Gastric-type extremely well-differentiated adenocarcinoma of the stomach: A rare tumor with diagnostic difficulties and high inter-observer variation in endoscopic pinch biopsies.

Extremely well-differentiated gastric-type adenocarcinoma (EWDGA) is a rare type of gastric cancer composed of deceptively bland-looking malignant cells resembling normal foveolar or pyloric epithelium. The histological features of this tumor have not been recognized by many pathologists, and inter-observer variation studies are lacking. Here, we report seven EWDGAs and inter-observer variation of six preoperative biopsies was evaluated by 11 pathologists in a single institute. Based on the pathological diagnosis of the endoscopic biopsy slides, the average rate of definite malignancy diagnosis was 15.2 %, and the overall diagnostic concordance rate was 34.9 % among 11 pathologists. Microscopically, the surface epithelium was preserved and only a few atypical tumor glands were scattered in most endoscopic biopsies. Structural atypia was minimal, and the tumor glands were barely distinguishable from normal glands. Although nuclear atypia was minimal, enlarged nuclei, relatively large glands with irregular shapes, and abundant cytoplasmic mucin were observed in gastric pinch biopsies. In preoperative biopsies, no cases showed p53 overexpression, and Ki-67 labeling index ranged from 3 % to 35 % and was higher compared to non-neoplastic glands in 3 cases. After gastrectomy, four (57.1 %) patients had advanced gastric cancer and three (42.9 %) had lymph node metastasis. Genomic profiling of the four patients revealed mutations of TP53, BRAF, KRAS, STK11, and MDM2/CCND1 amplification. Immunohistochemistry for p53 was not helpful while Ki-67 may be helpful when staining pattern is distinct from the non-neoplastic mucosa. In conclusion, it is challenging to diagnose EWDGA using biopsy specimens. Recognizing and addressing this rare entity will increase diagnostic accuracy to ensure the early diagnosis of cancer.

Age-related annual changes in arterial stiffness in healthy adults: Insights from a large Korean cohort study.

BACKGROUND AND AIMS: Arterial stiffness, a known cardiovascular risk factor, is associated with increasing age and arteriosclerosis. This study examines age-related annual changes in arterial stiffness in a large cohort of healthy individuals without cardiovascular disease, hypertension, or diabetes mellitus. METHODS: The study included 195,405 Korean adults aged 30-79 years who attended a health check-up between 2006 and 2019. Arterial stiffness was assessed using brachial-ankle pulse wave velocity (baPWV), and the final cohort for the baPWV annual change analysis comprised 147,313 participants. RESULTS: The study found that baPWV values increase progressively with age in both sexes, with the most notable changes occurring in the 70-79 age group. The spread in baPWV measurements, as indicated by the interquartile ranges, generally increases with age but was particularly pronounced in women in the 50s and 60s age groups, with men showing a greater spread in the 70-79 age group. The average annual change in baPWV (ΔbaPWV) values increased from 1.48 cm/s (95 % CI: 0.80-2.16) in the 30-39 age group to 23.72 cm/s (95 % CI: 16.25-31.19) in the 70-79 age group in men. Similarly, for women, the average ΔbaPWV values increased from 1.80 cm/s (95 % CI: 0.93-2.68) to 18.51 cm/s (95 % CI: 7.18-29.85) in the 30-39 and 70-79 age groups, respectively. The study observed that arterial stiffness in men consistently increases across all age groups, whereas in women, it does not significantly increase annually before age 50 but shows a steeper rise after this age. CONCLUSIONS: This study emphasizes the progressive nature of arterial stiffness with aging in a healthy population. It highlights notable differences in the rate of progression and the distribution of baPWV between men and women, with men exhibiting a greater spread in the oldest age group.

Chitosan-based electrospun fibers for bone-tissue engineering: Recent research advancements.

