Revolutionizing tumor immunotherapy: unleashing the power of progenitor exhausted T cells.

In exploring persistent infections and malignancies, a distinctive subgroup of CD8+ T cells, progenitor exhausted CD8+ T (Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-renewal and rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that Tpex cells expand and differentiate into responsive exhausted CD8+ T cells, thus underscoring their critical role in the immunotherapeutic retort. Clinical examinations have further clarified a robust positive correlation between the proportional abundance of Tpex cells and enhanced clinical prognosis. Tpex cells have found noteworthy applications in the formulation of inventive immunotherapeutic approaches against tumors. This review describes the functions of Tpex cells in the tumor milieu, particularly their potential utility in tumor immunotherapy. Precisely directing Tpex cells may be essential to achieving successful outcomes in immunotherapy against tumors.

Melamine Polymerization Promotes Compact Phosphorus/Carbon Composite for High-Performance and Safe Lithium Storage.

Phosphorus is regarded as a promising material for high-performance lithium-ion batteries (LIBs) due to its high theoretical capacity, appropriate lithiation potential, and low lithium-ion diffusion barrier. Phosphorus/carbon composites (PC) are engineered to serve as high-capacity high-rate anodes; the interaction between phosphorus and carbon, long-term capacity retention, and safety problems are important issues that must be well addressed simultaneously. Herein, an in situ polymerization approach to fabricate a poly-melamine-hybridized (pMA) phosphorus/carbon composite (pMA-PC) is employed. The pMA hybridization enhances the density and electrical conductivity of the PC, improves the structural integrity, and facilitates stable electron transfer within the pMA-PC composite. Moreover, the pMA-PC composite exhibits efficient adsorption of lithium polysulfides, enabling stable transport of Li+ ions. Therefore, the pMA-PC anode demonstrates a high specific charging capacity of 1,381 mAh g-1 at 10 A g-1, and a great capacity retention of 86.7% at 1 A g-1 over 500 cycles. The synergistic effect of phosphorus and nitrogen further confers excellent flame retardant properties to the pMA-PC anode, including self-extinguishing in 2.5 s, and a much lower combustion temperature than PC. The enhanced capacity and safety performance of pMA-PC show potential in future high-capacity and high-rate LIBs.

Christensenella strain resources, genomic/metabolomic profiling, and association with host at species level.

The gut commensal bacteria Christensenellaceae species are negatively associated with many metabolic diseases, and have been seen as promising next-generation probiotics. However, the cultured Christensenellaceae strain resources were limited, and their beneficial mechanisms for improving metabolic diseases have yet to be explored. In this study, we developed a method that enabled the enrichment and cultivation of Christensenellaceae strains from fecal samples. Using this method, a collection of Christensenellaceae Gut Microbial Biobank (ChrisGMB) was established, composed of 87 strains and genomes that represent 14 species of 8 genera. Seven species were first described and the cultured Christensenellaceae resources have been significantly expanded at species and strain levels. Christensenella strains exerted different abilities in utilization of various complex polysaccharides and other carbon sources, exhibited host-adaptation capabilities such as acid tolerance and bile tolerance, produced a wide range of volatile probiotic metabolites and secondary bile acids. Cohort analyses demonstrated that Christensenellaceae and Christensenella were prevalent in various cohorts and the abundances were significantly reduced in T2D and OB cohorts. At species level, Christensenellaceae showed different changes among healthy and disease cohorts. C. faecalis, F. tenuis, L. tenuis, and Guo. tenuis significantly reduced in all the metabolic disease cohorts. The relative abundances of C. minuta, C. hongkongensis and C. massiliensis showed no significant change in NAFLD and ACVD. and C. tenuis and C. acetigenes showed no significant change in ACVD, and Q. tenuis and Geh. tenuis showed no significant change in NAFLD, when compared with the HC cohort. So far as we know, this is the largest collection of cultured resource and first exploration of Christensenellaceae prevalences and abundances at species level.

Megalin-targeting and ROS-responsive elamipretide-conjugated polymeric prodrug for treatment of acute kidney injury.

