Impact and correlation of fermentation temperature on the bacterial community, flavor characteristics, and proteolysis of Harbin dry sausages.

Proteins undergo degradation to produce peptides and free amino acids, which in turn promote the production of volatile compounds with important contributions to the taste and aroma. This study investigated the effect of fermentation temperatures (8, 15, and 25 °C) on the bacterial community, flavor profile, and protein degradation of Harbin dry sausages. The physical and chemical properties were improved at 25 °C compared with 8 and 15 °C. Staphylococcus xylosus increased with the increase in fermentation temperature, whereas Latilactobacillus sakei decreased. The degree of protein degradation increased, and the content and proportion of taste peptides and free amino acids increased. Similarly, a higher fermentation temperature led to an increase in volatile compounds, such as aldehydes, alcohols, and esters. In conclusion, there is an inseparable relationship between proteolysis and microbial proteases. The fermentation temperature of 25 °C best contributed to the sensory quality and flavor characteristics of Harbin dry sausages.

Speech-Processing Network Formation of Cochlear-Implanted Toddlers With Early Hearing Experiences.

To reveal the formation process of speech processing with early hearing experiences, we tracked the development of functional connectivity in the auditory and language-related cortical areas of 84 (36 female) congenitally deafened toddlers using repeated functional near-infrared spectroscopy for up to 36 months post cochlear implantation (CI). Upon hearing restoration, the CI children lacked the modular organization of the mature speech-processing network and demonstrated a higher degree of immaturity in temporo-parietal than temporo-frontal connections. The speech-processing network appeared to form rapidly with early CI experiences, with two-thirds of the developing connections following nonlinear trajectories reflecting possibly more than one synaptogenesis-pruning cycle. A few key features of the mature speech-processing network emerged within the first year of CI hearing, including left-hemispheric advantage, differentiation of the dorsal and ventral processing streams, and functional state (speech listening vs. resting) specific patterns of connectivity development. The developmental changes were predictable of future auditory and verbal communication skills of the CI children, with prominent contribution from temporo-parietal connections in the dorsal stream, suggesting a mediating role of speech-processing network formation with early hearing experiences in speech acquisition.

One novel transfer learning-based CLIP model combined with self-attention mechanism for differentiating the tumor-stroma ratio in pancreatic ductal adenocarcinoma.

PURPOSE: To develop a contrastive language-image pretraining (CLIP) model based on transfer learning and combined with self-attention mechanism to predict the tumor-stroma ratio (TSR) in pancreatic ductal adenocarcinoma on preoperative enhanced CT images, in order to understand the biological characteristics of tumors for risk stratification and guiding feature fusion during artificial intelligence-based model representation. MATERIAL AND METHODS: This retrospective study collected a total of 207 PDAC patients from three hospitals. TSR assessments were performed on surgical specimens by pathologists and divided into high TSR and low TSR groups. This study developed one novel CLIP-adapter model that integrates the CLIP paradigm with a self-attention mechanism for better utilizing features from multi-phase imaging, thereby enhancing the accuracy and reliability of tumor-stroma ratio predictions. Additionally, clinical variables, traditional radiomics model and deep learning models (ResNet50, ResNet101, ViT_Base_32, ViT_Base_16) were constructed for comparison. RESULTS: The models showed significant efficacy in predicting TSR in PDAC. The performance of the CLIP-adapter model based on multi-phase feature fusion was superior to that based on any single phase (arterial or venous phase). The CLIP-adapter model outperformed traditional radiomics models and deep learning models, with CLIP-adapter_ViT_Base_32 performing the best, achieving the highest AUC (0.978) and accuracy (0.921) in the test set. Kaplan-Meier survival analysis showed longer overall survival in patients with low TSR compared to those with high TSR. CONCLUSION: The CLIP-adapter model designed in this study provides a safe and accurate method for predicting the TSR in PDAC. The feature fusion module based on multi-modal (image and text) and multi-phase (arterial and venous phase) significantly improves model performance.

Sinogram-characteristic-informed network for efficient restoration of low-dose SPECT projection data.

