Selective omission of sentinel lymph node biopsy in mastectomy for ductal carcinoma in situ: identifying eligible candidates.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is recommended for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy, given the concerns regarding upstaging and technical difficulties of post-mastectomy SLNB. However, this may lead to potential overtreatment, considering favorable prognosis and de-escalation trends in DCIS. Data regarding upstaging and axillary lymph node metastasis among these patients remain limited. METHODS: We retrospectively reviewed patients with DCIS who underwent mastectomy with SLNB or axillary lymph node dissection at Gangnam Severance Hospital between January 2010 and December 2021. To explore the feasibility of omitting SLNB, we assessed the rates of DCIS upgraded to invasive carcinoma and axillary lymph node metastasis. Binary Cox regression analysis was performed to identify clinicopathologic factors associated with upstaging and axillary lymph node metastasis. RESULTS: Among 385 patients, 164 (42.6%) experienced an invasive carcinoma upgrade: microinvasion, pT1, and pT2 were confirmed in 53 (13.8%), 97 (25.2%), and 14 (3.6%) patients, respectively. Seventeen (4.4%) patients had axillary lymph node metastasis. Multivariable analysis identified age ≤ 50 years (adjusted odds ratio [OR], 12.73; 95% confidence interval [CI], 1.18-137.51; p = 0.036) and suspicious axillary lymph nodes on radiologic evaluation (adjusted OR, 9.31; 95% CI, 2.06-41.99; p = 0.004) as independent factors associated with axillary lymph node metastasis. Among patients aged > 50 years and/or no suspicious axillary lymph nodes, only 1.7-2.3%) experienced axillary lymph node metastasis. CONCLUSIONS: Although underestimation of the invasive component was relatively high among patients with DCIS undergoing mastectomy, axillary lymph node metastasis was rare. Our findings suggest that omitting SLNB may be feasible for patients over 50 and/or without suspicious axillary lymph nodes on radiologic evaluation.

KSCBi005-A-10(hiPSC-HIF1αKO), a HIF1α knockout human induced pluripotent stem cell line, for demonstrating the role of cellular response to hypoxia.

Under hypoxia, hypoxia-inducible factor (HIF)-1 regulates hypoxia-inducible genes, such as vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2. It is an oxygen-dependent transcriptional activator that plays a crucial role in tumor angiogenesis and mammalian embryo development. It is a heterodimeric protein comprising a constitutively expressed HIF-1ß subunit and the highly regulated HIF-1α subunits. Using CRISPR-Cas9 genome editing, we generated biallelic HIF-1α mutants in human induced pluripotent stem cells (hiPSCs). The HIF-1α homozygous-knockout hiPSCs retained their normal morphology, gene expression, and in vivo differentiation potential.

Exercise affects high-fat diet-stimulated breast cancer metastasis through irisin secretion by altering cancer stem cell properties.

Background: Regular physical activities reduce the growth of breast cancer, but research on the effects of steady exercise on metastasis and its mechanisms is limited. In this study, the effects of steady exercise on breast cancer metastasis and its possible mechanism were demonstrated. Methods: Experimental metastasis was induced after 8 weeks of steady exercise using a mouse model. Furthermore, one of the myokines, irisin, was studied to elucidate the effects of metastasis-regulating protein expression, and colony and sphere formation, which are cancer stem cell properties. Results: Low- and moderate-intensity exercise significantly reduced the number and volume of metastasized tumors. Among myokines, only irisin was significantly increased by steady exercise but decreased by a high-fat diet. In vitro studies, irisin significantly decreased the number of colonies and sphere formation. Irisin also inhibited cell migration and invasion and suppressed the malignancy of breast cancer cells by reducing the expression of vimentin, MMP-2, MMP-9, and HIF-1 and by increasing the expression of TIMP-1 and TIMP-2. Conclusion: Steady exercise modulates myokine secretions and among them, irisin suppresses breast cancer metastasis by decreasing self-renewal properties and invasion regulating protein expressions. Thus, regular exercise may be beneficial in the prevention of breast tumor metastasis.

