Trephination-based autonomous robotic surgery for dental implant placement: A proof of concept.

OBJECTIVES: To present a novel drilling protocol of trephine osteotomy technique for autologous bone grafting with simultaneous implant placement using an autonomous robotic system. METHODS: The novel protocol consists of 1) preoperative procedures: marker fabrication and fixation, data acquisition, and preoperative planning; 2) intraoperative procedures: registration and calibration, and osteotomy and implant placement performed by an autonomous dental implant robot; 3) postoperative procedures: CBCT acquisition and accuracy assessment. RESULT: The protocol was an effective method for implant osteotomy, with no reported intraoperative complications. The implant surgery was successfully completed, and autogenous bone was obtained. Meanwhile, the accuracy of implant placement was clinically acceptable, with minor deviations. CONCLUSIONS: Trephination-based robotic surgery can be successfully implemented in implant osteotomy, which might replace freehand implant surgery and conventional drilling protocol. However, further clinical studies are necessary. CLINICAL SIGNIFICANCE: The main finding of this case is a potential alternative for preserving autogenous bone during implant surgery.

Identification of Novel Regulators of Leaf Senescence Using a Deep Learning Model.

Deep learning has emerged as a powerful tool for investigating intricate biological processes in plants by harnessing the potential of large-scale data. Gene regulation is a complex process that transcription factors (TFs), cooperating with their target genes, participate in through various aspects of biological processes. Despite its significance, the study of gene regulation has primarily focused on a limited number of notable instances, leaving numerous aspects and interactions yet to be explored comprehensively. Here, we developed DEGRN (Deep learning on Expression for Gene Regulatory Network), an innovative deep learning model designed to decipher gene interactions by leveraging high-dimensional expression data obtained from bulk RNA-Seq and scRNA-Seq data in the model plant Arabidopsis. DEGRN exhibited a compared level of predictive power when applied to various datasets. Through the utilization of DEGRN, we successfully identified an extensive set of 3,053,363 high-quality interactions, encompassing 1430 TFs and 13,739 non-TF genes. Notably, DEGRN's predictive capabilities allowed us to uncover novel regulators involved in a range of complex biological processes, including development, metabolism, and stress responses. Using leaf senescence as an example, we revealed a complex network underpinning this process composed of diverse TF families, including bHLH, ERF, and MYB. We also identified a novel TF, named MAF5, whose expression showed a strong linear regression relation during the progression of senescence. The mutant maf5 showed early leaf decay compared to the wild type, indicating a potential role in the regulation of leaf senescence. This hypothesis was further supported by the expression patterns observed across four stages of leaf development, as well as transcriptomics analysis. Overall, the comprehensive coverage provided by DEGRN expands our understanding of gene regulatory networks and paves the way for further investigations into their functional implications.

TRIANGLE operation, combined with adequate adjuvant chemotherapy, can improve the prognosis of pancreatic head cancer: A retrospective study.

BACKGROUND: The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein, celiac axis-common hepatic artery, and superior mesenteric artery to improve patient prognosis. Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma (PDAC), data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy (PD). AIM: To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC. METHODS: This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023, with or without the TRIANGLE operation. Patients were divided into the PDTRIANGLE and PDnon-TRIANGLE groups. Surgical and survival outcomes were compared between the two groups. Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy ≥ 6 months. RESULTS: The PDTRIANGLE and PDnon-TRIANGLE groups included 52 and 55 patients, respectively. There were no significant differences in the baseline characteristics or perioperative indexes between the two groups. Furthermore, the recurrence rate was lower in the PDTRIANGLE group than in the PDnon-TRIANGLE group (48.1% vs 81.8%, P < 0.001), and the local recurrence rate of PDAC decreased from 37.8% to 16.0%. Multivariate Cox regression analysis revealed that PDTRIANGLE (HR = 0.424; 95%CI: 0.256-0.702; P = 0.001), adequate adjuvant chemotherapy ≥ 6 months (HR = 0.370; 95%CI: 0.222-0.618; P < 0.001) and margin status (HR = 2.255; 95%CI: 1.252-4.064; P = 0.007) were found to be independent factors for the recurrence rate. CONCLUSION: The TRIANGLE operation is safe for PDAC patients undergoing PD. Moreover, it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

A xenogeneic extracellular matrix-based 3D printing scaffold modified by ceria nanoparticles for craniomaxillofacial hard tissue regeneration via osteo-immunomodulation.