BACKGROUND: Single Photon Emission Computed Tomography (SPECT) sinogram restoration for low-dose imaging is a critical challenge in medical imaging. Existing methods often overlook the characteristics of the sinograms, necessitating innovative approaches. PURPOSE: In this study, we introduce the Sinogram-characteristic-informed network (SCI-Net) to address the restoration of low-dose SPECT sinograms. Our aim is to build and train a model based on the characteristics of sinograms, including continuity, periodicity, multi-scale properties of lines in sinograms, and others, to enhance the model's understanding of the restoration process. METHODS: SCI-Net incorporates several novel mechanisms tailored to exploit the inherent characteristics of sinograms. We implement a channel attention module with a decay mechanism to leverage continuity across adjacent sinograms, while a position attention module captures global correlations within individual sinograms. Additionally, we propose a multi-stage progressive integration mechanism to balance local detail and overall structure. Multiple regularization terms, customized to sinogram image characteristics, are embedded into the loss function for model training. RESULTS: The experimental evaluations are divided into two parts: simulation data evaluation and clinical evaluation. The simulation data evaluation is conducted on a dataset comprising ten organ types, generated by the SIMIND Monte Carlo program from extended cardiac-torso (XCAT) anatomical phantoms. The dataset includes a total of SPECT sinograms with low-dose as input data and normal-dose as ground truth, consisting of 3881 sinograms in the training dataset and 849 sinograms in the testing set. When comparing the restoration of low-dose sinograms to normal-dose references, SCI-Net effectively improves performance. Specifically, the peak signal-to-noise ratio (PSNR) and the structural similarity (SSIM) on sinograms increase from 15.72 to 34.66 ( p < $\text{p}< $ 0.001) and 0.6297 to 0.9834 ( p < $\text{p}<$ 0.001), respectively, and on reconstructed images, reconstructed by maximum likelihood-expectation maximization (ML-EM), the PSNR and the SSIM improve from 21.95 to 33.14 ( p < $\text{p}<$ 0.001) and 0.9084 to 0.9866 ( p < $\text{p}<$ 0.001), respectively. We compared SCI-Net with existing methods, including baseline models, traditional reconstruction algorithms, end-to-end methods, sinogram restoration methods, and image post-processing methods. The experimental results and visual examples demonstrate that SCI-Net surpasses these existing methods in SPECT sinogram restoration. The clinical evaluation is conducted on clinical data of low-dose SPECT sinograms for spleen, thyroid, skull, and bone. These SPECT projection data are obtained from Discovery NM/CT670 scans. We compare the reconstructed images from the SCI-Net restored sinograms, the reconstructed images from the original low-dose sinograms, and the reconstructed images using the built-in algorithm of the Discovery NM/CT670. The results show that our method effectively reduces the coefficient of variation (COV) in the regions of interest (ROI) of the reconstructed images, thereby enhancing the quality of the reconstructed images through SPECT sinogram restoration. CONCLUSIONS: Our proposed SCI-Net exhibits promising performance in the restoration of low-dose SPECT projection data. In the SCI-Net, we have implemented three mechanisms based on distinct forms, which are advantageous for the model to more effectively leverage the characteristics of sinograms and achieve commendable restoration outcomes.

[Expression and its clinical significance of cell-cycle dependent kinase 1 in malignant peripheral nerve sheath tumors].

Objective: To explore the role and clinical significance of cell-cycle dependent kinase 1 (CDK1) and its upstream and downstream molecules in the development of malignant peripheral nerve sheath tumor (MPNST) through the analysis of clinical tissue samples. Methods: A total of 56 tumor samples from MPNST patients ("Tianjin" dataset) who underwent surgical resection, confirmed by histology and pathology between September 2011 and March 2020, along with 17 normal tissue samples, were selected as the research subjects. MPNST-related hub genes were identified through transcriptome sequencing, bioinformatics analysis, immunohistochemistry staining, and survival analysis, and their expression levels and prognostic associations were analyzed. Results: Transcriptome sequencing and bioinformatics analysis revealed that upregulated genes in MPNST were predominantly enriched in cell cycle-related pathways, with CDK1 occupying a central position among all differentially expressed genes. Further differential analysis demonstrated that CDK1 mRNA expression in sarcoma tissues was significantly higher than in normal tissues [based on searching the cancer genome atlas (TCGA) dataset, P<0.05]. In MPNST tissues, CDK1 mRNA expression was not only significantly higher than in normal tissues (based on Tianjin, GSE141438 datasets, P<0.05), but also significantly higher than in neurofibromatosis (NF) and plexiform neurofibromas (PNF) (based on GSE66743 and GSE145064 datasets, P<0.05). Immunohistochemical staining results indicated that the expression rate of CDK1 protein in MPNST tissues was 40.31%. Survival analysis results demonstrated that CDK1 expression was associated with poor prognosis. The survival time of MPNST patients with high CDK1 mRNA expression was significantly lower than that of the low expression group ( P<0.05), and the overall survival trend of patients with positive CDK1 protein expression was worse than that of patients with negative CDK1 expression. Additionally, differential analysis of CDK family genes (CDK1-8) revealed that only CDK1 was significantly upregulated in MPNST, NF, and PNF. Conclusion: Increased expression of CDK1 is associated with poor prognosis in MPNST patients. Compared to other CDK family members, CDK1 exhibits a unique expression pattern, suggesting its potential as a therapeutic target for MPNST.