Chitosan, a sustainable and highly abundant animal-derived biopolymer, possesses versatile properties, such as solubility, film-forming ability, viscosity, ion binding, and antimicrobial qualities, which are suitable for biomedical applications. Due to its charged nature, chitosan is a lucrative biopolymer for scaffold fabrication, especially for bone-tissue engineering applications, using the electrospinning method, which is an industrially suitable, scalable, and swift method for fabricating porous nanocomposite structures. Despite a lot of research being conducted on chitosan-based electrospun materials for bone tissue engineering, the research on this topic has not been thoroughly reviewed. This review article aims to fill this knowledge gap and provides an in-depth discussion of the research on this topic. To start with, a brief overview of bone tissue engineering has been provided, followed by the properties of chitosan, which make it an important biopolymer for this application. Also, the important factors that must be considered while electrospinning chitosan, especially considering its application in bone tissue engineering, have been debated. Further, the type of chitosan-based electrospun material has been discussed along with the recent advancements in this research area. Finally, a brief perspective on the future of this technology has been provided.

Thermal imaging and deep learning-based fit-checking for respiratory protection.

This study develops an artificial intelligence model to quickly and easily determine correct mask-wearing in real time using thermal videos that ascertained temperature changes caused by air trapped inside the mask. Five types of masks approved by the Korean Ministry of Food and Drug Safety were worn in four different ways across 50 participants, generating 5000 videos. The results showed that 3DCNN outperformed ConvLSTM in both binary and multi-classification for mask wearing methods, with the highest AUROC of 0.986 for multi-classification. Each mask type scored AUROC values > 0.9, with KF-AD being the best classified. This improved use of thermal imaging and deep learning for mask fit-checking could be useful in high-risk environments. It can be applied to various mask types, which enables easy generalizability and advantages in public and occupational health and healthcare system.

Proteomic analysis of CD29+ Müller cells reveals metabolic reprogramming in rabbit myopia model.

The prevalence of myopia is rapidly increasing, significantly impacting the quality of life of affected individuals. Prior research by our group revealed reactive gliosis in Müller cells within myopic retina, prompting further investigation of their role in myopia, which remains unclear. In this study, we analyzed protein expression changes in CD29+ Müller cells isolated from a form deprivation-induced rabbit model of myopia using magnetic activated cell sorting to investigate the role of these cells in myopia. As the principal glial cells in the retina, Müller cells exhibited significant alterations in the components of metabolic pathways, particularly glycolysis and angiogenesis, including the upregulation of glycolytic enzymes, such as lactate dehydrogenase A and pyruvate kinase, implicated in the adaptation to increased metabolic demands under myopic stress. Additionally, a decrease in the expression of proteins associated with oxygen transport suggested enhanced vulnerability to oxidative stress. These findings highlight the proactive role of CD29+ Müller cells in modifying the retinal environment in response to myopic stress and provide valuable insights into mechanisms that could help mitigate myopia progression.

Correlation between fetal subcutaneous fat thickness and insulin resistance through cord blood analysis immediately after delivery.

OBJECTIVES: This study aimed to determine whether fetal subcutaneous tissue (SCT) thickness, measured using ultrasound immediately before and after delivery, can reflect changes in glucose metabolism immediately after delivery. We also evaluated the impact of insulin resistance changes during pregnancy by comparing pregnant women with well-controlled gestational diabetes mellitus (GDM) and those with normal glucose metabolism. STUDY DESIGN: The study participants were 117 pregnant women, including 97 controls and 20 patients with GDM who visited our obstetric clinic between February and December 2022. The participants were scheduled for cesarean delivery at a gestational age of ≥37 weeks. SCT thickness before delivery was measured using ultrasound and within 48 h after delivery using Holtain calipers. The glucose and insulin concentrations were quantified from cord blood collected immediately after delivery. Based on these results, a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was performed to assess insulin resistance. Independent t-test or Wilcoxon rank-sum test for continuous variables and Fisher's exact test for categorical variables were used to compare the various parameters. Correlations among the variables in each group were assessed by calculating the correlation coefficient (Pearson's correlation). RESULTS: SCT thickness measured using ultrasound and calipers demonstrated a strong correlation where pregnant women with GDM exhibited thicker fetal SCT and neonate skinfolds than in those without GDM. Glucose and insulin levels in the cord blood were significantly elevated (p < 0.05) in the gestational diabetic group, along with remarkable differences (p < 0.001) in HOMA-IR. These variables indicated a higher prevalence of glucose intolerance in the neonates of mothers with GDM. In pregnant women with GDM, there was a statistically significant correlation between fetal abdominal SCT thickness and glucose levels (r = 0.64, p < 0.01) and HOMA-IR (r = 0.48, p < 0.05). CONCLUSIONS: Measuring the subcutaneous fat thickness of the fetus shortly before delivery is beneficial for predicting insulin resistance in neonates. This is considered particularly useful for women with effectively managed GDM, where the presence of conditions such as macrosomia may not be pronounced.