Scalable Dry Process for Fabricating a Na Superionic Conductor-Type Solid Electrolyte Sheet.

The cost reduction and mass production of oxide-based solid electrolytes are critical for the commercialization of all-solid-state batteries. In this study, an environmentally friendly, low-cost, and high-density oxide-based Na superionic conductor-type solid electrolyte sheet was fabricated via a dry process without the use of any solvent. The polytetrafluoroethylene (PTFE), used as a binder, was transformed into thin thread-like structures via shear force, resulting in a flexible solid electrolyte sheet. The solid electrolyte powder quantity was limited to 50 wt % for fabricating a uniform green sheet via the wet process. However, when the dry process was employed for green sheet fabrication, the solid electrolyte powder quantity could be increased to values exceeding 95 wt %. Therefore, the green sheets produced by using the dry process demonstrated a higher density than those fabricated by using the wet process. The binder content and particle size affected the ionic conductivity of a solid electrolyte sheet fabricated via a dry process. The sheet obtained via the blending of 3 wt % PTFE binder with a solid electrolyte powder, finely ground using a planetary ball mill, which exhibited the highest total ionic conductivity of 1.03 mS cm-1.

Bee Venom Stimulates Growth Factor Release from Adipose-Derived Stem Cells to Promote Hair Growth.

Limited evidence suggests that stimulating adipose-derived stem cells (ASCs) indirectly promotes hair growth. We examined whether bee venom (BV) activated ASCs and whether BV-induced hair growth was facilitated by enhanced growth factor release by ASCs. The induction of the telogen-to-anagen phase was studied in mice. The underlying mechanism was investigated using organ cultures of mouse vibrissa hair follicles. When BV-treated ASCs were injected subcutaneously into mice, the telogen-to-anagen transition was accelerated and, by day 14, the hair weight increased. Quantitative polymerase chain reaction (qPCR) revealed that BV influenced the expression of several molecules, including growth factors, chemokines, channels, transcription factors, and enzymes. Western blot analysis was employed to verify the protein expression levels of extracellular-signal-regulated kinase (ERK) and phospho-ERK. Both the Boyden chamber experiment and scratch assay confirmed the upregulation of cell migration by BV. Additionally, ASCs secreted higher levels of growth factors after exposure to BV. Following BV therapy, the gene expression levels of alkaline phosphatase (ALP), fibroblast growth factor (FGF)-1 and 6, endothelial cell growth factor, and platelet-derived growth factor (PDGF)-C were upregulated. The findings of this study suggest that bee venom can potentially be utilized as an ASC-preconditioning agent for hair regeneration.

A mouse model of Zhu-Tokita-Takenouchi-Kim syndrome reveals indispensable SON functions in organ development and hematopoiesis.

Rare diseases are underrepresented in biomedical research, leading to insufficient awareness. Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is a rare disease caused by genetic alterations that result in heterozygous loss of function of SON. While patients with ZTTK syndrome live with numerous symptoms, the lack of model organisms hampers our understanding of SON and this complex syndrome. Here, we developed Son haploinsufficiency (Son+/-) mice as a model of ZTTK syndrome and identified the indispensable roles of Son in organ development and hematopoiesis. Son+/- mice recapitulated clinical symptoms of ZTTK syndrome, including growth retardation, cognitive impairment, skeletal abnormalities, and kidney agenesis. Furthermore, we identified hematopoietic abnormalities in Son+/- mice, including leukopenia and immunoglobulin deficiency, similar to those observed in human patients. Surface marker analyses and single-cell transcriptome profiling of hematopoietic stem and progenitor cells revealed that Son haploinsufficiency shifted cell fate more toward the myeloid lineage but compromised lymphoid lineage development by reducing genes required for lymphoid and B cell lineage specification. Additionally, Son haploinsufficiency caused inappropriate activation of erythroid genes and impaired erythropoiesis. These findings highlight the importance of the full gene expression of Son in multiple organs. Our model serves as an invaluable research tool for this rare disease and related disorders associated with SON dysfunction.

