Cep131-Cep162 and Cby-Fam92 complexes cooperatively maintain Cep290 at the basal body and contribute to ciliogenesis initiation.

Cilia play critical roles in cell signal transduction and organ development. Defects in cilia function result in a variety of genetic disorders. Cep290 is an evolutionarily conserved ciliopathy protein that bridges the ciliary membrane and axoneme at the basal body (BB) and plays critical roles in the initiation of ciliogenesis and TZ assembly. How Cep290 is maintained at BB and whether axonemal and ciliary membrane localized cues converge to determine the localization of Cep290 remain unknown. Here, we report that the Cep131-Cep162 module near the axoneme and the Cby-Fam92 module close to the membrane synergistically control the BB localization of Cep290 and the subsequent initiation of ciliogenesis in Drosophila. Concurrent deletion of any protein of the Cep131-Cep162 module and of the Cby-Fam92 module leads to a complete loss of Cep290 from BB and blocks ciliogenesis at its initiation stage. Our results reveal that the first step of ciliogenesis strictly depends on cooperative and retroactive interactions between Cep131-Cep162, Cby-Fam92 and Cep290, which may contribute to the complex pathogenesis of Cep290-related ciliopathies.

Gp130-HIF1α axis-induced vascular damage is prevented by the short-term inhibition of IL-6 receptor signaling.

Protection against endothelial damage is recognized as a frontline approach to preventing the progression of cytokine release syndrome (CRS). Accumulating evidence has demonstrated that interleukin-6 (IL-6) promotes vascular endothelial damage during CRS, although the molecular mechanisms remain to be fully elucidated. Targeting IL-6 receptor signaling delays CRS progression; however, current options are limited by persistent inhibition of the immune system. Here, we show that endothelial IL-6 trans-signaling promoted vascular damage and inflammatory responses via hypoxia-inducible factor-1α (HIF1α)-induced glycolysis. Using pharmacological inhibitors targeting HIF1α activity or mice with the genetic ablation of gp130 in the endothelium, we found that inhibition of IL-6R (IL-6 receptor)-HIF1α signaling in endothelial cells protected against vascular injury caused by septic damage and provided survival benefit in a mouse model of sepsis. In addition, we developed a short half-life anti-IL-6R antibody (silent anti-IL-6R antibody) and found that it was highly effective at augmenting survival for sepsis and severe burn by strengthening the endothelial glycocalyx and reducing cytokine storm, and vascular leakage. Together, our data advance the role of endothelial IL-6 trans-signaling in the progression of CRS and indicate a potential therapeutic approach for burns and sepsis.

3D reconstruction and multi-omics analysis reveal a unique pattern of embryogenesis in Ginkgo biloba.

Ginkgo (Ginkgo biloba L.) is one of the earliest extant species in seed plant phylogeny. Embryo development patterns can provide fundamental evidence for the origin, evolution, and adaptation of seeds. However, the architectural and morphological dynamics during embryogenesis in Ginkgo biloba (G. biloba) remain elusive. Herein, we obtained over 2200 visual slices from three stages of embryo development using micro-computed tomography imaging with improved staining methods. Based on 3D spatio-temporal pattern analysis, we found that a shoot apical meristem with seven highly differentiated leaf primordia, including apical and axillary leaf buds, is present in mature Ginkgo embryos. 3D rendering from the front, top, and side views showed two separate transport systems of tracheids located in the hypocotyl and cotyledon, representing a unique pattern of embryogenesis. Furthermore, the morphological dynamic analysis of secretory cavities indicated their strong association with cotyledons during development. In addition, we identified genes GbLBD25a (lateral organ boundaries domain 25a), GbCESA2a (cellulose synthase 2a), GbMYB74c (myeloblastosis 74c), GbPIN2 (PIN-FORMED 2) associated with vascular development regulation, and GbWRKY1 (WRKYGOK 1), GbbHLH12a (basic helix-loop-helix 12a), GbJAZ4 (jasmonate zim-domain 4) potentially involved in the formation of secretory cavities. Moreover, we found that flavonoid accumulation in mature embryos could enhance post-germinative growth and seedling establishment in harsh environments. Our 3D spatial reconstruction technique combined with multi-omics analysis opens avenues for investigating developmental architecture and molecular mechanisms during embryogenesis and lays the foundation for evolutionary studies of embryo development and maturation.

