

Altered resting-state brain activity in major depressive disorder comorbid with subclinical hypothyroidism: A regional homogeneity analysis.

BACKGROUND: Major depressive disorder (MDD), a common mental disorder worldwide, frequently coexists with various physical illnesses, and recent studies have shown an increased prevalence of subclinical hypothyroidism (SHypo) among MDD patients. However, the neural mechanisms shared and unique to these disorders and the associated alterations in brain function remain largely unknown. This study investigated the potential brain function mechanisms underlying comorbid MDD and SHypo. METHOD: Thirty MDD patients (non-comorbid group), 30 MDD patients comorbid with SHypo (comorbid group), 26 patients with SHypo, and 30 healthy controls were recruited for resting-state functional magnetic resonance imaging (rs-fMRI). We used regional homogeneity (ReHo) to examine differences in internal cerebral activity across the four groups. RESULTS: Compared with the non-comorbid group, the comorbid group exhibited significantly higher ReHo values in the right orbital part of the middle frontal gyrus (ORBmid) and bilateral middle frontal gyrus; decreased ReHo values in the right middle temporal gyrus, right thalamus, and right superior temporal gyrus, and right insula. Within the comorbid group, serum TSH levels were negatively associated with the ReHo values of the right insula; the ReHo values of the right Insula were negatively associated with the retardation factor score; the ReHo values of the right ORBmid were positively correlated with the anxiety/somatization factor scores. CONCLUSIONS: These findings provide valuable clues for exploring the shared neural mechanisms between MDD and SHypo and have important implications for understanding the pathophysiological mechanisms of the comorbidity of the two disorders.

Designing Multimodal ON-OFF Nanoswitches of DNA-Functionalized Nanoparticles by Stimuli-Responsive Polymers.

It is a challenging task to realize highly reversible ON-OFF nanoswitches over a wide range of temperatures, which emerge as a versatile toolbox for use in nanobiotechnology. Herein, nanoparticles (NPs) bifunctionalized by DNA strands and stimuli-responsive polymers are proposed to construct multimodal ON-OFF nanoswitches by the coarse-grained model. The successful achievement of multimodal ON-OFF nanoswitches for bifunctionalized NPs at lower temperatures is attributed to the synergistic effects of the contraction and expansion configurations of stimuli-responsive polymers, combined with the hybridization-dehybridization event of DNA strands. Importantly, our simulations isolate the conditions of programmable self-assembly of bifunctionalized NPs to realize the multimodal ON-OFF nanoswitches by the changes of temperature and chain rigidity. In addition, it is found that the bifunctionalized NPs in the ON state display anisotropic and patchy features due to an introduction of stimuli-responsive polymers. Our simulation results provide fundamental insights on qualitative predictions of ON/OFF states of DNA-based NPs, which can aid in realizing a set of ON-OFF nanoswitches by the rational design of functionalization molecules.

Image-Specific Information Suppression and Implicit Local Alignment for Text-Based Person Search.

Text-based person search (TBPS) is a challenging task that aims to search pedestrian images with the same identity from an image gallery given a query text. In recent years, TBPS has made remarkable progress, and state-of-the-art (SOTA) methods achieve superior performance by learning local fine-grained correspondence between images and texts. However, most existing methods rely on explicitly generated local parts to model fine-grained correspondence between modalities, which is unreliable due to the lack of contextual information or the potential introduction of noise. Moreover, the existing methods seldom consider the information inequality problem between modalities caused by image-specific information. To address these limitations, we propose an efficient joint multilevel alignment network (MANet) for TBPS, which can learn aligned image/text feature representations between modalities at multiple levels, and realize fast and effective person search. Specifically, we first design an image-specific information suppression (ISS) module, which suppresses image background and environmental factors by relation-guided localization (RGL) and channel attention filtration (CAF), respectively. This module effectively alleviates the information inequality problem and realizes the alignment of information volume between images and texts. Second, we propose an implicit local alignment (ILA) module to adaptively aggregate all pixel/word features of image/text to a set of modality-shared semantic topic centers and implicitly learn the local fine-grained correspondence between modalities without additional supervision and cross-modal interactions. Also, a global alignment (GA) is introduced as a supplement to the local perspective. The cooperation of global and local alignment modules enables better semantic alignment between modalities. Extensive experiments on multiple databases demonstrate the effectiveness and superiority of our MANet.

