Lecithin-cholesterol acyltransferase is a potential tumor suppressor and predictive marker for hepatocellular carcinoma metastasis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide, and metastasis is the main cause of early recurrence and poor prognosis. However, the mechanism of metastasis remains poorly understood. AIM: To determine the possible mechanism affecting HCC metastasis and provide a possible theoretical basis for HCC treatment. METHODS: The candidate molecule lecithin-cholesterol acyltransferase (LCAT) was screened by gene microarray and bioinformatics analysis. The expression levels of LCAT in clinical cohort samples was detected by quantitative real-time polymerase chain reaction and western blotting. The proliferation, migration, invasion and tumor-forming ability were measured by Cell Counting Kit-8, Transwell cell migration, invasion, and clonal formation assays, respectively. Tumor formation was detected in nude mice after LCAT gene knockdown or overexpression. The immunohistochemistry for Ki67, E-cadherin, N-cadherin, matrix metalloproteinase 9 and vascular endothelial growth factor were performed in liver tissues to assess the effect of LCAT on HCC. Gene set enrichment analysis (GSEA) on various gene signatures were analyzed with GSEA version 3.0. Three machine-learning algorithms (random forest, support vector machine, and logistic regression) were applied to predict HCC metastasis in The Cancer Genome Atlas and GEO databases. RESULTS: LCAT was identified as a novel gene relating to HCC metastasis by using gene microarray in HCC tissues. LCAT was significantly downregulated in HCC tissues, which is correlated with recurrence, metastasis and poor outcome of HCC patients. Functional analysis indicated that LCAT inhibited HCC cell proliferation, migration and invasion both in vitro and in vivo. Clinicopathological data showed that LCAT was negatively associated with HCC size and metastasis (HCC size ≤ 3 cm vs 3-9 cm, P < 0.001; 3-9 cm vs > 9 cm, P < 0.01; metastatic-free HCC vs extrahepatic metastatic HCC, P < 0.05). LCAT suppressed the growth, migration and invasion of HCC cell lines via PI3K/AKT/mTOR signaling. Our results indicated that the logistic regression model based on LCAT, TNM stage and the serum level of α-fetoprotein in HCC patients could effectively predict high metastatic risk HCC patients. CONCLUSION: LCAT is downregulated at translational and protein levels in HCC and might inhibit tumor metastasis via attenuating PI3K/AKT/mTOR signaling. LCAT is a prognostic marker and potential therapeutic target for HCC.

High levels of mitochondrial dynamics, autophagy, and apoptosis contribute to stable testicular status in hibernating Daurian ground squirrels.

Daurian ground squirrels (Spermophilus dauricus) experience various stress states during winter hibernation, but the impact on testicular function remains unclear. This study focused on the effects of changes in testicular autophagy, apoptosis, and mitochondrial homeostasis signaling pathways at various stages on the testes of Daurian ground squirrels. Results indicated that: (1) During winter hibernation, there was a significant increase in seminiferous tubule diameter and seminiferous epithelium thickness compared to summer. Spermatogonia number and testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were higher during inter-bout arousal, suggesting that the testes remained stable during hibernation. (2) An increased number of mitochondria with intact morphology were observed during hibernation, indicating that mitochondrial homeostasis may contribute to testicular stability. (3) DNA fragmentation was evident in the testes during the hibernation and inter-bout arousal stages, with the highest level of caspase3 enzyme activity detected during inter-bout arousal, together with elevated levels of Bax/Bcl-2 and Lc3 II/Lc3 I, indicating an up-regulation of apoptosis and autophagy signaling pathways during hibernation. (4) The abundance of DRP1, MFF, OPA1, and MFN2 proteins was increased, suggesting an up-regulation of mitochondrial dynamics-related pathways. Overall, testicular autophagy, apoptosis, and mitochondrial homeostasis-related signaling pathways were notably active in the extreme winter environment. The well-maintained mitochondrial morphology may favor the production of reproductive hormones and support stable testicular morphology.

Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma.

