Actin-bundling protein fimbrin serves as a new auxin biosynthesis orchestrator in Arabidopsis root tips.

Plants delicately regulate endogenous auxin levels through the coordination of transport, biosynthesis, and inactivation, which is crucial for growth and development. While it is well-established that the actin cytoskeleton can regulate auxin levels by affecting polar transport, its potential role in auxin biosynthesis has remained largely unexplored. Using LC-MS/MS-based methods combined with fluorescent auxin marker detection, we observed a significant increase in root auxin levels upon deletion of the actin bundling proteins AtFIM4 and AtFIM5. Fluorescent observation, immunoblotting analysis, and biochemical approaches revealed that AtFIM4 and AtFIM5 affect the protein abundance of the key auxin synthesis enzyme YUC8 in roots. AtFIM4 and AtFIM5 regulate the auxin synthesis enzyme YUC8 at the protein level, with its degradation mediated by the 26S proteasome. This regulation modulates auxin synthesis and endogenous auxin levels in roots, consequently impacting root development. Based on these findings, we propose a molecular pathway centered on the 'actin cytoskeleton-26S proteasome-YUC8-auxin' axis that controls auxin levels. Our findings shed light on a new pathway through which plants regulate auxin synthesis. Moreover, this study illuminates a newfound role of the actin cytoskeleton in regulating plant growth and development, particularly through its involvement in maintaining protein homeostasis via the 26S proteasome.

Association between physical activity and thyroid function in American adults: a survey from the NHANES database.

OBJECTIVE: Physical activity (PA) is closely related to our lives, and the effects of PA on thyroid function have not been elucidated. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2012, we included 5877 participants and analyzed the associations of thyroid function with weekly physical activity (PAM, expressed in metabolic equivalents of task) and physical activity time (PAT) in American adults. Univariate and multivariate logistic analyses were used to demonstrate the associations of PAM and PAT with the primary outcome. Linear regression analysis was performed to determine the associations between thyroid biochemical indicators/diseases and PAM/PAT. RESULTS: Our study revealed noticeable sex differences in daily PA among the participants. The odds ratio of the fourth versus the first quartile of PAM was 3.07 (confidence interval, CI [1.24, 7.58], p = 0.02) for overt hypothyroidism, 3.25 (CI [1.12, 9.45], p = 0.03) for subclinical hyperthyroidism in adult men. PAT in the range of 633-1520 min/week was found to be associated with the occurrence of subclinical hyperthyroidism [p < 0.001, OR (95% CI) = 5.89 (1.85, 18.80)], PAT of the range of > 1520 min/week was found to be associated with the occurrence of overt hypothyroidism [p < 0.001, OR (95% CI) = 8.70 (2.80, 27.07)] and autoimmune thyroiditis (AIT) [p = 0.03, OR (95% CI) = 1.42 (1.03, 1.97)] in adult men. When PAM < 5000 MET*minutes/week or PAT < 1000 min/week, RCS showed an L-shaped curve for TSH and an inverted U-shaped curve for FT4. The changes in FT3 and TT3 in men were linearly positively correlated with PAM and PAT, while TT4 is linearly negatively correlated. CONCLUSION: The amount of daily physical activity of American adults is strongly associated with changes in thyroid function, including thyroid hormone levels and thyroid diseases. Thyroid hormone levels were varied to a certain extent with changes in PAM and PAT.

Association between serum ß-oestradiol and health-related quality of life in postmenopausal women with degenerative lumbar scoliosis.

