Association of outdoor artificial light at night with myopia among Chinese adolescents: a representative cross-sectional study.

Background: The association between the rapid increase in myopia among adolescents and the amount of outdoor artificial light at night (ALAN) remains unclear. The aim of this study was to investigate the association between outdoor ALAN and myopia in adolescents. Methods: Stratified cluster random sampling was used to obtain a sample of 33,160 students (age range: 9-18 years; mean: 13.51 years) with complete data from 120 primary and secondary schools across the Ningxia region in China in 2021. Myopia was defined as a spherical equivalent (SE) ≤-0.5 diopters (D) in at least one eye, determined by automated refractometers without cycloplegia. Outdoor ALAN data were obtained from satellite data and the two-year average outdoor ALAN exposure for each participant was determined by matching it to their school address (home addresses were not available). The association between ALAN and myopia was assessed using multiple logistic regression models and restricted cubic spline (RCS) regression. Stratified analyses were performed by age, sex, residence, school level, and outdoor exercise time. Results: The myopia group had higher outdoor ALAN levels than the non-myopia group [median (interquartile spacing): 14.44 (3.88-26.56) vs. 6.95 (1.21-21.74) nanoWatts/cm2/sr]. After adjusting for covariates identified through stepwise regression, it was observed that the prevalence of myopia increased by 4% for every 10-unit change [95% confidence interval (CI): 1.02-1.07]. Compared to the first quantile (Q1) of outdoor ALAN exposure, the odds ratio (OR) of myopia was 1.20 (95% CI: 1.08-1.34) in the fourth quantile. RCS further showed a positive nonlinear relationship between outdoor ALAN exposure and myopia (p for nonlinear <0.001). Stronger effects were not found in subgroup analyses. Conclusion: Outdoor ALAN exposure is positively and nonlinearly associated with the prevalence of myopia in adolescents. Controlling outdoor light pollution may constitute a potential strategy to reduce the incidence of myopia in adolescents.

Twisted Structure Induced Solid-State Fluorescence and Room-Temperature Phosphorescence from Furan-Based Carbon Dots.

Boron doping can effectively induce solid-state fluorescence (SSF) in carbon dots (CDs); however, research on the intrinsic mechanism underlying this phenomenon is lacking. Herein, a design strategy for boron-doped furan-based CDs is proposed, CDs with aggregation-induced emission (AIE) properties are synthesized, and the mechanism by which boron atom dopants induces SSF and room-temperature phosphorescence (RTP) is elucidated. The morphology and structural characterization of the CDs indicate that boron doping leads to structural twisting of the CDs. The AIE phenomenon of CDs arises from the inhibition of the twisted structure motions and a reduction in the nonradiative relaxation rate during the aggregation process. In addition, CDs with twisted structures exhibit a smaller overlap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), effectively reducing the singlet-triplet splitting energy (ΔEST). CDs embedded in microcrystalline cellulose (MCC) exhibit green RTP because the nonradiative transitions are suppressed, and the excited triplet species remain stable. For the first time, this study reveals the structure-activity relationship between the twisted structure and optical properties of CDs, providing a new approach for the preparation of solid-state light-emitting CDs.

Solid-State Fluorescent Carbon Dots with Hydrophobic Modification Induced Red Emission for White Light-Emitting Diodes.

Herein, we developed red solid-state fluorescent carbon dots (SSF-CDs) through a one-step solvothermal method, utilizing acetone as the carbonization solvent. Optical and structural characterization revealed that the sp2 domains in the core of the R-CDs were consistently interrupted and that the oxygen-containing groups on the surface were replaced by alkyl groups. This substitution mitigates excessive π-π interactions, thereby preventing quenching of fluorescence in the solid state. Adjusting the molar ratio of citric acid (CA) and urea yielded solid fluorescent carbon dots (CDs) with panchromatic luminescence, indicating enhanced π-π interactions and more pronounced red shifts in the emission peaks. Furthermore, we found that this strategy is applicable to other carbon sources, including phenylenediamine, salicylic acid, and lignin. This research presents an innovative strategy for the fabrication of solid-state luminescent CDs.

Tannic Acid Film Based on One-Dimensional Supramolecular Self-Assembly for Electrical Conductivity and Oil-Water Separation.