Carnosine dipeptidase 1 (CNDP1), an enzyme integral to the hydrolysis of dipeptides containing histidine, plays an indispensable role in myriad physiological processes, including hydrolysis of proteins, maturation of specific biochemical functionalities within proteins, tissue regeneration, and regulation of cell cycle. However, the implications of CNDP1 in oncogenesis and its prognostic value are not yet fully elucidated. Initially, we procured the GSE40367 dataset from the Gene Expression Omnibus and established a protein-protein interaction network. Thereafter, we conducted functional and pathway enrichment analyses utilizing GO, KEGG, and GSEA. Moreover, we undertook an association analysis concerning the expression of CNDP1 with immune infiltration, along with survival analysis across various cancers and specifically in hepatocellular carcinoma (HCC). Our study uncovered a total of 2,248 differentially expressed genes, with a down-regulation of CNDP1 in HCC and other cancers. Our explorations into the relationship between CNDP1 and immune infiltration disclosed a negative correlation between CNDP1 expression and the presence of immune cells in HCC. Survival analyses revealed that diminished expression of CNDP1 correlates with an adverse prognosis in HCC and several other types of cancer. These observations intimate that CNDP1 holds promise as a novel prognostic biomarker for both pan-cancer and HCC.

Nomogram for preoperative estimation of microvascular invasion risk in hepatocellular carcinoma.

Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167-7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922-41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374-12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780-10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771-0.894) and 0.821 (95 % CI 0.720-0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively.

High-Pressure Induced Continuous Structural Evolution of Kagome Antiferromagnet MgMn3(OH)6Cl2: A Structural Analogue to Quantum Spin Liquid Herbertsmithite.

MgMn3(OH)6Cl2 serves readily as the classical Heisenberg kagome antiferromagnet lattice spin frustration material, due to its similarity to herbertsmithite in composition and crystal structure. In this work, nanosheets of MgMn3(OH)6Cl2 are synthesized through a solid-phase reaction. Low-temperature magnetic measurements revealed two antiferromagnetic transitions, occurring at ∼8 and 55 K, respectively. Utilizing high-pressure synchrotron radiation X-ray diffraction techniques, the topological structural evolution of MgMn3(OH)6Cl2 under pressures up to 24.8 GPa was investigated. The sample undergoes a second-order structural phase transition from the rhombohedral phase to the monoclinic phase at pressures exceeding 7.8 GPa. Accompanying the disappearance of the Fano-like line shape in the high-pressure Raman spectra were the emergence of new Raman active modes and discontinuities in the variations of Raman shifts in the high-frequency region. The phase transition to a structure with lower symmetry was attributed to the pressure-induced enhancement of cooperative Jahn-Teller distortion, which is caused by the mutual substitution of Mn2+ ions from the kagome layer and Mg2+ ions from the triangular interlayer. High-pressure ultraviolet-visible absorption measurements support the structural evolution. This research provides a robust experimental approach and physical insights for further exploration of classical geometrical frustration materials with kagome lattice.

The Relationship between Viral Replication and the Severity of Hepatic Necroinflammatory Damage Changed before HBeAg Loss in Patients with Chronic Hepatitis B Virus Infection.

Background and Aims: Disease progression of chronic hepatitis B virus (HBV) infection is driven by the interactions between viral replication and the host immune response against the infection. This study aimed to clarify the relationship between HBV replication and hepatic inflammation during disease progression. Methods: Two cross-sectional, one validation cohort, and meta-analyses were used to explore the relationship between HBV replication and liver inflammation. Spearman analysis, multiple linear regression, and logistic regression were used to explore the relationship between variables. Results: In the cross-sectional cohorts A and B including 1,350 chronic hepatitis B patients, Spearman analysis revealed a negative relationship between HBV replication (such as HBV DNA) and liver inflammation (such as ALT) in HBeAg-positive patients with higher HBV DNA >2×106 IU/mL (rho=-0.160 and -0.042) which turned to be positive in HBeAg-positive patients with HBV DNA ≤2×106 IU/mL (rho=0.278 and 0.260) and HBeAg-negative patients (rho=0.450 and 0.363). After adjustment for sex, age, and anti-HBe, results from logistic regression and multiple linear regression showed the opposite relationship still existed in HBeAg-positive patients with different DNA levels; the opposite relationship in HBeAg-positive patients with different DNA levels was validated in a third cohort; the opposite relationship in patients with different HBeAg status was partially confirmed by meta-analysis (overall R: -0.004 vs 0.481). Conclusions: These results suggested a negative relationship between viral replication and liver inflammation in HBeAg-positive patients with high HBV DNA, which changed to a positive relationship for those HBeAg-positive patients with DNA less than 2×106 IU/mL and HBeAg-negative patients.

