[Synthesis and tissue distribution of bufadienolides in Bufo bufo gargarizans].

This study explored the biosynthesis of bufadienolides(BDs) in Bufo bufo gargarizans to solve the dilemma of the decreasing resources of B. bufo gargarizans and provide a theoretical basis for the sustainable utilization of the resources. Ultra-high performance liquid chromatography-Orbitrap-mass spectrometry(UHPLC-Orbitrap-MS) was employed to detect the synthesis sites of BDs in B. bufo gargarizans, and the results were verified by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI) and homogenate incubation experiments. BDs in B. bufo gargarizans had the highest content in the liver and the highest concentration in the gallbladder, in addition to the parotid gland and skin, which suggested that the liver could synthesize BDs. The results of DESI-MSI also showed that BDs were mainly enriched in the liver rather than the immature parotid gland. The incubation experiment of liver homogenates demonstrated the liver of B. bufo gargarizans had the ability to synthesize BDs. This study showed that the liver was a major organ for the synthesis of BDs in B. bufo gargarizans during metamorphosis, development, and growth, which provided strong theoretical support for the biosynthesis of BDs and the sustainable utilization of B. bufo gargarizans resources.

Biomimetic Nanoporous Transparent Universal Fire-Resistant Coatings.

The inherent flammability of most polymeric materials poses a significant fire hazard, leading to substantial property damage and loss of life. A universal flame-retardant protective coating is considered as a promising strategy to mitigate such risks; however, simultaneously achieving high transparency of the coatings remains a great challenge. Here, inspired by the moth eye effect, we designed a nanoporous structure into a protective coating that leverages a hydrophilic-hydrophobic interactive assembly facilitated by phosphoric acid protonated amino siloxane. The coating demonstrates robust adhesion to a diverse range of substrates, including but not limited to fabrics, foams, paper, and wood. As expected, its moth-eye-inspired nanoporous structure conferred a high visible light transparency of >97% and water vapor transmittance of 96%. The synergistic effect among phosphorus (P), nitrogen (N), and silicon (Si) largely enhanced the char-forming ability and restricted the decomposition of the coated substrates, which successfully endowed the coating with high fire-fighting performance. More importantly, for both flexible and rigid substrates, the coated samples all possessed great mechanical properties. This work provides a new insight for the design of protective coatings, particularly focusing on achieving high transparency.

An endogenous promoter LpSUT2 discovered in duckweed: a promising transgenic tool for plants.

Promoters are one of the most critical elements in regulating gene expression. They are considered essential biotechnological tools for heterologous protein production. The one most widely used in plants is the 35S promoter from cauliflower mosaic virus. However, our study for the first time discovered the 35S promoter reduced the expression of exogenous proteins under increased antibiotic stress. We discovered an endogenous strong promoter from duckweed named LpSUT2 that keeps higher initiation activity under antibiotic stress. Stable transformation in duckweed showed that the gene expression of eGFP in the LpSUT2:eGFP was 1.76 times that of the 35S:eGFP at 100 mg.L-1 G418 and 6.18 times at 500 mg.L-1 G418. Notably, with the increase of G418 concentration, the gene expression and the fluorescence signal of eGFP in the 35S:eGFP were weakened, while the LpSUT2:eGFP only changed slightly. This is because, under high antibiotic stress, the 35S promoter was methylated, leading to the gene silencing of the eGFP gene. Meanwhile, the LpSUT2 promoter was not methylated and maintained high activity. This is a previously unknown mechanism that provides us with new insights into screening more stable promoters that are less affected by environmental stress. These outcomes suggest that the LpSUT2 promoter has a high capacity to initiate the expression of exogenous proteins. In conclusion, our study provides a promoter tool with potential application for plant genetic engineering and also provides new insights into screening promoters.

Emission of CO2 and its related carbonate system dynamics in a hotspot area during winter and summer: The Changjiang River estuary.