Clinical Outcomes of Pleomorphic High-grade Squamous Intraepithelial Lesions of the Uterine Cervix: A Single-institutional Experience of 44 Cases.

BACKGROUND/AIM: Pleomorphic high-grade squamous intraepithelial lesions (PHSILs) of the uterine cervix are characterized by strikingly pleomorphic and enlarged nuclei with brisk mitotic activity. The aim of this study was to analyze the clinical outcomes of patients with PHSIL. PATIENTS AND METHODS: Clinical data were collected from the electronic medical records of 44 patients with PHSIL. RESULTS: The patients' mean age was 52.1 years. The initial cytological diagnosis was HSIL in 43.2% of patients. High-risk human papillomavirus was detected in 89.5% of patients. The human papillomavirus type was not predominated by one specific type. The patients were treated with conization alone or with conization with subsequent hysterectomy. Two cases of squamous cell carcinoma coexisting with PHSIL, and one case of adenoid basal carcinoma were detected among the surgical specimens. Follow-up cytology revealed negative results for intraepithelial lesions in all patients, except for one patient who experienced recurrent PHSIL 41 months after hysterectomy and underwent laser ablation. CONCLUSION: The incidence rates of concurrent squamous cell carcinoma (4.5%) and recurrence (2.3%) in our PHSIL cohort were lower than those previously reported in patients with conventional HSIL. Our findings suggest that pleomorphic nuclear change alone in PHSIL was not associated with worse clinical outcomes than conventional HSIL and support the notion that PHSIL does not require more aggressive clinical management than conventional HSIL. However, close follow-up with cytological examination may be necessary to determine the potential risk of recurrence.

A Stool DNA-Based SDC2 Methylation Test for the Early Detection of Colorectal Cancer in an Asymptomatic, High-Risk Population: A Multicenter Prospective Randomized Trial.

INTRODUCTION: Noninvasive stool DNA-based methylation testing has emerged as an effective strategy for the early colorectal cancer (CRC) detection. Syndecan-2 (SDC2) methylation frequently occurs in all stages of CRC; therefore, the aim of this study was to evaluate the clinical performance of a stool DNA-based SDC2 methylation test for detecting CRC in asymptomatic or high-risk CRC populations. METHODS: This multicenter prospective study was conducted to determine the clinical performance of the SDC2 methylation test on stool DNA using real-time polymerase chain reaction. Stool samples were collected from asymptomatic individuals before colonoscopy, and the test results were independently analyzed through comparison with colonoscopic findings and pathological outcomes as reference standards. RESULTS: Of the 1,124 evaluable participants, 20 had CRC, 73 had advanced adenomatous polyps (≥1.0 cm), 469 had nonadvanced adenomatous polyps (<1.0 cm), 178 had non-neoplastic polyps, and 384 had negative colonoscopy results. The stool SDC2 methylation test had a sensitivity and specificity of 95.0% and 81.5%, respectively, for detecting CRC, while the sensitivity for detecting advanced adenomatous polyps and CRC was 58.1%. The rate of adenoma detection increased with polyp size (P < 0.01), and sensitivity was not associated with CRC stage (P = 0.864). DISCUSSION: The stool DNA-based SDC2 methylation test attained a high sensitivity for CRC detection in an asymptomatic high-risk population. Further large-scale clinical studies are required to validate the clinical utility of this test as a population-based CRC screening tool.

Effects of Kimchi Intake on the Gut Microbiota and Metabolite Profiles of High-Fat-Induced Obese Rats.