Hard tissue engineering scaffolds especially 3D printed scaffolds were considered an excellent strategy for craniomaxillofacial hard tissue regeneration, involving crania and facial bones and teeth. Porcine treated dentin matrix (pTDM) as xenogeneic extracellular matrix has the potential to promote the stem cell differentiation and mineralization as it contains plenty of bioactive factors similar with human-derived dentin tissue. However, its application might be impeded by the foreign body response induced by the damage-associated molecular patterns of pTDM, which would cause strong inflammation and hinder the regeneration. Ceria nanoparticles (CNPs) show a great promise at protecting tissue from oxidative stress and influence the macrophages polarization. Using 3D-bioprinting technology, we fabricated a xenogeneic hard tissue scaffold based on pTDM xenogeneic TDM-polycaprolactone (xTDM/PCL) and we modified the scaffolds by CNPs (xTDM/PCL/CNPs). Through series ofin vitroverification, we found xTDM/PCL/CNPs scaffolds held promise at up-regulating the expression of osteogenesis and odontogenesis related genes including collagen type 1, Runt-related transcription factor 2 (RUNX2), bone morphogenetic protein-2, osteoprotegerin, alkaline phosphatase (ALP) and DMP1 and inducing macrophages to polarize to M2 phenotype. Regeneration of bone tissues was further evaluated in rats by conducting the models of mandibular and skull bone defects. Thein vivoevaluation showed that xTDM/PCL/CNPs scaffolds could promote the bone tissue regeneration by up-regulating the expression of osteogenic genes involving ALP, RUNX2 and bone sialoprotein 2 and macrophage polarization into M2. Regeneration of teeth evaluated on beagles demonstrated that xTDM/PCL/CNPs scaffolds expedited the calcification inside the scaffolds and helped form periodontal ligament-like tissues surrounding the scaffolds.

Reactive Oxygen Species-Responsive Delivery of a Notch Inhibitor to Alleviate Nonalcoholic Steatohepatitis by Inhibiting Hepatic de Novo Lipogenesis and Inflammation.

With the increased prevalence of nonalcoholic steatohepatitis (NASH) in the world, effective pharmacotherapy in clinical practice is still lacking. Previous studies have shown that dibenzazepine (DBZ), a Notch inhibitor, could alleviate NASH development in a mouse model. However, low bioavailability, poor water solubility, and extrahepatic side effects restrict its clinical application. To overcome these barriers, we developed a reactive oxygen species (ROS)-sensitive nanoparticle based on the conjugation of bilirubin to poly(ethylene glycol) (PEG) chains, taking into account the overaccumulation of hepatic ROS in the pathologic state of nonalcoholic steatohepatitis (NASH). The PEGylated bilirubin can self-assemble into nanoparticles in an aqueous solution and encapsulate insoluble DBZ into its hydrophobic cavity. DBZ nanoparticles (DBZ Nps) had good stability, rapidly released DBZ in response to H2O2, and effectively scavenged intracellular ROS of hepatocytes. After systemic administration, DBZ Nps could accumulate in the liver of the NASH mice, extend persistence in circulation, and improve the bioavailability of DBZ. Furthermore, DBZ Nps significantly improved glucose intolerance, relieved hepatic lipid accumulation and inflammation, and ameliorated NASH-induced liver fibrosis. Additionally, DBZ Nps had no significant extrahepatic side effects. Taken together, our results highlight the potential of the ROS-sensitive DBZ nanoparticle as a promising therapeutic strategy for NASH.