Thymic hyperplasia with lymphoepithelial sialadenitis (LESA)-like features: a case report and literature review.

BACKGROUND: Thymic hyperplasia with lymphoepithelial sialadenitis-like features (LESA-like TH) is a rare form of thymic hyperplasia, characterized by a prominent expansion of the thymic medulla containing hyperplastic lymphoid follicles with germinal centers, while an almost total absence of thymic cortex. Since the first report in 2012, only a few cases of LESA-like TH have been reported in the literature to date. Due to the rarity of LESA-like TH and the tumor-like morphology, it is easy to be misdiagnosed as other common diseases of the thymus in routine practice, such as thymoma and lymphoma. CASE PRESENTATION: Herein, we present a case report of a 52-year-old Chinese female patient with LESA-like TH, without any discomforting symptoms. Computer-tomography imaging revealed a cystic solid mass in the anterior mediastinum, with well-defined boundaries and multiple internal septa. Histologically, prominent features were florid lymphoid follicles containing germinal centers, as well as hyperplasia of thymic epithelial cells and proliferation of Hassall bodies. However, the thymic cortex rich in immature T cells was almost completely absent. Furthermore, mature plasma cells, lymphoepithelial lesions, and cholesterol clefts were frequently seen. CONCLUSION: We made a diagnosis of LESA-like TH and performed a literature review to better understand the clinicopathological features of LESA-like TH and reduce misdiagnosis.

A case report of spontaneous pectoral hematoma in a male with background antiplatelet therapy after severe COVID-19 infection.

BACKGROUND: Spontaneous muscle hematoma is a rare complication in hospitalized patients with COVID-19. We present a case of spontaneous pectoral hematoma occurring after COVID-19 infection and anticoagulation therapy. CASE PRESENTATION: A 69-year-old male presented to the hospital with a two-week history of shortness of breath and a one-week history of high fever. Despite testing positive for COVID-19, the patient's symptoms did not improve with two doses of ritonavir-boosted nirmatrelvir (Paxlovid). A chest CT scan revealed pulmonary infection and SpO2 tested between 80% and 85% at rest in local hospital. The patient transferred to our intensive care unit, then received multiple treatments, including high flow nasal oxygen (HFNO), antibiotics, methylprednisolone, IL-6 receptor antagonist monoclonal antibody (tocilizumab), and an increased D-Dimer level leaded to intermediate dose of anticoagulation therapy. However, on the 10th day of hospitalization, the patient developed a hematoma in the left pectoralis major muscle. This was accompanied by hemorrhagic shock, necessitating the administration of norepinephrine, fluid resuscitation, and a blood transfusion. Arterial embolization was performed to manage the bleeding, resulting in stabilization of the patient's condition. Following discharge, the patient experienced an uneventful recovery over a period of six months. CONCLUSIONS: Severe COVID-19 patients undergoing routine therapeutic anticoagulation may experience fatal bleeding complications. The ideal dosage of anticoagulants for these patients remains uncertain, especially in the patient with a background of anticoagulation or dual antiplatelet therapy. We present a case of spontaneous muscle hematoma accompanied by hemorrhagic shock. The notable reduction in hemoglobin levels indicated significant bleeding, which was confirmed through contrast angiography and cured by arterial embolization. This case underscores the importance of additional research to determine the appropriate utilization of therapeutic anticoagulation in severe COVID-19 patients already undergoing antithrombotic therapy.

Au-CeO2 composite aerogels with tunable Au nanoparticle sizes as plasmonic photocatalysts for CO2 reduction.

