The predictive value of serum tumor markers for EGFR mutation in non-small cell lung cancer patients with non-stage IA.

Objective: The predictive value of serum tumor markers (STMs) in assessing epidermal growth factor receptor (EGFR) mutations among patients with non-small cell lung cancer (NSCLC), particularly those with non-stage IA, remains poorly understood. The objective of this study is to construct a predictive model comprising STMs and additional clinical characteristics, aiming to achieve precise prediction of EGFR mutations through noninvasive means. Materials and methods: We retrospectively collected 6711 NSCLC patients who underwent EGFR gene testing. Ultimately, 3221 stage IA patients and 1442 non-stage IA patients were analyzed to evaluate the potential predictive value of several clinical characteristics and STMs for EGFR mutations. Results: EGFR mutations were detected in 3866 patients (57.9 %) of all NSCLC patients. None of the STMs emerged as significant predictor for predicting EGFR mutations in stage IA patients. Patients with non-stage IA were divided into the study group (n = 1043) and validation group (n = 399). In the study group, univariate analysis revealed significant associations between EGFR mutations and the STMs (carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and cytokeratin-19 fragment (CYFRA21-1)). The nomogram incorporating CEA, CYFRA 21-1, pathology, gender, and smoking history for predicting EGFR mutations with non-stage IA was constructed using the results of multivariate analysis. The area under the curve (AUC = 0.780) and decision curve analysis demonstrated favorable predictive performance and clinical utility of nomogram. Additionally, the Random Forest model also demonstrated the highest average C-index of 0.793 among the eight machine learning algorithms, showcasing superior predictive efficiency. Conclusion: CYFRA21-1 and CEA have been identified as crucial factors for predicting EGFR mutations in non-stage IA NSCLC patients. The nomogram and 8 machine learning models that combined STMs with other clinical factors could effectively predict the probability of EGFR mutations.

Disulfiram mediated anti-tumour effect in pituitary neuroendocrine tumours by inducing cuproptosis.

CONTEXT: Medical treatment plays a critical role in pituitary neuroendocrine tumour (PitNET) treatment. Dopamine agonists and somatostatin receptor agonists are the only known drugs for effectively treating PitNET. Thus, the identification of potential therapeutic targets and drugs is urgently needed. OBJECTIVE: To discover potential drugs that can suppress PitNET growth and to further investigate the underlying mechanism involved. METHODS: High-throughput drug screening of primary cultures of 17 patient-derived PitNETs was performed to identify potential therapeutic compounds. Cell viability assays, Western blot analysis and flow cytometry were used to investigate pituitary neuroendocrine tumour cell lines and patient-derived PitNET cultures in vitro. In vivo drug efficacy was examined in a mouse xenograft model. RESULTS: Seventeen primary PitNET samples were collected for high-throughput drug screening, and a class of copper ionophores that can effectively inhibit cell growth, such as zinc pyrithione, elesclomol, and disulfiram (DSF), was identified. Subsequent experiments initially validated the dose-dependent cell growth-suppressing effect of these copper ionophores on AtT20, GH3, and MMQ cells and several primary PitNET cell lines. Moreover, we confirmed that the cytotoxic effect of DSF depends on the presence of copper. Additionally, we determined that cell death occurs via cuproptosis, with events such as Fe-S cluster protein loss, dihydrolipoyl transacetylase oligomerization and heat shock protein 70 upregulation. Finally, we verified the cytotoxic effects of DSF in vivo. CONCLUSION: The present study revealed copper ionophores as a potential class of drugs for PitNET treatment. DSF induced PitNET cell death via cuproptosis and might be a promising option for PitNET therapy.

Treatment algorithms of relapsing multiple sclerosis: an exploration based on the available disease-modifying therapies in China.