Study on the involvement of microglial S100A8 in neuroinflammation and microglia activation during migraine attacks.

BACKGROUND: Microglia is the primary source of inflammatory factors during migraine attacks. This study aims to investigate the role of microglia related genes (MRGs) in migraine attacks. METHODS: The RNA sequencing results of migraineurs and the panglaodb database were used to obtain differentially expressed genes (DEGs) in migraine related to microglia. A migraine rat model was established for validating and localizing of the MRGs, and subsequent screening for target genes was conducted. A shRNA was designed to interference the expression of target genes and administered into the trigeminal ganglion (TG) of rats. Pain sensitivity in rats was evaluated via the hot water tail-flick (HWTF) and formalin-induced pain (FIP) experiments. ELISA was used to quantify the levels of inflammatory cytokines and CGRP. WB and immunofluorescence assays were applied to detect the activation of microglia. RESULTS: A total of five DEGs in migraine related to microglia were obtained from RNA sequencing and panglaodb database. Animal experiments showed that these genes expression were heightened in the TG and medulla oblongata (MO) of migraine rats. The gene S100A8 co-localized with microglia in both TG and MO. The HWTF and FIP experiments demonstrated that interference with S100A8 alleviated the sense of pain in migraine rats. Moreover, the levels of TNFα, IL-1ß, IL-6, and CGRP in the TG and MO of rats in the model rats were increased, and the expression of microglia markers IBA-1, M1 polarization markers CD86 and iNOS was upregulated. Significantly, interference with S100A8 reversed these indicators. CONCLUSION: Interference with S100A8 in microglia increased the pain threshold during migraine attacks, and inhibited neuroinflammation and microglia activation.

Altered counts and mitochondrial mass of peripheral blood leucocytes in patients with chronic hepatitis B virus infection.

Hepatitis B virus (HBV) damages liver cells through abnormal immune responses. Mitochondrial metabolism is necessary for effector functions of white blood cells (WBCs). The aim was to investigate the altered counts and mitochondrial mass (MM) of WBCs by two novel indicators of mitochondrial mass, MM and percentage of low mitochondrial membrane potential, MMPlow%, due to chronic HBV infection. The counts of lymphocytes, neutrophils and monocytes in the HBV infection group were in decline, especially for lymphocyte (p = 0.034) and monocyte counts (p = 0.003). The degraded MM (p = 0.003) and MMPlow% (p = 0.002) of lymphocytes and MM (p = 0.005) of monocytes suggested mitochondrial dysfunction of WBCs. HBV DNA within WBCs showed an extensive effect on mitochondria metabolic potential of lymphocytes, neutrophils and monocytes indicated by MM; hepatitis B e antigen was associated with instant mitochondrial energy supply indicated by MMPlow% of neutrophils; hepatitis B surface antigen, antiviral therapy by nucleos(t)ide analogues and prolonged infection were also vital factors contributing to WBC alterations. Moreover, degraded neutrophils and monocytes could be used to monitor immune responses reflecting chronic liver fibrosis and inflammatory damage. In conclusion, MM combined with cell counts of WBCs could profoundly reflect WBC alterations for monitoring chronic HBV infection. Moreover, HBV DNA within WBCs may be a vital factor in injuring mitochondria metabolic potential.

Effects of paclobutrazol seed priming on seedling quality, photosynthesis, and physiological characteristics of fragrant rice.

BACKGROUND: Paclobutrazol is widely used in the agricultural field. This study investigated the effects of seed priming with different concentrations of paclobutrazol on seedling quality, 2-acetyl-1-pyrroline (2-AP, a key aroma component of fragrant rice) biosynthesis, and related physiological and biochemical indicators in fragrant rice seedlings. RESULTS: The experiment is being conducted at the College of Agriculture, South China Agricultural University. In the experiment, three concentrations of paclobutrazol (Pac 1: 20 mg·L-1; Pac 2: 40 mg·L-1; Pac 3: 80 mg·L-1) were used to initiate the treatment of fragrant rice seeds, while water treatment was used as a control (CK). The results showed that compared with CK, paclobutrazol treatment reduced plant height, increased stem diameter, and increased fresh and dry weight of aromatic rice seedlings. Moreover, paclobutrazol treatment also increased the seedlings' photosynthetic pigment content and net photosynthetic rate. CONCLUSIONS: This study demonstrates that paclobutrazol primarily increases the content of proline by reducing the content of glutamate and down-regulating the expression of P5CS2, thereby promoting the conversion of proline to the aromatic substance 2-AP. Under the appropriate concentration of paclobutrazol (40 mg·L-1~80 mg·L-1), the seedling quality, stress resistance, and aroma of fragrant rice can be improved.

