miR-142-3p alleviates neuronal apoptosis in Parkinson's disease via negatively regulating C9orf72.

Although microRNA (miRNA) have important clinical prospects in the early diagnosis and treatment of PD, the functions and mechanisms of miRNAs in PD models remain poorly defined. In this study, we screened 9 miRNAs that differently expressed in PD patients and found that miR-142-3p expression was downregulated in both animal and cell models of PD. We showed that overexpression of miR-142-3p significantly alleviates the neuronal damage induced by MPP+, while knockdown of miR-142-3p exacerbates the neuronal damage caused by MPP+. We further found that miR-142-3p targets and inhibits the expression of C9orf72. Knockdown of C9orf72 mitigated neuronal autophagy dysfunction by reducing excessive activation of the AKT/mTOR pathway after MPP+ stimulation, thereby exerted neuroprotective effects. This study reveals that miR-142-3p protects neuron in PD pathogenesis via negatively regulating C9orf72 and enhancing autophagy. Our findings provides an insight into the development of potential biomarkers and therapeutic targets for PD.

Attention spotlight in V1-based cortico-cortical interactions in human visual hierarchy.

Attention is often viewed as a mental spotlight, which can be scaled like a zoom lens at specific spatial locations and features a center-surround gradient. Here, we demonstrate a neural signature of attention spotlight in signal transmission along the visual hierarchy. fMRI background connectivity analysis was performed between retinotopic V1 and downstream areas to characterize the spatial distribution of inter-areal interaction under two attentional states. We found that, compared to diffused attention, focal attention sharpened the spatial gradient in the strength of the background connectivity. Dynamic causal modeling analysis further revealed the effect of attention in both the feedback and feedforward connectivity between V1 and extrastriate cortex. In a context which induced a strong effect of crowding, the effect of attention in the background connectivity profile diminished. Our findings reveal a context-dependent attention prioritization in information transmission via modulating the recurrent processing across the early stages in human visual cortex.

Effects of Vergence Eye Movement Planning on Size Perception and Early Visual Processing.

Our perception of objects depends on non-oculomotor depth cues, such as pictorial distance cues and binocular disparity, and oculomotor depth cues, such as vergence and accommodation. Although vergence eye movements are always involved in perceiving real distance, previous studies have mainly focused on the effect of oculomotor state via "proprioception" on distance and size perception. It remains unclear whether the oculomotor command of vergence eye movement would also influence visual processing. To address this question, we placed a light at 28.5 cm and a screen for stimulus presentation at 57 cm from the participants. In the NoDivergence condition, participants were asked to maintain fixation on the light regardless of stimulus presentation throughout the trial. In the WithDivergence condition, participants were instructed to initially maintain fixation on the near light and then turn their two eyes outward to look at the stimulus on the far screen. The stimulus was presented for 100 msec, entirely within the preparation stage of the divergence eye movement. We found that participants perceived the stimulus as larger but were less sensitive to stimulus sizes in the WithDivergence condition than in the NoDivergence condition. The earliest visual evoked component C1 (peak latency 80 msec), which varied with stimulus size in the NoDivergence condition, showed similar amplitudes for larger and smaller stimuli in the WithDivergence condition. These results show that vergence eye movement planning affects the earliest visual processing and size perception, and demonstrate an example of the effect of motor command on sensory processing.

Whole-transcriptome sequencing of phagocytes reveals a ceRNA network contributing to natural resistance to tuberculosis infection.

