Development of purity certified reference materials to establish metrological traceability for the measurement of nitroimidazoles in agricultural products.

It is of significant importance to public health that reliable monitoring of nitroimidazoles be conducted, while certified reference materials (CRMs) are essential for accurate and reliable detection. A project has been initiated with the objective of developing nitroimidazole purity CRMs to ensure that results from nationwide monitoring laboratories for nitroimidazoles in antibiotic residues can be compared and traced. The candidates were successively characterized in terms of their structure by means of infrared (IR) spectroscopy and mass spectrometry (MS). The mass balance (MB) method and the quantitative nuclear magnetic resonance (qNMR) method were utilized to determine the purity of nitroimidazoles with remarkable accuracy. Furthermore, a methodical investigation was conducted on homogeneity, stability, and uncertainty. Six nitroimidazole purity CRMs, including tinidazole (GBW09252), secnidazole (GBW09286), ronidazole (GBW09288), metronidazole (GBW(E)090755), dimetridazole (GBW(E)090819), and ornidazole (GBW(E)090820), were finally manufactured following authorization from China's State Administration for Market Regulation (SAMR). By using these CRMs, it is possible to improve the traceability, accuracy, and comparability of nitroimidazole measurements in a range of agricultural products, protecting public health.

Allergo-immunopathology mechanism of thymol-inhibiting airway remodeling in asthmatic mice by regulating TGF-ß/Smad3 pathway.

Allergic asthma is an important public health problem and is a complicated respiratory sickness that is characterized by bronchial inflammation, bronchoconstriction, and breathlessness. Asthma is orchestrated by type 2 immune response and remodeling is one of the important outputted problem in chronic asthma. Thymol is a naturally occurring monocyclic phenolic, it has a series of biological properties, and its immunomodulatory and anti-remodeling effects on allergic asthma were evaluated. The OVA-LPS-induced asthmatic mice were treated with thymol. Methacholine challenge test, eosinophil count, and levels of IL-4, IL-5, IL-13, and IL-33 in bronchoalveolar lavage fluid, total and OVA-specific IgE levels in serum, remodeling factors, gene expression of TGF-ß, Smad2, Smad3, and lung histopathology were done. Treatment with thymol could control AHR, eosinophil percentage levels of Th2 cytokines and Igs, remodeling factors, expression of TGF-ß, Smad2 and Smad3 genes, inflammation, goblet cell hyperplasia, and mucus production in asthmatic mice. Thymol can control asthma pathogens and related remodeling and fibrosis bio-factors and can be a potential treatment of asthma.

Preoperative inter-arm differences and normative-based thresholds for lymphedema in Chinese breast cancer patients: Insights from a large cohort study.

Objective: Early detection and diagnosis of lymphedema are crucial for effective treatment and prevention of its progression. Normative-based diagnostic thresholds can enhance diagnostic accuracy in the absence of preoperative measurements. This study aimed to investigate preoperative inter-arm differences and the associated factors, as well as to determine normative-based thresholds for lymphedema in Chinese breast cancer patients. Methods: This study utilized baseline data from a large cohort of Chinese breast cancer patients. Bilateral arm circumferences were measured at the wrist and at 10 cm intervals proximally up to 40 cm. Arm volumes were calculated using the truncated cone formula. Paired t test, repeated measures analysis of variance, and regression analysis were performed. Results: A total of 1707 breast cancer patients were included. Paired t tests showed that the dominant arm circumferences and volumes were significantly larger than those of the nondominant arm (P < 0.001). Regression analysis and repeated measures analysis of variance revealed that hand dominance was the influencing factor of inter-arm differences (P < 0.05). Normative-based thresholds determined by two standard deviations above the mean inter-arm volume ratio were 1.057 for the dominant arm and 1.079 for the nondominant arm. Conclusions: The absolute and relative normative-based thresholds for Chinese breast cancer patients differed slightly from the commonly used diagnostic criteria and those reported in Western populations and among Chinese healthy women. The normal variability and asymmetry associated with arm dominance underscore the importance of preoperative baseline assessments. Implementing normative-based diagnostic thresholds can facilitate more accurate lymphedema diagnosis when preoperative measurements are unavailable. Trial registration: Registration No. ChiCTR2200057083.

