The endometrial cancer detection using non-invasive hypermethylation of CDO1 and CELF4 genes in women with postmenopausal bleeding in Northwest China.

Objective: The objective of this study was to verify the clinical predictive performance of methylated cysteine dioxygenase type 1 (CDO1m) and CUGBP Elav-like family member 4 (CELF4m) in endometrial cancer (EC) women with postmenopausal bleeding (PMB). Material and Methods: A single-center, prospective, and case-control study was conducted in the Gansu Provincial Maternity and Child-care Hospital with 138 female postmenopausal patients enrolled in 2022. All patients underwent body mass index (BMI) detection, transvaginal ultrasonography (TVUS) detection, carbohydrate antigen 125 detection, and the cervical exfoliated cell CDO1/CELF4 gene methylation detection to analyze the sensitivity, specificity, and accuracy of different screening tests statistically with the biopsy and/or dilation and curettage (D&C) pathological diagnosis under hysteroscopy as the gold standard. Results: There was no significant difference in age between the EC group and the non-EC group, P = 0.492. Using quantitative polymerase chain reaction (qPCR) technology, we validated the CDO1 and CELF4 methylation detection with 87.5% sensitivity and 95.9% specificity as a useful strategy for the triage of women with PMB for the detection of EC. In addition, 100% of type II EC (n = 6) were positively detected by the CDO1 or CELF4 methylation test. Conclusion: The CDO1 and CELF4 methylation test with high specificity as an auxiliary diagnostic tool or alternative method provides physicians with a reference to distinguish between benign and malignant tumors in women with postmenopausal bleeding, to justify the necessity of using invasive methods to confirm diagnosis.

Pickering emulsion stabilized by quercetin-ß-cyclodextrin-diglyceride particles: Effect of diglyceride content on interfacial behavior and emulsifying property of complex particles.

This research develops diacylglycerol (DAG) based Pickering emulsions with enhanced oxidative stability stabilized by self-assembled quercetin/DAG/ß-cyclodextrin (ß-CD) complexes (QDCCs) using a one-step agitation method. Influence of DAG content (5%, 15%, 40%, and 80%, w/w) on the self-assembly behavior, interfacial properties, and emulsifying ability of complex particles was investigated. SEM, XRD and ATR-FTIR studies confirmed the formation of ternary composite particles. QDCCs in 80% DAG oil had the highest quercetin encapsulation efficiency (6.09 ± 0.01%), highest DPPH radical scavenging rate and ferric reducing antioxidant property (FRAP). ß-CD and quercetin adsorption rates in emulsion with 80% DAG oil were 88.4 ± 2.53% and 98.34 ± 0.15%, respectively. Pickering emulsions with 80% DAG had the smallest droplet size (8.90 ± 1.87 µm) and excellent oxidation stability. This research develops a novel approach to regulate the physicochemical stability of DAG-based emulsions by anchoring natural antioxidants at the oil-water interface through a one-pot self-assembly method.

Glomerular basement membrane ultrastructural changes in a patient with COQ2 glomerulopathy: A case report.

Primary coenzyme Q10 deficiency-1, caused by COQ2 disease-causing variants, is an autosomal recessive disorder, and genetic testing is the gold standard for diagnosing this condition. A Chinese boy with steroid-resistant nephrotic syndrome, focal segmental glomerulosclerosis, and progressive kidney insufficiency was included in the study. Electron microscopy revealed the glomerular basement membrane with irregular thickness and lamellation with diffuse effacement of foot processes in the podocytes, and swollen mitochondria with abnormal cristae in the podocytes. Coenzyme Q10 supplementation started about 3 weeks after the onset of mild kidney dysfunction did not improve the proband's kidney outcome. Proband-only whole-exome sequencing and Sanger sequencing revealed two heteroallelic COQ2 variants: a maternally inherited novel variant c.1013G > A[p.(Gly338Glu)] in exon 6 and a variant of unknown origin c.1159C > T[p.(Arg387*)] in exon 7. Subsequent long-read sequencing demonstrated these two variants were located on different alleles. Our report extends the phenotypic and genotypic spectrum of COQ2 glomerulopathy.