Increased antibody titers but induced T cell AICD and apoptosis response in COVID-19 convalescents by inactivated vaccine booster.

It is urgently needed to evaluate the necessity and benefits of booster vaccination against the coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) Omicron to facilitate clinical decision-making for 2019 coronavirus disease (COVID-19) convalescents. We conducted a multicenter, prospective clinical trial (registration number: ChiCTR2100045810) in the first patients with COVID-19 from 28 January 2020 to 20 February 2020 to assess the long-term durability of neutralizing antibodies against live Omicron BA.5 and further assess the efficiency and safety of CoronaVac in the convalescent group. A total of 96 COVID-19 convalescents were enrolled in this study. Neutralizing antibody titers in convalescents were significantly reduced in 9-10 months. A dose-refreshing vaccination in 28 convalescents with an antibody titer below 96 significantly induced neutralizing antibodies against live Omicron by 4.84-fold. Meanwhile, the abundance of naive T cells increased dramatically, and TEMRA and TEM cells gradually decreased after vaccination. Activation-induced cell death and apoptosis-related genes were significantly elevated after vaccination in all T-cell subtypes. One-dose booster vaccination was effective in inducing a robust antibody response against SARS-CoV-2 Omicron in COVID-19 convalescents with low antibody titers. However, vaccine-mediated T-cell consumption and regeneration patterns may be detrimental to the antiviral response.IMPORTANCEThe globally dominant coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) Omicron variant raises the possibility of repeat infections among 2019 coronavirus disease (COVID-19) convalescents with low neutralizing antibody titers. The importance of this multicenter study lies in its evaluation of the long-term durability of neutralizing antibodies in COVID-19 convalescents and the efficacy of a booster vaccination against the live Omicron. The findings suggest that a one-dose booster vaccination is effective in inducing a robust antibody response against SARS-CoV-2 Omicron in convalescents with low antibody titers. However, the study also highlights the potential detrimental effects on the antiviral response due to vaccine-mediated T-cell consumption and regeneration patterns. These results are crucial for facilitating clinical decision-making for COVID-19 convalescents and informing public health policies regarding booster vaccinations.

Fabrication of polyamide nanofiltration membrane with tannic acid/poly(sodium 4-styrenesulfonate) network-like interlayer for enhanced desalination performance.

The traditional polyamide composite nanofiltration membranes have high selectivity and low water permeance, so it is necessary to find strategies to raise the permeance. Herein, a novel polyamide nanofiltration membranes with high permeance were fabricated by coating a loose hydrophilic network-like interlayer, where tannic acid (TA) with pentapophenol arm structure binds to poly(4-styrenesulfonate) (PSS) polymer through hydrogen and ionic interactions. The effects of the network-like TA/PSS interlayer on surface morphology, surface hydrophobicity, and the interfacial polymerization mechanism were investigated. The outcomes demonstrated that the TA/PSS interlayer can offer a favorable environment for interfacial polymerization, enhance the hydrophilicity of the substrate membrane, and delay the release of piperazine (PIP). The optimized TFC-2 presents pure water flux of 22.7 ± 2.8 L m-2 h-1 bar-1, Na2SO4 rejection of 97.1 ± 0.5 %, and PA layer thickness of about 38.9 ± 2.5 nm. This provides new strategies for seeking to prepare simple interlayers to obtain high-performance nanofiltration membranes.

A fast and non-invasive artificial intelligence olfactory-like system that aids diagnosis of Parkinson's disease.

