Interferon-γ induces tumor resistance to anti-PD-1 immunotherapy by promoting YAP phase separation.

Interferon-γ (IFN-γ)-mediated adaptive resistance is one major barrier to improving immunotherapy in solid tumors. However, the mechanisms are not completely understood. Here, we report that IFN-γ promotes nuclear translocation and phase separation of YAP after anti-PD-1 therapy in tumor cells. Hydrophobic interactions of the YAP coiled-coil domain mediate droplet initiation, and weak interactions of the intrinsically disordered region in the C terminus promote droplet formation. YAP partitions with the transcription factor TEAD4, the histone acetyltransferase EP300, and Mediator1 and forms transcriptional hubs for maximizing target gene transcriptions, independent of the canonical STAT1-IRF1 transcription program. Disruption of YAP phase separation reduced tumor growth, enhanced immune response, and sensitized tumor cells to anti-PD-1 therapy. YAP activity is negatively correlated with patient outcome. Our study indicates that YAP mediates the IFN-γ pro-tumor effect through its nuclear phase separation and suggests that YAP can be used as a predictive biomarker and target of anti-PD-1 combination therapy.

LATS2 condensates organize signalosomes for Hippo pathway signal transduction.

Biomolecular condensates have been proposed to mediate cellular signaling transduction. However, the mechanism and functional consequences of signal condensates are not well understood. Here we report that LATS2, the core kinase of the Hippo pathway, responds to F-actin cytoskeleton reduction and forms condensates. The proline-rich motif (PRM) of LATS2 mediates its condensation. LATS2 partitions with the main components of the Hippo pathway to assemble a signalosome for LATS2 activation and for its stability by physically compartmentalizing from E3 ligase FBXL16 complex-dependent degradation, which in turn mediates yes-associated protein (YAP)-transcriptional coactivator with PDZ-binding motif (TAZ) recruitment and inactivation. This oncogenic FBXL16 complex blocks LATS2 condensation by binding to the PRM region to promote its degradation. Disruption of LATS2 condensation leads to tumor progression. Thus, our study uncovers that the signalosomes assembled by LATS2 condensation provide a compartmentalized and reversible platform for Hippo signaling transduction and protein stability, which have potential implications in cancer diagnosis and therapeutics.

Identification of toll-like receptor family and the immune function of new Sptlr-6 gene of Scylla paramamosain.

As a crucial member of pattern-recognition receptors (PRRs), the Tolls/Toll-like receptors (TLRs) gene family has been proven to be involved in innate immunity in crustaceans. In this study, nine members of TLR gene family were identified from the mud crab (Scylla paramamosain) transcriptome, and the structure and phylogeny of different SpTLRs were analyzed. It was found that different SpTLRs possessed three conserved structures in the TIR domain. Meanwhile, the expression patterns of different Sptlr genes in examined tissues detected by qRT-PCR had wide differences. Compared with other Sptlr genes, Sptlr-6 gene was significantly highly expressed in the hepatopancreas and less expressed in other tissues. Therefore, the function of Sptlr-6 was further investigated. The expression of the Sptlr-6 gene was up-regulated by Poly I: C, PGN stimulation and Vibrio parahaemolyticus infection. In addition, the silencing of Sptlr-6 in hepatopancreas mediated by RNAi technology resulted in the significant decrease of several conserved genes involved in innate immunity in mud crab after V. parahaemolyticus infection, including relish, myd88, dorsal, anti-lipopolysaccharide factor (ALF), anti-lipopolysaccharide factor 2 (ALF-2) and glycine-rich antimicrobial peptide (glyamp). This study provided new knowledge for the role of the Sptlr-6 gene in defense against V. parahaemolyticus infection in S. paramamosain.

Sagittal en bloc resection of thoracolumbar tumours: a report of thirty one cases.

