A Simple Scoring System for Identifying Favorable Neurologic Outcomes Among Out-of-Hospital Cardiac Arrest Patients With Asystole.

STUDY OBJECTIVE: Asystole is the most common initial rhythm in out-of-hospital cardiac arrest (OHCA) but indicates a low likelihood of neurologic recovery. This study aimed to develop a novel scoring system to be easily applied at the time of emergency department arrival for identifying favorable neurologic outcomes in OHCA survivors with an asystole rhythm. METHODS: This study is a secondary analysis based on a previously collected nationwide database, targeting nontraumatic adult OHCA patients aged ≥18 years with an asystole rhythm who achieved return of spontaneous circulation (ROSC) between January 2016 and December 2020. The primary outcome was a favorable neurologic outcome defined as Cerebral Performance Categories scores of 1 or 2 at hospital discharge. A prediction model was developed through multivariable logistic regression analysis in a derivation cohort in the form of a scoring system (WBC-ASystole). The performance and calibration of the model were tested using an internal validation cohort. RESULTS: Among 19,803 OHCA patients with survival to hospital admission, 6,322 had asystole, and 285 (4.5%) achieved good neurologic outcomes. Factors associated with favorable outcomes included age, witness arrest, bystander cardiopulmonary resuscitation, time from call to hospital arrival, and out-of-hospital ROSC achievement. The WBC-ASystole score, totaling 11 points, exhibited a predictive performance with an area under the receiver operating characteristic curve of 0.80 (95% confidence interval [CI] 0.76 to 0.83) and 0.79 (95% CI 0.74 to 0.83) in the derivation and validation cohorts, respectively. After categorizing patients into 3 groups based on probability for good neurologic outcomes, the sensitivity and specificity were as follows: 0.98 (95% CI 0.97 to 0.99) and 0.09 (95% CI 0.09 to 0.10) for the very low predicted probability group (WBC-ASystole ≤2), 0.85 (95% CI 0.82 to 0.89) and 0.54 (95% CI 0.53 to 0.55) for the low predicted probability group (WBC-ASystole 3 to 4), and 0.36 (95% CI 0.34 to 0.39) and 0.93 (95% CI 0.92 to 0.93) for fair predicted probability group (WBC-ASystole≥5), respectively. CONCLUSIONS: Although external validation studies must be performed, among OHCA patients with asystole, the WBC-ASystole scoring system may identify those patients who are likely to have a favorable neurologic outcome.

Mucor germinans, a novel dimorphic species resembling Paracoccidioides in a clinical sample: questions on ecological strategy.

Dimorphism is known among the etiologic agents of endemic mycoses as well as in filamentous Mucorales. Under appropriate thermal conditions, mononuclear yeast forms alternate with multi-nucleate hyphae. Here, we describe a dimorphic mucoralean fungus obtained from the sputum of a patient with Burkitt lymphoma and ongoing graft-versus-host reactions. The fungus is described as Mucor germinans sp. nov. Laboratory studies were performed to simulate temperature-dependent dimorphism, with two environmental strains Mucor circinelloides and Mucor kunryangriensis as controls. Both strains could be induced to form multinucleate arthrospores and subsequent yeast-like cells in vitro. Multilateral yeast cells emerge in all three Mucor species at elevated temperatures. This morphological transformation appears to occur at body temperature since the yeast-like cells were observed in the lungs of our immunocompromised patient. The microscopic appearance of the yeast-like cells in the clinical samples is easily confused with that of Paracoccidioides. The ecological role of yeast forms in Mucorales is discussed.IMPORTANCEMucormycosis is a devastating disease with high morbidity and mortality in susceptible patients. Accurate diagnosis is required for timely clinical management since antifungal susceptibility differs between species. Irregular hyphal elements are usually taken as the hallmark of mucormycosis, but here, we show that some species may also produce yeast-like cells, potentially being mistaken for Candida or Paracoccidioides. We demonstrate that the dimorphic transition is common in Mucor species and can be driven by many factors. The multi-nucleate yeast-like cells provide an effective parameter to distinguish mucoralean infections from similar yeast-like species in clinical samples.

Exploring transfer effects on memory and its neural mechanisms through a computerized cognitive training in mild cognitive impairment: randomized controlled trial.