Acute kidney injury (AKI) is associated with both kidney function loss and increased mortality. In the pathological progression of ischemia-reperfusion-induced AKI, the surge of reactive oxygen species (ROS) plays a crucial role. To combat this, mitochondrial-targeted antioxidant therapy shows great promise as mitochondria are the primary source of ROS in AKI. However, most strategies aiming to target mitochondria directly result in nanodrugs that are too large to pass through the glomerular system and reach the renal tubules, which are the main site of damage in AKI. This study focused on synthesizing a Megalin receptor-targeted polymeric prodrug, low molecular weight chitosan-thioketal-elamipretide (LMWC/TK/Ela), to mitigate excessive ROS in renal tubular epithelial cells for AKI. This soluble polymeric prodrug has the ability to successfully reach the tubular site by crossing the glomerular barrier. Once there, it can responsively release elamipretide, which possesses excellent antioxidative properties. Therefore, this research offers a novel approach to actively target renal tubular epithelial cells and intracellular mitochondria for the relief of AKI.

Alkaloids in Uncaria rhynchophylla improves AD pathology by restraining CD4+ T cell-mediated neuroinflammation via inhibition of glycolysis in APP/PS1 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla (Miq.) Miq.ex Havil. was a classical medicinal plant exhibiting the properties of extinguishing wind, arresting convulsions, clearing heat and pacifying the liver. Clinically, it could be utilized for the treatment of central nervous system-related diseases, such as Alzheimer's disease. U. rhynchophylla (UR) and its major ingredient alkaloid compounds (URA) have been proved to exert significant neuroprotective effects. However, the potential mechanism aren't fully understood. AIM OF THE STUDY: This study systematically examined the therapeutic effects of URA on AD pathology in APP-PS1 mice, and revealed the potential mechanism of action. MATERIALS AND METHODS: The cognitive ability was evaluated by morris water maze test in APP-PS1 mice. The H&E staining was used to observe the tissue pathological changes. The ELISA kits were used to detect the level of inflammatory factors. The flow cytometry was used to analyze the percentage of CD4+ effector T cells (Teffs) in spleen. The immunofluorescent staining was performed to count the Teffs and microglia in brain. The protein expression was analyzed by western blot. In vitro, the lymphocyte proliferation induced by ConA was performed by CCK-8 kits. The IFN-γ, IL-17, and TNF-α production were detected by ELISA kits. The effects of URA on glycolysis and the involvement of PI3K/Akt/mTOR signaling pathway was analyzed by Lactic Acid assay kit and western blot in ConA-induced naive T cell. RESULTS: URA treatment improved AD pathology effectively as demonstrated by enhanced cognitive ability, decreased Aß deposit and Tau phosphorylation, as well as reduced neuron apoptosis. Also, the neuroinflammation was significantly alleviated as evidenced by decreased IFN-γ, IL-17 and increased IL-10, TGF-ß. Notably, URA treatment down-regulated the percentage of Teffs (Th1 and Th17) in spleen, and reduced the infiltration of Teffs and microglia in brain. Meanwhile, the Treg cell was up-regulated both in spleen and brain. In vitro, URA was capable of attenuating the spleen lymphocyte proliferation and release of inflammatory factors provoked by ConA. Interestingly, glycolysis was inhibited by URA treatment as evidenced by the decrease in Lactic Acid production and expression of HK2 and GLUT1 via regulating PI3K/Akt/mTOR signaling pathway in ConA-induced naive T cell. CONCLUSION: This study proved that URA could improve AD pathology which was possibly attributable to the restraints of CD4+ T cell mediated neuroinflammation via inhibiting glycolysis.

Does environmental public interest litigation improve the urban land green use efficiency?-Evidence from a quasi-natural experiment in China.

Environmental public interest litigation (EPIL) is a significant part of the judicial system; it is aimed at strengthening judicial protections and safeguarding public interests. Based on the quasi-natural experimental setting of China's EPIL pilot project, this study examines the impact of EPIL on the country's urban land green use efficiency (ULGUE). The findings show that effectively implementing EPIL enhances ULGUE. Specifically, this policy has led to a 6.6% increase in ULGUE in pilot cities, and its impact has grown stronger over time. Mechanism analysis results show that EPIL mainly enhances ULGUE by strengthening environmental supervision and law enforcement, by increasing public participation in environmental governance, and by promoting green innovation and industrial structure upgrades. Furthermore, heterogeneity analysis revealed that the positive effects of this policy implementation are more pronounced in resource-based cities, cities with open environmental information, and cities with high marketization. This paper provides empirical evidence for the effectiveness of environmental governance via EPIL.

