Effect of age on orthodontic tooth movement in mice.

Background/purpose: The number of middle-aged and elderly orthodontic patients is increasing due to changes in age composition. It is important to investigate the detailed mechanisms of bone remodeling in orthodontic tooth movement (OTM) in the elderly. However, there are few reports on the mechanism of tooth movement in the elderly. The purpose of the present study was to analyze OTM and osteoclastogenesis in aged mice and to elucidate the mechanism. Materials and methods: It has been reported that tumor necrosis factor (TNF)-α plays an important role in osteoclast formation and OTM. First, 8-week-old and 78-week-old male C57BL/6J mice were subcutaneously injected with TNF-α into the calvaiae, and micro-CT, tartrate-resistant acid phosphatase (TRAP) staining, and real-time PCR were performed to evaluate osteoclast formation and bone resorption. Furthermore, osteoclastogenesis by TNF-α and receptor activator of nuclear factor-kappa B ligand (RANKL) using bone marrow cells was evaluated in vitro. Finally, a nickel-titanium closed-coil spring was attached, mesial movement of the maxillary left first molar was performed, and tooth movement distance and osteoclast formation were evaluated. Results: Compared to 8-week-old mice, 78-week-old mice had decreased TNF-α-induced bone resorption, osteoclastogenesis, and TRAP and cathepsin K expression in the calvariae. In vitro osteoclast formation also decreased in 78-week-old mice. Furthermore, tooth movement distance and osteoclastogenesis were reduced. Conclusion: OTM decreased in aged mice, which was shown to be caused by a decrease in osteoclastogenesis. Therefore, it was suggested that it is necessary to keep in mind that tooth movement may be suppressed when treating elderly patients.

Protective effect of carbon dots as antioxidants on intestinal inflammation by regulating oxidative stress and gut microbiota in nematodes and mouse models.

Inflammatory bowel disease (IBD) is a recurrent chronic colitis disease with increasing incidence and prevalence year by year. The single efficacy and significant side effects of traditional IBD treatment drugs have promoted the flourishing development of new drugs. Inspired by many health benefits of carbon dots (CDs) based nanomedicine in biomedical applications, a metal-free carbon dots (CP-CDs) was synthesized from citric acid and polyethylene polyamine to treat colitis. Oxidative stress tests at the cellular and nematode levels demonstrated CP-CDs have good antioxidant effects, while the toxicity of CP-CDs to cells and nematodes is low. CP-CDs were further applied to dextran sodium sulfate (DSS)-induced colitis in mice models, and it was found that CP-CDs can reduce the disease activity index (DAI) score of colon tissue and restore the intestinal barrier. Further, the anti-colitis mechanisms of CP-CDs were explored, one of which is to regulate intestinal oxidative stress in inflammatory mice, further reducing the expression of inflammatory cytokines, and thus alleviating colitis. Notably, 16S rRNA sequence analysis showed that the abundance of beneficial bacteria (Ligilactobacillus and Enterorhabdus) in the intestinal tract increased, while that of harmful bacteria (unclassified_Clostridia_UCG_014) decreased after CP-CDs treatment, indicating that CP-CDs rebalancing the gut microbiota destroyed by DSS is another important mechanism. In short, these non-toxic carbon dots not only have the potential for multi-factor combined relief of colitis but also offer an alternative therapy medicine for patients suffering from IBD.

