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Abstract Objective Sarcopenia is a common complication in elderly patients with coronary heart disease (CHD). This study aims to analyse and explore the occurrence of sarcopenia in elderly patients with CHD and its associations with short-term prognosis. Methods A total of 318 elderly patients with CHD were enrolled between March 2020 and March 2022. Sarcopenia was assessed at admission using grip strength and gait speed; subsequently, clinical data, cardiac function indicators, adverse events and mortality were compared between the two groups to explore the associations of sarcopenia with the short-term prognosis of elderly patients with CHD. Results Among the 318 elderly patients with CHD included in this study, 69 developed sarcopenia, with an incidence rate of 21.70%. The sarcopenia group showed lower cardiac output and left ventricular ejection fraction levels than the non-sarcopenia group, while higher left ventricular end-diastolic diameter, left ventricular end-systolic diameter, interventricular septum thickness and left ventricular posterior wall thickness levels were greater than in the non-sarcopenia group, with p

The significance of glomerular IgM deposit intensity in IgA Nephropathy (IgAN) remained ambiguous and requires further research. Patients with biopsy-proven IgAN in our hospital from January 2018 to May 2023 were recruited into this retrospective single-center study. Patients who presented with positive IgM deposit were included in IgM + cohort while patients with negative IgM deposit were included in IgM– cohort. Of the IgM+, patients whose IF intensity of IgM deposits exceeded 1+ formed IgM-H cohort while patients whose IF intensity of IgM deposits was equal to 1+ consisted IgM-L cohort. Pairwise comparisons were performed among these cohorts to determine clinical disparities, following the propensity score matching process. Among 982 IgAN patients, 539 patients presented with positive IgM deposit. The Kaplan–Meier analysis showed that the IgM deposit did not contribute adversely to the outcomes (eGFR decreased from the baseline ≥ 50% continuously or reached end-stage renal disease). However, the Cox regression analysis showed that increased intensity of IgM deposit was an independent risk factor (p = 0.03) in IgM+. The IgM-H exhibited more pronounced segmental glomerulosclerosis (p = 0.02) than the IgM-L, which may also be associated more directly with higher urine protein levels (p = 0.02). Moreover, our generalized linear mixed model demonstrated a remarkably higher urine albumin/creatinine ratio (p

Abstract Background Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL‐S) is a rare autosomal dominant systemic microvascular disorder attributed to TREX1 (three‐prime repair exonuclease‐1) gene mutations, often proned to misdiagnosed. Methods We reported a case of RVCL‐S coexisting with systemic lupus erythematosus due to a mutation in the TREX1 gene. This study provided a summary and discussion of previously documented cases related to TREX1 mutations or RVCL‐S. Results A 39‐year‐old female patient visited the clinic due to progressive memory loss and speech difficulties. Magnetic resonance imaging results showed corpus callosum atrophy and multiple subcortical calcifications in both brain hemispheres. Genetic testing revealed a TREX1 gene mutation (c.294dupA). Treatment with immunosuppressive therapy for 2 months led to improvements in communication and mobility. We also summarized previously reported cases providing an overview of TREX1 gene mutation or RCVL‐S. Conclusion Our case establishes a compelling foundation for future RVCL‐S diagnosis and treatment paradigms. Notably, conducting systemic immunity screening in patients with RVCL‐S emerges as a strategic approach to prevent potential diagnostic oversights.