OBJECTIVES: Degenerative lumbar scoliosis (DLS) is an age-related spinal disease. It is an important cause of low back pain, lower limb pain and intermittent claudication, which seriously affects the quality of life of middle-aged and elderly people. DESIGN: This article aims to study the changes in serum oestrogen levels in postmenopausal women with DLS and its relationship. PATIENTS: One hundred and sixty-eight postmenopausal women diagnosed with DLS (DLS group) and 140 healthy postmenopausal women (control group) were recruited. MEASUREMENTS: Lumbar spinal bone mineral density (LSBMD) was measured by dual-energy X-ray absorptiometry and a chemiluminescence immunoassay analyser was used to detect serum ß-oestradiol (E2) levels. The severity of lower back pain was assessed by the visual analogue scale score and dysfunction was evaluated by Oswestry Disability Index (ODI). The quality of life was evaluated by Medical Outcomes Study 36-item Short Form Health Survey (SF-36). Diagnostic efficiency was evaluated by the receiver-operating characteristics curve (ROC). RESULTS: LSBMD and the level of E2 in the serum in DLS patients were significantly reduced when compared with the control group. The levels of E2 in the serum of postmenopausal women are reliable for predicting DLS revealed by ROC (p < .001). Serum E2 levels were negatively correlated with Cobb angle, VAS and ODI and were positively correlated with LSBMD and SF-36 scores. CONCLUSIONS: In postmenopausal women, serum E2 levels in DLS patients are significantly reduced and low levels of E2 are associated with lower bone density and poorer quality of life.

Optomechanically-induced nonreciprocal conversion between microwave and optical photons.

We theoretically propose a scheme of the nonreciprocal conversion device between photons of two arbitrary frequencies in a hybrid cavity optomechanical system, where two optical cavities and two microwave cavities are coupled to two different mechanical resonators via radiation pressure. Two mechanical resonators are coupled together via the Coulomb interaction. We study the nonreciprocal conversions between both the same and different types of frequency photons. The device is based on multichannel quantum interference to break the time-reversal symmetry. Our results show the perfect nonreciprocity conditions. By adjusting the Coulomb interaction and the phase differences, we find that the nonreciprocity can be modulated and even transformed into reciprocity. These results provide new insight into the design of nonreciprocal devices, including isolators, circulators, and routers in quantum information processing and quantum networks.

HLA-DR+ mucosal-associated invariant T cells predict poor prognosis in patients with sepsis: A prospective observational study.

Mucosal-associated invariant T (MAIT) cells are important in antibacterial immune responses; however, during sepsis, they are few in number and exhibit highly activated phenotypes. The relationship between MAIT cells in peripheral blood and the prognosis of sepsis is not well understood. Thus, this study aimed to examine the levels and phenotypes of MAIT cells in early sepsis, evaluate their clinical relevance, and investigate their association with patient prognosis. This prospective observational study enrolled 72 septic patients defined according to the Sepsis 3.0 criteria and 21 healthy controls matched for age and sex. Their peripheral blood samples were used to assay the expression of immune activation (CD69 and HLA-DR) and immune checkpoint (PD-1 and PD-L1) markers on MAIT cells. The systemic inflammatory response syndrome, acute physiology and chronic health evaluation (APACHE) II, and sequential organ failure assessment scores were recorded. Subsequently, the association between MAIT cell characteristics and clinical indicators was assessed using Spearman's rank correlation analysis, and binary logistic regression analysis with a forward stepwise approach assessed independent risk factors for 28-day mortality. We noted a decrease in the percentage of MAIT cells in the patients' peripheral blood, which exhibited an activated phenotype. Besides, HLA-DR+ MAIT cell percentage and the APACHE II score were independently associated with the 28-day mortality and, in combination, were the best indicators of mortality. Thus, the percentage of HLA-DR+ MAIT cells in early sepsis serves as a novel prognostic biomarker for predicting mortality and improves the predictive capacity of the APACHE II score.

Inhibition of Phosphoinositide 3-Kinase Gamma Protects Endothelial Cells via the Akt Signaling Pathway in Sepsis-Induced Acute Kidney Injury.

