Endothelial lincRNA-p21 alleviates cerebral ischemia/reperfusion injury by maintaining blood-brain barrier integrity.

Blood-brain barrier (BBB) disruption is increasingly recognized as an early contributor to the pathophysiology of cerebral ischemia/reperfusion (I/R) injury, and is also a key event in triggering secondary damage to the central nervous system. Recently, long non-coding RNA (lncRNA) have been found to be associated with ischemic stroke. However, the roles of lncRNA in BBB homeostasis remain largely unknown. Here, we report that long intergenic non-coding RNA-p21 (lincRNA-p21) was the most significantly down-regulated lncRNA in human brain microvascular endothelial cells (HBMECs) after oxygen and glucose deprivation/reoxygenation (OGD/R) treatment among candidate lncRNA, which were both sensitive to hypoxia and involved in atherosclerosis. Exogenous brain-endothelium-specific overexpression of lincRNA-p21 could alleviate BBB disruption, diminish infarction volume and attenuate motor function deficits in middle cerebral artery occlusion/reperfusion (MCAO/R) mice. Further results showed that lincRNA-p21 was critical to maintain BBB integrity by inhibiting the degradation of junction proteins under MCAO/R and OGD/R conditions. Specifically, lincRNA-p21 could inhibit autophagy-dependent degradation of occludin by activating PI3K/AKT/mTOR signaling pathway. Besides, lincRNA-p21 could inhibit VE-cadherin degradation by binding with miR-101-3p. Together, we identify that lincRNA-p21 is critical for BBB integrity maintenance, and endothelial lincRNA-p21 overexpression could alleviate cerebral I/R injury in mice, pointing to a potential strategy to treat cerebral I/R injury.

Biomarker-driven targeted therapy in patients with recurrent platinum-resistant epithelial ovarian cancer (BRIGHT): protocol for an open-label, multicenter, umbrella study.

BACKGROUND: Platinum-resistant, recurrent ovarian cancer has an abysmal prognosis with limited treatment options. Poly-(ADP-ribose)-polymerase (PARP), angiogenesis, and immune checkpoint inhibitors might improve the outcomes of platinum-resistant, recurrent ovarian cancer, but accurate patient selections for those therapies remain a significant clinical challenge. PRIMARY OBJECTIVE: To evaluate the efficacy and safety of biomarker-driven combinatorial therapies of pamiparib, tislelizumab, bevacizumab, and nab-paclitaxel in platinum-resistant, recurrent ovarian cancer. STUDY HYPOTHESIS: A precision medicine combination of PARP inhibitors, anti-angiogenic therapy, immunotherapy, and chemotherapy will improve disease outcomes of platinum-resistant, recurrent ovarian cancer by accounting for genomic and immunologic features. TRIAL DESIGN: The BRIGHT Trial is a prospective, open-label, multicenter, phase II, umbrella study planning to enroll 160 patients with serous, endometrioid, or clear cell platinum-resistant, recurrent ovarian cancer from 11 clinical centers in China. Patients are assigned to one of three experimental arms based on biomarkers. Patients with BRCA1/2 mutations will receive pamiparib plus bevacizumab (arm 1, n=40) regardless of CD8+ tumor-infiltrating lymphocytes count. Patients with wild-type BRCA1/2 (BRCAwt) and ≥3 CD8+ tumor-infiltrating lymphocytes count will receive the combination of tislelizumab, bevacizumab, and nab-paclitaxel (arm 2, n=50), while BRCAwt patients with <3 CD8+ tumor-infiltrating lymphocytes count will receive bevacizumab plus dose-dense nab-paclitaxel (arm 3, n=50). After completing patient enrollment in arm 2, another 20 BRCAwt patients with ≥3 CD8+ tumor-infiltrating lymphocytes count will be included as an arm 2 expansion. Treatment will continue until disease progression or intolerable toxicity, and all adverse events will be recorded. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients include those aged ≥18 with serous, endometrioid, or clear cell ovarian cancer, platinum-resistant recurrence, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. PRIMARY ENDPOINT: Objective response rate (ORR) assessed by the investigators by the RECIST 1.1 criteria. SAMPLE SIZE: 160 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Recruitment is estimated to be completed by 2024 and results may be published by 2027. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05044871.