Multiple sclerosis (MS) was defined as a rare disease in China due to its low prevalence. For a long time, interferon ß was the only approved disease-modifying therapy (DMT). Since the first oral DMT was approved in 2018, DMT approval accelerated, and seven DMTs were approved within 5 years. With an increasing number of DMTs being prescribed in clinical practice, it is necessary to discuss the standardized MS treatment algorithms depending on the disease activity and DMT availability. In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country.

Treatment algorithms of relapsing multiple sclerosis in China In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country: 1) CIS and RRMS account for more than 90% of the MS patients and most of them are mild to moderate; 2) MS patients should initiate DMT treatments as soon as the disease has been diagnosed in order to reduce the risk of disease progression; 3) Patients who have been diagnosed with MS should start treatment with fundamental DMTs unless the disease course has been highly active; 4) MAGNIMS score may be a suitable and simplified assessment tool for measuring treatment response to DMTs; 5) Patients treated with corticosteroids and NSIS should be switched to the standardized DMT treatment during remission in accordance with disease activity.

Cerastecins inhibit membrane lipooligosaccharide transport in drug-resistant Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii infections have limited treatment options. Synthesis, transport and placement of lipopolysaccharide or lipooligosaccharide (LOS) in the outer membrane of Gram-negative bacteria are important for bacterial virulence and survival. Here we describe the cerastecins, inhibitors of the A. baumannii transporter MsbA, an LOS flippase. These molecules are potent and bactericidal against A. baumannii, including clinical carbapenem-resistant Acinetobacter baumannii isolates. Using cryo-electron microscopy and biochemical analysis, we show that the cerastecins adopt a serpentine configuration in the central vault of the MsbA dimer, stalling the enzyme and uncoupling ATP hydrolysis from substrate flipping. A derivative with optimized potency and pharmacokinetic properties showed efficacy in murine models of bloodstream or pulmonary A. baumannii infection. While resistance development is inevitable, targeting a clinically unexploited mechanism avoids existing antibiotic resistance mechanisms. Although clinical validation of LOS transport remains undetermined, the cerastecins may open a path to narrow-spectrum treatment modalities for important nosocomial infections.

Therapeutic potential of targeting Nrf2 by panobinostat in pituitary neuroendocrine tumors.

We aimed to identify the druggable cell-intrinsic vulnerabilities and target-based drug therapies for PitNETs using the high-throughput drug screening (HTS) and genomic sequencing methods. We examined 9 patient-derived PitNET primary cells in HTS. Based on the screening results, the potential target genes were analyzed with genomic sequencing from a total of 180 PitNETs. We identified and verified one of the most potentially effective drugs, which targeted the Histone deacetylases (HDACs) both in in vitro and in vivo PitNET models. Further RNA sequencing revealed underlying molecular mechanisms following treatment with the representative HDACs inhibitor, Panobinostat. The HTS generated a total of 20,736 single-agent dose responses which were enriched among multiple inhibitors for various oncogenic targets, including HDACs, PI3K, mTOR, and proteasome. Among these drugs, HDAC inhibitors (HDACIs) were, on average, the most potent drug class. Further studies using in vitro, in vivo, and isolated PitNET primary cell models validated HDACIs, especially Panobinostat, as a promising therapeutic agent. Transcriptional surveys revealed substantial alterations to the Nrf2 signaling following Panobinostat treatment. Moreover, Nrf2 is highly expressed in PitNETs. The combination of Panobinostat and Nrf2 inhibitor ML385 had a synergistic effect on PitNET suppression. The current study revealed a class of effective anti-PitNET drugs, HDACIs, based on the HTS and genomic sequencing. One of the representative compounds, Panobinostat, may be a potential drug for PitNET treatment via Nrf2-mediated redox modulation. Combination of Panobinostat and ML385 further enhance the effectiveness for PitNET treatment.

Single-cell transcriptomics reveal distinct immune-infiltrating phenotypes and macrophage-tumor interaction axes among different lineages of pituitary neuroendocrine tumors.