Novel compound heterozygous variants in FANCI cause premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is a common reproductive aging disorder due to a dramatic decline of ovarian function before 40 years of age. Accumulating evidence reveals that genetic defects, particularly those related to DNA damage response, are a crucial contributing factor to POI. We have demonstrated that the functional Fanconi anemia (FA) pathway maintains the rapid proliferation of primordial germ cells to establish a sufficient reproductive reserve by counteracting replication stress, but the clinical implications of this function in human ovarian function remain to be established. Here, we screened the FANCI gene, which encodes a key component for FA pathway activation, in our whole-exome sequencing database of 1030 patients with idiopathic POI, and identified two pairs of novel compound heterozygous variants, c.[97C > T];[1865C > T] and c.[158-2A > G];[c.959A > G], in two POI patients, respectively. The missense variants did not alter FANCI protein expression and nuclear localization, apart from the variant c.158-2A > G causing abnormal splicing and leading to a truncated mutant p.(S54Pfs*5). Furthermore, the four variants all diminished FANCD2 ubiquitination levels and increased DNA damage under replication stress, suggesting that the FANCI variants impaired FA pathway activation and replication stress response. This study first links replication stress response defects with the pathogenesis of human POI, providing a new insight into the essential roles of the FA genes in ovarian function.

Understanding the role of transition metal single-atom electronic structure in oxysulfur radical-mediated oxidative degradation.

The ubiquity of refractory organic matter in aquatic environments necessitates innovative removal strategies. Sulfate radical-based advanced oxidation has emerged as an attractive solution, offering high selectivity, enduring efficacy, and anti-interference ability. Among many technologies, sulfite activation, leveraging its cost-effectiveness and lower toxicity compared to conventional persulfates, stands out. Yet, the activation process often relies on transition metals, suffering from low atom utilization. Here we introduce a series of single-atom catalysts (SACs) employing transition metals on g-C3N4 substrates, effectively activating sulfite for acetaminophen degradation. We highlight the superior performance of Fe/CN, which demonstrates a degradation rate constant significantly surpassing those of Ni/CN and Cu/CN. Our investigation into the electronic and spin polarization characteristics of these catalysts reveals their critical role in catalytic efficiency, with oxysulfur radical-mediated reactions predominating. Notably, under visible light, the catalytic activity is enhanced, attributed to an increased generation of oxysulfur radicals and a strengthened electron donation-back donation dynamic. The proximity of Fe/CN's d-band center to the Fermi level, alongside its high spin polarization, is shown to improve sulfite adsorption and reduce the HOMO-LUMO gap, thereby accelerating photo-assisted sulfite activation. This work advances the understanding of SACs in environmental applications and lays the groundwork for future water treatment technologies.

(D-Ala2)GIP Inhibits Inflammatory Bone Resorption by Suppressing TNF-α and RANKL Expression and Directly Impeding Osteoclast Formation.

Glucose-insulinotropic polypeptide (GIP) is an incretin hormone that induces insulin secretion and decreases blood glucose levels. In addition, it has been reported to suppress osteoclast formation. Native GIP is rapidly degraded by dipeptidyl peptidase-4 (DPP-4). (D-Ala2)GIP is a newly developed GIP analog that demonstrates enhanced resistance to DPP-4. This study aimed to evaluate the influence of (D-Ala2)GIP on osteoclast formation and bone resorption during lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro. In vivo, mice received supracalvarial injections of LPS with or without (D-Ala2)GIP for 5 days. Osteoclast formation and bone resorption were evaluated, and TNF-α and RANKL expression were measured. In vitro, the influence of (D-Ala2)GIP on RANKL- and TNF-α-induced osteoclastogenesis, LPS-triggered TNF-α expression in macrophages, and RANKL expression in osteoblasts were examined. Compared to the LPS-only group, calvariae co-administered LPS and (D-Ala2)GIP led to less osteoclast formation, lower bone resorption, and decreased TNF-α and RANKL expression. (D-Ala2)GIP inhibited osteoclastogenesis induced by RANKL and TNF-α and downregulated TNF-α expression in macrophages and RANKL expression in osteoblasts in vitro. Furthermore, (D-Ala2)GIP suppressed the MAPK signaling pathway. The results suggest that (D-Ala2)GIP dampened LPS-triggered osteoclast formation and bone resorption in vivo by reducing TNF-α and RANKL expression and directly inhibiting osteoclastogenesis.