Multi-omics integration highlights the role of ubiquitination in endometriosis fibrosis.

BACKGROUND: Endometriosis, characterized by the presence of active endometrial-like tissues outside the uterus, causes symptoms like dysmenorrhea and infertility due to the fibrosis of endometrial cells, which involves excessive deposition of extracellular matrix (ECM) proteins. Ubiquitination, an important post-transcriptional modification, regulates various biological processes in human diseases. However, its role in the fibrosis process in endometriosis remains unclear. METHODS: We employed multi-omics approaches on two cohorts of endometriosis patients with 39 samples. GO terms and KEGG pathways enrichment analyses were used to investigate the functional changes involved in endometriosis. Pearson's correlation coefficient analysis was conducted to explore the relationship between global proteome and ubiquitylome in endometriosis. The protein expression levels of ubiquitin-, fibrosis-related proteins, and E3 ubiquitin-protein ligase TRIM33 were validated via Western blot. Transfecting human endometrial stroma cells (hESCs) with TRIM33 small interfering RNA (siRNA) in vitro to explore how TRIM33 affects fibrosis-related proteins. RESULTS: Integration of proteomics and transcriptomics showed genes with concurrent change of both mRNA and protein level which involved in ECM production in ectopic endometria. Ubiquitylomics distinguished 1647 and 1698 ubiquitinated lysine sites in the ectopic (EC) group compared to the normal (NC) and eutopic (EU) groups, respectively. Further multi-omics integration highlighted the essential role of ubiquitination in key fibrosis regulators in endometriosis. Correlation analysis between proteome and ubiquitylome showed correlation coefficients of 0.32 and 0.36 for ubiquitinated fibrosis proteins in EC/NC and EC/EU groups, respectively, indicating positive regulation of fibrosis-related protein expression by ubiquitination in ectopic lesions. We identified ubiquitination in 41 pivotal proteins within the fibrosis-related pathway of endometriosis. Finally, the elevated expression of TGFBR1/α-SMA/FAP/FN1/Collagen1 proteins in EC tissues were validated across independent samples. More importantly, we demonstrated that both the mRNA and protein levels of TRIM33 were reduced in endometriotic tissues. Knockdown of TRIM33 promoted TGFBR1/p-SMAD2/α-SMA/FN1 protein expressions in hESCs but did not significantly affect Collagen1/FAP levels, suggesting its inhibitory effect on fibrosis in vitro. CONCLUSIONS: This study, employing multi-omics approaches, provides novel insights into endometriosis ubiquitination profiles and reveals aberrant expression of the E3 ubiquitin ligase TRIM33 in endometriotic tissues, emphasizing their critical involvement in fibrosis pathogenesis and potential therapeutic targets.

Predicting long-term outcomes in patients with classical trigeminal neuralgia following microvascular decompression with an MRI-based radiomics nomogram: a multicentre study.