With rising global obesity rates, the demand for effective dietary strategies for obesity management has intensified. This study evaluated the potential of kimchi with various probiotics and bioactive compounds as a dietary intervention for high-fat diet (HFD)-induced obesity in rats. Through a comprehensive analysis incorporating global and targeted metabolomics, gut microbiota profiling, and biochemical markers, we investigated the effects of the 12-week kimchi intake on HFD-induced obesity. Kimchi intake modestly mitigated HFD-induced weight gain and remarkably altered gut microbiota composition, steroid hormones, bile acids, and metabolic profiles, but did not reduce adipose tissue accumulation. It also caused significant shifts in metabolomic pathways, including steroid hormone metabolism, and we found substantial interactions between dietary interventions and gut microbiota composition. Although more research is required to fully understand the anti-obesity effects of kimchi, our findings support the beneficial role of kimchi in managing obesity and related metabolic disorders.

Elevated α-1,2-mannosidase MAN1C1 in glioma stem cells and its implications for immunological changes and prognosis in glioma patients.

Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor, and the presence of glioma stem cells (GSCs) has been linked to its resistance to treatments and recurrence. Additionally, aberrant glycosylation has been implicated in the aggressiveness of cancers. However, the influence and underlying mechanism of N-glycosylation on the GSC phenotype and GBM malignancy remain elusive. Here, we performed an in-silico analysis approach on publicly available datasets to examine the function of N-glycosylation-related genes in GSCs and gliomas, accompanied by a qRT-PCR validation experiment. We found that high α-1,2-mannosidase MAN1C1 is associated with immunological functions and worse survival of glioma patients. Differential gene expression analysis and qRT-PCR validation revealed that MAN1C1 is highly expressed in GSCs. Furthermore, higher MAN1C1 expression predicts worse outcomes in glioma patients. Also, MAN1C1 expression is increased in the perinecrotic region of GBM and is associated with immunological and inflammatory functions, a hallmark of the GBM mesenchymal subtype. Further analysis confirmed that MAN1C1 expression is closely associated with infiltrating immune cells and disrupted immune response in the GBM microenvironment. These suggest that MAN1C1 is a potential biomarker for gliomas and may be important as an immunotherapeutic target for GBM.

Time to Treat First Acute Attack of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Importance: A proportion of people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have a relapsing disease course and persistent anti-myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) seropositivity. Few studies have investigated whether treatment of the first MOGAD attack is associated with the long-term disease course and/or MOG-IgG seronegative conversion. Objective: To investigate the association of time to treat the first acute MOGAD attack with relapse risk and MOG-IgG serostatus. Design, Setting, and Participants: This was a retrospective, nationwide, multicenter cohort study involving 14 secondary or tertiary hospitals in South Korea between November 2009 and August 2023. People with adult-onset MOGAD, who either had a relapse or were followed up for more than 12 months after disease onset and had a detailed medical record of their first attack, were included. Individuals were excluded for adolescent-onset MOGAD or short disease duration. Exposures: Patients were categorized based on the time to treat the first acute MOGAD attack: early (<5 days), intermediate (5-14 days), and late (not treated within 14 days). Main Outcomes and Measures: A multivariable analysis for clinical and treatment factors associated with relapsing disease course and/or MOG-IgG seronegative conversion. Further subgroup analyses were conducted among those without long-term nonsteroidal immunosuppressant (NSIS) maintenance treatment. Results: Among the 315 individuals screened, 75 were excluded. A total of 240 patients (median [IQR] age at onset, 40.4 [28.8-56.1] years; 125 female [52.1%]) with median (IQR) disease duration of 3.07 (1.95-6.15) years were included. A total of 110 of 240 patients (45.8%) relapsed after a median (IQR) of 0.45 (0.18-1.68) years, and 29 of 116 patients (25.0%) experienced a conversion to seronegative MOG-IgG. Both the time to treatment of the first MOGAD attack (late vs early: adjusted hazard ratio [aHR], 2.64; 95% CI, 1.43-4.84; P = .002; intermediate vs early: aHR, 2.02; 95% CI, 1.10-3.74; P = .02) and NSIS maintenance treatment (aHR, 0.24; 95% CI, 0.14-0.42; P < .001) were independently associated with the risk of relapse. In a subgroup without NSIS maintenance, the time to treat of the first MOGAD attack was still associated with higher risk of relapse (late vs early: aHR, 3.51; 95% CI, 1.64-7.50; P = .001; intermediate vs early: aHR, 2.68; 95% CI, 1.23-5.85; P = .01). Lastly, the time to treat of the first MOGAD attack was also associated with MOG-IgG seronegative conversion (early vs late: adjusted odds ratio, 7.04; 95% CI, 1.58-31.41; P = .01), whereas NSIS maintenance treatment was not. Conclusions and Relevance: Results of this cohort study suggest that early treatment of the first acute MOGAD attack was associated with a reduction in the proportion of relapsing disease course and an increase in the likelihood of MOG-IgG seronegative conversion. These data suggest that timing of acute phase treatment for the first MOGAD attack can be associated with the long-term prognosis and autoimmune status of patients.