Generating Bone Marrow Chimeric Mouse Using GPR120 Deficient Mouse for the Study of DHA Inhibitory Effect on Osteoclast Formation and Bone Resorption.

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that exerts physiological effects via G protein-coupled receptor 120 (GPR120). In our previous studies, we figured out the inhibitory effects of DHA on TNF-α (Tumor necrosis factor-α)-induced osteoclastogenesis via GPR120 in vivo. Moreover, DHA directly suppressed RANKL expression in osteoblasts via GPR120 in vitro. In this study, we generated bone marrow chimeric mice using GPR120 deficient mice (GPR120-KO) to study the inhibitory effects of DHA on bone resorption and osteoclast formation. Bone marrow cells of wild-type (WT) or GPR120-KO mice were transplanted into irradiated recipient mice, which were WT or GPR120 deficient mice. The resulting chimeric mice contained stromal cells from the recipient and bone marrow cells, including osteoclast precursors, from the donor. These chimeric mice were used to perform a series of histological and microfocus computed tomography (micro-CT) analyses after TNF-α injection for induction of osteoclast formation with or without DHA. Osteoclast number and bone resorption were found to be significantly increased in chimeric mice, which did not express GPR120 in stromal cells, compared to chimeric mice, which expressed GPR120 in stromal cells. DHA was also found to suppress specific signaling pathways. We summarized that DHA suppressed TNF-α-induced stromal-dependent osteoclast formation and bone resorption via GPR120.

Azilsartan inhibits inflammation-triggered bone resorption and osteoclastogenesis in vivo via suppression of TNF-α expression in macrophages.

Introduction: Hypertension is a major risk factor for cardiovascular disease (CVD) and is associated with increased bone loss due to excessive activity of the local renin-angiotensin system (RAS). Angiotensinogen/Angiotensin (ANG) II/Angiotensin II type 1 receptor (AT1R) axis is considered as the core axis regulating RAS activity. Azilsartan is an FDA-approved selective AT1R antagonist that is used to treat hypertension. This study aimed to determine whether azilsartan affects formation of osteoclast, resorption of bone, and the expression of cytokines linked with osteoclastogenesis during lipopolysaccharide (LPS)-triggered inflammation in vivo. Methods: In vivo, following a 5-day supracalvarial injection of LPS or tumor necrosis factor-alpha (TNF-α) with or without azilsartan, the proportion of bone resorption and the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, which are identified as osteoclasts on mice calvariae were counted. The mRNA expression levels of TRAP, cathepsin K, receptor activator of NF-κB ligand (RANKL), and TNF-α were also evaluated. In vitro, the effect of azilsartan (0, 0.01, 0.1, 1, and 10 µM) on RANKL and TNF-α-triggered osteoclastogenesis were investigated. Also, whether azilsartan restrains LPS-triggered TNF-α mRNA and protein expression in macrophages and RANKL expression in osteoblasts were assessed. Furthermore, western blotting for analysis of mitogen-activated protein kinases (MAPKs) signaling was conducted. Results: Azilsartan-treated calvariae exhibited significantly lower bone resorption and osteoclastogenesis than those treated with LPS alone. In vivo, LPS with azilsartan administration resulted in lower levels of receptor activator of RANKL and TNF-α mRNA expression than LPS administration alone. Nevertheless, azilsartan did not show inhibitory effect on RANKL- and TNF-α-triggered osteoclastogenesis in vitro. Compared to macrophages treated with LPS, TNF-α mRNA and protein levels were lower in macrophages treated by LPS with azilsartan. In contrast, RANKL mRNA and protein expression levels in osteoblasts were the same in cells co-treated with azilsartan and LPS and those exposed to LPS only. Furthermore, azilsartan suppressed LPS-triggered MAPKs signaling pathway in macrophages. After 5-day supracalvarial injection, there is no difference between TNF-α injection group and TNF-α with azilsartan injection group. Conclusion: These findings imply that azilsartan prevents LPS-triggered TNF-α production in macrophages, which in turn prevents LPS-Triggered osteoclast formation and bone resorption in vivo.