lncSNHG16 promotes hepatocellular carcinoma development by inhibiting autophagy.

OBJECTIVE: To investigate the expression of long non-coding RNA lncSNHG16 in hepatocellular carcinoma (HCC), associations between its expression and patient survival, and its potential role in regulating autophagy in the disease. METHODS: Expression of lncSNHG16 was measured using quantitative real-time PCR in HCC cells in culture and HCC tissues from patients. Effects of lncSNHG16 overexpression were examined in HCC cultures using assays of cell proliferation, wound healing, and migration or invasion in Transwell dishes. Effects of lncSNHG16 overexpression were also examined in subcutaneous tumor in mice. Relationships of lncSNHG16 expression to autophagy and apoptosis in HCC cultures were explored using western blotting and flow cytometry. RESULTS: Higher lncSNHG16 expression in HCC tissues was associated with significantly worse overall and recurrence-free survival of patients. Overexpressing lncSNHG16 in HCC cell culture promoted cell proliferation, migration, and invasion while suppressing apoptosis. lncSNHG16 was associated with upregulation of STAT3 as well as inhibition of autophagy and associated apoptosis. Overexpressing lncSNHG16 accelerated tumor growth and weight in mice. CONCLUSION: The non-coding RNA lncSNHG16 suppresses autophagy and associated apoptosis in HCC, making it a potential therapeutic target.

Probing spin hydrodynamics on a superconducting quantum simulator.

Characterizing the nature of hydrodynamical transport properties in quantum dynamics provides valuable insights into the fundamental understanding of exotic non-equilibrium phases of matter. Experimentally simulating infinite-temperature transport on large-scale complex quantum systems is of considerable interest. Here, using a controllable and coherent superconducting quantum simulator, we experimentally realize the analog quantum circuit, which can efficiently prepare the Haar-random states, and probe spin transport at infinite temperature. We observe diffusive spin transport during the unitary evolution of the ladder-type quantum simulator with ergodic dynamics. Moreover, we explore the transport properties of the systems subjected to strong disorder or a tilted potential, revealing signatures of anomalous subdiffusion in accompany with the breakdown of thermalization. Our work demonstrates a scalable method of probing infinite-temperature spin transport on analog quantum simulators, which paves the way to study other intriguing out-of-equilibrium phenomena from the perspective of transport.

Enhancing boundary detection of radiofrequency ablation lesions through photoacoustic mapping.

Atrial fibrillation (A-fib) is the most common type of heart arrhythmia, typically treated with radiofrequency catheter ablation to isolate the heart from abnormal electrical signals. Monitoring the formation of ablation-induced lesions is crucial for preventing recurrences and complications arising from excessive or insufficient ablation. Existing imaging modalities lack real-time feedback, and their intraoperative usage is in its early stages. A critical need exists for an imaging-based lesion indexing (LSI) method that directly reflects tissue necrosis formation. Previous studies have indicated that spectroscopic photoacoustic (sPA) imaging can differentiate ablated tissues from their non-ablated counterparts based on PA spectrum variation. In this paper, we introduce a method for detecting ablation lesion boundaries using sPA imaging. This approach utilizes ablation LSI, which quantifies the ratio between the signal from ablated tissue and the total tissue signal. We enhance boundary detection accuracy by adapting a regression model-based compensation. Additionally, the method was cross-validated with clinically used intraoperative monitoring parameters. The proposed method was validated with ex vivo porcine cardiac tissues with necrotic lesions created by different ablation durations. The PA-measured lesion size was compared with gross pathology. Statistical analysis demonstrates a strong correlation (R > 0.90) between the PA-detected lesion size and gross pathology. The PA-detected lesion size also exhibits a moderate to strong correlation (R > 0.75) with local impedance changes recorded during procedures. These results suggest that the introduced PA imaging-based LSI has great potential to be incorporated into the clinical workflow, guiding ablation procedures intraoperatively.

