Structural and functional dissection of the Pacinian corpuscle reveals an active role of the inner core in touch detection.

Pacinian corpuscles are rapidly adapting mechanoreceptor end-organs that detect transient touch and high-frequency vibration. In the prevailing model, these properties are determined by the outer core, which acts as a mechanical filter limiting static and low-frequency stimuli from reaching the afferent terminal-the sole site of touch detection in corpuscles. Here, we determine the detailed 3D architecture of corpuscular components and reveal their contribution to touch detection. We show that the outer core is dispensable for rapid adaptation and frequency tuning. Instead, these properties arise from the inner core, composed of gap junction-coupled lamellar Schwann cells (LSCs) surrounding the afferent terminal. By acting as additional touch sensing structures, LSCs potentiate mechanosensitivity of the terminal, which detects touch via fast-inactivating ion channels. We propose a model in which Pacinian corpuscle function is mediated by an interplay between mechanosensitive LSCs and the afferent terminal in the inner core.

[Application of folded flap in laryngeal and hypopharyngeal function reconstructions after surgery of piriform sinus cancer].

Objective: To investigate the use of folded flap for repair of laryngeal and hypopharyngeal defect and the clinical efficacies of laryngeal and hypopharyngeal function reconstructions after surgery of piriform sinus cancer. Methods: A retrospective analysis was performed for 10 cases of piriform sinus cancer that were treated in the Second Norman Bethune Hospital of Jilin University from January 2020 to April 2023 and all patients were males, aged 42-68 years. The first choice of treatment for all patients was surgery. After function neck dissection and tracheotomy, partial laryngectomy and hypopharyngectomy were carried out. The folded island flaps were prepared and used for the repairs of laryngeal and hypopharyngeal defects and the reconstructions laryngeal and hypopharyngeal functions. The patients were followed up. Results: The laryngeal and pharyngeal cavities were reconstructed well in 10 patients, and all the flaps survived, with no case of pharyngeal fistula. All patients were able to eat normally through the mouth at 2 weeks after surgery without obvious choking, and 4 patients completed the swallowing function evaluation without aspiration or only a small amount of aspiration. All the 10 patients underwent postoperative radiotherapy. The postoperative follow-up time was 5.4-41.4 months, and there was no case with tumor recurrence or death. Laryngoscopy showed that 8 patients had a spacious new laryngeal orifice, which met the conditions for extubation, of whom 7 patients had their tracheal tubes removed and 1 patient was still under observation, and that 2 patients had a slightly narrowed new laryngeal orifice due to a thick skin flap, with further follow-up observation. All patients retained their phonatory functions after surgery. Conclusion: Folded island flap can be used for the function reconstructions of the larynx and hypopharynx after surgery of pyriform sinus cancer.

[Therapeutic efficacy of transoral robotic surgery with the da Vinci robot system for the treatment of oropharyngeal squamous cell carcinoma].

Objective: To evaluate the clinical efficacy of transoral robotic surgery (TORS) with the da Vinci robot system in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). Methods: A mixed cohort study was conducted to collect and analyze the clinical data of OPSCC patients who underwent TORS at the Eye & ENT Hospital, Fudan University between July 2020 and February 2023 (TORS group). OPSCC patients who underwent conventional surgery between January 2016 and September 2020 were included as the control group. The baseline information, incidence of complications and follow-up data were compared between the two groups. Results: A total of 166 patients were included, with 102 cases (81 males and 21 females) in the TORS group [mean age: (59.1±9.8) years] and 64 cases (54 males and 10 females) in the control group [ mean age: (57.6±9.7) years]. Compared with the control group, the TORS group had lower postoperative bleeding rate [2.9% (3/102) vs 10.9% (7/64), P=0.035] and infection rate [1.0% (1/102) vs 18.8% (12/64), P<0.001]. No statistically significant differences were observed in tracheotomy rate [46.1% (47/102) vs 59.4% (38/64), P=0.070] and median length of hospital stay [8 (7, 10) d vs 10 (4, 12) d, P=0.088]. After propensity score matching, compared with the control group, the TORS group had lower postoperative infection rate [0 (0/31) vs 19.4% (6/31), P=0.032] and median length of hospital stay [7 (7, 10) d vs 10 (8, 12) d, P=0.031]. No statistically significant differences were found in postoperative bleeding rate [3.2% (1/31) vs 6.5% (2/31), P=1.000] and tracheotomy rate [22.6% (7/31) vs 45.2% (14/31), P=0.060] between the two groups. Moreover, 1-and 2-year disease-free survival rates were 96.3% and 94.6% in the TORS group, and 90.6% and 84.3% in the control group, respectively (P=0.233). The 1-and 2-year cancer-specific survival rates were both 100% in the TORS group, and 96.9% and 93.8% in the control group, respectively (P=0.539). Conclusion: TORS for OPSCC is associated with high clinical safety and favorable oncological outcomes.

