Bifurcated Polymorphic Transition and Thermochromic Fluorescence of a Molecular Crystal Involving Three-Dimensional Supramolecular Gear Rotation.

The ability of molecules to move and rearrange in the solid state accounts for the polymorphic transition and stimuli-responsive properties of molecular crystals. However, how the crystal structure determines the molecular motion ability remains poorly understood. Here, we report that a three-dimensional (3D) supramolecular gear network in the green-emissive polymorph 1G of a dialkylamino-substituted anthracene-pentiptycene π-system (1) enables an unusual bifurcated polymorphic transition into a yellow-emissive polymorph (1Y) and a new green-emissive polymorph (1G*) via 3D correlated supramolecular rotation. The 90° forward correlated rotation causes the molecular conformation between the octyl and the anthracene units to change from syn to anti, the ladder-like supramolecular columns to constrict, and the gear network to disengage. This cooperative molecular motion is marked by the gradual formation of an intermediate state (1I) across the entire crystal from 170 to 230 °C, which then undergoes bifurcated (forward or backward rotation) and irreversible transitions to form polymorphs 1Y and 1G* at 230-235 °C. Notably, 1G* is similar to 1G but lacks gear engagement, preventing its transformation into 1Y. Nevertheless, 1G can be restored by grinding 1Y or 1G* or fuming with dichloromethane (DCM) vapor. This work illustrates the correlation between the crystal structure and solid-state molecular motion behavior and demonstrates how a 3D molecular gear system efficiently transmits thermal energy to drive the polymorphic transition and induce fluorochromism through significant conformational and packing changes.

Gene identification, expression analysis, and molecular docking of SAT and OASTL in the metabolic pathway of selenium in Cardamine hupingshanensis.

KEY MESSAGE: Identification of selenium stress-responsive expression and molecular docking of serine acetyltransferase (SAT) and O-acetyl serine (thiol) lyase (OASTL) in Cardamine hupingshanensis. A complex coupled with serine acetyltransferase (SAT) and O-acetyl serine (thiol) lyase (OASTL) is the key enzyme that catalyzes selenocysteine (Sec) synthesis in plants. The functions of SAT and OASTL genes were identified in some plants, but it is still unclear whether SAT and OASTL are involved in the selenium metabolic pathway in Cardamine hupingshanensis. In this study, genome-wide identification and comparative analysis of ChSATs and ChOASTLs were performed. The eight ChSAT genes were divided into three branches, and the thirteen ChOASTL genes were divided into four branches by phylogenetic analysis and sequence alignment, indicating the evolutionary conservation of the gene structure and its association with other plant species. qRT-PCR analysis showed that the ChSAT and ChOASTL genes were differentially expressed in different tissues under various selenium levels, suggesting their important roles in Sec synthesis. The ChSAT1;2 and ChOASTLA1;2 were silenced by the VIGS system to investigate their involvement in selenium metabolites in C. hupingshanensis. The findings contribute to understanding the gene functions of ChSATs and ChOASTLs in the selenium stress and provide a reference for further exploration of the selenium metabolic pathway in plants.

Age Estimation by Machine Learning and CT-Multiplanar Reformation of Cranial Sutures in Northern Chinese Han Adults.

OBJECTIVES: To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation (MPR), and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population. METHODS: The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected. Volume reconstruction (VR) and MPR were performed on the skull, and 160 cranial suture tomography images were generated for each sample. Then the MPR images of cranial sutures were scored according to the closure grading criteria, and the mean closure grades of sagittal suture, coronal sutures (both left and right) and lambdoid sutures (both left and right) were calculated respectively. Finally taking the above grades as independent variables, the linear regression model and four machine learning models for age estimation (gradient boosting regression, support vector regression, decision tree regression and Bayesian ridge regression) were established for northern Chinese Han adults age estimation. The accuracy of each model was evaluated. RESULTS: Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest. All four machine learning models had higher age estimation accuracy than linear regression model. The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years. CONCLUSIONS: The combination of skull CT-MPR and machine learning model can be used for age estimation in northern Chinese Han adults, but it is still necessary to combine with other adult age estimation indicators in forensic practice.