Peripheral human red blood cell development in human immune system mouse model with heme oxygenase-1 deficiency.

A challenge for human immune system (HIS) mouse models has been the lack of human red blood cells (hRBCs) survival after engraftment of these immune-deficient mice with human CD34+ hematopoietic stem cells (HSCs). This limits the use of HIS models for preclinical testing of targets directed at hRBCs-related diseases. Even though human white blood cells can develop in the peripheral blood of these human HSC-engrafted mice, peripheral hRBCs are quickly phagocytosed by murine macrophages upon egress from the bone marrow (BM). Genetic ablation of murine myeloid cells results in severe pathology in resulting mice, rendering such an approach to increase hRBC survival in HIS mice impractical. Heme oxygenase-1 (HMOX-1) deficient mice have reduced macrophages due to toxic build-up of intracellular heme upon engulfment of red blood cells, but do not have an overall loss of myeloid cells. We took advantage of this observation and generated a HMOX-1-/- on a humanized M-CSF/SIRPa/CD47 Rag2-/- IL-2Rg-/- background. These mice have reduced murine macrophages but comparable level of murine myeloid cells to HMOX-1+/+ control mice in the same background. Injected hRBCs survive longer in HMOX-1-/- mice than in HMOX-1+/+ controls. Additionally, upon human HSC-engraftment, hRBCs can be observed in the peripheral blood of HMOX-1-/- humanized M-CSF/SIRPa/CD47 Rag2-/- IL-2Rg-/- mice and hRBC levels can be increased by treatment with human erythropoietin. Since hRBC are present in the peripheral blood of engrafted HMOX-1-/- mice, these mice have the potential to be used for hematological disease modeling, and to test therapeutic treatments for hRBC diseases in vivo.

Clinical applications of circulating biomarkers in non-small cell lung cancer.

Despite recent advances in cancer diagnostics and treatment, the mortality associated with lung cancer is still the highest in the world. Late-stage diagnosis, often accompanied by metastasis, is a major contributor to the high mortality rates, emphasizing the urgent need for reliable and readily accessible diagnostic tools that can detect biomarkers unique to lung cancer. Circulating factors, such as circulating tumor DNA and extracellular vesicles, from liquid biopsy have been recognized as diagnostic or prognostic markers in lung cancer. Numerous clinical studies are currently underway to investigate the potential of circulating tumor DNA, circulating tumor RNA, exosomes, and exosomal microRNA within the context of lung cancer. Those clinical studies aim to address the poor diagnostics and limited treatment options for lung cancer, with the ultimate goal of developing clinical markers and personalized therapies. In this review, we discuss the roles of each circulating factor, its current research status, and ongoing clinical studies of circulating factors in non-small cell lung cancer. Additionally, we discuss the circulating factors specifically found in lung cancer stem cells and examine approved diagnostic assays designed to detect circulating biomarkers in lung cancer patients.

Association between Use of Combustible Cigarettes and Noncombustible Nicotine or Tobacco Products and Health-Related Quality of Life in Korean Men: A Nationwide Population-Based Study.