Background and aim: A genome-wide association study has indicated the association of numerous genes in the 6p21.3 region with chronic hepatitis B virus (HBV) infection. In this study, we screened 12 representative single-nucleotide polymorphisms (SNPs) from the 6p21.3 region and investigated their association with the risk of chronic hepatitis B (CHB) to better understand the molecular etiology underlying CHB risk in the Han Chinese population. Methods: Between March 2021 and November 2022, we included 183 patients with CHB (case group) and 196 with natural HBV clearance (control group). Allele typing of the selected SNPs was performed using snapshot technology. The correlation between the 12 chosen SNPs and the risk of chronic HBV infection was examined using binary logistic regression analysis. Interacting genes of the variants were identified, and expression quantitative trait loci (eQTL) were analyzed using the 3DSNP database. Results: We validated 12 previously reported CHB susceptibility sites, including rs1419881 of transcription factor 19 (TCF19), rs3130542 and rs2853953 of human leukocyte antigen (HLA)-C, rs652888 of euchromatic histone-lysine-methyltransferase 2 (EHMT2), rs2856718, rs9276370, rs7756516, and rs7453920 of HLA-DQ, rs378352 of HLA-DOA, and rs3077, rs9277535, and rs9366816 of HLA-DP. Logistic regression analyses revealed that polymorphisms such as rs9276370, rs7756516, rs7453920, rs3077, rs9277535, and rs9366816 were positively correlated with natural HBV clearance in the dominant model. Conversely, rs3130542 and rs378352 were identified as risk factors for CHB. Haplotype analysis revealed that rs9276370, rs7756516, and rs7453920 in HLA-DQ were TTG and GCA haplotypes. Although the TTG haplotype was positively correlated with a higher risk of CHB, the GCA haplotype significantly influenced the natural clearance of HBV. Bioinformatics analysis demonstrated that rs378352, rs3077, and rs9366816 were located within enhancer states; rs3077 and rs9366816 overlapped with nine transcription factor-binding sites, whereas rs378352 altered five sequence motifs. Furthermore, eQTL analysis demonstrated the functional tendencies of eight statistically significant SNPs (rs3130542, rs9276370, rs7756516, rs7453920, rs378352, rs3077, rs9277535, and rs9366816). Conclusions: Genetic variations within the 6p21.3 region were associated with chronic HBV infection in the Han Chinese population in southern China. Furthermore, the GCA haplotype including rs9276370, rs7756516, and rs7453920 of HLA-DQ contributed significantly to natural HBV clearance, implying that multiple SNPs exert a cumulative allelic effect on HBV infection.

Highlights An ultraconformable skin-like integrated wireless charging micro-supercapacitor (IWC-MSC) could be wireless charged to store electricity into high capacitive micro-supercapacitors (11.39 F cm−3), and fits well with human surface. Building blocks of IWC-MSC skin are all evaporated by liquid precursor, and each part of the device attached firmly benefitting from the liquid permeation, forming a compact and all-in-one configuration. The electrode thickness easily regulated varying from 11.7 to 112.5 μm by controlling the volume of electrode solution precursor.

Abstract Toll-like receptor 9 (TLR9) recognizes self-DNA and plays intricate roles in systemic lupus erythematosus (SLE). However, the molecular mechanism regulating the endosomal TLR9 response is incompletely understood. Here, we report that palmitoyl-protein thioesterase 1 (PPT1) regulates systemic autoimmunity by removing S-palmitoylation from TLR9 in lysosomes. PPT1 promotes the secretion of IFNα by plasmacytoid dendritic cells (pDCs) and TNF by macrophages. Genetic deficiency in or chemical inhibition of PPT1 reduces anti-nuclear antibody levels and attenuates nephritis in B6.Sle1yaa mice. In healthy volunteers and patients with SLE, the PPT1 inhibitor, HDSF, reduces IFNα production ex vivo. Mechanistically, biochemical and mass spectrometry analyses demonstrated that TLR9 is S-palmitoylated at C258 and C265. Moreover, the protein acyltransferase, DHHC3, palmitoylates TLR9 in the Golgi, and regulates TLR9 trafficking to endosomes. Subsequent depalmitoylation by PPT1 facilitates the release of TLR9 from UNC93B1. Our results reveal a posttranslational modification cycle that controls TLR9 response and autoimmunity.