Effects of SpGSH1 and SpPCS1 overexpression or co-overexpression on cadmium accumulation in yeast and Spirodela polyrhiza.

Cadmium (Cd) is one of the most toxic elements to all organisms. Glutathione (GSH)-dependent phytochelatin (PC) synthesis pathway is considered an extremely important mechanism in Cd detoxification in plants. However, few studies have focused on the roles of glutamate-cysteine ligase (GSH1) and phytochelatin synthase (PCS1) in Cd accumulation and detoxification in plants. In this study, SpGSH1 and SpPCS1 were identified and cloned from Spirodela polyrhiza and analyzed their functions in yeast and S. polyrhiza via single- or dual-gene (SpGP1) overexpression. The findings of this study showed that SpGSH1, SpPCS1, and SpGP1 could dramatically rescue the growth of the yeast mutant Δycf1. In S. polyrhiza, SpGSH1 was located in the cytoplasm and could promote Mn and Ca accumulation. SpPCS1 was located in the cytoplasm and nucleus, mainly expressed in meristem regions, and promoted Cd, Fe, Mn, and Ca accumulation. SpGSH1 and SpPCS1 co-overexpression increased the Cd, Mn, and Ca contents. Based on the growth data of S. polyrhiza, it was recommended that biomass as the preferable indicator for assessing plant tolerance to Cd stress compared to frond number in duckweeds. Collectively, this study for the first time systematically elaborated the function of SpGSH1 and SpPCS1 for Cd detoxification in S. polyrhiza.

Acoustic Controllable Spatiotemporal Cell Micro-oscillation for Noninvasive Intracellular Drug Delivery.

Intracellular cargo delivery is crucial for drug evaluation, nanomedicine development, and gene therapy, in which high efficiency while maintaining cell viability is needed for downstream analysis. Here, an acoustic-mediated precise drug delivering mechanism is proposed by directly modulating cell micro-oscillation mode and membrane permeability. Through phase shifting keying-based spatiotemporal acoustic tweezers, controllable oscillating cell arrays can be achieved in shaking potentials. At the same time, continually oscillating radiation force and fluid shear stress exerted on cells effectively disturbs cellular membrane mobility and enhances permeability, thereby facilitating nanodrug entrance. In experiments, cell oscillation is tunable in frequency (10-2 to 102 Hz), shaking direction, amplitude (0 to quarter acoustic wavelength), and speed. Doxorubicin is actively delivered across cellular membranes and accumulates in inner cells, with a concentration more than 8 times that of the control group. Moreover, there is no obvious compromise in cell activity during oscillation, exhibiting excellent biocompatibility. This "dancing acoustic waves" scheme introduces a new dimension of cell manipulation in both space and time domains and an effective drug delivering strategy, offering advantages of flexibility, gentleness, and high throughput. It may advance related fields like nanobiological research, drug and nanomedicine development, and medical treatment.

Unraveling the molecular mechanisms of Ace2-mediated post-COVID-19 cognitive dysfunction through systems genetics approach.

The dysregulation of Angiotensin-converting enzyme 2 (ACE2) in central nervous system is believed associates with COVID-19 induced cognitive dysfunction. However, the detailed mechanism remains largely unknown. In this study, we performed a comprehensive system genetics analysis on hippocampal ACE2 based on BXD mice panel. Expression quantitative trait loci (eQTLs) mapping showed that Ace2 was strongly trans-regulated, and the elevation of Ace2 expression level was significantly correlated with impaired cognitive functions. Further Gene co-expression analysis showed that Ace2 may be correlated with the membrane proteins in Calcium signaling pathway. Further, qRT-PCR confirmed that SARS-CoV-2 spike S1 protein upregulated ACE2 expression together with eight membrane proteins in Calcium Signaling pathway. Moreover, such elevation can be attenuated by recombinant ACE2. Collectively, our findings revealed a potential mechanism of Ace2 in cognitive dysfunction, which could be beneficial for COVID-19-induced cognitive dysfunction prevention and potential treatment.

