Synergistic Buried Interface Regulation of Tin-Lead Perovskite Solar Cells via Co-Self-Assembled Monolayers.

Tin-lead (Sn-Pb) perovskite solar cells (PSCs) hold considerable potential for achieving efficiencies near the Shockley-Queisser (S-Q) limit. Notably, the inverted structure stands as the preferred fabrication method for the most efficient Sn-Pb PSCs. In this regard, it is imperative to implement a strategic customization of the hole selective layer to facilitate carrier extraction and refine the quality of perovskite films, which requires effective hole selectivity and favorable interactions with Sn-Pb perovskites. Herein, we propose the development of Co-Self-Assembled Monolayers (Co-SAM) by integrating both [2-(9H-carbazol-9-yl)ethyl]phosphonic acid (2PACz) and glycine at the buried contacts. The one-step deposition process employed in the fabrication of the Co-SAM ensures uniform coverage, resulting in a homogeneous surface potential. This is attributed to the molecular interactions occurring between 2PACz and glycine in the processing solution. Furthermore, the amine (-NH2) and ammonium (-NH3+) groups in glycine effectively passivate Sn4+ defects at the buried interface of Sn-Pb perovskite films, even under thermal stress. Consequently, the synergistic buried interface regulation of Co-SAM leads to a power conversion efficiency (PCE) of 23.46%, which outperforms devices modified with 2PACz or glycine alone. The Co-SAM-modified Sn-Pb PSC demonstrates enhanced thermal stability, maintaining 88% of its initial PCE under 65 °C thermal stress for 590 h.

Emergence of the mobile colistin resistance gene mcr-1 in a Leclercia adecarboxylata strain isolated from wastewater in Seoul.

Colistin is considered the last resort for treating infections caused by multidrug-resistant bacteria. However, the spread of the plasmid-borne colistin-resistance gene mcr-1 has become a public health threat. In this study, we identified mcr-1-harboring Leclercia adecarboxylata strain (WWCOL-134) isolated from wastewater in Seoul. The strain had a colistin MIC value of 2 µg/ml and was resistant to cefotaxime, gentamicin, tetracycline, trimethoprim, and sulfamethoxazole. The mcr-1 gene, along with an array of resistance genes, was located on a 236-kb plasmid (pCOL134-1), which contained the typical IncHI2 backbone of reported mcr-1-carrying plasmids, and was transferred to an Escherichia coli strain by conjugation. To the best of our knowledge, this is the first study to report the emergence of mcr-1-harboring Leclercia sp. isolate. Our findings demonstrate the ongoing spread of colistin resistance among Enterobacterales species, emphasizing the need for surveillance of antimicrobial resistance in wastewater environments.

Raphanus sativus Linne Protects Human Nucleus Pulposus Cells against H2O2-Induced Damage by Inhibiting TREM2.

Intervertebral disc degeneration (IDD) progresses owing to damage and depletion of nucleus pulposus (NP) cells. Cytoprotection mitigates oxidative stress, nutrient deprivation, and mechanical stress, which lead to cell damage and necrosis. We aimed to examine the protective effect of Raphanus sativus Linne (RSL), common radish, against oxidative stress by H2O2 in human NP cells and whether the RSL extracts can inhibit triggering receptor expressed on myeloid cells 2 (TREM2), an inducer of apoptosis and degeneration in NP cells. We administered hydrogen peroxide (H2O2) to cultured human NP cells treated with RSL extracts. We used immunoblotting and quantitative PCR to investigate expression of the apoptosis-associated proteins in cultured cells. RSL significantly enhanced cell survival by suppressing the activation of cleaved caspase-3 and Bax. In contrast, RSL extract increased Bcl2 concentration to downregulate apoptosis. Additionally, RSL treatment notably enhanced the mRNA levels of ACAN and Col2a1 while significantly reducing those of ADAMTS-4, ADAMTS-5, MMP3, and MMP13, key genes involved in NP degeneration. While H2O2 elevated TREM2 expression, causing disc degeneration, RSL downregulated TREM2 expression. Thus, our findings imply that RSL supports human NP cells under oxidative stress and regulates the pathways underlying disc degeneration, particularly TREM2, and that RSL extracts may potentially prevent IDD.

Non-invasive prediction of post-sustained virological response HCC in HCV: A systematic review and meta-analysis.