The carbonate chemistry in river-dominated marginal seas is highly heterogeneous, and there is ongoing debate regarding the definition of atmospheric CO2 source or sink. On this basis, we investigated the carbonate chemistry and air-sea CO2 fluxes in a hotspot estuarine area: the Changjiang Estuary during winter and summer. The spatial characteristics of the carbonate system were influenced by water mixing of three end-members in winter, including the Changjiang freshwater with low total alkalinity (TA) concentration, the less saline Yellow Sea Surface Water with high TA, and the saline East China Sea (ECS) offshore water with moderate TA. While in summer with increased river discharge, the carbonate system was regulated by simplified two end-member mixing between the Changjiang freshwater and the ECS offshore water. By performing the end-member mixing model on DIC variations in the river plume region, significant biological addition of DIC was found in winter with an estimation of -120 ± 113 µmol kg-1 caused by wintertime organic matter remineralization from terrestrial source. While this biological addition of DIC shifted to DIC removal due to biological production in summer supported by the increased nutrient loading from Changjiang River. The pCO2 dynamics in the river plume and the ECS offshore were both subjected to physical mixing of freshwater and seawater, whether in winter and summer. In the inner estuary without horizontal mixing, the pCO2 dynamics were mainly influenced by biological uptake in winter and temperature in summer. The inner estuary, the river plume, and the ECS offshore were sources of atmospheric CO2, with their contributions varying seasonally. The Changjiang runoff enhanced the inner estuary's role as a CO2 source in summer, while intensive biological uptake reduced the river plume's contribution.

Communication-Efficient Hybrid Federated Learning for E-Health With Horizontal and Vertical Data Partitioning.

Electronic healthcare (e-health) allows smart devices and medical institutions to collaboratively collect patients' data, which is trained by artificial intelligence (AI) technologies to help doctors make diagnosis. By allowing multiple devices to train models collaboratively, federated learning is a promising solution to address the communication and privacy issues in e-health. However, applying federated learning in e-health faces many challenges. First, medical data are both horizontally and vertically partitioned. Since single horizontal federated learning (HFL) or vertical federated learning (VFL) techniques cannot deal with both types of data partitioning, directly applying them may consume excessive communication cost due to transmitting a part of raw data when requiring high modeling accuracy. Second, a naive combination of HFL and VFL has limitations including low training efficiency, unsound convergence analysis, and lack of parameter tuning strategies. In this article, we provide a thorough study on an effective integration of HFL and VFL, to achieve communication efficiency and overcome the above limitations when data are both horizontally and vertically partitioned. Specifically, we propose a hybrid federated learning framework with one intermediate result exchange and two aggregation phases. Based on this framework, we develop a hybrid stochastic gradient descent (HSGD) algorithm to train models. Then, we theoretically analyze the convergence upper bound of the proposed algorithm. Using the convergence results, we design adaptive strategies to adjust the training parameters and shrink the size of transmitted data. The experimental results validate that the proposed HSGD algorithm can achieve the desired accuracy while reducing communication cost, and they also verify the effectiveness of the adaptive strategies.

Multiparametric MRI subregion radiomics for preoperative assessment of high-risk subregions in microsatellite instability of rectal cancer patients: A multicenter study.

BACKGROUND: Microsatellite instability (MSI) is associated with treatment response and prognosis in patients with rectal cancer (RC). However, intratumoral heterogeneity limits MSI testing in patients with RC. We developed a subregion radiomics model based on multiparametric magnetic resonance imaging (MRI) to preoperatively assess high-risk subregions with MSI and predict the MSI status of patients with RC. METHODS: This retrospective study included 475 patients (training cohort, 382; external test cohort, 93) with RC from two participating hospitals between April 2017 and June 2023. In the training cohort, subregion radiomic features were extracted from multiparametric MRI, which included T2-weighted, T1-weighted, diffusion-weighted, and contrast-enhanced T1-weighted imaging. MSI-related subregion radiomic features, classical radiomic features, and clinicoradiological variables were gathered to build five predictive models using logistic regression. Kaplan-Meier survival analysis was conducted to explore the prognostic information. RESULTS: Among the 475 patients (median age, 64 years [interquartile range, IQR: 55-70 years];304 men and 171 women), the prevalence of MSI was 11.16% (53/475). The subregion radiomics model outperformed the classical radiomics and clinicoradiological models in both training (area under the curve [AUC]=0.86, 0.72, and 0.59, respectively) and external test cohorts (AUC=0.83, 0.73, and 0.62, respectively). The subregion-clinicoradiological model combining clinicoradiological variables and subregion radiomic features performed the optimal, with AUCs of 0.87 and 0.85 in the training and external test cohorts, respectively. The 3-year disease-free survival rate of MSI groups predicted based on the model was higher than that of the predicted microsatellite stability (MSS) groups in both patient cohorts (training, P=0.032; external test, P=0.046). CONCLUSIONS: We developed and validated a model based on subregion radiomic features of multiparametric MRI to evaluate high-risk subregions with MSI and predict the MSI status of RC preoperatively, which may assist in individualized treatment decisions and positioning for biopsy.