Local Excitation of Kagome Spin Ice Magnetism Seen by Scanning Tunneling Microscopy.

The kagome spin ice can host frustrated magnetic excitations by flipping its local spin. Under an inelastic tunneling condition, the tip in a scanning tunneling microscope can flip the local spin, and we apply this technique to kagome metal HoAgGe with a long-range ordered spin ice ground state. Away from defects, we discover a pair of pronounced dips in the local tunneling spectrum at symmetrical bias voltages with negative intensity values, serving as a striking inelastic tunneling signal. This signal disappears above the spin ice formation temperature and has a dependence on the magnetic fields, demonstrating its intimate relation with the spin ice magnetism. We provide a two-level spin-flip model to explain the tunneling dips considering the spin ice magnetism under spin-orbit coupling. Our results uncover a local emergent excitation of spin ice magnetism in a kagome metal, suggesting that local electrical field induced spin flip climbs over a barrier caused by spin-orbital locking.

Interferon-responsive neutrophils and macrophages extricate SARS-CoV-2 Omicron critical patients from the nasty fate of sepsis.

The SARS-CoV-2 Omicron variant is characterized by its high transmissibility, which has caused a worldwide epidemiological event. Yet, it turns ominous once the disease progression degenerates into severe pneumonia and sepsis, presenting a horrendous lethality. To elucidate the alveolar immune or inflammatory landscapes of Omicron critical-ill patients, we performed single-cell RNA-sequencing (scRNA-seq) of bronchoalveolar lavage fluid (BALF) from the patients with critical pneumonia caused by Omicron infection, and analyzed the correlation between the clinical severity scores and different immune cell subpopulations. In the BALF of Omicron critical patients, the alveolar violent myeloid inflammatory environment was determined. ISG15+ neutrophils and CXCL10+ macrophages, both expressed the interferon-stimulated genes (ISGs), were negatively correlated with clinical pulmonary infection score, while septic CST7+ neutrophils and inflammatory VCAN+ macrophages were positively correlated with sequential organ failure assessment. The percentages of ISG15+ neutrophils were associated with more protective alveolar epithelial cells, and may reshape CD4+ T cells to the exhaustive phenotype, thus preventing immune injuries. The CXCL10+ macrophages may promote plasmablast/plasma cell survival and activation as well as the production of specific antibodies. As compared to the previous BALF scRNA-seq data from SARS-CoV-2 wild-type/Alpha critical patients, the subsets of neutrophils and macrophages with pro-inflammatory and immunoregulatory features presented obvious distinctions, suggesting an immune disparity in Omicron variants. Overall, this study provides a BALF single-cell atlas of Omicron critical patients, and suggests that alveolar interferon-responsive neutrophils and macrophages may extricate SARS-CoV-2 Omicron critical patients from the nasty fate of sepsis.

Urban flooding simulation and flood risk assessment based on the InfoWorks ICM model: A case study of the urban inland rivers in Zhengzhou, China.

Urban flooding intensifies with escalating urbanization. This study focuses on Xiong'er river as the study area and couples a 1D/2D urban flooding model using InfoWorks ICM (Integrated Catchment Modeling). Ten scenarios are set respectively with a rainfall return period of 5a 10a, 20a, 50a, and 100a, alongside rainfall durations of 1 and 24 h. Subsequently, the H-V (hazard-vulnerability) method was applied to evaluate urban flooding risk. Three indicators were selected for each of hazard factors and vulnerability factors. The relative weight values of each indicator factor were calculated using the AHP method. The result shows that (1) flood depth, rate, and duration escalate with longer rainfall return periods, yet decrease as the duration of rainfall increases; (2) as the rainfall return period lengthens, the proportion of node overflow rises, whereas it diminishes with longer rainfall durations, leading to an overall overloaded state in the pipeline network; and (3) the distribution in the research area is mainly low-risk areas, with very few extremely high-risk. Medium to high-risk areas are mainly distributed on both sides of the river, in densely built and low-lying urban areas. This study demonstrates that the model can accurately simulate urban flooding and provide insights for flood analyses in comparable regions.