BACKGROUND: Pituitary neuroendocrine tumors (PitNETs) are common gland neoplasms demonstrating distinctive transcription factors. Although the role of immune cells in PitNETs has been widely recognized, the precise immunological environment and its control over tumor cells are poorly understood. METHODS: The heterogeneity, spatial distribution, and clinical significance of macrophages in PitNETs were analyzed using single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, spatial transcriptomics, immunohistochemistry, and multiplexed quantitative immunofluorescence (QIF). Cell viability, cell apoptosis assays, and in vivo subcutaneous xenograft experiments have confirmed that INHBA-ACVR1B influences the process of tumor cell apoptosis. RESULTS: The present study evaluated scRNA-seq data from 23 PitNET samples categorized into 3 primary lineages. The objective was to explore the diversity of tumors and the composition of immune cells across these lineages. Analyzed data from scRNA-seq and 365 bulk RNA sequencing samples conducted in-house revealed the presence of three unique subtypes of tumor immune microenvironment (TIME) in PitNETs. These subtypes were characterized by varying levels of immune infiltration, ranging from low to intermediate to high. In addition, the NR5A1 lineage is primarily associated with the subtype characterized by limited infiltration of immune cells. Tumor-associated macrophages (TAMs) expressing CX3CR1+, C1Q+, and GPNMB+ showed enhanced contact with tumor cells expressing NR5A1 + , TBX19+, and POU1F1+, respectively. This emphasizes the distinct interaction axes between TAMs and tumor cells based on their lineage. Moreover, the connection between CX3CR1+ macrophages and tumor cells via INHBA-ACVR1B regulates tumor cell apoptosis. CONCLUSIONS: In summary, the different subtypes of TIME and the interaction between TAM and tumor cells offer valuable insights into the control of TIME that affects the development of PitNET. These findings can be utilized as prospective targets for therapeutic interventions.

A Comparative Study of Deep Learning Dose Prediction Models for Cervical Cancer Volumetric Modulated Arc Therapy.

Purpose: Deep learning (DL) is widely used in dose prediction for radiation oncology, multiple DL techniques comparison is often lacking in the literature. To compare the performance of 4 state-of-the-art DL models in predicting the voxel-level dose distribution for cervical cancer volumetric modulated arc therapy (VMAT). Methods and Materials: A total of 261 patients' plans for cervical cancer were retrieved in this retrospective study. A three-channel feature map, consisting of a planning target volume (PTV) mask, organs at risk (OARs) mask, and CT image was fed into the three-dimensional (3D) U-Net and its 3 variants models. The data set was randomly divided into 80% as training-validation and 20% as testing set, respectively. The model performance was evaluated on the 52 testing patients by comparing the generated dose distributions against the clinical approved ground truth (GT) using mean absolute error (MAE), dose map difference (GT-predicted), clinical dosimetric indices, and dice similarity coefficients (DSC). Results: The 3D U-Net and its 3 variants DL models exhibited promising performance with a maximum MAE within the PTV 0.83% ± 0.67% in the UNETR model. The maximum MAE among the OARs is the left femoral head, which reached 6.95% ± 6.55%. For the body, the maximum MAE was observed in UNETR, which is 1.19 ± 0.86%, and the minimum MAE was 0.94 ± 0.85% for 3D U-Net. The average error of the Dmean difference for different OARs is within 2.5 Gy. The average error of V40 difference for the bladder and rectum is about 5%. The mean DSC under different isodose volumes was above 90%. Conclusions: DL models can predict the voxel-level dose distribution accurately for cervical cancer VMAT treatment plans. All models demonstrated almost analogous performance for voxel-wise dose prediction maps. Considering all voxels within the body, 3D U-Net showed the best performance. The state-of-the-art DL models are of great significance for further clinical applications of cervical cancer VMAT.

Different binding properties of odorant-binding protein 8 to insecticides in Orius sauteri.