Psychosocial Factors Associated With Long-Term Cognitive Impairment Among COVID-19 Survivors: A Cross-Sectional Study.

ABSTRACT: COVID-19 survivors complained of the experience of cognitive impairments, which also called "brain fog" even recovered. The study aimed to describe long-term cognitive change and determine psychosocial factors in COVID-19 survivors. A cross-sectional study was recruited 285 participants from February 2020 to April 2020 in 17 hospitals in Sichuan Province. Cognitive function, variables indicative of the virus infection itself, and psychosocial variables were collected by telephone interview. Univariate logistic regression and Lasso logistic regression models were used for variable selection which plugged into a multiple logistics model. Overall prevalence of moderate or severe cognitive impairment was 6.3%. Logistic regression showed that sex, religion, smoking status, occupation, self-perceived severity of illness, sleep quality, perceived mental distress after COVID-19, perceived discrimination from relatives and friends, and suffered abuse were associated with cognitive impairment. The long-term consequences of cognitive function are related to multiple domains, in which psychosocial factors should be taken into consideration.

Incorporation of cross-linked/acetylated tapioca starches on the gelling properties, rheological behaviour, and microstructure of low-salt myofibrillar protein gels: Perspective on phase transition.

This study investigated the gelling properties, rheological behaviour, and microstructure of heat-induced, low-salt myofibrillar protein (MP) gels containing different levels (2%, 4%, 6%, and 8%, w/w) of cross-linked (CTS) or acetylated (ATS) tapioca starch. The results indicated that either CTS or ATS significantly enhanced the gel strength and water-holding capacity of low-salt MP gels (P < 0.05), an outcome verified by the rheological behaviour test results under different modes. Furthermore, iodine-staining images indicated that the MP-dominated continuous phase gradually transited to a starch-dominated phase with increasing CTS or ATS levels, and 4% was the critical point for this phase transition. In addition, hydrophobic interactions and disulphide bonds constituted the major intermolecular forces of low-salt MP gels, effectively promoting phase transition. In brief, modified tapioca starches possess considerable potential application value in low-salt meat products.

Regulating the Distribution and Accumulation of Charged Molecules by Progressive Electroporation for Improved Intracellular Delivery.

The cell membrane separates the intracellular compartment from the extracellular environment, constraining exogenous molecules to enter the cell. Conventional electroporation typically employs high-voltage and short-duration pulses to facilitate the transmembrane transport of molecules impermeable to the membrane under natural conditions by creating temporary hydrophilic pores on the membrane. Electroporation not only enables the entry of exogenous molecules but also directs the intracellular distribution of the electric field. Recent advancements have markedly enhanced the efficiency of intracellular molecule delivery, achieved through the utilization of microstructures, microelectrodes, and surface modifications. However, little attention is paid to regulating the motion of molecules during and after passing through the membrane to improve delivery efficiency, resulting in an unsatisfactory delivery efficiency and high dose demand. Here, we proposed the strategy of regulating the motion of charged molecules during the delivery process by progressive electroporation (PEP), utilizing modulated electric fields. Efficient delivery of charged molecules with an expanded distribution and increased accumulation by PEP was demonstrated through numerical simulations and experimental results. The dose demand can be reduced by 10-40% depending on the size and charge of the molecules. We confirmed the safety of PEP for intracellular delivery in both short and long terms through cytotoxicity assays and transcriptome analysis. Overall, this work not only reveals the mechanism and effectiveness of PEP-enhanced intracellular delivery of charged molecules but also suggests the potential integration of field manipulation of molecular motion with surface modification techniques for biomedical applications such as cell engineering and sensitive cellular monitoring.