UV Light-Mediated Hydrolytic Reaction to Develop Magnetic Hydrogel Actuators with Spatially Distributed Ferriferous Oxide Microparticles.

Magnetic hydrogel actuators are developed by incorporating magnetic fillers into the hydrogel matrix. Regulating the distribution of these fillers is key to the exhibited functionalities but is still challenging. Here a facile way to spatially synthesize ferrosoferric oxide (Fe3O4) microparticles in situ in a thermal-responsive hydrogel is reported. This method involves the photo-reduction of Fe3+ ions coordinated with carboxylate groups in polymer chains, and the hydrolytic reaction of the reduced Fe2+ ions with residual Fe3+ ions. By controlling the irradiation time and position, the concentration of Fe3O4 microparticles can be spatially controlled, and the resulting Fe3O4 pattern enables the hydrogel to exhibit complex locomotion driven by magnet, temperature, and NIR light. This method is convenient and extendable to other hydrogel systems to realize more complicated magneto-responsive functionalities.

Growth of 1D Carbon Nanotube@Perovskite Core-Shell van der Waals Heterostructures through Chemical Vapor Deposition.

Perovskite is an emerging material with immense potential in the field of optoelectronics. 1D perovskite nanowires are crucial building blocks for the development of optoelectronic devices. However, producing perovskite nanowires with high quality and controlled alignment is challenging. In this study, the direct epitaxial growth of perovskite on oriented carbon nanotube (CNT) templates is presented through a chemical vapor deposition method. The deposition process of lead iodide and methylammonium iodide is systematically investigated, and a layer plus island growth mechanism is proposed to interpret the experimental observations. The aligned long CNTs serve as 1D templates and allow the growth of CNT@perovskite core-shell heterostructure with a high aspect ratio to withstand large deformation. The obtained 1D perovskite materials can be easily manipulated and transferred, enabling the facile preparation of microscale flexible devices. For proof of concept, a photodetector based on an individual CNT@methylammonium lead iodide heterostructure is fabricated. This work provides a new approach to prepare 1D hetero-nanostructure and may inspire the design of novel flexible nanophotodetectors.

Full-Color "Off-On" Thermochromic Fluorescent Fibers for Customizable Smart Wearable Displays in Personal Health Monitoring.

Responsive thermochromic fiber materials capable of miniaturization and integrating comfortably and compliantly onto the soft and dynamically deforming human body are promising materials for visualized personal health monitoring. However, their development is hindered by monotonous colors, low-contrast color changes, and poor reversibility. Herein, full-color "off-on" thermochromic fluorescent fibers are prepared based on self-crystallinity phase change and Förster resonance energy transfer for long-term and passive body-temperature monitoring, especially for various personalized customization purposes. The off-on switching luminescence characteristic is derived from the reversible conversion of the dispersion state and fluorescent emission by fluorophores and quencher molecules, which are embedded in the matrix of a phase-change material, during the crystallizing/melting processes. The achievement of full-color fluorescence is attributed to the large modulation range of fluorescence colors according to primary color additive theory. These thermochromic fluorescent fibers exhibit good mechanical properties, fluorescent emission contrast, and reversibility, showing their great potential in flexible smart display devices. Moreover, the response temperature of the thermochromic fibers is controllable by adjusting the phase-change material, enabling body-temperature-triggered luminescence; this property highlights their potential for human body-temperature monitoring and personalized customization. This work presents a new strategy for designing and exploring flexible sensors with higher comprehensive performances.

Altered interhemispheric functional connectivity in patients with obsessive-compulsive disorder and its potential in therapeutic response prediction.

