An immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.

NP105-113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.

Combined analyses of RNA-sequence and Hi-C along with GWAS loci-A novel approach to dissect keloid disorder genetic mechanism.

Keloid disorder is a tumour-like disease with invasive growth and a high recurrence rate. Genetic contribution is well expected due to the presence of autosomal dominant inheritance and various genetic mutations in keloid lesions. However, GWAS failed to reveal functional variants in exon regions but single nucleotide polymorphisms in the non-coding regions, suggesting the necessity of innovative genetic investigation. This study employed combined GWAS, RNA-sequence and Hi-C analyses to dissect keloid disorder genetic mechanisms using paired keloid tissues and normal skins. Differentially expressed genes, miRNAs and lncRNAs mined by RNA-sequence were identified to construct a network. From which, 8 significant pathways involved in keloid disorder pathogenesis were enriched and 6 of them were verified. Furthermore, topologically associated domains at susceptible loci were located via the Hi-C database and ten differentially expressed RNAs were identified. Among them, the functions of six molecules for cell proliferation, cell cycle and apoptosis were particularly examined and confirmed by overexpressing and knocking-down assays. This study firstly revealed unknown key biomarkers and pathways in keloid lesions using RNA-sequence and previously reported mutation loci, indicating a feasible approach to reveal the genetic contribution to keloid disorder and possibly to other diseases that are failed by GWAS analysis alone.

Therapy-induced senescent tumor cell-derived extracellular vesicles promote colorectal cancer progression through SERPINE1-mediated NF-κB p65 nuclear translocation.

BACKGROUND: Cellular senescence frequently occurs during anti-cancer treatment, and persistent senescent tumor cells (STCs) unfavorably promote tumor progression through paracrine secretion of the senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) have recently emerged as a novel component of the SASP and primarily mediate the tumor-promoting effect of the SASP. Of note, the potential effect of EVs released from STCs on tumor progression remains largely unknown. METHODS: We collected tumor tissues from two cohorts of colorectal cancer (CRC) patients to examine the expression of p16, p21, and SERPINE1 before and after anti-cancer treatment. Cohort 1 included 22 patients with locally advanced rectal cancer (LARC) who received neoadjuvant therapy before surgical resection. Cohort 2 included 30 patients with metastatic CRC (mCRC) who received first-line irinotecan-contained treatment. CCK-8, transwell, wound-healing assay, and tumor xenograft experiments were carried out to determine the impacts of EVs released from STCs on CRC progression in vitro and in vivo. Quantitative proteomic analysis was applied to identify protein cargo inside EVs secreted from STCs. Immunoprecipitation and mass spectrometer identification were utilized to explore the binding partners of SERPINE1. The interaction of SERPINE1 with p65 was verified by co-immunoprecipitation, and their co-localization was confirmed by immunofluorescence. RESULTS: Chemotherapeutic agents and irradiation could potently induce senescence in CRC cells in vitro and in human CRC tissues. The more significant elevation of p16 and p21 expression in patients after anti-cancer treatment displayed shorter disease-free survival (DFS) for LARC or progression-free survival (PFS) for mCRC. We observed that compared to non-STCs, STCs released an increased number of EVs enriched in SERPINE1, which further promoted the progression of recipient cancer cells. Targeting SERPINE1 with a specific inhibitor, tiplaxtinin, markedly attenuated the tumor-promoting effect of STCs-derived EVs. Additionally, the patients with greater increment of SERPINE1 expression after anti-cancer treatment had shorter DFS for LARC or PFS for mCRC. Mechanistically, SERPINE1 bound to p65, promoting its nuclear translocation and subsequently activating the NF-κB signaling pathway. CONCLUSIONS: We provide the in vivo evidence of the clinical prognostic implications of therapy-induced senescence. Our results revealed that STCs were responsible for CRC progression by producing large amounts of EVs enriched in SERPINE1. These findings further confirm the crucial role of therapy-induced senescence in tumor progression and offer a potential therapeutic strategy for CRC treatment.

Rapid, Micron-Resolution 3D Printing of Nd:YAG Ceramic with Optical Gain.