Stereotactically intracerebral transplantation of neural stem cells for ischemic stroke attenuated inflammatory responses and promoted neurogenesis: an experimental study with monkeys.

BACKGROUND: Ischemic stroke is a common neurovascular disorder with high morbidity and mortality. However, the underlying mechanism of stereotactically intracerebral transplantation of human neural stem cells (hNSCs) is not well elucidated. MATERIALS AND METHODS: Four days after ischemic stroke induced by Rose Bengal photothrombosis, seven cynomolgus monkeys were transplanted with hNSCs or vehicles stereotactically and followed up for 84 days. Behavioral assessments, magnetic resonance imaging, blood tests, and pathological analysis were performed before and after treatment. The proteome profiles of the left and right precentral gyrus and hippocampus were evaluated. Extracellular vesicle micro-RNA (miRNA) from the peripheral blood was extracted and analyzed. RESULTS: hNSC transplantation reduced the remaining infarcted lesion volume of cynomolgus monkeys with ischemic stroke without remarkable side effects. Proteomic analyses indicated that hNSC transplantation promoted GABAergic and glutamatergic neurogenesis and restored the mitochondrial electron transport chain function in the ischemic infarcted left precentral gyrus or hippocampus. Immunohistochemical staining and quantitative real-time reverse transcription PCR confirmed the promoting effects on neurogenesis and revealed that hNSCs attenuated post-infarct inflammatory responses by suppressing resident glia activation and mediating peripheral immune cell infiltration. Consistently, miRNA-sequencing revealed the miRNAs that were related to these pathways were downregulated after hNSC transplantation. CONCLUSIONS: This study indicates that hNSCs can be effectively and safely used to treat ischemic stroke by promoting neurogenesis, regulating post-infarct inflammatory responses, and restoring mitochondrial function in both the infarct region and hippocampus.

Influence of flaxseed-derived diglyceride-based high internal phase Pickering emulsions on the rheological and physicochemical properties of myofibrillar protein gels.

The study aimed to investigate the influence of flaxseed-derived diglyceride-based high internal phase Pickering emulsions (HIPPE) at different levels (0%, 10%, 20%, 30%, 40%, and 50%) on the rheological and physicochemical properties of myofibrillar protein (MPs) gels. The study indicated that with increasing HIPPE levels, there was a significant increase in whiteness while a decrease in water-holding capacity. The gels with 10% HIPPE levels had higher ionic bonds, while those with 40% and 50% HIPPE levels showed higher hydrogen bonds. By increasing HIPPE levels in the formation of MP gels, the T2 relaxation time was found to decrease. Additionally, in all MP gels, G' values were significantly higher than G" values over time. Adding lower contents of HIPPE levels resulted in a more compact microstructure. These findings indicate that flaxseed-derived diglyceride-based HIPPEs could be utilized as fat substitutes in meat products to enhance their nutritional quality.

Anti-phasic oscillatory development for speech and noise processing in cochlear implanted toddlers.

Human brain demonstrates amazing readiness for speech and language learning at birth, but the auditory development preceding such readiness remains unknown. Cochlear implanted (CI) children (n = 67; mean age 2.77 year ± 1.31 SD; 28 females) with prelingual deafness provide a unique opportunity to study this stage. Using functional near-infrared spectroscopy, it was revealed that the brain of CI children was irresponsive to sounds at CI hearing onset. With increasing CI experiences up to 32 months, the brain demonstrated function, region and hemisphere specific development. Most strikingly, the left anterior temporal lobe showed an oscillatory trajectory, changing in opposite phases for speech and noise. The study provides the first longitudinal brain imaging evidence for early auditory development preceding speech acquisition.

Myofibrillar protein hydrolysis under hydroxyl radical oxidative stress: Structural changes and their impacts on binding to selected aldehydes.

In this study, a hydroxyl radical oxidation system was established to simulate the oxidation process in fermented meat products. This system was employed to examine the structural changes in myofibrillar proteins (MPs) resulting from tryptic hydrolysis after a hydroxyl radical oxidative regime. The effect of these changes on the ability of MPs to bind selected aldehydes (3-methyl butanal, pentanal, hexanal, and heptanal) was also investigated. Moderate oxidation (H2O2 ≤ 1.0 mM) unfolded the structure of MPs, facilitating trypsin-mediated hydrolysis and increasing their binding capacity for the four selected aldehydes. However, excessive oxidation (H2O2 ≥ 2.5 mM) led to cross-linking and aggregation of MPs, inhibiting trypsin-mediated hydrolysis. The oxidised MPs had the best binding capacity for heptanal. The interaction of the oxidised trypsin-hydrolysed MPs with heptanal was driven by hydrophobic interactions. The binding of heptanal affected the structure of the oxidised trypsin-hydrolysed MPs and reduced their α-helix content.

