Selenium alloyed tellurium oxide for amorphous p-channel transistors.

Compared to polycrystalline semiconductors, amorphous semiconductors offer inherent cost-effective, simplicity, and uniform manufacturing. Traditional amorphous hydrogenated Si falls short in electrical properties, necessitating the exploration of new materials. The creation of high-mobility amorphous n-type metal oxides, such as a-InGaZnO1, and their integration into thin-film transistors (TFTs) have propelled advancements in modern large-area electronics and new-generation displays2-8. However, finding comparable p-type counterparts poses significant challenges, impeding the progress of complementary metal-oxide-semiconductor (CMOS) technology and integrated circuits9-11. Here, we introduce a pioneering design strategy for amorphous p-type semiconductors, incorporating high-mobility tellurium within an amorphous tellurium sub-oxide matrix, and demonstrate its utility in high-performance, stable p-channel TFTs, and complementary circuits. Theoretical analysis unveils a delocalised valence band from tellurium 5p bands with shallow acceptor states, enabling excess hole doping and transport. Selenium alloying suppresses hole concentrations and facilitates the p orbital connectivity, realising high-performance p-channel TFTs with an average field-effect hole mobility of ~15 cm2 V-1 s-1 and on/off current ratios of 106 ~ 107, along with wafer-scale uniformity and long-term stabilities under bias stress and ambient aging. This study represents a crucial stride towards establishing commercially viable amorphous p-channel TFT technology and complementary electronics in a low-cost and industry-compatible manner.

The Effects of Fermented Rice Drink With Lactiplantibacillus plantarum JSA22 in Overweight Irritable Bowel Syndrome Patients: A Randomized, Double-blind, Placebo-controlled Study.

Background/Aims: This study aims to investigate the effect of a fermented rice drink with Lactiplantibacillus plantarum JSA22 on symptoms, blood tests, microbiomes, and fecal metabolites in patients with irritable bowel syndrome (IBS) who were overweight. Methods: Sixty overweight (body mass index ≥ 23 kg/m2) patients aged between 20 and 65 with IBS were enrolled. Patients were divided into 2 groups and administered either a fermented rice drink or an nonfermented rice drink for a month. The symptom questionnaire, blood samples, and stool samples for microbiome and metabolite were collected before and after the month of rice drink administration. The primary efficacy variable was the subject's global assessment of IBS symptoms. Results: In both groups, global IBS symptoms, including abdominal pain, bowel habit, urgency, and abdominal distension, improved significantly (P < 0.01). The abdominal bloating was more significantly improved in the fermented rice drink group than in the nonfermented rice drink group (P < 0.05). Significant changes were not observed in metabolic syndrome-related blood tests or fecal metabolites in either group. However, microbiome analysis showed significant differences in genus levels before and after consuming fermented rice drink, such as in Blautia in stool (P = 0.020) and Prevotella (P = 0.017) and Oribacterium (P = 0.018) in saliva. Conclusions: The fermented rice drink with L. plantarum JSA22 showed a beneficial effect in reducing abdominal distension in IBS patients. Bacteria that reduce visceral fat accumulation increased in the stool and saliva of patients who consumed fermented rice drinks.

Intracerebroventricular administration of TRH Agonist, RX-77368 alleviates visceral pain induced by colorectal distension in rats.

Thyrotropin-releasing hormone (TRH) acts centrally to exert pleiotropic actions independently from its endocrine function, including antinociceptive effects against somatic pain in rodents. Whether exogenous or endogenous activation of TRH signaling in the brain modulates visceral pain is unknown. Adult male Sprague-Dawley rats received an intracerebroventricular (ICV) injection of the stable TRH analog, RX-77368 (10, 30 and 100 ng/rat) or saline (5 µl) or were semi-restrained and exposed to cold (4°C) for 45 min. The visceromotor response (VMR) to graded phasic colorectal distensions (CRD) was monitored using non-invasive intracolonic pressure manometry. Naloxone (1 mg/kg) was injected subcutaneously 10 min before ICV RX-77368 or saline. Fecal pellet output was monitored for 1 h after ICV injection. RX-77368 ICV (10, 30 and 100 ng/rat) reduced significantly the VMR by 56.7%, 67.1% and 81.1% at 40 mmHg and by 30.3%, 58.9% and 87.4% at 60 mmHg respectively vs ICV saline. Naloxone reduced RX-77368 (30 and 100 ng, ICV) analgesic response by 51% and 28% at 40 mmHg and by 30% and 33% at 60 mmHg respectively, but had no effect per se. The visceral analgesia was mimicked by the acute exposure to cold. At the doses of 30 and 100 ng, ICV RX-77368 induced defecation within 30 min. These data established the antinociceptive action of RX-77368 injected ICV in a model of visceral pain induced by colonic distension through recruitment of both opioid and non-opioid dependent mechanisms.