PURPOSE: To develop a novel classification of sagittal en bloc resection (SEBR) based on anatomical locations for thoracolumbar spine tumors and assess the clinical outcomes of this surgical procedure. METHODS: 31 patients with thoracolumbar tumours treated with SEBR were enrolled in this study. The individualized surgical strategy was adopted based on our surgical classification. Demographics, perioperative outcomes, complications and postoperative outcomes were assessed. RESULTS: Based on our surgical classifications, patients were divided into four types. All bony resection margins were negative, wide resection was achieved in 25 patients, marginal resection in four, and intralesional resection in two. 18 patients underwent anterior reconstruction. Complications were encountered in five patients, and instrumentation failure occurred in one patient. The median follow-up was 24 (range, 6-72) months and recurrence was found in only one patient. CONCLUSION: SEBR is a safe and effective surgical procedure for patients with thoracolumbar spinal tumours in specific anatomical locations. The proposed surgical classification covers all SEBR types and is easy to apply, it may assist surgical decision-making in patients with spinal tumours.

High uniformity red µ-LED array with a current efficiency of 2.6 cd/A and ns-level response time.

This paper demonstrates an AlGaInP-based 620-nm red micro-light-emitting-diode (µ-LED) array and studies the enhancement effect of the surface treatments using (NH4)2Sx solutions by comparing the characteristics of µ-LED arrays with and without the (NH4)2Sx treatment. Furthermore, our µ-LED array demonstrates a measurement of the current efficiency (2.6 cd/A), which improves the light output uniformity. Also, we apply a setup for measuring the response time at the fast ns-level to analyze the effect of passivation in AlGaInP-based µ-LED arrays.

Minimally invasive separation surgery for the treatment of spinal metastases with small incision and freehand pedicle screw fixation: the surgical learning curve.

BACKGROUND: Minimally invasive separation surgery (MISS) is a safe and effective surgical technique, the current optimal treatment for spinal metastases. However, the learning curve for this technique has not been analyzed. This study aimed to define and analyze the surgical learning curve of MISS for the treatment of spinal metastases with small incision and freehand pedicle screw fixation. METHODS: A continuous series of 62 patients with spinal metastases who underwent MISS were included. Each patient's operative data were accurately counted. The improvement of the patients' neurological function was followed up after surgery to evaluate the surgical treatment effect. Logarithmic curve-fit regression was used to analyze the surgical learning curve of MISS. The number of cases needed to achieve proficiency was analyzed. Based on this cut-off point, this series of cases was divided into the early phase and later phase groups. The influence of the time sequence of MISS on surgical data and surgical efficacy was analyzed. RESULTS: The operative time decreased gradually with the number of surgical cases increasing and stabilized after the 20th patient. There was no statistical difference in demographic characteristics and preoperative characteristics between the two groups. The mean operative time in the later phase group was about 39 min shorter than that in the early phase group (mean 227.95 vs. 189.02 min, P = 0.027). However, it did not affect other operative data or the surgical treatment effect. CONCLUSION: The learning curve of MISS for spinal metastases is not steep. With the increase of surgeons' experience, the operative time drops rapidly and stabilizes within a certain range. MISS can be safely and effectively performed at the beginning of a surgeon's caree.

Waterborne Polyurethane Enhanced, Adhesive, and Ionic Conductive Hydrogel for Multifunctional Sensors.

In the past two decades, ionic conductive hydrogel has attracted tremendous research interests for their intrinsic characteristics in the field of flexible sensor. However, synchronous achievement of high mechanical strength, satisfied ionic conductivity, and broad adhesion to various substrates is still a challenge. Herein, a novel zwitterionic composite hydrogel that displayed excited strechability (up to 900%), satisfied strength (about 30 kPa), high ionic conductivity (1.2 mS cm-1 ), and adhesion to polar and nonpolar materials is fabricated though the combination of waterborne polyurethanes (PU) and poly(sulfobetaine zwitterion-co-acrylamide) (SAm). Especially, this facile strategy demonstrates that PU has a synergistic effect on enhancing mechanical strength and ionic conductivity for ionic conductive hydrogel. Moreover, the hydrogel-based strain/stress sensor shows high sensitivity, wide sensing range, great stability, and accuracy for human body movements detecting and voice recognition. This novel ionic conductive hydrogel has promoted the development of wearable devices.

Distinct H3K9me3 and DNA methylation modifications during mouse spermatogenesis.