Epigenetic repression of CHCHD2 enhances survival from single cell dissociation through attenuated Rho A kinase activity.

During in vitro culture, human pluripotent stem cells (hPSCs) often acquire survival advantages characterized by decreased susceptibility to mitochondrial cell death, known as "culture adaptation." This adaptation is associated with genetic and epigenetic abnormalities, including TP53 mutations, copy number variations, trisomy, and methylation changes. Understanding the molecular mechanisms underlying this acquired survival advantage is crucial for safe hPSC-based cell therapies. Through transcriptome and methylome analysis, we discovered that the epigenetic repression of CHCHD2, a mitochondrial protein, is a common occurrence during in vitro culture using enzymatic dissociation. We confirmed this finding through genetic perturbation and reconstitution experiments in normal human embryonic stem cells (hESCs). Loss of CHCHD2 expression conferred resistance to single cell dissociation-induced cell death, a common stress encountered during in vitro culture. Importantly, we found that the downregulation of CHCHD2 significantly attenuates the activity of Rho-associated protein kinase (ROCK), which is responsible for inducing single cell death in hESCs. This suggests that hESCs may survive routine enzyme-based cell dissociation by downregulating CHCHD2 and thereby attenuating ROCK activity. These findings provide insights into the mechanisms by which hPSCs acquire survival advantages and adapt to in vitro culture conditions.

Efficacy of Allogeneic and Xenogeneic Exosomes for the Treatment of Canine Atopic Dermatitis: A Pilot Study.

Canine atopic dermatitis (CAD) is a genetically predisposed inflammatory pruritic skin disease. The available treatments for CAD have several adverse effects and vary in efficacy, indicating the need for the development of improved treatments. In this study, we aimed to elucidate the therapeutic effects of allogeneic and xenogeneic exosomes on CAD. Six laboratory beagle dogs with CAD were randomly assigned to three treatment groups: control, canine exosome (cExos), or human exosome (hExos) groups. Dogs in the cExos and hExos groups were intravenously administered 1.5 mL of cExos (5 × 1010) and hExos (7.5 × 1011) solutions, respectively, while those in the control group were administered 1.5 mL of normal saline three times per week for 4 weeks. Skin lesion score and transepidermal water loss decreased in cExos and hExos groups compared with those in the control group. The exosome treatments decreased the serum levels of inflammatory cytokines (interferon-γ, interleukin-2, interleukin-4, interleukin-12, interleukin-13, and interleukin-31) but increased those of anti-inflammatory cytokines (interleukin-10 and transforming growth factor-ß), indicating the immunomodulatory effect of exosomes. Skin microbiome analysis revealed that the exosome treatments alleviated skin bacterial dysbiosis. These results suggest that allogeneic and xenogeneic exosome therapy may alleviate CAD in dogs.

4D Printing of Ultrastretchable Magnetoactive Soft Material Architectures for Soft Actuators.

Magnetoactive soft materials (MSMs) comprising magnetic particles and soft matrices have emerged as smart materials for realizing soft actuators. 4D printing, which involves fabricating 3D architectures that can transform shapes under external magnetic fields, is an effective way to fabricate MSMs-based soft actuators with complex shapes. The printed MSMs must be flexible, stretchable, and adaptable in their magnetization profiles to maximize the degrees of freedom for shape morphing. This study utilizes a facile 4D printing strategy for producing ultrastretchable (stretchability > 1000%) MSM 3D architectures for soft-actuator applications. The strategy involves two sequential steps: (i) direct ink writing (DIW) of the MSM 3D architectures with ink composed of NdFeB and styrene-isoprene block copolymers (SIS) at room temperature and (ii) programming and reconfiguration of the magnetization profiles of the printed architecture using an origami-inspired magnetization method (magnetization field, Hm = 2.7 T). Various differently shaped MSM 3D architectures, which can be transformed into desired shapes under an actuation magnetic field (Ba = 85 mT), are successfully fabricated. In addition, two different soft-actuator applications are demonstrated: a multifinger magnetic soft gripper and a Kirigami-shaped 3D electrical switch with conductive and magnetic functionalities. Our strategy shows potential for realizing multifunctional, shape-morphing, and reprogrammable magnetoactive devices for advanced soft-actuator applications.