Background: Despite advances in antiviral therapy for hepatitis C virus (HCV) infection, hepatocellular carcinoma (HCC) still develops even after sustained viral response (SVR) in patients with advanced liver fibrosis or cirrhosis. This meta-analysis investigated the predictive performance of transient elastography (TE) and fibrosis 4-index (FIB-4) for the development of HCC after SVR. Methods: We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library for studies examining the predictive performance of these tests in adult patients with HCV. Two authors independently screened the studies' methodological quality and extracted data. Pooled estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for HCC development using random-effects bivariate logit normal and linear-mixed effect models. Results: We included 27 studies (169,911 patients). Meta-analysis of HCC after SVR was possible in nine TE and 15 FIB-4 studies. Regarding the prediction of HCC development after SVR, the pooled AUCs of pre-treatment TE >9.2-13 kPa and FIB-4 >3.25 were 0.79 and 0.73, respectively. TE >8.4-11 kPa and FIB-4 >3.25 measured after SVR, maintained good predictive performance, albeit slightly reduced (pooled AUCs: 0.77 and 0.70, respectively). The identified optimal cut-off value for HCC development after SVR was 12.6 kPa for pre-treatment TE. That of TE measured after the SVR was 11.2 kPa. Conclusion: TE and FIB-4 showed acceptable predictive performance for HCC development in patients with HCV who achieved SVR, underscoring their utility in clinical practice for guiding surveillance strategies. Future studies are needed to validate these findings prospectively and validate their clinical impact.

Discovery of novel disease-causing mutation in SSBP1 and its correction using adenine base editor to improve mitochondrial function.

Mutations in nuclear genes regulating mitochondrial DNA (mtDNA) replication are associated with mtDNA depletion syndromes. Using whole-genome sequencing, we identified a heterozygous mutation (c.272G>A:p.Arg91Gln) in single-stranded DNA-binding protein 1 (SSBP1), a crucial protein involved in mtDNA replisome. The proband manifested symptoms including sensorineural deafness, congenital cataract, optic atrophy, macular dystrophy, and myopathy. This mutation impeded multimer formation and DNA-binding affinity, leading to reduced efficiency of mtDNA replication, altered mitochondria dynamics, and compromised mitochondrial function. To correct this mutation, we tested two adenine base editor (ABE) variants on patient-derived fibroblasts. One variant, NG-Cas9-based ABE8e (NG-ABE8e), showed higher editing efficacy (≤30%) and enhanced mitochondrial replication and function, despite off-target editing frequencies; however, risks from bystander editing were limited due to silent mutations and off-target sites in non-translated regions. The other variant, NG-Cas9-based ABE8eWQ (NG-ABE8eWQ), had a safer therapeutic profile with very few off-target effects, but this came at the cost of lower editing efficacy (≤10% editing). Despite this, NG-ABE8eWQ-edited cells still restored replication and improved mtDNA copy number, which in turn recovery of compromised mitochondrial function. Taken together, base editing-based gene therapies may be a promising treatment for mitochondrial diseases, including those associated with SSBP1 mutations.

Interobserver Variability in the International Study Group for Pancreas Surgery (ISGPS)-Defined Complications After Pancreatoduodenectomy: An International Cross-Sectional Multicenter Study.

OBJECTIVE: To determine the interobserver variability for complications of pancreatoduodenectomy as defined by the International Study Group for Pancreatic Surgery (ISGPS) and others. SUMMARY BACKGROUND DATA: Good interobserver variability for the definitions of surgical complications is of major importance in comparing surgical outcomes between and within centers. However, data on interobserver variability for pancreatoduodenectomy-specific complications are lacking. METHODS: International cross-sectional multicenter study including 52 raters from 13 high-volume pancreatic centers in 8 countries on 3 continents. Per center, 4 experienced raters scored 30 randomly selected patients after pancreatoduodenectomy. In addition, all raters scored six standardized case vignettes. This variability and the 'within centers' variability were calculated for twofold scoring (no complication/grade A vs grade B/C) and threefold scoring (no complication/grade A vs grade B vs grade C) of postoperative pancreatic fistula (POPF), post-pancreatoduodenectomy hemorrhage (PPH), chyle leak (CL), bile leak (BL), and delayed gastric emptying (DGE). Interobserver variability is presented with Gwet's AC-1 measure for agreement. RESULTS: Overall, 390 patients after pancreatoduodenectomy were included. The overall agreement rate for the standardized cases vignettes for twofold scoring was 68% (95%-CI: 55%-81%, AC1 score: moderate agreement) and for threefold scoring 55% (49%-62%, AC1 score: fair agreement). The mean 'within centers' agreement for twofold scoring was 84% (80%-87%, AC1 score; substantial agreement). CONCLUSION: The interobserver variability for the ISGPS defined complications of pancreatoduodenectomy was too high even though the 'within centers' agreement was acceptable. Since these findings will decrease the quality and validity of clinical studies, ISGPS has started efforts aimed at reducing the interobserver variability.

