Correction: DPPA2/4 and SUMO E3 ligase PIAS4 opposingly regulate zygotic transcriptional program.

[This corrects the article DOI: 10.1371/journal.pbio.3000324.].

Mitochondrial Dysfunction of Peripheral Platelets as a Predictive Biomarker for Postoperative Delirium in Elderly Patients.

OBJECTIVE: To determine the association between the preoperative Bioenergetic Health Index (BHI) of platelets and the occurrence of postoperative delirium (POD) in elderly patients. METHODS: Elderly patients scheduled for major abdominal surgery under general anesthesia were included. The presence of POD was assessed within the 3 days after surgery. Seahorse XF analysis and transmission electron microscopy were utilized to evaluate the mitochondrial metabolism and morphology of platelets. RESULTS: A total of 20 out of 162 participants developed POD. Participants with POD showed lower preoperative Mini-Mental State Examination scores and total protein levels, fewer educational years, longer surgery duration, higher mean platelet volume, and lower platelet BHI compared with those without POD. Damaged mitochondria with swollen appearance and distorted cristae was detected in platelets from participants with POD. Preoperative platelet BHI was independently associated with the occurrence of POD after adjusting for age, education, preoperative Mini-Mental State Examination score, preoperative mean platelet volume and total protein levels, surgical type and duration, and lymphocyte counts on the first postoperative day (OR 0.11, 95% CI 0.03-0.37, p < 0.001). The areas under the receiver operating curves for predicting POD were 0.83 (95% CI 0.76-0.88) for platelet BHI. It showed a sensitivity of 85.00% and specificity of 73.24%, with an optimal cutoff value of 1.61. Using a serial combination (mean platelet volume followed by BHI) yielded a sensitivity of 80.00% and specificity of 82.39%. INTERPRETATION: Preoperative platelet BHI was independently associated with the occurrence of POD in elderly patients and has the potential as a screening biomarker for POD risk. ANN NEUROL 2024;96:74-86.

Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction.

T cells become dysfunctional when they encounter self antigens or are exposed to chronic infection or to the tumour microenvironment1. The function of T cells is tightly regulated by a combinational co-stimulatory signal, and dominance of negative co-stimulation results in T cell dysfunction2. However, the molecular mechanisms that underlie this dysfunction remain unclear. Here, using an in vitro T cell tolerance induction system in mice, we characterize genome-wide epigenetic and gene expression features in tolerant T cells, and show that they are distinct from effector and regulatory T cells. Notably, the transcription factor NR4A1 is stably expressed at high levels in tolerant T cells. Overexpression of NR4A1 inhibits effector T cell differentiation, whereas deletion of NR4A1 overcomes T cell tolerance and exaggerates effector function, as well as enhancing immunity against tumour and chronic virus. Mechanistically, NR4A1 is preferentially recruited to binding sites of the transcription factor AP-1, where it represses effector-gene expression by inhibiting AP-1 function. NR4A1 binding also promotes acetylation of histone 3 at lysine 27 (H3K27ac), leading to activation of tolerance-related genes. This study thus identifies NR4A1 as a key general regulator in the induction of T cell dysfunction, and a potential target for tumour immunotherapy.

Dimensional and Doping Engineering of Chiral Perovskites with Enhanced Spin Selectivity for Green Emissive Spin Light-Emitting Diodes.

Chiral perovskites play a pivotal role in spintronics and optoelectronic systems attributed to their chiral-induced spin selectivity (CISS) effect. Specifically, they allow for spin-polarized charge transport in spin light-emitting diodes (LEDs), yielding circularly polarized electroluminescence at room temperature without external magnetic fields. However, chiral lead bromide-based perovskites have yet to achieve high-performance green emissive spin-LEDs, owing to limited CISS effects and charge transport. Herein, we employ dimensional regulation and Sn2+-doping to optimize chiral bromide-based perovskite architecture for green emissive spin-LEDs. The optimized (PEA)x(S/R-PRDA)2-xSn0.1Pb0.9Br4 chiral perovskite film exhibits an enhanced CISS effect, higher hole mobility, and better energy level alignment with the emissive layer. These improvements allow us to fabricate green emissive spin-LEDs with an external quantum efficiency (EQE) of 5.7% and an asymmetry factor |gCP-EL| of 1.1 × 10-3. This work highlights the importance of tailored perovskite architectures and doping strategies in advancing spintronics for optoelectronic applications.