Cross-cultural adaptation of the Korean Synkinesis Assessment Questionnaire: A validation study.

Objective: The Synkinesis Assessment Questionnaire (SAQ) is a reliable tool to assess synkinesis symptoms; however, it is yet to be validated in Korea. Thus, this study aimed to translate and validate the Korean SAQ. Methods: This validation study was set in a clinic in Seoul, Korea, that provides general integrative medicine services. A total of 100 participants with facial palsy were enrolled. Participants completed the SAQ, House-Brackmann grade (HB grade), Sunnybrook Facial Grading System (SB), and Facial Disability Index (FDI). The forward-backward translation method was followed. Of the 100 participants, 31 underwent a second assessment for test-retest reliability. Internal consistency and test-retest reliability were evaluated using Cronbach's alpha coefficient. The construct validity of the Korean version of the SAQ was tested using Spearman's rank correlation coefficient. Results: The internal consistency score for the SAQ was 0.789, and the test-retest reliability score was 0.787. According to Spearman's rank correlation coefficient, the SAQ correlations to the synkinesis subdomain of SB score, total SB score, HB grade, and physical function domain in the FDI score were 0.366 (p < .001), -0.386 (p < .001), 0.315 (p = .001), and -0.269 (p = .007), respectively. All values were statistically significant. Conclusions: The Korean SAQ is a valid and reliable tool used to evaluate synkinesis in patients with facial palsy. Level of Evidence: Level 3.

Applying Sequential Pattern Mining to Investigate the Temporal Relationships between Commonly Occurring Internal Medicine Diseases and Intervals for the Risk of Concurrent Disease in Canine Patients.

Sequential pattern mining (SPM) is a data mining technique used for identifying common association rules in multiple sequential datasets and patterns in ordered events. In this study, we aimed to identify the relationships between commonly occurring internal medicine diseases in canine patients. We obtained medical records of dogs referred to the Konkuk University Veterinary Medicine Teaching Hospital. The data used for SPM included comorbidities and intervals between the diagnoses of internal medicine diseases. Additionally, we estimated the 3-year risk of developing an additional disease after the initial diagnosis of a commonly occurring veterinary internal medicine disease using logistic regression. We identified 547 canine patients diagnosed with ≥ 1 internal medicine disease. The SPM-based analysis assessed comorbidities and intervals for each of the five most common internal medical diseases, including hyperadrenocorticism, myxomatous mitral valve disease, canine atopic dermatitis, chronic kidney disease, and chronic pancreatitis. The highest values of the association rule were 3.01%, 6.02%, 3.9%, 4.1%, and 4.84%, and the shortest intervals were 1.64, 13.14, 5.37, 17.02, and 1.7 days, respectively. This study proposes that SPM is an effective technique for identifying common associations and temporal relationships between internal medicine diseases, and can be used to assess the probability of additional admission due to the development of the subsequent disease that may be diagnosed in canine patients. The results of this study will help veterinarians suggest appropriate preventive measures or other medical treatments for canine patients with medical conditions that have not yet been diagnosed, but are likely to develop in the short term.

Invasive FoxM1 phosphorylated by PLK1 induces the polarization of tumor-associated macrophages to promote immune escape and metastasis, amplified by IFITM1.