BACKGROUND: Computerized cognitive training (CCT) has been proposed as a potential therapy for cognitive decline. One of the benefits of CCT is a transfer effect, but its mechanism on the memory domain is unclear. This study aimed to investigate the transfer effect of non-memory multidomain CCT on the memory domain and its neural basis in patients with mild cognitive impairment (MCI) through a randomized controlled trial. METHODS: Patients with MCI recruited from memory clinics were randomly assigned to either the CCT or the control group. The CCT group received multidomain CCT training excluding memory training, while the control group read educational books with learning-based quizzes twice a week for 8 weeks. Participants underwent memory tests yielding a composite score, other cognitive domain tests, non-cognitive scales, and resting-state functional magnetic resonance imaging (rsfMRI), at baseline and after intervention. Within- and between-group comparisons, group × time interactions, and seed-to-voxel analyses in memory-involving brain networks were performed. RESULTS: The CCT group showed improvement over the control group in memory domain (Group × time, F = 5.87, P = 0.03, η2 = 0.31), which was related with the increased connectivity in the hippocampal-frontal and fusiform-occipital network. No other cognitive and non-cognitive symptoms differed between groups after adjusting for covariates. CONCLUSION: Eight weeks of multidomain CCT without memory training improved memory function and restored functional network in the hippocampal and medial temporal region in MCI patients. These results can provide evidence for the transferring ability of CCT on memory functioning with its neural basis.

Comparison of the impact of longitudinal body mass index changes on cardiac arrest risk between normal and overweight populations.

BACKGROUND: Being overweight is a key modifiable risk factor for cardiovascular disease. However, the impact of longitudinal changes in body mass index (BMI) on the risk of out-of-hospital cardiac arrests (OHCA) remains unclear, especially among overweight populations. METHODS: This nested case-control study utilized data from the Korean National Health Information Database between 2009 and 2018. A total of 23 453 OHCA patients, who underwent national health check-ups within 1 and 2-4 years before OHCA occurrence, and 31 686 controls, who underwent similar national health check-ups, were included. The study population was matched for sex, age and survival status. Conditional logistic regression was employed to analyse the odds ratios (ORs) and 95% confidence intervals (CIs) of each BMI per cent change in assessing the risk of OHCA occurrence within 1 year. RESULTS: A reverse J-shaped association between BMI per cent change and OHCA risk was observed, even among overweight populations. Among the overweight populations, weight loss significantly increased OHCA risk, with ORs (95% CI) of 4.10 (3.23-5.20) for severe weight loss (BMI decrease > 15%), 2.72 (2.33-3.17) for moderate weight loss (BMI decrease 10-15%) and 1.46 (1.35-1.59) for mild weight loss (BMI decrease 5-10%). Conversely, mild weight gain (BMI increase 5-10%) did not significantly increase OHCA risk. The impact of weight changes on the occurrence of OHCA differed by sex, being more prominent in males. CONCLUSIONS: Significant weight changes within a 4-year period increase the risk of OHCA with a reverse J-shaped association, even among overweight and obese individuals. Maintaining a stable weight could be a reliable public health strategy irrespective of the weight status, particularly for males.

The therapeutic effects of vitamin D3 administration on the embryo implantation.

Various adjuvants have been tested clinically for patients with problems with embryo implantation during in vitro fertilization (IVF)-embryo transfer (ET). Vitamin D3, an essential modulator of various physiological processes, has received attention as an important adjuvant for successful pregnancy, as many studies have shown a strong association between vitamin D deficiency and implantation failure and fetal growth restriction. However, vitamin D has been widely utilized in different protocols, resulting in non-reproducible and debatable outcomes. In the present study, we demonstrated that cyclic intrauterine administration of vitamin D3 increased endometrial receptivity and angiogenesis, which could be attributed to increased recruitment of uterus-resident natural killer cells. In particular, cyclic treatment of vitamin D3 promoted stable attachment of the embryo onto endometrial cells in vitro, suggesting its merit during the early stage of embryo implantation to support the initial maternal-fetal interactions. Our findings suggest that women with repeated implantation failure may benefit from the use of vitamin D3 as a risk-free adjuvant prior to IVF-ET procedures to improve the uterine environment, and make it favorable for embryo implantation.

Advanced age and neurological recovery in elderly patients with out-of-hospital cardiac arrest treated with targeted temperature management: a nationwide population­based registry study 2016-2020.