Full-length transcriptome analysis of Ophioglossum vulgatum: effects of experimentally identified chloroplast gene clusters on expression and evolutionary patterns.

Genes with similar or related functions in chloroplasts are often arranged in close proximity, forming clusters on chromosomes. These clusters are transcribed coordinated to facilitate the expression of genes with specific function. Our previous study revealed a significant negative correlation between the chloroplast gene expression level of the rare medicinal fern Ophioglossum vulgatum and its evolutionary rates as well as selection pressure. Therefore, in this study, we employed a combination of SMRT and Illumina sequencing technology to analyze the full-length transcriptome sequencing of O. vulgatum for the first time. In particular, we experimentally identified gene clusters based on transcriptome data and investigated the effects of chloroplast gene clustering on expression and evolutionary patterns. The results revealed that the total sequenced data volume of the full-length transcriptome of O. vulgatum amounted to 71,950,652,163 bp, and 110 chloroplast genes received transcript coverage. Nine different types of gene clusters were experimentally identified in their transcripts. The chloroplast cluster genes may cause a decrease in non-synonymous substitution rate and selection pressure, as well as a reduction in transversion rate, transition rate, and their ratio. While expression levels of chloroplast cluster genes in leaf, sporangium, and stem would be relatively elevated. The Mann-Whitney U test indicated statistically significant in the selection pressure, sporangia and leaves groups (P < 0.05). We have contributed novel full-length transcriptome data resources for ferns, presenting new evidence on the effects of chloroplast gene clustering on expression land evolutionary patterns, and offering new theoretical support for transgenic research through gene clustering.

Stimulus-Induced Dynamic Behavior Regulation of Flexible Crystals through the Tuning of Module Rigidity.

Introducing dynamic behavior into periodic frameworks has borne fruit in the form of flexible porous crystals. The detailed molecular design of frameworks in order to control their collective dynamics is of particular interest, for example, to achieve stimulus-induced behavior. Herein, by varying the degree of rigidity of ditopic pillar linkers, two isostructural flexible metal-organic frameworks (MOFs) with common rigid supermolecular building bilayers were constructed. The subtle substitution of single (in bibenzyl-4,4'-dicarboxylic acid; H2BBDC) with double (in 4,4'-stilbenedicarboxylic acid; H2SDC) C-C bonds in pillared linkers led to markedly different flexible behavior of these two MOFs. Upon the removal of guest molecules, both frameworks clearly show reversible single-crystal-to-single-crystal transformations involving the cis-trans conformation change and a resulting swing of the corresponding pillar linkers, which gives rise to Flex-Cd-MOF-1a and Flex-Cd-MOF-2a, respectively. Strikingly, a more favorable gas-induced dynamic behavior in Flex-Cd-MOF-2a was verified in detail by stepwise C3H6/C3H8 sorption isotherms and the corresponding in situ powder X-ray diffraction experiments. These insights are strongly supported by molecular modeling studies on the sorption mechanism that explores the sorption landscape. Furthermore, a consistency between the macroscopic elasticity and microscopic flexibility of Flex-Cd-MOF-2 was observed. This work fuels a growing interest in developing MOFs with desired chemomechanical functions and presents detailed insights into the origins of flexible MOFs.

Repetition rate tuning and locking of solitons in a microrod resonator.

Recently, there has been significant interest in the generation of coherent temporal solitons in optical microresonators. In this Letter, we present a demonstration of dissipative Kerr soliton generation in a microrod resonator using an auxiliary-laser-assisted thermal response control method. In addition, we are able to control the repetition rate of the soliton over a range of 200 kHz while maintaining the pump laser frequency, by applying external stress tuning. Through the precise control of the PZT voltage, we achieve a stability level of 3.9 × 10-10 for residual fluctuation of the repetition rate when averaged 1 s. Our platform offers precise tuning and locking capabilities for the repetition frequency of coherent mode-locked combs in microresonators. This advancement holds great potential for applications in spectroscopy and precision measurements.