[Topological properties of white matter network in first untreated children and adolescents with obsessive-compulsive disorder].

Objective: To investigate the topological properties of the white matter network in the drug-naive first-episode children and adolescent with obsessive-compulsive disorder (OCD). Methods: This study was a case-control study. First-episode OCD childhren and adolescents(OCD group) who were treated in the outpatient or inpatient department of the Second Affiliated Hospital of Xinxiang Medical University from July 2018 to October 2023 were collected as the research subjects. Healthy controls (control group)matched by gender, age and education level were used as controls. Deterministic tractography technique was used to construct the whole brain white matter structural network, and graph theory analysis method was used to analyze the topological attributes of the whole brain white matter structure network in OCD children and adolescents. A network-based statistical method was used to examine the inter-group differences in the functional connectivity strength of the whole brain network. Results: Finally, 31 cases were included in the obsessive-compulsive disorder group, including 22 males and 9 females, with an age of (13.5±1.6) years; There were 34 cases in the control group, including 22 males and 12 females, with an age of (12.7±1.4) years. The global efficiency and local efficiency of the OCD group (0.62±0.03, 0.70±0.07) were significantly higher than those of the control group (0.50±0.06, 0.54±0.21) [both P<0.01, false discovery rate(FDR)correction]; while the characteristic path length (1.77±0.08) was significantly smaller than that of the control group (2.10±0.23) (P<0.01, FDR correction).The centrality comparison of nodal betweenness centrality showed that in the OCD group, the connections were enhanced in the left lateral orbitofrontal gyrus, right dorsal agranular insula, left dorsal granular insula, right granular insula, right posterior central gyrus main area of parietal lobe, left ventral granular insula, granular insula, left ventral granulosa, left granular insula, and left dorsal agranular insula [all P<0.001, family wise error (FWE) correction], while the connection of right thalamic was weakened (P<0.001, FWE correction), There were sub-networks characterized by significantly enhanced connection strength of relevant nodes in subcortical, visual network, and default mode network (P<0.05, permutation test 5 000 times). Conclusions: The topological properties of the brain's functional network in children and adolescents with OCD exhibit abnormalities, indicating an immature state of brain functional connectivity.

Catalpol improves insulin resistance and lipid metabolism disorder in diabetic mice by inhibiting microRNA-101-3p to up-regulate FOS-related antigen 2.

Disorders of glucose and lipid metabolism are important causes of type 2 diabetes mellitus (T2DM). Defining the molecular mechanisms of metabolic disorders and exploring drug targets are key to the treatment of T2DM. The study discovered the effects of catalpol on insulin resistance (IR) and lipid metabolism disorder (LMD) in type 2 diabetes mellitus (T2DM). A T2DM mouse model was established by a high-fat diet and a single intraperitoneal injection of streptozotocin. and injected with catalpol at 10 mg/kg for 12 weeks, and the lentiviral vector of miR-101-3p or Fos-related antigen 2 (FOSL2) expression was interfered with intravenously mouse insulin resistance (IR) and lipid metabolism disorder (LMD)-related indices were then measured. Pancreatic histopathology was observed by hematoxylin and eosin (HE) staining and TUNEL staining. The miR-101-3p and FOSL2 were detected by RT-qPCR or Western blot. In results: catalpol improved IR and LMD (both P<0.05) in diabetic mice, and alleviated the histopathological changes in the pancreas. miR-101-3p was upregulated (P<0.05), and FOSL2 was downregulated (P<0.05) in T2DM mice, while catalpol rescued their expression pattern (both P<0.05). The miR-101-3p targeted FOSL2. Down-regulating miR-101-3p or up-regulating FOSL2 improved IR and LMD (all P<0.05) in diabetic mice, and alleviated pancreatic histopathological changes. Overexpressing miR-101-3p or suppressing FOSL2 weakened the ameliorative effects of catalpol in T2DM mice (all P<0.05). We conclude that catalpol improves IR and LMD in diabetic mice by inhibiting miR-101-3p to up-regulate FOSL2.