Tuberculosis (TB) is a major fatal infectious disease globally, exhibiting high morbidity rates and impacting public health and other socio-economic factors. However, some individuals are resistant to TB infection and are referred to as "Resisters". Resisters remain uninfected even after exposure to high load of Mycobacterium tuberculosis (Mtb). To delineate this further, this study aimed to investigate the factors and mechanisms influencing the Mtb resistance phenotype. We assayed the phagocytic capacity of peripheral blood mononuclear cells (PBMCs) collected from Resisters, patients with latent TB infection (LTBI), and patients with active TB (ATB), following infection with fluorescent Mycobacterium bovis Bacillus Calmette-Guérin (BCG). Phagocytosis was stronger in PBMCs from ATB patients, and comparable in LTBI patients and Resisters. Subsequently, phagocytes were isolated and subjected to whole transcriptome sequencing and small RNA sequencing to analyze transcriptional expression profiles and identify potential targets associated with the resistance phenotype. The results revealed that a total of 277 mRNAs, 589 long non-coding RNAs, 523 circular RNAs, and 35 microRNAs were differentially expressed in Resisters and LTBI patients. Further, the endogenous competitive RNA (ceRNA) network was constructed from differentially expressed genes after screening. Bioinformatics, statistical analysis, and quantitative real-time polymerase chain reaction were used for the identification and validation of potential crucial targets in the ceRNA network. As a result, we obtained a ceRNA network that contributes to the resistance phenotype. TCONS_00034796-F3, ENST00000629441-DDX43, hsa-ATAD3A_0003-CYP17A1, and XR_932996.2-CERS1 may be crucial association pairs for resistance to TB infection. Overall, this study demonstrated that the phagocytic capacity of PBMCs was not a determinant of the resistance phenotype and that some non-coding RNAs could be involved in the natural resistance to TB infection through a ceRNA mechanism.

Potential coupling of microbial methane, nitrogen, and sulphur cycling in the Okinawa Trough cold seep sediments.

The Okinawa Trough (OT) is a back-arc basin with a wide distribution of active cold seep systems. However, our understanding of the metabolic function of microbial communities in the cold seep sediments of the OT remains limited. In this study, we investigated the vertical profiles of functional genes involved in methane, nitrogen, and sulphur cycling in the cold seep sediments of the OT. Furthermore, we explored the possible coupling mechanisms between these biogeochemical cycles. The study revealed that the majority of genes associated with the nitrogen and sulphur cycles were most abundant in the surface sediment layers. However, only the key genes responsible for sulphur disproportionation (sor), nitrogen fixation (nifDKH), and methane metabolism (mcrABG) were more prevalent within sulfate-methane transition zone (SMTZ). Significant positive correlations (P < 0.05) were observed between functional genes involved in sulphur oxidation, thiosulphate disproportionation with denitrification, and dissimilatory nitrate reduction to ammonium (DNRA), as well as between AOM/methanogenesis and nitrogen fixation, and between sulphur disproportionation and AOM. A genome of Filomicrobium (class Alphaproteobacteria) has demonstrated potential in chemoautotrophic activities, particularly in coupling DNRA and denitrification with sulphur oxidation. Additionally, the characterized sulfate reducers such as Syntrophobacterales have been found to be capable of utilizing nitrate as an electron acceptor. The predominant methanogenic/methanotrophic groups in the OT sediments were identified as H2-dependent methylotrophic methanogens (Methanomassiliicoccales and Methanofastidiosales) and ANME-1a. This study offered a thorough understanding of microbial ecosystems in the OT cold seep sediments, emphasizing their contribution to nutrient cycling.IMPORTANCEThe Okinawa Trough (OT) is a back-arc basin formed by extension within the continental lithosphere behind the Ryukyu Trench arc system. Cold seeps are widespread in the OT. While some studies have explored microbial communities in OT cold seep sediments, their metabolic potential remains largely unknown. In this study, we used metagenomic analysis to enhance comprehension of the microbial community's role in nutrient cycling and proposed hypotheses on the coupling process and mechanisms involved in biogeochemical cycles. It was revealed that multiple metabolic pathways can be performed by a single organism or microbes that interact with each other to carry out various biogeochemical cycling. This data set provided a genomic road map on microbial nutrient cycling in OT sediment microbial communities.

Unveiling the ventral morphology of a rare early Cambrian great appendage arthropod from the Chengjiang biota of China.