Intraindividual comparison of prognostic imaging features of HCCs between MRIs with extracellular and hepatobiliary contrast agents.

BACKGROUND & AIMS: Accumulating evidence suggests that certain imaging features of hepatocellular carcinoma (HCC) may have prognostic implications. This study aimed to intraindividually compare MRIs with extracellular contrast agent (ECA-MRI) and hepatobiliary agent (HBA-MRI) for prognostic imaging features of HCC and to compare the prediction of microvascular invasion (MVI) and early recurrence between the two MRIs. METHODS: The present study included 102 prospectively enrolled at-risk patients (median age, 61.0 years; 83 men) with surgically resected single HCC with both preoperative ECA-MRI and HBA-MRI between July 2019 and June 2023. The McNemar test was used to compare each prognostic imaging feature between the two MRIs. Significant imaging features associated with MVI were identified by multivariable logistic regression analysis, and early recurrence rates (<2 years) were compared between the two MRIs. RESULTS: The frequencies of prognostic imaging features were not significantly different between the two MRIs (p = .07 to >.99). Non-smooth tumour margin (ECA-MRI, odds ratio [OR] = 5.30; HBA-MRI, OR = 7.07) and peritumoral arterial phase hyperenhancement (ECA-MRI, OR = 4.26; HBA-MRI, OR = 4.43) were independent factors significantly associated with MVI on both MRIs. Two-trait predictor of venous invasion (presence of internal arteries and absence of hypoattenuating halo) on ECA-MRI (OR = 11.24) and peritumoral HBP hypointensity on HBA-MRI (OR = 20.42) were other predictors of MVI. Early recurrence rates of any two or more significant imaging features (49.8% on ECA-MRI vs 51.3% on HBA-MRI, p = .75) were not significantly different between the two MRIs. CONCLUSION: Prognostic imaging features of HCC may be comparable between ECA-MRI and HBA-MRI.

Randomized controlled trial on the efficacy of a custom-made, fully guided implant system for flapless crestal sinus floor elevation: Accuracy and patient-reported outcomes.

OBJECTIVE: To compare fully guided flapless implant surgery using a light-cured surgical guide (FG group) with partially guided open flap surgery (PG group) in the posterior maxilla when performing simultaneous sinus floor elevation in terms of the accuracy, time requirements, and patient/clinician-reported outcomes (PROMs and CROMs). MATERIALS AND METHODS: In this study, 56 tissue-level implants were placed with crestal sinus floor elevation in 56 patients at single-tooth sites, with 28 implants allocated to the PG group and 28 to the FG group. The deviations of the placed implants from the virtually planned positions were measured at the implant platform and apex and for the angular deviation. The presurgical preparation time and the duration of surgery were measured. PROMs and CROMs were made by administering questionnaires at multiple time points. RESULTS: Horizontal deviations at the platform and apex and the angular deviation were significantly smaller in the FG group than the PG group (p < .05). Presurgical preparation and surgery times were significantly shorter in the FG group (p < .001). Patient satisfaction and willingness to receive repeat treatment were significantly better in the FG group than in the PG group (p < .005 and .025, respectively). Clinicians were more satisfied in the FG group than the PG group (p < .05). CONCLUSION: When placing an implant with sinus floor elevation, the flapless approach using a fully guided surgical system can be more accurate, faster, and increase the satisfaction of both the clinician and patient compared to the partially guided surgery.

Comparing clinical and genomic features based on the tumor location in patients with resected pancreatic cancer.