[Application of whole exome sequencing technology in the diagnosis of hereditary eye diseases].

Objective: To evaluate the application of whole exome sequencing (WES) in the diagnosis of hereditary eye diseases. Methods: A total of 24 patients who came to the Obstetrics and Gynecology Hospital of Fudan University for reproductive genetic counseling from December 2020 to December 2023 with the main complaint of congenital eye disorders were included in this study. All cases had no known infections or exposure to known teratogenic drugs, karyotype and chromosome microarray analysis (CMA) abnormalities. Genomic DNA was extracted from the peripheral blood of the probands and their family members and tested for WES. Among them, three individual WES and 21 Trio WES were performed. Potential pathogenic sites were screened and analyzed by Sanger sequencing. For RPGRIP1:c.1611+26G>A site, minigene vector was constructed and RT-qPCR was performed to detect the effect of mRNA splicing. Results: A total of 24 families were collected in this study, of which 20 yielded positive results, achieving a diagnosis rate of 83.3% (20/24). The results involved 21 genes and identified 30 distinct variants, 19 of which were new variants reported. Prenatal diagnostic analysis of family 3 revealed that the fetus carried a c.6970G>T heterozygous nonsense mutation in the PRPF8 gene. The results of RT-PCR with the minigene vector at the non-classical splice site in family 24 indicated that the transcription product of the mutant plasmid was partially retained 104 bp in intron 12, resulting in a p.Glu538Valfs*12 alteration of the protein. Conclusions: The high detection rate of WES in the diagnosis of hereditary eye diseases further supports the advantages of its application as an important molecular detection tool for determining the etiology of hereditary eye diseases.

Introduction and validation of the open symptom framework: a public domain modular framework for patient-reported measurement of symptoms related to cancer and its treatment.

PURPOSE: We provide an initial description and validation of some public domain patient-reported outcome (PRO) items to assess cancer symptom burden to address immediate barriers to symptom assessment use in clinical practice and facilitate future research. METHODS: We created the Open Symptom Framework (OSF), a flexible tool for clinical cancer-related symptom assessment. The items comprise six components: recall period, concept, symptom, qualifier(s), a definition, and a 5-point Likert-type response. We recruited patients receiving cancer therapy in the United States and United Kingdom. We assessed external construct validity by comparing OSF scores to the PRO-CTCAE measure and assessed reliability, scalability, dimensionality, and item ordering within a non-parametric item response theory framework. We tested differential item functioning for country, age, gender, and level of education. RESULTS: We developed a framework alongside clinical and psychometric experts and debrieifed with 10 patients. For validation, we recruited 331patients. All items correlated with the PRO-CTCAE equivalents (r = 0.55-0.96, all p < 0.01). Mokken analysis confirmed the scalability and unidimensionality of all symptom scales with multiple items at the scale (Ho = 0.61-0.75) and item level (Hi = 0.60-0.76). Items are interpreted consistently between demographic groups (Crit = 0 for all groups). CONCLUSION: The public domain OSF has excellent psychometric properties including face, content, and criterion validity and can facilitate the development of flexible, robust measurements to fulfil stakeholder need. The OSF was designed specifically to support clinical assessment but will function well for research. Further work is planned to increase the number of symptoms and number of questions per symptom within the framework.

A terahertz solid-state source interferometer-polarimeter designed for long pulse discharges on EAST.