Inhibition Effect of Non-Host Plant Volatile Extracts on Reproductive Behaviors in the Diamondback Moth Plutella xylostella (Linnaeus).

The pest management of Plutella xylostella, the global pest of cruciferous plants, is primarily dependent upon continued applications of insecticides, which has led to severe insecticide resistance and a series of ecological concerns. The essential oils (EOs) of non-host plants are considered to have a high application potential in pest behavioral control. In P. xylostella, the insecticidal properties, antifeeding activities, and oviposition inhibition effects of many EOs have been studied in larvae and female moths. However, less focus has been placed on the inhibitory effect on sex pheromone communication during courtship, which is vital for the reproduction of the offspring. In this study, by combining electrophysiological studies, laboratory behavioral assays, and field traps, we demonstrated that non-host plant EOs significantly inhibited the reproductive behaviors of both sexes. Notably, the calamus (Acorus gramineus) EO inhibited the preference of male moths for synthetic sex pheromone blends and reduced the egg-laying number of female moths on host plants, with the highest inhibition rates of 72% and 100%, respectively, suggesting a great application prospect of calamus and its EO on the behavioral control strategies of P. xylostella.

Vectorial holography over a multimode fiber.

Vectorial holography through a strongly scattering medium can facilitate various applications in optics and photonics. However, the realization of vectorial holography with arbitrary distribution of optical intensity is still limited because of experimental noise during the calibration of vectorial transmission matrix (TM) and reconstruction noise during the retrieval of input wavefront for a given holographic target. Herein, we propose and experimentally demonstrate the vectorial holography with arbitrary distribution of optical intensity over a multimode fiber (MMF) using the Tikhonov regularization. By optimizing the noise factor, the performance of vectorial holography over an MMF is improved compared with the conjugate transpose and inverse TM methods. Our results might shed new light on the optical communication and detection mediated by MMFs.

Evaluation of the efficacy and safety of immunotherapy in sarcoma: a two-center study.

Background: Sarcoma is a highly heterogeneous malignancy with a poor prognosis. Although chemotherapy and targeted therapy have improved the prognosis to some extent, the efficacy remains unsatisfactory in some patients. The efficacy and safety of immunotherapy in sarcoma need further evaluation. Methods: We conducted a two-center study of sarcoma patients receiving PD-1 immunotherapy at Tianjin Medical University Cancer Institute and Hospital and Henan Provincial Cancer Hospital. The treatment regimens included PD-1 inhibitor monotherapy and combination therapy based on PD-1 inhibitors. The observed primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). Survival curves were compared using the Kaplan-Meier method. Results: A total of 43 patients were included from the two centers. The median follow-up time for all patients was 13 months (range, 1-48 months). In the group of 37 patients with advanced or unresectable sarcoma, the mPFS was 6 months (95%CI: 5-12 months), and the mOS was 16 months (95%CI: 10-28 months). The ORR was 10.8% (4/37), and the DCR was 18.9% (7/37). Subgroup analysis showed no significant differences in mPFS (p=0.11) and mOS (p=0.88) between patients with PD-L1 negative/positive expression. There were also no significant differences in mPFS (p=0.13) or mOS (p=0.72) between PD-1 inhibitor monotherapy and combination therapy. Additionally, there were no significant differences in mPFS (p=0.52) or mOS (p=0.49) between osteogenic sarcoma and soft tissue sarcoma. Furthermore, the results showed no significant differences in mPFS (p=0.66) or mOS (p=0.96) between PD-1 inhibitors combined with targeted therapy and PD-1 inhibitors combined with AI chemotherapy. Among the 6 patients receiving adjuvant therapy after surgery, the mPFS was 15 months (95%CI: 6-NA months), and the mOS was not reached. In terms of safety, most adverse events were mild (grade 1-2) and manageable. The most severe grade 4 adverse events were bone marrow suppression, which occurred in 4 patients but resolved after treatment. There was also one case of a grade 4 adverse event related to hypertension. Conclusion: Immunotherapy is an effective treatment modality for sarcoma with manageable safety. Further inclusion of more patients or prospective clinical trials is needed to validate these findings.