The trajectory of voxel-mirrored homotopic connectivity (VMHC) after medical treatment in obsessive-compulsive disorder (OCD) and its value in prediction of treatment response remains unclear. This study aimed to investigate the pathophysiological mechanism of OCD, as well as biomarkers for prediction of pharmacological efficacy. Medication-free patients with OCD and healthy controls (HCs) underwent magnetic resonance imaging. The patients were scanned again after a 4-week treatment with paroxetine. The acquired data were subjected to VMHC, support vector regression (SVR), and correlation analyses. Compared with HCs (36 subjects), patients with OCD (34 subjects after excluding two subjects with excessive head movement) exhibited significantly lower VMHC in the bilateral superior parietal lobule (SPL), postcentral gyrus, and calcarine cortex, and VMHC in the postcentral gyrus was positively correlated with cognitive function. After treatment, the patients showed increased VMHC in the bilateral posterior cingulate cortex/precuneus (PCC/PCu) with the improvement of symptoms. SVR results showed that VMHC in the postcentral gyrus at baseline could aid to predict a change in the scores of OCD scales. This study revealed that SPL, postcentral gyrus, and calcarine cortex participate in the pathophysiological mechanism of OCD while PCC/PCu participate in the pharmacological mechanism. VMHC in the postcentral gyrus is a potential predictive biomarker of the treatment effects in OCD.

Bright solitons in a spin-orbit-coupled dipolar Bose-Einstein condensate trapped within a double-lattice.

By effectively controlling the dipole-dipole interaction, we investigate the characteristics of the ground state of bright solitons in a spin-orbit coupled dipolar Bose-Einstein condensate. The dipolar atoms are trapped within a double-lattice which consists of a linear and a nonlinear lattice. We derive the motion equations of the different spin components, taking the controlling mechanisms of the dipole-dipole interaction into account. An analytical expression of dipole-dipole interaction is derived. By adjusting the dipole polarization angle, the dipole interaction can be adjusted from attraction to repulsion. On this basis, we study the generation and manipulation of the bright solitons using both the analytical variational method and numerical imaginary time evolution. The stability of the bright solitons is also analyzed and we map out the stability phase diagram. By adjusting the long-range dipole-dipole interaction, one can achieve manipulation of bright solitons in all aspects, including the existence, width, nodes, and stability. Considering the complexity of our system, our results will have enormous potential applications in quantum simulation of complex systems.

Real-imaginary spectrum decomposition of the transparency spectra in microwave dressed Rydberg systems.

To distinguish the contributions of electromagnetically induced transparency (EIT) and Autler-Townes splitting (ATS) in their applications in precision laser spectroscopy, we propose a real-imaginary spectrum decomposition method to investigate the transparency spectra in a four-level microwave (MW) dressed Rydberg system. We show that the opening transparency windows in the absorption spectra of probe field is a prominent character by EIT, EIT-ATS crossover, and ATS when the MW field is turned off and the intensity of the control field is adjusted. When the MW field is turned on and gradually increased, the EIT is destroyed and disappears. In addition, the most prominent characters that open a transparency window are the EIT-ATS crossover and the ATS. Then, if we further increase the intensity of the MW field, we find that the transparency windows open mainly due to the ATS. Compared to the previous considerations of this issue, which were limited to three-level systems, our four-level scheme reported here is useful for understanding the features of quantum interference in multilevel atomic systems, and has potential applications to study enhanced sensitivity, measurement spectroscopic, quantum processing, quantum communication, and transmission.

Differentiation of granulomatous nodules with lobulation and spiculation signs from solid lung adenocarcinomas using a CT deep learning model.