Safflower Yellow Injection Alleviates Myocardial Ischemia/Reperfusion Injury by Reducing Oxidative and Endoplasmic Reticulum Stress.

Safflower yellow is an extract of the famous Chinese medicine Carthamus tinctorious L, and safflower yellow injection (SYI) is widely used clinically to treat angina pectoris. However, there are few studies on the anti-myocardial ischemia/reperfusion (I/R) injury effect of SYI, and its mechanisms are unclear. In the present study, we aimed to investigate the protective effect of SYI on myocardial I/R injury and explore its underlying mechanisms. Male Sprague Dawley rats were randomly divided into a control group, sham group, model group, and SYI group (20 mg/kg, femoral vein injection 1 h before modeling). The left anterior descending coronary artery was ligated to establish a myocardial I/R model. H9c2 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) after incubation with 80 µg/mL SYI for 24 h. In vivo, TsTC, HE, and TUNEL staining were performed to evaluate myocardial injury and apoptosis. A kit was used to detect superoxide dismutase (SOD) and malondialdehyde (MDA) to assess oxidative stress. In vitro, flow cytometry was used to detect the reactive oxygen species (ROS) content and apoptosis rate. Protein levels were determined via Western blotting. Pretreatment with SYI significantly reduced infarct size and pathological damage in rat hearts and suppressed cardiomyocyte apoptosis in vivo and in vitro. In addition, SYI inhibited oxidative stress by increasing SOD activity and decreasing MDA content and ROS production. Myocardial I/R and OGD/R activate endoplasmic reticulum (ER) stress, as evidenced by increased expression of activating transcription factor 6 (ATF6), glucose-regulated protein 78 (GRP78), cysteinyl aspartate-specific proteinase caspase-12, and C/EBP-homologous protein (CHOP), which were all inhibited by SYI. SYI ameliorated myocardial I/R injury by attenuating apoptosis, oxidative damage, and ER stress, which revealed new mechanistic insights into its application.

Predicting Drugs Suspected of Causing Adverse Drug Reactions Using Graph Features and Attention Mechanisms.

BACKGROUND: Adverse drug reactions (ADRs) refer to an unintended harmful reaction that occurs after the administration of a medication for therapeutic purposes, which is unrelated to the intended pharmacological action of the drug. In the United States, ADRs account for 6% of all hospital admissions annually. The cost of ADR-related illnesses in 2016 was estimated at USD 528.4 billion. Increasing the awareness of ADRs is an effective measure to prevent them. Assessing suspected drugs in adverse events helps to enhance the awareness of ADRs. METHODS: In this study, a suspect drug assisted judgment model (SDAJM) is designed to identify suspected drugs in adverse events. This framework utilizes the graph isomorphism network (GIN) and an attention mechanism to extract features based on patients' demographic information, drug information, and ADR information. RESULTS: By comparing it with other models, the results of various tests show that this model performs well in predicting the suspected drugs in adverse reaction events. ADR signal detection was conducted on a group of cardiovascular system drugs, and case analyses were performed on two classic drugs, Mexiletine and Captopril, as well as on two classic antithyroid drugs. The results indicate that the model can accomplish the task of predicting drug ADRs. Validation using benchmark datasets from ten drug discovery domains shows that the model is applicable to classification tasks on the Tox21 and SIDER datasets. CONCLUSIONS: This study applies deep learning methods to construct the SDAJM model for three purposes: (1) identifying drugs suspected to cause adverse drug events (ADEs), (2) predicting the ADRs of drugs, and (3) other drug discovery tasks. The results indicate that this method can offer new directions for research in the field of ADRs.