INTRODUCTION: Sepsis is a primary cause of death in critically ill patients and is characterized by multiple organ dysfunction, including sepsis-induced acute kidney injury (AKI), which contributes to high mortality in sepsis. However, its pathophysiological mechanisms remain unclear. The kidney has one of the richest and most diversified endothelial cell populations in the body. This study was designed to investigate the effects of endothelial dysfunction in sepsis-induced AKI and explore possible intervention measures to offer new insight into the pathogenesis and treatment of sepsis-induced AKI. METHODS: The circulating levels of endothelial adhesion molecules were detected in patients with sepsis and healthy controls to observe the role of endothelial damage in sepsis and sepsis-induced AKI. A murine sepsis model induced by cecal ligation and perforation was pretreated with a phosphoinositide 3-kinase gamma (PI3Kγ) inhibitor (CZC24832), and survival, kidney damage, and renal endothelial injury were assessed by pathological examination, immunohistochemistry, quantitative polymerase chain reaction, and Western blotting. Lipopolysaccharides and CZC24832 were administered to human umbilical vein endothelial cells in vitro, and endothelial cell function and the expression of adhesion molecules were evaluated. RESULTS: Endothelial damage was more serious in sepsis-induced AKI than that in non-AKI, and the inhibition of PI3Kγ alleviates renal endothelial injury in a murine sepsis model, protecting endothelial cell function and repairing endothelial cell injury through the Akt signaling pathway. CONCLUSIONS: In this study, endothelial cell dysfunction plays an important role in sepsis-induced AKI, and the inhibition of PI3Kγ alleviates endothelial cell injury in sepsis-induced AKI through the PI3Kγ/Akt pathway, providing novel targets for treating sepsis and related kidney injury.

Deep tillage reduces the dependence of tobacco (Nicotiana tabacum L.) on arbuscular mycorrhizal fungi and promotes the growth of tobacco in dryland farming.

The traditional shallow tillage method reduces soil quality and affects the efficiency of agricultural production. Using conventional rotary tillage (12 cm) as the control, Yunyan 87 as the test variety, and paddy soil as the test site, we studied the effects of deep tillage (subsoiling 30 cm) on soil nutrients, arbuscular mycorrhizal fungi (AMF), and tobacco (Nicotiana tabacum L.) growth. The results showed that deep tillage increased the content of organic carbon, available phosphorus (AP), and available potassium (AK) in the 20-40 cm soil layer. The AMF community was also affected by deep tillage. Glomus, the dominant genus in both groups, increased significantly in soil after deep tillage. The AMF colonization rate was lower than that of conventional rotary tillage. Deep tillage was beneficial for tobacco growth in the middle and late stages. The root growth and nutrient content of the tobacco plants increased. Deep tillage significantly improved the output value of tobacco plants. Deep tillage is conducive to improving soil fertility, promoting the vigorous growth of roots, reducing the dependence of tobacco on AMF, and promoting the high quality and yield of tobacco in the drylands of Hunan.

Sites and Causes of Infection in Patients with Sepsis-Associated Liver Dysfunction: A Population Study from the Medical Information Mart for Intensive Care III.

BACKGROUND Little is known about the relationship between the site of infection, type of pathogen, and the occurrence of sepsis-associated liver dysfunction (SALD). This population study aimed to identify the sites and types of infection in SALD patients. MATERIAL AND METHODS We conducted a retrospective observational study using the Medical Information Mart for Intensive Care III. Patients with sepsis were divided into a SALD group and a control group. We evaluated the effect of the location of culture-positive specimens and the distribution of pathogens on the occurrence of SALD and then compared the clinical outcomes. RESULTS A total of 14 596 admissions were included, and the incidence of SALD was 11.96%. Positive bile culture (odds ratio [OR] 7.450, P<0.001), peritoneal fluid culture (OR 3.616, P<0.001), and blood culture (OR 1.957, P<0.001) were correlated with the occurrence of SALD. Infection with Enterococcus faecium (OR 3.065, P<0.001), Bacteroides fragilis (OR 2.061, P<0.001), Klebsiella oxytoca (OR 2.066, P<0.001), Enterobacter aerogenes (OR 1.92, P=0.001), and Aspergillus fumigatus (OR 2.144, P=0.001) were correlated with the occurrence of SALD. The Intensive Care Unit mortality and hospital mortality were higher in the SALD group than in the control group (24.7% vs 9.0%, P<0.001; 34.2% vs 13.8%, P<0.001, respectively). CONCLUSIONS SALD should be considered for patients with sepsis whose infection site is the biliary system, abdominal cavity, or blood and the pathogen is Enterococcus faecium, B. fragilis, K. oxytoca, Enterobacter aerogenes, or A. fumigatus. When SALD occurs in patients with sepsis, the above infection sites and pathogens should be considered first.