Chemical sensing systems are vital in the growth and development of insects. Orius sauteri (Poppius) (Hemiptera: Anthocoridae) is an important natural enemy of many pests. The molecular mechanism of odorant binding proteins (OBPs) binding with common insecticides is still unknow in O. sauteri. In this study, we expressed in vitro OsauOBP8 and conducted fluorescence competition binding assay to investigate the function of OsauOBP8 to insecticides. The results showed that OsauOBP8 could bind with four common insecticides (phoxim, fenitrothion, chlorpyrifos, deltamethrin). Subsequently, we used molecular docking to predict and obtained candidate six amino acid residues (K4, K6, K13, R31, K49, K55) and then mutated. The result showed that three key residues (K4, K6, R31) play important role in OsauOBP8 bound to insecticides. Our study identified the key binding sites of OsauOBP8 to insecticides and help to better understand the molecular mechanism of OBPs to insecticides in O. sauteri.

Experimental Study on the Fatigue Crack Propagation Rate of 925A Steel for a Ship Rudder System.

The low-temperature fatigue crack propagation rate of 925A steel, as a rudder steel for polar special ships, has a crucial impact on the evaluation of the fatigue strength of polar ships. The purpose of this article is to study the fatigue crack propagation rate of 925A steel under different low-temperature conditions from room temperature (RT) to -60 °C. The material was subjected to fatigue crack propagation tests and stress intensity factor tests. The experimental tests were conducted according to the Chinese Standard of GB/T6398-2017. The results show that as the temperature decreases, the lifespan of 925A increases. Within a certain stress intensity factor, as the temperature decreases, the fatigue crack propagation rate decreases. At -60 °C, it exhibits ductile fracture; within normal polar temperatures, it can be determined that 925A meets the requirements for low-temperature fatigue crack propagation rates in polar regions. However, in some extreme polar temperatures below -60 °C, preventing brittle failure becomes a key focus of fatigue design. Finally, the fatigue crack propagation behavior at the microscale of 925A steel at low temperatures was described using fracture morphology. The experimental data can provide reference for the design of polar ships to further resist low-temperature fatigue and cold brittle fracture.

Design of Evodiamine-Glucose Conjugates with Improved In Vivo Antitumor Activity.

Natural product evodiamine is a multitargeting antitumor lead compound. However, clinical development of evodiamine derivatives was hampered by poor water solubility and limited in vivo antitumor potency. Herein, a series of evodiamine-glucose conjugates were designed by additional targeting glucose transporter-1 (GLUT1). Compared with the lead compound, conjugate 8 exhibited obvious enhancement in water solubility and in vivo antitumor efficacy. Furthermore, the effect of GLUT1 targeting also led to lower cytotoxicity to normal cells. Antitumor mechanism studies manifested that conjugate 8 acted by Top1/Top2 dual inhibition, apoptosis induction, and G2/M cell cycle arrest, which selectively targeted tumor cells with a high expression level of GLUT1. Thus, evodiamine-glucose conjugates showed promising features as potential antitumor agents.

Exploring the Correlation between Azido-Tetrazolo Tautomerizations and Isomer Structures: Electron Density of Bonding N Atoms and N-N Bond Polarity.

Azido-tetrazolo tautomerizations between azido N-heteroaromatic compounds and tetrazole-fused energetic materials can produce a new generation of high-energy density compounds. Density functional theory (DFT) computations are performed to explore the relationship between reaction barriers and electron densities of bonding N atoms, i.e., the terminal N1 and heterocyclic N2 atoms, for six reported tautomerizations. The results reveal four linear correlations between reverse reaction barriers (Gr) and the electron densities of N1 and N2 atoms in the product. N1 electron density (ρN1) and N-N bond polarity, as measured by the difference between the electron densities on the two N atoms (ΔρN = ρN1 - ρN2) in products, are inversely proportional to the reverse reaction barriers. They are also proportional to the energy barrier differences between the forward and reverse reactions (ΔG = Gf - Gr). Polar solvents, including DMSO, water, and acetone, can effectively increase the reverse reaction barriers (Gr) by improving the stability of products. This regularity is further confirmed by its application to four additional tautomerizations and can be used to screen out unfavorable azido-tetrazolo tautomerization reactions and increase the success rate of such synthesis.