The likelihood of neurological recovery after out-of-hospital cardiac arrest (OHCA) may be influenced by advanced age. This study aims to evaluate the impact of advanced age on neurological recovery in elderly OHCA survivors treated with targeted temperature management (TTM). This retrospective observational study, using a nationwide population-based OHCA registry, was conducted from January 2016 to December 2020. Non-traumatic elderly (≥ 65 years) comatose OHCA survivors treated with TTM were categorized according to age (65-69, 70-74, 75-79, and ≥ 80 years). Among 23,336 admitted OHCA patients, 3,398 were treated with TTM. Excluding 2,033 non-elderly patients, 1,365 were analyzed. Among the four groups, the rate of good neurological outcomes decreased by advanced age (24.2%, 16.1%, 11.4%, and 5.9%, respectively), which was also observed after subgroup analysis based on the initial shockable (40.6%, 31.5%, 28.6%, and 14.9%, respectively) and non-shockable rhythm (10.6%, 7.2%, 4.1%, and 3.4%, respectively). Multivariate analysis showed the adjusted odds ratio (aOR) for good neurological outcome decreased as age increased (65-69: reference, 70-74: aOR 0.70, 75-79: aOR 0.49, and ≥ 80 years: aOR 0.25). The optimal age cutoffs for good outcomes in elderly OHCA survivors with shockable and non-shockable rhythm were 77 and 72 years, respectively. The neurologic recovery rate in OHCA survivors treated with TTM gradually decreased with increasing age. However, even patients aged ≥ 80 years with shockable rhythm had a good neurologic outcome of 14.9% compared with patients aged 65-69 years with non-shockable rhythm (10.6%).

Micropropagation and Shoot Tip Cryopreservation of 'Sunny Gold' Freesia.

Cryopreservation is a promising method for the long-term preservation of plant germplasm, especially for vegetatively propagated species like freesias. In this study, we investigate streamlining the cryopreservation process for 'Sunny Gold' Freesia, starting from effective in vitro initiation and proliferation using various plant growth regulator combinations. We also assess the impact of subculture on regrowth rates after cryopreservation. The shoot tips were successfully initiated in vitro after sterilization. The shoots were multiplied an average of three times in media containing N6-benzyladenine and kinetin. The regrowth rates of non-cryopreserved shoot tips excised from different subculture cycles did not differ significantly, with rates of 44% observed for plants from more than five subcultures and 47% for those from three subcultures. However, only the shoot tips excised from cultures subjected to three subculture cycles were able to recover after cryopreservation, with a regrowth rate of 31%. Our findings lay the groundwork for the development of an efficient cryopreservation protocol for freesias in the future.

Prevalence and risk factors for in-hospital mortality of adult patients on veno-arterial extracorporeal membrane oxygenation for cardiogenic shock and cardiac arrest: A systematic review and meta-analysis.

OBJECTIVES: To synthesize quantitative research findings on the prevalence and risk factors for in-hospital mortality of patients on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: A comprehensive search was conducted for the period from May 2008 to December 2023 by searching the five electronic databases of PubMed, CINAHL, Web of Science, EMBASE, and Cochrane library. The quality of included studies was assessed using the Newcastle-Ottawa scale. The meta-analysis estimated the pooled odds ratio or standard mean difference and 95% confidence intervals. RESULTS: A total of twenty-five studies with 10,409 patients were included in the analysis. The overall in-hospital mortality of patients on VA-ECMO was 56.7 %. In the subgroup analysis, in-hospital mortality of VA-ECMO for cardiogenic shock and cardiac arrest was 49.2 % and 75.2 %, respectively. The number of significant factors associated with an increased risk of in-hospital mortality in the pre-ECMO period (age, body weight, creatinine, chronic kidney disease, pH, and lactic acid) was greater than that in the intra- and post-ECMO periods. Renal replacement, bleeding, and lower limb ischemia were the most significant risk factors for in-hospital mortality in patients receiving VA-ECMO. CONCLUSION: Early detection of the identified risk factors can contribute to reducing in-hospital mortality in patients on VA-ECMO. Intensive care unit nurses should provide timely and appropriate care before, during, and after VA-ECMO. IMPLICATIONS FOR CLINICAL PRACTICE: Intensive care unit nurses should be knowledgeable about factors associated with the in-hospital mortality of patients on VA-ECMO to improve outcomes. The present findings may contribute to developing guidelines for reducing in-hospital mortality among patients considering ECMO.

Whole-genome sequence of Mucor velutinosus NIH1002, a strain associated with disseminated disease.

The draft genome of Mucor velutinosus NIH1002, a 2011 isolate from a case of disseminated disease, was sequenced using PacBio long-read and HiSeq short-read technologies. The genome has 43 contigs, an N50 of 2.65 Mb, and 13,295 protein-coding genes. It is the most complete M. velutinosus genome to date.