An Elastic Organic Crystal Enables Macroscopic Photoinduced Crystal Elongation.

Among the various types of photomechanical deformations of organic crystals, photoinduced elongation of millimeter-scale crystals has yet to be demonstrated. Here we report that the millimeter-sized crystalline rods of an anthracene-pentiptycene hybrid organic π-system (1) are highly elastic and able to elongate up to 21.6% or 0.40 mm without fragmentation upon undergoing [4 + 4] photodimerization reactions. Both the mechanical and photomechanical effects reveal a strong cohesion of the system, even at the interface of 1 and its photodimer 2 and under the conditions of randomized molecular packing, representing a new class of mechanically adaptive organic crystals.

Distinct Failure Patterns in Hypopharyngeal Cancer Patients Receiving Surgery-Based Versus Radiation-Based Treatment.

BACKGROUND: To cure advanced hypopharyngeal squamous cell carcinoma (HPSCC), primary operation followed by adjuvant (chemo-)radiotherapy (OP-CRT) or definitive chemoradiation (CCRT) are the two primary options. This study aimed to compare the failure patterns and long-term survival outcomes of HPSCC patients treated with these two strategies. PATIENTS AND METHODS: From 2007 to 2015, 198 pathologically confirmed HPSCC patients receiving either OP-CRT or CCRT were retrospectively reviewed. Failure patterns and survival outcomes stratified by the 7th American Joint Committee on Cancer staging system and treatment modalities were compared. RESULTS: One hundred and eighty-nine patients (95.4%) were stage III/IV and 62 patients (31.3%) received OP-CRT. Median follow-up duration was 4.9 years. Compared with CCRT, OP-CRT provided better 3-year local relapse-free survival for T3 (93 vs 48%, p < 0.0001), T4a (88 vs 37%, p = 0.0005) and better 3-year regional relapse-free survival for N2b+2c (93 vs 60%, p < 0.0001). Of note, for stage IVA subjects, OP-CRT provided better 3-year loco-regional relapse-free survival (85 vs 37%, p < 0.0001), marginal poor 3-year distant metastasis-free survival (62 vs 79%, p = 0.06), but comparable 3-year OS (52 vs 44%, p = 0.37) and 5-year OS (44 vs 31%, p = 0.15) compared with CCRT. CONCLUSIONS: For patients with advanced HPSCC, although OP-CRT and CCRT provided similar overall survival, failure patterns were distinct. OP-CRT provided better loco-regional control but was more likely to encounter distant metastases than CCRT. The detailed analysis of failure patterns will pave the way to improve this devastating disease.

All-day uninterrupted thermoelectric generator by simultaneous harvesting of solar heating and radiative cooling.

Passive power generation has recently stimulated interest in thermoelectric generators (TEGs) using the radiative cooling mechanism. However, the limited and unstable temperature difference across the TEGs significantly degrades the output performance. In this study, an ultra-broadband solar absorber with a planar film structure is introduced as the hot side of the TEG to increase the temperature difference by utilizing solar heating. This device not only enhances the generation of electrical power but also realizes all-day uninterrupted electrical output due to the stable temperature difference between the cold and hot sides of the TEG. Outdoor experiments show the self-powered TEG obtains maximum temperature differences of 12.67 °C, 1.06 °C, and 5.08 °C during sunny daytime, clear nighttime, and cloudy daytime, respectively, and generates output voltages of 166.2 mV, 14.7 mV, and 95 mV, respectively. Simultaneously, the corresponding output powers of 879.25 mW/m2, 3.85 mW/m2, and 287.27 mW/m2 are produced, achieving 24-hour uninterrupted passive power generation. These findings propose a novel strategy to combine solar heating and outer space cooling by a selective absorber/emitter to generate all-day continuous electricity for unsupervised small devices.

Meta-analysis of clinical adverse events after CABG vs. PCI in patients with chronic kidney disease and coronary artery disease.