Abstract To investigate the influence of thermal treatment on the rockburst in granite caverns, true-triaxial compression tests were conducted on pre-heated granite cubic samples containing a circular through-hole using a true-triaxial test system, and the micro camera was used to monitor and record the rockburst process in realtime. Test results show that the uniaxial compressive strength and elastic modulus first increase and then decrease as the temperature increases, which reach the maximums at 200 °C and sharply decrease at temperatures from 400 to 600 °C. The density and P-wave velocity decrease and the peak strain increases with increasing temperature. The main failure mode is X-shaped shear-tension failure at 25 and 200 °C, and single-slope shear failure at 400 and 600 °C. Thermal treatment exhibits slight effect on the rockburst incubation process in granite caverns. The stress required for rockburst decreases when the temperature increases or decreases from 200 °C. The higher the temperature, the lower the required stress. At 25 and 200 °C, rockburst is violent, and fine particles and large slabs are mainly produced; at 400 and 600 °C, the intensity of rockburst is relatively weak, and fine particles are mainly generated. Thermal treatment exhibits double effects on rockburst. The mechanism of thermal treatment on granite rockburst is the strengthening effect caused by water loss and the weakening effect caused by thermal expansion cracking. This study can provide theoretical guidance for the stability analysis and rockburst prevention of temperature-affected granite caverns.

Engineering rock containing flaws or defects under a large water source is frequently subject to the couple influence of constant crack water pressure and geostress. To investigate the fracture behavior of precracked rock under hydromechanical coupling with constant crack water pressure, compression tests were conducted on red sandstone specimens containing a single crack of different angles using a device to realize the constant crack water pressure during loading, and the failure process of rock specimens was monitored by acoustic emission (AE) technique. The results show that the presence of constant crack water pressure has a significant promotion effect on the development of shear wing cracks, and the promotion effect is influenced by the prefabricated crack angle and water pressure. As the constant crack water pressure increases, the failure mode of the 0° precrack specimen changes from “X”- shear failure to the single oblique shear failure along the shear wing crack direction, the main failure crack of the inclined precracked specimens (precrack angles of 15°, 45°, and 60°) changes from a small acute angle with the prefabricated crack to a direction along the shear wing crack, and irregular cracks occur at the chipped prefabricated crack in the 90° precracked specimen. With an increase in the constant crack water pressure, the average energy for a single hit, cumulative AE energy, and cumulative AE hits decrease, and the proportion of the tensile cracks increases and that of the shear cracks decreases.

Abstract Background The “missing” link of complex and multifaceted interplay among endogenous retroviruses (ERVs) transcription, chronic immuno-inflammation, and the development of psychiatric disorders is still far from being completely clarified. The present study was aimed to investigate the mechanism of protective role of inhibiting ERVs on reversing microglial immuno-inflammation in basolateral amygdala (BLA) in chronic stress-induced negative emotional behaviors in mice. Methods Male C57BL/6 mice were exposed to chronic unpredictable mild stress (CUMS) for 6 w. Negative emotional behaviors were comprehensively investigated to identify the susceptible mice. Microglial morphology, ERVs transcription, intrinsic nucleic acids sensing response, and immuno-inflammation in BLA were assessed. Results Mice with chronic stress were presented as obviously depressive- and anxiety-like behaviors, and accompanied with significant microglial morphological activation, murine ERVs genes MuERV-L, MusD, and IAP transcription, cGAS–IFI16–STING pathway activation, NF-κB signaling pathway priming, as well as NLRP3 inflammasome activation in BLA. Antiretroviral therapy, pharmacological inhibition of reverse transcriptases, as well as knocking-down the ERVs transcriptional regulation gene p53 significantly inhibited microglial ERVs transcription and immuno-inflammation in BLA, as well as improved the chronic stress-induced negative emotional behaviors. Conclusions Our results provided an innovative therapeutic approach that targeting ERVs-associated microglial immuno-inflammation may be beneficial to the patients with psychotic disorders.