Tannic acid is widely regarded as one of the most promising natural polyphenolic compounds. However, current research predominantly focuses on the utilization of its phenolic hydroxyl groups, with limited exploration of the functional potential of its aromatic structure. Herein, one-dimensional nanofibers based on supramolecular self-assembly were successfully prepared through the simple alkylation reaction of tannic acid and the π-π stacking of aromatic structures. These fibers, with lengths reaching tens of micrometers and an average height of 10 nm, were clearly observed using SEM and AFM. A film with excellent electrical conductivity (σ = 37.9 µS/cm) was fabricated by vacuum filtering the organic suspension of these fibers, which was 100-fold higher than that of the TA film. Additionally, the hydrophobic and lipophilic properties of Bn-TA were further investigated through oil-water separation experiments, where the Bn-TA membrane displayed excellent separation efficiency and durability, maintaining stable performance over multiple cycles. This strategy presents opportunities for the high-value utilization of tannic acid.

The balance between alleviating copper damage and maintaining root function during root pruning with excessive copper.

Coating high concentrations of copper (Cu) on the inner wall of containers can efficiently inhibit root entanglement of container-grown seedlings. However, how the protective and defensive responses of roots maintain root structure and function during Cu-root pruning is still unclear. Here, Duranta erecta seedlings were planted in the containers coated with 40 (T1), 80 (T2), 100 (T3), 120 (T4), 140 (T5), and 160 (T6) g L-1 Cu(OH)2 with containers without Cu(OH)2 as the control. Although T5 and T6 produced the best inhibitory effect on root entanglement, root anatomy structure was damaged. T1 and T2 not only failed to completely control root circling, but also led to decreased root activity and stunted growth. Cu(OH)2 treatments significantly increased lignin concentration of roots with the highest values at T3 and T4. Compared with T3, seedlings at T4 had higher height, biomass, and root activity and no significant root entanglement. Excessive Cu accumulation in Cu(OH)2 treatments changed the absorption of other mineral nutrients and their allocation in the roots, stems, and leaves. Overall, Ca was decreased while Mg, Mn, Fe, and K were increased, especially K and Mn at T4 which is related to defense capacity. The results indicate that there is a Cu threshold to balance root entanglement control, defense capacity, and nutrient uptake function under excessive Cu for container-grown D. erecta seedlings.

Association between cardiometabolic index and kidney stone from NHANES: a population-based study.

Purpose: The Cardiometabolic Index (CMI) is a novel marker of visceral obesity and dyslipidemia. Our study aimed to explore the association between CMI and kidney stones among US adults. Methods: This cross-sectional study was conducted among adults with complete records of CMI and kidney stones information from the 2011 to 2018 National Health and Nutrition Examination Survey (NHANES). Inverse probability treatment weighting (IPTW) was used to balance the baseline characteristics of the study population. The independent relationship between CMI and kidney stones was evaluated using IPTW-adjusted multivariate logistic regression, restricted cubic splines (RCS), and subgroup analysis. Results: A total of 9,177 participants, with an average CMI of 0.72 (0.99), were included in this study. The IPTW-adjusted logistic regression revealed that CMI was an independent risk factor for kidney stones. The adjusted odds ratio (OR) for kidney stones were 1.39 (95% CI: 1.24 - 1.56, P < 0.001) for the second CMI tertile and 1.31 (95% CI: 1.17 - 1.47, P < 0.001) for the third CMI tertile, compared with the first CMI tertile. A linear relationship between CMI levels and kidney stone risk was observed in the RCS analysis. Subgroup analysis showed that the association between CMI levels and kidney stone risk remained stable across groups. Conclusions: A positive association between CMI level and the risk of kidney stones was observed among US adults in our study. Further large-scale prospective studies are needed to validate our findings.

An Overview of Secondary Metabolites from Soft Corals of the Genus Capnella over the Five Decades: Chemical Structures, Pharmacological Activities, NMR Data, and Chemical Synthesis.

There has been no specific review on the secondary metabolites from soft corals of the genus Capnella till now. In this work, all secondary metabolites from different species of the title genus were described. It covered the first work from 1974 to May 2024, spanning five decades. In the viewpoint of the general structural features, these chemical constituents were classified into four groups: sesquiterpenes, diterpenes, steroids, and lipids. Additionally, the 1H and 13C NMR data of these metabolites were provided when available in the literature. Among them, sesquiterpenes were the most abundant chemical compositions from soft corals of the genus Capnella. A variety of pharmacological activities of these compounds were evaluated, such as cytotoxic, antibacterial, antifungal, and anti-inflammatory activities. In addition, the chemical synthesis works of several representative sesquiterpenes were provided. This review aims to provide an up-to-date knowledge of the chemical structures, pharmacological activities, and chemical synthesis of the chemical constituents from soft corals of the genus Capnella.