Tunable terahertz absorption of ion gel-graphene hybrids based on the Salisbury effect.

The gate-tunable absorption properties of graphene make it suitable for terahertz (THz) absorbers. However, the realization of a graphene-based THz absorber faces challenges between the difficulty of patterning graphene for processing and the intrinsically low absorbance of graphene with the high electric field needed to change the conductivity of graphene. This report presents an electrically tunable graphene THz absorber where a single-layer graphene film and a gold reflective layer are separated by a polyimide (PI) dielectric layer to form an easily fabricated three-layer Salisbury screen structure. The carrier density of the graphene layer can be efficiently tuned by a small external electrical gating (-5V-5 V) with the assistance of an ion gel layer. The voltage modulation of the Fermi energy level (EF) of graphene was confirmed by Raman spectra, and the variation of the device absorbance was confirmed using a THz time-domain spectroscopy system (THz-TDS). The measurements show that the EF is adjusted in the range of 0-0.5 eV, and THz absorbance is adjusted in the range of 60%-99%. The absorber performs well under different curvatures, and the peak absorbance is all over 95%. We conducted further analysis of the absorber absorbance by varying the thickness of the PI dielectric layer, aiming to examine the correlation between the resonant frequency of the absorber and the dielectric layer thickness. Our research findings indicate that the proposed absorber holds significant potential for application in diverse fields such as communication, medicine, and sensing.

Phloridzin reduces synovial hyperplasia and inflammation in rheumatoid arthritis rat by modulating mTOR pathway.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease and management of it still a challenge. Given report evaluates protective effect of phlorizin on RA and also postulates the molecular mechanism of its action. Bovine type II collagen (CIA) and Freund's incomplete adjuvant (1:1 and 1 mg/ml) was administered on 1st and 8th day of protocol to induce RA in rats and treatment with phlorizin 60 and 120 mg/kg was started after 4th week of protocol. Level of inflammatory cytokines and expression of proteins were estimated in phlorizin treated RA rats. Moreover in-vitro study was performed on Fibroblast-like synoviocytes (FLSs) and effect of phlorizin was estimated on proliferation, apoptosis and expression of mTOR pathway protein after stimulating these cell lines with Tumour Necrosis Factor alpha (TNF-α). Data of study suggest that phlorizin reduces inflammation and improves weight in CIA induced RA rats. Level of inflammatory cytokines in the serum and expression of Akt/PI3K/mTOR proteins in the join tissue was reduced in phlorizin treated RA rats. Phlorizin also reported to reverse the histopathological changes in the joint tissue of RA rats. In-vitro study supports that phlorizin reduces proliferation and no apoptotic effect on TNF-α stimulated FLSs. Expression of Akt/PI3K/mTOR proteins also downregulated in phlorizin treated TNF-α stimulated FLSs. In conclusion, phlorizin protects inflammation and reduces injury to the synovial tissues in RA, as it reduces autophagy by regulating Akt/PI3K/mTOR pathway.

Phlorizin Regulates Synovial Hyperplasia and Inflammation in Rats With Rheumatoid Arthritis by Regulating the mTOR Pathway.