Analysis of drought and heat stress response genes in rice using co-expression network and differentially expressed gene analyses.

Studies on Oryza sativa (rice) are crucial for improving agricultural productivity and ensuring global sustenance security, especially considering the increasing drought and heat stress caused by extreme climate change. Currently, the genes and mechanisms underlying drought and heat resistance in rice are not fully understood, and the scope for enhancing the development of new strains remains considerable. To accurately identify the key genes related to drought and heat stress responses in rice, multiple datasets from the Gene Expression Omnibus (GEO) database were integrated in this study. A co-expression network was constructed using a Weighted Correlation Network Analysis (WGCNA) algorithm. We further distinguished the core network and intersected it with differentially expressed genes and multiple expression datasets for screening. Differences in gene expression levels were verified using quantitative real-time polymerase chain reaction (PCR). OsDjC53, MBF1C, BAG6, HSP23.2, and HSP21.9 were found to be associated with the heat stress response, and it is also possible that UGT83A1 and OsCPn60a1, although not directly related, are affected by drought stress. This study offers significant insights into the molecular mechanisms underlying stress responses in rice, which could promote the development of stress-tolerant rice breeds.

Development and validation of a nomogram to predicting the efficacy of PD-1/PD-L1 inhibitors in patients with nasopharyngeal carcinoma.

PURPOSE: With the treatment of nasopharyngeal carcinoma (NPC) by PD-1/PD-L1 inhibitors used widely in clinic, it becomes very necessary to anticipate whether patients would benefit from it. We aimed to develop a nomogram to evaluate the efficacy of anti-PD-1/PD-L1 in NPC patients. METHODS: Totally 160 NPC patients were enrolled in the study. Patients were measured before the first PD-1/PD-L1 inhibitors treatment and after 8-12 weeks of immunotherapy by radiological examinations to estimate the effect. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to screen hematological markers and establish a predictive model. The nomogram was internally validated by bootstrap resampling and externally validated. Performance of the model was evaluated using concordance index, calibration curve, decision curve analysis and receiver operation characteristic curve. RESULTS: Patients involved were randomly split into training cohort ang validation cohort. Based on Lasso logistic regression, systemic immune-inflammation index (SII) and ALT to AST ratio (LSR) were selected to establish a predictive model. The C-index of training cohort and validating cohort was 0.745 and 0.760. The calibration curves and decision curves showed the precise predictive ability of this nomogram. The benefit of the model showed in decision curve was better than TNM stage. The area under the curve (AUC) value of training cohort and validation cohort was 0.745 and 0.878, respectively. CONCLUSION: The predictive model helped evaluating efficacy with high accuracy in NPC patients treated with PD-1/PD-L1 inhibitors.

Association Between Added Sugar Intake and Urinary Incontinence in Females: A Cross-sectional Population-based Study.

INTRODUCTION AND HYPOTHESIS: Urinary incontinence (UI) is a widespread issue in women that severely impacts quality of life. The addition of sugar is associated with multiple adverse effects on health. This study examined the potential association between added sugar intake and UI. METHODS: Adult females from the National Health and Nutrition Examination Survey database (2005-2018) were included in this study. The primary outcomes were the prevalence of stress urinary incontinence (SUI), urge urinary incontinence (UUI), and mixed urinary incontinence (MUI). Weighted logistic regression, stratified logistic regression, restricted cubic spline regression, and sensitivity analyses were utilized to determine whether added sugar was associated with UI after multivariate adjustment. RESULTS: A total of 14,927 participants met the inclusion criteria. The results revealed a heightened prevalence of SUI, UUI, and MUI in the fourth quartile of added sugar energy percentage (OR = 1.304, 95% confidence interval [CI] = 1.105-1.539; OR = 1.464, 95% CI = 1.248-1.717; OR = 1.657, 95% CI = 1.329-2.065 respectively). The effect was more pronounced in young women and the subgroup analyses did not reveal any noteworthy interaction effects. According to the sensitivity analyses, the results for SUI and the MUI were consistent with those of the primary analyses. CONCLUSIONS: The excessive intake of added sugar among women may increase their risk of SUI and MUI. Our study highlights the negative effects of added sugar on female genitourinary health and highlights the need for universal access to healthy diets.