A novel RAV transcription factor from pear interacts with viral RNA-silencing suppressors to inhibit viral infection.

In plants, RNA silencing constitutes a strong defense against viral infection, which viruses counteract with RNA-silencing suppressors (RSSs). Understanding the interactions between viral RSSs and host factors is crucial for elucidating the molecular arms race between viruses and host plants. We report that the helicase motif (Hel) of the replicase encoded by apple stem grooving virus (ASGV)-the main virus affecting pear trees in China-is an RSS that can inhibit both local and systemic RNA silencing, possibly by binding double-stranded (ds) siRNA. The transcription factor related to ABSCISIC ACID INSENSITIVE3/VIVIPAROUS1 from pear (PbRAV1) enters the cytoplasm and binds Hel through its C terminus, thereby attenuating its RSS activity by reducing its binding affinity to 21- and 24-nt ds siRNA, and suppressing ASGV infection. PbRAV1 can also target p24, an RSS encoded by grapevine leafroll-associated virus 2 (GLRaV-2), with similar negative effects on p24's suppressive function and inhibition of GLRaV-2 infection. Moreover, like the positive role of the PbRAV1 homolog from grapevine (VvRAV1) in p24's previously reported RSS activity, ASGV Hel can also hijack VvRAV1 and employ the protein to sequester 21-nt ds siRNA, thereby enhancing its own RSS activity and promoting ASGV infection. Furthermore, PbRAV1 neither interacts with CP, an RSS encoded by grapevine inner necrosis virus, nor has any obvious effect on CP's RSS activity. Our results identify an RSS encoded by ASGV and demonstrate that PbRAV1, representing a novel type of RAV transcription factor, plays a defensive role against viral infection by targeting viral RSSs.

hsa_circ_0000129 targets miR-383-5p/tropomyosin 3 axis to facilitate ovarian cancer progression.

Ovarian cancer is one of the most prevalent malignancies among women. CircRNAs play key roles in the progression of ovarian cancer. This study aimed to investigate the mechanism of action of hsa_circ_0000129 and its effects on ovarian cancer. Expression of hsa_circ_0000129, tropomyosin 3 (TPM3), and miR-383-5p in ovarian cancer cell lines and tissue specimens was detected using qRT-PCR or western blotting. Cell counting kit-8 (CCK-8), colony formation, and transwell assays were performed to assess viability, proliferation, and migration of ovarian cancer cells. A xenograft model was used to study tumorigenicity of ovarian cancer cells in vivo. Luciferase and RNA immunoprecipitation assays were performed to determine binding between miR-383-5p and hsa_circ_0000129 or TPM3. Upregulation of hsa_circ_0000129 and TPM3 and downregulation of miR-383-5p were observed in ovarian cancer. Low hsa_circ_0000129 and TPM3 expression repressed viability, migration, and proliferation of ovarian cancer cells. Inhibition of miR-383-5p had a contrary effect. Furthermore, knockdown of hsa_circ_0000129 restricted the tumorigenicity of ovarian cancer cells. Mechanistically, hsa_circ_0000129 has a sponging effect on miR-383-5p, which targets TPM3. Hsa_circ_0000129 stimulated development of the malignant ovarian cancer phenotype by sponging miR-383-5p and releasing TPM3.

ß-Ga2O3 Nanoribbon with Ultra-High Solar-Blind Ultraviolet Polarization Ratio.

Solar-blind ultraviolet (UV) detection plays a critical role in imaging and communication due to its low-noise background, high signal-to-noise ratio, and strong anti-interference capabilities. Detecting the polarization state of UV light can enhance image information and expand the communication dimension. Although polarization detection is explored in visible and infrared light, and applied in fields such as astrophysics and submarine seismic wave detection, solar-blind UV polarization detection remains largely unreported. This is primarily due to the challenge of creating UV polarizers with high transmittance, high extinction ratio, and strong resistance to UV radiation. In this study, it is discovered that the space symmetry breaking of the ß-Ga2O3's b-c plane results in a significant optical absorption dichroic ratio. Leveraging ß-Ga2O3's high solar-blind UV response, a lensless solar-blind UV polarization-sensitive photodetector, circumventing the challenges associated with solar-blind UV polarizers is designed. This photodetector exhibits an exceptionally high intrinsic polarization ratio under 254 nm linearly polarized light, approximately two orders of magnitude higher than other reported nanomaterial-based polarization-sensitive photodetectors. Additionally, it demonstrates significant advantages in solar-blind UV imaging and light communication. This work introduces a novel strategy for solar-blind ultraviolet polarization detection and offers a promising approach for solar-blind light communication.