Extracorporeal Membrane Oxygenation as a Bridge between Transfer and Perioperative Periods in Refractory Cardiogenic Shock Secondary to a Large Left Atrial Myxoma.

A 63-year-old man was admitted for acute left heart failure after doing farm work. He rapidly developed refractory cardiogenic shock due to a large left atrial myxoma which was found by bedside echocardiography. Venoarteriovenous extracorporeal membrane oxygenation (ECMO) was performed immediately, and the patient was transferred for further surgery with a good outcome. Therefore, timely echocardiographic evaluation and surgical removal of myxomas is recommended, and ECMO could be used as a bridge between the transfer and perioperative period.

S-Acylation controls functional coupling of BK channel pore-forming α-subunits and ß1-subunits.

The properties and physiological function of pore-forming α-subunits of large conductance calcium- and voltage-activated potassium (BK) channels are potently modified by their functional coupling with regulatory subunits in many tissues. However, mechanisms that might control functional coupling are very poorly understood. Here we show that S-acylation, a dynamic post-translational lipid modification of proteins, of the intracellular S0-S1 loop of the BK channel pore-forming α-subunit controls functional coupling to regulatory ß1-subunits. In HEK293 cells, α-subunits that cannot be S-acylated show attenuated cell surface expression, but expression was restored by co-expression with the ß1-subunit. However, we also found that nonacylation of the S0-S1 loop reduces functional coupling between α- and ß1-subunits by attenuating the ß1-subunit-induced left shift in the voltage for half-maximal activation. In mouse vascular smooth muscle cells expressing both α- and ß1-subunits, BK channel α-subunits were endogenously S-acylated. We further noted that S-acylation is significantly reduced in mice with a genetic deletion of the palmitoyl acyltransferase (Zdhhc23) that controls S-acylation of the S0-S1 loop. Genetic deletion of Zdhhc23 or broad-spectrum pharmacological inhibition of S-acylation attenuated endogenous BK channel currents independently of changes in cell surface expression of the α-subunit. We conclude that functional effects of S-acylation on BK channels depend on the presence of ß1-subunits. In the absence of ß1-subunits, S-acylation promotes cell surface expression, whereas in its presence, S-acylation controls functional coupling. S-Acylation thus provides a mechanism that dynamically regulates the functional coupling with ß1-subunits, enabling an additional level of conditional, cell-specific control of ion-channel physiology.

Engineering Trienoic Fatty Acids into Cottonseed Oil Improves Low-Temperature Seed Germination, Plant Photosynthesis and Cotton Fiber Quality.

Alpha-linolenic acid (ALA, 18:3Δ9,12,15) and γ-linolenic acid \ (GLA, 18:3Δ6,9,12) are important trienoic fatty acids, which are beneficial for human health in their own right, or as precursors for the biosynthesis of long-chain polyunsaturated fatty acids. ALA and GLA in seed oil are synthesized from linoleic acid (LA, 18:2Δ9,12) by the microsomal ω-3 fatty acid desaturase (FAD3) and Δ6 desaturase (D6D), respectively. Cotton (Gossypium hirsutum L.) seed oil composition was modified by transforming with an FAD3 gene from Brassica napus and a D6D gene from Echium plantagineum, resulting in approximately 30% ALA and 20% GLA, respectively. The total oil content in transgenic seeds remained unaltered relative to parental seeds. Despite the use of a seed-specific promoter for transgene expression, low levels of GLA and increased levels of ALA were found in non-seed cotton tissues. At low temperature, the germinating cottonseeds containing the linolenic acid isomers elongated faster than the untransformed controls. ALA-producing lines also showed higher photosynthetic rates at cooler temperature and better fiber quality compared to both untransformed controls and GLA-producing lines. The oxidative stability of the novel cottonseed oils was assessed, providing guidance for potential food, pharmaceutical and industrial applications of these oils.

MiR-203 regulates estrogen receptor α and cartilage degradation in IL-1ß-stimulated chondrocytes.