Tuning the size of Au nanoparticles is always an interesting task when constructing Au/semiconductor heterojunctions for surface plasmon resonance-enhanced photocatalysis. In particular, the size of Au nanoparticles in the newly emerging "plasmonic aerogel" photocatalyst concept could approach the size of the semiconductor phase. This work provides an alternative route to realize the size tuning of Au nanoparticles in Au-CeO2 composite aerogels to some extent, within the framework of the well-established epoxide addition sol-gel method. The size tuning is achieved by exploiting the multi-functionalities of a mixed organic acid additive containing a thiol group in the gelation step. The obtained aerogel photocatalysts are composed of a porous backbone of interconnected CeO2 nanoparticles and Au nanoparticles, and the size of Au nanoparticles ranges from ∼30 nm to sub-10 nm, while the size of CeO2 remains at ∼15-10 nm. The surface plasmon resonance peak position and intensity contributed by the Au nanoparticles then vary accordingly. Photocatalytic CO2 reduction at the gas-solid interface is chosen as a model reaction to study the effect of Au nanoparticle size on the photocatalytic activity of composite aerogel photocatalysts. The addition of Au nanoparticles undoubtedly enhances the overall activity of the CeO2 aerogel photocatalyst, while the degree of enhancement (in terms of total charge consumption) and product selectivity (CH4 or CO) are different and correlated with the size of the Au nanoparticles. The best performance can be achieved in a composite in which the Au sizes are the smallest.

Elevated Expression of Two Pore Potassium Channel THIK-1 in Alzheimer's Disease: An Inflammatory Mechanism.

INTRODUCTION: Tandem pore domain halothane-inhibited K+ channel 1 (THIK-1, coded by KCNK13) provides an upstream regulation of the activation of the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, which has been suggested as one of the key mechanisms of the pathological process in neurodegeneration mainly from in vitro and in vivo model systems studies. However, unequivocal evidence from neurodegenerative disorders has been lacking. OBJECTIVE: To investigate the involvement of the THIK-1/NLRP3 pathway in the pathological process of Alzheimer's disease (AD) and Parkinson's disease (PD). METHODS: This study investigated gene expression of markers in the THIK-1/NLRP3 pathway in an animal model representing AD as well as in human postmortem brains of AD and PD by quantitative real-time PCR. THIK-1 protein expression was determined using automated capillary electrophoresis immunoblotting. Furthermore, DNA methylation of KCNK13 was analysed in AD cohort by pyrosequencing. RESULTS: A substantial upregulation of KCNK13, glial activation markers, NLRP3 inflammasome components, and IL1B was observed in the animal study. Increased expression of KCNK13 support an inflammatory glial cell activation in both advanced AD and PD. The increase in KCNK13 expression was also supported by downregulation in DNA methylation of KCNK13 in AD. CONCLUSIONS: The association between THIK-1 K+ channels expression and pathology changes indicates a THIK-1-induced activation of this glial subtype in AD and PD. Therefore, specific blocks of the microglial THIK-1 K+ channels at the early stage of AD and PD may be beneficial for the patients.

The relationship between disrupted anhedonia-related circuitry and suicidal ideation in major depressive disorder: A network-based analysis.