Direct investigations of the effects of nicardipine on calcium channels of astrocytes by Atomic Force Microscopy.

Calcium channel blockers (CCB) of astrocytes can blockade the calcium ions entry through the voltage gated calcium channels (VGCC), and is widely used in the diseases related with VGCC of astrocytes. But many aspects of the interaction mechanisms between the CCB and VGCC of astrocytes still remain unclear due to the limited resolution of the approaches. Herein the effects of the nicardipine (a type of CCB) on VGCC of astrocytes were investigated at very high spatial, force and electrical resolution by multiple modes of Atomic Force Microscopy (AFM) directly. The results reveal that after the addition of nicardipine, the recognition signals of VGCC disappeared; the specific unbinding forces vanished; the conductivity of the astrocytes decreased (the current decreased about 2.9 pA and the capacitance was doubled); the surface potential of the astrocytes reduced about 14.2 mV. The results of electrical properties investigations are consistent with the simulation experiments. The relations between these biophysical and biochemical properties of VGCC have been discussed. All these demonstrate that the interactions between nicardipine and VGCC have been studied at nanometer spatial resolution, at picoNewton force resolution and very high electrical signal resolution (pA in current, pF in capacitance and 0.1 mV in surface potential) level. The approaches are considered to be high resolution and high sensitivity, and will be helpful and useful in the further investigations of the effects of other types of CCB on ion channels, and will also be helpful in the investigations of mechanisms and therapy of ion channelopathies.

Pembrolizumab in patients from China with microsatellite instability-high/mismatch repair deficient tumors: KEYNOTE-158.

Aim: To evaluate pembrolizumab in patients of Chinese descent with microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) tumors enrolled in KEYNOTE-158 (Cohort L). Methods: Patients with MSI-H/dMMR advanced tumors received pembrolizumab 200 mg IV Q3W. Primary end point was overall response rate (ORR). Secondary end points were duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results: 24 patients were enrolled (20 were evaluable for efficacy). With median follow-up of 12.4 months, the ORR was 70%. DOR, PFS and OS were all not reached. A total of 19 (79%) patients had a treatment-related adverse event (AE; grade ≥3 in 4 [17%]), and 8 (33%) had an immune-mediated AE (grade ≥3 in (4 [17%]). Conclusion: Pembrolizumab provided meaningful and durable responses with manageable safety. These results are consistent with those reported for the global trial.

Pyroptotic T cell-derived active IL-16 has a driving function in ovarian endometriosis development.

Endometriosis, affecting 6%-10% of women, often leads to pain and infertility and its underlying inflammatory mechanisms are poorly understood. We established endometriosis models in wild-type and IL16KO mice, revealing the driver function of IL-16 in initiating endometriosis-related inflammation. Using an in vitro system, we confirmed iron overload-induced GSDME-mediated pyroptosis as a key trigger for IL-16 activation and release. In addition, our research led to the development of Z30702029, a compound inhibiting GSDME-NTD-mediated pyroptosis, which shows promise as a therapeutic intervention for endometriosis. Importantly, our findings extend beyond endometriosis, highlighting GSDME-mediated pyroptosis as a broader pathway for IL-16 release and offering insights into potential treatments for various inflammatory conditions.

Two cases of driver death caused by airbag rupture.