AIM: To investigate the efficacy and postoperative clinical adverse events of coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) for chronic kidney disease (CKD) study participants combined with coronary artery disease (CAD). METHODS: All randomized controlled trials (RCTs) that focus on the therapeutic effect evaluation of CABG and PCI and their effect on postoperative clinical adverse events as well as main adverse cardiovascular and cerebrovascular events (MACCEs) in CKD study participants with CAD were screened from the following databases, including CNKI, CBM, Wan Fang, VIP, Embase, PubMed, as well as Cochrane library clinical controlled trials. The study was conducted under the PRISMA 2020 criteria. Data were extracted, and quality control was evaluated from the modified Jadad rating scale. Meta-analysis was then undertaken through STATA 16.0 software. RESULTS: A total of 5 RCTs were obtained, including 1198 patients. Study participants were subdivided into two groups, including the PCI group (n = 604) and the CABG group (n = 594). Meta-analysis of clinical adverse events results showed that the long-term survival results of CAD patients with CKD who underwent PCI were worsened compared to CABG, such as long-term MACCEs (RR = 1.59, 95%CI: 1.04-2.43) and the long-term repeated revascularization (RR = 2.48, 95%CI: 1.76-3.49). Also, cardiac death (RR = 1.68, 95%CI:1.04-2.71), as well as cerebrovascular accident (RR = 1.74, 95%CI:1.04-2.90) in CABG group was significantly lower than that in PCI group. CONCLUSION: This meta-analysis showed that CABG provided a better therapeutic effect than PCI in CKD patients with CAD when considering long-term prognosis. However, more prospective RCTs are needed to define the proper revascularization strategy for CAD patients with CKD.

Prevalence and risk factors for subjective cognitive decline and the correlation with objective cognition among community-dwelling older adults in China: Results from the Hubei memory and aging cohort study.

INTRODUCTION: The prevalence and risk factors for subjective cognitive decline (SCD) and its correlation with objective cognition decline (OCD) among community-dwelling older adults is inconsistent. METHODS: Older adults underwent neuropsychological and clinical evaluations to reach a consensus on diagnoses. RESULTS: This study included 7486 adults without mild cognitive impairment and dementia (mean age: 71.35 years [standard deviation = 5.40]). The sex-, age-, and residence-adjusted SCD prevalence was 58.33% overall (95% confidence interval: 58.29% to 58.37%), with higher rates of 61.25% and 59.87% in rural and female subgroups, respectively. SCD global and OCD language, SCD memory and OCD global, SCD and OCD memory, and SCD and OCD language were negatively correlated in fully adjusted models. Seven health and lifestyle factors were associated with an increased risk for SCD. DISCUSSION: SCD affected 58.33% of older adults and may indicate concurrent OCD, which should prompt the initiation of preventative intervention for dementia. HIGHLIGHTS: SCD affects 58.33% of older adults in China. SCD may indicate concurrent objective cognitive decline. Difficulty finding words and memory impairments may indicate a risk for AD. The presence of SCD may prompt preventative treatment initiation of MCI or dementia. Social network factors may be initial targets for the early prevention of SCD.

Microglia Modulate Neurodevelopment in Autism Spectrum Disorder and Schizophrenia.

Neurodevelopmental disorders (NDDs) include various neurological disorders with high genetic heterogeneity, characterized by delayed or impaired cognition, communication, adaptive behavior, and psychomotor skills. These disorders result in significant morbidity for children, thus burdening families and healthcare/educational systems. However, there is a lack of early diagnosis and effective therapies. Therefore, a more connected approach is required to explore these disorders. Microglia, the primary phagocytic cells within the central nervous system, are crucial in regulating neuronal viability, influencing synaptic dynamics, and determining neurodevelopmental outcomes. Although the neurobiological basis of autism spectrum disorder (ASD) and schizophrenia (SZ) has attracted attention in recent decades, the role of microglia in ASD and SZ remains unclear and requires further discussion. In this review, the important and frequently multifaceted roles that microglia play during neurodevelopment are meticulously emphasized and potential microglial mechanisms that might be involved in conditions such as ASD and SZ are postulated. It is of utmost importance to acquire a comprehensive understanding of the complexities of the interplay between microglia and neurons to design effective, targeted therapeutic strategies to mitigate the effects of NDDs.