INTRODUCTION: Estrogen receptor α (ERα) plays important roles in the etiology of osteoarthritis (OA), in which cartilage degradation and cellular inflammation are involved. MiR-203 is reported to direct target ERα, but its roles in chondrocytes remain uncovered. METHODS: In this study, ELISA showed that the level of estrogen hormone in the serum of postmenopausal OA patients was significantly lower than the one in patients without OA. RT-PCR revealed that the expression level of miR-203 was significantly up-regulated in the OA patients. Furthermore, western blotting demonstrated the lower expression levels of aggrecan, Col2A1, and ERα in the isolated articular cartilage tissues of OA patients. To decipher the association between ERα and miR-203 in the pathogenesis of OA, IL-1ß stimulated cultured chondrocyte cell model was established to measure the cell viability, cellular inflammation, cell injury, as well as cartilage degradation with miR-203 inhibitor and ERα. RESULTS: The results showed that IL-1ß stimulation induced the expression of miR-203, which promoted cellular inflammation and cell injury, and caused down-regulation of aggrecan and Col2A1. Luciferase assay indicated the direct binding between miR-203 and ERα, and ERα-specific SiRNA inversed the protective role of miR-203 inhibitor in the progression of OA in the cell system. CONCLUSIONS: MiR-203 is critical in the onset and progression of OA, at least in part, caused by estrogen deficiency and ERα instability in OA patients, providing a novel therapeutic target for the treatment of OA.

Association of HLA-DQA1 gene polymorphisms with the risk of children primary nephrotic syndrome in Chinese population.

BACKGROUND: The association between gene polymorphisms and the risk of primary nephrotic syndrome (PNS) is uncovering recently. This study aims to investigate the relationship between single nucleotide polymorphisms (SNPs) on HLA-DQA1 gene and the risk of PNS. METHODS: In this study, we genotyped eight single nucleotide polymorphisms (SNPs) in the HLA-DQA1 gene in 501 PNS patients and 532 healthy people in Chinese population. Then we analyzed associations of these SNPs with the clinical features in primary nephrotic syndrome of children in Chinese population. RESULTS: Significant associations with PNS were found on missense SNP rs1129740 (GG vs AA, odds ratio (OR) = 1.987, 95% confidence interval (CI) = 1.468-2.652, P = 0.00177049) and rs1047992 (AA vs GG, OR = 1.857, 95% CI = 1.325-2.391, P = 1.1073E-10) of the HLA-DQA1 gene. CONCLUSIONS: This work suggests SNPs of HLA-DQA1 are risk factors for PNS in Chinese population, which implies roles of immune response in the pathogenesis of PNS.

Interleukin-7 gene polymorphism rs766736182 associates with the risk of asthma in children.

BACKGROUND: Recently studies uncovered associations between polymorphisms of interleukin genes and the risk of asthma. However, the relationship between polymorphisms of interleukin-7 gene and the risk of children asthma has not been discovered yet. This study aims to investigate the relationship between single nucleotide polymorphisms (SNPs) on interleukin-7 gene and the risk of children asthma. METHODS: We genotyped eight SNPs of interleukin-7 gene in blood samples from 437 asthma patients and 489 healthy controls to analyze potential associations of these SNPs with the risk of asthma in children. RESULTS: A missense SNP rs766736182 (odds ratio (OR) = 2.185, 95% confidence interval (CI) = 1.561-2.252, P-value = 8.69468E-19) of the interleukin-7 gene is associated with the risk of children asthma. CONCLUSIONS: This study reveals that SNP rs766736182 of interleukin-7 is the risk factor for children asthma and implies potential role of immune system in the pathogenesis of children asthma.

Analysis of the clinical diagnosis data of four experimental detection methods for pediatric syphilis.