Polycrystalline yttrium aluminum garnet (YAG) ceramic doped with neodymium (Nd), referred to as Nd:YAG, is widely used in solid-state lasers. However, conventional powder metallurgy methods suffer from expenses, time consumption, and limitations in customizing structures. This study introduces a novel approach for creating Nd:YAG ceramics with 3D free-form structures from micron (∼70 µm) to centimeter scales. Firstly, sol-gel synthesis is employed to form photocurable colloidal solutions. Subsequently, by utilizing a home-built micro-continuous liquid interface printing process, precursors are printed into 3D poly(acrylic acid) hydrogels containing yttrium, aluminum, and neodymium hydroxides, with a resolution of 5.8 µm pixel-1 at a speed of 10 µm s-1. After the hydrogels undergo thermal dehydration, debinding, and sintering, polycrystalline Nd:YAG ceramics featuring distinguishable grains are successfully produced. By optimizing the concentrations of the sintering aids (tetraethyl orthosilicate) and neodymium trichloride (NdCl3), the resultant samples exhibit satisfactory photoluminescence, emitting light concentrated at 1064 nm when stimulated by a 532 nm laser. Additionally, Nd:YAG ceramics with various 3D geometries (e.g., cone, spiral, and angled pillar) are printed and characterized, which demonstrates the potential for applications, such as laser and amplifier fibers, couplers, and splitters in optical circuits, as well as gain metamaterials or metasurfaces.

Quorum Sensing Interference Assisted Therapy-Based Magnetic Hyperthermia Amplifier for Synergistic Biofilm Treatment.

Biofilms offer bacteria a physical and metabolic barrier, enhancing their tolerance to external stress. Consequently, these biofilms limit the effectiveness of conventional antimicrobial treatment. Recently, quorum sensing (QS) has been linked to biofilm's stress response to thermal, oxidative, and osmotic stress. Herein, a multiple synergistic therapeutic strategy that couples quorum sensing interference assisted therapy (QSIAT)-mediated enhanced thermal therapy with bacteria-triggered immunomodulation in a single nanoplatform, is presented. First, as magnetic hyperthermia amplifier, hyaluronic acid-coated ferrite (HA@MnFe2 O4 ) attenuates the stress response of biofilm by down-regulating QS-related genes, including agrA, agrC, and hld. Next, the sensitized bacteria are eliminated with magnetic heat. QS interference and heat also destruct the biofilm, and provide channels for further penetration of nanoparticles. Moreover, triggered by bacterial hyaluronidase, the wrapped hyaluronic acid (HA) decomposes into disaccharides at the site of infection and exerts healing effect. Thus, by reversing the bacterial tissue invasion mechanism for antimicrobial purpose, tissue regeneration following pathogen invasion and thermal therapy is successfully attained. RNA-sequencing demonstrates the QS-mediated stress response impairment. In vitro and in vivo experiments reveal the excellent antibiofilm and anti-inflammatory effects of HA@MnFe2 O4 . Overall, QSIAT provides a universal enhancement strategy for amplifying the bactericidal effects of conventional therapy via stress response interference.

Fucoidan modulates SIRT1 and NLRP3 to alleviate hypertensive retinopathy: in vivo and in vitro insights.