An experimental study of acoustic bird repellents for reducing bird encroachment in pear orchards.

Bird invasion will reduce the yield of high-value crops, which threatens the healthy development of agricultural economy. Sonic bird repellent has the advantages of large range, no time and geographical restrictions, and low cost, which has attracted people's attention in the field of agriculture. At present, there are few studies on the application of sonic bird repellents in pear orchards to minimize economic losses and prolong the adaptive capacity of birds. In this paper, a sound wave bird repellent system based on computer vision is designed, which combines deep learning target recognition technology to accurately identify birds and drive them away. The neural network model that can recognize birds is first trained and deployed to the server. Live video is captured by an installed webcam, and the sonic bird repellent is powered by an ESP-8266 relay switch. In a pear orchard, two experimental areas were divided into two experimental areas to test the designed sonic bird repellent device, and the number of bad fruits pecked by birds was used as an indicator to evaluate the bird repelling effect. The results showed that the pear pecked fruit rate was 6.03% in the pear orchard area that used the acoustic bird repeller based on computer recognition, 7.29% in the pear orchard area of the control group that used the acoustic bird repeller with continuous operation, and 13.07% in the pear orchard area that did not use any bird repellent device. While acoustic bird repellers based on computer vision can be more effective at repelling birds, they can be used in combination with methods such as fruit bags to reduce the economic damage caused by birds.

Peptide and Protein Cysteine Modification Enabled by Hydrosulfuration of Ynamide.

Efficient functionalization of peptides and proteins has widespread applications in chemical biology and drug discovery. However, the chemoselective and site-selective modification of proteins remains a daunting task. Herein, a highly efficient chemo-, regio-, and stereoselective hydrosulfuration of ynamide was identified as an efficient method for the precise modification of peptides and proteins by uniquely targeting the thiol group of cysteine (Cys) residues. This novel method could be facilely operated in aqueous buffer and was fully compatible with a wide range of proteins, including small model proteins and large full-length antibodies, without compromising their integrity and functions. Importantly, this reaction provides the Z-isomer of the corresponding conjugates exclusively with superior stability, offering a precise approach to peptide and protein therapeutics. The potential application of this method in peptide and protein chemical biology was further exemplified by Cys-bioconjugation with a variety of ynamide-bearing functional molecules such as small molecule drugs, fluorescent/affinity tags, and PEG polymers. It also proved efficient in redox proteomic analysis through Cys-alkenylation. Overall, this study provides a novel bioorthogonal tool for Cys-specific functionalization, which will find broad applications in the synthesis of peptide/protein conjugates.

What do we need to address when we treat neglected Monteggia fracture in children.

Monteggia fracture is a relatively uncommon injury in pediatric patients, accounting for less than 2% of forearm fractures, characterized by a combination of ulna fracture and radial head dislocation. Neglected Monteggia fractures define as those that have not received treatment within 3 weeks. In children, ulna fractures are easily diagnosed while radial head dislocation may be overlooked, necessitating open reduction after neglecting the Monteggia fracture and potentially causing additional trauma to the child. This study aims to review the pathological characteristics of neglected Monteggia fractures based on the length ratio of the ulna and radius, relative positions between the proximal ends of the ulna and radius, the integrality of annular ligament and the pathological change of proximal radioulnar joint. The findings will provide valuable insights and guidance for managing neglected Monteggia fractures.

RETRACTED: Liu et al. Antiproliferative Activity of Triterpene Glycoside Nutrient from Monk Fruit in Colorectal Cancer and Throat Cancer. Nutrients 2016, 8, 360.

The journal retracts the article, "Antiproliferative Activity of Triterpene Glycoside Nutrient from Monk Fruit in Colorectal Cancer and Throat Cancer" [...].

Comparison and identification of aroma components in 21 kinds of frankincense with variety and region based on the odor intensity characteristic spectrum constructed by HS-SPME-GC-MS combined with E-nose.