Normal value of neuron-specific enolase for predicting good neurological outcomes in comatose out-of-hospital cardiac arrest survivors.

Research on prognostic factors for good outcomes in out-of-hospital cardiac arrest (OHCA) survivors is lacking. We assessed whether normal levels of normal neuron-specific enolase (NSE) value would be useful for predicting good neurological outcomes in comatose OHCA survivors treated with targeted temperature management (TTM). This registry-based observational study with consecutive adult (≥18 years) OHCA survivors with TTM who underwent NSE measurement 48 hours after cardiac arrest was conducted from October 2015 to November 2022. Normal NSE values defined as the upper limit of the normal range by the manufacturer (NSE <16.3 µg/L) and guideline-suggested (NSE < 60 µg/L) were examined for good neurologic outcomes, defined as Cerebral Performance Categories ≤2, at 6 months post-survival. Among 226 OHCA survivors with TTM, 200 patients who underwent NSE measurement were enrolled. The manufacturer-suggested normal NSE values (<16.3 µg/L) had a specificity of 99.17% for good neurological outcomes with a very low sensitivity of 12.66%. NSE <60 µg/L predicted good outcomes with a sensitivity of 87.34% and specificity of 72.73%. However, excluding 14 poor-outcome patients who died from multi-organ dysfunction excluding hypoxic brain injury, the sensitivity and specificity of normal NSE values were 12.66% and 99.07% of NSE < 16.3 µg/L, and 87.34% and 82.24% of NSE < 60 µg/L. The manufacturer-suggested normal NSE had high specificity with low sensitivity, but the guideline-suggested normal NSE value had a comparatively low specificity for good outcome prediction in OHCA survivors. Our data demonstrate normal NSE levels can be useful as a tool for multimodal appropriation of good outcome prediction.

Real-Time Shape Estimation of Hyper-Redundant Flexible Manipulator Using Coiled Fiber Sensors.

The shape of flexible endoscopic surgical robot should be obtained to increase control accuracy and prevent unwanted tissue damage. To estimate the shape of flexible manipulator, space efficiency, cost-effectiveness, system complexity, and ease of calibration should be considered to integrate sensors into the manipulator. In this article, we propose a real-time method to estimate the shape of a hyper-redundant manipulator having embedded coiled fiber sensors. The main advantage of this method is guaranteeing shape recognition even when the manipulator is subjected to an external load. The fiber sensors are highly flexible, compact, and inexpensive, as well as they can functionally measure both compressive and tensile strain of hyper-redundant manipulator. The sensor design was optimized to achieve durability and sensitivity. The numbers of sensor and the placements were determined by the analysis of the kinematics and moment distribution of the manipulator. The accuracy of shape estimation was validated experimentally under both free-loading and loading conditions. The proposed method achieved real-time estimating capability with a mean maximum error of each joint position smaller than 3.54% in free-loading condition and 5.47% in loading condition.

Study of the soothing effects of troxerutin in alleviating skin sensitivity.

BACKGROUND: Transient receptor potential vanilloid 1 (TRPV1) is associated with skin sensitivity and mainly activated by capsaicin and heat. Interestingly, troxerutin can inhibit TRPV1 activation. However, its efficacy in reducing skin sensitivity remains undetermined. AIMS: We evaluated the efficacy of troxerutin in alleviating skin sensitivity using clinical tests and in vitro experiments. METHODS: For the in vitro experiment, HaCaT keratinocytes were pretreated with different concentrations of troxerutin, followed by incubation with 50 µM capsaicin for 1, 24, or 48 h. The gene and protein expressions of four inflammatory cytokines involved in skin irritation were determined. Among 35 Korean women with sensitive skin recruited for the clinical trial, 13 were involved in assessing the immediate soothing effects of 0.1% and 0.0095% troxerutin following capsaicin irritation, whereas 22 participated in evaluating the preventive soothing effect of 10% and 1% troxerutin over 4 weeks against capsaicin- and heat-induced irritation. We evaluated the soothing rate using skin redness, visual analog scale, and high temperature sensitive index as evaluation indices. RESULTS: Troxerutin inhibited the mRNA and protein expressions of cytokines in capsaicin-treated keratinocytes. In the clinical study, 0.1% and 0.0095% troxerutin promptly alleviated capsaicin-induced skin redness, whereas 10% troxerutin notably decreased both the visual analog scale and high temperature sensitive index for capsaicin- and heat-related irritation. However, 1% troxerutin was only effective in reducing the visual analog scale in response to capsaicin irritation. CONCLUSIONS: Troxerutin can inhibit TRPV1 activation in clinical and in vitro tests.