BACKGROUND: The aim of this study was to analyze the clinical testing data of syphilis suspected children, to give more comprehensive detection information and offer experimental basis for the clinical diagnosis of syphilis. METHODS: From April 2010 to December 2012, 141 suspected syphilis children, 0-3 years old in XuZhou Children's Hospital were selected and divided into two groups: infants group (0-1 years old, 119 cases) and children group (1-3 years old, 22 cases). Blood samples were collected from these children and following experimental detection methods were used: the rapid plasma reagin (RPR) test, the colloidal gold test (SYP), the enzyme-linked immuno-sorbent assay (ELISA) and the Treponema pallidum particle agglutination (TPPA) test. The relevant experimental data were analyzed by SPSS 13.0 software. RESULTS: The positive rate of ELISA was the highest, RPR was the lowest; the positive rate of SYP and TPPA were higher than RPR, the positive rate of SYP and TPPA were lower than ELISA, and the differences were statistically significant. Among the 86 false positives, the rate for ELISA was the highest, and no TPPA false positive was found. False positive were higher in the children group than the infant group. CONCLUSIONS: High false positive rate of ELISA could be caused by hemolysis. RPR had low sensitivity in suspected syphilis neonates, and SYP was suitable for emergency treatment. TPPA was fit for the diagnosis of syphilis. Thus a combination of all these methods would be the best choice to cure syphilis infection in children. Final diagnosis can only be confirmed after periodically reexamining samples of suspected syphilis children.

The downregulation of miR-3173 in B-cell acute lymphoblastic leukaemia promotes cell invasion via PTK2.

MicroRNAs are important regulators of the pathogenesis of B-cell acute lymphoblastic leukaemia (B-ALL). In this study, we identified miR-3173 and its predicted target gene PTK2 were correspondingly differentially expressed in B-ALL patients. In B-ALL cell lines, CCK-8 proliferation assay revealed that miR-3173 could inhibit the cell proliferation. Moreover, transwell assay revealed that miR-3173 could also inhibit cell migration and invasion in B-ALL cell lines. Luciferase assays revealed that miR-3173 directly bound to the 3'untranslated region of PTK2, and western blotting showed that miR-3173 suppressed the expression of PTK2 at the protein level. Generally, this study indicates that miR-3173 negatively regulates PTK2 and inhibits proliferation and invasion of B-ALL cell lines. Thus, miR-3173 may represent a potential therapeutic molecule for B-ALL intervention.

Substrate recognition by the cell surface palmitoyl transferase DHHC5.

The cardiac phosphoprotein phospholemman (PLM) regulates the cardiac sodium pump, activating the pump when phosphorylated and inhibiting it when palmitoylated. Protein palmitoylation, the reversible attachment of a 16 carbon fatty acid to a cysteine thiol, is catalyzed by the Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferases. The cell surface palmitoyl acyltransferase DHHC5 regulates a growing number of cellular processes, but relatively few DHHC5 substrates have been identified to date. We examined the expression of DHHC isoforms in ventricular muscle and report that DHHC5 is among the most abundantly expressed DHHCs in the heart and localizes to caveolin-enriched cell surface microdomains. DHHC5 coimmunoprecipitates with PLM in ventricular myocytes and transiently transfected cells. Overexpression and silencing experiments indicate that DHHC5 palmitoylates PLM at two juxtamembrane cysteines, C40 and C42, although C40 is the principal palmitoylation site. PLM interaction with and palmitoylation by DHHC5 is independent of the DHHC5 PSD-95/Discs-large/ZO-1 homology (PDZ) binding motif, but requires a ∼ 120 amino acid region of the DHHC5 intracellular C-tail immediately after the fourth transmembrane domain. PLM C42A but not PLM C40A inhibits the Na pump, indicating PLM palmitoylation at C40 but not C42 is required for PLM-mediated inhibition of pump activity. In conclusion, we demonstrate an enzyme-substrate relationship for DHHC5 and PLM and describe a means of substrate recruitment not hitherto described for this acyltransferase. We propose that PLM palmitoylation by DHHC5 promotes phospholipid interactions that inhibit the Na pump.

Palmitoylation of the ß4-subunit regulates surface expression of large conductance calcium-activated potassium channel splice variants.