BACKGROUND: Hypertension influences the inflammatory pathological changes in the retina. The function of the inflammasomes is significant. To see if Sirtuin 1 (SIRT1) regulates angiotensin II (Ang II)-induced hypertensive retinopathy and inflammation by modulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation and the potential protective effects of fucoidan (FO) in mouse retinal vascular endothelial cells (mRECs) and mice retina. METHODS: The diagnosis of hypertensive retinopathy was made after three weeks of Ang II infusion (3000 ng/kg/min). One day prior to the commencement of Ang II infusion, the mice were treatment with NLRP3 inhibitor MCC950 (10 mg/kg/day, intraperitoneal injections) or FO (300 mg/kg/day, oral gavage). A blood pressure was recorded. Hematoxylin and eosin (H&E) staining was used to conduct pathological alterations, dihydroethidium bromide (DHE) was utilized to assess oxidative stress damage in the retina, and fluorescence angiography was used to identify vascular disorders in the eye. Using immunohistochemical labeling, NLRP3 expression was found. Reactive protein and mRNA expression levels in mouse retina and cells were assessed using Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: NLRP3 inflammasome activation and SIRT1 decrease were brought about by Ang II infusion. Retinopathy and dysfunction were lessened by MCC950 target-induced NLRP3 inflammasome activation, while overexpression of SIRT1 had the opposite impact on NLRP3 inflammasome activation, indicating that SIRT1 functions as an upstream regulator of NLRP3 activity. FO may improve SIRT1 expression and decrease NLRP3 activation in retinopathy and dysfunction brought on by Ang II, and the effects were consistent across both in vivo and in vitro models. CONCLUSIONS: SIRT1 adversely regulates the NLRP3 inflammasome pathway, which in turn increases Ang II-induced inflammation and hypertensive retinopathy. FO may mitigate Ang II-induced retinopathy and dysfunction via modulating the expression of SIRT1/NLRP3. This implies practical approaches to the management of hypertensive retinopathy.

Effect of preservation fluid contamination and associated possible donor-derived infections on early postoperative prognosis in kidney transplant recipients.

BACKGROUND: The study aims to analyze the epidemiology of preservation fluid (PF) contamination and investigate the impact of PF contamination and possible donor-derived infections(p-DDI) on early postoperative prognosis in kidney transplant (KT) recipients. METHODS: A total of 256 PF samples were collected for microbiological evaluation from all KT recipients who received deceased donor donations in our hospital from June 2018 to August 2022. Data on the baseline and clinical characteristics of these PF corresponding to recipients and donors were extracted from the electronic medical record. It mainly included the early postoperative complications and prognosis of KT recipients. RESULTS: From June 2018 to August 2022, 597 kidney transplants were performed in our center, with 260 recipients receiving kidney transplantation from donation after citizens' death. A total of 256 samples of PF were collected, of which 64.5% (165/256) were culture positive, and 24.6% (63/165) of the culture-positive PF were polymicrobial contamination. A total of 238 strains were isolated, of which coagulase-negative staphylococci (CoNS) had the highest proportion of 34.0% (81/238), followed by Klebsiella pneumoniae with 20.6% (49/238) and Escherichia coli with 8.8% (21/238). Recipients with culture-positive PF had a significantly higher incidence of postoperative infection (55.8% vs. 20.9%, P < 0.001) and DGF (38.2% vs. 24.2%, P = 0.023). In addition, the incidence of p-DDI was 12.9% (33/256). CRKP was the most common pathogen causing p-DDI. The recipients who developed p-DDI had a higher rate of graft loss (9.1% vs. 0.4%, P < 0.001), mortality (12.1% vs. 3.1%, P = 0.018), and longer postoperative hospital stay (30 days (19.5-73.5) vs. (22 days (18-32), P < 0.05) compared with recipients who did not develop p-DDI. CONCLUSIONS: Culture-positive PF is potentially significant for KT recipients, and p-DDI may increase the risk of poor prognosis for recipients. Prophylactic anti-infective treatment should be actively performed for highly virulent or multidrug-resistant (MDR) pathogens (especially Carbapenem-resistant Klebsiella pneumoniae, CRKP) in PF to avoid the occurrence of p-DDI.

Using capillary electrophoresis sodium dodecyl sulfate (CE-SDS) and liquid chromatograph mass spectrometry (LC-MS) to identify glycosylated heavy chain heterogeneity in the anti-VEGFR-2 monoclonal antibody.

