Inhibition of the RPS6KA1/FoxO1 signaling axis by hydroxycitric acid attenuates HFD-induced obesity through MCE suppression.

BACKGROUND: Because obesity is associated with a hyperplasia-mediated increase in adipose tissue, inhibiting cell proliferation during mitotic clonal expansion (MCE) is a leading strategy for preventing obesity. Although (-)-hydroxycitric acid (HCA) is used to control obesity, the molecular mechanisms underlying its effects on MCE are poorly understood. PURPOSE: This study aimed to investigate the potential effects of HCA on MCE and underlying molecular mechanisms affecting adipogenesis and obesity improvements. METHODS: Preadipocyte cell line, 3T3-L1, were treated with HCA; oil red O, cell proliferation, cell cycle, and related alterations in signaling pathways were examined. High-fat diet (HFD)-fed mice were administered HCA for 12 weeks; body and adipose tissues weights were evaluated, and the regulation of signaling pathways in epidydimal white adipose tissue were examined in vivo. RESULTS: Here, we report that during MCE, HCA attenuates the proliferation of the preadipocyte cell line, 3T3-L1, by arresting the cell cycle at the G0/G1 phase. In addition, HCA markedly inhibits Forkhead Box O1 (FoxO1) phosphorylation, thereby inducing the expression of cyclin-dependent kinase inhibitor 1B and suppressing the levels of cyclin-dependent kinase 2, cyclin E1, proliferating cell nuclear antigen, and phosphorylated retinoblastoma. Importantly, we found that ribosomal protein S6 kinase A1 (RPS6KA1) influences HCA-mediated inactivation of FoxO1 and its nuclear exclusion. An animal model of obesity revealed that HCA reduced high-fat diet-induced obesity by suppressing adipocyte numbers as well as epididymal and mesenteric white adipose tissue mass, which is attributed to the regulation of RPS6KA1, FoxO1, CDKN1B and PCNA that had been consistently identified in vitro. CONCLUSIONS: These findings provide novel insights into the mechanism by which HCA regulates adipogenesis and highlight the RPS6KA1/FoxO1 signaling axis as a therapeutic target for obesity.

Localization of hyperpolarization-activated cyclic nucleotide-gated channels in the vertebrate retinas across species and their physiological roles.

Transmembrane proteins known as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control the movement of Na+ and K+ ions across cellular membranes. HCN channels are known to be involved in crucial physiological functions in regulating neuronal excitability and rhythmicity, and pacemaker activity in the heart. Although HCN channels have been relatively well investigated in the brain, their distribution and function in the retina have received less attention, remaining their physiological roles to be comprehensively understood. Also, because recent studies reported HCN channels have been somewhat linked with the dysfunction of photoreceptors which are affected by retinal diseases, investigating HCN channels in the retina may offer valuable insights into disease mechanisms and potentially contribute to identifying novel therapeutic targets for retinal degenerative disorders. This paper endeavors to summarize the existing literature on the distribution and function of HCN channels reported in the vertebrate retinas of various species and discuss the potential implications for the treatment of retinal diseases. Then, we recapitulate current knowledge regarding the function and regulation of HCN channels, as well as their relevance to various neurological disorders.

Tumour-associated myeloid cells expressing IL-10R2/IL-22R1 as a potential biomarker for diagnosis and recurrence of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor survival rate, largely due to the lack of early diagnosis. Although myeloid cells are crucial in the tumour microenvironment, whether their specific subset can be a biomarker of PDAC progression is unclear. METHODS: We analysed IL-22 receptor expression in PDAC and peripheral blood. Additionally, we analysed gene expression profiles of IL-10R2+/IL-22R1+ myeloid cells and the presence of these cells using single-cell RNA sequencing and murine orthotropic PDAC models, respectively, followed by examining the immunosuppressive function of IL-10R2+/IL-22R1+ myeloid cells. Finally, the correlation between IL-10R2 expression and PDAC progression was evaluated. RESULTS: IL-10R2+/IL-22R1+ myeloid cells were present in PDAC and peripheral blood. Blood IL-10R2+ myeloid cells displayed a gene expression signature associated with tumour-educated circulating monocytes. IL-10R2+/IL-22R1+ myeloid cells from human myeloid cell culture inhibited T cell proliferation. By mouse models for PDAC, we found a positive correlation between pancreatic tumour growth and increased blood IL-10R2+/IL-22R1+ myeloid cells. IL-10R2+/IL-22R1+ myeloid cells from an early phase of the PDAC model suppressed T cell proliferation and cytotoxicity. IL-10R2+ myeloid cells indicated tumour recurrence 130 days sooner than CA19-9 in post-pancreatectomy patients. CONCLUSIONS: IL-10R2+/IL-22R1+ myeloid cells in the peripheral blood might be an early marker of PDAC prognosis.