Enhanced generation of oxysulfur radicals by the BiOBr/Montmorillonite activated sulfite system: Performance and mechanism.

The easily synthesized, cost-effective, and stable photocatalysts for sulfite activation are always required for the enhancement of organic contaminants degradation. Herein, the facile coprecipitation synthesis of Bismuth oxybromide (BiOBr)/Montmorillonite (MMT) was reported, which could activate sulfite (SO32-/HSO3-) under sunlight and accelerate the catalytic performance more effectively than pristine BiOBr. After adding sulfite to the photocatalysis system, the photodegradation efficiency of atrazine (ATZ) achieved 73.7% ± 1.5% after 5 min and 94.4% ± 1.6% after 30 min of sunlight irradiation with BiOBr/MMT. The BiOBr/MMT-sulfite system also presented remarkable photocatalytic performance to eliminate various contaminants, including ciprofloxacin, sulfadiazine, tetracycline, and carbamazepine. The various features of the photocatalyst materials were studied, including their surface morphology, structure, optical properties, and composition. The results illustrated that by adding MMT, the bandgap of the pristine BiOBr was reduced and the surface area was increased, which led to an increased ability to adsorb materials. Results of various influence factors showed this enhanced system had satisfactory and stable removal performance of ATZ in the pH range of 3.0-6.5, but HPO42- had a strong negative effect on the system performance. Oxysulfur radicals (SO5·- and SO4·-), h+, and 1O2 were discovered as the prevailing active species in the BiOBr/MMT-sulfite system. The proposed degradation mechanism of this photocatalyst-enhanced system revealed that sulfite adsorption on the surface of the photocatalyst played a vital role during the initial phase, and the degradation pathway of ATZ was discussed. This study provides a new synthesis strategy of a photocatalyst for sulfite activation and expands the potential uses of Bi-based photocatalysts in degrading difficult-to-remove organic pollutants.

Prognostic value of initial routine laboratory blood tests in patients with aneurysmal subarachnoid hemorrhage requiring mechanical ventilation: a retrospective cohort study.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) necessitating mechanical ventilation (MV) presents a serious challenge for intensivists. Laboratory blood tests reflect individual physiological and biochemical states, and provide a useful tool for identifying patients with critical condition and stratifying risk levels of death. This study aimed to determine the prognostic role of initial routine laboratory blood tests in these patients. Methods: This retrospective cohort study included 190 aSAH patients requiring MV in the neurosurgical intensive care unit from December 2019 to March 2022. Follow-up evaluation was performed in May 2022 via routine outpatient appointment or telephone interview. The primary outcomes were death occurring within 7 days after discharge (short-term mortality) or reported at time of follow-up (long-term mortality). Clinico-demographic and radiological characteristics, initial routine laboratory blood tests (e.g., metabolic panels and arterial blood gas analysis), and treatment were analyzed and compared in relation to mortality. Multivariable logistic and Cox regression analyses, with adjustment of other clinical predictors, were performed to determine independent laboratory test predictors for short- and long-term mortality, respectively. Results: The patients had a median age of 62 years, with a median World Federation of Neurosurgical Societies grade (WFNS) score of 5 and a median modified Fisher grade (mFisher) score of 4. The short- and long-term mortality of this cohort were 60.5% and 65.3%, respectively. Compared with survivors, non-survivors had more severe disease upon admission based on neurological status and imaging features and a shorter disease course, and were more likely to receive conservative treatment. Initial ionized calcium was found to be independently associate with both short-term [adjusted odds ratio (OR): 0.92; 95% confidence interval (CI): 0.86 to 0.99; P=0.020] and long-term mortality [adjusted hazard ratio (HR): 0.95; 95% CI: 0.92 to 0.99; P=0.010], after adjusting for potential confounders. Moreover, the admission glucose level was found to be associated only with short-term mortality (adjusted OR: 1.19; 95% CI: 1.06 to 1.34; P=0.004). Conclusions: Laboratory screening may provide a useful tool for the management of aSAH patients requiring MV in stratifying risk levels for mortality and for better clinical decision-making. Further study is needed to validate the effects of calcium supplementation and glucose-lowering therapy on the outcomes in this disease.