BACKGROUND: Pancreatic cancer is anatomically divided into pancreatic head and body/tail cancers, and some studies have reported differences in prognosis. However, whether this discrepancy is induced from the difference of tumor biology is hotly debated. Therefore, we aimed to evaluate the differences in clinical outcomes and tumor biology depending on the tumor location. METHODS: In this retrospective cohort study, we identified 800 patients with pancreatic ductal adenocarcinoma who had undergone upfront curative-intent surgery. Cox regression analysis was performed to explore the prognostic impact of the tumor location. Among them, 153 patients with sufficient tumor tissue and blood samples who provided informed consent for next-generation sequencing were selected as the cohort for genomic analysis. RESULTS: Out of the 800 patients, 500 (62.5%) had pancreatic head cancer, and 300 (37.5%) had body/tail cancer. Tumor location in the body/tail of the pancreas was not identified as a significant predictor of survival outcomes compared to that in the head in multivariate analysis (hazard ratio, 0.94; 95% confidence interval, 0.77-1.14; P = 0.511). Additionally, in the genomic analyses of 153 patients, there were no significant differences in mutational landscapes, distribution of subtypes based on transcriptomic profiling, and estimated infiltration levels of various immune cells between pancreatic head and body/tail cancers. CONCLUSIONS: We could not find differences in prognosis and tumor biology depending on tumor location in pancreatic ductal adenocarcinoma. Discrepancies in prognosis may represent a combination of lead time, selection bias, and clinical differences, including the surgical burden between tumor sites.

Effect of intramolecular energy transfer in a dual-functional molecular dyad on the performance of solution-processed TADF OLEDs.

This paper introduces the design concept of a dual-functional molecular dyad tailored specifically for solution-processable organic light-emitting diodes (OLEDs). Cy-tmCPBN, characterized by an asymmetric molecular dyad structure, integrates a host unit (tmCP) and a multiple-resonance (MR) emitter (CzBN) via a non-conjugated cyclohexane linker. Cy-tmCPBN exhibited efficient intramolecular energy transfers (EnTs) from tmCP to the CzBN unit, as confirmed by time-resolved fluorescence experiments. The fluorescence lifetime of the tmCP unit was approximately three times shorter in a highly diluted solution of Cy-tmCPBN than in a mixed solution of Cy-tmCP and Cy-CzBN. In addition, Cy-tmCPBN exhibited excellent solubility and film-forming ability, making it suitable for solution processing. Notably, OLEDs utilizing Cy-tmCPBN achieved over twice the brightness and improved external quantum efficiency of 12.3% compared to OLEDs using Cy-CzBN with the same concentration of CzBN in the emitting layer. The improved OLED performance can be explained by the increased EnT efficiency from Cy-tmCP to Cy-tmCPBN and the intramolecular EnT within Cy-tmCPBN. In our dual-functional dyad, incorporating both host and emitter units in an asymmetric molecular dyad structure, we induced a positive synergy effect with the host moiety, enhancing OLED performance through intramolecular EnT.

Development and validation of the self-consciousness type scale.

Introduction: Previous research has highlighted the duality of self-consciousness, which simultaneously plays adaptive and maladaptive roles. This study aims to develop a measure that categorically distinguishes between different types of self-consciousness styles based on the Regulatory Focus Theory (RFT) and examines their relationship with mental health-related indicators. Methods: Data were gathered through an online mental health survey conducted at a University Student Counseling Center in Seoul. The study involved exploratory factor analysis, confirmatory factor analysis, and reliability and validity analysis, which resulted in the development of a 14-question Self-Consciousness Type Scale (SCTS). Results: Both exploratory and confirmatory factor analyses validated the two-factor structure of the SCTS. The fit indices of the final model indicated a good fit, with high internal consistency for both sub-factors. Convergent and discriminant validity were confirmed through correlations between the sub-scales. Cluster analysis identified four distinct subtypes of self-consciousness styles: Growth-oriented, Defensive, Ambivalent, and Low-focus self-consciousness. Group difference analysis revealed significant differences in mental health-related variables among the subtypes, supporting the 2 × 2 model of prevention-focused and promotion-focused self-consciousness. Discussion: The findings support the SCTS as a valid measurement tool capable of distinguishing four distinct types of self-consciousness, aligning with the multidimensional model of self-consciousness. The study's limitations and implications were discussed based on the results, emphasizing the potential applications of the SCTS in mental health research and practice.