BACKGROUND/AIM: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, and management of it is still a challenge. The present investigation assessed the potential preventive effect of phlorizin on rats with RA. MATERIALS AND METHODS: A total of 40 healthy Wistar rats were used for this study. Bovine type II collagen and Freund's incomplete adjuvant (1:1 and 1 mg/ml) were administered on days 1 and 8 of the protocol to induce RA in rats; treatment with phlorizin at 60 or 120 mg/kg was started after the 4th week of the protocol, and its effect on inflammation, level of inflammatory cytokines, and expression of proteins were estimated in RA rats. Moreover, an in vitro study was performed on fibroblast-like synoviocytes (FLSs), and the effects of phlorizin on proliferation, apoptosis, and expression of the mechanistic target of rapamycin kinase pathway protein after stimulating these cells with tumor necrosis factor α (TNF-α) were estimated. RESULTS: The data obtained from the study indicate that phlorizin has the potential to mitigate inflammation and enhance weight management in rats with RA induced by bovine type II collagen (CII). The level of inflammatory cytokines in the serum and the expression of protein kinase B (AKT), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and mechanistic target of rapamycin kinase (mTOR) proteins in the joint tissue were reduced in phlorizin-treated rats with RA. In this investigation, phlorizin was shown to reverse the histological abnormalities in the joint tissue of rats with RA. The in-vitro study showed that phlorizin reduced proliferation and had no apoptotic effect on TNF-α-stimulated FLSs. Expression of AKT, PI3K, and mTOR proteins was also down-regulated in phlorizin-treated TNF-α-stimulated FLSs. CONCLUSION: Phlorizin protects against inflammation and reduces injury to synovial tissues in RA by modulating the AKT/PI3K/mTOR pathway.

Effects of freeze-thaw cycles on the quality of Hot-dry noodles: From the moisture, starch, and protein characteristics.

Freeze-thaw cycles (FTC) could cause damage to food during storage. The effects of different FTC on Hot-dry noodles (HDN) in terms of quality, moisture, starch, and protein characteristics were studied. This study showed that FTC decreased the texture properties and water absorption of HDN. Meanwhile, cooking loss was significantly increased after FTC. The water content of HDN was decreased and water migration was increased during FTC. In addition, results showed that FTC destroyed the order structure and increased the crystallinity of starch in HDN. Under FTC, the disulfide bond of HDN was broken, the free sulfhydryl group was increased, and the electrophoretic patterns confirmed the protein depolymerization. The microstructure also showed that the gluten network became incomplete and starch was exposed outside the substrate. This study expounded the mechanism of HDN quality deterioration during FTC, which laid a foundation for the development and improvement of frozen and freeze-thaw noodles.

Effect of moxibustion for "nourishing the kidney and benefiting the marrow" on knee osteoarthritis. / "补肾益髓"æ³•è‰¾ç¸æ²»ç–—è†å ³èŠ‚éª¨å ³èŠ‚ç‚Žçš„ç–—æ•ˆè§‚å¯Ÿ.

OBJECTIVES: To compare the clinical effect between two acupoint regimens of moxibustion on knee osteoarthritis (KOA), and observe the influences on the serum content of interleukin 1α (IL-1α), interleukin-17A (IL-17A), tumor necrosis factor α (TNF-α), bone gla protein (BGP) and osteoprotegerin (OPG). METHODS: KOA patients were randomly divided into an observation group (40 cases, 2 cases dropped off) and a control group (40 cases, 3 cases dropped off). In the observation group, moxibustion was applied to Xiyan (EX-LE5), Dubi (ST35), Zusanli (ST36), Dazhu (BL11), Xuanzhong (GB39) and Yongquan (KI1) on the affected side. In the control group, EX-LE5, ST35 and ST36 were selected on the affected side. One session of treatment took 30 min in each group, delivered 3 times a week and the duration of treatment was 4 weeks. The scores of Western Ontario and McMaster University (WOMAC) and visual analogue scale (VAS) were observed and the serum content of IL-1α, IL-17A, TNF-α, BGP and OPG of the two groups were measured before and after treatment. RESULTS: Compared with those before treatment, the WOMAC score, VAS score and the serum content of IL-1α, IL-17A and TNF-α were decreased (P<0.05), and the content of BGP and OPG were increased (P<0.05) after treatment. Compared with the control group, the WOMAC score, VAS score and the serum content of IL-1α and TNF-α in the observation group were lower (P<0.05), and the content of BGP and OPG were higher (P<0.05). The total effective rate of the observation group was 89.5% (34/38), and that of the control group was 83.8% (31/37), with no statistically significant difference. CONCLUSIONS: Moxibustion therapy of "nourishing the kidney and benefiting the marrow" can relieve joint pain, improve joint function, reduce the level of inflammatory factors and ameliorate bone metabolic indicators. The effect of the acupoint regimen in this moxibustion therapy is better than that of the local acupoint selection.