The size variant, which can be measured by capillary electrophoresis sodium dodecyl sulfate (CE-SDS), is a critical quality attribute of monoclonal antibodies (mAbs). The CE-SDS size heterogeneity can hardly be identified by tandem mass spectrometry, which is an intractable obstacle of mAb development and quality control across the industry. We analyzed the purity of an anti-vascular endothelial growth factor receptor 2 (VEGFR-2) mAb, an antagonist of the human VEGFR-2, through reduced CE-SDS and observed glycosylated heavy chain heterogeneity. The heterogeneity has potential impact on safety, efficacy, and stability of drugs for clinical use. Therefore, it should be characterized so as to evaluate its potential risk. In order to identify the heterogeneity, we used mass spectrometry to confirm that the molecular size heterogeneity was not due to peptide bond cleavage in the heavy chain. Subsequently, we employed mass-spectrometry-glycosylation profiling and CE-SDS analysis of various glycosidase-treated samples, in addition to the preparation of mAb references with different glycoforms. Ultimately, we demonstrated that the heavy chain heterogeneity was induced by different levels of galactosylation modifications which will potentially impact the efficacy of antibody drugs (i.e., complement-dependent cytotoxicity). In this study, potential risk caused by heavy chain size heterogeneity was evaluated, which addressed the obstacle of mAb development and quality control. Therefore, this study offers a feasible approach for the investigation and identification of heavy chain heterogeneity in reduced CE-SDS, providing a novel strategy for mAb quality control and evaluation.

Chemical Design of Supramolecular Reversible Adhesives for Promising Applications.

Supramolecular reversible adhesives have garnered significant attention due to their potential applications in various fields. These adhesives exhibit remarkable properties such as reversible adhesion, self-healing, and high flexibility. This concept aims to present a comprehensive overview of the current research progress in developing supramolecular reversible adhesives. Firstly, the fundamentals of supramolecular chemistry and the principles underlying the design and synthesis of reversible adhesive systems are discussed. Next, the concept focuses on characterizing the reversible adhesion strength of supramolecular adhesive systems that have been developed. The adhesion performance of supramolecular reversible adhesives is summarized, highlighting their unique characteristics and promising applications. Finally, the challenges and future perspectives in the field of supramolecular reversible adhesives are discussed. The comprehensive overview provided in this concept aims to inspire further research and innovation in this exciting field.

Knockdown of phosphatases of regenerating liver-1 prolongs the lifespan of Caenorhabditis elegans via activating DAF-16/FOXO.

Phosphatases of regenerating liver (PRLs) are dual-specificity protein phosphatases. The aberrant expression of PRLs threatens human health, but their biological functions and pathogenic mechanisms are unclear yet. Herein, the structure and biological functions of PRLs were investigated using the Caenorhabditis elegans (C. elegans). Structurally, this phosphatase in C. elegans, named PRL-1, consisted of a conserved signature sequence WPD loop and a single C(X)5 R domain. Besides, by Western blot, immunohistochemistry and immunofluorescence staining, PRL-1 was proved to mainly express in larval stages and express in intestinal tissues. Afterward, by feeding-based RNA-interference method, knockdown of prl-1 prolonged the lifespan of C. elegans but also improved their healthspan, such as locomotion, pharyngeal pumping frequency, and defecation interval time. Furthermore, the above effects of prl-1 appeared to be taken without acting on germline signaling, diet restriction pathway, insulin/insulin-like growth factor 1 signaling pathway, and SIR-2.1 but through a DAF-16-dependent pathway. Moreover, knockdown of prl-1 induced the nuclear translocation of DAF-16, and upregulated the expression of daf-16, sod-3, mtl-1, and ctl-2. Finally, suppression of prl-1 also reduced the ROS. In conclusion, suppression of prl-1 enhanced the lifespan and survival quality of C. elegans, which provides a theoretical basis for the pathogenesis of PRLs in related human diseases.

Pro-vasculogenic Fibers by PDA-Mediated Surface Functionalization Using Cell-Free Fat Extract (CEFFE).