OBJECTIVE: This article reports two accidents caused by defective Takata airbags ruptured, which led to the deaths of the drivers. This is the first public report on the deaths caused by Takata airbags in China. METHODS: Determine the relationship between the driver death and airbag rupture through autopsy indings and vehicle inspection. RESULTS: Due to defects in the design of Takata's inflator, moist air was permitted to slowly enter the inflator, resulting the PSAN slowly degraded physically. The damaged propellant burned more rapidly than intended and overpressurized the inflator's steel housing, causing fragmentation and flying debris at high speed, killing or injuring vehicle occupants. CONCLUSIONS: To date, there are still tens of millions of defective Takata airbags that have not been recalled for repair, posing safety risks. This article suggests taking preventive measures to avoid the occurrence of similar accidents.

Atomic force microscopy correlates mechanical and electrical properties of HepG2 cells with curcumin concentration.

Hepatocellular carcinoma (HCC) is a highly prevalent cancer with a significant impact on human health. Curcumin, a natural compound, induces cytoskeletal changes in liver cancer cells and modifies the distribution of lipids, proteins, and polysaccharides on plasma membranes, affecting their mechanical and electrical properties. In this study, we used nanomechanical indentation techniques and Kelvin probe force microscopy (KPFM) based on atomic force microscopy (AFM) to investigate the changes in surface nanomechanical and electrical properties of nuclear and cytoplasmic regions of HepG2 cells in response to increasing curcumin concentrations. CCK-8 assays and flow cytometry results demonstrated time- and concentration-dependent inhibition of HepG2 cell proliferation by curcumin. Increasing curcumin concentration led to an initial increase and then decrease in the mechanical properties of nuclear and cytoplasmic regions of HepG2 cells, represented by the Young's modulus (E), as observed through nanoindentation. KPFM measurements indicated decreasing trends in both cell surface potential and height. Fluorescence microscopy results indicated a positive correlation between curcumin concentration and phosphatidylserine translocation from the inner to the outer membrane, which influenced the electrical properties of HepG2 cells. This study provides valuable insights into curcumin's mechanisms against cancer cells and aids nanoscale evaluation of therapeutic efficacy and drug screening.

All-Photolithography Fabrication of Ion-Gated Flexible Organic Transistor Array for Multimode Neuromorphic Computing.

Organic ion-gated transistors (OIGTs) demonstrate commendable performance for versatile neuromorphic systems. However, due to the fragility of organic materials to organic solvents, efficient and reliable all-photolithography methods for scalable manufacturing of high-density OIGT arrays with multimode neuromorphic functions are still missing, especially when all active layers are patterned in high-density. Here, a flexible high-density (9662 devices per cm2 ) OIGT array with high yield and minimal device-to-device variation is fabricated by a modified all-photolithography method. The unencapsulated flexible array can withstand 1000 times' bending at a radius of 1 mm, and 3 months' storage test in air, without obvious performance degradation. More interesting, the OIGTs can be configured between volatile and nonvolatile modes, suitable for constructing reservoir computing systems to achieve high accuracy in classifying handwritten digits with low training costs. This work proposes a promising design of organic and flexible electronics for affordable neuromorphic systems, encompassing both array and algorithm aspects.

Monocytes Release Pro-Cathepsin D to Drive Blood-to-Brain Transcytosis in Diabetes.

BACKGROUND: Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined. METHODS: High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter. In vivo 2-photon imaging, behavioral tests, immunofluorescence, transmission electron microscopy, Western blot analysis, vascular leakage assay, and single-cell RNA sequencing were performed to clarify the phenotype and elucidate the molecular mechanism. RESULTS: Monocytes expressed high-level CTSD in patients with type 2 diabetes. The transgenic mice expressing human CTSD in the monocytes showed increased brain microvascular permeability resembling the diabetic microvascular phenotype, accompanied by cognitive deficit. Mechanistically, the monocytes release nonenzymatic pro-CTSD to upregulate caveolin expression in brain endothelium triggering caveolae-mediated transcytosis, without affecting the paracellular route of brain microvasculature. The circulating pro-CTSD activated the caveolae-mediated transcytosis in brain endothelial cells via its binding with low-density LRP1 (lipoprotein receptor-related protein 1). Importantly, genetic ablation of CTSD in the monocytes exhibited a protective effect against the diabetes-enhanced brain microvascular transcytosis and the diabetes-induced cognitive impairment. CONCLUSIONS: These findings uncover the novel role of circulatory pro-CTSD from monocytes in the pathogenesis of cerebral microvascular lesions in diabetes. The circulatory pro-CTSD is a potential target for the intervention of microvascular complications in diabetes.