Characteristics and Risk Factors for Pediatric Sepsis.

OBJECTIVE: Sepsis is considered a major cause of health loss in children and had high mortality and morbidity. Currently, there is no reliable model for predicting the prognosis of pediatric patients with sepsis. This study aimed to analyze the clinical characteristics of sepsis in children and assess the risk factors associated with poor prognosis in pediatric sepsis patients to identify timely interventions and improve their outcomes. METHODS: This study analyzed the clinical indicators and laboratory results of septic patients hospitalized in the Pediatric Intensive Care Unit of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, from January 1, 2019, to December 31, 2021. Risk factors for sepsis were identified by logistic regression analyses. RESULTS: A total of 355 children with sepsis were enrolled, with 333 children (93.8%) in the good prognosis group, and 22 children (6.2%) in the poor prognosis group. Among them, there were 255 patients (71.8%) in the sepsis group, and 100 patients (28.2%) in the severe sepsis group. The length of hospital stay in the poor prognosis group was longer than that in the good prognosis group (P<0.01). The levels of interleukin 1ß (IL-1ß) in the poor prognosis group were higher than those in the good prognosis group (P>0.05), and the platelet (PLT), albumin (ALB), and hemoglobin (Hb) levels were lower in the poor prognosis group (P<0.01). The IL-8 levels in the severe sepsis group were higher than those in the sepsis group (P<0.05). Multiple logistic regression analysis suggested that lower Hb levels, ALB levels, peak PLT counts, and higher IL-1ß levels were independent risk factors for poor prognosis in children with sepsis. CONCLUSION: Lower Hb, ALB, and PLT counts and elevated IL-1ß are independent risk factors for poor prognosis in children with sepsis.

Three undescribed dihydrostilbene glycosides from leaves of Camellia oleifera Abel. And their anti-inflammatory activity.

Three previously unidentified dihydrostilbene glycosides, named oleiferaside A (1), oleiferaside B (2), and oleiferaside C (3), were discovered through a phytochemical exploration on Camellia oleifera Abel. leaves. Additionally, nine known secondary metabolites (4-12) were also identified. The undescribed secondary metabolites 1-3 were elucidated as 3,5-dimethoxydihydrostilbene 4'-O-α-l-arabinofuranosyl-(1 â†’ 6)-ß-d- glucopyranoside, 3,5-dimethoxydihydrostilbene 4'-O-α-l-arabinopyranosyl-(1 â†’ 6)-ß-d- glucopyranoside and 3,5-dimethoxydihydrostilbene 4'-O-ß-d-apiofuranosyl-(1 â†’ 6)-ß-d- glucopyranoside, respectively. HR-MS and NMR spectroscopy were utilized for determining the structures of the isolates. The natural products were assessed for their anti-inflammatory effect using RAW264.7 macrophage stimulated by LPS. The findings demonstrated that compounds 1-4 exhibited inhibitory activities on NO and PGE2 production without causing cytotoxicity. These observations suggest that these compounds may have potential anti-inflammatory properties.

Genetically predicted biomarkers of iron homeostasis and risk of non-ischemic cardiomyopathy: A mendelian randomization study.