BACKGROUND: The diagnosis of solitary pulmonary nodules has always been a difficult and important point in clinical research, especially granulomatous nodules (GNs) with lobulation and spiculation signs, which are easily misdiagnosed as malignant tumors. Therefore, in this study, we utilised a CT deep learning (DL) model to distinguish GNs with lobulation and spiculation signs from solid lung adenocarcinomas (LADCs), to improve the diagnostic accuracy of preoperative diagnosis. METHODS: 420 patients with pathologically confirmed GNs and LADCs from three medical institutions were retrospectively enrolled. The regions of interest in non-enhanced CT (NECT) and venous contrast-enhanced CT (VECT) were identified and labeled, and self-supervised labels were constructed. Cases from institution 1 were randomly divided into a training set (TS) and an internal validation set (IVS), and cases from institutions 2 and 3 were treated as an external validation set (EVS). Training and validation were performed using self-supervised transfer learning, and the results were compared with the radiologists' diagnoses. RESULTS: The DL model achieved good performance in distinguishing GNs and LADCs, with area under curve (AUC) values of 0.917, 0.876, and 0.896 in the IVS and 0.889, 0.879, and 0.881 in the EVS for NECT, VECT, and non-enhanced with venous contrast-enhanced CT (NEVECT) images, respectively. The AUCs of radiologists 1, 2, 3, and 4 were, respectively, 0.739, 0.783, 0.883, and 0.901 in the (IVS) and 0.760, 0.760, 0.841, and 0.844 in the EVS. CONCLUSIONS: A CT DL model showed great value for preoperative differentiation of GNs with lobulation and spiculation signs from solid LADCs, and its predictive performance was higher than that of radiologists.

Amide Proton Transfer-Weighted Magnetic Resonance Imaging for Application in Renal Fibrosis: A Radiological-Pathological-Based Analysis.

INTRODUCTION: Renal fibrosis (RF), being the most important pathological change in the progression of CKD, is currently assessed by the evaluation of a biopsy. This present study aimed to apply a novel functional MRI (fMRI) protocol named amide proton transfer (APT) weighting to evaluate RF noninvasively. METHODS: Male Sprague-Dawley (SD) rats were initially subjected to bilateral kidney ischemia/reperfusion injury (IRI), unilateral ureteral obstruction, and sham operation, respectively. All rats underwent APT mapping on the 7th and 14th days after operation. Besides, 26 patients underwent renal biopsy at the Nephrology Department of Shanghai Tongji Hospital between July 2022 and May 2023. Patients underwent APT and apparent diffusion coefficient (ADC) mappings within 1 week before biopsy. MRI results of both patients and rats were calculated by comparing with gold standard histology for fibrosis assessment. RESULTS: In animal models, the cortical APT (cAPT) and medullary APT (mAPT) values were positively correlated with the degree of RF. Compared to the sham group, IRI group showed significantly increased cAPT and mAPT values on the 7th and 14th days after surgery, but no group differences were found in ADC values. Similar results were found in human patients. Cortical/medullary APT values were significantly increased in patients with moderate-to-severe fibrosis than in patients with mild fibrosis. ROC curve analysis indicated that APT value displayed a better diagnostic value for RF. Furthermore, combination of cADC and cAPT improved fibrosis detection by imaging variables alone (p < 0.1). CONCLUSION: APT values had better diagnostic capability at early stage of RF compared to ADC values, and the addition of APT imaging to conventional ADC will significantly improve the diagnostic performance for predicting kidney fibrosis.

Development of an ELISA with acidification treatment for an antibody conjugate incorporating Exatecans.

The successful development of Sacituzumab Govitecan and Trastuzumab Deruxtecan has made camptothecin derivatives one of the most popular payloads for antibody-drug conjugates (ADCs). Camptothecin and its derivatives all exist in a pH-dependent equilibrium between the carboxylate and lactone forms. Such transformation may lead to differences in the ratio of the two molecular forms in calibration standards and biological matrix (bio-matrix) samples, thereby leading to inaccurate conjugated antibody results. In this study, we reported an enzyme-linked immunosorbent assay (ELISA) free of the aforementioned influence for the detection of the Exatecans-conjugated antibody (conjugated SM001) in cynomolgus monkey serum. The assay was developed by first acidifying all samples with glacial acetic acid (HAc), then performing neutralization and thereafter capturing conjugated SM001 with anti-Exatecan monoclonal antibody (mAb) and detecting it with biotinylated Nectin4 (hNectin4-Bio) and horseradish peroxidase-labeled streptavidin (SA-HRP). Results showed that all tested performance parameters met the acceptance criteria. The conjugated SM001 concentrations obtained were in parallel to but slightly lower than total antibody (TAb) throughout the pharmacokinetic (PK) study, revealing that the assay strategy implemented for conjugated SM001 measurement worked well for the elimination of interference triggered by the heterogeneous existence of the lactone and carboxylate forms of Exatecan (lactone-Exatecan and carboxylate-Exatecan).