Masculinity, Rather Than Biological Sex, Is Associated With Psychological Comorbidities in Patients With Irritable Bowel Syndrome.

Background/Aims: Irritable bowel syndrome (IBS) generally shows sex differences, and psychiatric comorbidities play an important role in its pathogenesis. We aim to measure the levels of gender roles and investigate their relationship with psychiatric factors in patients with IBS versus healthy controls. Methods: Patients diagnosed with IBS by Rome III and whose colonoscopy findings were normal were enrolled at multiple sites in Korea. The participants completed the Korean Sex Role Inventory-Short Form (KSRI-SF) to assess masculinity and femininity, the stress questionnaire, the Hospital Anxiety Depression Scale (HADS), and the 36-item Short Form Health Survey questionnaire to assess the quality of life (QOL). Results: In total, 102 patients with IBS (male:female = 35:67; mean age 42.6 ± 16.7 years) and 55 controls (male:female = 20:35; mean age 42.4 ± 11.1 years) were recruited. IBS patients had higher stress (9.69 ± 8.23 vs 4.56 ± 8.31, P < 0.001) and HADS scores (16.12 ± 7.17 vs 10.22 ± 5.74, P < 0.001) than the control group, but showed no significant difference in KSRI-SF scores. No significant differences in HADS and KSRI-SF scores were found between males and females. However, IBS patients whose symptoms worsened due to stress and patients with anxiety or depression had significantly lower masculinity. QOL was poorer in IBS patients than in controls. In stepwise multivariate analyses, the anxiety score, depression score, and the degree of daily life disturbance, not masculinity, were associated with the QOL of IBS patients. Conclusions: IBS patients had higher stress, more psychiatric comorbidities, and lower QOL than controls. Low masculinity, rather than sex, was associated with stress and psychological comorbidities, which deteriorated the QOL in IBS patients.

Conversion of Host Cell Receptor into Virus Destructor by Immunodisc to Neutralize Diverse SARS-CoV-2 Variants.

The decreasing efficacy of antiviral drugs due to viral mutations highlights the challenge of developing a single agent targeting multiple strains. Using host cell viral receptors as competitive inhibitors is promising, but their low potency and membrane-bound nature have limited this strategy. In this study, the authors show that angiotensin-converting enzyme 2 (ACE2) in a planar membrane patch can effectively neutralize all tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that emerged during the COVID-19 pandemic. The ACE2-incorporated membrane patch implemented using nanodiscs replicated the spike-mediated membrane fusion process outside the host cell, resulting in virus lysis, extracellular RNA release, and potent antiviral activity. While neutralizing antibodies became ineffective as the SARS-CoV-2 evolved to better penetrate host cells the ACE2-incorporated nanodiscs became more potent, highlighting the advantages of using receptor-incorporated nanodiscs for antiviral purposes. ACE2-incorporated immunodisc, an Fc fusion nanodisc developed in this study, completely protected humanized mice infected with SARS-CoV-2 after prolonged retention in the airways. This study demonstrates that the incorporation of viral receptors into immunodisc transforms the entry gate into a potent virucide for all current and future variants, a concept that can be extended to different viruses.

Progranulin haploinsufficiency mediates cytoplasmic TDP-43 aggregation with lysosomal abnormalities in human microglia.