Background: Although the association between smoking and health-related quality of life (HRQoL) has been established, the effects of tobacco products, including combustible cigarettes (CCs) and non-combustible nicotine or tobacco products (NNTPs), on HRQoL remain unclear. This study examined the association between tobacco use and HRQoL in Korean men. Methods: Data from the Korea National Health and Nutrition Examination Survey conducted between 2013 and 2020 were analyzed. A total of 16,429 male participants aged ≥19 years completed the European Quality of Life-5 Dimensions (EQ-5D). Impaired HRQoL was defined as scoring in the lowest 20% of the EQ-5D index and having some or extreme problems in the following five domains of the EQ-5D: mobility, self-care, usual activities, pain/ discomfort, and anxiety/depression. Multiple logistic regression was conducted to evaluate the risk of impaired HRQoL in current tobacco users. Results: Current tobacco users exhibited a significantly higher risk of impaired HRQoL compared with never users (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.05-1.92). Compared to never users, current tobacco users reported more problems with mobility and pain/discomfort (all P<0.05). Moreover, compared with former tobacco users, current tobacco users had a higher risk of impaired HRQoL (OR, 1.60; 95% CI, 1.18-2.17). Compared to former tobacco users, current tobacco users reported more problems with mobility and pain/discomfort (all P<0.05). Conclusion: Use of CCs and NNTPs is associated with impaired HRQoL in Korean men. Therefore, further interventions for lifestyle modification and smoking cessation treatments are required to reduce the risk of impaired HRQoL among current tobacco users.

Quenched Zwitterionic Cyclic Arg-Gly-Asp-Containing Pentapeptide Probe for Real-Time Brain Tumor Imaging.

The efficacy of glioblastoma treatment is closely associated with complete tumor resection. However, conventional surgical techniques often result in incomplete removal, leading to poor prognosis. A major challenge is the accurate delineation of tumor margins from healthy tissues. Imaging-guided surgery, particularly using fluorescent probes, is a promising solution for intraoperative guidance. The recently developed 'always-on' types of targeted fluorescence probes generate signals irrespective of their presence in tumor cells or in blood circulation, hampering their effectiveness. Here, we propose a novel activatable fluorescence imaging probe, Q-cRGD, that targets glioma cells via the specific binding of the cyclic Arg-Gly Asp-containing pentapeptide (cRGD) to integrins. The Q-cRGD probe was synthesized by conjugating a near-infrared (NIR) dye to a tryptophan quencher via a disulfide linkage, including a cRGD-targeting ligand. This activatable probe remained inactive until the redox-responsive cleavage of the disulfide linkage occurred within the target cell. The zwitterionic nature of NIR dyes minimizes nonspecific interactions with serum proteins, thereby enhancing the tumor-to-background signal ratio (TBR). An in vivo fluorescence imaging study demonstrated a TBR value of 2.65 within 3 h of the intravenous injection of Q-cRGD, confirming its potential utility in imaging-guided brain cancer surgery.

Influenza vaccination stimulates maturation of the human T follicular helper cell response.

The differentiation and specificity of human CD4+ T follicular helper cells (TFH cells) after influenza vaccination have been poorly defined. Here we profiled blood and draining lymph node (LN) samples from human volunteers for over 2 years after two influenza vaccines were administered 1 year apart to define the evolution of the CD4+ TFH cell response. The first vaccination induced an increase in the frequency of circulating TFH (cTFH) and LN TFH cells at week 1 postvaccination. This increase was transient for cTFH cells, whereas the LN TFH cells further expanded during week 2 and remained elevated in frequency for at least 3 months. We observed several distinct subsets of TFH cells in the LN, including pre-TFH cells, memory TFH cells, germinal center (GC) TFH cells and interleukin-10+ TFH cell subsets beginning at baseline and at all time points postvaccination. The shift toward a GC TFH cell phenotype occurred with faster kinetics after the second vaccine compared to the first vaccine. We identified several influenza-specific TFH cell clonal lineages, including multiple responses targeting internal influenza virus proteins, and found that each TFH cell state was attainable within a clonal lineage. Thus, human TFH cells form a durable and dynamic multitissue network.