Frankincense is an important seasoning and spice known for its distinctive and intricate flavor profile. Considering the considerable variation in the aromatic quality of frankincense due to geographical origin, species diversity and cultivation conditions, frankincense from major global origins was characterized holistically for the first time. The electronic nose (E-nose) with headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) and sensory evaluation were implemented to characterize the aroma components of 21 commercial varieties of frankincense from around the world. The results showed that a total of 149 volatile organic compounds (VOCs) of 10 categories were identified in frankincense, among which the numbers of alcohols, terpenes and esters compounds accounted for 22.15 %, 18.79 % and 15.44 % of the total VOCs of frankincense, respectively. The PLS-DA model effectively distinguished frankincense from Oman/Somalia and other origins. Furthermore, the study identified two differential VOCs with VIP > 1 in three Asian countries and five in six African countries. The total VOCs content and sensory characteristic score of "Lemon/Citrus" in Oman frankincense is significantly higher than other regions. The OAV results showed that 61 substances (e.g., Diacety, alpha-Pinene, Camphene, Myrcene) as key aroma compounds and OICS model indicated that p-Cymenol was found to contribute significantly to the citrus aroma in frankincense. This study identified the fundamental components of frankincense flavor and revealed different flavor descriptors of frankincense, which are crucial for reconstructing frankincense flavor and improving flavor quality.

Critical-Layered MoS2 for the Enhancement of Supercontinuum Generation in Photonic Crystal Fibre.

Supercontinuum generation (SCG) from silica-based photonic crystal fibers (PCFs) is of highly technological significance from microscopy to metrology, but has been hindered by silica's relatively low intrinsic optical nonlinearity. The prevailing approaches of filling PCF with nonlinear gases or liquids can endow fibre with enhanced optical nonlinearity and boosted SCG efficiency, yet these hybrids are easily plagued by fusion complexity, environmental incompatibility or transmission mode instability. Here this work presents a strategy of embedding solid-state 2D MoS2 atomic layers into the air-holes of PCF to efficiently enhance SCG. This work demonstrates a 4.8 times enhancement of the nonlinear coefficient and a 70% reduction of the threshold power for SCG with one octave spanning in the MoS2-PCF hybrid. Furthermore, this work finds that the SCG enhancement is highly layer-dependent, which only manifests for a real 2D regime within the thickness of five atomic layers. Theoretical calculations reveal that the critical thickness arises from the trade-off among the layer-dependent enhancement of the nonlinear coefficient, leakage of fundamental mode and redshift of zero-dispersion wavelength. This work provides significant advances toward efficient SCG, and highlights the importance of matching an appropriate atomic layer number in the design of functional 2D material optical fibers.

Large-Area Epitaxial Growth of Transition Metal Dichalcogenides.

Over the past decade, research on atomically thin two-dimensional (2D) transition metal dichalcogenides (TMDs) has expanded rapidly due to their unique properties such as high carrier mobility, significant excitonic effects, and strong spin-orbit couplings. Considerable attention from both scientific and industrial communities has fully fueled the exploration of TMDs toward practical applications. Proposed scenarios, such as ultrascaled transistors, on-chip photonics, flexible optoelectronics, and efficient electrocatalysis, critically depend on the scalable production of large-area TMD films. Correspondingly, substantial efforts have been devoted to refining the synthesizing methodology of 2D TMDs, which brought the field to a stage that necessitates a comprehensive summary. In this Review, we give a systematic overview of the basic designs and significant advancements in large-area epitaxial growth of TMDs. We first sketch out their fundamental structures and diverse properties. Subsequent discussion encompasses the state-of-the-art wafer-scale production designs, single-crystal epitaxial strategies, and techniques for structure modification and postprocessing. Additionally, we highlight the future directions for application-driven material fabrication and persistent challenges, aiming to inspire ongoing exploration along a revolution in the modern semiconductor industry.

Association between hypothyroidism and nephrotic syndrome: a bidirectional two-sample Mendelian randomization analysis.