BACKGROUND: The early Cambrian arthropod clade Megacheira, also referred to as great appendage arthropods, comprised a group of diminutive and elongated predators during the early Palaeozoic era, around 518 million years ago. In addition to those identified in the mid-Cambrian Burgess Shale biota, numerous species are documented in the renowned 518-million-year-old Chengjiang biota of South China. Notably, one species, Tanglangia longicaudata, has remained inadequately understood due to limited available material and technological constraints. In this study, we, for the first time, examined eight fossil specimens (six individuals) utilizing state-of-the-art µCT and computer-based 3D rendering techniques to unveil the hitherto hidden ventral and appendicular morphology of this species. RESULTS: We have identified a set of slender endopodites gradually narrowing distally, along with a leaf-shaped exopodite adorned with fringed setae along its margins, and a small putative exite attached to the basipodite. Our techniques have further revealed the presence of four pairs of biramous appendages in the head, aligning with the recently reported six-segmented head in other early euarthropods. Additionally, we have discerned two peduncle elements for the great appendage. These findings underscore that, despite the morphological diversity observed in early euarthropods, there exists similarity in appendicular morphology across various groups. In addition, we critically examine the existing literature on this taxon, disentangling previous mislabelings, mentions, descriptions, and, most importantly, illustrations. CONCLUSIONS: The µCT-based investigation of fossil material of Tanglangia longicaudata, a distinctive early Cambrian euarthropod from the renowned Chengjiang biota, enhances our comprehensive understanding of the evolutionary morphology of the Megacheira. Its overall morphological features, including large cup-shaped eyes, raptorial great appendages, and a remarkably elongated telson, suggest its potential ecological role as a crepuscular predator and adept swimmer in turbid waters.

Regulating the frontier orbital of iron phthalocyanine with nitrogen doped carbon nanosheets for improving oxygen reduction activity.

Iron phthalocyanine (FePc) has attracted widespread attention for its tunable electronic structure. However, the Fe-N sites suffer from undesirable oxygen reduction activity due to the symmetric geometries. A suitable substrate was thus needed to induce electron redistribution around Fe-N to improve the activity. Herein, ultrathin nitrogen-doped carbon nanosheets (N-CNSs) were prepared by a simple high temperature pyrolysis. Then iron phthalocyanine was loaded on the ultrathin nitrogen-doped carbon nanosheets (FePc@N-CNSs) by a low-cost and simple solution method. This composite catalyst shows an excellent ORR activity with a half potential of 0.88 V, an onset potential of 0.99 V and durability superior to commercial Pt/C. When used as an air cathode catalyst for rechargeable zinc-air batteries, FePc@N-CNS modified batteries outperform Pt/C + RuO2 modified batteries with higher power density and superior constant current charge-discharge cycling stability of 37 hours. The regulated electronic structure of FePc by the N-CNS substrate was revealed further by DFT calculations, which explained the enhanced adsorption of the active center to the intermediates and the increased ORR performance.

Corrigendum: Targeting HER3 to overcome RGFR TKI resistance in NSCLC.

[This corrects the article DOI: 10.3389/fimmu.2023.1332057.].

Profiles of visual perceptual learning in feature space.

Visual perceptual learning (VPL), experience-induced gains in discriminating visual features, has been studied extensively and intensively for many years, its profile in feature space, however, remains unclear. Here, human subjects were trained to perform either a simple low-level feature (grating orientation) or a complex high-level object (face view) discrimination task over a long-time course. During, immediately after, and one month after training, all results showed that in feature space VPL in grating orientation discrimination was a center-surround profile; VPL in face view discrimination, however, was a monotonic gradient profile. Importantly, these two profiles can be emerged by a deep convolutional neural network with a modified AlexNet consisted of 7 and 12 layers, respectively. Altogether, our study reveals for the first time a feature hierarchy-dependent profile of VPL in feature space, placing a necessary constraint on our understanding of the neural computation of VPL.

Evaluation of Sulfasalazine as an Adjunctive Therapy in Treating Pulmonary Pre-XDR-TB: Efficacy, Safety, and Treatment Implication.