OBJECTIVES: This study aimed to develop a clinical-radiomics nomogram to predict the long-term outcomes of patients with classical trigeminal neuralgia (CTN) following microvascular decompression (MVD). MATERIALS AND METHODS: This retrospective study included 455 patients with CTN who underwent MVD from three independent institutions A total of 2030 radiomics features from the cistern segment of the trigeminal nerve were extracted computationally from the three-dimensional steady-state free precession and three-dimensional time-of-flight magnetic resonance angiography sequences. Using the least absolute shrinkage and selection operator regression, 16 features were chosen to develop radiomics signatures. A clinical-radiomics nomogram was subsequently developed in the development cohort of 279 patients via multivariate Cox regression. The predictive performance and clinical application of the nomogram were assessed in an external cohort consisting of 176 patients. RESULTS: Sixteen highly outcome-related radiomics features extracted from multisequence images were used to construct the radiomics model, with concordance indices (C-index) of 0.804 and 0.796 in the development and test cohorts, respectively. Additionally, a clinical-radiomics nomogram was developed by incorporating both radiomics features and clinical characteristics (i.e., pain type and degree of neurovascular compression) and yielded higher C-indices of 0.865 and 0.834 in the development and test cohorts, respectively. K‒M survival analysis indicated that the nomogram successfully stratified patients with CTN into high-risk and low-risk groups for poor outcomes (hazard ratio: 37.18, p < 0.001). CONCLUSION: Our study findings indicated that the clinical-radiomics nomogram exhibited promising performance in accurately predicting long-term pain outcomes following MVD. CLINICAL RELEVANCE STATEMENT: This model had the potential to aid clinicians in making well-informed decisions regarding the treatment of patients with CTN. KEY POINTS: Trigeminal neuralgia recurs in about one-third of patients after undergoing MVD. The clinical-radiomics nomogram stratified patients into high- and low-risk groups for poor surgical outcomes. Using this nomogram could better inform patients of recurrence risk and allow for discussion of alternative treatments.

Normobaric Hyperoxia Combined With Endovascular Treatment Based on Temporal Gradient: A Dose-Escalation Study.

BACKGROUND: Normobaric hyperoxia (NBO) has neuroprotective effects in acute ischemic stroke. Thus, we aimed to identify the optimal NBO treatment duration combined with endovascular treatment. METHODS: This is a single-center, randomized controlled, open-label, blinded-end point dose-escalation clinical trial. Patients with acute ischemic stroke who had an indication for endovascular treatment at Tianjin Huanhu Hospital were randomly assigned to 4 groups (1:1 ratio) based on NBO therapy duration: (1) control group (1 L/min oxygen for 4 hours); (2) NBO-2h group (10 L/min for 2 hours); (3) NBO-4h group (10 L/min for 4 hours); and (4) NBO-6h group (10 L/min for 6 hours). The primary outcome was cerebral infarction volume at 72 hours after randomization using an intention-to-treat analysis model. The primary safety outcome was the 90-day mortality rate. RESULTS: Between June 2022 and September 2023, 100 patients were randomly assigned to the following groups: control group (n=25), NBO-2h group (n=25), NBO-4h group (n=25), and NBO-6h group (n=25). The 72-hour cerebral infarct volumes were 39.4±34.3 mL, 30.6±30.1 mL, 19.7±15.4 mL, and 22.6±22.4 mL, respectively (P=0.013). The NBO-4h and NBO-6h groups both showed statistically significant differences (adjusted P values: 0.011 and 0.027, respectively) compared with the control group. Compared with the control group, both the NBO-4h and NBO-6h groups showed significant differences (P<0.05) in the National Institutes of Health Stroke Scale scores at 24 hours, 72 hours, and 7 days, as well as in the change of the National Institutes of Health Stroke Scale scores from baseline to 24 hours. Additionally, there were no significant differences among the 4 groups in terms of 90-day mortality rate, symptomatic intracranial hemorrhage, early neurological deterioration, or severe adverse events. CONCLUSIONS: The effectiveness of NBO therapy was associated with oxygen administration duration. Among patients with acute ischemic stroke who underwent endovascular treatment, NBO therapy for 4 and 6 hours was found to be more effective. Larger-scale multicenter studies are needed to validate these findings. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05404373.

Renal function affects the safety and efficacy of tirofiban in acute ischemic stroke thrombectomy patients.