Formation of adequate vascular network within engineered three-dimensional (3D) tissue substitutes postimplantation remains a major challenge for the success of biomaterials-based tissue regeneration. To better mimic the in vivo angiogenic and vasculogenic processes, nowadays increasing attention is given to the strategy of functionalizing biomaterial scaffolds with multiple bioactive agents. Aimed at engineering electrospun biomimicking fibers with pro-vasculogenic capability, this study was proposed to functionalize electrospun fibers of polycaprolactone/gelatin (PCL/GT) by cell-free fat extract (CEFFE or FE), a newly emerging natural "cocktail" of cytokines and growth factors extracted from human adipose tissue. This was achieved by having the electrospun PCL/GT fiber surface coated with polydopamine (PDA) followed by PDA-mediated immobilization of FE to generate the pro-vasculogenic fibers of FE-PDA@PCL/GT. It was found that the PDA-coated fibrous mat of PCL/GT exhibited a high FE-loading efficiency (∼90%) and enabled the FE to be released in a highly sustained manner. The engineered FE-PDA@PCL/GT fibers possess improved cytocompatibility, as evidenced by the enhanced cellular proliferation, migration, and RNA and protein expressions (e.g., CD31, vWF, VE-cadherin) in the human umbilical vein endothelial cells (huvECs) used. Most importantly, the FE-PDA@PCL/GT fibrous scaffolds were found to enormously stimulate tube formation in vitro, microvascular development in the in ovo chick chorioallantoic membrane (CAM) assay, and vascularization of 3D construct in a rat subcutaneous embedding model. This study highlights the potential of currently engineered pro-vasculogenic fibers as a versatile platform for engineering vascularized biomaterial constructs for functional tissue regeneration.

Efficacy and safety of intragastric expandable oral capsules in adults with overweight or obesity: A randomized, double-blind, placebo-controlled trial.

AIM: This trial assessed the efficacy and safety of 2.24 g intragastric expandable capsules twice per day versus placebo for weight management in adults with overweight or obesity. METHODS: This double-blind, placebo-controlled study included adults with a body mass index of at least 24 kg/m2 and no more than 40 kg/m2 . In total, 280 participants were recruited from six hospitals in China and were assigned in a 1:1 ratio to receive 2.24 g oral intragastric expandable capsules or placebo for 24 weeks. Coprimary endpoints were the percentage change in body weight from baseline and the rate of weight reduction of ≥5%, assessed using both the full analysis set and per protocol set. RESULTS: At baseline, the mean body weight was 81.8 kg, and the mean body mass index was 29.4 kg/m2 . The mean body weight change at week 24 was -4.9% with intragastric expandable capsules versus -1.9% with placebo [estimated treatment difference (ETD) -3.0%, 95% confidence interval (CI) -4.1 to -1.9; p < .001] using the full analysis set and -6.1% versus -2.5% (ETD -3.6%, 95% CI -5.0 to -2.3; p < .001), respectively, using the per protocol set. The percentage of participants who had weight loss exceeding 5% was 45.0% in the intragastric expandable capsule group versus 19.7% in the placebo group (ETD 25.3%, 95% CI 14.7-35.9; p < .001) in the full analysis set and 55.9% versus 26.2% (ETD 29.6%, 95% CI 17.1-42.2; p < .001), respectively, in the per protocol set. Waist circumference significantly decreased at week 24 (intragastric expandable capsules vs. placebo: -5.6 ± 8.3 cm vs. -2.9 ± 4.8 cm; p = .003). The most common adverse events associated with the use of intragastric expandable capsules were gastrointestinal disorders (intragastric expandable capsule vs. placebo, 25.0% vs. 21.9%), and most were mild and transient. CONCLUSIONS: In this 24-week trial including participants with overweight or obesity, 2.24 g of intragastric expandable capsules twice daily led to a clinically meaningful reduction in body weight compared with placebo.

Effects of Several Auxiliary Acceptors and Anchoring Groups on Charge Transfer and Photophysical Properties of D-A-π-A Type DSSCs: A DFT Study.

In this paper, we performed theoretical studies on the twelve D-A-π-A type organic dyes (G-1 ~ G-3, M-1 ~ M-3, J-1 ~ J-3, and S-1 ~ S-3) with 9-phenylcarbazole as the electron donor in anticipation of the application of these dyes in dye-sensitized solar cells (DSSCs). DFT and TD-DFT methods are applied to investigate in detail the molecular geometries, frontier molecular orbitals (FMOs), absorption spectra, charge density difference (CDD), and transition density matrix (TDM) of several dyes. The results show that the M-series (M-1 ~ M-3) dyes have the largest dihedral angles between the electron donor and the auxiliary acceptor and also has the largest energy gaps in HOMO-LUMO orbitals, which greatly reduces the charge transfer efficiency. Finally, the UV-Vis absorption spectra inferred that the anchoring groups modified with o-nitrobenzoic acid (G-3, M-3, J-3, S-3) can red-shift the absorption peaks of the dyes, which results in higher light-harvesting efficiency and improves the power conversion efficiency of DSSCs. Overall, all of these dyes contribute to the improvement of photovoltaic power conversion efficiency and have potential for application in DSSCs devices.