A pilot trial of neoadjuvant pyrotinib plus trastuzumab, dalpiciclib, and letrozole for triple-positive breast cancer.

Triple-positive breast cancer (TPBC) poorly responds to current standard neoadjuvant therapy (trastuzumab plus pertuzumab and chemotherapy). Our previous MUKDEN 01 study showed a promising total pathological complete response (tpCR) rate of 30.4% with neoadjuvant pyrotinib (pan-human epidermal growth factor receptor tyrosine kinase inhibitor) plus dalpiciclib (cyclin-dependent kinase 4/6 inhibitor) and letrozole, but the efficacy remains suboptimal. This pilot study (NCT05228951) explored adding trastuzumab to this triplet neoadjuvant regimen in patients with stage II-III TPBC. The primary endpoint was tpCR (ypT0/is, ypN0) rate. Between February 2022 and June 2022, 12 patients were enrolled, and seven (58%; 95% confidence interval [CI], 27.7%-84.8%) patients achieved tpCR. The rate of residual cancer burden (RCB) 0-I was 75% (95% CI, 46.8%-91.1%). The objective response rate (ORR) was 92% (95% CI, 64.6%-98.5%). Mean Ki-67 level was significantly reduced from 45.0% (95% CI, 19.5%-70.5%) at baseline to 17.2% (95% CI, 0.7%-33.7%) after neoadjuvant therapy (p = 0.03). The most common grade 3 adverse events were diarrhea (four [33%]) and decreased neutrophil count (three [25%]). No grade 4 adverse events or treatment-related deaths occurred. This four-drug neoadjuvant regimen shows promising pathological response with an acceptable safety profile in patients with TPBC. A randomized controlled trial (NCT05638594) of this regimen is being conducted.

Catalytic polymer self-cleavage for CO2 generation before combustion empowers materials with fire safety.

Polymeric materials, rich in carbon, hydrogen, and oxygen elements, present substantial fire hazards to both human life and property due to their intrinsic flammability. Overcoming this challenge in the absence of any flame-retardant elements is a daunting task. Herein, we introduce an innovative strategy employing catalytic polymer auto-pyrolysis before combustion to proactively release CO2, akin to possessing responsive CO2 fire extinguishing mechanisms. We demonstrate that potassium salts with strong nucleophilicity (such as potassium formate/malate) can transform conventional polyurethane foam into materials with fire safety through rearrangement. This transformation results in the rapid generation of a substantial volume of CO2, occurring before the onset of intense decomposition, effectively extinguishing fires. The inclusion of just 1.05 wt% potassium formate can significantly raise the limiting oxygen index of polyurethane foam to 26.5%, increase the time to ignition by 927%, and tremendously reduce smoke toxicity by 95%. The successful application of various potassium salts, combined with a comprehensive examination of the underlying mechanisms, underscores the viability of this strategy. This pioneering catalytic approach paves the way for the efficient and eco-friendly development of polymeric materials with fire safety.

Molecular insights into the catabolism of dibutyl phthalate in Pseudomonas aeruginosa PS1 based on biochemical and multi-omics approaches.

A comprehensive understanding of the molecular mechanisms underlying microbial catabolism of dibutyl phthalate (DBP) is still lacking. Here, we newly isolated a bacterial strain identified as Pseudomonas aeruginosa PS1 with high efficiency of DBP degradation. The degradation ratios of DBP at 100-1000 mg/L by this strain reached 80-99 % within 72 h without a lag phase. A rare DBP-degradation pathway containing two monobutyl phthalate-catabolism steps was proposed based on intermediates identified by HPLC-TOF-MS/MS. In combination with genomic and transcriptomic analyses, we identified 66 key genes involved in DBP biodegradation and revealed the genetic basis for a new complete catabolic pathway from DBP to Succinyl-CoA or Acetyl-CoA in the genus Pseudomonas for the first time. Notably, we found that a series of homologous genes in Pht and Pca clusters were simultaneously activated under DBP exposure and some key intermediate degradation related gene clusters including Pht, Pca, Xyl, Ben, and Cat exhibited a favorable coexisting pattern, which contributed the high-efficient DBP degradation ability and strong adaptability to this strain. Overall, these results broaden the knowledge of the catabolic diversity of DBP in microorganisms and enhance our understanding of the molecular mechanism underlying DBP biodegradation.