The primary side and secondary side of the 10-kV digital circuit breaker is deeply integrated. Wherein, an electronic transformer is deployed together with the breaker inside a cabinet, and a digital unit is closely connected to the output port of the electronic transform. This compact and close arrangement makes the secondary side face a severe electromagnetic environment during the switching operation of the breaker. In this paper, we report the measured electromagnetic disturbances resulting from the opening/closing of 20 kA current by the breaker. The results show that the disturbance voltage at the secondary side port of the voltage transformer has the waveform of damped oscillatory waves, a peak value of up to 1.1kV, and dominant frequencies of 4.4 MHz and 15 MHz. The disturbance voltage at the secondary side port of the current transformer has a peak value of 350 V. The peak value of dH/dt of the spatial magnetic field is 0.387 kA $\cdot \text{m}^{-1}\cdot \mu \text{s}^{-1}$ . By comparing the measured waveforms with these specified in IEC 61000-4-18 and IEC 61000-4-10 standards, we advise that the level of immunity test is the third level of the fast-damped oscillatory wave for voltage port and the fourth level of the damped oscillatory magnetic for enclosure port.

Abstract Background Cholangiocarcinoma is a kind of invasive malignant tumor followed by hepatocellular carcinoma. miR-451 was suggested to function as regulator in various human tumors, but its role in mediating tumor progression and predicting the prognosis of cholangiocarcinoma remains unknown. The clinical significance and biological function of miR-451 in cholangiocarcinoma were assessed in this study. Results The tissue and serum expression of miR-451 was decreased in cholangiocarcinoma compared with corresponding normal samples. The downregulation of miR-451 was associated with the progressive TNM stage and positive lymph node metastasis of patients. miR-451 was identified to be an indicator of the diagnosis and prognosis of cholangiocarcinoma distinguishing cholangiocarcinoma patients from healthy volunteers and predicting the poor outcome of patients. miR-451 also served as a tumor suppressor negatively regulating the cellular processes of cholangiocarcinoma. Conclusions miR-451 played a vital role in the early detection and risk prediction of cholangiocarcinoma. miR-451 also suppressed the progression of cholangiocarcinoma, which provides a potential therapeutical target for cholangiocarcinoma treatment.

Abstract Retinoblastoma (RB) is the most common pediatric intraocular malignancy and is a serious vision- and life-threatening disease. The biallelic mutation of the retinoblastoma gene RB1 is the initial event in the malignant transformation of RB, but the exact molecular mechanism is still unclear. E2F transcription factors can be activated by RB1 loss of function and lead to uncontrolled cell division. Among E2F family numbers, E2F1 has higher expression abundance than E2F2 and E2F3 in RB clinical samples. By integrating E2F1 ChIP-seq data, RNA-seq profiling from RB samples and RNA-seq profiling upon E2F1 knockdown, together with pathway analysis, literature searching and experimental validation, we identified Cyclin-dependent kinases regulatory subunit 2 (CKS2) as a novel regulator in regulating tumor-associated phenotypes in RB. CKS2 exhibited aberrantly higher expression in RB. Depletion of CKS2 in Y79 retinoblastoma cell line led to reduced cell proliferation, delayed DNA replication and decreased clonogenic growth. Downregulation of CKS2 also slowed tumor xenograft growth in nude mice. Importantly, reversed expression of CKS2 rescued cancer-associated phenotypes. Mechanistically, transcription factor E2F1 enhanced CKS2 expression through binding to its promoter and CKS2 regulated the cancer-associated PI3K–AKT pathway. This study discovered E2F1/CKS2/PTEN signaling axis regulates malignant phenotypes in pediatric retinoblastoma, and CKS2 may serve as a potential therapeutic target for this disease.