Use of Patient-Reported Outcome Measures in Lower Extremity Research.

Background: A large number of patient reported outcome measures (PROMs) have been developed for specific lower extremity orthopaedic pathologies. However, a consensus as to which PROMs are recommended for use in evaluating treatment outcomes for patients with hip, knee, ankle and/or foot pathology based on the strength of their psychometric properties is lacking. Objective: To identify PROMs that are recommended in systematic reviews (SRs) for those with orthopaedic hip, knee, foot, and ankle pathologies or surgeries and identify if these PROMs are used in the literature. Study design: Umbrella Review. Methods: PubMed, Embase, Medline, Cochrane, CINAHL, SPORTDisucs and Scopus were searched for SRs through May 2022. A second search was done to count the use of PROMs in seven representative journals from January 2011 through May 2022.SRs that recommended the use of PROMs based on their psychometric properties were included in the first search. SRs or PROMs not available in the English were excluded. The second search included clinical research articles that utilized a PROM. Case reports, reviews, and basic science articles were excluded. Results: Nineteen SRs recommended 20 PROMs for 15 lower extremity orthopaedic pathologies or surgeries. These results identified consistency between recommended PROMs and utilization in clinical research for only two of the 15 lower extremity pathologies or surgeries. This included the use of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Copenhagen Hip and Groin Outcome Score to assess outcomes (HAGOS) for those with knee osteoarthritis and groin pain, respectively. Conclusion: A discrepancy was found between the PROMs that were recommended by SRs and those used to assess clinical outcomes in published research. The results of this study will help to produce more uniformity with the use of PROMs that have the most appropriate psychometric properties when the reporting treatment outcomes for those with extremity pathologies. Level of evidence: 3a.

Cross-Culturally Adapted Versions of Patient Reported Outcome Measures for the Lower Extremity.

Background: A large number of patient reported outcome measures (PROMs) have been developed in the English language for various lower extremity orthopaedic pathologies. Twenty different PROMs were recommended for 15 specific musculoskeletal lower extremity pathologies or surgeries. However, the availability of cross-culturally adapted versions of these recommended PROMs is unknown. Purpose: The purpose of this study was to identify the cross-culturally adapted versions of recommended PROMs for individuals experiencing orthopedic lower extremity pathologies or undergoing surgeries, and to identify the psychometric evidence that supports their utilization. Study design: Literature Review. Methods: PubMed, Embase, Medline, Cochrane, CINAHL, SPORTDisucs and Scopus were searched for cross-culturally adapted translated studies through May 2022. The search strategy included the names of the 20 recommended PROMs from previous umbrella review along with the following terms: reliability, validity, responsiveness, psychometric properties and cross-cultural adaptation. Studies that presented a non-English language version of the PROM with evidence in at least one psychometric property to support its use were included. Two authors independently evaluated the studies for inclusion and independently extracted data. Results: Nineteen PROMS had cross-culturally adapted and translated language versions. The KOOS, WOMAC, ACL-RSL, FAAM, ATRS, HOOS, OHS, MOXFQ and OKS were available in over 10 different language versions. Turkish, Dutch, German, Chinese and French were the most common languages, with each language having more than 10 PROMs with psychometric properties supporting their use. The WOMAC and KOOS were both available in 10 languages and had all three psychometric properties of reliability, validity, and responsiveness supporting their use. Conclusion: Nineteen of the 20 recommended instruments were available in multiple languages. The PROM most frequently cross-culturally adapted and translated were the KOOS and WOMAC. PROMs were most frequently cross-culturally adapted and translated into Turkish. International researchers and clinicians may use this information to more consistently implement PROMs with the most appropriate psychometric evidence available to support their use. Level of evidence: 3a.