Therapeutic potential of dihydroartemisinin in mitigating radiation-induced lung injury: Inhibition of ferroptosis through Nrf2/HO-1 pathways in mice.

BACKGROUND: Radiation-induced lung injury (RILI) is a common consequence of thoracic radiation therapy that lacks effective preventative and treatment strategies. Dihydroartemisinin (DHA), a derivative of artemisinin, affects oxidative stress, immunomodulation, and inflammation. It is uncertain whether DHA reduces RILI. In this work, we investigated the specific mechanisms of action of DHA in RILI. METHODS: Twenty-four C57BL/6J mice were randomly divided into four groups of six mice each: Control group, irradiation (IR) group, IR + DHA group, and IR + DHA + Brusatol group. The IR group received no interventions along with radiation treatment. Mice were killed 30 days after the irradiation. Morphologic and pathologic changes in lung tissue were observed with hematoxylin and eosin staining. Detection of hydroxyproline levels for assessing the extent of pulmonary fibrosis. Tumor necrosis factor α (TNF-α), transforming growth factor-ß (TGF-ß), glutathione peroxidase (GPX4), Nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) expression in lung tissues were detected. In addition, mitochondrial ultrastructural changes in lung tissues were also observed, and the glutathione (GSH) content in lung tissues was assessed. RESULTS: DHA attenuated radiation-induced pathological lung injury and hydroxyproline levels. Additionally, it decreased TNF-α and TGF-ß after irradiation. DHA may additionally stimulate the Nrf2/HO-1 pathway. DHA upregulated GPX4 and GSH levels and inhibited cellular ferroptosis. Brusatol reversed the inhibitory effect of DHA on ferroptosis and its protective effect on RILI. CONCLUSION: DHA modulated the Nrf2/HO-1 pathway to prevent cellular ferroptosis, which reduced RILI. Therefore, DHA could be a potential drug for the treatment of RILI.

BTLA contributes to acute-on-chronic liver failure infection and mortality through CD4+ T-cell exhaustion.

B- and T-lymphocyte attenuator (BTLA) levels are increased in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). This condition is characterized by susceptibility to infection and T-cell immune exhaustion. However, whether BTLA can induce T-cell immune exhaustion and increase the risk of infection remains unclear. Here, we report that BTLA levels are significantly increased in the circulating and intrahepatic CD4+ T cells from patients with HBV-ACLF, and are positively correlated with disease severity, prognosis, and infection complications. BTLA levels were upregulated by the IL-6 and TNF signaling pathways. Antibody crosslinking of BTLA activated the PI3K-Akt pathway to inhibit the activation, proliferation, and cytokine production of CD4+ T cells while promoting their apoptosis. In contrast, BTLA knockdown promoted their activation and proliferation. BTLA-/- ACLF mice exhibited increased cytokine secretion, and reduced mortality and bacterial burden. The administration of a neutralizing anti-BTLA antibody reduced Klebsiella pneumoniae load and mortality in mice with ACLF. These data may help elucidate HBV-ACLF pathogenesis and aid in identifying novel drug targets.

Deep Learning-Based Reconstruction Improves the Image Quality of Low-Dose CT Colonography.