BACKGROUND: Acute ischemic stroke poses a significant health threat, and thrombectomy has become a routine treatment. Tirofiban has emerged as a promising adjunct therapy to minimize reocclusion after thrombectomy. We aimed to investigate whether renal function influences the safety and efficacy of tirofiban in patients undergoing endovascular therapy. METHODS: Patients' clinical data collected from the stroke unit were analyzed. The modified Rankin scale score and symptomatic intracranial hemorrhage (sICH) were used as outcome measures. RESULTS: A total of 409 patients (mean age: 66.5 years, 292 males [71.4%]) were included. Tirofiban significantly improved 3-month functional outcomes (adjusted odds ratio [aOR] = 2.408, 95% confidence interval [CI] 1.120-5.175), reduced 3-month mortality (aOR = 0.364, 95% CI 0.155-0.856), and decreased the incidence of sICH (aOR = 0.339, 95% CI 0.149-0.767) in patients with estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m². However, no significant improvement in prognosis was observed with tirofiban in patients with eGFR < 90 mL/min/1.73 m². Interaction analysis suggested a potential influence of renal function on tirofiban efficacy. CONCLUSION: Renal function may impact the efficacy of tirofiban. Administration of tirofiban in direct thrombectomy patients with normal renal function is safe and improves prognosis. However, the prognostic benefits of tirofiban are limited in patients with impaired renal function.

Cobalt-Catalyzed Domino Transformations via Enantioselective C-H Activation/Nucleophilic [3 + 2] Annulation toward Chiral Bridged Bicycles.

Selective synthesis of chiral bridged (hetero)bicyclic scaffolds via asymmetric C-H activation constitutes substantial challenges due to the multiple reactivities of strained bicyclic structures. Herein, we develop the domino transformations through an unprecedented cobalt-catalyzed enantioselective C-H activation/nucleophilic [3 + 2] annulation with symmetrical bicyclic alkenes. The methods offer straightforward access to a wide range of chiral molecules bearing [2.2.1]-bridged bicyclic cores with four and five consecutive stereocenters in a single step. Two elaborate salicyloxazoline (Salox) ligands were synthesized based on the rational design and mechanistic understanding. The well-defined chiral pockets generated from asymmetric coordination around the trivalent cobalt catalyst direct the orientation of bicyclic alkenes, leading to excellent enantioselectivity.

Tea-Derived Polyphenols Enhance Drought Resistance of Tea Plants (Camellia sinensis) by Alleviating Jasmonate-Isoleucine Pathway and Flavonoid Metabolism Flow.

Extreme drought weather has occurred frequently in recent years, resulting in serious yield loss in tea plantations. The study of drought in tea plantations is becoming more and more intensive, but there are fewer studies on drought-resistant measures applied in actual production. Therefore, in this study, we investigated the effect of exogenous tea polyphenols on the drought resistance of tea plant by pouring 100 mg·L-1 of exogenous tea polyphenols into the root under drought. The exogenous tea polyphenols were able to promote the closure of stomata and reduce water loss from leaves under drought stress. Drought-induced malondialdehyde (MDA) accumulation in tea leaves and roots was also significantly reduced by exogenous tea polyphenols. Combined transcriptomic and metabolomic analyses showed that exogenous tea polyphenols regulated the abnormal responses of photosynthetic and energy metabolism in leaves under drought conditions and alleviated sphingolipid metabolism, arginine metabolism, and glutathione metabolism in the root system, which enhanced the drought resistance of tea seedlings. Exogenous tea polyphenols induced jasmonic acid-isoleucine (JA-ILE) accumulation in the root system, and the jasmonic acid-isoleucine synthetase gene (TEA028623), jasmonic acid ZIM structural domain proteins (JAMs) synthesis genes (novel.22237, TEA001821), and the transcription factor MYC2 (TEA014288, TEA005840) were significantly up-regulated. Meanwhile, the flavonoid metabolic flow was significantly altered in the root; for example, the content of EGCG, ECG, and EGC was significantly increased. Thus, exogenous tea polyphenols enhance the drought resistance of tea plants through multiple pathways.

col1a2+ fibroblasts/muscle progenitors finetune xanthophore countershading by differentially expressing csf1a/1b in embryonic zebrafish.