BACKGROUND: Understanding the mechanism behind immune cell plasticity in cancer metastasis is crucial for identifying key regulators. Previously we found that mitotic factors regulate epithelial-mesenchymal transition, but how these factors convert to metastatic players in the tumor microenvironment (TME) is not fully understood. METHODS: The clinical importance of mitotic factors was analyzed by heatmap analysis, a KM plot, and immunohistochemistry in lung adenocarcinoma (LUAD) patients. Immunoprecipitation, LC-MS/MS, kinase assay, and site-directed mutagenesis were performed for the interaction and phosphorylation. A tail-vein injection mouse model, Transwell-based 3D culture, microarray analysis, coculture with monocytes, and chromatin immunoprecipitation assays were used to elucidate the function of phosphorylated FoxM1 in metastasis of TME. RESULTS: The phosphorylated FoxM1 at Ser25 by PLK1 acquires the reprogramming ability to stimulate the invasive traits in cancer and influence immune cell plasticity. This invasive form of p-FoxM1 upregulates the expression of IL1A/1B, VEGFA, and IL6 by direct activation, recruiting monocytes and promoting the polarization of M2d-like tumor-associated macrophages (TAMs). Upregulation of PD-L1 in LUAD having phosphomimetic FoxM1 facilitates immune evasion. In invasive LUAD with phosphomimetic FoxM1, IFITM1 is the most highly expressed through the activation of the STING-TBK1-IRF3 signaling, which enhances FoxM1-mediated signaling. Clinically, higher expression of FOXM1, PLK1, and IFITM1 is inversely correlated with the survival rate of advanced LUAD patients, providing a promising therapeutic strategy for the treatment of LUAD. CONCLUSION: FoxM1-based therapy would be a potential therapeutic strategy for LUAD to reduce TAM polarization, immune escape, and metastasis, since FoxM1 functions as a genetic reprogramming factor reinforcing LUAD malignancy in the TME.

A multicellular liver organoid model for investigating hepatitis C virus infection and nonalcoholic fatty liver disease progression.

BACKGROUND AND AIMS: HCV infection can be successfully managed with antiviral therapies; however, progression to chronic liver disease states, including NAFLD, is common. There is currently no reliable in vitro model for investigating host-viral interactions underlying the link between HCV and NAFLD; although liver organoids (LOs) show promise, they currently lack nonparenchymal cells, which are key to modeling disease progression. APPROACH AND RESULTS: Here, we present a novel, multicellular LO model using a coculture system of macrophages and LOs differentiated from the same human pluripotent stem cells (PSCs). The cocultured macrophages shifted toward a Kupffer-like cell type, the liver-resident macrophages present in vivo , providing a suitable model for investigating NAFLD pathogenesis. With this multicellular Kupffer-like cell-containing LO model, we found that HCV infection led to lipid accumulation in LOs by upregulating host lipogenesis, which was more marked with macrophage coculture. Reciprocally, long-term treatment of LOs with fatty acids upregulated HCV amplification and promoted inflammation and fibrosis. Notably, in our Kupffer-like cell-containing LO model, the effects of 3 drugs for NASH that have reached phase 3 clinical trials exhibited consistent results with the clinical outcomes. CONCLUSIONS: Taken together, we introduced a multicellular LO model consisting of hepatocytes, Kupffer-like cells, and HSCs, which recapitulated host-virus intercommunication and intercellular interactions. With this novel model, we present a physiologically relevant system for the investigation of NAFLD progression in patients with HCV.

Long-term adjuvant metronomic chemotherapy in a dog with recurrent maxillofacial osteosarcoma.