Development of a fit-for-purpose multi-marker panel for early diagnosis of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) suffers from lack of an effective diagnostic method, which hampers improvement in patient survival. Carbohydrate antigen 19-9 (CA19-9) is the only FDA-approved blood biomarker for PDAC, yet its clinical utility is limited due to suboptimal performance. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a burgeoning technology in clinical proteomics for discovery, verification, and validation of novel biomarkers. A plethora of protein biomarker candidates for PDAC have been identified using LC-MS, yet few has successfully transitioned into clinical practice. This translational standstill is owed partly to insufficient considerations of practical needs and perspectives of clinical implementation during biomarker development pipelines, such as demonstrating analytical robustness of proposed biomarkers which is critical for transitioning from research-grade to clinical-grade assays. Moreover, throughput and cost-effectiveness of proposed assays ought to be considered concomitantly from early phases of the biomarker pipelines for enhancing widespread adoption in clinical settings. Here, we developed a fit-for-purpose multi-marker panel for PDAC diagnosis by consolidating analytically robust biomarkers as well as employing a relatively simple LC-MS protocol. In discovery phase, we comprehensively surveyed putative PDAC biomarkers from both in-house data and prior studies. In verification phase, we developed a multiple-reaction monitoring (MRM)-MS-based proteomic assay using surrogate peptides that passed stringent analytical validation tests. We adopted a high-throughput protocol including short gradient (<10 min) and simple sample preparation (no depletion or enrichment steps). Additionally, we developed our assay using serum samples, which are usually the preferred biospecimen in clinical settings. We developed predictive models based on our final panel of 12 protein biomarkers combined with CA19-9, which showed improved diagnostic performance compared to using CA19-9 alone in discriminating PDAC from non-PDAC controls including healthy individuals and patients with benign pancreatic diseases. A large-scale clinical validation is underway to demonstrate the clinical validity of our novel panel.

10-Year Clinical Outcomes of V4c Implantable Collamer Lens Implantation: Longitudinal Analysis of Visual Acuity, Endothelial Cell Density, and Vault Dynamics.

PURPOSE: This study aimed to evaluate the long-term clinical outcomes of V4c Implantable Collamer Lens (ICL) implantation for myopia correction over a 10-year period. DESIGN: Retrospective interventional case series METHODS: This retrospective interventional study involved 103 myopic eyes from 54 patients. Visual outcomes, including visual acuity and manifest refraction were assessed. Annual measurements of endothelial cell density (ECD), vault, anterior chamber depth, and intraocular pressure were analyzed using mixed-effects models. RESULTS: At the 10-year follow-up, the mean Logarithm of the Minimum Angle of Resolution (logMAR) uncorrected distance visual acuity and corrected distance visual acuity (CDVA) were -0.037 ± 0.052 and -0.041 ± 0.046, respectively. The mean efficacy and safety indices were 1.11 ± 0.13 and 1.12 ± 0.12. A loss of one line of CDVA occurred in 2% of cases, while 59% gained one or more lines. Postoperative manifest refraction spherical equivalent (MRSE) was within ±0.5 diopters (D) and ±1.0 D in 74% and 99% of cases, respectively, with a mean MRSE of -0.19 ± 0.41 D. Data for ECD and vault fit an exponential decay model, demonstrating a continuous yet gradually slowing decrease over time. Decay rates were 0.012 ± 0.001/year for ECD and 0.056 ± 0.003/year for the vault. Notably, ECD lower outliers had significantly lower preoperative ECD values. There were no instances of cataract formation, angle closure, glaucoma, or ICL removal throughout the study. CONCLUSIONS: The 10-year outcomes of V4c ICL implantation demonstrate effective and safe visual results. Both ECD and vault exhibit exponential decay patterns over the decade. Patients with lower preoperative ECD values require careful post-implantation monitoring.

Doctor shopping trend of patients before undergoing rotator cuff repair in Korea: a multicenter study.