Implementation of an enhanced recovery after surgery program in the treatment of uterine fibroids with focused ultrasound ablation surgery.

BACKGROUND: Enhanced recovery after surgery (ERAS) can reduce the length of hospital stay, incidence of surgery-related complications, and postoperative pain. We aimed to demonstrate the implementation of an ERAS pathway in the treatment of uterine fibroids with focused ultrasound ablation surgery (FUAS). MATERIALS AND METHODS: A retrospective data analysis was performed on clinical outcomes encompassing the following three phases: before ERAS (pre-ERAS), during adjustment of ERAS (interim-ERAS), and after the introduction of an ERAS program (post-ERAS). The purpose of describing the interim-ERAS was to provide references for the formulation of the program during the course of FUAS by describing the adjustment processes. Data from patients admitted to the hospital from September 2019 to December 2019 and April 2020 to November 2020 and who met the criteria for FUAS in the treatment of their uterine fibroids were examined. Length of stay, cost of surgery, postoperative pain score, utilization of postoperative analgesics, and incidence of postoperative adverse events were compared across the abovementioned three phases. RESULTS: Compared with the pre-phase, the cost of treatment and length of stay were reduced after the implementation of ERAS. The use of analgesics before leaving the operating room, as well as the incidence of postoperative nausea and vomiting, were also reduced. CONCLUSION: The implementation of an ERAS protocol might benefit patients with uterine fibroids treated with FUAS in terms of requiring a shorter hospitalization period, lower costs, and reduced opioid use.

Lycium barbarum Polysaccharides and Capsaicin Inhibit Oxidative Stress, Inflammatory Responses, and Pain Signaling in Rats with Dextran Sulfate Sodium-Induced Colitis.

Ulcerative colitis (UC) is an inflammatory disease with chronic relapsing symptoms. This study investigated the effects of Lycium barbarum polysaccharides (LBP) and capsaicin (CAP) in dextran sulfate sodium (DSS)-induced UC rats. Rats were divided into normal, DSS-induced UC, and UC treated with 100 mg LBP/kg bw, 12 mg CAP/kg bw, or 50 mg LBP/kg bw and 6 mg CAP/kg bw. Rats were fed LBP or CAP orally by gavage for 4 weeks, and UC model was established by feeding 5% DSS in drinking water for 6 days during week 3. Oral CAP and mixture significantly reduced disease activity index. Oral LBP significantly decreased serum malondialdehyde, interleukin (IL)-6, colonic tumor necrosis factor (TNF)-α levels, and protein expression of transient receptor potential cation channel V1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1), but increased serum catalase activity. Oral CAP significantly suppressed serum IL-6, colonic TRPV1 and TRPA1 protein expression, but elevated IL-10 levels, serum superoxide dismutase and catalase activities. The mixture of LBP and CAP significantly reduced serum IL-6, colonic TNF-α and TRPA1 protein. In conclusion, administration of LBP and/or CAP attenuate DSS-induced UC symptoms through inhibiting oxidative stress, proinflammatory cytokines, and protein expression of TRPV1 and TRPA1.

Lycium barbarum polysaccharides and capsaicin modulate inflammatory cytokines and colonic microbiota in colitis rats induced by dextran sulfate sodium.

Active ingredients in the natural products have been considered to be used for alleviating the symptoms of ulcerative colitis, hence the effects of Lycium barbarum polysaccharides (LP) and capsaicin on dextran sulfate sodium (DSS)-induced colitis in rats were investigated. Rats were grouped into normal, DSS induced colitis, and colitis treated with 100 mg LP/kg body weight, 12 mg capsaicin/kg body weight, or combined 50 mg LP/kg body weight and 6 mg capsaicin/kg body weight. Treatment with LP or capsaicin was orally fed by gavage for 4 weeks, and 5% DSS was fed via drinking water for 6 days during week 3. Colon tissue and cecum content were collected for analysis. Treatments with LP and/or capsaicin ameliorated disease activity index scores, severity of colon distortion, and shrinkage of colon length. LP and capsaicin decreased colonic pro-inflammatory cytokine (IFN-γ, IL-17A, and IL-22) levels. Cecal microbiota in colitis rats were enriched with the genus Turicibacter and Lachnospira. The relative abundance of genus Ruminiclostridium_9 and Ruminoclostridium_1 was increased by LP and capsaicin treatment, respectively. Pretreatment with LP or capsaicin inhibits the severity of colonic damage in rats with DSS-induced colitis via anti-inflammation and modulation of colonic microbiota.