Osteosarcoma (OSA) is the most common malignant bone tumour in dogs; however, OSA of the maxilla is uncommon compared to appendicular OSA. Oral melanoma also commonly occurs in dogs with frequent distant metastasis. The role of adjuvant chemotherapy has been questioned in maxillary OSA and melanoma. A 17-year-old English Cocker Spaniel was referred with a growing mass on the right maxilla and a right lower lip mass. Osteosarcoma was diagnosed after partial maxillectomy, and the right lower lip mass was diagnosed as oral melanoma. Metronomic chemotherapy (MC) was performed, and the number of doses was tapered due to side effects at 5 weeks after initiation of MC. After 130 weeks of MC, chemotherapy was suspended due to kidney disease. After the suspension of chemotherapy, findings suggesting recurrence and metastasis were detected. The dog suddenly died 193 weeks after surgery, which was 8-14 times longer than the expected survival time. To the best of our knowledge, this is the first case report of successful long-term combination therapy, including surgery and MC, in a dog with maxillary OSA and lip melanoma. Our results show that the survival time can be greatly extended if MC is performed with proper management.

A mouse model of ZTTK syndrome reveals indispensable SON functions in organ development and hematopoiesis.

Rare diseases are underrepresented in biomedical research, leading to insufficient awareness. Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is a rare disease caused by genetic alterations that result in heterozygous loss-of-function of SON. While ZTTK syndrome patients suffer from numerous symptoms, the lack of model organisms hamper our understanding of both SON and this complex syndrome. Here, we developed Son haploinsufficiency (Son+/-) mice as a model of ZTTK syndrome and identified the indispensable roles of Son in organ development and hematopoiesis. Son+/- mice recapitulated clinical symptoms of ZTTK syndrome, including growth retardation, cognitive impairment, skeletal abnormalities, and kidney agenesis. Furthermore, we identified hematopoietic abnormalities in Son+/- mice, similar to those observed in human patients. Surface marker analyses and single-cell transcriptome profiling of hematopoietic stem and progenitor cells revealed that Son haploinsufficiency inclines cell fate toward the myeloid lineage but compromises lymphoid lineage development by reducing key genes required for lymphoid and B cell lineage specification. Additionally, Son haploinsufficiency causes inappropriate activation of erythroid genes and impaired erythroid maturation. These findings highlight the importance of the full gene dosage of Son in organ development and hematopoiesis. Our model serves as an invaluable research tool for this rare disease and related disorders associated with SON dysfunction.

Case report: Adjuvant therapy with toceranib for an incompletely resected renal cell carcinoma with suspected pulmonary metastasis in a dog.

Primary renal neoplasia is rare in humans and dogs, with renal cell carcinoma (RCC) being the most common form of this cancer. As RCC is often diagnosed at an advanced stage, pulmonary metastasis is frequently observed. Tyrosine kinase inhibitors (TKIs) are the standard adjuvant treatments for metastatic RCC in humans. Similarly, in veterinary medicine, recent trials have employed TKIs for early-stage RCC patients who underwent complete surgical resection and showed no distant metastasis. However, the use of TKIs has not yet been reported commonly in cases of advanced RCC with metastasis. This case study presents the first clinical outcomes of TKI therapy in a dog with incompletely resected RCC and metastasis. A 5-year-old spayed female Chihuahua was referred to our hospital with a right renal mass and multiple pulmonary nodules suspected to be metastases. A portion of the renal mass was surgically removed, and histopathological examination revealed RCC with a high mitotic index. Adjuvant chemotherapy was administered, owing to incomplete resection with suspected pulmonary metastasis. An anticancer drug response prediction test was conducted using patient tissues. Since toceranib showed the most favorable responsiveness, it was selected as a therapeutic agent. Toceranib was orally administered at a dosage of 2.27 mg/kg every 48 h. Regular medical records for potential adverse effects were obtained, including systemic blood pressure, complete blood count, serum biochemical examination, and urinalysis. After 2 weeks of toceranib therapy, partial remission of pulmonary nodules continued for 2 months. The patient did not experience any adverse effects of the anticancer drug during the 4-month follow-up period. However, the patient died from an unidentified cause 6 months after the initial detection of the renal mass. This report describes the use of toceranib in dogs with RCC. In the present case, the patient showed an initial response to chemotherapy, and despite the presence of several poor prognostic factors, the dog survived beyond the expected 3-month lifespan to 6 months. Notably, no adverse events were observed during treatment.