BACKGROUND AND AIMS: Both iron overload and iron deficiency have been associated with cardiovascular diseases in observational studies. Previous Mendelian Randomization (MR) studies discovered a protective effect of higher iron status on coronary atrial disease, while a neutral effect on all-cause heart failure. Using two-sample MR, we evaluated how genetically predicted systemic iron status affects the risk of non-ischemic cardiomyopathy and different phenotypes. METHODS AND RESULTS: Two-sample MR analyses were performed to estimate the causal effect of four biomarkers of systemic iron status on diagnosed cardiomyopathy and its subtypes in 242,607 participants from the FinnGen research project. The level of transferrin saturation was significantly associated with an increased risk of cardiomyopathy (OR, 1.17; 95% CI, 1.13-1.38) when using nine separately selected genetic instruments. An increase in genetically determined serum iron (odds ratio [OR] per standard deviation [SD], 1.25; 95% confidence interval [CI], 1.13-1.38) and ferritin (OR, 1.49; 95% CI, 1.02-2.18) were associated with an increased risk of cardiomyopathy. Total iron binding capacity, a marker of reduced iron status, was inversely linked with cardiomyopathy (OR, 0.80; 95% CI, 0.65-0.98). The risk effect of iron status was more evident in hypertrophic cardiomyopathy and related heart failure. CONCLUSIONS: These analyses support the causal effect of increased systemic iron status on a higher risk of non-ischemic cardiomyopathy. A screening test for cardiomyopathy should be considered in patients with evidence of iron overload. Future study is needed for exploring the mechanism of these causal variants on cardiomyopathy.

Preparation and Performance Evaluation of a Zinc Oxide-Graphene Oxideloaded Chitosan-Based Thermosensitive Gel.

This study aimed to develop and assess a chitosan biomedical antibacterial gel ZincOxideGrapheneOxide/Chitosan/ß-Glycerophosphate (ZnO-GO/CS/ß-GP) loaded with nano-zinc oxide (ZnO) and graphene oxide (GO), known for its potent antibacterial properties, biocompatibility, and sustained drug release. ZnO nanoparticles (ZnO-NPs) were modified and integrated with GO sheets to create 1% and 3% ZnO-GO/CS/ß-GP thermo-sensitive hydrogels based on ZnO-GO to Chitosan (CS) mass ratio. Gelation time, pH, structural changes, and microscopic morphology were evaluated. The hydrogel's antibacterial efficacy against Porphyromonas gingivalis, biofilm biomass, and metabolic activity was examined alongside its impact (MC3T3-e1). The findings of this study revealed that both hydrogel formulations exhibited temperature sensitivity, maintaining a neutral pH. The ZnO-GO/CS/ß-GP formulation effectively inhibited P. gingivalis bacterial activity and biofilm formation, with a 3% ZnO-GO/CS/ß-GP antibacterial rate approaching 100%. MC3T3-e1 cells displayed good biocompatibility when cultured in the hydrogel extract.The ZnO-GO/CS/ß-GP thermo-sensitive hydrogel demonstrates favorable physical and chemical properties, effectively preventing P. gingivalis biofilm formation. It exhibits promising biocompatibility, suggesting its potential as an adjuvant therapy for managing and preventing peri-implantitis, subject to further clinical investigations.

Differences in ocular adverse events associated with phosphodiesterase-5 inhibitors: a real-world pharmacovigilance study.

OBJECTIVE: Our study aims to characterize the ocular safety profiles of phosphodiesterase type 5 (PDE5) inhibitors and explore the differences among different PDE5 inhibitors. METHODS: We analyzed reports on ocular adverse events associated with sildenafil, vardenafil and tadalafil submitted to the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the first quarter of 2023. Disproportionality analysis was conducted to evaluate reporting risk profiles. RESULTS: Among 61,211 reports qualifying for analysis, 5,127 involved sildenafil, 832 vardenafil, and 3,733 tadalafil. All PDE5 inhibitors showed increased reporting odds ratios (ROR) for ocular adverse events, with vardenafil highest (ROR 4.47) followed by sildenafil and tadalafil. Key ocular adverse events included cyanopsia, optic ischemic neuropathy, visual field defects, unilateral blindness and blindness. Sildenafil showed the highest disproportionality for cyanopsia (ROR 1148.11) while vardenafil and tadalafil showed the highest disproportionality for optic ischemic neuropathy. Time-to-onset analysis also revealed significant differences, with sildenafil having a later median time-to-onset compared to vardenafil and tadalafil. CONCLUSIONS: This comprehensive pharmacovigilance study reveals distinct patterns of ocular adverse events associated with PDE5 inhibitors. These findings contribute to a better understanding of the safety profiles of PDE5 inhibitors and may guide healthcare professionals in clinical decision-making.

Cervical extracellular matrix hydrogel optimizes tumor heterogeneity of cervical squamous cell carcinoma organoids.