A 0.65 THz Solid-state Source Interferometer-Polarimeter (SSIP) with vertical viewing has been installed for line-integrated density and Faraday rotation measurements on Experimental Advanced Superconducting Tokamak (EAST). The SSIP utilizes three independent solid-state diode sources based on frequency multiplier (X48) to provide the probing beam at a fixed frequency of 0.65 THz with ∼2.5 mW output power, which provide an Intermediate Frequency (IF) with wide range, and the highest IF is up to ∼10 MHz. The mixers optimized for high sensitivity, ∼750 mV/mW, are used in the SSIP system, which permits multichannel interferometer-polarimeter on EAST with a low phase noise. The resolution of the integrated density is 3.3 × 1017 m-2, and the Faraday rotation is about 1.5°. The density measurement has been implemented with IF ∼0.85 MHz, in a plasma with plasma current ∼300 kA on EAST. The line-averaged density, 3.5 × 1019 m-3, measured by the SSIP shows good agreement with the results measured by the POlarimeter-INTerferometer (POINT) system and the CO2 dispersion interferometer system in the same discharge.

[Epidemiological characteristics and spatial aggregation of acute myocardial infarction in Shandong Province].

Objective: To understand the characteristics and trends of acute myocardial infarction (AMI) in Shandong Province and to provide evidence for formulating prevention and control strategies. Methods: Data were derived from the AMI incidence reports of Shandong Province's Chronic Disease Surveillance Information Management System in 2012-2021. The crude and standardized incidence rates were used as indicators to describe the incidence level of AMI. Joinpoint regression analysis was used to analyze the trends in the incidence and age of onset over the years. The contribution of population aging to the increase in AMI incidence was assessed using the rate difference decomposition method. The incidence of AMI in each district (county) in Shandong Province was visualized using ArcGIS 10.8 software, and global and local spatial autocorrelation analysis was performed using DeoDa 1.12 software. Results: From 2012 to 2021, 198 233 cases of AMI were reported from 19 provincial monitoring sites in Shandong Province, of which 53.13% were males and 97.12% were ≥45 years old. The reported crude incidence increased from 90.12 per 100 000 in 2012 to 176.54 per 100 000 in 2021, with an average annual increase of 7.01% (Z=7.35, P<0.001). There was no significant upward trend in standardized incidence (Z=1.64, P=0.140), but the standardized incidence of male residents showed an increasing trend (Z=2.76, P=0.028). Before 2014, the reported crude incidence of males was similar to that of females, but after 2014, the reported crude incidence of males was continuously higher than that of females. However, males' standardized incidence was higher than females in all years. Both crude and standardized incidence rates were higher in rural residents than in urban areas. The median onset of AMI increased from 71.6 years old in 2012 to 73.5 years old in 2021. The median age of onset in males was lower than that in females in all years, and in most years, the median age of onset in urban residents was lower than that in rural residents. The incidence of AMI in males showed a trend in younger age groups. According to the seasonal decomposition, the incidence peak of AMI was in January, and the trough was in September. The contribution of aging population to the increase in crude incidence of AMI increased from 8.63% in 2013 to 52.58% in 2021. The global spatial autocorrelation analysis showed that the incidence of AMI presented an obvious spatial clustering distribution. Local spatial autocorrelation analysis found that the high-incidence areas (counties) were mainly concentrated in Liaocheng City and Dezhou City in the northwest region of Shandong Province and Heze City in the southwest. Conclusions: The incidence of AMI among residents in Shandong Province was rising, with spatial clustering and seasonal clustering characteristics. People aged 45 years and older, male residents, and rural residents were at high risk of developing AMI. There was a certain trend of younger age at onset among men. Targeted prevention and control measures should be taken for high-incidence seasons, high-risk groups, and high-incidence clustering areas in northwestern Shandong Province.

Transport and Organization of Individual Vimentin Filaments Within Dense Networks Revealed by Single Particle Tracking and 3D FIB-SEM.