BACKGROUND AND PURPOSE: Several previous studies have shown that skin sebum analysis can be used to diagnose Parkinson's disease (PD). The aim of this study was to develop a portable artificial intelligence olfactory-like (AIO) system based on gas chromatographic analysis of the volatile organic compounds (VOCs) in patient sebum and explore its application value in the diagnosis of PD. METHODS: The skin VOCs from 121 PD patients and 129 healthy controls were analyzed using the AIO system and three classic machine learning models were established, including the gradient boosting decision tree (GBDT), random forest and extreme gradient boosting, to assist the diagnosis of PD and predict its severity. RESULTS: A 20-s time series of AIO system data were collected from each participant. The VOC peaks at a large number of time points roughly concentrated around 5-12 s were significantly higher in PD subjects. The gradient boosting decision tree model showed the best ability to differentiate PD from healthy controls, yielding a sensitivity of 83.33% and a specificity of 84.00%. However, the system failed to predict PD progression scored by Hoehn-Yahr stage. CONCLUSIONS: This study provides a fast, low-cost and non-invasive method to distinguish PD patients from healthy controls. Furthermore, our study also indicates abnormal sebaceous gland secretion in PD patients, providing new evidence for exploring the pathogenesis of PD.

Clinicopathological characteristics of 3 probable pediatric cases with acute severe hepatitis of unknown aetiology.

Background: Acute severe hepatitis with unknown aetiology in children (ASHep-UA) has become a global health alert. This article reported clinicopathological characteristics of 3 probable ASHep-UA cases. Methods: We respectively collected serological data and liver biopsies of 3 suspected cases of ASHep-UA. Neutralizing antibodies titer for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants were determined by virus neutralization test (VNT). Histological assessment, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for cytomegalovirus (CMV), Epstein-Barr virus (EBV), human adenoviruses (HAdV), adeno-associated virus (AAV2), human herpes virus type 6 (HHV-6) were performed to identify possible aetiologies. Results: Remarkable elevation of transaminase (median ALT level, 1100 IU/liter; median AST level, 500 IU/liter) were revealed with undetectable hepatitis A-E and non-hepatotropic virus in both sera and tissues. Weakness, jaundice, pale stools and splenomegaly were observed. Interestingly, two individuals had SARS-CoV-2 Omicron variants infection. Histologically, moderate or severe lobular necroinflammation, active interface hepatitis and portal inflammatory infiltrate with lymphocytic, plasma cells, neutrophils and eosinophilic cells were noted. Conclusions: The exact aetiology of ASHep-UA was still unknown. By reporting the 3 probable cases, we expect to enrich the clinical experience in diagnosis and treatment of ASHep-UA as well as the pathological characteristics.