Associations between accelerometer-measured physical activity and sedentary behaviour with physical function among older women: a cross-sectional study.

BACKGROUND: This study aimed to investigate the relationships between accelerometer-measured physical activity (PA) and sedentary behaviour (SB) with physical function (PF) among older Chinese women in the community. METHODS: The present study comprised 1,113 community-dwelling older females, with an average age of 65 ± 2 years. We employed a linear regression analysis to investigate the relationship between patterns of PA and SB with PF. PA variables consisted of total PA time, bouted PA time (a continuous PA that lasts equal to or more than 10 min), and sporadic PA time (a continuous PA that lasts less than 10 min). SB variables included total SB time, 30-min bout of SB (a continuous SB that lasts equal to or more than 30 min), and 60-min bout of SB (a continuous SB that lasts equal to or more than 60 min). PF variables comprised handgrip strength (HGS), one-legged stance test with eyes closed (OLSTEC), usual walking speed (UWS), maximum walking speed (MWS) and chair-stand time (CT). To explore the joint effects of moderate-to-vigorous-intensity PA (MVPA) and SB on PF, we divided the duration of SB and MVPA participation in older women into different combinations: low MVPA & high SB, low MVPA & low SB, high MVPA & high SB, high MVPA & low SB. RESULTS: The study revealed a significant association between 30-min bout of SB and CT, which remained after adjusting for total MVPA time (P = 0.021). Both total MVPA and bouted MVPA were found to be positively associated with better UWS, MWS, CT, and PF Z-score. When the combination of low MVPA & high SB was used as a reference, the regression coefficients for PF ascended by 1.32 (P < 0.001) in the high MVPA & high SB group and by 1.13 (P < 0.001) in the high MVPA & low SB group. CONCLUSIONS: A significant association was observed between poorer lower limb function and prolonged, uninterrupted SB in older women, rather than with the total SB time. Concurrently, the insufficient engagement in MVPA may also be a crucial factor contributing to poorer PF in older women. Engaging in longer durations and higher intensity of PA, such as bouts of MVPA lasting a minimum of 10 min or longer, may contribute to better PF.

Clinical Analysis of Superficial Temporal Artery-Middle Cerebral Artery Bypass Combined with Brain-Temporal Muscle Sticking in the Treatment of Chronic Internal Carotid Artery Occlusion.

Objective: NHISS score, MMSE scale, craniocerebral CTA or DSA, and craniocerebral magnetic resonance 3D-ASL were used to evaluate the efficacy and safety of superficial temporal artery-middle cerebral artery (STA-MCA) shunt combined with cranial-muscular-merging (EMS) in the treatment of symptomatic chronic internal carotid artery occlusion. Methods: The purpose of this study was to retrospectively analyze the clinical data of 15 patients with symptomatic chronic internal carotid artery occlusion who received STA-MCA shunt combined with EMS treatment at Weifang Brain Hospital and Weifang Traditional Chinese Medicine Hospital from July 2016 to December 2020. The patients' neurological and cognitive functions were evaluated by NHISS score and MMSE examination before surgery and 6 months after surgery. Adverse reactions after surgery were observed, and preoperative and postoperative cerebral hemodynamics, the patency of the shunt anastomosis, and the compensation of collateral circulation were evaluated by cranial CTA or DSA and cranial MRI 3D-ASL. Results: All 15 patients underwent successful surgery. One patient experienced transient mild cerebral hyperperfusion syndrome postoperatively. Six months after surgery, the NHISS score was significantly improved compared with that before surgery (P = .0001), and the MMSE score was also significantly improved compared with before surgery (P = .0124). No adverse events of poor scalp healing, intracranial infection, subcutaneous fluid accumulation, subdural hematoma, or cerebral hemorrhage were observed postoperatively. Imaging examination showed that the shunt vessels were unobstructed, the middle cerebral artery was dilated, collateral circulation in the surgical area was increased, and cerebral blood flow increased. Conclusion: STA-MCA shunt combined with EMS treatment is safe and effective for symptomatic chronic internal carotid artery occlusion. It has the potential to improve cerebral blood flow and reduce clinical symptoms.