Background: The rising prevalence and limited efficacy of treatments for pre-extensively drug-resistant tuberculosis (pre-XDR-TB) underscore an immediate need for innovative therapeutic options. A combination of host-directed therapy (HDT) and anti-TB treatment presents a viable alternative for pre-XDR-TB management. Sulfasalazine (SASP), by targeting the amino acid transport system xc (xCT), potentially reduces the intracellular Mycobacterium tuberculosis load and mitigates lung pathology, positioning it as a promising TB HDT agent. This study aims to assess the efficacy of SASP as a supplementary therapy for pre-XDR-TB. Methods: A pilot study examined the safety and effectiveness of two 9-month short-course, all-oral regimens for pre-XDR-TB treatment: Bdq-regimen (consisting of Bdq, linezolid, cycloserine, clofazimine, and pyrazinamide) and SASP-regimen (comprising SASP, linezolid, cycloserine, clofazimine, and pyrazinamide). The primary endpoint was the incidence of unfavorable outcomes 12 months post-treatment. Results: Of the 44 participants enrolled, 43 were assessable 12 months post-treatment. Culture conversion rates stood at 73.2% by Month 2 and escalated to 95.1% by Month 6. Overall, 88.4% (38/43) of the participants exhibited favorable outcomes, 85.2% (19/23) for the Bdq-regimen and 93.8% (14/15) for the SASP-regimen. The SASP-regimen group recorded no deaths or treatment failures. Conclusion: Both 9-month short-course, all-oral regimens manifested commendable primary efficacy in treating pre-XDR-TB patients. The SASP-regimen emerged as effective, safe, well-tolerated, and cost-effective.

Improving the diagnosis of active tuberculosis: a novel approach using magnetic particle-based chemiluminescence LAM assay.

OBJECTIVES: Tuberculosis (TB) is a significant global health concern, given its high rates of morbidity and mortality. The diagnosis using urine lipoarabinomannan (LAM) primarily benefits HIV co-infected TB patients with low CD4 counts. The focus of this study was to develop an ultra-sensitive LAM assay intended for diagnosing tuberculosis across a wider spectrum of TB patients. DESIGN & METHODS: To heighten the sensitivity of the LAM assay, we employed high-affinity rabbit monoclonal antibodies and selected a highly sensitive chemiluminescence LAM assay (CLIA-LAM) for development. The clinical diagnostic criteria for active TB (ATB) were used as a control. A two-step sample collection process was implemented, with the cutoff determined initially through a ROC curve. Subsequently, additional clinical samples were utilized for the validation of the assay. RESULTS: In the assay validation phase, a total of 87 confirmed active TB patients, 19 latent TB infection (LTBI) patients, and 104 healthy control samples were included. Applying a cutoff of 1.043 (pg/mL), the CLIA-LAM assay demonstrated a sensitivity of 55.2% [95%CI (44.13%~65.85%)], and a specificity of 100% [95%CI (96.52%~100.00%)], validated against clinical diagnostic results using the Mann-Whitney U test. Among 11 hematogenous disseminated TB patients, the positive rate was 81.8%. Importantly, the CLIA-LAM assay consistently yielded negative results in the 19 LTBI patients. CONCLUSION: Overall, the combination of high-affinity antibodies and the CLIA method significantly improved the sensitivity and specificity of the LAM assay. It can be used for the diagnosis of active TB, particularly hematogenous disseminated TB.

ABLIM1, a novel ubiquitin E3 ligase, promotes growth and metastasis of colorectal cancer through targeting IĸBα ubiquitination and activating NF-ĸB signaling.

Actin-binding LIM protein 1 (ABLIM1), a member of the LIM-domain protein family, has been reported as a suppressor in several tumors whereas its role in colorectal cancer (CRC) remains unknown. In this study, we find that ABLIM1 is up-regulated in CRC patients and high levels of ABLIM1 predict short disease-free survival time. Knock-down of ABLIM1 in CRC cell lines by lenti-virus leads to inhibited cell proliferation, migration, and invasion capabilities in vitro and impaired growth of tumor xenografts and liver metastasis lesions in vivo, while ABLIM1 overexpression accelerates tumor growth and invasion in vitro. Mechanistically, we uncover that ABLIM1 activates the NF-ĸB/CCL-20 signaling through modulating IĸBα ubiquitination and proteasomal-mediated degradation. Further co-immunoprecipitation, in vivo and in vitro ubiquitination assays reveal ABLIM1 as a novel ubiquitin E3 ligase binding to IĸBα. Interestingly, The E3 ligase catalysis activity of ABLIM1 depends on its 402-778aa rather than its LIM domains and its interaction with IĸBα relies on the HP domain. Our findings delineate the oncogenic role of ABLIM1 in CRC progression and reveal it as a novel E3 ligase targeting IĸBα, providing new insights into the regulation of NF-ĸB signaling in tumors.

Genetic factors associated with acquired phenotypic drug resistance and its compensatory evolution during tuberculosis treatment.