Risk Factors and Prognosis of Early Neurological Deterioration after Bridging Therapy.

BACKGROUND: Early neurological deterioration (END) after bridging therapy (BT) of acute ischemic stroke (AIS) patients is associated with poor outcomes. OBJECTIVE: We aimed to study the incidence, risk factors and prognosis of END after BT. METHODS: From January to December 2021, the clinical data of AIS patients treated by BT (intravenous thrombolysis with alteplase prior to mechanical thrombectomy) from three comprehensive stroke centers were analyzed. Patients were divided into non-END group and END group according to whether they developed END within 72 hours of symptom onset. Modified Rankin scale (mRS) was used to assess the patient's prognosis at 90 days, and favorable outcomes were defined as mRS≤2. The incidence of END was investigated, and binary logistic regression analysis was used to explore its associated factors. RESULTS: The incidence of END after BT was 33.67%. The eligible 90 patients included 29 cases in the END group and 61 cases in the non-END group. Multivariate Logistic regression analysis showed that increase of systolic blood pressure (SBP) (OR=1.026, 95%CI:1.001-1.051, p =0.043), higher level of blood glucose at admission (OR=1.389, 95%CI:1.092-1.176, p =0.007) and large artery atherosclerosis (LAA) subtype (OR=8.009, 95%CI:2.357-27.223, p =0.001) were independent risk factors of END. Compared with the non-END group, the END group had significantly lower rates of good outcomes (6.90% versus 65.57%, p =0.001) while higher rates of mortality (44.83% versus 4.92%, p =0.001). CONCLUSION: It was found that the incidence of END after BT in AIS patients was 33.67%. An increase in SBP, higher glucose levels at admission, and LAA were independent risk factors of END that predicted a poor prognosis.

Fusarium sacchari FsNis1 induces plant immunity.

Pokkah Boeng disease (PBD), caused by Fusarium sacchari, severely affects sugarcane yield and quality. Necrosis-inducing secreted protein 1 (Nis1) is a fungal secreted effector that induces necrotic lesions in plants. It interacts with host receptor-like kinases and inhibits their kinase activity. FsNis1 contains the Nis1 structure and triggered a pathogen-associated molecular pattern-triggered immune response in Nicotiana benthamiana, as reflected by causing reactive oxygen species production, callose accumulation, and the upregulated expression of defense response genes. Knockout of this gene in F. sacchari revealed a significant reduction in its pathogenicity, whereas the pathogenicity of the complementary mutant recovered to the wild-type levels, making this gene an important virulence factor for F. sacchari. In addition, the signal peptide of FsNis1 was required for the induction of cell death and PTI response in N. benthamiana. Thus, FsNis1 may not only be a key virulence factor for F. sacchari but may also induce defense responses in plants. These findings provide new insights into the function of Nis1 in host-pathogen interactions.

Protecting meat color: The interplay of betanin red and myoglobin through antioxidation and coloration.

Myoglobin (Mb) responsible for meat color is easily oxidized resulting in meat discoloration. Here, betanin red (BR), as a natural pigment and antioxidant, was chosen for enhancing redness and inhibiting oxidation. Multiple spectroscopies, isothermal titration calorimetry and molecular docking demonstrated that BR changed the microenvironment of heme group and amino acid residues of Mb, inhibited the oxidation of oxymyoglobin. The main interaction force was hydrogen bond and one variable binding site provided a continuous protective barrier to realize antioxidation. The combination of antioxidation with the inherent red color of BR offered dual color protection effect on processed beef with the addition amount of 0.2 % BR. BR treatment enhanced the redness by 25.59 âˆ¼ 53.24 % and the sensory acceptance by 4.89 âˆ¼ 14.24 %, and decreased the lipid oxidation by 0.58 âˆ¼ 15.92 %. This study paves a theoretical basis for the application of BR and its structural analogues in meat color protection and other quality improvement.