Single-particle tracking demonstrates that individual filaments in bundles of vimentin intermediate filaments are transported in the cytoplasm by motor proteins along microtubules. Furthermore, using 3D FIB-SEM the authors showed that vimentin filament bundles are loosely packed and coaligned with microtubules. Vimentin intermediate filaments (VIFs) form complex, tight-packed networks; due to this density, traditional ensemble labeling and imaging approaches cannot accurately discern single filament behavior. To address this, we introduce a sparse vimentin-SunTag labeling strategy to unambiguously visualize individual filament dynamics. This technique confirmed known long-range dynein and kinesin transport of peripheral VIFs and uncovered extensive bidirectional VIF motion within the perinuclear vimentin network, a region we had thought too densely bundled to permit such motility. To examine the nanoscale organization of perinuclear vimentin, we acquired high-resolution electron microscopy volumes of a vitreously frozen cell and reconstructed VIFs and microtubules within a ~50 µm3 window. Of 583 VIFs identified, most were integrated into long, semi-coherent bundles that fluctuated in width and filament packing density. Unexpectedly, VIFs displayed minimal local co-alignment with microtubules, save for sporadic cross-over sites that we predict facilitate cytoskeletal crosstalk. Overall, this work demonstrates single VIF dynamics and organization in the cellular milieu for the first time.

Comparison of Efficacy and Safety of Different Second-line Therapies for Patients With Advanced Thymic Carcinoma.

AIMS: Thymic carcinoma (TC) is a rare form of highly invasive tumors. Currently, the standard first-line therapy involves paclitaxel plus carboplatin treatment, while the recommended regimen for second-line therapy remains uncertain. The purpose of this study is to explore the second-line mode of TC patients. MATERIALS AND METHODS: We evaluated the outcome of subjects with advanced TC between 2009 and 2023 in three medical centers, retrospectively. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Kaplan-Meier was used for calculating Progression-free survival (PFS) and overall survival (OS). The factors affecting survival in the real world were evaluated by Cox analysis. RESULTS: Totally 136 patients were included in this study, the median PFS (mPFS) for all subjects was 5.97 months, and the median OS (mOS) was 25.03 months. According to patient's treatment modes, they are divided into monotherapy (n = 95) and combination therapy (n = 41), PFS manifested the difference between two groups (5.17 vs. 9.00 months, P = 0.043). OS also indicated a significant distinction (22.50 vs. 38.00 months, P = 0.017). Furthermore, there was a significant difference in PFS between patients using immunotherapy combined with chemotherapy and those with antivascular therapy (8.57 vs. 13.10 months, P = 0.047). CONCLUSION: In the second-line therapy for advanced TC, the efficacy of combination therapy was better than monotherapy, especially for immunotherapy combined with antivascular therapy.

Spatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity.

The hepatocytes within the liver present an immense capacity to adapt to changes in nutrient availability. Here, by using high resolution volume electron microscopy, we map how hepatic subcellular spatial organization is regulated during nutritional fluctuations and as a function of liver zonation. We identify that fasting leads to remodeling of endoplasmic reticulum (ER) architecture in hepatocytes, characterized by the induction of single rough ER sheet around the mitochondria, which becomes larger and flatter. These alterations are enriched in periportal and mid-lobular hepatocytes but not in pericentral hepatocytes. Gain- and loss-of-function in vivo models demonstrate that the Ribosome receptor binding protein1 (RRBP1) is required to enable fasting-induced ER sheet-mitochondria interactions and to regulate hepatic fatty acid oxidation. Endogenous RRBP1 is enriched around periportal and mid-lobular regions of the liver. In obesity, ER-mitochondria interactions are distinct and fasting fails to induce rough ER sheet-mitochondrion interactions. These findings illustrate the importance of a regulated molecular architecture for hepatocyte metabolic flexibility.

Elevated venous lactate level as an early predictive marker of organ failure in acute pancreatitis: a retrospective study.