Predictors for non-attainment of meropenem target concentrations when treating infections in critically ill patients
.

BACKGROUND: Failure to achieve target concentrations of ß-lactam antibiotics is not uncommon despite administration of high doses. The objective of this study was to identify risk factors predicting non-attainment of ß-lactams target concentration in critically ill patients receiving meropenem as an intravenous infusion. MATERIALS AND METHODS: The retrospective study included adult patients receiving meropenem by intravenous infusion and undergoing therapeutic drug monitoring (TDM) in the intensive care units (ICU) at Nanjing First Hospital. Blood samples were analyzed using UPLC-MS. Potential risk factors were evaluated by correlating them with meropenem trough concentrations (Cmin) lower than the targeted concentration (the minimum inhibitory concentration (MIC)). RESULTS: Non-attainment of target concentrations was observed in 41 patients (19.5%) of the 210 patients examined. Predictors for non-attainment using multivariate logistic regression analysis were: age (p = 0.013), dosage (p = 0.042), augmented renal clearance (ARC), (p = 0.041). CONCLUSION: In addition to the expected risk factors (age and dosage), ARC was a predictor for non-attainment of the target concentration. The risk of non-attainment of target concentrations increased with an increase in creatinine clearance. Attention should be given to ARC and creatinine clearance when administering meropenem by intravenous infusion.

Network pharmacology analysis of the renal protective effects of bracken (Pteridium aquilinum) using experimental data obtained in an avian (quail) hyperuricemia model.

OBJECTIVE: To investigate the nephroprotective potential of orally administered bracken Pteridium aquilinum extract against renal damage in quails, induced by a high-purine diet, to form a foundation for subsequent clinical studies and applications. MATERIALS AND METHODS: A mass spectrometry analysis was conducted on the pteridophyte subjected to steam explosion. Network pharmacological methods were then utilized to pinpoint shared targets and pathways, which suggested that Pteridium aquilinum has a capability to counteract renal injury. A total of 48 specific-pathogen-free (SPF) "Difaku" quails were selected and segregated into six distinct groups. The control group received a standard diet, whereas the other groups were fed a high-purine diet. Beginning on day 14, each group was subjected to designated therapeutic measures. The study continued for 40 days, after which relevant biological markers were assessed. RESULTS: Active compound peaks from the steam-exploded Pteridium aquilinum were isolated. Subsequently, 101 targets and several pathways associated with renoprotective effects were discerned, indicating that the Pteridium aquilinum achieves its nephroprotective function through comprehensive regulatory mechanisms. The high-purine diet successfully induced hyperuricemia in the quails, resulting in renal impairment. Following intervention with varied Pteridium aquilinum dosages, renal protective outcomes were evident, though xanthine oxidase activity remained unaffected. Histological analyses demonstrated a notable decrease in renal lesion dimensions post-intervention. CONCLUSION: The steam-exploded bracken Pteridium aquilinum may provide nephroprotective benefits against hyperuricemia-induced renal damage in quails through comprehensive regulatory processes. This highlights the Pteridium aquilinum's potential as an innovative nephroprotective therapeutic and dietary solution, presenting a promising avenue for hyperuricemia and renal damage treatment and prevention.

Population Genomic Screening for Three Common Hereditary Conditions : A Cost-Effectiveness Analysis.