Evaluating the effectiveness of a novel digital evaluation technology on dental preclinical crown preparation training.

OBJECTIVES: To evaluate the assessment scores of a novel digital training program versus traditional training in dental preclinical crown preparation. METHODS: Crown preparations in two consecutive preclinical training sessions were retrospectively collected and assigned to three groups: traditional group (TG), scanning group (SG), and digital evaluation group (DG). Students in the TG (n = 20) were taught by conventional visual grading, while students in the SG (n = 25) received three-dimensional feedback from digitally scanned preparations. All the SG students continued with supplementary digital evaluation and preparations were allocated into the DG (n = 25). Comparison of total scores between groups was investigated using independent samples t-test and paired samples t-test. Mann‒Whitney U-test and Wilcoxon signed-rank test were used to statistically analyze the differences in subdividing categories. The level of significance was p < 0.05. Questionnaires on the digital evaluation procedure were answered by students in DG. RESULTS: The results showed a significant improvement (p < 0.01) in the total scores of DG than those of TG and SG, while there were no statistically significant differences between TG and SG. Scores of surface finish and undercut improved significantly in DG compared to TG and SG. The reduction scores of DG were significantly higher than those of SG. Students' feedback indicated a positive perspective on the implementation of the novel digital evaluation technology. CONCLUSIONS: These findings suggest that digital evaluation technology is useful for preclinical crown preparation training. Attention should also be paid to studying the optimal integration of digital dentistry into traditional dental curricula and its effects on students' learning curves.

Transcriptome Sequencing Reveals the Mechanism of Auxin Regulation during Root Expansion in Carrot.

Carrot is an important vegetable with roots as the edible organ. A complex regulatory network controls root growth, in which auxin is one of the key players. To clarify the molecular mechanism on auxin regulating carrot root expansion, the growth process and the indole-3-acetic acid (IAA) content in the roots were measured in this experiment. It was found that the rapid expansion period of the root was from 34 to 41 days after sowing and the IAA content was the highest during this period. The root growth then slowed down and the IAA levels decreased. Using the transcriptome sequencing database, we analyzed the expression of IAA-metabolism-related genes and found that the expression of most of the IAA synthesis genes, catabolism genes, and genes related to signal transduction was consistent with the changes in IAA content during root expansion. Among them, a total of 31 differentially expressed genes (DEGs) were identified, including 10 IAA synthesis genes, 8 degradation genes, and 13 genes related to signal transduction. Analysis of the correlations between the DEGs and IAA levels showed that the following genes were closely related to root development: three synthesis genes, YUCCA10 (DCAR_012429), TAR2 (DCAR_026162), and AMI1 (DCAR_003244); two degradation genes, LPD1 (DCAR_023341) and AACT1 (DCAR_010070); and five genes related to signal transduction, IAA22 (DCAR_012516), IAA13 (DCAR_012591), IAA27 (DCAR_023070), IAA14 (DCAR_027269), and IAA7 (DCAR_030713). These results provide a reference for future studies on the mechanism of root expansion in carrots.

The relationship between dietary phosphorus and peripheral neuropathy in the general population of the United States: A preliminary research.