Tangshen Formula alleviates inflammatory injury against aged diabetic kidney disease through modulating gut microbiota composition and related amino acid metabolism.

Diabetic kidney disease (DKD) is leading causes and one of the fastest growing causes of chronic kidney disease worldwide, and leads to high morbidity and mortality. Emerging evidences have revealed gut microbiota dysbiosis and related metabolism dysfunction play a dominant role in DKD progression and treatment through modulating inflammation. Our previous studies showed that Tangshen Formula (TSF), a Chinese herbal prescription, exhibited anti-inflammatory effect on DKD, but underlying mechanism that involved gut microbiota and related metabolism in aged model remained obscure. Here, BTBR ob/ob mice were used to establish aged DKD model, and 16S rRNA sequence and untargeted metabolomic analyses were employed to investigate the correlation between colonic microbiota and serum metabolism. The aged ob/ob mice exhibited obvious glomerular and renal tubule injury and kidney function decline in kidney, while TSF treatment significantly attenuated these abnormalities. TSF also exhibited potent anti-inflammatory effect in aged ob/ob mice indicating by reduced proinflammatory factor IL-6 and TNF-α, MCP-1 and COX-2 in serum, kidney and intestine, which suggested the involvement of gut microbiota with TSF effect. The 16S rDNA sequencing of the colonic microbiome and untargeted serum metabolomics analysis revealed significant differences in gut microbiota structure and serum metabolomic profiles between WT and ob/ob mice. Notably, TSF treatment reshaped the structure of gut microbiota and corrected the disorder of metabolism especially tryptophan metabolism and arginine biosynthesis. TSF increased Anaeroplasma and Barnesiella genera and decreased Romboutsia, Akkermansia, and Collinsella genera, and further elevated tryptophan, 5-hydroxyindoleacetate, glutamic acid, aspartate and reduced 4-hydroxy-2-quinolinecarboxylic acid, indole-3-acetic acid, xanthurenic acid, glutamine. Further correlation analysis indicated that disturbed gut microbiota was linked to tryptophan metabolism and arginine biosynthesis to regulate inflammation in aged DKD. Our data revealed that TSF attenuated renal inflammation by modulating gut microbiota and related amino acid metabolism in aged DKD model, highlighting gut microbiota and related metabolism functioned as potential therapeutic target for DKD in elderly patients.

Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the ß-common receptor in mice with cerebral ischemic stroke.

AIM: To explore the neuroprotective effects of ARA290 and the role of ß-common receptor (ßCR) in a mouse model of middle cerebral artery occlusion (MCAO). METHODS: This study included male C57BL/6J mice that underwent MCAO and reperfusion. The neuroprotective effect of ARA290 on MCAO-induced brain injury was investigated using neurological function tests (Longa and modified neurological severity score). Cerebral infarction was examined by 2, 3, 5-triphenyl tetrazolium chloride staining, neuronal apoptosis was assessed by immunofluorescence staining, blood parameters were measured using a flow cytometry-based automated hematology analyzer, liquid chromatography with tandem mass spectrometry was used to identify the serum metabolomics signature, inflammatory cytokines and liver index were detected by commercially available kits, and the protein levels of the erythropoietin (EPO) receptor and ßCR were measured by western blot. RESULTS: ARA290 exerted a qualitatively similar neuroprotective effect after MCAO as EPO. ARA290 significantly reduced neuronal apoptosis and the level of inflammatory cytokines in the brain tissue. However, ARA290's neuroprotective effect was significantly suppressed following the injection of siRNA against ßCR. CONCLUSION: ARA290 provided a neuroprotective effect via ßCR in cerebral ischemic mice without causing erythropoiesis. This study provides novel insights into the role of ARA290 in ischemic stroke intervention.

Multiomic study of the protective mechanism of Persicaria capitata (Buch.-Ham. ex D.Don) H.Gross against streptozotocin-induced diabetic nephropathy in Guizhou miniature pigs.