High-Fat Diet Consumption Induces Neurobehavioral Abnormalities and Neuronal Morphological Alterations Accompanied by Excessive Microglial Activation in the Medial Prefrontal Cortex in Adolescent Mice.

The association between a high-fat diet (HFD) consumption and emotional/cognitive disorders is widely documented. One distinctive feature of the prefrontal cortex (PFC), a kernel emotion- and cognition-related brain region, is its protracted adolescent maturation, which makes it highly vulnerable to the detrimental effects of environmental factors during adolescence. Disruption of the PFC structure and function is linked to emotional/cognitive disorders, especially those that emerge in late adolescence. A HFD consumption is common among adolescents, yet its potential effects on PFC-related neurobehavior in late adolescence and any related underlying mechanisms are yet to be established. In the present study, adolescent (postnatal days 28-56) male C57BL/6J mice were fed a control diet (CD) or a HFD and underwent behavioral tests in addition to Golgi staining and immunofluorescence targeting of the medial PFC (mPFC). The HFD-fed adolescent mice exhibited anxiety- and depression-like behavior and abnormal mPFC pyramidal neuronal morphology accompanied by alterations in microglial morphology indicative of a heightened state of activation and increased microglial PSD95+ inclusions signifying excessive phagocytosis of the synaptic material in the mPFC. These findings offer novel insights into the neurobehavioral effects due to adolescent HFD consumption and suggest a contributing role in microglial dysfunction and prefrontal neuroplasticity deficits for HFD-associated mood disorders in adolescents.

OCRFinder: a noise-tolerance machine learning method for accurately estimating open chromatin regions.

Open chromatin regions are the genomic regions associated with basic cellular physiological activities, while chromatin accessibility is reported to affect gene expressions and functions. A basic computational problem is to efficiently estimate open chromatin regions, which could facilitate both genomic and epigenetic studies. Currently, ATAC-seq and cfDNA-seq (plasma cell-free DNA sequencing) are two popular strategies to detect OCRs. As cfDNA-seq can obtain more biomarkers in one round of sequencing, it is considered more effective and convenient. However, in processing cfDNA-seq data, due to the dynamically variable chromatin accessibility, it is quite difficult to obtain the training data with pure OCRs or non-OCRs, and leads to a noise problem for either feature-based approaches or learning-based approaches. In this paper, we propose a learning-based OCR estimation approach with a noise-tolerance design. The proposed approach, named OCRFinder, incorporates the ideas of ensemble learning framework and semi-supervised strategy to avoid potential overfitting of noisy labels, which are the false positives on OCRs and non-OCRs. Compared to different noise control strategies and state-of-the-art approaches, OCRFinder achieved higher accuracies and sensitivities in the experiments. In addition, OCRFinder also has an excellent performance in ATAC-seq or DNase-seq comparison experiments.

Prolonged Early Exposure to a High-Fat Diet Augments the Adverse Effects on Neurobehavior and Hippocampal Neuroplasticity: Involvement of Microglial Insulin Signaling.