Research on the RZB-Type Three-Dimensional Drilling Strain Measurement System.

Borehole strain gauges play a crucial role in geophysical, seismological, and crustal dynamics studies. While existing borehole strain gauges are proficient in measuring horizontal strains within vertical boreholes, their effectiveness in capturing vertical and oblique strains is limited due to technical constraints arising from the cylindrical probe's characteristics. However, the accurate measurement of three-dimensional strain is essential for a comprehensive understanding of crustal tectonics, dynamics, and geophysics, particularly considering the diverse geological structures and force sources within the crustal medium. In this study, we present a novel approach to address this challenge by enhancing an existing horizontal-component borehole strain gauge with a bellows structure and line strain measurement technology to enable vertical and borehole oblique strain measurements. Integrating these enhancements with horizontal strain measurement capabilities enables comprehensive three-dimensional borehole strain measurements within the same hole section. The system was deployed and tested at the Gongxian seismic station in Sichuan Province. Clear observations of solid tides were recorded across horizontal, oblique, and vertical measurement units, with the tidal morphology and amplitude being consistent with the theoretical calculations. The achieved measurement sensitivity of 10-10 meets the requirements for borehole strain measurement, enabling the characterization of three-dimensional strain states within boreholes through association methods.

Mu-Suppression Neurofeedback Training Targeting the Mirror Neuron System: A Pilot Study.

Neurofeedback training (NFT) is a promising adjuvant intervention method. The desynchronization of mu rhythm (8-13 Hz) in the electroencephalogram (EEG) over centro-parietal areas is known as a valid indicator of mirror neuron system (MNS) activation, which has been associated with social skills. Still, the effect of neurofeedback training on the MNS requires to be well investigated. The present study examined the possible impact of NFT with a mu suppression training protocol encompassing 15 NFT sessions (45 min each) on 16 healthy neurotypical participants. In separate pre- and post-training sessions, 64-channel EEG was recorded while participants (1) observed videos with various types of movements (including complex goal-directed hand movements and social interaction scenes) and (2) performed the "Reading the Mind in the Eyes Test" (RMET). EEG source reconstruction analysis revealed statistically significant mu suppression during hand movement observation across MNS-attributed fronto-parietal areas after NFT. The frequency analysis showed no significant mu suppression after NFT, despite the fact that numerical mu suppression appeared to be visible in a majority of participants during goal-directed hand movement observation. At the behavioral level, RMET accuracy scores did not suggest an effect of NFT on the ability to interpret subtle emotional expressions, although RMET response times were reduced after NFT. In conclusion, the present study exhibited preliminary and partial evidence that mu suppression NFT can induce mu suppression in MNS-attributed areas. More powerful experimental designs and longer training may be necessary to induce substantial and consistent mu suppression, particularly while observing social scenarios.

Multiple interface coupling on natural tourmaline enables high-efficiency removal of antibiotic: Superior property and mechanism.