BACKGROUND: The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown. OBJECTIVE: To estimate the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH). DESIGN: Decision analytic Markov model. DATA SOURCES: Published literature. TARGET POPULATION: Separate age-based cohorts (ages 20 to 60 years at time of screening) of racially and ethnically representative U.S. adults. TIME HORIZON: Lifetime. PERSPECTIVE: U.S. health care payer. INTERVENTION: Population genomic screening using clinical sequencing with a restricted panel of high-evidence genes, cascade testing of first-degree relatives, and recommended preventive interventions for identified probands. OUTCOME MEASURES: Incident breast, ovarian, and colorectal cancer cases; incident cardiovascular events; quality-adjusted survival; and costs. RESULTS OF BASE-CASE ANALYSIS: Screening 100 000 unselected 30-year-olds resulted in 101 (95% uncertainty interval [UI], 77 to 127) fewer overall cancer cases and 15 (95% UI, 4 to 28) fewer cardiovascular events and an increase of 495 quality-adjusted life-years (QALYs) (95% UI, 401 to 757) at an incremental cost of $33.9 million (95% UI, $27.0 million to $41.1 million). The incremental cost-effectiveness ratio was $68 600 per QALY gained (95% UI, $41 800 to $88 900). RESULTS OF SENSITIVITY ANALYSIS: Screening 30-, 40-, and 50-year-old cohorts was cost-effective in 99%, 88%, and 19% of probabilistic simulations, respectively, at a $100 000-per-QALY threshold. The test costs at which screening 30-, 40-, and 50-year-olds reached the $100 000-per-QALY threshold were $413, $290, and $166, respectively. Variant prevalence and adherence to preventive interventions were also highly influential parameters. LIMITATIONS: Population averages for model inputs, which were derived predominantly from European populations, vary across ancestries and health care environments. CONCLUSION: Population genomic screening with a restricted panel of high-evidence genes associated with 3 CDC Tier 1 conditions is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions. PRIMARY FUNDING SOURCE: National Human Genome Research Institute.

The mRNA-destabilizing protein Tristetraprolin targets "meiosis arrester" Nppc mRNA in mammalian preovulatory follicles.

C-natriuretic peptide (CNP) and its receptor guanylyl cyclase, natriuretic peptide receptor 2 (NPR2), are key regulators of cyclic guanosine monophosphate (cGMP) homeostasis. The CNP-NPR2-cGMP signaling cascade plays an important role in the progression of oocyte meiosis, which is essential for fertility in female mammals. In preovulatory ovarian follicles, the luteinizing hormone (LH)-induced decrease in CNP and its encoding messenger RNA (mRNA) natriuretic peptide precursor C (Nppc) are a prerequisite for oocyte meiotic resumption. However, it has never been determined how LH decreases CNP/Nppc In the present study, we identified that tristetraprolin (TTP), also known as zinc finger protein 36 (ZFP36), a ubiquitously expressed mRNA-destabilizing protein, is the critical mechanism that underlies the LH-induced decrease in Nppc mRNA. Zfp36 mRNA was transiently up-regulated in mural granulosa cells (MGCs) in response to the LH surge. Loss- and gain-of-function analyses indicated that TTP is required for Nppc mRNA degradation in preovulatory MGCs by targeting the rare noncanonical AU-rich element harbored in the Nppc 3' UTR. Moreover, MGC-specific knockout of Zfp36, as well as lentivirus-mediated knockdown in vivo, impaired the LH/hCG-induced Nppc mRNA decline and oocyte meiotic resumption. Furthermore, we found that LH/hCG activates Zfp36/TTP expression through the EGFR-ERK1/2-dependent pathway. Our findings reveal a functional role of TTP-induced mRNA degradation, a global posttranscriptional regulation mechanism, in orchestrating the progression of oocyte meiosis. We also provided a mechanism for understanding CNP-dependent cGMP homeostasis in diverse cellular processes.

Growth Properties and Metabolomic Analysis Provide Insight into Drought Tolerance in Barley (Hordeum vulgare L.).