Activatable near-infrared fluorescence probe for real-time imaging of PD-L1 expression in tumors.

In clinical practice, determining programmed death-ligand 1 (PD-L1) expression is crucial for selecting patients and monitoring immune checkpoint blockade therapies. Currently, PD-L1 expression is quantified using immunohistochemistry (IHC). However, IHC-based methods do not capture the heterogeneous and dynamic nature of PD-L1 expression. Thus, there is a pressing need for a rapid and efficient method for monitoring PD-L1 expression both in vitro and in vivo, which would considerably aid in prognosis and treatment selection. In this study, we present for the first time an activatable near-infrared (NIR) fluorescence imaging probe (Q-Atezol) for the real-time monitoring of PD-L1 expression in vitro and in vivo. The ability of Q-Atezol to detect PD-L1 expression quickly and in real-time was evaluated in both tumor spheroid and lung cancer xenograft models. An always-on optical probe (ON-Atezol) was synthesized and tested for comparison. In vivo NIR fluorescence imaging studies were conducted on A549 and H1975 tumor-bearing mice, and their tumor-to-background ratios (TBRs) were analyzed. The quenched NIR fluorescence of Q-Atezol is activated upon binding to PD-L1 proteins on the surface of cancer cells, thereby enabling PD-L1 detection in the three-dimensional (3D) tumor spheroids without a washing step. Notably, PD-L1-positive H1975 tumors were clearly visualized with a high TBR 6 hours after Q-Atezol injection, whereas ON-Atezol treatment could not detect H1975 tumors even 24 hours post-injection. The activatable fluorescence probe Q-Atezol demonstrated great potential as an exceptional sensor for assessing PD-L1 expression in 3D cell structures and for in vivo applications.

Central Role of Hypothalamic Circuits for Acupuncture's Anti-Parkinsonian Effects.

Despite clinical data stretching over millennia, the neurobiological basis of the effectiveness of acupuncture in treating diseases of the central nervous system has remained elusive. Here, using an established model of acupuncture treatment in Parkinson's disease (PD) model mice, we show that peripheral acupuncture stimulation activates hypothalamic melanin-concentrating hormone (MCH) neurons via nerve conduction. We further identify two separate neural pathways originating from anatomically and electrophysiologically distinct MCH neuronal subpopulations, projecting to the substantia nigra and hippocampus, respectively. Through chemogenetic manipulation specifically targeting these MCH projections, their respective roles in mediating the acupuncture-induced motor recovery and memory improvements following PD onset are demonstrated, as well as the underlying mechanisms mediating recovery from dopaminergic neurodegeneration, reactive gliosis, and impaired hippocampal synaptic plasticity. Collectively, these MCH neurons constitute not only a circuit-based explanation for the therapeutic effectiveness of traditional acupuncture, but also a potential cellular target for treating both motor and non-motor PD symptoms.

Battery-Free, Wireless Multi-Modal Sensor, and Actuator Array System for Pressure Injury Prevention.

Simultaneous monitoring of critical parameters (e.g., pressure, shear, and temperature) at bony prominences is essential for the prevention of pressure injuries in a systematic manner. However, the development of wireless sensor array for accurate mapping of risk factors has been limited due to the challenges in the convergence of wireless technologies and wearable sensor arrays with a thin and small form factor. Herein, a battery-free, wireless, miniaturized multi-modal sensor array is introduced for continuous mapping of pressure, shear, and temperature at skin interfaces. The sensor array includes an integrated pressure and shear sensor consisting of 3D strain gauges and micromachined components. The mechanically decoupled design of the integrated sensor enables reliable data acquisition of pressure and shear at skin interfaces without the need for additional data processing. The sensor platform enables the analysis of interplay among localized pressure, shear, and temperature in response to changes in the patient's movement, posture, and bed inclination. The validation trials using a novel combination of wireless sensor arrays and customized pneumatic actuator demonstrate the efficacy of the platform in continuous monitoring and efficient redistribution of pressure and shear without repositioning, thereby improving the patient's quality of life.