BACKGROUND: Several epidemiological studies and psychological models have suggested that major depressive disorder (MDD) with anhedonia is associated with suicidal ideation (SI). However, little is known about whether the functional network pattern and intrinsic topologically disrupted in patients with anhedonia are related to SI. METHODS: The resting-fMRI by applying network-based statistic (NBS) and graph-theory analyses was estimated in 273 patients with MDD (144 high anhedonia [HA], 129 low anhedonia [LA]) and 150 healthy controls. In addition, we quantified the SI scores of each patient. Finally, the mediation analysis assessed whether anhedonia symptoms could mediate the relationship between anhedonia-related network metrics and SI. RESULT: The NBS analysis demonstrated that individuals with HA have a single abnormally increased functional connectivity component in a frontal-limbic circuit (termed the "anhedonia-related network", including the frontal cortex, striatum, anterior cingulate cortex and amygdala). The graph-theory analysis demonstrated that the anhedonia-related network showed a significantly disrupted topological organization (lower gamma and lambda), which the small-world property trend randomized. Furthermore, the anhedonia symptoms could mediate the relationship between the anhedonia-related network metrics (the mean functional connectivity values, the area under the curves values of gamma and nodal local efficiency in nucleus accumbens) and SI. CONCLUSIONS: We found that disruption of the reward-related network in MDD leads to SI through anhedonia symptoms. These findings show the abnormal topological construction of functional brain network organization in anhedonia, shedding light on the neurological processes underlying SI in MDD patients with anhedonia symptoms.

Autophagy inhibition mediated by trillin promotes apoptosis in hepatocellular carcinoma cells via activation of mTOR/STAT3 signaling.

Apoptosis and autophagy have been shown to act cooperatively and antagonistically in self-elimination process. On the one side, apoptosis and autophagy can act as partners to induce cell death in a coordinated or cooperative manner; on the flip side, autophagy acts as an antagonist to block apoptotic cell death by promoting cell survival. Our previous research indicated that trillin could induce apoptosis of PLC/PRF/5 cells, but the effects of trillin on autophagy as well as its functional relationship to apoptosis have not been elucidated. Here, the running study aims to investigate the function and molecular mechanism of trillin on autophagy with hepatocellular carcinoma (HCC) cells. The objective of this study is to investigate the molecular mechanism of trillin on autophagy in HCC cells. Protein levels of autophagy markers beclin1, LC3B, and p62 were detected by western blotting. 6-Hydroxyflavone and stattic were used to test the role of trillin regulation of autophagy via serine threonine kinase (AKT)/extracellular-regulated protein kinases (ERK) 1/2/mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Flow cytometry was used to detect caspase 3 activity and apoptosis in PLC/PRF/5 cells treated with trillin for 24 h with or without rapamycin, stattic, and 6-hydroxyflavone. The protein level of autophagy marker beclin1 was decreased, whilst the protein level of p62 was significantly increased by trillin treatment, indicating trillin treatment led to inhibition of autophagy in HCC cells. Trillin treatment could reduce the protein levels of p-AKT and p-ERK1/2, but enhance the protein levels of mTOR and p-mTOR, suggesting that trillin could inhibit AKT/ERK rather than mTOR. The AKT/ERK activator 6-hydroxyflavone could reverse the loss of AKT and ERK1/2 phosphorylation induced by trillin, implying that trillin impairs autophagy through activated mTOR rather than AKT/ERK. STAT3 and p-STAT3 were significantly upregulated by the trillin treatment with an increase in dose from 0 to 50 µM, suggesting that autophagy inhibition is mediated by trillin via activation of STAT3 signaling. The STAT3 inhibitor stattic significantly reversed the increased STAT3 phosphorylation at tyrosine 705 induced by trillin. The mTOR signaling inhibitor rapamycin reversed the trillin-induced mTOR phosphorylation enhancement but exerted no effects on total mTOR levels, suggesting trillin treatment led to inhibition of autophagy in HCC cells through activating mTOR/STAT3 pathway. Furthermore, caspase 3 activities and the total rate of apoptosis were increased by trillin treatment, which was reversed by rapamycin, stattic, and 6-hydroxyflavone, proving that trillin promotes apoptosis via activation of mTOR/STAT3 signaling. Trillin induced autophagy inhibition and promoted apoptosis in PLC/PRF/5 cells via the activation of mTOR/STAT3 signaling. Trillin has the potential to be a viable therapeutic option for HCC treatment.

Cooperation between neurovascular dysfunction and Aß in Alzheimer's disease.