Cervical cancer, primarily squamous cell carcinoma, is the most prevalent gynecologic malignancy. Organoids can mimic tumor development in vitro, but current Matrigel inaccurately replicates the tissue-specific microenvironment. This limitation compromises the accurate representation of tumor heterogeneity. We collected para-cancerous cervical tissues from patients diagnosed with cervical squamous cell carcinoma (CSCC) and prepared uterine cervix extracellular matrix (UCEM) hydrogels. Proteomic analysis of UCEM identified several tissue-specific signaling pathways including human papillomavirus, phosphatidylinositol 3-kinase-AKT, and extracellular matrix receptor. Secreted proteins like FLNA, MYH9, HSPA8, and EEF1A1 were present, indicating UCEM successfully maintained cervical proteins. UCEM provided a tailored microenvironment for CSCC organoids, enabling formation and growth while preserving tumorigenic potential. RNA sequencing showed UCEM-organoids exhibited greater similarity to native CSCC and reflected tumor heterogeneity by exhibiting CSCC-associated signaling pathways including virus protein-cytokine, nuclear factor κB, tumor necrosis factor, and oncogenes EGR1, FPR1, and IFI6. Moreover, UCEM-organoids developed chemotherapy resistance. Our research provides insights into advanced organoid technology through native matrix hydrogels.

Megalin-targeted acetylcysteine polymeric prodrug ameliorates ischemia-reperfusion-induced acute kidney injury.

Acute kidney injury (AKI), a condition associated with reactive oxygen species (ROS), causes high mortality in clinics annually. Active targeted antioxidative therapy is emerging as a novel strategy for AKI treatment. In this study, we developed a polymeric prodrug that targets the highly expressed Megalin receptor on proximal tubule cells, enabling direct delivery of N-Acetylcysteine (NAC) for the treatment of ischemia reperfusion injury (IRI)-induced AKI. We conjugated NAC with low molecular weight chitosan (LMWC), a biocompatible and biodegradable polymer consisting of glucosamine and N-acetylglucosamine, to enhance its internalization by tubular epithelial cells. Moreover, we further conjugated triphenylphosphonium (TPP), a lipophilic cation with a delocalized positive charge, to low molecular weight chitosan-NAC in order to enhance the distribution of NAC in mitochondria. Our study confirmed that triphenylphosphonium-low molecular weight chitosan-NAC (TLN) exhibits remarkable therapeutic effects on IRI-AKI mice. This was evidenced by improvements in renal function, reduction in oxidative stress, mitigation of pathological progress, and decreased levels of kidney injury molecule-1. These findings suggested that the polymeric prodrug TLN holds promising potential for IRI-AKI treatment.

Development of neonatal connectome dynamics and its prediction for cognitive and language outcomes at age 2.

The functional brain connectome is highly dynamic over time. However, how brain connectome dynamics evolves during the third trimester of pregnancy and is associated with later cognitive growth remains unknown. Here, we use resting-state functional Magnetic Resonance Imaging (MRI) data from 39 newborns aged 32 to 42 postmenstrual weeks to investigate the maturation process of connectome dynamics and its role in predicting neurocognitive outcomes at 2 years of age. Neonatal brain dynamics is assessed using a multilayer network model. Network dynamics decreases globally but increases in both modularity and diversity with development. Regionally, module switching decreases with development primarily in the lateral precentral gyrus, medial temporal lobe, and subcortical areas, with a higher growth rate in primary regions than in association regions. Support vector regression reveals that neonatal connectome dynamics is predictive of individual cognitive and language abilities at 2  years of age. Our findings highlight network-level neural substrates underlying early cognitive development.

A Multi-Modal Foundation Model to Assist People with Blindness and Low Vision in Environmental Interaction.