RATIONALE AND OBJECTIVES: To evaluate the image quality of low-dose CT colonography (CTC) using deep learning-based reconstruction (DLR) compared to iterative reconstruction (IR). MATERIALS AND METHODS: Adults included in the study were divided into four groups according to body mass index (BMI). Routine-dose (RD: 120 kVp) CTC images were reconstructed with IR (RD-IR); low-dose (LD: 100kVp) images were reconstructed with IR (LD-IR) and DLR (LD-DLR). The subjective image quality was rated on a 5-point scale by two radiologists independently. The parameters for objective image quality included noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The Friedman test was used to compare the image quality among RD-IR, LD-IR and LD-DLR. The KruskalWallis test was used to compare the results among different BMI groups. RESULTS: A total of 270 volunteers (mean age: 47.94 years ± 11.57; 115 men) were included. The effective dose of low-dose CTC was decreased by approximately 83.18% (5.18mSv ± 0.86 vs. 0.86mSv ± 0.05, P < 0.001). The subjective image quality score of LD-DLR was superior to that of LD-IR (3.61 ± 0.56 vs. 2.70 ± 0.51, P < 0.001) and on par with the RD- IR's (3.61 ± 0.56 vs. 3.74 ± 0.52, P = 0.486). LD-DLR exhibited the lowest noise, and the maximum SNR and CNR compared to RD-IR and LD-IR (all P < 0.001). No statistical difference was found in the noise of LD-DLR images between different BMI groups (all P > 0.05). CONCLUSION: Compared to IR, DLR provided low-dose CTC with superior image quality at an average radiation dose of 0.86mSv, which may be promising in future colorectal cancer screening.

Efficacy of early clinical interventions for children with global developmental delay.

OBJECTIVE: To evaluate the efficacy of early clinical interventions for children with global developmental delay. METHODS: A total of 127 initial subjects with GDD met the complete inclusion criteria. Seven cases were excluded due to withdrawal or refusal for follow-up. Eventually, the remaining 120 children were divided into two groups based on different treatment regimens: an experimental group and a control group. Ninety children received individualized treatment in the experimental group, while 30 children, due to various reasons, did not receive inpatient treatment and only underwent home-based intervention therapy in the control group. The developmental progress under different intervention methods was compared, and their clinical effectiveness was analyzed. RESULTS: Both groups of patients showed no significant differences in general characteristics such as gender and age (p > 0.05), demonstrating comparability. The initial comparison of developmental quotient scores in all patients before treatment revealed no significant differences. Post-treatment, there was improvement observed in both groups. However, children in the experimental group exhibited significantly higher scores in gross motor skills, fine motor skills, adaptability, language, and personal-social skills compared to those in the control group (p < 0.05). Additionally, the clinical effective rate in the experimental group was notably higher than that in the control group (p < 0.05). CONCLUSION: The combined use of acupuncture with home-based intervention therapy demonstrates favorable therapeutic outcomes in young children with comprehensive developmental delays. This approach has the potential to enhance gross motor skills, fine motor skills, cognition, language, and overall intellectual development in affected children.

Comparison of Diatrizoate and Iohexol for Patient Acceptance and Fecal-Tagging Performance in Noncathartic CT Colonography.

OBJECTIVE: The aim of this study was to compare diatrizoate and iohexol regarding patient acceptance and fecal-tagging performance in noncathartic computed tomography colonography. METHODS: This study enrolled 284 volunteers with fecal tagging by either diatrizoate or iohexol at an iodine concentration of 13.33 mg/mL and an iodine load of 24 g. Patient acceptance was rated on a 4-point scale of gastrointestinal discomfort. Two gastrointestinal radiologists jointly analyzed image quality, fecal-tagging density and homogeneity, and residual contrast agent in the small intestine. The results were compared by the generalized estimating equation method. RESULTS: Patient acceptance was comparable between the 2 groups (3.95 ± 0.22 vs 3.96 ± 0.20, P = 0.777). The diatrizoate group had less residual fluid and stool than the iohexol group ( P = 0.019, P = 0.004, respectively). There was no significant difference in colorectal distention, residual fluid, and stool tagging quality between the 2 groups (all P 's > 0.05). The mean 2-dimensional image quality score was 4.59 ± 0.68 with diatrizoate and 3.60 ± 1.14 with iohexol ( P < 0.001). The attenuation of tagged feces was 581 ± 66 HU with diatrizoate and 1038 ± 117 HU with iohexol ( P < 0.001). Residual contrast agent in the small intestine was assessed at 55.3% and 62.3% for the diatrizoate group and iohexol group, respectively ( P = 0.003). CONCLUSIONS: Compared with iohexol, diatrizoate had better image quality, proper fecal-tagging density, and more homogeneous tagging along with comparable excellent patient acceptance, and might be more suitable for fecal tagging in noncathartic computed tomography colonography.