The amyloid-ß (Aß) hypothesis was once believed to represent the pathogenic process of Alzheimer's disease (AD). However, with the failure of clinical drug development and the increasing understanding of the disease, the Aß hypothesis has been challenged. Numerous recent investigations have demonstrated that the vascular system plays a significant role in the course of AD, with vascular damage occurring prior to the deposition of Aß and neurofibrillary tangles (NFTs). The question of how Aß relates to neurovascular function and which is the trigger for AD has recently come into sharp focus. In this review, we outline the various vascular dysfunctions associated with AD, including changes in vascular hemodynamics, vascular cell function, vascular coverage, and blood-brain barrier (BBB) permeability. We reviewed the most recent findings about the complicated Aß-neurovascular unit (NVU) interaction and highlighted its vital importance to understanding disease pathophysiology. Vascular defects may lead to Aß deposition, neurotoxicity, glial cell activation, and metabolic dysfunction; In contrast, Aß and oxidative stress can aggravate vascular damage, forming a vicious cycle loop.

Mitochondria-targeting nanozyme alleviating temporomandibular joint pain by inhibiting the TNFα/NF-κB/NEAT1 pathway.

Inflammatory cytokines that are secreted into the spinal trigeminal nucleus caudalis (Sp5C) may augment inflammation and cause pain associated with temporomandibular joint disorders (TMD). In a two-step process, we attached triphenylphosphonium (TPP) to the surface of a cubic liposome metal-organic framework (MOF) loaded with ruthenium (Ru) nanozyme. The design targeted mitochondria and was designated Mito-Ru MOF. This structure scavenges free radicals and reactive oxygen species (ROS) and alleviates oxidative stress. The present study aimed to investigate the effects and mechanisms by which Mito-Ru MOF ameliorates TMD pain. Intra-temporomandibular joint (TMJ) injections of complete Freund's adjuvant (CFA) induced inflammatory pain for ≥10 d in the skin areas innervated by the trigeminal nerve. Tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), long non-coding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1), and ROS also have been proved to be significantly upregulated in the Sp5C of TMD mice. Moreover, a single Mito-Ru MOF treatment alleviated TMD pain for 3 d and downregulated TNF-α, NF-κB, lncRNA NEAT1, and ROS. NF-κB knockdown downregulated NEAT1 in the TMD mice. Hence, Mito-Ru MOF inhibited the production of ROS and alleviated CFA-induced TMD pain via the TNF-α/NF-κB/NEAT1 pathway. Therefore, Mito-Ru MOF could effectively treat the pain related to TMD and other conditions associated with severe acute inflammatory activation.

Rutin intake mitigates the injury of blue light irradiation by altering aging rates of mortality in Drosophila model.

Blue light is known as one of the harmful light pollution that has complex effects on organisms. The massive use of LED lights in cities has greatly increased the frequency of human exposure to blue light, and therefore the hazards of blue light are receiving widespread attention. In our study, Drosophila was used as the model organism to explore the ability of the flavonoid rutin to resist blue light damage under the intensity of 3000 Lux. Siler model analysis was performed. Our results showed sex-specific pattern of rutin as an effective antioxidant. Rutin could help female flies to reduce the initial adult mortality and male flies to slow the increase of adult mortality under blue light irradiation, thus prolonging their average lifespan. Furthermore, after the intake of rutin, the locomotor activity of Drosophila under blue light irradiation was significantly increased, and the total sleep time was significantly decreased. In summary, our results provide preliminary support for exploring the mechanism of rutin against blue light damage.

Micropterus salmoides rhabdovirus enters cells via clathrin-mediated endocytosis pathway in a pH-, dynamin-, microtubule-, rab5-, and rab7-dependent manner.