People with blindness and low vision (pBLV) encounter substantial challenges when it comes to comprehensive scene recognition and precise object identification in unfamiliar environments. Additionally, due to the vision loss, pBLV have difficulty in accessing and identifying potential tripping hazards independently. Previous assistive technologies for the visually impaired often struggle in real-world scenarios due to the need for constant training and lack of robustness, which limits their effectiveness, especially in dynamic and unfamiliar environments, where accurate and efficient perception is crucial. Therefore, we frame our research question in this paper as: How can we assist pBLV in recognizing scenes, identifying objects, and detecting potential tripping hazards in unfamiliar environments, where existing assistive technologies often falter due to their lack of robustness? We hypothesize that by leveraging large pretrained foundation models and prompt engineering, we can create a system that effectively addresses the challenges faced by pBLV in unfamiliar environments. Motivated by the prevalence of large pretrained foundation models, particularly in assistive robotics applications, due to their accurate perception and robust contextual understanding in real-world scenarios induced by extensive pretraining, we present a pioneering approach that leverages foundation models to enhance visual perception for pBLV, offering detailed and comprehensive descriptions of the surrounding environment and providing warnings about potential risks. Specifically, our method begins by leveraging a large-image tagging model (i.e., Recognize Anything Model (RAM)) to identify all common objects present in the captured images. The recognition results and user query are then integrated into a prompt, tailored specifically for pBLV, using prompt engineering. By combining the prompt and input image, a vision-language foundation model (i.e., InstructBLIP) generates detailed and comprehensive descriptions of the environment and identifies potential risks in the environment by analyzing environmental objects and scenic landmarks, relevant to the prompt. We evaluate our approach through experiments conducted on both indoor and outdoor datasets. Our results demonstrate that our method can recognize objects accurately and provide insightful descriptions and analysis of the environment for pBLV.

Subacute combined degeneration of the spinal cord with cerebellar lesions: A case report.

RATIONALE: Subacute combined degeneration of the spinal cord is a degenerative disease of the central and peripheral nervous systems caused by vitamin B12 deficiency, mainly involving the spinal cord posterior, lateral, and peripheral nerves, but rarely involving the cerebellum. PATIENT CONCERNS: A 41-year-old woman presented with a 2-year history of walking unsteadily. Her hematologic examination revealed megaloblastic anemia and vitamin B12 deficiency. Electromyography showed multiple peripheral nerve damage (sensory fibers and motor fibers were involved). Imaging examination showed long T2 signal in the cervical, thoracic and lumbar spinal cord and cerebellum. Gastroscopy revealed autoimmune gastritis. DIAGNOSES: Subacute combined degeneration of the spinal cord. INTERVENTIONS: By supplementing with vitamin B12. OUTCOMES: The patient's symptoms of limb weakness, diet, and consciousness were improved, and the muscle strength of both lower limbs recovered to grade IV. LESSONS: The symptomatic people should seek medical treatment in time to avoid further deterioration of the disease. When esophagogastroduodenoscopy is performed as part of routine physical examination in asymptomatic people, it should be checked for the presence of autoimmune gastritis. Early diagnosis can prevent irreversible neuropathy.

Transcranial volumetric imaging using a conformal ultrasound patch.

Accurate and continuous monitoring of cerebral blood flow is valuable for clinical neurocritical care and fundamental neurovascular research. Transcranial Doppler (TCD) ultrasonography is a widely used non-invasive method for evaluating cerebral blood flow1, but the conventional rigid design severely limits the measurement accuracy of the complex three-dimensional (3D) vascular networks and the practicality for prolonged recording2. Here we report a conformal ultrasound patch for hands-free volumetric imaging and continuous monitoring of cerebral blood flow. The 2 MHz ultrasound waves reduce the attenuation and phase aberration caused by the skull, and the copper mesh shielding layer provides conformal contact to the skin while improving the signal-to-noise ratio by 5 dB. Ultrafast ultrasound imaging based on diverging waves can accurately render the circle of Willis in 3D and minimize human errors during examinations. Focused ultrasound waves allow the recording of blood flow spectra at selected locations continuously. The high accuracy of the conformal ultrasound patch was confirmed in comparison with a conventional TCD probe on 36 participants, showing a mean difference and standard deviation of difference as -1.51 ± 4.34 cm s-1, -0.84 ± 3.06 cm s-1 and -0.50 ± 2.55 cm s-1 for peak systolic velocity, mean flow velocity, and end diastolic velocity, respectively. The measurement success rate was 70.6%, compared with 75.3% for a conventional TCD probe. Furthermore, we demonstrate continuous blood flow spectra during different interventions and identify cascades of intracranial B waves during drowsiness within 4 h of recording.