DNA methylation and histone modifications critically regulate the expression of many genes and repeat regions during spermatogenesis. However, the molecular details of these processes in male germ cells remain to be addressed. Here, using isolated murine sperm cells, ultra-low-input native ChIP-Seq (ULI-NChIP-Seq), and whole genome bisulfite sequencing (WGBS), we investigated genome-wide DNA methylation patterns and histone 3 Lys-9 trimethylation (H3K9me3) modifications during mouse spermatogenesis. We found that DNA methylation and H3K9me3 have distinct sequence preferences and dynamics in promoters and repeat elements during spermatogenesis. H3K9me3 modifications in histones at gene promoters were highly enriched in round spermatids. H3K9me3 modification on long terminal repeats (LTRs) and long interspersed nuclear elements (LINEs) was involved in silencing active transcription from these regions in conjunction with reestablishment of DNA methylation. Furthermore, H3K9me3 remodeling on the X chromosome was involved in meiotic sex chromosome inactivation and in partial transcriptional reactivation of sex chromosomes in spermatids. Our findings also revealed the DNA methylation patterns and H3K9me3 modification profiles of paternal and maternal germline imprinting control regions (gICRs) during spermatogenesis. Taken together, our results provide a genome-wide map of H3K9me3 modifications during mouse spermatogenesis that may be helpful for understanding male reproductive disorders.

Biomechanical effect of anterior talofibular ligament injury in Weber B lateral malleolus fractures after lateral plate fixation: A finite element analysis.

OBJECTIVE: To determine the biomechanical effect of anterior talofibular ligament injury in Weber B lateral malleolus fractures after lateral plate fixation. METHOD: A three-dimensional model was established based on CT images from a healthy volunteer. The simulation of lateral malleolus fracture, and the modeling and assembly of plate were completed by referring to characteristics of Weber B lateral malleolus fractures, as well as the technical characteristics of open reduction and internal fixation of lateral plate. Operating conditions were set up for groups A-D. The proximal end of the model was restrained in all four groups, 200N of upward force and 100N of backward force were applied at anterior of talus head in order to simulate the dorsiflexion of ankle joint. Biomechanical differences of the lateral plate were observed under various conditions of different ligament ruptures. RESULTS: The maximum stress value of group A was the smallest, approximately 78.47N, while that of group C was the largest, approximately 238.83N. The maximum stress value of group B was about 91.69N; and that of group D was about 184.08N. Importantly, location of the maximum stress in group D (CUT ATaF) was displaced from the posterior edge to the anterior edge of the plate, which was different from those of the other three groups. CONCLUSIONS: The anterior talofibular ligament injury may be a major contributing factor to the stress of lateral plate fixation following Weber B lateral malleolus fracture. It should be considered as an essential risk factor for evaluation of the stability in these fractures.

Toward self-powered and reliable visible light communication using amorphous silicon thin-film solar cells.

Enhancing robustness and energy efficiency is critical in visible light communication (VLC) to support large-scale data traffic and connectivity of smart devices in the era of fifth-generation networks. To this end, we demonstrate that amorphous silicon (a-Si) thin-film solar cells with a high light absorption coefficient are particularly useful for simultaneous robust signal detection and efficient energy harvesting under the condition of weak light in this study. Moreover, a first-generation prototype called AquaE-lite is developed that consists of an a-Si thin-film solar panel and receiver circuits, which can detect weak light as low as 1 µW/cm2. Using AquaE-lite and a white-light laser, orthogonal frequency-division multiplexing signals with data rates of 1 Mb/s and 908.2 kb/s are achieved over a 20-m long-distance air channel and 2.4-m turbid outdoor pool water, respectively, under the condition of strong background light. The reliable VLC system based on energy-efficient a-Si thin-film solar cells opens a new pathway for future satellite-air-ground-ocean optical wireless communication to realize connectivity among millions of Internet of Things devices.

Bibliometric Mapping of Psychological Flexibility Research: Trends and Future Directions.