BACKGROUND: Persicaria capitata (Buch.-Ham. ex D.Don) H.Gross (P. capitata, PCB), a traditional drug of the Miao people in China, is potential traditional drug used for the treatment of diabetic nephropathy (DN). PURPOSE: The purpose of this study is to investigate the function of P. capitata and clarify its protective mechanism against DN. METHODS: We induced DN in the Guizhou miniature pig with injections of streptozotocin, and P. capitata was added to the pigs' diet to treat DN. In week 16, all the animals were slaughtered, samples were collected, and the relative DN indices were measured. 16S rRNA sequencing, metagenomics, metabolomics, RNA sequencing, and proteomics were used to explore the protective mechanism of P. capitata against DN. RESULTS: Dietary supplementation with P. capitata significantly reduced the extent of the disease, not only in term of the relative disease indices but also in hematoxylin-eosin-stained tissues. A multiomic analysis showed that two microbes (Clostridium baratii and Escherichia coli), five metabolites (oleic acid, linoleic acid, 4-phenylbutyric acid, 18-ß-glycyrrhetinic acid, and ergosterol peroxide), four proteins (ENTPD5, EPHX1, ARVCF and TREH), four important mRNAs (encoding ENTPD5, EPHX1, ARVCF, and TREH), six lncRNAs (TCONS_00024194, TCONS_00085825, TCONS_00006937, TCONS_00070981, TCONS_00074099, and TCONS_00097913), and two circRNAs (novel_circ_0001514 and novel_circ_0017507) are all involved in the protective mechanism of P. capitata against DN. CONCLUSIONS: Our results provide multidimensional theoretical support for the study and application of P. capitata.

CAR T treatment beyond cancer: Hope for immunomodulatory therapy of non-cancerous diseases.

Engineering a patient's own T cells to accurately identify and eliminate cancer cells has effectively cured individuals afflicted with previously incurable hematologic cancers. These findings have stimulated research into employing chimeric antigen receptor (CAR) T therapy across various areas within the field of oncology. However, evidence from both clinical and preclinical investigations emphasize the broader potential of CAR T therapy, extending beyond oncology to address autoimmune disorders, persistent infections, cardiac fibrosis, age-related ailments and other conditions. Concurrently, the advent of novel technologies and platforms presents additional avenues for utilizing CAR T therapy in non-cancerous contexts. This review provides an overview of the rationale behind CAR T therapy, delineates ongoing challenges in its application to cancer treatment, summarizes recent findings in non-cancerous diseases, and engages in discourse regarding emerging technologies that bear relevance. The review delves into prospective applications of this therapeutic approach across a diverse range of scenarios. Lastly, the review underscores concerns related to precision and safety, while also outlining the envisioned trajectory for extending CAR T therapy beyond cancer treatment.

Arbuscular Mycorrhizal Fungus Alleviates Charged Nanoplastic Stress in Host Plants via Enhanced Defense-Related Gene Expressions and Hyphal Capture.

Contamination of small-sized plastics is recognized as a factor of global change. Nanoplastics (NPs) can readily enter organisms and pose significant ecological risks. Arbuscular mycorrhizal (AM) fungi are the most ubiquitous and impactful plant symbiotic fungi, regulating essential ecological functions. Here, we first found that an AM fungus, Rhizophagus irregularis, increased lettuce shoot biomass by 25-100% when exposed to positively and negatively charged NPs vs control, although it did not increase that grown without NPs. The stress alleviation was attributed to the upregulation of gene expressions involving phytohormone signaling, cell wall metabolism, and oxidant scavenging. Using a root organ-fungus axenic growth system treated with fluorescence-labeled NPs, we subsequently revealed that the hyphae captured NPs and further delivered them to roots. NPs were observed at the hyphal cell walls, membranes, and spore walls. NPs mediated by the hyphae were localized at the root epidermis, cortex, and stele. Hyphal exudates aggregated positively charged NPs, thereby reducing their uptake due to NP aggregate formation (up to 5000 nm). This work demonstrates the critical roles of AM fungus in regulating NP behaviors and provides a potential strategy for NP risk mitigation in terrestrial ecosystems. Consequent NP-induced ecological impacts due to the affected AM fungi require further attention.

Study on the potential mechanism of Qingxin Lianzi Yin Decoction on renoprotection in db/db mice via network pharmacology and metabolomics.