BACKGROUND: Progranulin (PGRN) haploinsufficiency due to progranulin gene (GRN) variants can cause frontotemporal dementia (FTD) with aberrant TAR DNA-binding protein 43 (TDP-43) accumulation. Despite microglial burden with TDP-43-related pathophysiology, direct microglial TDP-43 pathology has not been clarified yet, only emphasized in neuronal pathology. Thus, the objective of this study was to investigate TDP-43 pathology in microglia of patients with PGRN haploinsufficiency. METHODS: To design a human microglial cell model with PGRN haploinsufficiency, monocyte-derived microglia (iMGs) were generated from FTD-GRN patients carrying pathogenic or likely pathogenic variants (p.M1? and p.W147*) and three healthy controls. RESULTS: iMGs from FTD-GRN patients with PGRN deficiency exhibited severe neuroinflammation phenotype and failure to maintain their homeostatic molecular signatures, along with impaired phagocytosis. In FTD-GRN patients-derived iMGs, significant cytoplasmic TDP-43 aggregation and accumulation of lipid droplets with profound lysosomal abnormalities were observed. These pathomechanisms were mediated by complement C1q activation and upregulation of pro-inflammatory cytokines. CONCLUSIONS: Our study provides considerable cellular and molecular evidence that loss-of-function variants of GRN in human microglia can cause microglial dysfunction with abnormal TDP-43 aggregation induced by inflammatory milieu as well as the impaired lysosome. Elucidating the role of microglial TDP-43 pathology in intensifying neuroinflammation in individuals with FTD due to PGRN deficiency and examining consequential effects on microglial dysfunction might yield novel insights into the mechanisms underlying FTD and neurodegenerative disorders.

Layer-Controlled Growth of Single-Crystalline 2D Bi2O2Se Film Driven by Interfacial Reconstruction.

As semiconductor scaling continues to reach sub-nanometer levels, two-dimensional (2D) semiconductors are emerging as a promising candidate for the post-silicon material. Among these alternatives, Bi2O2Se has risen as an exceptionally promising 2D semiconductor thanks to its excellent electrical properties, attributed to its appropriate bandgap and small effective mass. However, unlike other 2D materials, growth of large-scale Bi2O2Se films with precise layer control is still challenging due to its large surface energy caused by relatively strong interlayer electrostatic interactions. Here, we present the successful growth of a wafer-scale (∼3 cm) Bi2O2Se film with precise thickness control down to the monolayer level on TiO2-terminated SrTiO3 using metal-organic chemical vapor deposition (MOCVD). Scanning transmission electron microscopy (STEM) analysis confirmed the formation of a [BiTiO4]1- interfacial structure, and density functional theory (DFT) calculations revealed that the formation of [BiTiO4]1- significantly reduced the interfacial energy between Bi2O2Se and SrTiO3, thereby promoting 2D growth. Additionally, spectral responsivity measurements of two-terminal devices confirmed a bandgap increase of up to 1.9 eV in monolayer Bi2O2Se, which is consistent with our DFT calculations. Finally, we demonstrated high-performance Bi2O2Se field-effect transistor (FET) arrays, exhibiting an excellent average electron mobility of 56.29 cm2/(V·s). This process is anticipated to enable wafer-scale applications of 2D Bi2O2Se and facilitate exploration of intriguing physical phenomena in confined 2D systems.

An analysis of variants in TARDBP in the Korean population with amyotrophic lateral sclerosis: comparison with previous data.

The TARDBP gene variant is a known major cause of amyotrophic lateral sclerosis (ALS), with limited reports of Korean patients with ALS harboring the variants in TARDBP. This large cohort study introduces four ALS patients who share the p.M337V variant of the TARDBP, allowing for an investigation of clinical characteristics and prognosis by analyzing previously reported cases with the same variant. From November 2014 to August 2022, participants were recruited from two tertiary hospitals in Seoul, Korea. Clinical characteristics of patients diagnosed with ALS carrying the variant in TARDBP were evaluated. Previous articles demonstrating subjects' characteristics were reviewed. Four patients were identified with the pathogenic missense variant (c.1009A>G; p.M337V) in the TARDBP. The mean age of onset was 55 years old, and none of the patients showed severe cognitive impairment. Sixty-three patients carrying the p.M337V variant in TARDBP from this study and previous reports delineated young age of onset (51.6 years), high frequency of bulbar onset patients (61.9%), and low comorbidity of frontotemporal dementia. This study reveals the presence of pathogenic variant of TARDBP in Korea and emphasizes the importance of genetic screening of the TARDBP gene, in diagnosing ALS and evaluating prognosis among familial and simplex ALS patients in Korea.