In this article, we offer an exhaustive analysis of academic work on psychological flexibility using bibliometric techniques. We identify emerging trends in a dataset of 3535 scholarly articles from the Web of Science database. We highlight key publications, map out the field's intellectual framework, and anticipate future research avenues through co-citation and co-word analytics. The co-citation assessment revealed five distinct clusters, while the co-word analysis showed three. Although research regarding psychological flexibility has gained recent popularity, there remains a need for more scholarly initiatives to achieve a nuanced understanding of this subject.

Transcriptomics reveals different response mechanisms of Litopenaeus vannamei hemocytes to injection of Vibrio parahaemolyticus and WSSV.

As the most important cultural crustacean species worldwide, studies about Pacific white shrimp (Litopenaeus vannamei) have received more attention. It has been well-documented that various pathogens could infect L. vannamei, resulting in huge economic losses. The studies about the responding mechanism of L. vannamei to sole pathogens such as Vibrio parahaemolyticus and white spot virus (WSSV) have been extensively reported, while the studies about the differently responding mechanisms remain unclear. In the present study, we identified the differently expressed genes (DEGs) of L. vannamei hemocytes post V. parahaemolyticus and WSSV infection with RNA-seq technology and compared the DEGs between the two groups. The results showed 2672 DEGs post the V. parahaemolyticus challenge (1079 up-regulated and 1593 down-regulated genes), while 1146 DEGs post the WSSV challenge (1067 up-regulated and 513 down-regulated genes). In addition, we screened the genes that simultaneously respond to WSSV and V. parahaemolyticus (434), solely respond to WSSV (1146), and V. parahaemolyticus challenge (2238), respectively. Six DEGs involved in innate immunity were quantified to validate the RNA-seq results, and the results confirmed the high consistency of both methods. Furthermore, we found plenty of innate immunity-related genes that responded to V. parahaemolyticus and WSSV infection, including pattern recognition receptors (PRRs), the proPO activating system, antimicrobial peptides (AMPs), and other immunity-related proteins. The results revealed that they were differently expressed after different pathogen challenges, demonstrating the complex and specific recognition systems involved in defending against the invasion of different pathogens in the environment. The present study improved our understanding of the molecular response of hemocytes of L. vannamei to V. parahaemolyticus and WSSV stimulation.

3D-printed modular prostheses for reconstruction of intercalary bone defects after joint-sparing limb salvage surgery for femoral diaphyseal tumours.

Aims: The aim of this study was to investigate the safety and efficacy of 3D-printed modular prostheses in patients who underwent joint-sparing limb salvage surgery (JSLSS) for malignant femoral diaphyseal bone tumours. Methods: We retrospectively reviewed 17 patients (13 males and four females) with femoral diaphyseal tumours who underwent JSLSS in our hospital. Results: In all, 17 patients with locally aggressive bone tumours (Enneking stage IIB) located in the femoral shaft underwent JSLSS and reconstruction with 3D-printed modular prostheses between January 2020 and June 2022. The median surgical time was 153 minutes (interquartile range (IQR) 117 to 248), and the median estimated blood loss was 200ml (IQR 125 to 400). Osteosarcoma was the most common pathological type (n = 12; 70.6%). The mean osteotomy length was 197.53 mm (SD 12.34), and the median follow-up was 25 months (IQR 19 to 38). Two patients experienced local recurrence and three developed distant metastases. Postoperative complications included wound infection in one patient and screw loosening in another, both of which were treated successfully with revision surgery. The median Musculoskeletal Tumor Society score at the final follow-up was 28 (IQR 27 to 28). Conclusion: The 3D-printed modular prosthesis is a reliable and feasible reconstruction option for patients with malignant femoral diaphyseal tumours. It helps to improve the limb salvage rate, restore limb function, and achieve better short-term effectiveness.

DNA Image Cytometry for Screening the Carcinogenetic Risk of Oral Potential Malignant Disorders.