Background: To investigate the doctor shopping trend of patients with rotator cuff tear (RCT) before undergoing surgery and the relevance of the results to the public. Methods: A survey was conducted of 326 patients from 10 hospitals (male, 176; female, 150) who underwent arthroscopic rotator cuff repair (ARCR) for symptomatic RCT between September 2019 and February 2020. A questionnaire was used to obtain data regarding the type of medical care service, medical institutions visited before surgery, number of treatments received, and cost of treatment. Results: A total of 326 patients (87%) received treatment at least once at another medical institution before visiting the hospital where the surgery was performed. Patients visited an average of 9.4 health providers or physicians for shoulder pain before visiting the hospital where surgery was performed. Among the 326 patients, 148 (45%) visited more than two medical institutions and spent an average of 641,983 Korean won (KRW; $466, 50,000-5,000,000 KRW) before surgery. Medical expenses before surgery were proportional to the number of medical institutions visited (P=0.002), symptom duration (P=0.002), and initial visual analog scale (VAS) pain score (P=0.007) but were not associated with gender, age, VAS pain score immediately before surgery, or RCT size. Conclusions: Medical expense before ARCR was associated with the severity of preoperative pain and duration of symptoms. After onset of shoulder symptoms, patients should visit as soon as possible a hospital that has surgeons who specialize in shoulder repair to prevent unnecessary medical expense and proper treatment.

Senescent fibroblasts in the tumor stroma rewire lung cancer metabolism and plasticity.

Senescence has been demonstrated to either inhibit or promote tumorigenesis. Resolving this paradox requires spatial mapping and functional characterization of senescent cells in the native tumor niche. Here, we identified senescent p16 Ink4a + cancer-associated fibroblasts with a secretory phenotype that promotes fatty acid uptake and utilization by aggressive lung adenocarcinoma driven by Kras and p53 mutations. Furthermore, rewiring of lung cancer metabolism by p16 Ink4a + cancer-associated fibroblasts also altered tumor cell identity to a highly plastic/dedifferentiated state associated with progression in murine and human LUAD. Our ex vivo senolytic screening platform identified XL888, a HSP90 inhibitor, that cleared p16 Ink4a + cancer-associated fibroblasts in vivo. XL888 administration after establishment of advanced lung adenocarcinoma significantly reduced tumor burden concurrent with the loss of plastic tumor cells. Our study identified a druggable component of the tumor stroma that fulfills the metabolic requirement of tumor cells to acquire a more aggressive phenotype.

Early postoperative fever as a predictor of pancreatic fistula after pancreaticoduodenectomy: a single-center retrospective observational study.

BACKGROUND: The connection between early postoperative fever and clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy remains unclear. This study aimed to investigate this association and assess the predictive value of early postoperative fever for CR-POPF. METHODS: This retrospective observational study included adult patients who underwent pancreaticoduodenectomy at a tertiary teaching hospital between 2007 and 2019. Patients were categorized into those with early postoperative fever (≥ 38 °C in the first 48 h after surgery) and those without early postoperative fever groups. Weighted logistic regression analysis using stabilized inverse probability of treatment weighting (sIPTW) and multivariable logistic analysis were performed. The c-statistics of the receiver operating characteristic curves were calculated to evaluate the impact on the predictive power of adding early postoperative fever to previously identified predictors of CR-POPF. RESULTS: Of the 1997 patients analyzed, 909 (45.1%) developed early postoperative fever. The overall incidence of CR-POPF among all the patients was 14.3%, with an incidence of 19.5% in the early postoperative fever group and 9.9% in the group without early postoperative fever. Early postoperative fever was significantly associated with a higher risk of CR-POPF after sIPTW (adjusted odds ratio [OR], 1.73; 95% confidence interval [CI], 1.34-2.22; P < 0.001) and multivariable logistic regression analysis (adjusted OR, 1.88; 95% CI, 1.42-2.49; P < 0.001). The c-statistics for the models with and without early postoperative fever were 0.76 (95% CI, 0.73-0.79) and 0.75 (95% CI, 0.72-0.78), respectively, showing a significant difference between the two (difference, 0.02; 95% CI, 0.00-0.03; DeLong's test, P = 0.005). CONCLUSIONS: Early postoperative fever is a significant but not highly discriminative predictor of CR-POPF after pancreaticoduodenectomy. However, its widespread occurrence limits its applicability as a predictive marker.

Development of Non-Invasive miRNA Markers for Assessing the Quality of Human Induced Pluripotent Stem Cell-Derived Retinal Organoids.