Identifying a key spot for electron mediator-interaction to tailor CO dehydrogenase's affinity.

Fe‒S cluster-harboring enzymes, such as carbon monoxide dehydrogenases (CODH), employ sophisticated artificial electron mediators like viologens to serve as potent biocatalysts capable of cleaning-up industrial off-gases at stunning reaction rates. Unraveling the interplay between these enzymes and their associated mediators is essential for improving the efficiency of CODHs. Here we show the electron mediator-interaction site on ChCODHs (Ch, Carboxydothermus hydrogenoformans) using a systematic approach that leverages the viologen-reactive characteristics of superficial aromatic residues. By enhancing mediator-interaction (R57G/N59L) near the D-cluster, the strategically tailored variants exhibit a ten-fold increase in ethyl viologen affinity relative to the wild-type without sacrificing the turn-over rate (kcat). Viologen-complexed structures reveal the pivotal positions of surface phenylalanine residues, serving as external conduits for the D-cluster to/from viologen. One variant (R57G/N59L/A559W) can treat a broad spectrum of waste gases (from steel-process and plastic-gasification) containing O2. Decoding mediator interactions will facilitate the development of industrially high-efficient biocatalysts encompassing gas-utilizing enzymes.

Robotic transabdominal preperitoneal repair for bilateral obturator hernia: a video vignette.

Obturator hernias (OHs) are a rare cause of bowel obstruction that requires immediate surgical intervention to prevent morbidity and mortality. Patients with OHs present with acute intestinal obstruction secondary to incarceration, with a high morbidity and mortality rate due to delayed diagnosis and treatment. Although several surgical approaches have been reported, a standard approach for OH treatment has not yet been established. Here, we report the case of a 74-year-old woman who presented with bilateral OHs. The patient presented at our institution with pain in the left lower quadrant. Computed tomography revealed preperitoneal fat in both obturator foramen. Robotic transabdominal preperitoneal (R-TAPP) bilateral OH repair was performed, and a mesh was placed over both obturator foramen. The patient recovered without postoperative complications and was discharged on postoperative day 2. This suggests that the R-TAPP approach is safe for OH repair without incarceration.

Shoulder balance in Lenke type 2 adolescent idiopathic scoliosis: correlations among radiological indices, cosmetic indices, and patient-reported outcomes.

OBJECTIVE: The aim of this study was to investigate the correlation between radiological indices of shoulder balance (SB) and cosmetic indices of shoulder deformity in patients with Lenke type 2 adolescent idiopathic scoliosis (AIS) and to determine the extent to which patient-reported outcomes (PROs) correlate with these measurements. Current management decisions and outcomes for SB in AIS are primarily based on radiological measurements. It is crucial to understand how these radiological parameters and cosmetic indices relate to patient satisfaction. METHODS: The authors analyzed the preoperative radiological and photographic indices of SB, along with PROs, in patients with Lenke type 2 AIS. Lateral SB parameters included the radiological shoulder height (RSH) and clavicle angle, while medial SB parameters included the first rib angle and T1 tilt angle. Photographic indices included the shoulder height angle (SHA), axilla height angle (AHA), and the left/right trapezius angle (LRTA) ratio. The authors assessed the self-image, mental health, and total score domains of the Korean version of the 22-item Scoliosis Research Society questionnaire. RESULTS: In their analysis of Lenke type 2 patients, the authors found that correlation coefficients between radiological measurements and photographic indices ranged from -0.25 to 0.47, among which only lateral SB including clavicle angle and RSH showed a significant correlation with anterior and posterior photographic indices. No statistically significant correlations were found between radiological measurements and PROs. Anterior photographic indices including SHA and AHA significantly correlated with all three PROs (p < 0.05). CONCLUSIONS: Radiological shoulder parameters did not accurately reflect the perceived SB. Anterior photographic indices were reliable for evaluating clinical SB in patients with Lenke type 2 AIS and correlated with PROs. Spine surgeons may benefit from paying more attention to anterior photographic indices when making surgical decisions regarding clinical SB.

Serial Nerve Conduction Studies in Guillain-Barré Syndrome: Its Usefulness and Precise Timing.