Phase I/II Clinical Study of PRaG Regimen Combined With Intraperitoneal Infusion of PD-1 Inhibitor for Advanced Refractory Solid Tumors With Cancerous Ascites (PRaG4.0P Study).

Objective: The prognosis of malignant tumors with peritoneal metastases and cancerous ascites has generally been poor, with limited treatment options. The PRaG regimen, which comprised of hypofractionated radiotherapy, programmed cell death-1 (PD-1) inhibitor, and granulocyte-macrophage colony-stimulating factor (GM-CSF), showed a survival advantage in patients with advanced solid tumors who failed at least the first line of standard systemic treatment. Intraperitoneal infusion of PD-1 inhibitors may be a novel therapeutic strategy for managing malignant ascites. Integrating the PRaG regimen with intraperitoneal perfusion of a PD-1 inhibitor might control malignant ascites and provide further survival benefits in these patients. This proposed study aims to investigate the safety and efficacy of intraperitoneal infusion of serplulimab in combination with the PRaG regimen in patients with simultaneous advanced solid tumors and cancerous ascites who fail at least the first-line treatment. Methods: This proposed study is a prospective, single-arm, open-label, multicenter clinical trial. All eligible patients will receive 2 cycles of intensive treatment, a combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor. The patients who are beneficially treated with intensive treatment will receive consolidation treatment every 2 weeks until ascites disappear, disease progression occurs, intolerable toxicity occurs, or for up to 1 year. Phase I of this study will be conducted using a modified 3 + 3 design. The dose of intraperitoneal infusion of PD-1 inhibitor for phase II will be determined according to dose-limiting toxicity evaluation in the phase I study. Conclusion: This prospective, open-label, multicenter study will potentially lead to intraperitoneal perfusion of a PD-1 inhibitor being a new strategy for malignant ascites patients and provide a meaningful efficacy and safety of the combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor for these patients.

Uncovering the Interaction between TRAF1 and MAVS in the RIG-I Pathway to Enhance the Upregulation of IRF1/ISG15 during Classical Swine Fever Virus Infection.

Classical swine fever (CSF) is caused by the classical swine fever virus (CSFV), which poses a threat to swine production. The activation of host innate immunity through linker proteins such as tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) is crucial for the induction of the NF-κB pathway. Recent research has revealed the involvement of mitochondrial antiviral-signaling protein (MAVS) in the interaction with TRAF2, 3, 5, and 6 to activate both the NF-κB and IRF3 pathways. This study revealed that CSFV infection led to the upregulation of TRAF1 mRNA and protein levels; moreover, TRAF1 overexpression inhibited CSFV replication, while TRAF1 knockdown promoted replication, highlighting its importance in the host response to CSFV infection. Additionally, the expression of RIG-I, MAVS, TRAF1, IRF1, and ISG15 were detected in PK-15 cells infected with CSFV, revealing that TRAF1 plays a role in regulating IRF1 and ISG15 within the RIG-I pathway. Furthermore, Co-IP, GST pull-down, and IFA analyses demonstrated that TRAF1 interacted with MAVS and co-localized in the cytoplasm during CSFV infection. Ultimately, TRAF1 acted as a novel member of the TRAF family, bound to MAVS as a linker molecule, and functioned as a mediator downstream of MAVS in the RIG-I/MAVS pathway against CSFV replication.

Detection of zearalenone in miscellaneous beans by functionalized SERS sensor based on sea urchin aptamer.