OBJECTIVES: We elucidated the factors, evolution, and compensation of antimicrobial resistance (AMR) in Mycobacterium tuberculosis (MTB) isolates under dual pressure from the intra-host environment and anti-tuberculosis (anti-TB) drugs. METHODS: This retrospective case-control study included 337 patients with pulmonary tuberculosis from 15 clinics in Tianjin, China, with phenotypic drug susceptibility testing results available for at least two time points between January 1, 2009 and December 31, 2016. Patients in the case group exhibited acquired AMR to isoniazid (INH) or rifampicin (RIF), while those in the control group lacked acquired AMR. The whole-genome sequencing (WGS) was conducted on 149 serial longitudinal MTB isolates from 46 patients who acquired or reversed phenotypic INH/RIF-resistance during treatment. The genetic basis, associated factors, and intra-host evolution of acquired phenotypic INH/RIF-resistance were elucidated using a combined analysis. RESULTS: Anti-TB interruption duration of ≥30 days showed association with acquired phenotypic INH/RIF resistance (aOR = 2·2, 95% CI, 1·0-5·1) and new rpoB mutations (p = 0·024). The MTB evolution was 1·2 (95% CI, 1·02-1·38) single nucleotide polymorphisms per genome per year under dual pressure from the intra-host environment and anti-TB drugs. AMR-associated mutations occurred before phenotypic AMR appearance in cases with acquired phenotypic INH (10 of 16) and RIF (9 of 22) resistances. DISCUSSION: Compensatory evolution may promote the fixation of INH/RIF-resistance mutations and affect phenotypic AMR. The TB treatment should be adjusted based on gene sequencing results, especially in persistent culture positivity during treatment, which highlights the clinical importance of WGS in identifying reinfection and AMR acquisition before phenotypic drug susceptibility testing.

EspB and HtpG interact with the type III-A CRISPR/Cas system of Mycobacterium tuberculosis.

Introduction: Mycobacterium tuberculosis (MTB) has a type III-A clustered regularly interspaced short palindromic repeat/CRISPR-associated protein (CRISPR/Cas) system consisting of a Csm1-5 and CRISPR RNA (crRNA) complex involved in the defense against invading nucleic acids. However, CRISPR/Cas system in the MTB still is clearly unknown and needs to be further explored. Methods: In our work, two non-Cas system proteins EspB and HtpG protein were found and identified by LC-MS/MS. The effect of EspB and HtpG on Type III-A CRISPR/Cas System of M. tuberculosis was examined by using Plasmid interference assay and Co-immunoprecipitation analyses. We explored that EspB could interact with the crRNA RNP complex, but HtpG could inhibit the accumulation of the MTB Csm proteins and defense the mechanism of CRISPR/Cas system. Results: The proteins ESAT-6 secretion system-1(Esx-1) secreted protein B (EspB) and high-temperature protein G (HtpG), which were not previously associated with CRISPR/Cas systems, are involved in mycobacterial CRISPR/Cas systems with distinct functions. Conclusion: EspB is a novel crRNA-binding protein that interacts directly with the MTB crRNP complex. Meanwhile, HtpG influences the accumulation of MTB Csm proteins and EspB and interferes with the defense mechanism of the crRNP complex against foreign DNA in vivo. Thereby, our study not only leads to developing more precise clinical diagnostic tool to quickly detect for MTB infection, but also knows these proteins merits for TB biomarkers/vaccine candidates.

Theoretical investigation of synergistically boosting the anchoring and electrochemical performance of lithiophilic/sulfiphilic transition metal carbides for lithium-sulfur batteries.

Lithium-sulfur (Li-S) battery is one of the most promising next-generation energy-storage systems with a high energy density and low cost. However, their commercial applications face several challenges, such as the shuttle effect caused by the soluble lithium polysulfide (LiPSs) intermediates and the sluggish sulfur redox reaction. In this article, we systematically investigated the anchoring and electrochemical performance of a series of transition metal carbides (TMCs: TiC, VC, ZrC, NbC, HfC, TaC) as cathode materials for Li-S batteries by theoretical calculations. The lithiophilic/sulfiphilic non-polar (001) surfaces of TMCs can offer moderate binding strength with LiPS intermediates, ensuring good performance of sulfur immobilization. These TMCs can also facilitate lithium diffusion, indicating the good rate performance of Li-S batteries. We also demonstrated that the studied TMCs can be classified into two classes according to their catalytic activity for Li2S decomposition which originated from their different electronic structural features. Furthermore, TiC, ZrC, and HfC exhibited excellent bifunctional electrochemical activity through reducing the Gibbs free energy for sulfur reduction reactions (SRRs) and lowering the barrier for Li2S decomposition which facilitates accelerating electrode kinetics and elevating utilization of sulfur. Our results offer a systematic approach to designing and screening non-polar materials for high-performance Li-S batteries, based on the rational electronic structure and lattice match strategy.