ICAM5 as a Novel Target for Treating Cognitive Impairment in Fragile X Syndrome.

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, resulted from the silencing of the Fmr1 gene and the subsequent loss of fragile X mental retardation protein (FMRP). Spine dysgenesis and cognitive impairment have been extensively characterized in FXS; however, the underlying mechanism remains poorly understood. As an important regulator of spine maturation, intercellular adhesion molecule 5 (ICAM5) mRNA may be one of the targets of FMRP and involved in cognitive impairment in FXS. Here we show that in Fmr1 KO male mice, ICAM5 was excessively expressed during the late developmental stage, and its expression was negatively correlated with the expression of FMRP and positively related with the morphological abnormalities of dendritic spines. While in vitro reduction of ICAM5 normalized dendritic spine abnormalities in Fmr1 KO neurons, and in vivo knockdown of ICAM5 in the dentate gyrus rescued the impaired spatial and fear memory and anxiety-like behaviors in Fmr1 KO mice, through both granule cell and mossy cell with a relative rate of 1.32 ± 0.15. Furthermore, biochemical analyses showed direct binding of FMRP with ICAM5 mRNA, to the coding sequence of ICAM5 mRNA. Together, our study suggests that ICAM5 is one of the targets of FMRP and is implicated in the molecular pathogenesis of FXS. ICAM5 could be a therapeutic target for treating cognitive impairment in FXS.SIGNIFICANCE STATEMENT Fragile X syndrome (FXS) is characterized by dendritic spine dysgenesis and cognitive dysfunctions, while one of the FMRP latent targets, ICAM5, is well established for contributing both spine maturation and learning performance. In this study, we examined the potential link between ICAM5 mRNA and FMRP in FXS, and further investigated the molecular details and pathological consequences of ICAM5 overexpression. Our results indicate a critical role of ICAM5 in spine maturation and cognitive impairment in FXS and suggest that ICAM5 is a potential molecular target for the development of medication against FXS.

3D-Stretched Film Ni3 S2 Nanosheet/Macromolecule Anthraquinone Derivative Polymers for Electrocatalytic Overall Water Splitting.

For the first time, a new polymer electrode AQS/S is prepared by compositing Ni3 S2 nanosheets and macromolecular anthraquinone derivative (AQD) supported on nickel foam with flying colors. The AQS/S exhibits high crystalline structure and abundant S defects. Density of state calculation shows that AQD has stable internal bonding and easy external bonding with metals, conducive to the dispersion of metal reaction sites, ensuring excellent activity and high stability. Under 1.0 m KOH solution, ultralow overpotentials of 62 and 133 mV at 10 mA cm-2 on AQS/S for hydrogen evolution reaction and on activated AQS/S (A-AQS/S) for oxygen evolution reaction, respectively, are achieved. 100 h chronopotentiometry and the cyclic voltammetry tests show that catalysts have high durability. The AQS/S‖A-AQS/S two-electrode system is also found to have good electrocatalytic activity for 1.43 V to get 10 mA cm-2  in overall water splitting, better than the state-of-the-art 20% Pt/C‖RuO2 combination.

Fingerprint detection in the mid-infrared region based on guided-mode resonance and phonon-polariton coupling of analyte.

Mid-infrared absorption spectroscopy is an effective method for detecting analyte fingerprints without labeling, but the inherent loss of metals in current methods is a main issue. Here, a sensing scheme was proposed that uses an all-dielectric grating metasurface and angular scanning of polarized light, and then it was verified by numerical simulation. The proposed fingerprint detection scheme could effectively couple a guided-mode resonance spectrum peak with the characteristic peak of the analyte's phonon-polariton in the mid-infrared region, significantly enhancing the interaction between light and the analyte. The novel scheme would realize broadband enhancement to detect a variety of substances, and facilitate mid-infrared sensing and analysis of trace substances.