BACKGROUND: Diabetic nephropathy (DN) was one of the most popular and most significant microvascular complications of diabetes mellitus. Qingxin Lianzi Yin Decoction (QXLZY) was a traditional Chinese classical formula, suitable for chronic urinary system diseases. QXLZY had good clinical efficacy in early DN, but the underlying molecular mechanism remained unrevealed. PURPOSE: This study aimed to establish the content determination method of QXLZY index components and explore the mechanism of QXLZY on DN by network pharmacology and metabolomics studies. METHODS: Firstly, the content determination methods of QXLZY were established with calycosin-7-O-ß-d-glucoside, acteoside, baicalin and glycyrrhizic acid as index components. Secondly, pharmacological experiments of QXLZY were evaluated using db/db mice. UHPLC-LTQ-Orbitrap MS was used to carry out untargeted urine metabolomics, serum metabolomics, and kidney metabolomics studies. Thirdly, employing network pharmacology, key components and targets were analyzed. Finally, targeted metabolomics studies were performed on the endogenous constituents in biological samples for validation based on untargeted metabolomics results. RESULTS: A method for the simultaneous determination of multiple index components in QXLZY was established, which passed the comprehensive methodological verification. It was simple, feasible, and scientific. The QXLZY treatment alleviated kidney injury of db/db mice, included the degree of histopathological damage and the level of urinary microalbumin/creatinine ratio. Untargeted metabolomics studies had identified metabolic dysfunction in pathways associated with amino acid metabolism in db/db mice. Treatment with QXLZY could reverse metabolite abnormalities and influence the pathways related to energy metabolism and amino acid metabolism. It had been found that pathways with a high degree were involved in signal transduction, prominently on amino acids metabolism and lipid metabolism, analyzed by network pharmacology. Disorders of amino acid metabolism did occur in db/db mice. QXLZY could revert the levels of metabolites, such as quinolinic acid, arginine, and asparagine. CONCLUSION: This study was the first time to demonstrate that QXLZY alleviated diabetes-induced pathological changes in the kidneys of db/db mice by correcting disturbances in amino acid metabolism. This work could provide a new experimental basis and theoretical guidance for the rational application of QXLZY on DN, exploring the new pharmacological effect of traditional Chinese medicine, and promoting in-depth research and development.

Deciphering the link: ferroptosis and its role in glioma.

Glioma, as the most frequently occurring primary malignancy in the central nervous system, significantly impacts patients' quality of life and cognitive abilities. Ferroptosis, a newly discovered form of cell death, is characterized by significant iron accumulation and lipid peroxidation. This process is fundamentally dependent on iron. Various factors inducing ferroptosis can either directly or indirectly influence glutathione peroxidase, leading to reduced antioxidant capabilities and an increase in lipid reactive oxygen species (ROS) within cells, culminating in oxidative cell death. Recent research indicates a strong connection between ferroptosis and a range of pathophysiological conditions, including tumors, neurological disorders, ischemia-reperfusion injuries, kidney damage, and hematological diseases. The regulation of ferroptosis to intervene in the progression of these diseases has emerged as a major area of interest in etiological research and therapy. However, the exact functional alterations and molecular mechanisms underlying ferroptosis remain to be extensively studied. The review firstly explores the intricate relationship between ferroptosis and glioma, highlighting how ferroptosis contributes to glioma pathogenesis and how glioma cells may resist this form of cell death. Then, we discuss recent studies that have identified potential ferroptosis inducers and inhibitors, which could serve as novel therapeutic strategies for glioma. We also examine the current challenges in targeting ferroptosis in glioma treatment, including the complexity of its regulation and the need for precise delivery methods. This review aims to provide a comprehensive overview of the current state of research on ferroptosis in glioma, offering insights into future therapeutic strategies and the broader implications of this novel cell death pathway in cancer biology.

Current state of immune checkpoints therapy for glioblastoma.

Glioblastoma (GBM), one of the most aggressive forms of brain cancer, has limited treatment options. Recent years have witnessed the remarkable success of checkpoint inhibitor immunotherapy across various cancer types. Against this backdrop, several clinical trials investigating checkpoint inhibitors for GBM are underway in multiple countries. Furthermore, the integration of immunotherapy with traditional treatment approaches is now emerging as a highly promising strategy. This review summarizes the latest advancements in checkpoint inhibitor immunotherapy for GBM treatment. We provide a concise yet comprehensive overview of current GBM immunotherapy options. Additionally, this review underscores combination strategies and potential biomarkers for predicting response and resistance in GBM immunotherapies.

Deep learning-assisted ultrasonic diagnosis of cervical lymph node metastasis of thyroid cancer: a retrospective study of 3059 patients.