Animals evolve diverse pigment patterns to adapt to the natural environment. Countershading, characterized by a dark-colored dorsum and a light-colored ventrum, is one of the most prevalent pigment patterns observed in vertebrates. In this study, we reveal a mechanism regulating xanthophore countershading in zebrafish embryos. We found that csf1a and csf1b mutants altered xanthophore countershading differently: csf1a mutants lack ventral xanthophores, while csf1b mutants have reduced dorsal xanthophores. Further study revealed that csf1a is expressed throughout the trunk, whereas csf1b is expressed dorsally. Ectopic expression of csf1a or csf1b in neurons attracted xanthophores into the spinal cord. Blocking csf1 signaling by csf1ra mutants disrupts spinal cord distribution and normal xanthophores countershading. Single-cell RNA sequencing identified two col1a2+ populations: csf1ahighcsf1bhigh muscle progenitors and csf1ahighcsf1blow fibroblast progenitors. Ablation of col1a2+ fibroblast and muscle progenitors abolished xanthophore patterns. Our study suggests that fibroblast and muscle progenitors differentially express csf1a and csf1b to modulate xanthophore patterning, providing insights into the mechanism of countershading.

Mechanical behaviors of a new elliptical valve stent in bicuspid aortic valve.

BACKGROUND AND OBJECTIVE: The conventional valve stents that are cylindrical in shape will become elliptical when implanted in bicuspid aortic valve, thereby reducing the durability of the artificial valve. In this study, a new design of valve stent is presented where valve stents have elliptical cross-section at the annulus and it is expected to have better expandability and circle shape during the interaction between the stent and bicuspid aortic valve, thereby extending the durability of artificial valve. METHODS: Finite element method (FEM) is used to study the mechanical behavior of the novel valve stent in the bicuspid aortic valve. The effects of three matching relationship between the ellipticity of the stents and the ellipticity of the annulus (i.e., the ellipticity of the stent is greater than, equal to and less than the annulus ellipticity, respectively) on the mechanical behavior of stent expansion are studied. In addition, the expansion mechanical behavior of the novel valve stent at different implantation depths is also compared. RESULTS: Results indicate that novel valve stent implantation with elliptical features is superior to conventional circular valve stent. When the novel valve stent ellipticity is less than the annulus ellipticity, the ellipticity of the novel valve stent after implantation is smaller than that of the conventional circular valve stent. This indicated that the novel valve stent has better expandability and post-expansion shape, making artificial valve to have better durability. The risk of paravalvular leak after implantation is lowest when the novel valve stent ellipticity is less than annulus ellipticity. When the novel valve stent ellipticity coincides with annulus ellipticity, the aortic wall is subjected to greatest stress. With the increase of implantation depth, the stress on the novel valve stent decrease. CONCLUSIONS: This study might provide insights for improving stent design for bicuspid aortic valve.

Identification of ecological security patterns of alpine wetland grasslands based on landscape ecological risks: A study in Zoigê County.

Climate change and human activities have increased ecological risks and degraded ecosystem functions in alpine wetland grassland regions, where ecological security remains largely unexplored. The construction of ecological security patterns (ESP) can help to synchronize regional ecological security and sustainable development and provide ideas to address these challenges. This article determines the current ESP of Zoigê County, China, by analyzing the spatial and temporal characteristics of landscape ecological risk (LER) and generating an ecological network by combining the InVEST model, the landscape connectivity index, and the circuit theory model. Management zoning and targeted conservation recommendations are proposed. The results indicate that the region has significant spatial heterogeneity in IER. Ecological risk exposure is increasing, with high values mainly concentrated in the central part of the region. Meanwhile, ecological protection areas were identified, which included 2578.44 km2 of ecological sources, 71 key ecological corridors, 25 potential ecological corridors, 4 river ecological corridors, 66 pinch points, and 58 barriers. This study provides a valuable reference for the ecological development of Zoigê County, as well as insights into the formation of ESP in other alpine wetland grassland regions.