Breakthrough of chemiluminescence-based LAM urine test beyond HIV-positive individuals: Clinical diagnostic value of pulmonary tuberculosis in the general population.

To investigate the diagnostic value of a novel high-sensitivity urine lipoarabinomannan (LAM) test (chemiluminescence-based) for active tuberculosis in the general population. A retrospective study was conducted on 250 clinical suspected tuberculosis patients who were HIV-negative and visited the Fourth People's Hospital of Foshan from January 2022 to December 2022. Among them, there were 135 cases of pulmonary tuberculosis, 34 cases of extrapulmonary tuberculosis, and 81 cases of non-tuberculosis. Urine samples were collected for LAM antigen detection before treatment, and laboratory data of sputum smear acid-fast staining (smear method), sputum culture, and GeneXpert method were collected. Using clinical diagnosis as the reference standard, the diagnostic efficacy of 4 methods for detecting active tuberculosis was evaluated. For the 135 cases of pulmonary tuberculosis, the sensitivity of sputum smears, sputm culture, sputm GeneXpert method, and urine LAM were 29.6% (40/135), 45.9% (62/135), 59.3% (80/135), and 51.9% (70/135), respectively. The combination of LAM + GeneXpert and LAM + culture had the highest sensitivity for detecting active pulmonary tuberculosis, which were 71.0% and 78.2%, respectively. For the detection of sputum culture-negative pulmonary tuberculosis, the positive rates of smear, GeneXpert, and LAM were 0.0% (0/73), 53.4% (39/73), and 52.1% (38/73), respectively. LAM + smear and LAM + Genexpert could detect 52.1% and 68.5% of sputum culture-negative patients, respectively. The high-sensitivity urine LAM test holds promise for tuberculosis diagnosis in the general population. It demonstrates high-sensitivity, enabling the detection of sputum culture-negative pulmonary tuberculosis patients. Furthermore, when combined with existing methods, it can enhance the overall detection rate.

Study protocol for safety and efficacy of all-oral shortened regimens for multidrug-resistant tuberculosis: a multicenter randomized withdrawal trial and a single-arm trial [SEAL-MDR].

INTRODUCTION: The urgent need for new treatments for multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is evident. However, the classic randomized controlled trial (RCT) approach faces ethical and practical constraints, making alternative research designs and treatment strategies necessary, such as single-arm trials and host-directed therapies (HDTs). METHODS: Our study adopts a randomized withdrawal trial design for MDR-TB to maximize resource allocation and better mimic real-world conditions. Patients' treatment regimens are initially based on drug resistance profiles and patient's preference, and later, treatment-responsive cases are randomized to different treatment durations. Alongside, a single-arm trial is being conducted to evaluate the potential of sulfasalazine (SASP) as an HDT for pre-XDR-TB, as well as another short-course regimen without HDT for pre-XDR-TB. Both approaches account for the limitations in second-line anti-TB drug resistance testing in various regions. DISCUSSION: Although our study designs may lack the internal validity commonly associated with RCTs, they offer advantages in external validity, feasibility, and ethical appropriateness. These designs align with real-world clinical settings and also open doors for exploring alternative treatments like SASP for tackling drug-resistant TB forms. Ultimately, our research aims to strike a balance between scientific rigor and practical utility, offering valuable insights into treating MDR-TB and pre-XDR-TB in a challenging global health landscape. In summary, our study employs innovative trial designs and treatment strategies to address the complexities of treating drug-resistant TB, fulfilling a critical gap between ideal clinical trials and the reality of constrained resources and ethical considerations. TRAIL REGISTRATION: Chictr.org.cn, ChiCTR2100045930. Registered on April 29, 2021.