Clustering and Beamwidth Optimization for UAV-Assisted Wireless Communication.

With the development of wireless communication technology, unmanned aerial vehicles (UAV) are now widely used in many complex communication scenarios. When a UAV serves as an aerial base station for urban and rural ground users or marine users, it is necessary to consider the clustering of ground users and the energy efficiency of the UAV since the users are usually randomly distributed. For the scenario with randomly distributed ground users and different densities of ground users in urban and rural areas, a clustering and beamwidth optimization method for UAV-assisted wireless communication is proposed. Firstly, the energy efficiency expression of a UAV serving ground users was derived in a downlink wireless communication system assisted by a UAV. Secondly, based on the geographical location information of non-uniformly distributed users, an improved k-means method is proposed to cluster ground users, ensuring that the number of users in each cluster is within an appropriate range. Then, based on the clustering results, a fixed-point iteration (FPI) algorithm was proposed to design the optimal beamwidth of UAVs and improve their energy efficiency. Finally, the superiority of the proposed algorithm in improving energy efficiency was verified through simulation analysis, and the impact of parameters such as the cluster number and transmission power on system energy efficiency was also analyzed.

Protocol for preparing patterned superlattice structures by printing assembly technology for multi-channel detection.

The transformation of superlattice structures into functional devices requires high-quality preparation. Inkjet printing is potentially a cutting-edge technology for nanofabrication. Here, we present a protocol to prepare inks for constructing patterned superlattice structures using print assembly techniques. We describe steps for preparing oleophobic substrates, optimizing ink parameters, and preparing the patterned superlattice array. We then detail procedures for preparing a multichannel surface-enhanced Raman scattering sensor and evaluating its performance. This protocol can potentially facilitate the commercialization of superlattice-related devices. For complete details regarding the use and execution of this protocol, please refer to Zhao et al.1.

Engineering of Amphiphilic Erlotinib Analogue as Novel Nanomedicine for Non-Small Cell Lung Cancer Therapy.

Purpose: Molecular targeted therapy is one of the most pivotal strategies in the treatment of non-small cell lung cancer, yet its curative effect is severely compromised by the poor aqueous solubility, low bioavailability and inadequate tumor accumulation of targeted agents. To enhance the efficacy of targeted agents, we demonstrate a novel self-assemble amphiphilic molecule based on erlotinib as an effective nanodrug for anti-cancer treatment. Methods: An amphiphilic molecule composed of hydrophobic erlotinib and hydrophilic biotin block was synthesized and characterized by nuclear magnetic resonance (NMR) as well as high-resolution mass spectrometry (HRMS). Then, nanoassemblies of the amphiphilic molecules are formulated by using nanoprecipitation method. Subsequently, the size, morphology, cell uptake, the anticancer activity and in vivo distribution of the newly constructed erlotinib nanodrug were systematically assessed by some methods, including transmission electron microscopy (TEM), dynamic light-scattering (DLS), flow cytometry, in vivo imaging system etc. Results: We developed a novel nanoformulation of erlotinib, which possesses a high drug loading of 45%. With the features of well-defined structure and small size, the obtained nanodrug could be effectively accumulated in tumor sites and rapidly internalized by cancer cells. Finally, the erlotinib-based nanoformulation showed considerably better anticancer activity compared to free erlotinib both in vitro and in vivo. Moreover, the nanodrug displayed great tolerability. Conclusion: Combining the advantageous features of both nanotechnology and self-assemble, this novel erlotinib nanomedicine constitutes a promising therapeutic candidate for cancer treatment. This study also underlines the potential use of amphiphilic molecule for improving drug efficacy as well as reducing drug toxicity, which could become a general strategy for the preparation of nanodrugs of active agents.