Deciphering Estrus Expression in Gilts: The Role of Alternative Polyadenylation and LincRNAs in Reproductive Transcriptomics.

The fertility rate and litter size of female pigs are critically affected by the expression of estrus. The objective of this study was to elucidate the regulatory mechanisms of estrus expression by analyzing the differential expression of genes and long intergenic non-coding RNAs (lincRNA), as well as the utilization of alternative polyadenylation (APA) sites, in the vulva and vagina during the estrus and diestrus stages of Large White and indigenous Chinese Mi gilts. Our study revealed that the number of differentially expressed genes (DEG) in the vulva was less than that in the vagina, and the DEGs in the vulva were enriched in pathways such as "neural" pathways and steroid hormone responses, including the "Calcium signaling pathway" and "Oxytocin signaling pathway". The DEGs in the vagina were enriched in the "Metabolic pathways" and "VEGF signaling pathway". Furthermore, 27 and 21 differentially expressed lincRNAs (DEL), whose target genes were enriched in the "Endocrine resistance" pathway, were identified in the vulva and vagina, respectively. Additionally, we observed that 63 and 618 transcripts of the 3'-untranslated region (3'-UTR) were lengthened during estrus in the vulva and vagina, respectively. Interestingly, the genes undergoing APA events in the vulva exhibited species-specific enrichment in neural or steroid-related pathways, whereas those in the vagina were enriched in apoptosis or autophagy-related pathways. Further bioinformatic analysis of these lengthened 3'-UTRs revealed the presence of multiple miRNAs binding sites and cytoplasmic polyadenylation element (CPE) regulatory aspects. In particular, we identified more than 10 CPEs in the validated lengthened 3'-UTRs of the NFIX, PCNX4, CEP162 and ABHD2 genes using RT-qPCR. These findings demonstrated the involvement of APA and lincRNAs in the regulation of estrus expression in female pigs, providing new insights into the molecular mechanisms underlying estrus expression in pigs.

Cancer testis antigen MAGEA3 in serum and serum-derived exosomes serves as a promising biomarker in lung adenocarcinoma.

Cancer testis antigen (CTA) Melanoma Antigen Gene A3 (MAGEA3) were overexpressed in multiple tumor types, but the expression pattern of MAGEA3 in the serum of lung adenocarcinoma (LUAD) remains unclear. Clinically derived serum and serum exosome samples were used to assess the mRNA expression of MAGEA3 and MAGEA4 by qRT-PCR, and serum MAGEA3 and MAGEA4 protein expression were evaluated by ELISA in total 133 healthy volunteers' and 289 LUAD patients' serum samples. An analysis of the relationship of the mRNA and protein expression of MAGEA3 and MAGEA4 with clinicopathologic parameters was performed and the diagnostic value of MAGEA3 and MAGEA4 was plotted on an ROC curve. In addition, the correlation of MAGEA3 mRNA with infiltrating immune cells was investigated through TIMER, the CIBERSORT algorithm and the TISIDB database. Expression of serum and serum exosome MAGEA3 and MAGEA4 mRNA were significantly higher in LUAD patients than in healthy donors. MAGEA3 mRNA associated with tumor diameter, TMN stage, and NSE in LUAD serum samples, and MAGEA3 mRNA correlated with N stage in serum-derived exosomes, possessing areas under the curve (AUC) of 0.721 and 0.832, respectively. Besides, serum MAGEA3 protein levels were elevated in LUAD patients, and were closely related to stage and NSE levels, possessing AUC of 0.781. Further analysis signified that the expression of MAGEA3 mRNA was positive correlation with neutrophil, macrophages M2, dendritic cells resting, and eosinophilic, but negatively correlated with B cells, plasma cells, CD8 + T cells, CD4 + T cells, Th17 cells, macrophages and dendritic cells. Collectively, our results suggested that the MAGEA3 expression in mRNA and protein were upregulated in LUAD, and MAGEA3 could be used as a diagnostic biomarker and immunotherapy target for LUAD patients.