High-fat diet (HFD) consumption may contribute to the high prevalence of cognitive-emotional issues in modern society. Mice fed a HFD for a prolonged period develop more severe neurobehavioral disturbances when first exposed to a HFD in the juvenile period than in adulthood, suggesting an initial age-related difference in the detrimental effects of long-term HFD feeding. However, the mechanism underlying this difference remains unclear. Here, male C57BL/6J mice initially aged 4 (IA4W) or 8 (IA8W) weeks were fed a control diet (CD) or HFD for 6 months and then subjected to metabolic, neurobehavioral, and histomorphological examinations. Although the detrimental effects of long-term HFD feeding on metabolism and neurobehavior were observed in mice of both ages, IA4W-HFD mice showed significant cognitive inflexibility accompanied by significantly greater levels of anxiety-like behavior than age-matched controls. Hippocampal neuroplasticity and microglial phenotype were altered by HFD feeding, whereas significant morphological alterations were more frequently observed in IA4W-HFD mice than in IA8W-HFD mice. Additionally, significantly increased hippocampal microglial engulfment of postsynaptic proteins and elevated phospho-insulin-receptor levels were observed in IA4W-HFD, but not in IA8W-HFD, mice. These findings suggest that aberrant microglia-related histomorphological changes in the hippocampus underlie the exacerbated detrimental neurobehavioral effects of prolonged early HFD exposure and indicate that enhanced insulin signaling might drive microglial dysfunction after prolonged early HFD exposure.

Fe Powder Catalytically Synthesized C3N3 toward High-Performance Anode Materials of Lithium-Ion Batteries.

Recently, carbon nitrides and their carbon-based derivatives have been widely studied as anode materials of lithium-ion batteries due to their graphite-like structure and abundant nitrogen active sites. In this paper, a layered carbon nitride material C3N3 consisting of triazine rings with an ultrahigh theoretical specific capacity was designed and synthesized by an innovative method based on Fe powder-catalyzed carbon-carbon coupling polymerization of cyanuric chloride at 260 °C, with reference to the Ullmann reaction. The structural characterizations indicated that the as-synthesized material had a C/N ratio close to 1:1 and a layered structure and only contained one type of nitrogen, suggesting the successful synthesis of C3N3. When used as a lithium-ion battery anode, the C3N3 material showed a high reversible specific capacity up to 842.39 mAh g-1 at 0.1 A g-1, good rate capability, and excellent cycling stability attributed to abundant pyridine nitrogen active sites, large specific surface area, and good structure stability. Ex situ XPS results indicated that Li+ storage relies on the reversible transformation of -C=N- and -C-N- groups as well as the formation of bridge-connected -C=C- bonds. To further optimize the performance, the reaction temperature was further increased to synthesize a series of C3N3 derivatives for the enhanced specific surface area and conductivity. The resulting derivative prepared at 550 °C showed the best electrochemical performance, with an initial specific capacity close to 900 mAh g-1 at 0.1 A g-1 and good cycling stability (94.3% capacity retention after 500 cycles at 1 A g-1). This work will undoubtedly inspire the further study of high-capacity carbon nitride-based electrode materials for energy storage.

Role of Innate Interferon Responses at the Ocular Surface in Herpes Simplex Virus-1-Induced Herpetic Stromal Keratitis.

Herpes simplex virus type 1 (HSV-1) is a highly successful pathogen that primarily infects epithelial cells of the orofacial mucosa. After initial lytic replication, HSV-1 enters sensory neurons and undergoes lifelong latency in the trigeminal ganglion (TG). Reactivation from latency occurs throughout the host's life and is more common in people with a compromised immune system. HSV-1 causes various diseases depending on the site of lytic HSV-1 replication. These include herpes labialis, herpetic stromal keratitis (HSK), meningitis, and herpes simplex encephalitis (HSE). HSK is an immunopathological condition and is usually the consequence of HSV-1 reactivation, anterograde transport to the corneal surface, lytic replication in the epithelial cells, and activation of the host's innate and adaptive immune responses in the cornea. HSV-1 is recognized by cell surface, endosomal, and cytoplasmic pattern recognition receptors (PRRs) and activates innate immune responses that include interferons (IFNs), chemokine and cytokine production, as well as the recruitment of inflammatory cells to the site of replication. In the cornea, HSV-1 replication promotes type I (IFN-α/ß) and type III (IFN-λ) IFN production. This review summarizes our current understanding of HSV-1 recognition by PRRs and innate IFN-mediated antiviral immunity during HSV-1 infection of the cornea. We also discuss the immunopathogenesis of HSK, current HSK therapeutics and challenges, proposed experimental approaches, and benefits of promoting local IFN-λ responses.