Characterization of Retinal VIP-Amacrine Cell Development During the Critical Period.

Retinal vasoactive intestinal peptide amacrine cells (VIP-ACs) play an important role in various retinal light-mediated pathological processes related to different developmental ocular diseases and even mental disorders. It is important to characterize the developmental changes in VIP-ACs to further elucidate their mechanisms of circuit function. We bred VIP-Cre mice with Ai14 and Ai32 to specifically label retinal VIP-ACs. The VIP-AC soma and spine density generally increased, from postnatal day (P)0 to P35, reaching adult levels at P14 and P28, respectively. The VIP-AC soma density curve was different with the VIP-AC spine density curve. The total retinal VIP content reached a high level plateau at P14 but was decreased in adults. From P14 to P16, the resting membrane potential (RMP) became more negative, and the input resistance decreased. Cell membrane capacitance (MC) showed three peaks at P7, P12 and P16. The RMP and MC reached a stable level similar to the adult level at P18, whereas input resistance reached a stable level at P21. The percentage of sustained voltage-dependent potassium currents peaked at P16 and remained stable thereafter. The spontaneous excitatory postsynaptic current and spontaneous inhibitory postsynaptic current frequencies and amplitudes, as well as charge transfer, peaked at P12 to P16; however, there were also secondary peaks at different time points. In conclusion, we found that the second, third and fourth weeks after birth were important periods of VIP-AC development. Many developmental changes occurred around eye opening. The development of soma, dendrite and electrophysiological properties showed uneven dynamics of progression. Cell differentiation may contribute to soma development whereas the changes of different ion channels may play important role for spine development.

SRS 16-86 promotes diabetic nephropathy recovery by regulating ferroptosis.

Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM), and cell death plays an important role. Ferroptosis is a recently discovered type of iron-dependent cell death and one that is different from other kinds of cell death including apoptosis and necrosis. However, ferroptosis has not been described in the context of DN. This study explored the role of ferroptosis in DN pathophysiology and aimed to confirm the efficacy of the ferroptosis inhibitor SRS 16-86 on DN. Streptozotocin injection was used to establish the DM and DN animal models. To investigate the presence or occurrence of ferroptosis in DN, we assessed the concentrations of iron, reactive oxygen species and specific markers associated with ferroptosis in a rat model of DN. Additionally, we performed haematoxylin-eosin staining, blood biochemistry, urine biochemistry and kidney function analysis to evaluate the efficacy of the ferroptosis inhibitor SRS 16-86 in ameliorating DN. We found that SRS 16-86 could improve the recovery of renal function after DN by upregulating glutathione peroxidase 4, glutathione and system xc -light chain and by downregulating the lipid peroxidation markers and 4-hydroxynonenal. SRS 16-86 treatment could improve renal organization after DN. The inflammatory cytokines interleukin 1ß and tumour necrosis factor α and intercellular adhesion molecule 1 were significantly decreased following SRS 16-86 treatment after DN. The results indicate that there is a strong connection between ferroptosis and the pathological mechanism of DN. The efficacy of the ferroptosis inhibitor SRS 16-86 in DN repair supports its use as a new therapeutic treatment for DN.

Sequential delivery of photosensitizers and checkpoint inhibitors by engineered bacteria for enhanced cancer photodynamic immunotherapy.

Engineered bacteria-based cancer therapy has increasingly been considered to be a promising therapeutic strategy due to the development of synthetic biology. Wherein, engineering bacteria-mediated photodynamic therapy (PDT)-immunotherapy shows greater advantages and potential in treatment efficiency than monotherapy. However, the unsustainable regeneration of photosensitizers (PSs) and weak immune responses limit the therapeutic efficiency. Herein, we developed an engineered bacteria-based delivery system for sequential delivery of PSs and checkpoint inhibitors in cancer PDT-immunotherapy. The biosynthetic pathway of 5-aminolevulinic acid (5-ALA) was introduced into Escherichia coli, yielding a supernatant concentration of 172.19 mg/L after 10 h of growth. And another strain was endowed with the light-controllable releasement of anti-programmed cell death-ligand 1 nanobodies (anti-PD-L1). This system exhibited a collaborative effect, where PDT initiated tumor cell death and the released tumor cell fragments stimulated immunity, followed by the elimination of residual tumor cells. The tumor inhibition rate reached 74.97%, and the portion of activated T cells and inflammatory cytokines were reinforced. The results demonstrated that the engineered bacteria-based collaborative system could sequentially deliver therapeutic substance and checkpoint inhibitors, and achieve good therapeutic therapy. This paper will provide a new perspective for the cancer PDT-immunotherapy.