PURPOSE: Nerve conduction study (NCS) is essential for subclassifying Guillain-Barré syndrome (GBS). It is well known that the GBS subclassification can change through serial NCSs. However, the usefulness of serial NCSs is debatable, especially in patients with early stage GBS. METHODS: Follow-up NCS data within 3 weeks (early followed NCS, EFN) and within 3 to 10 weeks (late-followed NCS, LFN) were collected from 60 patients with GBS who underwent their first NCS (FN) within 10 days after symptom onset. Each NCS was classified into five subtypes (normal, demyelinating, axonal, inexcitable, and equivocal), according to Hadden's and Rajabally's criteria. We analyzed the frequency of significant changes in classification (SCCs) comprising electrodiagnostic aggravation and subtype shifts between demyelinating and axonal types according to follow-up timing. RESULTS: Between FN and EFN, 33.3% of patients with Hadden's criteria and 18.3% with Rajabally's criteria showed SCCs. Between FN and LFN, 23.3% of patients with Hadden's criteria and 21.7% with Rajabally's criteria showed SCCs, of which 71.4% (Hadden's criteria) and 46.2% (Rajabally's criteria) already showed SCCs from the EFN. The conditions of delayed SCCs between EFN and LFN were very early FN, mild symptoms at the FN, or persistent electrophysiological deterioration 3 weeks after symptom onset. CONCLUSIONS: A substantial proportion of patients with GBS showed significant changes in neurophysiological classification at the early stage. Serial NCS may be helpful for precise neurophysiological classification. This study suggests that follow-up NCSs should be performed within 3 weeks of symptom onset in patients with GBS in whom FN was performed within 10 days of symptom onset.

Effect of hyperbilirubinemia on the accuracy of continuous non-invasive hemoglobin measurements in liver transplantation recipients.

This study evaluated the effect of hyperbilirubinemia on the accuracy of continuous non-invasive hemoglobin (SpHb) measurements in liver transplantation recipients. Overall, 1465 SpHb and laboratory hemoglobin (Hb) measurement pairs (n = 296 patients) were analyzed. Patients were grouped into normal (< 1.2 mg/dL), mild-to-moderate (1.2-3.0 mg/dL), and severe (> 3.0 mg/dL) hyperbilirubinemia groups based on the preoperative serum total bilirubin levels. Bland-Altman analysis showed a bias of 0.20 (95% limit of agreement, LoA: - 2.59 to 3.00) g/dL, 0.98 (95% LoA: - 1.38 to 3.35) g/dL, and 1.23 (95% LoA: - 1.16 to 3.63) g/dL for the normal, mild-to-moderate, and severe groups, respectively. The four-quadrant plot showed reliable trending ability in all groups (concordance rate > 92%). The rates of possible missed transfusion (SpHb > 7.0 g/dL for Hb < 7.0 g/dL) were higher in the hyperbilirubinemia groups (2%, 7%, and 12% for the normal, mild-to-moderate, and severe group, respectively. all P < 0.001). The possible over-transfusion rate was less than 1% in all groups. In conclusion, the use of SpHb in liver transplantation recipients with preoperative hyperbilirubinemia requires caution due to the positive bias and high risk of missed transfusion. However, the reliable trending ability indicated its potential use in clinical settings.

Improvement of the anthropogenic emission rate estimate in Ulaanbaatar, Mongolia, for 2020-21 winter.

Ulaanbaatar (UB), the fast-growing capital of Mongolia, is known for its world's worst level of particulate matter (PM) concentrations in winter. However, current anthropogenic emission inventories over the UB are based on data from more than fifteen years ago, and satellite observations are scarce because UB is in high latitudes. During the winter of 2020-21, the first period of the Fine Particle Research Initiative in East Asia considering the National Differences (FRIEND), several times higher concentrations of PM in UB compared to other urban sites in East Asia were observed but not reproduced with a chemical transport model mainly due to the underestimated anthropogenic emissions. Therefore, we devised a method for sequentially adjusting emissions based on the reactivity of PM precursors using ground observations. We scaled emission rates for the inert species (CO, elemental carbon (EC), and organic carbon (OC)) to reproduce their observed ambient concentrations, followed by SO2 to reproduce the concentration of SO42-, which was examined to have the least uncertainty based on the abundance of observed NH3, and finally NO and NH3 for NO3-, and NH4+. This improved estimation is compared to regional inventories for Asia and suggests more than an order of magnitude increase in anthropogenic emissions in UB. Using the improved emission inventory, we were able to successfully reproduce independent observation data on PM2.5 concentrations in UB in December 2021 from the U.S. Embassy. During the campaign period, we found more than 50% of the SO42-, NO3-, and NH4+ increased in UB due to the improvement could travel to Beijing, China (BJ), and about 20% of the SO42- could travel to Noto, Japan (NT), more than 3000 km away. Also, the anthropogenic emissions in UB can effectively increase OC, NO3-, and NH4+ concentrations in BJ when Gobi dust storms occur.