Reasonably designing highly active, environmentally friendly, and cost-effective catalysts for efficient elimination of pollutants from water is desirable but challenging. Herein, an efficient heterogeneous photo-Fenton catalyst tourmaline (TM)/tungsten oxide (WO3-x) (named TW10) containing tungsten/boron/iron (W/B/Fe) synergistic active centers and 90% of cheap natural tourmaline (TM) mineral rich in Fe and B elements. The TW10 catalyst can quickly activate peroxymonosulfate (PMS) to generate massive active free radicals, which may induce the rapid and efficient degradation of tetracycline (TC). The TW10/PMS/Visible light system can effectively degrade up to 98.7% of tetracycline (TC) in actual waters (i.e. seawater, Yellow River, and Yangtze River water), and the catalytic degradation rates reach 1.65, 5.569, and 2.38 times higher than those of TM, WO3-x, and commercial P25 (Degussa, Germany), respectively. In addition, the catalyst can be recycled and reused multiple times. Electron spin resonance spectroscopy (EPR), X-ray photoelectron spectroscopy (XPS), and liquid chromatograph-mass spectrometer (LC-MS) analyses confirm that the synergistic catalytic effect of W/B/Fe sites on the TW10 catalyst accelerates the electron transfer between Fe(II) and Fe(III), as well as between W(V) and W(VI), and thus promotes the rapid degradation of TC. The catalytic reaction mechanism and degradation pathway of TC were explored. This work provides a feasible route for the design and development of new eco-friendly and efficient catalyst.

CRTC2 activates the epithelial-mesenchymal transition of diabetic kidney disease through the CREB-Smad2/3 pathway.

BACKGROUND: Epithelial-mesenchymal transition (EMT) plays a key role in tubulointerstitial fibrosis, which is a hallmark of diabetic kidney disease (DKD). Our previous studies showed that CRTC2 can simultaneously regulate glucose metabolism and lipid metabolism. However, it is still unclear whether CRTC2 participates in the EMT process in DKD. METHODS: We used protein‒protein network (PPI) analysis to identify genes that were differentially expressed during DKD and EMT. Then, we constructed a diabetic mouse model by administering STZ plus a high-fat diet, and we used HK-2 cells that were verified to confirm the bioinformatics research results. The effects that were exerted by CRTC2 on epithelial-mesenchymal transition in diabetic kidney disease through the CREB-Smad2/3 signaling pathway were investigated in vivo and in vitro by real-time PCR, WB, IHC and double luciferase reporter gene experiments. RESULTS: First, bioinformatics research showed that CRTC2 may promote EMT in diabetic renal tubules through the CREB-Smad2/3 signaling pathway. Furthermore, the Western blotting and real-time PCR results showed that CRTC2 overexpression reduced the expression of E-cadherin in HK-2 cells. The CRTC2 and α-SMA levels were increased in STZ-treated mouse kidneys, and the E-cadherin level was reduced. The luciferase activity of α-SMA, which is the key protein in EMT, was sharply increased in response to the overexpression of CRTC2 and decreased after the silencing of CREB and Smad2/3. However, the expression of E-cadherin showed the opposite trends. In the real-time PCR experiment, the mRNA expression of α-SMA increased significantly when CRTC2 was overexpressed but partially decreased when CREB and Smad2/3 were silenced. However, E-cadherin expression showed the opposite result. CONCLUSION: This study demonstrated that CRTC2 activates the EMT process via the CREB-Smad2/3 signaling pathway in diabetic renal tubules.

Mass Spectrometry-Based Charge Heterogeneity Characterization of Therapeutic mAbs with Imaged Capillary Isoelectric Focusing and Ion-Exchange Chromatography as Separation Techniques.

Imaged capillary isoelectric focusing (icIEF) and ion-exchange chromatography (IEX) are two essential techniques that are routinely used for charge variant analysis of therapeutic monoclonal antibodies (mAbs) during their development and in quality control. These two techniques that separate mAb charge variants based on different mechanisms and IEX have been developed as front-end separation techniques for online mass spectrometry (MS) detection, which is robust for intact protein identification. Recently, an innovative, coupled icIEF-MS technology has been constructed for protein charge variant analysis in our laboratory. In this study, icIEF-MS developed and strong cation exchange (SCX)-MS were optimized for charge heterogeneity characterization of a diverse of mAbs and their results were compared based on methodological validation. It was found that icIEF-MS outperformed SCX-MS in this study by demonstrating outstanding sensitivity, low carryover effect, accurate protein identification, and higher separation resolution although SCX-MS contributed to higher analysis throughput. Ultimately, integrating our novel icIEF-HRMS analysis with the more common SCX-MS can provide a promising and comprehensive strategy for accelerating the development of complex protein therapeutics.