Effects of vesicular stomatitis virus on anti-tumour immunity, growth of xenografts, and lung metastasis in mouse mammary carcinoma 4T1 cells tumor-bearing mice / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探究野生型水疱性口炎病毒印第安纳株（VSV-IN）对小鼠三阴性乳腺癌4T1细胞移植模型小鼠的免疫调节及肿瘤转移的影响。方法：VSV以MOI=1、MOI=10、MOI=100感染4T1细胞12、24、48 h后，CCK-8法检测4T1细胞死亡率，划痕愈合实验检测细胞迁移能力，qPCR检测细胞中E-cadherin、MMP-2、MMP-9 mRNA的表达。于雌性BALB/c小鼠脂肪垫接种1×106个/mL的4T1细胞0.1 mL，构建4T1细胞荷瘤小鼠模型，待小鼠肿瘤体积达200 mm3，分别向移植瘤内注射PBS、紫杉醇（TAX）（15 mg/kg）、VSV-IN（1×106 pfu/只），每周1次。给药4次后，处死小鼠、剥离完整移植瘤组织，测量肿瘤体积及质量，肺组织病理切片经H-E染色后观察肿瘤肺部转移结节，流式细胞术检测脾组织中T细胞亚群比例，ELISA法检测小鼠血清IL-6及TNF-α水平，利用GEPIA在线分析乳腺肿中迁移相关蛋白mRNA的表达，免疫组化法检测肿瘤中MMP-2、MMP-9与E-cadherin的表达，利用蛋白-蛋白对接技术预测VSV-IN的G蛋白、M蛋白与ERK2、E-cadherin的亲和力。结果：经MOI=10、100的VSV-IN处理48 h后，4T1细胞死亡率显著高于对照组（均P<0.01）；与对照组相比，VSV-IN组（MOI=10）细胞迁移率明显降低（P<0.01），MMP-9 mRNA的相对表达量明显降低（P<0.05）；与对照组小鼠相比，VSV-IN组移植瘤生长较对照组减缓且终点体积显著减小（P<0.05），VSV-IN组小鼠肺转移结节数量显著减少[（12.86±1.86） vs （24±3.67）个，P<0.01]，脾内CD4+ T、CD8+ T细胞比例显著升高（均P<0.05），血清TNF-α、IL-6含量显著升高（均P<0.01）；GEPIA分析发现在乳腺癌中E-cadherin、MMP-9表达水平均高于癌旁组织（P<0.05）；VSV-IN组小鼠肿瘤细胞内MMP-9表达明显低于对照组（P<0.05）；VSV-IN的G、M蛋白与ERK2的结合自由能分别为–11.7 kcal/mol、–6.4 kcal/mol。结论：野生型VSV-IN可抑制4T1细胞荷瘤小鼠的移植瘤生长及转移，这可能与其促进抗肿瘤免疫及调控迁移相关蛋白表达有关。

[Characteristics of the left heart structure and function in 86 term neonates with intrauterine growth restriction]. / 86ä¾‹å®«å† ç”Ÿé•¿å—é™è¶³æœˆæ–°ç”Ÿå„¿çš„å·¦å¿ƒç»“æž„åŠåŠŸèƒ½åˆ†æž.

OBJECTIVES: To study the left heart structure and functional characteristics of term neonates with intrauterine growth restriction (IUGR). METHODS: This study included 86 term neonates with IUGR admitted to the Neonatal Ward of Beijing Friendship Hospital, Capital Medical University from January 2019 to January 2022 as the IUGR group, as well as randomly selected 86 term neonates without IUGR born during the same period as the non-IUGR group. The clinical data and echocardiographic data were compared between the two groups. RESULTS: The analysis of left heart structure and function showed that compared with the non-IUGR group, the IUGR group had significantly lower left ventricular mass, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, end-diastolic interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic volume, left ventricular end-systolic volume, and stroke volume (P<0.05) and significantly higher ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness, proportion of neonates with a mitral peak E/A ratio of ≥1, and cardiac index (P<0.05). The Spearman correlation analysis suggested that stroke volume was positively correlated with birth weight and body surface area (rs=0.241 and 0.241 respectively; P<0.05) and that the ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness was negatively correlated with birth weight and body surface area (rs=-0.229 and -0.225 respectively; P<0.05). CONCLUSIONS: The left ventricular systolic function of neonates with IUGR is not significantly different from that of neonates without IUGR. However, the ventricular septum is thicker in neonates with IUGR. This change is negatively correlated with birth weight and body surface area. The left ventricular diastolic function may be impaired in neonates with IUGR.

Structural phase transformation of quantum spin liquid herbertsmithite via pressure induced enhancement of the cooperative Jahn-Teller effect and antisite disorder.

Herbertsmithite, Cu3Zn(OH)6Cl2, serves as one of the most promising candidates for quantum spin liquids with a perfect quantum kagome Heisenberg antiferromagnetic system. It can comprise an ideal model system for studying the compression response of the unique structure as well as exotic properties of kagome quantum spin liquid materials, which is of fundamental importance from both scientific and technological viewpoints. In this work, the structural evolution of herbertsmithite was investigated via in situ X-ray diffraction and Raman scattering techniques up to 30 GPa. The trigonal herbertsmithite structure transformed into a monoclinic clinoatacamite-like structure at 12.6 GPa. High pressure seems to act in a reverse way as Zn-doping for herbertsmithite, with the distortion degree of the system changing continuously. The occurrence of the displacive and reversible phase transition between the polymorphs is a consequence of the interplay between the external pressure and cooperative Jahn-Teller (JT) effect, aided by the presence of antisite mutual substitution of magnetic Cu2+ ions and nonmagnetic Zn2+ ions between the kagome layer and interlayer sites.