BACKGROUND: Dietary phosphorus intake may serve as a potential predictor for peripheral neuropathy (PN). While past research has predominantly focused on the relationship between dietary phosphorus and bone health, relatively little is known about its role in the nervous system, particularly its association with PN. METHODS: A cross-sectional study was conducted using data from NHANES 1999-2004. Participants were categorized into different dietary phosphorus intake groups, and the relationship between dietary phosphorus and PN was explored using multifactorial logistic regression, restricted cubic splines (RCS) analysis, and threshold effect analysis based on dietary intake. RESULTS: The final study included 7726 participants, with 1378 diagnosed with PN and 6348 without. The study revealed a U-shaped non-linear relationship between dietary calcium and magnesium intake levels and PN, indicating that both excessive and insufficient dietary phosphorus intake may increase the risk of PN. Specifically, the incidence rates in the first quintile (1.433, 95% CI: 1.080-1.901), the fourth quintile (1.284, 95% CI: 1.000-1.648), and the fifth quintile (1.533, 95% CI: 1.155-2.035) significantly higher than the second quintile, with an overall trend showing a decrease followed by an increase in incidence rates. The results of RCS and threshold effect analysis indicate that when dietary phosphorus intake is below 939.44mg, the risk of PN decreases with increasing dietary phosphorus intake. On the contrary, when dietary phosphorus intake exceeds 939.44mg, the risk of PN increases with increasing dietary phosphorus intake. CONCLUSION: This study reveals a U-shaped correlation between dietary phosphorus intake and PN. Future research should further elucidate the molecular mechanisms underlying this association, providing guidance for more scientifically informed dietary adjustments to prevent the occurrence of PN.

Binding Properties of Odorant Binding Protein 37 in Plagiodera versicolora to Host Volatile, o-Cymene.

The chemosensory system plays an important role in the host plants location. Plagiodera versicolora (Coleoptera: Chrysomelidae) is a worldwide leaf-eating forest pest that feeds exclusively on salicaceous trees. There is no function study of odorant binding proteins (OBPs) in P. versicolora. In the current study, we found that PverOBP37 has a high expression in male and female antennae, heads, and legs by quantitative real-time PCR. The binding properties of PverOBP37 to 18 host plant volatiles were determined by fluorescence competition binding assays. The results showed that PverOBP37 could bind to the host plant volatile, o-cymene. Furthermore, four candidate key amino acid residues (F8, Y50, F103, and R107) of PverOBP37 to o-cymene were identified by molecular docking. The functional assay to confirm Y50, F103, and R107 mutations were key amino acid residues of PverOBP37 involved in the binding to o-cymene. Knockdown of PverOBP37 and Y-tube behavioral bioassays of mated females led to a significantly reduced attraction to o-cymene. This study not only revealed the molecular mechanism of PverOBP37 but also suggested that PverOBP37 is essential to detect host plant volatiles as cues to search for egg-laying sites in P. versicolora.

Study of Dandelion (Taraxacum mongolicum Hand.-Mazz.) Salt Response and Caffeic Acid Metabolism under Saline Stress by Transcriptome Analysis.

Utilizing salt-tolerant plants is a cost-effective strategy for agricultural production on salinized land. However, little is known about the mechanism of dandelion (Taraxacum mongolicum Hand.-Mazz.) in response to saline stress and caffeic acid biosynthesis. We investigated the morphological and physiological variations of two dandelions, namely, "BINPU2" (dandelion A) and "TANGHAI" (dandelion B) under gradient NaCl concentrations (0, 0.3%, 0.5%, 0.7%, and 0.9%), and analyzed potential mechanisms through a comparison analysis of transcriptomes in the two dandelions. Dandelion A had a high leaf weight; high ρ-coumaric acid, caffeic acid, ferulic acid, and caffeoyl shikimic acid contents; and high activities of POD and Pro. The maximum content of four kinds of phenolic acids mostly occurred in the 0.7% NaCl treatment. In this saline treatment, 2468 and 3238 differentially expressed genes (DEGs) in dandelion A and B were found, of which 1456 and 1369 DEGs in the two dandelions, respectively, showed up-regulation, indicating that more up-regulated DEGs in dandelion A may cause its high salt tolerance. Further, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that dandelion salt response and caffeic acid metabolism were mainly enriched in the phenylpropanoid biosynthesis pathway (ko00940) and response to ethylene (GO: 0009723). The caffeic acid biosynthesis pathway was reconstructed based on DEGs which were annotated to PAL, C4H, 4CL, HCT, C3'H, and CSE. Most of these genes showed a down-regulated mode, except for parts of DEGs of 4CL (TbA05G077650 and TbA07G073600), HCT (TbA03G009110, TbA03G009080, and novel.16880), and COMT (novel.13839). In addition, more up-regulated transcription factors (TFs) of ethylene TFs in dandelion A were found, but the TFs of ERF104, CEJ1, and ERF3 in the two dandelions under saline stress showed an opposite expression pattern. These up-regulated genes could enhance dandelion salt tolerance, and down-regulated DEGs in the caffeic acid biosynthesis pathway, especially CSE (TbA08G014310) and COMT (TbA04G07330), could be important candidate genes in the synthesis of caffeic acid under saline stress. The above findings revealed the potential mechanisms of salt response and caffeic acid metabolism in dandelion under saline stress, and provide references for salt-tolerant plant breeding and cultivation on saline-alkali land in the future.