Precise prediction of phase-separation key residues by machine learning.

Understanding intracellular phase separation is crucial for deciphering transcriptional control, cell fate transitions, and disease mechanisms. However, the key residues, which impact phase separation the most for protein phase separation function have remained elusive. We develop PSPHunter, which can precisely predict these key residues based on machine learning scheme. In vivo and in vitro validations demonstrate that truncating just 6 key residues in GATA3 disrupts phase separation, enhancing tumor cell migration and inhibiting growth. Glycine and its motifs are enriched in spacer and key residues, as revealed by our comprehensive analysis. PSPHunter identifies nearly 80% of disease-associated phase-separating proteins, with frequent mutated pathological residues like glycine and proline often residing in these key residues. PSPHunter thus emerges as a crucial tool to uncover key residues, facilitating insights into phase separation mechanisms governing transcriptional control, cell fate transitions, and disease development.

Instance-Specific Semantic Augmentation for Long-Tailed Image Classification.

Recent long-tailed classification methods generally adopt the two-stage pipeline and focus on learning the classifier to tackle the imbalanced data in the second stage via re-sampling or re-weighting, but the classifier is easily prone to overconfidence in head classes. Data augmentation is a natural way to tackle this issue. Existing augmentation methods either perform low-level transformations or apply the same semantic transformation for all instances. However, meaningful augmentations for different instances should be different. In this paper, we propose feature-level augmentation (FLA) and pixel-level augmentation (PLA) learning methods for long-tailed image classification. In the first stage, the feature space is learned from the original imbalanced data. In the second stage, we model the semantic within-class transformation range for each instance by a specific Gaussian distribution and design a semantic transformation generator (STG) to predict the distribution from the instance itself. We train STG by constructing ground-truth distributions for instances of head classes in the feature space. In the third stage, for FLA, we generate instance-specific transformations by STG to obtain feature augmentations of tail classes for fine-tuning the classifier. For PLA, we use STG to guide pixel-level augmentations for fine-tuning the backbone. The proposed augmentation strategy can be combined with different existing long-tail classification methods. Extensive experiments on five imbalanced datasets show the effectiveness of our method.

The dysfunction of CD8+ T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis.

Endometriosis is defined as an oestrogen-dependent and inflammatory gynaecological disease of which the pathogenesis remains unclear. This study aimed to investigate the cellular heterogeneity and reveal the effect of CD8+ T cells on the progress of endometriosis. Three ovarian endometriosis patients were collected, and single-cell RNA sequencing (scRNA-seq) progressed and delineated the cellular landscape of endometriosis containing five cell clusters. The endometrial cells (EMCs) were the major component, of which the mesenchymal cells were preponderant and characterized with increased inflammation and oestrogen synthesis in endometriosis. The proportion of T cells, mainly CD8+ T cells rather than CD4+, was reduced in endometriotic lesions, and the cytokines and cytotoxicity of ectopic T cells were depressed. CD8+ T cells depressed the proliferation of ESCs through inhibiting CDK1/CCNB1 pathway to arrest the cell cycle and triggered inflammation through activating STAT1 pathway. Correspondingly, the coculture with ESCs resulted in the dysfunction of CD8+ T cells through upregulating STAT1/PDCD1 pathway and glycolysis-promoted metabolism reprogramming. The endometriotic lesions were larger in nude mouse models with T-cell deficiency than the normal mouse models. The inhibition of T cells via CD90.2 or CD8A antibody increased the endometriotic lesions in mouse models, and the supplement of T cells to nude mouse models diminished the lesion sizes. In conclusion, this study revealed the global cellular variation of endometriosis among which the cellular count and physiology of EMCs and T cells were significantly changed. The depressed cytotoxicity and aberrant metabolism of CD8+ T cells were induced by ESCs with the activation of STAT1/PDCD1 pathway resulting in immune survival to promote endometriosis.