Regional thermal environment changes: Integration of satellite data and land use/land cover.

Land surface temperature (LST) is subject to location and environmental influences, which makes quantification difficult in terms of timeliness. Based on 10-d geostationary satellite LST TCI products, we quantitatively evaluated the thermal environment differentiation of various ground objects in North, South, and Northwest China from 2017 to 2021. We found that the thermal condition index (TCI) in Northwest China decreased, whereas it increased in North and South China. In contrast, Moran's I index increased in Northwest and South China, with strong spatial agglomeration. The TCI for artificial surfaces decreased from North (0.633) to Northwest (0.554) and South China (0.384). The bare land TCI was always the lowest among the land use/land cover (LULC) types in each region. Our results reflect the LULC thermal environment of China against the background of new urbanization and provide theoretical support for scientific planning to improve the ecological environment.

Integrated Uniformly Microporous C4 N/Multi-Walled Carbon Nanotubes Composite Toward Ultra-Stable and Ultralow-Temperature Proton Batteries.

Benefiting from the proton's small size and ultrahigh mobility in water, aqueous proton batteries are regarded as an attractive candidate for high-power and ultralow-temperature energy storage devices. Herein, a new-type C4 N polymer with uniform micropores and a large specific surface area is prepared by sulfuric acid-catalyzed ketone amine condensation reaction and employed as the electrode of proton batteries. Multi-walled carbon nanotubes (MWCNT) are introduced to induce the in situ growth of C4 N, and reaped significantly enhanced porosity and conductivity, and thus better both room- and low-temperature performance. When coupled with MnO2 @Carbon fiber (MnO2 @CF) cathode, MnO2 @CF//C4 N-50% MWCNT full battery shows unprecedented cycle stability with a capacity retention of 98% after 11 000 cycles at 10 A g-1 and even 100% after 70 000 cycles at 20 A g-1 . Additionally, a novel anti-freezing electrolyte (5 m H2 SO4  + 0.5 m MnSO4 ) is developed and showed a high ionic conductivity of 123.2 mS cm-1 at -70 °C. The resultant MnO2 @CF//C4 N-50% MWCNT battery delivers a specific capacity of 110.5 mAh g-1 even at -70 °C at 1 A g-1 , the highest in all reported proton batteries under the same conditions. This work is expected to offer a package solution for constructing high-performance ultralow-temperature aqueous proton batteries.

LCAT1 is an oncogenic LncRNA by stabilizing the IGF2BP2-CDC6 axis.

Long non-coding RNAs (lncRNAs) is known to play vital roles in modulating tumorigenesis. We previously reported that LCAT1, a novel lncRNA, promotes the growth and metastasis of lung cancer cells both in vitro and in vivo. However, the underlying mechanism(s) of LCAT1 as an oncogenic regulator remains elusive. Here, we showed that LCAT1 physically interacts with and stabilizes IGF2BP2, an m6A reader protein, by preventing its degradation via autolysosomes. IGF2BP2 is overexpressed in lung cancer tissues, which is associated with poor survival of non-small cell lung cancer patients, suggesting its oncogenic role. Biologically, IGF2BP2 depletion inhibits growth and survival as well as the migration of lung cancer cells. Mechanistically, the LCAT1/IGF2BP2 complex increased the levels of CDC6, a key cell cycle regulator, by stabilizing its mRNA in an m6A-dependent manner. Like IGF2BP2, CDC6 is also overexpressed in lung cancer tissues with poor patient survival, and CDC6 knockdown has oncogenic inhibitory activity. Taken together, the LCAT1-IGF2BP2-CDC6 axis appears to play a vital role in promoting the growth and migration of lung cancer cells, and is a potential therapeutic target for lung cancer. Importantly, our finding also highlights a previously unknown critical role of LCAT1 in m6A-dependent gene regulation by preventing autolytic degradation of IGF2BP2.