Alternations of Blood Pressure Following Surgical or Drug Therapy for Prolactinomas.

Several subtypes of pituitary neuroendocrine tumors (PitNETs), such as acromegaly and Cushing's disease, can result in hypertension. However, whether prolactinoma is associated with this complication remains unknown. Moreover, the effect of treatment with surgery or drugs on blood pressure (BP) is unknown. Herein, a retrospective study reviewed 162 patients with prolactinoma who underwent transsphenoidal surgery between January 2005 and December 2022. BP measurements were performed 1 day before and 5 days after surgery. Accordingly, patients' medical characteristics were recorded. In addition, in situ rat and xenograft nude-mice prolactinoma models have been used to mimic prolactinoma. In vivo BP and serum prolactin (PRL) levels were measured after cabergoline (CAB) administration in both rats and mice. Our data suggest that surgery can effectively decrease BP in prolactinoma patients with or without hypertension. The BP-lowering effect was significantly associated with several variables, including age, sex, disease duration, tumor size, invasion, dopamine agonists (DAs)-resistance, recurrence, and preoperative PRL levels. Moreover, in situ and xenograft prolactinomas induced BP elevation, which was alleviated by CAB treatment without and with a statistical difference in rats and mice, respectively. Thus, surgery or CAB can decrease BP in prolactinoma, indicating that pre- and postoperative BP management becomes essential.

Astrocytes in intracerebral hemorrhage: impact and therapeutic objectives.

Intracerebral hemorrhage (ICH) manifests precipitously and profoundly impairs the neurological function in patients who are affected. The etiology of subsequent injury post-ICH is multifaceted, characterized by the intricate interplay of various factors, rendering therapeutic interventions challenging. Astrocytes, a distinct class of glial cells, interact with neurons and microglia, and are implicated in a series of pathophysiological alterations following ICH. A comprehensive examination of the functions and mechanisms associated with astrocytic proteins may shed light on the role of astrocytes in ICH pathology and proffer innovative therapeutic avenues for ICH management.

Rab32 family proteins regulate autophagosomal components recycling.

In autophagy, autophagosomes deliver the lumenal contents to lysosomes for degradation via autophagosome-lysosome fusion. In contrast, autophagosome outer membrane components were recycled via autophagosomal components recycling (ACR), which is mediated by the recycler complex. The recycler complex, composed of SNX4, SNX5, and SNX17, cooperate with the dynein-dynactin complex to mediate ACR. However, how ACR is regulated remains unknown. Here, we found that Rab32 family proteins localize to autolysosomes and are required for ACR, rather than other autophagosomal or lysosomal Rab proteins. The GTPase activity of Rab32 family proteins, governed by their guanine nucleotide exchange factor and GTPase-activating protein, plays a key role in regulating ACR. This regulation occurs through the control of recycler complex formation, as well as the connection between the recycler-cargo and dynactin complex. Together, our study reveals an unidentified Rab32 family-dependent regulatory mechanism for ACR.