Background: Oral Submucosal Fibrosis (OSF) and Oral Leukoplakia (OLK) are well-known oral potentially malignant disorders, and cases of Oral Submucosal Fibrosis concomitant Oral Leukoplakia (OSF+OLK) are now being reported clinically. DNA image cytometry is an objective and non-invasive method for monitoring the risk of precancerous lesions in the oral cavity. Methods: A total of 111 patients with clinically characterized oral mucosal lesions underwent simultaneous and independent histopathological and DNA imaging cytometry assessments. Clinical data were also collected for each patient. Results: The frequency of DNA content abnormality was higher in the tongue than in other oral sites (P = 0.003) for OLK. The frequency of DNA content abnormality was higher in the tongue than in other oral sites (P = 0.035) for OSF+OLK. The differences of DNA content abnormality in age, sex, dietary habit, smoking, and alcohol intake were not observed in OLK and OSF+OLK. The study indicates an association between DNA content abnormality and pathological examination in OSF+OLK ( χ2 test, P = 0.007). OLK showed higher sensitivity and specificity than OSF, while the sensitivity and specificity of OSF+OLK are higher than OLK only and OSF only. Conclusion: DNA image cytometry can be utilized as an adjunctive device for the initial detection of oral potentially malignant disorders that require further clinical management.

Transforming higher education institutions through EDI leadership: A bibliometric exploration.

This comprehensive bibliometric study analyzes 1820 journal articles from the Web of Science database to explore Equity, Diversity, and Inclusion (EDI) leadership in higher education institutions (HEIs). Utilizing co-citation and co-word analysis, the study identifies distinct thematic clusters. The co-citation analysis reveals five key themes: Race, Diversity, and Inclusion (RDI), Diversity, Leadership, and Self-Efficacy (DLSE), Gender Dynamics and Leadership Challenges, Women's Representation in Academic Medicine Leadership, and Transformational Leadership in HEIs. Meanwhile, the co-word analysis highlights three critical areas: Transformative Collaborative Resilience in HEIs, Advancing Gender Equality in Academic Medicine and STEM, and Inclusive Educational Leadership in HEIs. These themes collectively provide a deep understanding of the EDI leadership field's intellectual structure, suggesting significant areas for future research and practical application. The study emphasizes the necessity for HEIs to engage comprehensively in EDI leadership research, shedding light on the importance of transformative collaborative resilience, gender equality in STEM, and inclusive leadership. This research offers valuable insights for developing effective EDI leadership policies and practices, highlighting the interconnectedness of these themes in fostering a more equitable, diverse, and inclusive environment in higher education and beyond.

SRCAP complex promotes lung cancer progression by reprograming the oncogenic transcription of Hippo-YAP/TAZ signaling pathway.

The activation of YAP/TAZ, a pair of paralogs of transcriptional coactivators, initiates a dysregulated transcription program, which is a key feature of human cancer cells. However, it is not fully understood how YAP/TAZ promote dysregulated transcription for tumor progression. In this study, we employed the BioID method to identify the interactome of YAP/TAZ and discovered that YAP/TAZ interact with multiple components of SRCAP complex, a finding that was further validated through endogenous and exogenous co-immunoprecipitation, as well as immunofluorescence experiments. CUT&Tag analysis revealed that SRCAP complex facilitates the deposition of histone variant H2A.Z at target promoters. The depletion of SRCAP complex resulted in a decrease in H2A.Z occupancy and the oncogenic transcription of YAP/TAZ target genes. Additionally, the blockade of SRCAP complex suppressed YAP-driven tumor growth. In a genetically engineered lung adenocarcinoma mouse model and non-small cell lung cancer patients, SRCAP complex and H2A.Z deposition were found to be upregulated. This upregulation was statistically correlated with YAP expression, pathological stages, and poor survival in lung cancer patients. Together, our study uncovers that SRCAP complex plays a critical role in YAP/TAZ oncogenic transcription by coordinating H2A.Z deposition during cancer progression, providing potential targets for cancer diagnosis and prevention.

Mass Spectrometry-Based Proteomics Identifies Serpin B9 as a Key Protein in Promoting Bone Metastases in Lung Cancer.