Real-time machine learning model to predict short-term mortality in critically ill patients: development and international validation.

BACKGROUND: A real-time model for predicting short-term mortality in critically ill patients is needed to identify patients at imminent risk. However, the performance of the model needs to be validated in various clinical settings and ethnicities before its clinical application. In this study, we aim to develop an ensemble machine learning model using routinely measured clinical variables at a single academic institution in South Korea. METHODS: We developed an ensemble model using deep learning and light gradient boosting machine models. Internal validation was performed using the last two years of the internal cohort dataset, collected from a single academic hospital in South Korea between 2007 and 2021. External validation was performed using the full Medical Information Mart for Intensive Care (MIMIC), eICU-Collaborative Research Database (eICU-CRD), and Amsterdam University Medical Center database (AmsterdamUMCdb) data. The area under the receiver operating characteristic curve (AUROC) was calculated and compared to that for the National Early Warning Score (NEWS). RESULTS: The developed model (iMORS) demonstrated high predictive performance with an internal AUROC of 0.964 (95% confidence interval [CI] 0.963-0.965) and external AUROCs of 0.890 (95% CI 0.889-0.891) for MIMIC, 0.886 (95% CI 0.885-0.887) for eICU-CRD, and 0.870 (95% CI 0.868-0.873) for AmsterdamUMCdb. The model outperformed the NEWS with higher AUROCs in the internal and external validation (0.866 for the internal, 0.746 for MIMIC, 0.798 for eICU-CRD, and 0.819 for AmsterdamUMCdb; p < 0.001). CONCLUSIONS: Our real-time machine learning model to predict short-term mortality in critically ill patients showed excellent performance in both internal and external validations. This model could be a useful decision-support tool in the intensive care units to assist clinicians.

Structure of recombinant formate dehydrogenase from Methylobacterium extorquens (MeFDH1).

Formate dehydrogenase (FDH) is critical for the conversion between formate and carbon dioxide. Despite its importance, the structural complexity of FDH and difficulties in the production of the enzyme have made elucidating its unique physicochemical properties challenging. Here, we purified recombinant Methylobacterium extorquens AM1 FDH (MeFDH1) and used cryo-electron microscopy to determine its structure. We resolved a heterodimeric MeFDH1 structure at a resolution of 2.8 Å, showing a noncanonical active site and a well-embedded Fe-S redox chain relay. In particular, the tungsten bis-molybdopterin guanine dinucleotide active site showed an open configuration with a flexible C-terminal cap domain, suggesting structural and dynamic heterogeneity in the enzyme.

Clinical characteristics of persistent postural-perceptual dizziness and its visual subtype in Korean patients: A multicenter cross-sectional study.

OBJECTIVES: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder for which the Bárány Society has established diagnostic criteria. This nationwide multicenter study aims to investigate the clinical features of individuals with definite PPPD and clinical variant PPPD who do not fully meet the diagnostic criteria, with a particular focus on visual exaggeration. METHODS: Between September 2020 and September 2021, a total of 76 individuals with definite PPPD and 109 individuals with clinical variant PPPD who did not meet all three exacerbating factors outlined in Criterion B were recruited from 18 medical centers in South Korea. The study gathered information on demographic factors, clinical manifestations, balance scales, and personality assessments. RESULTS: Comparative analysis between groups with definite PPPD and clinical variant with visual exacerbation revealed no significant differences in sociodemographic characteristics, clinical course, dizziness impact, and specific precipitants. Only disease duration was significantly longer in definite PPPD compared with variant with visual exacerbation. However, the variant without visual exacerbation displayed significantly reduced rates of panic disorder, diminished space-motion discomfort, lesser impact of dizziness, and decreased prevalence of depression when compared with the definitive PPPD. CONCLUSION: This is the first comprehensive nationwide study examining clinical features of both definite PPPD patients and its clinical variants, considering visual exacerbating factors. Differences in dizziness and personality traits emerged between definite PPPD and its potential variant without visual issues. Our results highlight the possibility of a distinct clinical variant of PPPD influenced by visual dependency.