Clinical data, survival, and prognosis of 426 cases of oropharyngeal cancer: a retrospective analysis.

OBJECTIVE: To determine factors influencing survival and prognosis of HPV-related and non-related oropharyngeal cancer. METHODS: Subjects were determined from the three hospitals in Anhui province of China between 2015 and 2020. Paraffin-embedded specimens from participants' tissues were analyzed, and the subjects were classified as P16 + and P16 - cases using immunohistochemical staining for P16 protein. RESULTS: A total of 426 patients with oropharyngeal cancer were recruited in this study; 108 cases were found to be P16 + . The subjects were treated with the three regimens: surgery/radiotherapy/chemotherapy (SRCT), radiotherapy/chemotherapy (RCT), and surgery/chemotherapy (SCT). There were no statistically significant differences in the survival rates within the P16 + or P16 - groups between the three treatment regimens (P > 0.05). The 1-, 3-, and 5-year survival rates for P16 + and P16 - groups were statistically different (P < 0.05). Multivariate analysis showed that age, physical health status, smoking, and alcohol abuse were independent risk factors affecting the prognosis of P16 + cases, while pathological grading and TNM staging were independent risk factors affecting the P16 - cases. CONCLUSION: The etiology, pathogenesis, survival status, and prognostic factors of HPV-related oropharyngeal cancer are very different from those of traditional oropharyngeal cancer. Thus, HPV-related oropharyngeal cancer could be classified as a separate type of disease. This distinction could be of great significance for treatment, prevention, and prognostication of oropharyngeal cancer.

BREAST-Q-Based Survey of the Satisfaction and Health Status of Patients with Breast Reconstruction.

AIMS: To explore the patients' satisfaction and health-related quality of life (HRQOL) of patients who received reconstruction after breast cancer surgery using the BREAST-Q questionnaire and further investigate the influencing risk factors. METHODS: This cross-sectional study enrolled patients who underwent first-ever breast reconstruction after unilateral or bilateral mastectomy at the Breast Surgery Department of First Affiliated Hospital of Zhengzhou University or People's Hospital of Zhengzhou between January 2016 and December 2021. Multivariable linear regression analysis was used to analyze the risk factors. RESULTS: A total of 202 participants were included. Age of >45 years (vs.≤35 years, ß = - 3.74, P < 0.001) was an independent risk factor influencing the satisfaction degree score. Age between 36 and 45 years (vs. ≤35 years, ß = - 0.26, P < 0.001), age of >45 years (vs. ≤35 years, ß = - 0.45, P < 0.001), nipple-preserving mastectomy (NSM)/ skin-preserving mastectomy (SSM) + sentinel lymph node dissection + prosthesis implantation + contralateral breast augmentation (vs. NSM/SSM + sentinel lymph node dissection + prosthesis implantation, ß = - 0.16, P=0.012), and the use of small intestinal submucosa (SIS) matrix (ß = 0.13, P = 0.044) were independent risk factors influencing the HRQOL scores. CONCLUSION: Age, the surgical procedure, and the use of matrix were associated with the satisfaction degree and HRQOL after breast reconstruction in patients receiving mastectomy. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Designing plant flavonoids: harnessing transcriptional regulation and enzyme variation to enhance yield and diversity.