Drought stress is a major meteorological threat to crop growth and yield. Barley (Hordeum vulgare L.) is a vital cereal crop with strong drought tolerance worldwide. However, the underlying growth properties and metabolomic regulatory module of drought tolerance remains less known. Here, we investigated the plant height, spike length, effective tiller, biomass, average spikelets, 1000-grain weight, number of seeds per plant, grain weight per plant, ash content, protein content, starch content, cellulose content, and metabolomic regulation mechanisms of drought stress in barley. Our results revealed that the growth properties were different between ZDM5430 and IL-12 under drought stress at different growth stages. We found that a total of 12,235 metabolites were identified in two barley genotype root samples with drought treatment. More than 50% of these metabolites showed significant differences between the ZDM5430 and IL-12 roots. The Kyoto Encyclopedia of Genes and Genomes pathway analysis identified 368 differential metabolites mainly involved in starch and sucrose metabolism, the pentose phosphate pathway, pyrimidine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis in ZDM5430 under drought stress, whereas the different metabolites of IL-12 under drought stress related to starch and sucrose metabolism, the pentose phosphate pathway, 2-oxocarboxylic acid metabolism, cutin, suberine and wax biosynthesis, carbon metabolism, fatty acid biosynthesis, and C5-branched dibasic acid metabolism. These metabolites have application in the tricarboxylic cycle, the urea cycle, the met salvage pathway, amino acid metabolism, unsaturated fatty acid biosynthesis, phenolic metabolism, and glycolysis. On the other hand, the expression patterns of 13 genes related to the abovementioned bioprocesses in different barley genotypes roots were proposed. These findings afford an overview for the understanding of barley roots' metabolic changes in the drought defense mechanism by revealing the differently accumulated compounds.

Role of corticosteroids in the treatment of critically ill sepsis patients: a meta-analysis review.

OBJECTIVE: It was to systematically evaluate the effect of corticosteroids on 28d all-cause mortality (ACM), in-hospital death rate, and ICU death rate in critically ill sepsis patients. METHODS: PubMed, Embase, and Medline databases were used to screen the published literatures on the therapeutic effect of corticosteroids in the treatment of critically ill sepsis patients. After evaluating the quality of the included literatures, RevMan 5.3 software was used for meta-analysis. 4524 literatures regarding the application of corticosteroids to treat critically ill sepsis patients were preliminarily searched. After screening was carried out, 9 literatures were finally included. 2,850 patients were treated with corticosteroids and 2867 patients were treated with placebo. RESULTS: The meta-analysis of the effect of corticosteroids versus placebo on 28dACM showed [OR = 0.87, 95% CI 0.78-0.98, Z = 2.22, P = 0.03], P < 0.05; the meta-analysis of the outcome of corticosteroids versus placebo on ICU death rate showed [OR = 0.77, 95% CI 0.63-0.94, Z = 2.60, P = 0.009], P < 0.05; and the meta-analysis of the effect of corticosteroids versus placebo on in-hospital death rate showed [OR = 0.80, 95% CI 0.66-0.96, Z = 2.34, P = 0.002], P < 0.05. CONCLUSION: In summary, corticosteroids can reduce the death rate of critically ill sepsis patients to a certain extent and have good clinical application value.

Application of fixed-frequency ultrasound in the cultivation of Saccharomyces cerevisiae for rice wine fermentation.

BACKGROUND: Rice wine (RW) fermentation is limited by its long fermentation time, weak taste and unpleasant flavors such as oil and odor. In this study, a novel ultrasound technology of Saccharomyces cerevisiae was used with the aim of improving fermentation efficiency and volatile flavor quality of RW. RESULTS: The results showed that fixed-frequency ultrasonic treatment (28 kHz, 45 W L-1, 20 min) of S. cerevisiae seed culture at its logarithmic metaphase significantly increased the biomass and alcohol yield by 31.58% and 26.45%, respectively, and reduced fermentation time by nearly 2 days. Flavor analysis indicated that the flavor compounds in RW, specifically the esters and alcohols, were also increased in quantity after the ultrasonic treatment of S. cerevisiae seed liquid. Isobutyl acetate, ethyl butyrate, ethyl hexanoate and phenethyl acetate contents were increased by 78.92%, 129.19%, 7.79% and 97.84%, respectively, as compared to the control. CONCLUSION: Ultrasonic treatment of S. cerevisiae reduced fermentation time and enhanced the flavor profile of RW. This study could provide a theoretical and/or technological basis for the research and development of RW. © 2024 Society of Chemical Industry.