Soft Polymer-Actuated Compliant Microgripper with Adaptive Vibration-Controlled Grasp and Release.

Microgrippers that incorporate soft actuators are appropriate for micromanipulation or microsurgery owing to their ability to grasp objects without causing damage. However, developing a microgripper with a large gripping range that can produce a large force with high speed remains challenging in soft actuation mechanisms. Herein, we introduce a compliant microgripper driven by a soft dielectric elastomer actuator (DEA) called a spiral flexure cone DEA (SFCDEA). The submillimeter-scale SFCDEA exhibited a controllable linear displacement over a high bandwidth and the capability of lifting 100.9 g, which was 670 times higher than its mass. Subsequently, we developed a compliant microgripper based on the SFCDEA using smart composite microstructure technology to fabricate three-dimensional gripper linkages. We demonstrated that the microgripper was able to grasp various millimeter-scale objects with different shapes, sizes, and weights without a complex feedback control owing to its compliance. We proved the versatility of our gripper in robotic manipulation by demonstrating adaptive grasping and releasing of small objects using vibrations owing to its high bandwidth.

Multi-Degree-of-Freedom Force Sensor Incorporated into Soft Robotic Gripper for Improved Grasping Stability.

In recent years, soft robotic grippers have emerged as a promising solution for versatile and safe manipulation of objects in various fields. However, precise force control is critical, especially when handling delicate or fragile objects, to avoid excessive grip force application or to prevent object slippage. Herein, we propose a novel three-degree-of-freedom force sensor incorporated within a soft robotic gripper to realize stable grasping with force feedback. The proposed optical sensor employs lightweight and compact optical fibers, thereby allowing for cost-effective fabrication, and a robust sensing system that is immune to electromagnetic fields. By innervating the soft gripper with optical fibers, a durable system is achieved with the fibers functioning as a strengthening layer, thereby eliminating the need for embedding an external stiffening structure for efficient bending actuation. The innovative contact-based light loss sensing mechanism allows for a robust and stable sensing mechanism with low drift (<0.1% over 9000 cycles) that can be applied to soft pneumatic bending grippers. We used the developed sensor-incorporated soft gripper to grasp various objects, including magnetic materials, and achieved slip detection along with grip force feedback without any signal interference. Overall, this study proposes a robust measuring multi-degree-of-freedom force sensor that can be incorporated into grippers for improved grasping stability.

Cisd2 deficiency impairs neutrophil function by regulating calcium homeostasis via Calnexin and SERCA.

In the context of aging, the susceptibility to infectious diseases increases, leading to heightened morbidity and mortality. This phenomenon, termed immunosenescence, is characterized by dysregulation in the aging immune system, including abnormal alterations in lymphocyte composition, elevated basal inflammation, and the accumulation of senescent T cells. Such changes contribute to increased autoimmune diseases, enhanced infection severity, and reduced responsiveness to vaccines. Utilizing aging animal models becomes imperative for a comprehensive understanding of immunosenescence, given the complexity of aging as a physiological process in living organisms. Our investigation focuses on Cisd2, a causative gene for Wolfram syndrome, to elucidate on immunosenescence. Cisd2 knockout (KO) mice, serving as a model for premature aging, exhibit a shortened lifespan with early onset of aging-related features, such as decreased bone density, hair loss, depigmentation, and optic nerve degeneration. Intriguingly, we found that the Cisd2 KO mice present a higher number of neutrophils in the blood; however, isolated neutrophils from these mice display functional defects. Through mass spectrometry analysis, we identified an interaction between Cisd2 and Calnexin, a protein known for its role in protein quality control. Beyond this function, Calnexin also regulates calcium homeostasis through interaction with sarcoendoplasmic reticulum calcium transport ATPase (SERCA). Our study proposes that Cisd2 modulates calcium homeostasis via its interaction with Calnexin and SERCA, consequently influencing neutrophil functions. [BMB Reports 2024; 57(5): 256-261].

Height-renderable morphable tactile display enabled by programmable modulation of local stiffness in photothermally active polymer.