The contribution of IL-17A-dependent low LCN2 levels to Helicobacter pylori infection: Insights from clinical and experimental studies.

BACKGROUND: Helicobacter pylori (H. pylori) infection is a common bacterial infection that is widespread globally. It is crucial to comprehend the molecular mechanisms that underlie the infection caused by H. pylori in order to devise successful therapeutic approaches. The objective of this study was to examine the involvement of Lipocalin-2 (LCN2) in the development of H. pylori infection. METHODS: LCN2 expression levels in human gastric mucosa and H. pylori-infected mouse models were analyzed using quantitative PCR and immunohistochemistry methods. The effects of LCN2 on the attachment of H. pylori to gastric mucosa cells were assessed using bacterial culture and fluorescence intensity tests. To investigate the correlation between LCN2, CCL20, and IL-17A, we performed gene expression analysis and measured serum levels. RESULTS: The findings indicated an increase in LCN2 levels in the gastric mucosa of both patients and mice infected with H. pylori. Blocking the natural LCN2 resulted in an increased attachment of H. pylori to cells in the gastric mucosa. In addition, we noticed that reduced levels of LCN2 promoted the attachment of H. pylori to cells in the gastric mucosa. Furthermore, H. pylori-infected patients exhibited increased expression of both LCN2 and CCL20, and there was a positive correlation between serum levels of CCL20 and LCN2. LCN2 expression was found to depend on the presence of IL-17A, and inhibiting IL-17A led to a higher H. pylori colonization. CONCLUSION: The persistence of H. pylori infection is facilitated by the presence of low levels of LCN2, which is dependent on IL-17A. This finding offers valuable perspectives for the development of novel therapeutic approaches for H. pylori infection.

Imaging and monitoring of granzyme B in the immune response.

Significant progress has been made in tumor immunotherapy that uses the human immune response to kill and remove tumor cells. However, overreactive immune response could lead to various autoimmune diseases and acute rejection. Accurate and specific monitoring of immune responses in these processes could help select appropriate therapies and regimens for the patient and could reduce the risk of side effects. Granzyme B (GzmB) is an ideal biomarker for immune response, and its peptide substrate could be coupled with fluorescent dyes or contrast agents for the synthesis of imaging probes activated by GzmB. These small molecules and nanoprobes based on PET, bioluminescence imaging, or fluorescence imaging have proved to be highly GzmB specific and accuracy. This review summarizes the design of different GzmB-responsive imaging probes and their applications in monitoring of tumor immunotherapy and overreactive immune response. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Feasibility Analysis and Surgical Details of Vestibular Schwannoma Resection via Retrolabyrinthine Approach With Preservation of Endolymphatic Sac.

Objectives: To study the feasibility of reserving the endolymphatic sac in the cerebellopontine angle (CPA) and the fundus of the internal auditory canal (IAC) by the retrolabyrinthine approach. Design: Single-center retrospective study. Methods: Through 3-dimensional preoperative computed tomography reconstruction, vestibular schwannoma (VS) resection was performed using a retrolabyrinthine approach with preservation of the endolymphatic sac in selected patients, and hearing and facial nerve functions were followed to assess the feasibility of this operation and the effectiveness of function preservation. Results: VS was completely removed in all cases and the postoperative detectable hearing retention rate (AAO-HNS hearing rating grade A, B, and C) was 80% (4/5). Postoperative facial nerve function was well preserved (HB grade I), no leakage of cerebrospinal fluid or other cranial complications was observed in all patients, and no recurrence was observed during follow-up. Conclusions: With less trauma and a promising route for hearing preservation and facial nerve functions, the retrolabyrinthine approach is a potential choice for the treatment of VS located in the IAC-CPA.