Micropterus salmoides rhabdovirus (MSRV) is an important fish pathogen that infects largemouth bass. To date, the entry process for MSRV remains obscure. Here, the dynamic process of MSRV entry and internalization was analyzed using biochemical inhibitors, RNA interference, and single-virus tracking technology. Accordingly, DiD was used as a fluorescent label for sensitive, long-term tracking of MSRV entry in living cells. The motion analysis suggested that MSRV initially experiences slow movement in the cell periphery, while it undergoes relatively faster and directed motion toward the cell interior, dependent on the microtubule. Besides, our data demonstrated that the MSRV enters epithelioma papulosum cyprinid (EPC) cells via clathrin-mediated endocytosis in a low pH-, dynamin-, and clathrin-dependent manner. Furthermore, after endocytosing into EPC cells, MSRV moves along the classical endosome/lysosome trajectory. This study reveals the entry pathway and intracellular dynamics of MSRV in EPC cells, providing new insights into the infection mechanism of rhabdoviruses. IMPORTANCE Although Micropterus salmoides rhabdovirus (MSRV) causes serious fish epidemics worldwide, the detailed mechanism of MSRV entry into host cells remains unknown. Here, we comprehensively investigated the mechanism of MSRV entry into epithelioma papulosum cyprinid (EPC) cells. This study demonstrated that MSRV enters EPC cells via a low pH, dynamin-dependent, microtubule-dependent, and clathrin-mediated endocytosis. Subsequently, MSRV transports from early endosomes to late endosomes and further into lysosomes in a microtubule-dependent manner. The characterization of MSRV entry will further advance the understanding of rhabdovirus cellular entry pathways and provide novel targets for antiviral drug against MSRV infection.

CT-derived extracellular volume and liver volumetry can predict posthepatectomy liver failure in hepatocellular carcinoma.

OBJECTIVES: Posthepatectomy liver failure (PHLF) is a severe complication of liver resection. We aimed to develop and validate a model based on extracellular volume (ECV) and liver volumetry derived from computed tomography (CT) for preoperative predicting PHLF in resectable hepatocellular carcinoma (HCC) patients. METHODS: A total of 393 resectable HCC patients from two hospitals were enrolled and underwent multiphasic contrast-enhanced CT before surgery. A total of 281 patients from our hospital were randomly divided into a training cohort (n = 181) and an internal validation cohort (n = 100), and 112 patients from another hospital formed the external validation cohort. CT-derived ECV was measured on nonenhanced and equilibrium phase images, and liver volumetry was measured on portal phase images. The model is composed of independent predictors of PHLF. The under the receiver operator characteristic curve (AUC) and calibration curve were used to reflect the predictive performance and calibration of the model. Comparison of AUCs used the DeLong test. RESULTS: CT-derived ECV, measured future liver remnant (mFLR) ratio, and serum albumin were independent predictors for PHLF in resectable HCC patients. The AUC of the model was significantly higher than that of the ALBI score in the training cohort, internal validation cohort, and external validation cohort (all p < 0.001). The calibration curve of the model showed good consistency in the training cohort and the internal and external validation cohorts. CONCLUSIONS: The novel model contributes to the preoperative prediction of PHLF in resectable HCC patients. CRITICAL RELEVANCE STATEMENT: The novel model combined CT-derived extracellular volume, measured future liver remnant ratio, and serum albumin outperforms the albumin-bilirubin score for predicting posthepatectomy liver failure in patients with resectable hepatocellular carcinoma. KEY POINTS: • CT-derived ECV correlated well with the fibrosis stage of the background liver. • CT-derived ECV and mFLR ratio were independent predictors for PHLF in HCC. • The AUC of the model was higher than the CT-derived ECV and mFLR ratio. • The model showed a superior predictive performance than that of the ALBI score.

CCL2 Knockdown Attenuates Inflammatory Response After Spinal Cord Injury Through the PI3K/Akt Signaling Pathway: Bioinformatics Analysis and Experimental Validation.