Large contributions of petrogenic and aged soil-derived organic carbon to Arctic fjord sediments in Svalbard.

Svalbard fjords are recognized as hotspots for organic carbon (OC) burial and storage due to their high sedimentation rates, which effectively trap terrestrial sediments and inhibit extensive OC remineralization. In this study, we investigated surface sediments (n = 48) from eight Svalbard fjords, along with bedrock (n = 17), soil (n = 28), and plant (n = 12) samples, to identify the sources of sedimentary OC in these fjords using geochemical parameters. All examined surface sediments from the fjords showed a depletion in 14Corg (- 666.9 ± 240.3‰), indicating that recently fixed terrestrial and marine biomass alone cannot account for the entire sedimentary OC pool. Conventional bulk indicators such as Norg/TOC ratio and δ13Corg were insufficient for fully determining the sources of sedimentary OC. Therefore, we employed a four-end-member approach, using Δ14Corg, δ13Corg, and lignin phenols to assess the relative contributions of petrogenic, soil-derived, plant-derived, and marine OC to the sedimentary OC pool. The analyzed fjord sediments consisted, on average, of 59.0 ± 28.1% petrogenic OC, 16.8 ± 12.1% soil-derived OC, 2.5 ± 2.2% plant-derived OC, and 21.8 ± 18.5% marine OC. This approach highlights the substantial contributions of petrogenic and aged soil-derived OC to present-day sedimentary OC in Svalbard fjords. Considering predicted global warming, accelerated inputs of petrogenic and soil-derived OC into fjords due to rapid glacier retreat may significantly impact the active carbon cycle and potentially contribute to CO2 emissions to the atmosphere, depending on burial efficiency.

All-Solid-State Synaptic Transistors with Lithium-Ion-Based Electrolytes for Linear Weight Mapping and Update in Neuromorphic Computing Systems.

Neuromorphic computing, an innovative technology inspired by the human brain, has attracted increasing attention as a promising technology for the development of artificial intelligence systems. This study proposes synaptic transistors with a Li1-xAlxTi2-x(PO4)3 (LATP) layer to analyze the conductance modulation linearity, which is essential for weight mapping and updating during on-chip learning processes. The high ionic conductivity of the LATP electrolyte provides a large hysteresis window and enables linear weight update in synaptic devices. The results demonstrate that optimizing the LATP layer thickness improves the conductance modulation and linearity of synaptic transistors during potentiation and degradation. A 20 nm-thick LATP layer results in the most nonlinear depression (αd = -6.59), whereas a 100 nm-thick LATP layer results in the smallest nonlinearity (αd = -2.22). Additionally, a device with the optimal 100 nm-thick LATP layer exhibits the highest average recognition accuracy of 94.8% and the smallest fluctuation, indicating that the linearity characteristics of a device play a crucial role in weight update during learning and can significantly affect the recognition accuracy.

KSCBi005-A-8(hiPSC-PD-L1KO), a PD-L1 knockout human induced pluripotent stem cell line for demonstrating the role of the PD-1/PD-L1 axis.

Programmed Cell Death Ligand 1 (PD-L1) is a trans-membrane protein that attenuates the host immune response to tumor cells. PD-L1 ligand on the surface of the cancer binds to PD-1 transmembrane receptors on T cells and exhausts T cells function. Using CRISPR-Cas9 genome editing, we generated biallelic PD-L1 mutants in human induced pluripotent stem cells (hiPSCs). The PD-L1 homozygous-knockout hiPSCs retained their normal morphology, gene expression, and in vivo differentiation potential.