High glucose impairs cognitive function through inducing mitochondrial calcium overload in Treg cells.

High glucose has been proved to impair cognitive function in type 2 diabetes, but the underlying mechanisms remain elusive. Here, we found that high glucose increased transcription factors' SP1 O-GlcNAcylation in regulatory T (Treg) cells. Glycosylated SP1 further enhanced HDAC2 recruitment and histone deacetylation on Na+/Ca2+/Li+ exchanger (NCLX) promoter, which downregulated NCLX expression and led to mitochondrial calcium overload and oxidative damage, thereby promoting Treg cell dysfunction, M1 microglia polarization, and diabetes-associated cognitive impairment. Importantly, GLP-1 receptor agonist alleviated these deleterious effects via GLP-1-receptor-mediated upregulation of OGA and inhibition of SP1 O-GlcNAcylation in Treg cells. Our study highlighted a link between high-glucose-mediated SP1 O-GlcNAcylation and HDAC2/NCLX signaling in control of mitochondrial calcium concentrations in Treg cells. It also revealed a mechanism for linking Treg cell dysfunction and cognitive impairment in type 2 diabetes and provides an insight into the mechanism underlying the neuroprotective effects of GLP-1 receptor agonist.

In vitro digestion and colonic fermentation characteristics of media-milled purple sweet potato particle-stabilized Pickering emulsions.

BACKGROUND: Pickering emulsions stabilized by multicomponent particles have attracted increasing attention. Research on characterizing the digestion and health benefit effects of these emulsions in the human gastrointestinal tract are quite limited. This work aims to reveal the digestive characteristics of media-milled purple sweet potato particle-stabilized Pickering emulsions (PSPP-Es) during in vitro digestion and colonic fermentation. RESULTS: The media-milling process improved the in vitro digestibility and fermentability of PSPP-Es by reaching afree fatty acids release rate of 43.11 ± 4.61% after gastrointestinal digestion and total phenolic content release of 101.00 ± 1.44 µg gallic acid equivalents/mL after fermentation. In addition, PSPP-Es exhibited good antioxidative activity (2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power assays), α-glucosidase inhibitory activity (half-maximal inhibitory concentration: 6.70%, v/v), and prebiotic effects, reaching a total short-chain fatty acids production of 9.90 ± 0.12 mol L-1, boosting the growth of Akkermansia, Bifidobacterium, and Blautia and inhibiting the growth of Escherichia-Shigella. CONCLUSIONS: These findings indicate that the media-milling process enhances the potential health benefits of purple sweet potato particle-stabilized Pickering emulsions, which is beneficial for their application as a bioactive component delivery system in food and pharmaceutical products. © 2024 Society of Chemical Industry.

Neuronal intranuclear inclusion disease with cortical involvement in left hemisphere: a case report.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a rare highly heterogeneous disease. In this paper, we present a case of NIID featured in cortical involvement in left hemisphere of brain and the imaging changes in the process of the disease. CASE PRESENTATION: A 57-year-old female was hospitalized due to recurrent attacks of headache with cognitive impairment and tremor for 2 years. The symptoms of headache episodes were reversible. The characteristic radiologic change was high intensity signal involving the grey matter-white matter junction on the brain diffusion-weighted imaging (DWI), which existed in the frontal lobe and then extended backwards. Atypical features on fluid-attenuated inversion recovery (FLAIR) sequences showing small patchy high signals in the cerebellar vermis. High signals and edema were detected on FLAIR images along the cortex of the left occipito-parieto-temporal lobes, expanding and gradually shrinking in the follow-up visit. Besides, cerebral atrophy and bilateral symmetrical leukoencephalopathy were also detected. Skin biopsy and genetic testing confirmed the diagnosis of NIID. CONCLUSION: Except for typical radiological change strongly suggesting NIID, it is also necessary to notice the insidious symptoms of NIID combining with some atypical imaging features to make an early diagnosis. Skin biopsies or genetic testing should be carried out early in patients with highly suspected NIID.