Effects of Positive End-expiratory Pressure on Pulmonary Perfusion Distribution and Intrapulmonary Shunt during One-lung Ventilation in Pigs: A Randomized Crossover Study.

BACKGROUND: During one-lung ventilation (OLV), positive end-expiratory pressure (PEEP) can improve lung aeration but might overdistend lung units and increase intrapulmonary shunt. The authors hypothesized that higher PEEP shifts pulmonary perfusion from the ventilated to the nonventilated lung, resulting in a U-shaped relationship with intrapulmonary shunt during OLV. METHODS: In nine anesthetized female pigs, a thoracotomy was performed and intravenous lipopolysaccharide infused to mimic the inflammatory response of thoracic surgery. Animals underwent OLV in supine position with PEEP of 0 cm H2O, 5 cm H2O, titrated to best respiratory system compliance, and 15 cm H2O (PEEP0, PEEP5, PEEPtitr, and PEEP15, respectively, 45 min each, Latin square sequence). Respiratory, hemodynamic, and gas exchange variables were measured. The distributions of perfusion and ventilation were determined by IV fluorescent microspheres and computed tomography, respectively. RESULTS: Compared to two-lung ventilation, the driving pressure increased with OLV, irrespective of the PEEP level. During OLV, cardiac output was lower at PEEP15 (5.5 ± 1.5 l/min) than PEEP0 (7.6 ± 3 l/min) and PEEP5 (7.4 ± 2.9 l/min; P = 0.004), while the intrapulmonary shunt was highest at PEEP0 (PEEP0: 48.1% ± 14.4%; PEEP5: 42.4% ± 14.8%; PEEPtitr: 37.8% ± 11.0%; PEEP15: 39.0% ± 10.7%; P = 0.027). The relative perfusion of the ventilated lung did not differ among PEEP levels (PEEP0: 65.0% ± 10.6%; PEEP5: 68.7% ± 8.7%; PEEPtitr: 68.2% ± 10.5%; PEEP15: 58.4% ± 12.8%; P = 0.096), but the centers of relative perfusion and ventilation in the ventilated lung shifted from ventral to dorsal and from cranial to caudal zones with increasing PEEP. CONCLUSIONS: In this experimental model of thoracic surgery, higher PEEP during OLV did not shift the perfusion from the ventilated to the nonventilated lung, thus not increasing intrapulmonary shunt.

Modelling of the in-stent thrombus formation by dissipative particle dynamics.

BACKGROUND: Stent implantation is a highly efficacious intervention for the treatment of coronary atherosclerosis. Nevertheless, stent thrombosis and other post-operative complications persist, and the underlying mechanism of adverse event remains elusive. METHODS: In the present study, a dissipative particle dynamics model was formulated to simulate the motion, adhesion, activation, and aggregation of platelets, with the aim of elucidating the mechanisms of in-stent thrombosis. FINDINGS: The findings suggest that stent thrombosis arises from a complex interplay of multiple factors, including endothelial injury resulting from stent implantation and alterations in the hemodynamic milieu. Furthermore, the results suggest a noteworthy association between in-stent thrombosis and both the length of the endothelial injured site and the degree of stent malposition. Specifically, the incidence of stent thrombosis appears to rise in tandem with the extent of the injured site, while moderate stent malposition is more likely to result in in-stent thrombosis compared to severe or minor malposition. INTERPRETATION: This study offers novel research avenues for investigating the plasticity mechanism of stent thrombosis, while also facilitating the clinical prediction of stent thrombosis formation and the development of more precise treatment strategies.