Reconfigurable tactile displays are being used to provide refreshable Braille information; however, the delivered information is currently limited to an alternative of Braille because of difficulties in controlling the deformation height. Herein, we present a photothermally activated polymer-bilayer-based morphable tactile display that can programmably generate tangible three-dimensional topologies with varying textures on a thin film surface. The morphable tactile display was composed of a heterogeneous polymer structure that integrated a stiffness-tunable polymer into a light-absorbing elastomer, near-infra-red light-emitting diode (NIR-LED) array, and small pneumatic chamber. Topological expression was enabled by producing localized out-of-plane deformation that was reversible, height-adjustable, and latchable in response to light-triggered stiffness modulation at each target area under switching of stationary pneumatic pressure. Notably, the tactile display could express a spatial softness map of the latched topology upon re-exposing the target areas to modulated light from the NIR-LED array. We expect the developed tactile display to open a pathway for generating high-dimensional tactile information on electronic devices and enable realistic interaction in augmented and virtual environments.

Comparison of Modified Shock Index and Shock Index for Predicting Massive Transfusion in Women with Primary Postpartum Hemorrhage: A Retrospective Study.

BACKGROUND The modified shock index (MSI) is calculated as the ratio of heart rate (HR) to mean arterial pressure (MAP) and has been used to predict the need for massive transfusion (MT) in trauma patients. This retrospective study from a single center aimed to compare the MSI with the traditional shock index (SI) to predict the need for MT in 612 women diagnosed with primary postpartum hemorrhage (PPH) at the Emergency Department (ED) between January 2004 and August 2023. MATERIAL AND METHODS The patients were divided into the MT group and the non-MT group. The predictive power of MSI and SI was compared using the areas under the receiver operating characteristic curve (AUC). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated. RESULTS Out of 612 patients, 105 (17.2%) required MT. The MT group had higher median values than the non-MT group for MSI (1.58 vs 1.07, P<0.001) and SI (1.22 vs 0.80, P<0.001). The AUC for MSI, with a value of 0.811 (95% confidence interval [CI], 0.778-0.841), did not demonstrate a significant difference compared to the AUC for SI, which was 0.829 (95% CI, 0.797-0.858) (P=0.066). The optimal cutoff values for MSI and SI were 1.34 and 1.07, respectively. The specificity and PPV for MT were 77.1% and 40.2% for MSI, and 83.2% and 45.9% for SI. CONCLUSIONS Both MSI and SI were effective in predicting MT in patients with primary PPH. However, MSI did not demonstrate superior performance to SI.

Novel PAX9 Mutations Causing Isolated Oligodontia.

Hypodontia, i.e., missing one or more teeth, is a relatively common human disease; however, oligodontia, i.e., missing six or more teeth, excluding the third molars, is a rare congenital disorder. Many genes have been shown to cause oligodontia in non-syndromic or syndromic conditions. In this study, we identified two novel PAX9 mutations in two non-syndromic oligodontia families. A mutational analysis identified a silent mutation (NM_006194.4: c.771G>A, p.(Gln257=)) in family 1 and a frameshift mutation caused by a single nucleotide duplication (c.637dup, p.(Asp213Glyfs*104)) in family 2. A minigene splicing assay revealed that the silent mutation resulted in aberrant pre-mRNA splicing instead of normal splicing. The altered splicing products are ones with an exon 4 deletion or using a cryptic 5' splicing site in exon 4. Mutational effects were further investigated using protein expression, luciferase activity assay and immunolocalization. We believe this study will not only expand the mutational spectrum of PAX9 mutations in oligodontia but also strengthen the diagnostic power related to the identified silent mutation.

TXNIP-mediated crosstalk between oxidative stress and glucose metabolism.

Thioredoxin-interacting protein (TXNIP) has emerged as a key player in cancer and diabetes since it targets thioredoxin (TRX)-mediated redox regulation and glucose transporter (GLUT)-mediated metabolism. TXNIP consists of two arrestin (ARR, N-ARR and C-ARR) domains at its amino-terminus and two PPxY (PY) motifs and a di-leucine (LL) motif for endocytosis at its carboxyl-terminus. Here, we report that TXNIP shuffles between TRX and GLUTs to regulate homeostasis of intracellular oxidative stress and glucose metabolism. While TXNIP functions as a gatekeeper of TRX by default, it robustly interacted with class I GLUTs through its C-ARR domain upon increase of intracellular reactive oxygen species. This interaction prompted the surface expression downregulation and lysosomal degradation of GLUTs by its carboxyl-terminal LL endocytic signaling motif to attenuate glucose uptake. Consequently, TXNIP expression significantly limited glucose uptake, leading to the suppression of glycolysis, hexosamine biosynthesis, and the pentose phosphate pathway. Our findings establish a fundamental link between ROS and glucose metabolism through TXNIP and provide a promising target for the drug development against GLUT-related metabolic disorders.