Background and aims: The sodium taurocholate co-transporting polypeptide (NTCP) is a functional receptor for the hepatitis B virus (HBV), and it is critical for bile acid homeostasis. Previous studies of the association between the S267F variant and chronic hepatitis B (CHB) have generated conflicting results. This study analyzed the correlation between the NTCP S267F variant and CHB susceptibility by using a large sample of participants classified by gender and age, and this study also analyzed the relationship between this variant and the level of serum total bile acids. Methods: In total, 543 patients with CHB and 429 control subjects underwent S267F variant genotyping using SNaPshot technology. Logistic regression was utilized to evaluate any association of the NTCP S267F variant with CHB susceptibility. Results: The S267F variant was inversely correlated with the risk of chronic HBV infection in both the dominant model (GG genotype vs. AG genotype: odds ratio (OR) = 0.46, 95% confidence interval (CI) 0.30–0.71, P

Retinal pigment epithelial (RPE) is primarily impaired in age-related macular degeneration (AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization (CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor, rapamycin, was greatly limited. To mediate the mTOR pathway in the retina by a noninvasive approach, we developed novel biomimetic nanocomplexes where rapamycin-loaded nanoparticles were coated with cell membrane derived from macrophages (termed as MRaNPs). Taking advantage of the macrophage-inherited property, intravenous injection of MRaNPs exhibited significantly enhanced accumulation in the CNV lesions, thereby increasing the local concentration of rapamycin. Consequently, MRaNPs effectively downregulated the mTOR pathway and attenuate angiogenesis in the eye. Particularly, MRaNPs also efficiently activated autophagy in the RPE, which was acknowledged to rescue RPE in response to deleterious stimuli. Overall, we design and prepare macrophage-disguised rapamycin nanocarriers and demonstrate the therapeutic advantages of employing biomimetic cell membrane materials for treatment of AMD.

ObjectiveThyroid-associated ophthalmopathy (TAO) is a disfiguring autoimmune disease, which destroys the structure of orbital tissues and even threatens vision. Metabolic reprograming is critical in autoimmune diseases; however, the metabolic basis of TAO remains to be clarified. Our study aimed to reveal the metabolic profile of TAO.MethodsOrbital adipose/connective tissues from eleven TAO patients and twelve control subjects were collected during surgeries and analyzed with liquid chromatograph-mass spectrometer. Orthogonal partial least-squares discrimination analysis (OPLS-DA), variable importance in projection (VIP), heat map, and volcano plot were used to reveal metabolic profile in TAO. Pathway analysis and metabolites-gene analysis were utilized to explore potential metabolic metabolism in TAO.Results3038 metabolites were detected in samples from the TAO patients and the controls. OPLS-DA analysis of the metabolomics results showed two distinguished groups, demonstrating that TAO has a unique metabolome. Univariate tests identified 593 dysregulated metabolites (P < 0.05), including 367 increased metabolites and 226 decreased metabolites. Pathway analysis showed that changed metabolites were enriched in cholesterol metabolism, choline metabolism in cancer, fat digestion and absorption, regulation of lipolysis in adipocytes, and insulin resistance. In addition, metabolites-gene analysis illustrated that cholesterol metabolism was involved in the pathogenesis of TAO. Endoplasmic reticulum stress-related genes (ATF6, PERK, and IRE1α) expressions were higher in TAO orbital tissues than in control orbital tissues verified by western blot. Additionally, the expression level of diacylglycerol acyltransferase 1 (DGAT1), a key metabolic protein for triacylglycerol synthesis, was increased in orbital tissues of TAO detected by qRT-PCR, indicating disrupted cholesterol metabolism in TAO.ConclusionThe present study demonstrated different metabolite profiles and potential metabolic mechanisms in TAO.

Zinc finger proteins are involved in the resolution of immune responses and function by degrading mRNA of inflammatory cytokines. Here the authors show MCPIP3 promotes skin inflammation via modification of cytokine profiles in pDCs and macrophages.

Miniaturized energy storage devices integrated with wireless charging bring opportunities for next generation electronics. Here, authors report seamlessly integrated wireless charging micro-supercapacitors with high energy density capable of driving a model electrical car.