Quantum-Geometry-Induced Anomalous Hall Effect in Nonunitary Superconductors and Application to Sr_{2}RuO_{4}.

The polar Kerr effect and the closely related anomalous charge Hall effect are among the most distinguishing signatures of the superconducting state in Sr_{2}RuO_{4}, as well as in several other compounds. These effects are often thought to be derived from chiral superconducting pairing, and different mechanisms have been invoked for the explanation. However, the intrinsic mechanisms proposed previously often involve unrealistically strong interband Cooper pairing. We show in this Letter that, even without interband pairing, nonunitary superconducting states can support the intrinsic anomalous charge Hall effect, thanks to the quantum geometric properties of the Bloch electrons. The key here is to have a normal-state spin Hall effect, for which a nonzero spin-orbit coupling is essential. A finite charge Hall effect then naturally arises at the onset of a spin-polarized nonunitary superconducting pairing. It depends on both the spin polarization and the normal-state electron Berry curvature, the latter of which is the imaginary part of the quantum geometric tensor of the Bloch states. Applying our results to the weakly paired Sr_{2}RuO_{4} we conclude that, if the reported Kerr effect is of intrinsic origin, the superconducting state is most likely nonunitary and has odd parity. Our theory may be generalized to other superconductors that exhibit the polar Kerr effect.

The fusion gene LRP1-SNRNP25 drives invasion and migration by activating the pJNK/37LRP/MMP2 signaling pathway in osteosarcoma.

Through transcriptome sequencing, we previously identified a new osteosarcoma-specific, frequent fusion gene, LRP1-SNRNP25, and found that it played an important role in tumor cell invasion and migration. However, the specific mechanism remains unclear. In this article, whole-genome sequencing further confirmed that the LRP1-SNRNP25 fusion gene is formed by fusion of LRP1 exon 8 and SNRNP25 exon 2. In vitro, scratch and Transwell assays demonstrated that the migration and invasion abilities of LRP1-SNRNP25-overexpressing osteosarcoma cells were significantly increased. To explore the molecular mechanism of the LRP1-SNRNP25 fusion in affecting osteosarcoma cell migration and invasion, we evaluated the migration and invasion-related molecular signaling pathways by western blotting. Some migration- and invasion-related genes, including pJNK and MMP2, were upregulated. Coimmunoprecipitation-mass spectrometry showed that 37LRP can interact with pJNK. Western blotting confirmed that LRP1-SNRNP25 overexpression upregulates 37LRP protein expression. Immunofluorescence staining showed the intracellular colocalization of LRP1-SNRNP25 with pJNK and 37LRP proteins and that LRP1-SNRNP25 expression increased the pJNK and 37LRP levels. Coimmunoprecipitation (co-IP) confirmed that LRP1-SNRNP25 interacted with pJNK and 37LRP proteins. The pJNK inhibitor SP600125 dose-dependently decreased the pJNK/37LRP/MMP2 levels. After siRNA-mediated 37LRP knockdown, the MMP2 protein level decreased. These two experiments proved the upstream/downstream relationship among pJNK, 37LRP, and MMP2, with pJNK the farthest upstream and MMP2 the farthest downstream. These results proved that the LRP1-SNRNP25 fusion gene exerts biological effects through the pJNK/37LRP/MMP2 signaling pathway. In vivo, LRP1-SNRNP25 promoted osteosarcoma cell growth. Tumor growth was significantly inhibited after SP600125 treatment. Immunohistochemical analysis showed that the pJNK, MMP2, and Ki-67 protein levels were significantly increased in tumor tissues of LRP1-SNRNP25-overexpressing cell-injected nude mice. Furthermore, lung and liver metastasis were more prevalent in these mice. In a word, LRP1-SNRNP25 promotes invasion, migration, and metastasis via pJNK/37LRP/MMP2 pathway. LRP1-SNRNP25 is a potential therapeutic target for LRP1-SNRNP25-positive osteosarcoma.