Hydroxyl ion absorption in on-chip high-Q resonators.

Thermal silica is a common dielectric used in all-silicon photonic circuits. Additionally, bound hydroxyl ions (Si-OH) can provide a significant component of optical loss in this material on account of the wet nature of the thermal oxidation process. A convenient way to quantify this loss relative to other mechanisms is through OH absorption at 1380 nm. Here, using ultra-high-quality factor (Q-factor) thermal-silica wedge microresonators, the OH absorption loss peak is measured and distinguished from the scattering loss baseline over a wavelength range from 680 nm to 1550 nm. Record-high on-chip resonator Q-factors are observed for near-visible and visible wavelengths, and the absorption limited Q-factor is as high as 8 billion in the telecom band. Hydroxyl ion content level around 2.4 ppm (weight) is inferred from both Q measurements and by secondary ion mass spectroscopy (SIMS) depth profiling.

AlGaAs soliton microcombs at room temperature.

Soliton mode locking in high-Q microcavities provides a way to integrate frequency comb systems. Among material platforms, AlGaAs has one of the largest optical nonlinearity coefficients, and is advantageous for low-pump-threshold comb generation. However, AlGaAs also has a very large thermo-optic effect that destabilizes soliton formation, and femtosecond soliton pulse generation has only been possible at cryogenic temperatures. Here, soliton generation in AlGaAs microresonators at room temperature is reported for the first time, to the best of our knowledge. The destabilizing thermo-optic effect is shown to instead provide stability in the high-repetition-rate soliton regime (corresponding to a large, normalized second-order dispersion parameter D2/κ). Single soliton and soliton crystal generation with sub-milliwatt optical pump power are demonstrated. The generality of this approach is verified in a high-Q silica microtoroid where manual tuning into the soliton regime is demonstrated. Besides the advantages of large optical nonlinearity, these AlGaAs devices are natural candidates for integration with semiconductor pump lasers. Furthermore, the approach should generalize to any high-Q resonator material platform.

Soliton Microcombs Multiplexing Using Intracavity-Stimulated Brillouin Lasers.

Solitons in microresonators have spurred intriguing nonlinear optical physics and photonic applications. Here, by combining Kerr and Brillouin nonlinearities in an over-modal microcavity, we demonstrate spatial multiplexing of soliton microcombs under a single external laser pumping operation. This demonstration offers an ideal scheme to realize highly coherent dual-comb sources in a compact, low-cost and energy-efficient manner, with uniquely low beating noise. Moreover, by selecting the dual-comb modes, the repetition rate difference of a dual-comb pair could be flexibly switched, ranging from 8.5 to 212 MHz. Beyond dual-comb, the high-density mode geometry allows the cascaded Brillouin lasers, driving the co-generation of up to 5 space-multiplexing frequency combs in distinct mode families. This Letter offers a novel physics paradigm for comb interferometry and provides a widely appropriate tool for versatile applications such as comb metrology, spectroscopy, and ranging.

IL-8-induced CXCR2 down-regulation in circulating monocytes in hepatocellular carcinoma is partially dependent on MAGL.

BACKGROUND: CXC-chemokine receptor 2 (CXCR2) expression was found to be down-regulated on circulating monocytes of cancer patients. Here, we analyze the percentage of CD14+CXCR2+ monocyte subsets in hepatocellular carcinoma (HCC) patients, and investigate the mechanisms that regulate CXCR2 surface expression on monocytes and its biological function. METHODS: Flow cytometry was used to analyze the proportion of the CD14+CXCR2+ subset from the total circulating monocytes of HCC patients. Interleukin 8 (IL-8) levels were measured from serum and ascites, and their correlation with the CD14+CXCR2+ monocyte subset proportion was calculated. THP-1 cells were cultured in vitro and treated with recombinant human IL-8 and CXCR2 surface expression was analyzed. CXCR2 was knocked down to examine how it affects the antitumor activity of monocytes. Finally, a monoacylglycerol lipase (MAGL) inhibitor was added to analyze its effect on CXCR2 expression. RESULTS: A decrease in the proportion of the CD14+CXCR2+ monocyte subset was observed in HCC patients compared with healthy controls. CXCR2+ monocyte subset proportion was associated with the AFP value, TNM stage, and liver function. Overexpression of IL-8 was observed in the serum and ascites of HCC patients, and negatively correlated with CXCR2+ monocyte proportion. IL-8 decreased CXCR2 expression in THP-1 cells, contributing to decreased antitumor activity toward HCC cells. MAGL expression in THP-1 cells was up-regulated after IL-8 treatment, and the MAGL inhibitor partially reversed the effects of IL-8 on CXCR2 expression. CONCLUSIONS: Overexpression of IL-8 drives CXCR2 down-regulation on circulating monocytes of HCC patients, which could be partially reversed by a MAGL inhibitor.