Engineering bispecific T-cell engagers to deplete eosinophils for the treatment of severe eosinophilic asthma.

Severe eosinophilic asthma (SEA) is characterized by elevated eosinophil counts in the blood and airway mucosa. While monoclonal antibody therapies targeting interleukin-5 (IL-5) and its receptor (IL-5Rα) have improved treatment, some patients remain unresponsive. We propose an alternative approach to eliminate eosinophils using T cells by engineering IL-5Rα × CD3 bispecific T-cell engagers (bsTCEs) that target both IL-5Rα on eosinophils and CD3 on T cells. We designed different formats of IL-5Rα × CD3 bsTCEs, incorporating variations in valency, geometry, and affinity for the target antigen binding. We identified the single-chain variable fragment (scFv)-Fc format with the highest affinity toward the membrane-proximal domain of IL-5Rα in the IL-5Rα-binding arm showed the most potent cytotoxicity against IL-5Rα-expressing peripheral eosinophils by activating autologous primary T cells from healthy donors. This study proposes IL-5Rα × CD3 bsTCEs as potential alternatives for SEA treatment. Importantly, it demonstrates the first application of bsTCEs in eliminating disease-associated cells, including eosinophils, beyond cancer cells.

Thermodynamically Driven Tilt Grain Boundaries of Monolayer Crystals Using Catalytic Liquid Alloys.

We report a method to precisely control the atomic defects at grain boundaries (GBs) of monolayer MoS2 by vapor-liquid-solid (VLS) growth using sodium molybdate liquid alloys, which serve as growth catalysts to guide the formations of the thermodynamically most stable GB structure. The Mo-rich chemical environment of the alloys results in Mo-polar 5|7 defects with a yield exceeding 95%. The photoluminescence (PL) intensity of VLS-grown polycrystalline MoS2 films markedly exceeds that of the films, exhibiting abundant S 5|7 defects, which are kinetically driven by vapor-solid-solid growths. Density functional theory calculations indicate that the enhanced PL intensity is due to the suppression of nonradiative recombination of charged excitons with donor-type defects of adsorbed Na elements on S 5|7 defects. Catalytic liquid alloys can aid in determining a type of atomic defect even in various polycrystalline 2D films, which accordingly provides a technical clue to engineer their properties.

Multi-omics data of gastric cancer cell lines.

OBJECTIVES: Gastric cancer (GC) is the fourth most common cancer worldwide, with the highest incidence and mortality regardless of sex. Despite technological advances in diagnosing and treating gastric cancer, GC still has high incidence and mortality rates. Therefore, continuous research is needed to overcome GC. In various studies, cell lines are used to find and verify the cause of specific diseases. Large-scale genomic studies such as ENCODE and Roadmap epigenomic projects provide multiomics data from various organisms and samples. However, few multi-omics data for gastric tissues and cell lines have been generated. Therefore, we performed RNA-seq, Exome-seq, and ChIP-seq with several gastric cell lines to generate a multi-omics data set in gastric cancer. DATA DESCRIPTION: Multiomic data, such as RNA-seq, Exome-seq, and ChIP-seq, were produced in gastric cancer and normal cell lines. RNA-seq data were generated from nine GC and one normal gastric cell line, mapped to a human reference genome (hg38) using the STAR alignment tool, and quantified with HTseq. Exome sequence data were produced in nine GC and two normal gastric lines. Sequenced reads were mapped and processed using BWA-MEM and GATK, variants were called by stralka2, and annotation was performed using ANNOVAR. Finally, for the ChIP-seq, nine GC cell lines and four GC cell lines were used in two experimental sets; chip-seq was performed to confirm changes in H3K4me3 and H3K27me3. Data was mapped to human reference hg38 with BWA-MEM, and peak calling and annotation were performed using the Homer tool. Since these data provide multi-omics data for GC cell lines, it will be useful for researchers who use the GC cell lines to study.

[Brain-Gut-Microbiota Axis].