Loss of Gucy1a3 causes poor post-stroke recovery by reducing angiogenesis via the HIF-1α/VEGFA signaling pathway in mice.

OBJECTIVES: Ischemic stroke is a common and debilitating disease that can cause permanent neurological damage. Gucy1a3, which encodes the α1 subunit of soluble guanylyl cyclase, has been reported to be associated with functional recovery after ischemic stroke. However, the mechanism is still not well understood. In the present study, we investigated the effects of Gucy1a3 on (i) post-stroke recovery; (ii) vascular endothelial growth factor A (VEGFA) and hypoxia inducible factor 1 alpha (HIF-1α) expression; and (iii) angiogenesis after ischemic stroke. MATERIALS AND METHODS: Wild-type and Gucy1a3 knockout C57BL/6J male mice were respectively used to establish the models of permanent middle cerebral artery occlusion (pMCAO). Neurological deficit scores were evaluated at 24 h and 96 h after pMCAO. Cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. For determining microvessel density, immunohistochemical analysis was performed with CD31. The expression of VEGFA and HIF-1α was detected by western blotting. RESULTS: Our results suggest that loss of Gucy1a3 increased the infarct volume and aggravated neurological deficits after pMCAO. In addition, the Gucy1a3 knockout brains exhibited significantly lower microvessel densities and VEGFA and HIF-1α expression levels than the wild-type brains at 96 h post-pMCAO. CONCLUSIONS: Our study indicates that GUCY1A3 might be involved in angiogenesis after ischemic stroke. Further investigation of GUCY1A3 will provide a new therapeutic target for stroke.

Efficacy and safety of a noninvasive, home-based radiofrequency device for facial rejuvenation: An open-label, intraindividual controlled trial.

BACKGROUND: Wrinkle formation is the most visible characteristic of facial aging. Radiofrequency (RF) technology is currently utilized to reduce facial wrinkles and contribute to skin rejuvenation. OBJECTIVE: To analyze the efficacy and safety of a noninvasive, home-based RF device applied for facial rejuvenation in Chinese people. METHODS: A single-center, open-label, intraindividual controlled trial was performed on subjects who received an 8-week treatment of the RF device. A total of 22 female individuals aged 25-60 years with Fitzpatrick skin type III-IV were enrolled. Efficacy of treatment was subjectively evaluated using the Fitzpatrick Wrinkle Classification Scale (FWCS) assessed by physician or overall satisfaction of subject with a 10-point VAS, and objectively using the skin ultrasound examination as well as the 3D skin analysis system. Adverse event was recorded at each visit. RESULTS: In comparison with the baseline, evaluator-assessed FWCS scores showed significant improvement at 4 weeks (p < 0.005) and 8 weeks (p < 0.005) after treatment. All subjects reported different degrees of improvement in facial wrinkles after 8 weeks of treatment. The results of skin ultrasound examination revealed significant increase of the dermal thickness at week 8 (p < 0.05) as compared to the baseline. In addition, a significant decrease in the proportion and density of perioral wrinkles evaluated by the 3D skin analysis system was observed from baseline to week 4. The treatment was well-tolerated, and no serious adverse event was observed. CONCLUSION: This noninvasive, home-based RF device was effective in improving skin texture and elasticity with a safe and well-tolerated treating procedure.

Visible-Light-Enhanced Hydrogen Evolution through Anodic Furfural Electro-Oxidation Using Nickel Atomically Dispersed Copper Nanoparticles.