Objective: This study aimed to develop a deep learning system to identify and differentiate the metastatic cervical lymph nodes (CLNs) of thyroid cancer. Methods: From January 2014 to December 2020, 3059 consecutive patients with suspected with metastatic CLNs of thyroid cancer were retrospectively enrolled in this study. All CLNs were confirmed by fine needle aspiration. The patients were randomly divided into the training (1228 benign and 1284 metastatic CLNs) and test (307 benign and 240 metastatic CLNs) groups. Grayscale ultrasonic images were used to develop and test the performance of the Y-Net deep learning model. We used the Y-Net network model to segment and differentiate the lymph nodes. The Dice coefficient was used to evaluate the segmentation efficiency. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were used to evaluate the classification efficiency. Results: In the test set, the median Dice coefficient was 0.832. The sensitivity, specificity, accuracy, PPV, and NPV were 57.25%, 87.08%, 72.03%, 81.87%, and 66.67%, respectively. We also used the Y-Net classified branch to evaluate the classification efficiency of the LNs ultrasonic images. The classification branch model had sensitivity, specificity, accuracy, PPV, and NPV of 84.78%, 80.23%, 82.45%, 79.35%, and 85.61%, respectively. For the original ultrasonic reports, the sensitivity, specificity, accuracy, PPV, and NPV were 95.14%, 34.3%, 64.66%, 59.02%, 87.71%, respectively. The Y-Net model yielded better accuracy than the original ultrasonic reports. Conclusion: The Y-Net model can be useful in assisting sonographers to improve the accuracy of the classification of ultrasound images of metastatic CLNs.

Evaluating magnetic resonance imaging characteristics and risk factors for hemifacial spasm.

PURPOSE: The specific neurovascular compression (NVC) event responsible for the symptomatic manifestation of hemifacial spasm (HFS) remains difficult to assess accurately using magnetic resonance imaging (MRI). We aim to evaluate the MRI characteristics of HFS. METHOD: We retrospectively included patients with HFS and divided them into a test group (n = 186) and a validation group (n = 28). The presence, severity, and offending vessel type of NVC in each portion, and the orientation of the offending vessel around the facial nerve, were recorded. Conditional logistic regression analyses were performed to evaluate correlations using test group. The validation group was used to verify whether our findings improved diagnostic performance. RESULTS: Deformity in the proximal cisternal segment was significantly correlated with HFS occurrence (odds ratio [OR]: 256.58, p = .002), whereas contact was not (p = .233). Both contact and deformity in the root detachment point (OR: 19.98 and 37.22, p < .001 and p = .013, respectively) or attached segment (OR: 4.99 and 252.52, p = .001 and p < .001, respectively) were significantly correlated with HFS occurrence. Our findings improved specificity, positive predictive value, and accuracy of diagnosis than conventional diagnostic methods. The vertebral artery predominantly compress the facial nerve in the inferior-anterior position, the anterior inferior cerebellar artery predominantly in the inferior position, the posterior inferior cerebellar artery predominantly in the inferior position, vein predominantly in the posterior-superior position. CONCLUSIONS: This study further demonstrates that within the susceptible portion of facial nerve, different portions of the nerve respond differently to NVC. Each offending vessel has its own preferred conflict orientation. Our study offers reference for neurosurgeons in diagnosis and treatment.

Late-stage gem-difluoroallylation of phenol in bioactive molecules and peptides with 3,3-difluoroallyl sulfonium salts.

An efficient method for the late-stage selective O-fluoroalkylation of tyrosine residues with a stable yet highly reactive fluoroalkylating reagent, 3,3-difluoroallyl sulfonium salts (DFASs), has been developed. The reaction proceeds in a mild basic aqueous buffer (pH = 11.6) with high efficiency, high biocompatibility, and excellent regio- and chemoselectivity. Various oligopeptides and phenol-containing bioactive molecules, including carbohydrates and nucleosides, could be selectively O-fluoroalkylated. The added vinyl and other functional groups from DFASs can be valuable linkers for successive modification, significantly expanding the chemical space for further bioconjugation. The synthetic utility of this protocol has been demonstrated by the fluorescently labeled anti-cancer drug and the synthesis of O-link type 1,4,7,10-tetraazacyclododecane-N,N',N,N'-tetraacetic acid-tyrosine3-octreotate (DOTA-TATE), showing the prospect of the method in medicinal chemistry and chemical biology.