The impact of tropical cyclones on the characteristics of barrier layer (BL) thickness is investigated in this study in combination with observations and numerical simulations. Statistical results based on Simple Ocean Data Assimilation reanalysis (SODA) data and Argo float measurements reveal a significant effect of TCs on the BL characteristics. The BL thickness increases remarkably with the TC approaching, reaches its maximum 1–5 days after the TC passage, and recovers to its pre-storm state within 30 days on average. The peak increase in BL thickness is slightly rightward biased relative to the TC track, reaching ∼1.31 m (26.93%) relative to the pre-storm state as revealed by SODA data. The changes in BL thickness show a strong correlation with TC characteristics in terms of intensity and translation speed, tending to be more significant with more intense or slower-moving TCs. The thickening of the isothermal layer on the right of TC tracks and shallowing of the mixed layer act together to determine the BL development. The three-dimensional Price–Weller–Pinkel (3DPWP) ocean model is applied to explore the influence of precipitation on BL thickness. The results show that the precipitation tends to decrease the mixed layer depth while the vertical mixing of TCs deepens the isothermal layer depth, both of which act together to increase the BL thickness.

Background/Aims The association between the kinesin family member 1B (KIF1B) gene polymorphism and the risk of hepatitis B virus-related hepatocellular carcinoma (HCC) has been investigated in many peer-reviewed studies. However, scholars have failed to replicate these results in validation tests. The purpose of the present study was to explore whether the KIF1B rs17401966 polymorphism was associated with susceptibility to HCC. Methods The results of case-controlled studies on the correlation between the KIF1B rs17401966 polymorphism and HCC susceptibility were collected using Google Scholar and the EMBASE, PubMed and CNKI databases. Based on inclusion and exclusion criteria, 5 papers with a total of 12 cohorts were included in this study. Results The 12 cohorts were integrated, and the results showed that the rs17401966 polymorphism reduced the risk for HCC under the allele, heterozygous, homozygous, and dominant models but not under the additive or recessive models. Moreover, the merged results showed strong heterogeneity, and the cumulative meta-analysis results were unreliable. A genetic differentiation analysis of the 12 cohorts found different degrees of genetic differentiation between the 5 cohorts in Zhang et al.’s study and the cohorts in the other studies. We further divided the 12 study cohorts into 2 subgroups based on fixation index value; however, the results of that analysis were inconsistent. Conclusions The results of this meta-analysis were not able to verify the association between the KIF1B rs1740199 polymorphism and HCC risk. Therefore, a well-designed, large-scale, multicenter validation study is needed to confirm the relationship.

Asiatic acid (AA), a pentacyclic triterpene derived from the tropical medicinal plant Centella asiatica, has been widely used as an antioxidant and anti-inflammatory agent. Evidence regarding the neuroprotective properties of AA is emerging. However, the protective effects of AA and its mechanism in glaucoma are poorly understood. In the current study, we investigate the neuroprotective effect and mechanism of AA on retinal ganglion cells (RGCs) in a rat model of glaucoma. Elevated intraocular pressure (IOP) was induced in adult rats by injecting microspheres into the anterior chamber. AA was intravitreally injected into glaucomatous rats. RGC densities were analyzed by evaluating surviving RGC number of the retinal flatmounts and retinal sections, and the apoptotic cell number were evaluated by analyzing retinal sections. RGC function was assessed by measuring the photopic negative response (PhNR). Retinal Bcl-2, Bax, and cleaved caspase-3 expression were determined using a Simple Western System, real-time PCR and immunofluorescence staining. AA reduced the loss of RGCs and decreased the apoptotic RGC number. AA exerted neuroprotective effects and ameliorated retinal dysfunction in impaired RGCs in a rat model of glaucoma. AA protected RGCs by upregulating the expression of the antiapoptotic protein Bcl-2 and downregulating the expression of the pro-apoptotic proteins Bax and caspase-3. This study has provided important evidence indicating that AA may be a potential therapeutic agent for glaucoma.