Pretreatment of the ROS Inhibitor Phenyl-N-tert-butylnitrone Alleviates Sleep Deprivation-Induced Hyperalgesia by Suppressing Microglia Activation and NLRP3 Inflammasome Activity in the Spinal Dorsal Cord.

Sleep deprivation, a common perioperative period health problem, causes ocular discomfort and affects postsurgical pain. However, the mechanism of sleep deprivation-induced increased pain sensitivity is elusive. This study aims to explore the role of ROS in sleep deprivation (SD)-induced hyperalgesia and the underlying mechanism. A 48-h continuous SD was performed prior to the hind paw incision pain modeling in mice. We measured ROS levels, microglial activation, DNA damage and protein levels of iNOS, NLRP3, p-P65 and P65 in mouse spinal dorsal cord. The involvement of ROS in SD-induced prolongation of postsurgical pain was further confirmed by intrathecal injection of ROS inhibitor, phenyl-N-tert-butylnitrone (PBN). Pretreatment of 48-h SD in mice significantly prolonged postsurgical pain recovery, manifesting as lowered paw withdrawal mechanical threshold and paw withdrawal thermal latency. It caused ROS increase and upregulation of iNOS on both Day 1 and 7 in mouse spinal dorsal cord. In addition, upregulation of NLRP3 and p-P65, microglial activation and DNA damage were observed in mice pretreated with 48-h SD prior to the incision. Notably, intrathecal injection of PBN significantly reversed the harmful effects of SD on postsurgical pain recovery, hyperalgesia, microglial activation and DNA damage via the NF-κB signaling pathway. Collectively, ROS increase is responsible for SD-induced hyperalgesia through activating microglial, triggering DNA damage and enhancing NLRP3 inflammasome activity in the spinal dorsal cord.

Periapical Lesions and Missed Canals in Endodontically Treated Teeth: A Cone-Beam Computed Tomographic Study of a Chinese Subpopulation.

BACKGROUND Periapical lesions (PL) are a common complication of endodontically treated teeth (ETT), which can result from a missed canal (MC). This study aimed to assess the prevalence of PL and MC in the ETT of a Chinese subpopulation and investigate potential associations between them. MATERIAL AND METHODS A total of 561 cone-beam computed tomography images were selected and analyzed. A total of 1024 endodontically treated posterior teeth excluding third molars were evaluated for the presence of PL and MC. The chi-square test or Fisher's exact test, as well as the odds ratio test, were used to determine whether there was an association and risk relationship between the incidence of PL and the occurrence of MC. RESULTS The overall prevalence of PL and MC in ETT was 56.1% and 19.0%, respectively. In endodontically treated molars, the incidence of PL and MC was 64.1% and 27.6%, whereas in premolars, it was 42.1% and 4.27%. The maxillary first molar showed the highest frequency of PL (71.5%) and MC (65.7%), with the mesiobuccal second canal being the most missed (78.8%). Teeth with an MC were found to be 3.658 times (95% confidence interval=2.541-5.301, P<0.0001) more likely to be associated with a PL. CONCLUSIONS Endodontically treated teeth with missed canals are associated with higher risks of periapical lesions. The high prevalence of these complications in a Chinese subpopulation underscores the importance of implementing enhanced diagnostic and treatment methods for root canal treatment or retreatment.