When and why PM2.5 is high in Seoul, South Korea: Interpreting long-term (2015-2021) ground observations using machine learning and a chemical transport model.

Seoul has high PM2.5 concentrations and has not attained the national annual average standard so far. To understand the reasons, we analyzed long-term (2015-2021) hourly observations of aerosols (PM2.5, NO3-, NH4+, SO42-, OC, and EC) and gases (CO, NO2, and SO2) from Seoul and Baekryeong Island, a background site in the upwind region of Seoul. We applied the weather normalization method for meteorological conditions and a 3-dimensional chemical transport model, GEOS-Chem, to identify the effect of policy implementation and aerosol formation mechanisms. The monthly mean PM2.5 ranges between about 20 µg m-3 (warm season) and about 40 µg m-3 (cold season) at both sites, but the annual decreasing rates were larger at Seoul than at Baengnyeong (-0.7 µg m-3 a-1 vs. -1.8 µg m-3 a-1) demonstrating the effectiveness of the local air quality policies including the Special Act on Air Quality in the Seoul Metropolitan Area (SAAQ-SMA) and the seasonal control measures. The weather-normalized monthly mean data shows the highest PM2.5 concentration in March and the lowest concentration in August throughout the 7 years with NO3- accounting for about 40 % of the difference between the two months at both sites. Taking together with the GEOS-Chem model results, which reproduced the elevated NO3- in March, we concluded the elevated atmospheric oxidant level increases in HNO3 (which is not available from the observation) and the still low temperatures in March promote rapid production of NO3-. We used Ox (≡ O3 + NO2) from the observation and OH from the GEOS-Chem as a proxy for the atmospheric oxidant level which can be a source of uncertainty. Thus, direct observations of OH and HNO3 are needed to provide convincing evidence. This study shows that reducing HNO3 levels through atmospheric oxidant level control in the cold season can be effective in PM2.5 mitigation in Seoul.

Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study.

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1-4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1-2) or a high-grade group (WHO/ISUP grade 3-4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5-18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6-17.4) in the high-grade group and 28.0 months (21.1-34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0-10.0) for the high-grade group and 10.0 months (6.8-13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135-2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient.

Microbiologic Profile of Nipple Swab Culture and its Association With Postoperative Complications in Prosthetic Breast Reconstruction.

BACKGROUND: In breast surgeries, lactiferous duct heading to lactic glands of breast parenchyma allows direct contamination of normal bacterial flora of nipple-areolar complex. Complete blockage of nipple flora to the intraoperative field is almost impossible. OBJECTIVES: Therefore, we aimed to analyze the microbiological profile of nipple flora of breast cancer patients who underwent an implant-based immediate breast reconstruction after a total mastectomy; and evaluate the association of nipple bacterial flora with postoperative complications. METHODS: A retrospective chart review was performed for patients who underwent an implant-based immediate breast reconstruction after a total mastectomy. A nipple swab culture was performed preoperatively. Patient demographics, surgical characteristics, and complications were compared between positive and negative nipple swab culture groups. Microbiological profile data including antibacterial resistance were collected. RESULTS: Among 128 breasts, 60 cases (46.9%) had positive preoperative nipple swab culture results. Staphylococcus epidermidis accounted for 41.4% of microorganisms isolated. A multivariate logistic regression analysis of postoperative complications revealed that the presence of nipple bacterial flora was a risk factor of capsular contracture. Seven cases of postoperative infection were analyzed. In 2 cases (40% of pathogen-proven infection), the causative pathogen matched with the patient's nipple bacterial flora, which was methicillin-resistant S. epidermidis in both cases. CONCLUSIONS: Nipple bacterial flora was associated with an increased risk of capsular contracture. Preoperative analysis of nipple bacterial flora can be an informative source for treating clinically diagnosed postoperative infections. More studies are needed to find out the effectiveness of active antibiotic decolonization of the nipple.

Regulation of long-range BMP gradients and embryonic polarity by propagation of local calcium-firing activity.

Many amniote vertebrate species including humans can form identical twins from a single embryo, but this only occurs rarely. It has been suggested that the primitive-streak-forming embryonic region emits signals that inhibit streak formation elsewhere but the signals involved, how they are transmitted and how they act has not been elucidated. Here we show that short tracks of calcium firing activity propagate through extraembryonic tissue via gap junctions and prevent ectopic primitive streak formation in chick embryos. Cross-regulation of calcium activity and an inhibitor of primitive streak formation (Bone Morphogenetic Protein, BMP) via NF-κB and NFAT establishes a long-range BMP gradient spanning the embryo. This mechanism explains how embryos of widely different sizes can maintain positional information that determines embryo polarity. We provide evidence for similar mechanisms in two different human embryo models and in Drosophila, suggesting an ancient evolutionary origin.