We report a comprehensive study on the role of the free layer thickness (tF) in electric-field controlled nanoscale perpendicular magnetic tunnel junctions (MTJs), comprising of free layer structure Ta/Co40Fe40B20/MgO, by using dc magnetoresistance and ultra-short magnetization switching measurements. Focusing on MTJs that exhibits positive effective device anisotropy (Keff), we observe that both the voltage-controlled magnetic anisotropy (ξ) and voltage modulation of coercivity show strong dependence on tF. We found that ξ varies dramatically and unexpectedly from ∼−3 fJ/V-m to ∼−41 fJ/V-m with increasing tF. We discuss the possibilities of electric-field tuning of the effective surface anisotropy term, KS as well as an additional interfacial magnetoelastic anisotropy term, K3 that scales with 1/tF2. Voltage pulse induced 180° magnetization reversal is also demonstrated in our MTJs. Unipolar switching and oscillatory function of switching probability vs. pulse duration can be observed at higher tF, and agrees well with the two key device parameters — Keff and ξ.

Background/Aims: Osteoporosis is a metabolic bone disorders that tortures about millions of people worldwide. Recent studies showed that Andrographolide (AP) is a promising natural compound for the treatment of osteoclast-related bone diseases. However, its potential in treatment of osteoporosis has not been fully explored. Methods: In this study, the effect of AP on osteoblasts metabolism was investigated via the detection of cell proliferation, cell viability, ALP activity, the expression of osteogenic specific genes including runt-related transcription factor 2 (RUNX2), bone sialoprotein (BSP), osteocalcin (OCN), Bone morphogenic protein-2 (BMP2) and Alkaline phosphatase(ALP) for 3, 5 and 7 days respectively. Further exploration of the association of AP with WNT/β-catenin signaling pathway was performed by examination of the expression of WNT related genes and proteins. Results: Results showed that AP of 4.46 and 8.92 µM, especially 8.92 µM was beneficial to osteogenic differentiation by upregulating ALP activity and expression of osteogenic related genes (PConclusion: This study indicates that AP exerts its pro-osteogenic potential via activation of the WNT/β-catenin in osteoblasts and thus may represent a candidate of therapeutic agent for osteoporosis.

We measure the voltage or electric field (EF) modulated change in anisotropy using two methods on the same nanometer sized device: 1) Directly using the area of the hard axis magnetization loop and 2) Indirectly using the switching field distribution method. Both methods yield similar values of efficiency. With the indirect method, the efficiency derived from the thermal stability was found to be more consistent than that from the anisotropy field. Our data also suggests that memory devices that rely solely on EF effects may benefit from larger device sizes.

Objective: Thyroid-associated ophthalmopathy (TAO) is a disfiguring autoimmune disease, which destroys the structure of orbital tissues and even threatens vision. Metabolic reprograming is critical in autoimmune diseases; however, the metabolic basis of TAO remains to be clarified. Our study aimed to reveal the metabolic profile of TAO. Methods: Orbital adipose/connective tissues from eleven TAO patients and twelve control subjects were collected during surgeries and analyzed with liquid chromatograph-mass spectrometer. Orthogonal partial least-squares discrimination analysis (OPLS-DA), variable importance in projection (VIP), heat map, and volcano plot were used to reveal metabolic profile in TAO. Pathway analysis and metabolites-gene analysis were utilized to explore potential metabolic metabolism in TAO. Results: 3038 metabolites were detected in samples from the TAO patients and the controls. OPLS-DA analysis of the metabolomics results showed two distinguished groups, demonstrating that TAO has a unique metabolome. Univariate tests identified 593 dysregulated metabolites (P < 0.05), including 367 increased metabolites and 226 decreased metabolites. Pathway analysis showed that changed metabolites were enriched in cholesterol metabolism, choline metabolism in cancer, fat digestion and absorption, regulation of lipolysis in adipocytes, and insulin resistance. In addition, metabolites-gene analysis illustrated that cholesterol metabolism was involved in the pathogenesis of TAO. Endoplasmic reticulum stress-related genes (ATF6, PERK, and IRE1a) expressions were higher in TAO orbital tissues than in control orbital tissues verified by western blot. Additionally, the expression level of diacylglycerol acyltransferase 1 (DGAT1), a key metabolic protein for triacylglycerol synthesis, was increased in orbital tissues of TAO detected by qRT-PCR, indicating disrupted cholesterol metabolism in TAO. Conclusion: The present study demonstrated different metabolite profiles and potential metabolic mechanisms in TAO. [ABSTRACT FROM AUTHOR]