Primary gross tumor volume is prognostic and suggests treatment in upper esophageal cancer.

BACKGROUND: To aid clinicians strategizing treatment for upper esophageal squamous cell carcinoma (ESCC), this retrospective study investigated associations between primary gross tumor volume (GTVp) and prognosis in patients given surgical resection, radiotherapy, or both resection and radiotherapy. METHODS: The population comprised 568 patients with upper ESCC given definitive treatment, including 238, 216, and 114 who underwent surgery, radiotherapy, or combined radiotherapy and surgery. GTVp as a continuous variable was entered into the multivariate Cox model using penalized splines (P-splines) to determine the optimal cutoff value. Propensity score matching (PSM) was used to adjust imbalanced characteristics among the treatment groups. RESULTS: P-spline regression revealed a dependence of patient outcomes on GTVp, with 30 cm3 being an optimal cut-off for differences in overall and progression-free survival (OS, PFS). GTVp ≥30 cm3 was a negative independent prognostic factor for OS and PFS. PSM analyses confirmed the prognostic value of GTVp. For GTVp < 30 cm3, no significant survival differences were observed among the 3 treatments. For GTVp ≥30 cm3, the worst 5-year OS rate was experienced by those given surgery. The 5-year PFS rate of patients given combined radiotherapy and surgery was significantly better than that of patients given radiotherapy. The surgical complications of patients given the combined treatment were comparable to those who received surgery, but radiation side effects were significantly lower. CONCLUSION: GTVp is prognostic for OS and PFS in upper ESCC. For patients with GTVp ≥30 cm3, radiotherapy plus surgery was more effective than either treatment alone.

Circular RNA hsa_circ_0000554 promotes progression and elevates radioresistance through the miR-485-5p/fermitin family members 1 axis in esophageal cancer.

Esophageal cancer is one of the most aggressive malignant cancers in the world. Circular RNA hsa_circ_0000554 (circ_0000554) and Fermitin family members 1 (FERMT1) are rated to the advancement of esophageal cancer. Nevertheless, the regulatory mechanisms between circ_0000554 and FERMT1 in the radioresistance of esophageal cancer are unclear. Quantitative real-time PCR (qRT-PCR) was applied to examine the expression of circ_0000554, FERMT1 mRNA, and miR-485-5p. Western blot analysis was employed to assess the protein expression levels of FERMT1, Ki-67, matrix metalloproteinase (MMP)-9 and MMP-2. Cell colony formation, migration, invasion, radiosensitivity and apoptosis were evaluated by cell colony formation, transwell or flow cytometry assays. The relationship between circ_0000554 or FERMT1 and miR-485-5p was verified with dual-luciferase reporter assay. Circ_0000554 and FERMT1 expression was enhanced in esophageal cancer tissues and radioresistant esophageal cancer tissues. Both circ_0000554 and FERMT1 repression blocked cell colony formation, migration, invasion and elevated cell radiosensitivity and apoptosis in esophageal cancer cells. Importantly, circ_0000554 served as a sponge for miR-485-5p in esophageal cancer cells. And FERMT1 acted as a downstream target for miR-485-5p. Additionally, circ_0000554 modulated FERMT1 expression via miR-485-5p. Furthermore, FERMT1 enhancement reversed circ_0000554 inhibition-mediated effects on the colony formation, migration, invasion, radiosensitivity and apoptosis of esophageal cancer cells. Circ_0000554 silencing repressed EC progression and enhanced cell radiosensitivity through downregulating FERMT1 via sponging miR-485-5p, which provided a possible method for improving the radioresistence of esophageal cancer.

Proteasome Activator Blm10 Regulates Transcription Especially During Aging.