In this work, a sea urchin gold nanoparticles-zearalenone aptamer- tetramethylrhodamine sensor was constructed. Sea urchin gold nanoparticles, prepared using the seed-mediated growth method, were used as Raman substrates. Nucleic acid aptamers were mainly used as specific recognition molecules. Zearalenone detection in miscellaneous beans was accomplished using the principle of conformational change in aptamer. In addition, we evaluated the linear range, sensitivity, and selectivity of our sensor. We observed that at the displacement of 814 cm-1, for Zearalenone concentrations of 0.01-60 ng/mL, the Raman signal intensity linearly correlated with the zearalenone concentration, with a limit of detection of 0.01 ng/mL, and recoveries of 91.7% to 108.3%. The optimum detection time was 30 min. Thus, our sensor exhibited great potential in zearalenone detection in food products.

WITHDRAWN: Coronary artery segmentation based on ACMA-Net and unscented Kalman filter algorithm.

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Daphnetin Ameliorates Neuropathic Pain via Regulation of Microglial Responses and Glycerophospholipid Metabolism in the Spinal Cord.

Neuropathic pain (NP) is a common type of chronic pain caused by a lesion or disease of the somatosensory nervous system. This condition imposes a considerable economic burden on society and patients. Daphnetin (DAP) is a natural product isolated from a Chinese medicinal herb with various pharmacological activities, such as anti-inflammatory and analgesic properties. However, the underlying mechanisms of these effects are not fully understood. In the present study, we aimed to investigate DAP's anti-inflammatory and analgesic effects and explore the underlying mechanisms of action. The NP model was established as chronic constrictive injury (CCI) of the sciatic nerve, and pain sensitivity was evaluated by measuring the mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT). The activation of microglia in the spinal dorsal horn was measured via immunofluorescence staining. Protein levels were measured using a western blot assay. Using a mass-spectrometry proteomics platform and an LC-MS/MS-based metabolomics platform, proteins and metabolites in spinal cord tissues were extracted and analyzed. DAP treatment ameliorated the MWT and TWT in CCI rats. The expression of IL-1ß, IL-6, and TNF-α was inhibited by DAP treatment in the spinal cords of CCI rats. Moreover, the activation of microglia was suppressed after DAP treatment. The elevation in the levels of P2X4, IRF8, IRF5, BDNF, and p-P38/P38 in the spinal cord caused by CCI was inhibited by DAP. Proteomics and metabolomics results indicated that DAP ameliorated the imbalance of glycerophospholipid metabolism in the spinal cords of CCI rats. DAP can potentially ameliorate NP by regulating microglial responses and glycerophospholipid metabolism in the CCI model. This study provides a pharmacological justification for using DAP in the management of NP.

Integrating GWAS, RNA-Seq and functional analysis revealed that BnaA02.SE mediates silique elongation by affecting cell proliferation and expansion in Brassica napus.

Rapeseed (Brassica napus) silique is the major carbohydrate source for seed development, and the final silique length has attracted great attention from breeders. However, no studies had focused on the dynamic character of silique elongation length (SEL). Here, the dynamic SEL investigation in a natural population including 588 lines over two years indicate that dynamic SEL during 0-20 days after flowering was the most essential stage associated with seed number per silique (SPS) and thousand seed weight (TSW). Then, nine loci were identified to be associated with SEL based on GWAS analysis, among which five SNPs (over 50%) distributed on the A02 chromosome within 6.08 to 6.48 Mb. Subsequently, we screened 5078 differentially expressed genes between two extreme materials. An unknown protein, BnaA02.SE, was identified combining with GWAS and RNA-Seq analysis. Subcellular localization and expression profiles analysis demonstrated that BnaA02.SE is a chloroplast- and nucleus-localized protein mainly expressed in pericarps and leaves. Furthermore, transgenic verification and dynamic cytological observation reveal that overexpressed BnaA02.SE can promote silique elongation by regulating JA and IAA contents, affecting cell proliferation and expansion, respectively, and finally enhance seed yield by influencing SPS and TSW. Haplotype analysis reveal that the homologs of BnaA02.SE may also be involved in silique elongation regulation. Our findings provided comprehensive insights into a newly SEL trait, and cloned the first gene (BnaA02.SE) controlling silique elongation in B. napus. The identified BnaA02.SE and its homologs can offer a valuable target for improving B. napus yield.