Isocitrate dehydrogenase 3 (IDH3) is a key enzyme in the mitochondrial tricarboxylic acid (TCA) cycle, which catalyzes the decarboxylation of isocitrate into α-ketoglutarate and concurrently converts NAD+into NADH. Dysfunction of IDH3B, the β subunit of IDH3, has been previously correlated with retinal degeneration and male infertility in humans, but tissue-specific effects of IDH3 dysfunction are unclear. Here, we generated Idh3b-KO mice and found that IDH3B is essential for IDH3 activity in multiple tissues. We determined that loss of Idh3b in mice causes substantial accumulation of isocitrate and its precursors in the TCA cycle, particularly in the testes, whereas the levels of the downstream metabolites remain unchanged or slightly increased. However, the Idh3b- KO mice did not fully recapitulate the defects observed in humans. Global deletion of Idh3b only causes male infertility but not retinal degeneration in mice. Our investigation showed that loss of Idh3b causes an energetic deficit and disrupts the biogenesis of acrosome and flagellum, resulting in spermiogenesis arrestment in sperm cells. Together, we demonstrate that IDH3B controls its substrate levels in the TCA cycle, and it is required for sperm mitochondrial metabolism and spermiogenesis, highlighting the importance of the tissue-specific function of the ubiquitous TCA cycle. [ABSTRACT FROM AUTHOR]

Choroidal neovascularization (CNV) is a leading cause of visual loss in age-related macular degeneration (AMD). However, the molecular mechanism for CNV progression is still unclear. This study aimed to identify CNV-related circular RNAs (circRNAs), a novel class of non-coding RNAs with diverse functions. A total of 117 circRNAs were differentially expressed in the murine CNV model by microarrays. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to identify the functions of selected circRNAs. The host genes of these circRNAs were predicted to be targeted to neurogenesis (ontology: biological process), proteinaceous extracellular matrix (ECM) (ontology: cellular component), and binding (ontology: molecular function). Differentially expressed circRNAs-mediated regulatory networks were enriched in ECM receptor interaction. Most of the dysregulated circRNAs could potentially bind to five different miRNAs by TargetScan and miRanda. Specifically, circ_15752 was identified in this circRNAs pool which may facilitate vascular endothelial cell proliferation, migration, and tube formation, suggesting a critical role in endothelial angiogenesis. Our work suggests that dysregulated circRNAs may be involved in CNV pathogenesis and serve as potential biomarkers for CNV. [ABSTRACT FROM AUTHOR]

The retinal pigment epithelium (RPE) is a monolayer of pigmented cells between the choroid and the retina. RPE dysfunction underlies many retinal degenerative diseases, including age-related macular degeneration, the leading cause of age-related blindness. To perform its various functions in nutrient transport, phagocytosis of the outer segment, and cytokine secretion, the RPE relies on an active energy metabolism. We previously reported that human RPE cells prefer proline as a nutrient and transport proline-derived metabolites to the apical, or retinal, side. In this study, we investigated how RPE utilizes proline in vivo and why proline is a preferred substrate. By using [13C]proline labeling both ex vivo and in vivo, we found that the retina rarely uses proline directly, whereas the RPE utilizes it at a high rate, exporting proline-derived mitochondrial intermediates for use by the retina. We observed that in primary human RPE cell culture, proline is the only amino acid whose uptake increases with cellular maturity. In human RPE, proline was sufficient to stimulate de novo serine synthesis, increase reductive carboxylation, and protect against oxidative damage. Blocking proline catabolism in RPE impaired glucose metabolism and GSH production. Notably, in an acute model of RPE-induced retinal degeneration, dietary proline improved visual function. In conclusion, proline is an important nutrient that supports RPE metabolism and the metabolic demand of the retina. [ABSTRACT FROM AUTHOR]