Spinal cord injury (SCI) is a common clinical problem in orthopedics with a lack of effective treatments and drug targets. In the present study, we performed bioinformatic analysis of SCI datasets GSE464 and GSE45006 in the Gene Expression Omnibus (GEO) public database and experimentally validated CCL2 expression in an animal model of SCI. This was followed by stimulation of PC-12 cells using hydrogen peroxide to construct a cellular model of SCI. CCL2 expression was knocked down using small interfering RNA (si-CCL2), and PI3K signaling pathway inhibitors and activators were used to validate and observe the changes in downstream inflammation. Through data mining, we found that the inflammatory chemokine CCL2 and PI3K/Akt signaling pathways after SCI expression were significantly increased, and after peroxide stimulation of PC-12 cells with CCL2 knockdown, their downstream cellular inflammatory factor levels were decreased. The PI3K/Akt signaling pathway was blocked by PI3K inhibitors, and the downstream inflammatory response was suppressed. In contrast, when PI3K activators were used, the inflammatory response was enhanced, indicating that the CCL2-PI3K/Akt signaling pathway plays a key role in the regulation of the inflammatory response. This study revealed that the inflammatory chemokine CCL2 can regulate the inflammatory response of PC-12 cells through the PI3K/Akt signaling pathway, and blocking the expression of the inflammatory chemokine CCL2 may be a promising strategy for the treatment of secondary injury after SCI.

Design of carbazole-based platinum complexes with steric hindrance for efficient organic light-emitting diodes.

The construction of platinum complexes with high steric hindrance is expected to suppress triple-triplet annihilation and π-π stacking to achieve high-performance organic light-emitting diodes (OLEDs) with low efficiency roll-off. Herein, two large steric hindrance platinum complexes (N-CzPhPtacac and N-CzCF3PhPtacac) were prepared by taking advantage of steric hindrance between the phenyl group on carbazole and the functional group (phenyl and trifluoromethyl substituted phenyl) at the 3-position of a pyridine moiety. Due to the similar electron cloud distribution and gap difference between the HOMO and LUMO, the two complexes showed similar orange-red emission peaks at 590 and 596 nm with high PL quantum yields of 90% and 92% and short excited state lifetimes of 2.77 and 3.08 µs in doped films, respectively. Consequently, OLEDs based on N-CzPhPtacac and N-CzCF3PhPtacac showed maximum external quantum efficiency (EQEmax) values of 15.4% and 18.9%, respectively. Importantly, benefitting from the more stretched spatial configuration from the -CF3 effect, the corresponding OLED exhibited a lower efficiency roll-off, with an EQE of 18.1% at 1000 cd m-2.

Valorization of lignin-derived compounds into poly(3-hydroxybutyrate-co-3-hydroxyvalerate) by engineered Halomonas sp. Y3.

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a biopolyester with great potential, but its high production cost via the propionate-dependent pathway has hindered its development. Herein, we engineer Halomonas sp. Y3 to achieve efficient conversion of various LDCs into PHBV without propionate supplement. Initially, we successfully achieve PHBV production without propionate supplement by overexpressing threonine synthesis. The resulting biopolyester exhibits a 3 HV proportion of up to 7.89 mol%, comparable to commercial PHBV (8 mol%) available from Sigma Aldrich (403105). To further enhance PHBV production, we rationally design the reconstruction of aromatic compound catabolism. The engineered strain Y3_18 efficiently assimilates all LDCs containing syringyl (S), guaiacyl (G), and p-hydroxyphenyl-type (H) units. From 1 g/L of S-, G-, and H-type LDCs, Y3_18 produces PHBV at levels of 449 mg/L, 488 mg/L, and 716 mg/L, respectively, with yields of 44.9 % (g/g), 48.8 % (g/g), and 71.6 % (g/g). Moreover, to improve PHBV yield from lignin, we integrate laccase-secretion and PHBV production modules. This integration leads to the accumulation of 425.84 mg/L of PHBV with a yield of 21.29 % (g/g) and a 3 HV proportion of 6.38 mol%. By harnessing the capabilities of Halomonas sp. Y3, we demonstrate an efficient and sustainable approach for PHBV production from a variety of LDCs.