Upregulated TC1 and downregulated Chibby were correlated with the aberrant ß-catenin expression in laryngeal squamous cell carcinoma.

As an important member of Wnt/ß-catenin signaling pathway, the aberrant expression of ß-catenin has been implicated in many cancers. Chibby, a ß-catenin binding partner, is an antagonist involved in this pathway. In contrast, thyroid cancer 1 (TC1) as an activator of this pathway can relieve the antagonistic activity of Chibby on the ß-catenin-mediated transcription and is high expressed in human tumors. The objectives of this study were to examine the expression of TC1, Chibby, and ß-catenin and investigate the association among them in laryngeal squamous cell carcinoma (LSCC). The expression of TC1, Chibby, ß-catenin, c-Myc, Cyclin D1, and matrix metalloproteinase-7 (MMP-7) were examined by immunohistochemistry in samples from 53 LSCC patients. Compared with normal laryngeal squamous epithelium (NLSE), there were upregulated expression of TC1, downregulated expression of Chibby, and aberrant cytoplasmic expression of ß-catenin in the LSCC tissues (P < .001). The high expression of TC1 was correlated with the tumor site, advanced TNM and T stage, lymphovascular invasion, and poor differentiation in LSCC tissues (P < .050). There were correlations between the aberrant expression of ß-catenin and the tumor site, advanced TNM and T stage, lymphovascular invasion, perineurial invasion, and poor differentiation in LSCC tissues (P < .050). Upregulated TC1 and downregulated Chibby were correlated with aberrant expression of ß-catenin (P < .001), but no correlation between them (P = .076). The percent of abnormal expression of ß-catenin in LSCC was 96.00% in TC1+/Chibby-, 73.68% in TC1+/Chibby+, 0.00% in TC1-/Chibby-, and 0.00% in TC1-/Chibby + group (P < .001). High expression of c-Myc, Cyclin D1, and MMP-7 was observed in LSCC tissues (P < .001). There was statistically significant about the expression of Cyclin D1 and MMP-7 among the groups of TC1+/Chibby-, TC1+/Chibby+, TC1-/Chibby-, and TC1-/Chibby + (P < .001), but was not significance about the expression of c-Myc among them (P = .339). No association was found between overall survival and the expression of TC1, Chibby, and ß-catenin (P > .05). The upregulated expression of TC1 and downregulated expression of Chibby were correlated with the aberrant expression of ß-catenin and the high expression of Cyclin D1 and MMP-7 in LSCC tissues.

Preparation of Strong and Thermally Conductive, Spider Silk-Inspired, Soybean Protein-Based Adhesive for Thermally Conductive Wood-Based Composites.

The development of formaldehyde-free functional wood composite materials through the preparation of strong and multifunctional soybean protein adhesives to replace formaldehyde-based resins is an important research area. However, ensuring the bonding performance of soybean protein adhesive while simultaneously developing thermally conductive adhesive and its corresponding wood composites is challenging. Taking inspiration from the microphase separation structure of spider silk, boron nitride (BN) and soy protein isolate (SPI) were mixed by ball milling to obtain a BN@SPI matrix and combined with the self-synthesized hyperbranched reactive substrates as amorphous region reinforcer and cross-linker triglycidylamine to prepare strong and thermally conductive soybean protein adhesive with cross-linked microphase separation structure. These findings indicate that mechanical ball milling can be employed to strip BN followed by combination with SPI, resulting in a tight bonded interface connection. Subsequently, the adhesive's dry and wet shear strengths increased by 14.3% and 90.5% to 1.83 and 1.05 MPa, respectively. The resultant adhesive also possesses a good thermal conductivity (0.363 W/mK). Impressively, because hot-pressing helps the resultant adhesive to establish a thermal conduction pathway, the thermal conductivity of the resulting wood-based composite is 10 times higher than that of the SPI adhesive, which shows a thermal conductivity similar to that of ceramic tile and has excellent potential for developing biothermal conductivity materials, geothermal floors, and energy storage materials. Moreover, the adhesive possessed effective flame retardancy (limit oxygen index = 36.5%) and mildew resistance (>50 days). This bionic design represents an efficient technique for developing multifunctional biomass adhesives and composites.