A novel copper nanoparticle variant, denoted as Cu98Ni2 NPs, which incorporate Ni atoms in an atomically dispersed manner, has been successfully synthesized via a straightforward one-pot electrochemical codeposition process. These nanoparticles were subsequently employed as an anode to facilitate the oxidation of furfural, leading to the production of hydrogen gas. Voltammetric measurements revealed that the inclusion of trace amounts of Ni atoms in the nanoparticles resulted in a pronounced synergistic electronic effect between Cu and Ni. Consequently, a 43% increase in current density at 0.1 V was observed in comparison to pure Cu NPs. Importantly, when the Cu98Ni2 NPs were irradiated with visible light, a remarkable current density enhancement factor of 505% at 0.1 V was achieved relative to that of pure Cu NPs in the absence of light. This enhancement can be attributed to localized surface plasmon resonance induced by visible light, which triggers photothermal and photoelectric effects. These effects collectively contribute to the significant overall improvement in the electrocatalytic oxidation of furfural, leading to enhanced hydrogen evolution.

Quantitative subcellular reconstruction reveals a lipid mediated inter-organelle biogenesis network.

The structures and functions of organelles in cells depend on each other but have not been systematically explored. We established stable knockout cell lines of peroxisomal, Golgi and endoplasmic reticulum genes identified in a whole-genome CRISPR knockout screen for inducers of mitochondrial biogenesis stress, showing that defects in peroxisome, Golgi and endoplasmic reticulum metabolism disrupt mitochondrial structure and function. Our quantitative total-organelle profiling approach for focussed ion beam scanning electron microscopy revealed in unprecedented detail that specific organelle dysfunctions precipitate multi-organelle biogenesis defects, impair mitochondrial morphology and reduce respiration. Multi-omics profiling showed a unified proteome response and global shifts in lipid and glycoprotein homeostasis that are elicited when organelle biogenesis is compromised, and that the resulting mitochondrial dysfunction can be rescued with precursors for ether-glycerophospholipid metabolic pathways. This work defines metabolic and morphological interactions between organelles and how their perturbation can cause disease.

Sequence differences between BAX and BAK core domains manifest as differences in their interactions with lipids.

The B-cell lymphoma 2 (BCL2) family members, BCL2-associated protein X (BAX) and BCL2 homologous antagonist killer (BAK), are required for programmed cell death via the mitochondrial pathway. When cells are stressed, damaged or redundant, the balance of power between the BCL2 family of proteins shifts towards BAX and BAK, allowing their transition from an inactive, monomeric state to a membrane-active oligomeric form that releases cytochrome c from the mitochondrial intermembrane space. That oligomeric state has an essential intermediate, a symmetric homodimer of BAX or BAK. Here we describe crystal structures of dimers of the core domain of BAX, comprising its helices α2-α5. These structures provide an atomic resolution description of the interactions that drive BAX homo-dimerisation and insights into potential interaction between core domain dimers and membrane lipids. The previously identified BAK lipid-interacting sites are not conserved with BAX and are likely to determine the differences between them in their interactions with lipids. We also describe structures of heterodimers of BAK/BAX core domains, yielding further insight into the differences in lipid binding between BAX and BAK.

Low expression of GOT2 promotes tumor progress and predicts poor prognosis in hepatocellular carcinoma.

Background: To explore the biological function and the underlying mechanisms of GOT2 in hepatocellular carcinoma (HCC). Materials & methods: The expression level and prognostic value of GOT2 were examined using International Cancer Genome Consortium and International Cancer Proteogenome Consortium databases. The cell counting kit-8 method, clone formation, Transwell® assays and western blotting were used to evaluate the effects of GOT2 on the biological function and autophagy of HCC cells. Results: The expression of GOT2 was downregulated in HCC tissues and correlated with poor prognosis of HCC patients. Knockdown of GOT2 promoted proliferation, migration and invasion of HCC cells and promoted cells' proliferation by inducing autophagy. Conclusion: GOT2 plays a tumor-inhibitory role in HCC and may be a potential therapeutic target for HCC.