Patients frequently report that stress causes or exacerbates gastrointestinal (GI) symptoms, indicating a functional relationship between the brain and the GI tract. The brain and GI tract are closely related embryologically and functionally, interacting in various ways. The concept of the brain-gut axis was originally established in the 19th and early 20th centuries based on physiological observations and experiments conducted in animals and humans. In recent years, with the growing recognition that gut microbiota plays a vital role in human health and disease, this concept has been expanded to the brain-gut-microbiota axis. The brain influences the motility, secretion, and immunity of the GI tract, with consequent effects on the composition and function of the gut microbiota. On the other hand, gut microbiota plays an essential role in the development and function of the brain and enteric nervous system. Although knowledge of the mechanisms through which the gut microbiota influences distant brain function is incomplete, studies have demonstrated communication between these organs through the neuronal, immune, and endocrine systems. The brain-gut-microbiota axis is an essential aspect of the pathophysiology of functional GI disorders such as irritable bowel syndrome, and is also involved in other GI diseases, including inflammatory bowel disease. This review summarizes the evolving concept of the brain-gut-microbiota axis and its implications for GI diseases, providing clinicians with new knowledge to apply in clinical practice.

Epigenetic Activation of Tensin 4 Promotes Gastric Cancer Progression.

Gastric cancer (GC) is a complex disease influenced by multiple genetic and epigenetic factors. Chronic inflammation caused by Helicobacter pylori infection and dietary risk factors can result in the accumulation of aberrant DNA methylation in gastric mucosa, which promotes GC development. Tensin 4 (TNS4), a member of the Tensin family of proteins, is localized to focal adhesion sites, which connect the extracellular matrix and cytoskeletal network. We identified upregulation of TNS4 in GC using quantitative reverse transcription PCR with 174 paired samples of GC tumors and adjacent normal tissues. Transcriptional activation of TNS4 occurred even during the early stage of tumor development. TNS4 depletion in GC cell lines that expressed high to moderate levels of TNS4, i.e., SNU-601, KATO III, and MKN74, reduced cell proliferation and migration, whereas ectopic expression of TNS4 in those lines that expressed lower levels of TNS4, i.e., SNU-638, MKN1, and MKN45 increased colony formation and cell migration. The promoter region of TNS4 was hypomethylated in GC cell lines that showed upregulation of TNS4. We also found a significant negative correlation between TNS4 expression and CpG methylation in 250 GC tumors based on The Cancer Genome Atlas (TCGA) data. This study elucidates the epigenetic mechanism of TNS4 activation and functional roles of TNS4 in GC development and progression and suggests a possible approach for future GC treatments.

Self-Assembled TaOX/2H-TaS2 as a van der Waals Platform of a Multilevel Memristor Circuit Integrated with a ß-Ga2O3 Transistor.

Two-dimensional (2D)-layered material tantalum disulfide (2H-TaS2) is known to be a van der Waals conductor at room temperature. Here, 2D-layered TaS2 has been partially oxidized by utraviolet-ozone (UV-O3) annealing to form a 12-nm-thin TaOX on conducting TaS2, so that the TaOX/2H-TaS2 structure might be self-assembled. Utilizing the TaOX/2H-TaS2 structure as a platform, each device of a ß-Ga2O3 channel MOSFET and a TaOX memristor has been successfully fabricated. An insulator structure of Pt/TaOX/2H-TaS2 shows good a dielectric constant (k ∼ 21) and strength (∼3 MV/cm) of achieved TaOX, which is enough to support a ß-Ga2O3 transistor channel. Based on the quality of TaOX and low trap density of the TaOX/ß-Ga2O3 interface, which is achieved via another UV-O3 annealing, excellent device properties such as little hysteresis (<∼0.04 V), band-like transport, and a steep subthreshold swing of ∼85 mV/dec are achieved. With a Cu electrode on top of the TaOX/2H-TaS2 structure, the TaOX acts as a memristor operating around ∼2 V for nonvolatile bipolar and unipolar mode memories. The functionalities of the TaOX/2H-TaS2 platform become more distinguished finally when the Cu/TaOX/2H-TaS2 memristor and ß-Ga2O3 MOSFET are integrated to form a resistive memory switching circuit. The circuit nicely demonstrates the multilevel memory functions.