Regulatory ß-subunits of large conductance calcium- and voltage-activated potassium (BK) channels play an important role in generating functional diversity and control of cell surface expression of the pore forming α-subunits. However, in contrast to α-subunits, the role of reversible post-translational modification of intracellular residues on ß-subunit function is largely unknown. Here we demonstrate that the human ß4-subunit is S-acylated (palmitoylated) on a juxtamembrane cysteine residue (Cys-193) in the intracellular C terminus of the regulatory ß-subunit. ß4-Subunit palmitoylation is important for cell surface expression and endoplasmic reticulum (ER) exit of the ß4-subunit alone. Importantly, palmitoylated ß4-subunits promote the ER exit and surface expression of the pore-forming α-subunit, whereas ß4-subunits that cannot be palmitoylated do not increase ER exit or surface expression of α-subunits. Strikingly, however, this palmitoylation- and ß4-dependent enhancement of α-subunit surface expression was only observed in α-subunits that contain a putative trafficking motif (… REVEDEC) at the very C terminus of the α-subunit. Engineering this trafficking motif to other C-terminal α-subunit splice variants results in α-subunits with reduced surface expression that can be rescued by palmitoylated, but not depalmitoylated, ß4-subunits. Our data reveal a novel mechanism by which palmitoylated ß4-subunit controls surface expression of BK channels through masking of a trafficking motif in the C terminus of the α-subunit. As palmitoylation is dynamic, this mechanism would allow precise control of specific splice variants to the cell surface. Our data provide new insights into how complex interplay between the repertoire of post-transcriptional and post-translational mechanisms controls cell surface expression of BK channels.

The relationship between thyroid peroxidase antibody and differentiated thyroid cancer: a systematic review and meta-analysis.

Background: Thyroglobulin antibody (TgAb) has been found to be associated with the occurrence and development of differentiated thyroid cancer (DTC) for several years, but there is still controversy over whether thyroid peroxidase antibody (TPOAb) is related to differentiated thyroid cancer. Methods: We scrutinized relevant studies published up to July 2023 across four major databases including PubMed, Embase, Cochrane Library, and Web of Science, to examine the association between TPOAb and DTC. Clinical outcome measures include the incidence of DTC, tumor size, extrathyroidal invasion, lymph node metastasis, multifocality, recurrence and bilaterality. Results: 12 original studies were included, involving a total of 20,330 subjects. Our analysis of the included studies revealed that TPOAb+ individuals exhibited a higher risk of developing DTC (OR=1.57 [95% CI: 1.00-2.45], p=0.049) than TPOAb- individuals. Furthermore, TPOAb+ DTC patients were more prone to present with bilateral (OR=1.40 [95% CI: 1.21-1.62], p<0.00001) and multifocal (OR=1.40 [95% CI: 1.23-1.60], p<0.00001) tumors than TPOAb- patients. Sensitivity analysis indicated a high sensitivity for these three findings. No significant differences in the risk of extrathyroidal extension and lymph node metastasis, recurrence rate, tumor size, were observed between TPOAb+ and TPOAb- DTC patients. Conclusion: The presence of TPOAb is correlated with an increase prevalence of DTC. However, its effectiveness as a prognostic marker for DTC patients warrants further investigation. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023448824.

Gene signature developed based on programmed cell death to predict the therapeutic response and prognosis for liver hepatocellular carcinoma.

Background: The prognosis and therapeutic response of patients with liver hepatocellular carcinoma (LIHC) can be predicted based on programmed cell death (PCD) as PCD plays a crucial role during tumor progression. We developed a PCD-related gene signature to evaluate the therapeutic response and prognosis for patients with LIHC. Methods: Molecular subtypes of LIHC were classified using ConsensusClusterPlus according to the gene biomarkers related to PCD. To predict the prognosis of high- and low-risk LIHC patients, a risk model was established by LASSO regression analysis based on the prognostic genes. Functional enrichment analysis was conducted using clusterProfiler package, and relative abundance of immune cells was quantified applying CIBERSORT package. Finally, to determine drug sensitivity, oncoPredict package was employed. Results: PCD was correlated with the clinicopathologic features of LIHC. Then, we defined four molecular subtypes (C1-C4) of LIHC using PCD-related prognostic genes. Specifically, subtype C1 had the worst prognosis with enriched T cells regulatory (Tregs) and Macrophage_M0 and higher expression of T cell exhaustion markers, meanwhile, C1 also had a relatively higher TIDE score and metastasis potential. A risk model was established using 5 prognostic genes. High-risk patients tended to have higher expression of T cell exhaustion markers and TIDE score and unfavorable outcomes, and they were more sensitive to small molecule drug 5.Fluorouracil. Conclusion: A PCD-related gene signature was developed and verified to be able to accurately predict the prognosis and drug sensitivity of LIHC patients.