Uptake of gadolinium and dexamethasone in rat inner ear and facial nerve using different administrations.

BACKGROUND: The pathway by which drugs are injected subcutaneously behind the ear to act on the inner ear has not been fully elucidated. OBJECTIVES: To compare the uptake of gadopentetate dimeglumine (Gd-DTPA) and dexamethasone (Dex) in the cochlea and facial nerve of rats following different administrations. MATERIALS AND METHODS: Magnetic resonance imaging was applied to observe the distribution of Gd-DTPA in the facial nerve and inner ear. We observed the uptake of Dex after it was injected with different methods. RESULTS: Images of the intravenous (IV) and intramuscular (IM) groups showed that the bilateral cochlea of the rat was visualized almost simultaneously. While in the left post-auricular (PA) injection group, it was asynchronous. The maximum accumulation (Cmax) of the Gd in the left facial nerve of the PA group (35.406 ± 5.32) was substantially higher than that of the IV group (16.765 ± 3.7542) (p < .01). CONCLUSIONS: Compared with systemic administration, PA has the advantages of long Gd and Dex action time and high accumulation concentration to treat facial nerve diseases. SIGNIFICANCE: The distribution of Gd and Dex in the inner ear and facial nerve of rats following PA injection might be unique.

Local Mechanical Modulation-Driven Evagination in Invaginated Epithelia.

Local cells can actively create reverse bending (evagination) in invaginated epithelia, which plays a crucial role in the formation of elaborate organisms. However, the precise physical mechanism driving the evagination remains elusive. Here, we present a three-dimensional vertex model, incorporating the intrinsic cell polarity, to explore the complex morphogenesis induced by local mechanical modulations. We find that invaginated tissues can spontaneously generate local reverse bending due to the shift of the apicobasal polarity. Their exact shapes can be analytically determined by the local apicobasal differential tension and the internal stress. Our continuum theory exhibits three regions in a phase diagram controlled by these two parameters, showing curvature transitions from ordered to disordered states. Additionally, we delve into epithelial curvature transition induced by the nucleus repositioning, revealing its active contribution to the apicobasal force generation. The uncovered mechanical principles could potentially guide more studies on epithelial folding in diverse systems.

The relationship between splenic dose and radiation-induced lymphopenia.

Lymphocytes, which are highly sensitive to radiation, play a crucial role in the body's defense against tumors. Radiation-induced lymphopenia has been associated with poorer outcomes in different cancer types. Despite being the largest secondary lymphoid organ, the spleen has not been officially designated as an organ at risk. This study hypothesizes a connection between spleen irradiation and lymphopenia and seeks to establish evidence-based dosage limits for the spleen. We retrospectively analyzed data from 96 patients with locally advanced gastric cancer who received postoperative chemoradiotherapy (CRT) between May 2010 and May 2017. Complete blood counts were collected before, during and after CRT. We established a model for predicting the minimum absolute lymphocyte count (Min ALC) and to investigate potential associations between spleen dosimetric variables and Min ALC. The median follow-up was 60 months. The 5-year overall survival (OS) and disease-free survival (DFS) were 65.2% and 56.8%, respectively. The median values of pre-treatment ALC, Min ALC and post-treatment ALC were 1.40 × 109, 0.23 × 109 and 0.28 × 109/L, respectively. Regression analysis confirmed that the primary tumor location, number of fractions and spleen V5 were significant predictors of Min ALC during radiation therapy. Changes in ALC (ΔALC) were identified as an independent predictor of both OS and DFS. Spleen V5 is an independent predictor for Min ALC, and the maximum dose of the spleen is associated with an increased risk of severe lymphopenia. Therefore, these doses should be restricted in clinical practice. Additionally, ΔALC can serve as a prognostic indicator for adjuvant radiotherapy in gastric cancer.