Human retinal organoids (ROs) have emerged as valuable tools for studying retinal development, modeling human retinal diseases, and screening drugs. However, their application is limited primarily due to time-intensive generation, high costs, and low reproducibility. Quality assessment of RO differentiation is crucial for their application in research. However, traditional methods such as morphological evaluation and immunohistochemical analysis have limitations due to their lack of precision and invasiveness, respectively. This study aims to identify non-invasive biomarkers for RO differentiation quality using exosomal microRNAs (miRNAs), which are known to reflect cell-specific functions and development in the retina. We differentiated ROs from human induced pluripotent stem cells (hiPSCs) and classified them into 'superior' and 'inferior' groups based on morphological and immunohistochemical criteria. Exosomes from the conditioned media were isolated and analyzed for miRNA content. Our findings revealed distinct miRNA profiles between superior and inferior ROs, with superior ROs exhibiting higher miRNA diversity and specifically up- or down-regulated miRNAs. Gene ontology and pathway enrichment analyses indicated that the target genes of these miRNAs are involved in neuron proliferation and differentiation. The study suggests the potential of exosomal hsa-miR-654-3p and hsa-miR-451a as non-invasive biomarkers for real-time monitoring of RO quality, facilitating the development of standardized, efficient, and cost-effective culture methods.

Early Developmental Characteristics and Features of a Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis.

X-linked juvenile retinoschisis (XLRS) is a hereditary retinal degeneration affecting young males caused by mutations in the retinoschisin (RS1) gene. We generated human induced pluripotent stem cells (hiPSCs) from XLRS patients and established three-dimensional retinal organoids (ROs) for disease investigation. This disease model recapitulates the characteristics of XLRS, exhibiting defects in RS1 protein production and photoreceptor cell development. XLRS ROs also revealed dysregulation of Na/K-ATPase due to RS1 deficiency and increased ERK signaling pathway activity. Transcriptomic analyses of XLRS ROs showed decreased expression of retinal cells, particularly photoreceptor cells. Furthermore, relevant recovery of the XLRS phenotype was observed when co-cultured with control ROs derived from healthy subject during the early stages of differentiation. In conclusion, our in vitro XLRS RO model presents a valuable tool for elucidating the pathophysiological mechanisms underlying XLRS, offering insights into disease progression. Additionally, this model serves as a robust platform for the development and optimization of targeted therapeutic strategies, potentially improving treatment outcomes for patients with XLRS.

Resistive Gas Sensors Based on 2D TMDs and MXenes.

ConspectusGas sensors are used in various applications to sense toxic gases, mainly for enhanced safety. Resistive sensors are particularly popular owing to their ability to detect trace amounts of gases, high stability, fast response times, and affordability. Semiconducting metal oxides are commonly employed in the fabrication of resistive gas sensors. However, these sensors often require high working temperatures, bringing about increased energy consumption and reduced selectivity. Furthermore, they do not have enough flexibility, and their performance is significantly decreased under bending, stretching, or twisting. To address these challenges, alternative materials capable of operating at lower temperatures with high flexibility are needed. Two-dimensional (2D) materials such as MXenes and transition-metal dichalcogenides (TMDs) offer high surface area and conductivity owing to their unique 2D structure, making them promising candidates for realization of resistive gas sensors. Nevertheless, their sensing performance in pristine form is typically weak and unacceptable, particularly in terms of response, selectivity, and recovery time (trec). To overcome these drawbacks, several strategies can be employed to enhance their sensing properties. Noble-metal decoration such as (Au, Pt, Pd, Rh, Ag) is a highly promising method, in which the catalytic effects of noble metals as well as formation of potential barriers with MXenes or TMDs eventually contribute to boosted response. Additionally, bimetallic noble metals such as Pt-Pd and Au/Pd with their synergistic properties can further improve sensor performance. Ion implantation is another feasible approach, involving doping of sensing materials with the desired concentration of dopants through control over the energy and dosage of the irradiation ions as well as creation of structural defects such as oxygen vacancies through high-energy ion-beam irradiation, contributing to enhanced sensing capabilities. The formation of core-shell structures is also effective, creating numerous interfaces between core and shell materials that optimize the sensing characteristics. However, the shell thickness needs to be carefully optimized to achieve the best sensing output. To reduce energy consumption, sensors can operate in a self-heating condition where an external voltage is applied to the electrodes, significantly lowering the power requirements. This enables sensors to function in energy-constrained environments, such as remote or low-energy areas. An important advantage of 2D MXenes and TMDs is their high mechanical flexibility. Unlike semiconducting metal oxides that lack mechanical flexibility, MXenes and TMDs can maintain their sensing performance even when integrated onto flexible substrates and subjected to bending, tilting, or stretching. This flexibility makes them ideal for fabricating flexible and portable gas sensors that rigid sensors cannot achieve.