Plant synthetic biology has emerged as a powerful and promising approach to enhance the production of value-added metabolites in plants. Flavonoids, a class of plant secondary metabolites, offer numerous health benefits and have attracted attention for their potential use in plant-based products. However, achieving high yields of specific flavonoids remains challenging due to the complex and diverse metabolic pathways involved in their biosynthesis. In recent years, synthetic biology approaches leveraging transcription factors and enzyme diversity have demonstrated promise in enhancing flavonoid yields and expanding their production repertoire. This review delves into the latest research progress in flavonoid metabolic engineering, encompassing the identification and manipulation of transcription factors and enzymes involved in flavonoid biosynthesis, as well as the deployment of synthetic biology tools for designing metabolic pathways. This review underscores the importance of employing carefully-selected transcription factors to boost plant flavonoid production and harnessing enzyme promiscuity to broaden flavonoid diversity or streamline the biosynthetic steps required for effective metabolic engineering. By harnessing the power of synthetic biology and a deeper understanding of flavonoid biosynthesis, future researchers can potentially transform the landscape of plant-based product development across the food and beverage, pharmaceutical, and cosmetic industries, ultimately benefiting consumers worldwide.

TaSINA2B, interacting with TaSINA1D, positively regulates drought tolerance and root growth in wheat (Triticum aestivum L.).

Wheat (Triticum aestivum L.) is an important food crop mainly grown in arid and semiarid regions worldwide, whose productivity is severely limited by drought stress. Although various E3 ubiquitin (Ub) ligases regulate drought stress, only a few SINA-type E3 Ub ligases are known to participate in such responses. Herein, we identified and cloned 15 TaSINAs from wheat. The transcription level of TaSINA2B was highly induced by drought, osmotic and abscisic acid treatments. Two-type promoters of TaSINA2B were found in 192 wheat accessions; furthermore wheat accessions with promoter TaSINA2BII showed a considerably higher level of drought tolerance and gene expression levels than those characterizing accessions with promoter TaSINA2BI that was mainly caused by a 64 bp insertion in its promoter. Enhanced drought tolerance of TaSINA2B-overexpressing (OE) transgenic wheat lines was found to be associated with root growth promotion. Further, an interaction between TaSINA2B and TaSINA1D was detected through yeast two-hybrid and bimolecular fluorescence complementation assays. And TaSINA1D-OE transgenic wheat lines showed similar drought tolerance and root growth phenotype to those observed when TaSINA2B was overexpressed. Therefore, the variation of TaSINA2B promoter contributed to the drought stress regulation, while TaSINA2B, interacting with TaSINA1D, positively regulated drought tolerance by promoting root growth.

Spinocerebellar ataxia type 8 presents as progressive supranuclear palsy.

Spinocerebellar ataxia type 8 is a progressive neurodegenerative disease induced by expansion of CTA/CTG repeats in an untranslated region of the ATXN8/ATXN8OS gene. We report an elderly female patient presenting with rigidity, bradykinesia, ataxia and oculomotor defect at the disease onset age of 65 years old without family history, and hummingbird sign in cranial MRI, initially diagnosed as progressive supranuclear palsy (PSP). But genetic test showed that one allele of ATXN8OS gene had more than 131 CTA/CTG repeats which was a full penetrance mutant. It's possible that this is a case of PSP with an ATXN8OS gene mutation that doesn't contribute to the phenotype. Whether the ATXN8OS gene CTA/CTG repeats cause PSP phenotype needs further investigation with larger samples and pathological findings.

Genome-wide association study reveals the genetic variation and candidate gene for grain calcium content in bread wheat.

KEY MESSAGE: This study provides important information on the genetic basis of GCaC in wheat, thus contributing to breeding efforts to improve the nutrient quality of wheat. Calcium (Ca) plays important roles in the human body. Wheat grain provides the main diet for billions of people worldwide but is low in Ca content. Here, grain Ca content (GCaC) of 471 wheat accessions was determined in four field environments. A genome-wide association study (GWAS) was performed to reveal the genetic basis of GCaC using the phenotypic data form four environments and a wheat 660 K single nucleotide polymorphism (SNP) array. Twelve quantitative trait locus (QTLs) for GCaC were identified on chromosomes 1A, 1D, 2A, 3B, 6A, 6D, 7A, and 7D, which was significant in at least two environments. Haplotype analysis revealed that the phenotypic difference between the haplotypes of TraesCS6D01G399100 was significant (P ≤ 0.05) across four environments, suggesting it as an important candidate gene for GCaC. This research enhances our understanding of the genetic architecture of GCaC for further improving the nutrient quality of wheat.