OBJECTIVE: The aim of this study was to elucidate the relationship between venous lactate levels and the severity of acute pancreatitis (AP). PATIENTS AND METHODS: Retrospective data analysis was conducted on patients diagnosed with acute pancreatitis. The comparative assessment encompassed baseline characteristics, laboratory data, illness severity, local consequences, and organ failure instances. This comparison was performed between patients exhibiting normal serum lactic acid levels (HL) and those displaying elevated HL levels. The association between serum HL levels and other pertinent clinical markers was investigated using linear regression. Logistic regression analysis was employed to evaluate the utility of elevated serum lactate levels in identifying high-risk groups. RESULTS: Significantly elevated serum HL levels were observed in patients with moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) in contrast to those with mild acute pancreatitis (MAP) (p<0.01). Multivariate logistic analysis demonstrated that higher lactate levels independently predicted organ failure (95% CI 0.738-0.902, p<0.05). Receiver operating characteristic (ROC) curve analysis indicated that the lactate (LAC) cut-off value of 2.45 mmol/L yielded sensitivity and specificity values of 76.5% and 79.1%, respectively, for predicting AP-associated organ failure. The corresponding area under the curve (AUC) was 0.820. CONCLUSIONS: In AP patients, elevated serum HL levels signify disease severity and hold predictive potential for assessing the risk of organ failure.

[Clinical efficacy of induction chemoimmunotherapy for locally advanced hypopharyngeal carcinoma: a prospective phase â ¡ study].

Objective: To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR. Methods: A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m2 day 1, cisplatin 25 mg/m2 days 1-3, and capecitabine 800 mg/m2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results: A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm3. The T stage (OR=12.71, 95%CI: 1.4-112.5, P=0.022) and the volume (OR=7.1, 95%CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion: The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Multi-center Dose Prediction Using Attention-aware Deep learning Algorithm Based on Transformers for Cervical Cancer Radiotherapy.

AIMS: Accurate dose delivery is crucial for cervical cancer volumetric modulated arc therapy (VMAT). We aimed to develop a robust deep-learning (DL) algorithm for fast and accurate dose prediction of cervical cancer VMAT in multicenter datasets and then explore the feasibility of the DL algorithm to endometrial cancer VMAT with different prescriptions. MATERIALS AND METHODS: We proposed the AtTranNet algorithm for three-dimensional dose prediction. A total of 367 cervical patients were enrolled in this study. Three hundred twenty-two cervical patients from 3 centers were randomly divided into 70%, 10%, and 20% as training, validation, and testing sets, respectively. Forty-five cervical patients from another center were selected for external testing. Moreover, 70 patients of endometrial cancer with different prescriptions were further selected to test the model. Prediction precision was evaluated by dosimetric difference, dose map, and dose-volume histogram metrics. RESULTS: The prediction results were all clinically acceptable. The mean absolute error within the body in internal testing was 0.66 ± 0.63%. The maximum |δD| for planning target volume was observed in D98, which is 1.24 ± 2.73 Gy. The maximum |δD| for organs at risk was observed in Dmean of bladder, which is 4.79 ± 3.14 Gy. The maximum |δV| were observed in V40 of pelvic bones, which is 4.77 ± 4.48%. CONCLUSION: AtTranNet showed the feasibility and reasonable accuracy in the dose prediction for cervical cancer in multiple centers. The model can also be generalized for endometrial cancer with different prescriptions without any transfer learning.

COPII with ALG2 and ESCRTs control lysosome-dependent microautophagy of ER exit sites.

Endoplasmic reticulum exit sites (ERESs) are tubular outgrowths of endoplasmic reticulum that serve as the earliest station for protein sorting and export into the secretory pathway. How these structures respond to different cellular conditions remains unclear. Here, we report that ERESs undergo lysosome-dependent microautophagy when Ca2+ is released by lysosomes in response to nutrient stressors such as mTOR inhibition or amino acid starvation in mammalian cells. Targeting and uptake of ERESs into lysosomes were observed by super-resolution live-cell imaging and focus ion beam scanning electron microscopy (FIB-SEM). The mechanism was ESCRT dependent and required ubiquitinated SEC31, ALG2, and ALIX, with a knockout of ALG2 or function-blocking mutations of ALIX preventing engulfment of ERESs by lysosomes. In vitro, reconstitution of the pathway was possible using lysosomal lipid-mimicking giant unilamellar vesicles and purified recombinant components. Together, these findings demonstrate a pathway of lysosome-dependent ERES microautophagy mediated by COPII, ALG2, and ESCRTS induced by nutrient stress.