Bone metastasis (BM) is one of the most common complications of advanced cancer. Immunotherapy for bone metastasis of lung cancer (LCBM) is not so promising and the immune mechanisms are still unknown. Here, we utilized a model of BM by injecting cancer cells through caudal artery (CA) to screen out a highly bone metastatic derivative (LLC1-BM3) from a murine lung cancer cell line LLC1. Mass spectrometry-based proteomics was performed in LLC1-parental and LLC1-BM3 cells. Combining with prognostic survival information from patients with lung cancer, we identified serpin B9 (SB9) as a key factor in BM. Molecular characterization showed that SB9 overexpression was associated with poor prognosis and high bone metastatic burden in lung cancer. Moreover, SB9 could increase the ability of lung cancer cells to metastasize to the bone. The mechanistic studies revealed that tumor-derived SB9 promoted BM through an immune cell-dependent way by inactivating granzyme B, manifesting with the decreased infiltration of cytotoxic T cells and increased expression level of exhausted markers. A specific SB9-targeting inhibitor [1,3-benzoxazole-6-carboxylic acid (BTCA)] significantly suppressed LCBM in the CA mouse model. This study reveals that SB9 may serve as a therapeutic target and potential prognostic marker for patients with LCBM. IMPLICATIONS: SB9 as a therapeutic target for LCBM.

Tribochemical mechanisms of abrasives for SiC and sapphire substrates in nanoscale polishing.

Strong acid, alkali, or active chemicals are generally employed in chemical mechanical polishing (CMP) slurry for the ultra-precision machining of semiconductor substrates, obstructing further improvement in machining accuracy and reduction in damaged layers. Understanding the material removal behavior of abrasives, which combines mechanical and chemical actions during nanoscale abrasive polishing, poses a significant challenge. In this study, the interfacial interaction mechanisms between abrasives and substrates during nanoscale polishing with only deionized water used as coolant were analyzed by utilizing concerned experiments and molecular dynamics (MD) simulations. The results showed that ultra-smooth SiC and sapphire substrate surfaces only with damage layer thicknesses of 2.06 nm and 0.76 nm were obtained by employing diamond abrasive and alumina abrasive, respectively. Tribochemical reactions could occur on substrate surfaces under the repeated interfacial fiction of fine abrasives without any chemical reagents during nanoscale polishing. The tribochemical reactions mainly depended on the chemical compatibility between the abrasives and substrates when the material removal size of abrasives was limited to nanoscale, not abrasive hardness. Furthermore, a new method of abrasive selection is proposed and widely applied in the ultra-precision polishing of semiconductor substrates, which could not only improve removal efficiency but also ensure good surface quality.

Validation of the Muscularity Bias Internalization Scale in Chinese women.

The Muscularity Bias Internalization Scale (MBIS) captures an individual's endorsement of stereotypical beliefs about muscularity and engagement in self-stigmatizing evaluations about their muscularity. The MBIS has been validated in Chinese men and Lebanese men and women, showing strong internal consistency reliability and construct validity. Because muscularity-related body image concerns are present in Chinese women, there is a need for research to validate the MBIS in Chinese women. The present study examined the factor structure and psychometric properties of the MBIS in a sample of Chinese women. Exploratory factor analysis (n = 300) identified a two-factor structure which showed adequate model fit in confirmatory factor analysis (n = 300), with χ2(76) = 294.63 (p < .001), CFI = 0.98, TLI = 0.98, and SRMR = 0.05. Results also showed that the MBIS in women had adequate internal consistency, two-week test-retest reliability, and good construct validity. Findings suggest that the MBIS is a useful tool for assessing muscularity bias internalization, a potentially important risk factor for muscularity-oriented eating and body image disturbances.

Assessing the factor structure of the Eating Attitude Test-26 among undergraduate students in Malaysia.

The objective of this study was to assess the factor structure of the 26-item Eating Attitude Test (EAT-26) through confirmatory factor analysis (CFA) among 1,084 undergraduate students in Malaysia. The initial findings indicated a lack of support for the proposed three-factor structure. Model modifications were made due to the inadequate initial fit. The fit of the model was significantly improved by excluding items with factor loadings below 0.40 and integrating residual covariances. In conclusion, it is necessary to make contextual modifications to the EAT-26 in order to effectively utilize it among Malaysian undergraduates. This highlights the significance of cultural adaptations in psychological instruments.