Investigation of Interface Characteristics and Physisorption Mechanism in Quantum Dots/TiO2 Composite for Efficient and Sustainable Photoinduced Interfacial Electron Transfer.

Owing to their superior stability compared to those of conventional molecular dyes, as well as their high UV-visible absorption capacity, which can be tuned to cover the majority of the solar spectrum through size adjustment, quantum dot (QD)/TiO2 composites are being actively investigated as photosensitizing components for diverse solar energy conversion systems. However, the conversion efficiencies and durabilities of QD/TiO2-based solar cells and photocatalytic systems are still inferior to those of conventional systems that employ organic/inorganic components as photosensitizers. This is because of the poor adsorption of QDs onto the TiO2 surface, resulting in insufficient interfacial interactions between the two. The mechanism underlying QD adsorption on the TiO2 surface and its relationship to the photosensitization process remain unclear. In this study, we established that the surface characteristics of the TiO2 semiconductor and the QDs (i.e., surface defects of the metal oxide and the surface structure of the QD core) directly affect the QD adsorption capacity by TiO2 and the interfacial interactions between the QDs and TiO2, which relates to the photosensitization process from the photoexcited QDs to TiO2 (QD* → TiO2). The interfacial interaction between the QDs and TiO2 is maximized when the shape/thickness-modulated triangular QDs are composited with defect-rich anatase TiO2. Comprehensive investigations through photodynamic analyses and surface evaluation using X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and photocatalysis experiments collectively validate that tuning the surface properties of QDs and modulating the TiO2 defect concentration can synergistically amplify the interfacial interaction between the QDs and TiO2. This augmentation markedly improved the efficiency of photoinduced electron transfer from the photoexcited QDs to TiO2, resulting in significantly increased photocatalytic activity of the QD/TiO2 composite. This study provides the first in-depth characterization of the physical adhesion of QDs dispersed on a heterogeneous metal-oxide surface. Furthermore, the prepared QD/TiO2 composite exhibits exceptional adsorption stability, resisting QD detachment from the TiO2 surface over a wide pH range (pH = 2-12) in aqueous media as well as in nonaqueous solvents during two months of immersion. These findings can aid the development of practical QD-sensitized solar energy conversion systems that require the long-term stability of the photosensitizing unit.

Combined antimicrobial effect of two peptide nucleic acids against Staphylococcus aureus and S. pseudintermedius veterinary isolates.

BACKGROUND: Staphylococcus aureus and S. pseudintermedius are the major etiological agents of staphylococcal infections in humans, livestock, and companion animals. The misuse of antimicrobial drugs has led to the emergence of antimicrobial-resistant Staphylococcus spp., including methicillin-resistant S. aureus (MRSA) and methicillin-resistant S. pseudintermedius (MRSP). One novel therapeutic approach against MRSA and MRSP is a peptide nucleic acid (PNA) that can bind to the target nucleotide strands and block expression. Previously, two PNAs conjugated with cell-penetrating peptides (P-PNAs), antisense PNA (ASP)-cmk and ASP-deoD, targeting two essential genes in S. aureus, were constructed, and their antibacterial activities were analyzed. OBJECTIVES: This study analyzed the combined antibacterial effects of P-PNAs on S. aureus and S. pseudintermedius clinical isolates. METHODS: S. aureus ATCC 29740 cells were treated simultaneously with serially diluted ASP-cmk and ASP-deoD, and the minimal inhibitory concentrations (MICs) were measured. The combined P-PNA mixture was then treated with S. aureus and S. pseudintermedius veterinary isolates at the determined MIC, and the antibacterial effect was examined. RESULTS: The combined treatment of two P-PNAs showed higher antibacterial activity than the individual treatments. The MICs of two individual P-PNAs were 20 and 25 µM, whereas that of the combined treatment was 10 µM. The application of a combined treatment to clinical Staphylococcus spp. revealed S. aureus isolates to be resistant to P-PNAs and S. pseudintermedius isolates to be susceptible. CONCLUSIONS: These observations highlight the complexity of designing ASPs with high efficacy for potential applications in treating staphylococcal infections in humans and animals.