BACKGROUND: There is a close clinical association between hypothyroidism and nephrotic syndrome (NS) was close, but whether there is genetic causality between the two is not known. OBJECTIVE: Using pooled data from a genome-wide association study (GWAS), the association between hypothyroidism and NS was explored via Mendelian randomization (MR) analysis. METHODS: Single-nucleotide polymorphisms (SNPs) associated with hypothyroidism (or NS) were screened as genetic instrumental variables (IVs) from pooled GWAS data, and inverse-variance weighting (IVW) was used for the main analysis to estimate causal effects, with MR-Egger, weighted median, and weighted mode used as complementary methods. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept, MR-PRESSO and leave-one-out, were also conducted to assess the robustness of the results. RESULTS: Genetically predicted hypothyroidism was positively associated with the risk of developing NS (IVW: OR = 1.18, 95% CI: 1.07-1.30, p = 0.00; MR-Egger: OR = 1.36, 95% CI: 1.10-1.68, p = 0.01), and the MR-Egger intercept (intercept = -0.02, p = 0.14), MR-PRESSO test (p = 0.14), Cochran's Q test (p = 0.15) and leave-one-out test results supported the robustness of the results. Genetically predicted NS status might not be associated with an increased risk of developing hypothyroidism (IVW: OR = 1.01, 95% CI: 1.00-1.03, p = 0.08; MR-Egger: OR = 1.01, 95% CI: 0.98-1.04, p = 0.43), and the MR-Egger intercept (intercept < 0.01, p = 0.69), MR-PRESSO test (p = 0.64), Cochran's Q test (p = 0.61) and leave-one-out test results supported the robustness of the results. CONCLUSION: Hypothyroidism status could increase the risk of developing NS.

Real-world retrospective study of anti-PD-1 antibody in combination with chemotherapy as a neoadjuvant treatment strategy for locally advanced resectable esophageal squamous cell carcinoma.

Background: Neoadjuvant therapy has become a mainstay of treatment for locally advanced resectable esophageal cancer. The objective of this research was to investigate the effectiveness and safety of neoadjuvant immunotherapy combined with chemotherapy in treating surgically removable esophageal squamous cell carcinoma (ESCC). Methods: From January 1, 2016 to April 1, 2023, we conducted a retrospective analysis of patients diagnosed with resectable esophageal cancer who underwent neoadjuvant immunotherapy combined with chemotherapy at The First Affiliated Hospital of Nanchang University. The primary endpoints of this study were pathologic complete response (pCR), major pathologic response (MPR) and disease-free survival (DFS). The secondary endpoints of this study were overall survival (OS), objective response rate (ORR) and safety. Results: A total of 122 patients with ESCC receiving neoadjuvant immune-chemotherapy (nICT) were included. Fifty-four patients achieved partial response (PR) and two patients achieved complete response (CR), with an ORR of 45.9%. Of the 106 patients who underwent surgery, a total of 28 patients achieved pCR (26.4%) and a total of 37 patients achieved MPR (34.9%). Grade 3 or higher adverse events occurred in 26 patients (21.3%). The most common postoperative complication was pneumonitis (25.5%). Conclusions: Neoadjuvant immunotherapy combined with chemotherapy demonstrates satisfactory efficacy in the treatment of locally advanced ESCC, with manageable treatment-related adverse events and postoperative complications.

Teplizumab induces persistent changes in the antigen-specific repertoire in individuals at risk for type 1 diabetes.

BACKGROUNDTeplizumab, a non-FcR-binding anti-CD3 mAb, is approved to delay progression of type 1 diabetes (T1D) in at-risk patients. Previous investigations described the immediate effects of the 14-day treatment, but longer-term effects of the drug remain unknown.METHODSWith an extended analysis of study participants, we found that 36% were undiagnosed or remained free of clinical diabetes after 5 years, suggesting operational tolerance. Using single-cell RNA sequencing, we compared the phenotypes, transcriptome, and repertoire of peripheral blood CD8+ T cells including autoreactive T cells from study participants before and after teplizumab and features of responders and non-responders.RESULTSAt 3 months, there were transcriptional signatures of cell activation in CD4+ and CD8+ T cells including signaling that was reversed at 18 months. At that time, there was reduced expression of genes in T cell receptor and activation pathways in clinical responders. In CD8+ T cells, we found increased expression of genes associated with exhaustion and immune regulation with teplizumab treatment. These transcriptional features were further confirmed in an independent cohort. Pseudotime analysis showed differentiation of CD8+ exhausted and memory cells with teplizumab treatment. IL7R expression was reduced, and patients with lower expression of CD127 had longer diabetes-free intervals. In addition, the frequency of autoantigen-reactive CD8+ T cells, which expanded in the placebo group over 18 months, did not increase in the teplizumab group.CONCLUSIONThese findings indicate that teplizumab promotes operational tolerance in T1D, involving activation followed by exhaustion and regulation, and prevents expansion of autoreactive T cells.TRIAL REGISTRATIONClinicalTrials.gov NCT01030861.FUNDINGNational Institute of Diabetes and Digestive and Kidney Diseases/NIH, Juvenile Diabetes Research Foundation.