Background: Histones are basic elements of the chromatin and are critical to controlling chromatin structure and transcription. The proteasome activator PA200 promotes the acetylation-dependent proteasomal degradation of the core histones during spermatogenesis, DNA repair, transcription, and cellular aging and maintains the stability of histone marks. Objective: The study aimed to explore whether the yeast ortholog of PA200, Blm10, promotes degradation of the core histones during transcription and regulates transcription especially during aging. Methods: Protein degradation assays were performed to detect the role of Blm10 in histone degradation during transcription. mRNA profiles were compared in WT and mutant BY4741 or MDY510 yeast cells by RNA-sequencing. Results: The core histones can be degraded by the Blm10-proteasome in the non-replicating yeast, suggesting that Blm10 promotes the transcription-coupled degradation of the core histones. Blm10 preferentially regulates transcription in aged yeast, especially transcription of genes related to translation, amino acid metabolism, and carbohydrate metabolism. Mutations of Blm10 at F2125/N2126 in its putative acetyl-lysine binding region abolished the Blm10-mediated regulation of gene expression. Conclusion: Blm10 promotes degradation of the core histones during transcription and regulates transcription, especially during cellular aging, further supporting the critical role of PA200 in maintaining the stability of histone marks from the evolutionary view. These results should provide meaningful insights into the mechanisms underlying aging and the related diseases.

MicroRNA-148a-3p suppresses cell proliferation and migration of esophageal carcinoma by targeting CEP55.

This study evaluated microRNA-148a-3p in esophageal carcinoma cells. The prediction of bioinformatics analysis revealed that microRNA-148a-3p may target CEP55. qRT-PCR and western blot showed that CEP55 level in esophageal carcinoma cells and tissue was dramatically higher than that of normal cells and tissue, while microRNA-148a-3p was the opposite. Forced expression of microRNA-148a-3p restrained cell malignant behaviors of esophageal carcinoma, and repression of microRNA-148a-3p resulted in the converse results in terms of cell function. Dual-luciferase assay confirmed that microRNA-148a-3p targeted CEP55. CEP55 attenuated the suppressive effect of microRNA-148a-3p on proliferation and migration of esophageal carcinoma cells, demonstrating that microRNA-148a-3p regulated function of esophageal carcinoma cells via decreasing CEP55 level. Microscopy observation indicated that cell morphology was also affected by the microRNA-148a-3p/CEP55 axis. Furthermore, western blot analysis revealed that the PI3K/AKT signaling pathway could be suppressed by activating the microRNA-148a-3p/CEP55 axis. Finally, in vivo experiments confirmed the effects of microRNA-148a-3p on tumorigenesis. Thus, microRNA-148a-3p could act as a repressor in esophageal carcinoma via binding to CEP55.

MicroRNA-29a in Osteoblasts Represses High-Fat Diet-Mediated Osteoporosis and Body Adiposis through Targeting Leptin.

Skeletal tissue involves systemic adipose tissue metabolism and energy expenditure. MicroRNA signaling controls high-fat diet (HFD)-induced bone and fat homeostasis dysregulation remains uncertain. This study revealed that transgenic overexpression of miR-29a under control of osteocalcin promoter in osteoblasts (miR-29aTg) attenuated HFD-mediated body overweight, hyperglycemia, and hypercholesterolemia. HFD-fed miR-29aTg mice showed less bone mass loss, fatty marrow, and visceral fat mass together with increased subscapular brown fat mass than HFD-fed wild-type mice. HFD-induced O2 underconsumption, respiratory quotient repression, and heat underproduction were attenuated in miR-29aTg mice. In vitro, miR-29a overexpression repressed transcriptomic landscapes of the adipocytokine signaling pathway, fatty acid metabolism, and lipid transport, etc., of bone marrow mesenchymal progenitor cells. Forced miR-29a expression promoted osteogenic differentiation but inhibited adipocyte formation. miR-29a signaling promoted brown/beige adipocyte markers Ucp-1, Pgc-1α, P2rx5, and Pat2 expression and inhibited white adipocyte markers Tcf21 and Hoxc9 expression. The microRNA also reduced peroxisome formation and leptin expression during adipocyte formation and downregulated HFD-induced leptin expression in bone tissue. Taken together, miR-29a controlled leptin signaling and brown/beige adipocyte formation of osteogenic progenitor cells to preserve bone anabolism, which reversed HFD-induced energy underutilization and visceral fat overproduction. This study sheds light on a new molecular mechanism by which bone integrity counteracts HFD-induced whole-body fat overproduction.