An LRPPRC-HAPSTR1-PSMD14 interaction regulates tumor progression in ovarian cancer.

Ovarian cancer is the second most common cause of gynecologic cancer death. Chemoresistance and metastasis remain major challenges for current treatment. Previously, HAPSTR1 was shown to be a target gene of a paclitaxel resistance-associated miRNA. However, the biological function and underlying molecular mechanisms of HAPSTR1 in ovarian cancer progression remain unclear. Herein, we aimed to measure HAPSTR1 expression in ovarian cancer specimens and examine its correlations with clinical features and key functional interactions with other genes and proteins. An immunohistochemistry assay showed that HAPSTR1 was overexpressed in ovarian cancer tissues and was significantly associated with the FIGO stage and clinical outcome. HAPSTR1 overexpression promoted proliferation, invasion and migration in cellular and mouse models, whereas inhibition induced the opposite effects. In addition, HAPSTR1 stimulated the EMT pathway and affected the expression of autophagy biomarkers. Mechanistically, we demonstrated that HAPSTR1 is bound to LRPPRC and PSMD14 via immunoprecipitation. HAPSTR1 suppressed LRPPRC ubiquitination and recruited PSMD14 to interact with LRPPRC. Moreover, LRPPRC knockdown reversed HAPSTR1-mediated improvement in cellular proliferation, invasion, and migration. Our study is the first detailed and comprehensive analysis of HAPSTR1 in cancer progression and offers an experimental basis for the clinical treatment of ovarian carcinoma.

Knowledge, attitudes, and practices among Chinese reproductive-age women toward uterine adenomyosis.

Objective: This study aimed to assess the knowledge, attitudes and practices (KAP) among Chinese reproductive-age women toward uterine adenomyosis. Methods: This web-based cross-sectional study was conducted between April 2023 and September 2023 at the Second Hospital of Hebei Medical University. A self-designed questionnaire was developed to collect demographic information of reproductive-age women, and assess their KAP toward uterine adenomyosis. Results: A total of 520 valid questionnaires were collected. Among the participants, 127 (24.42%) were diagnosed with uterine adenomyosis, and 120 (23.08%) were accompanied by uterine fibroids. The mean knowledge, attitudes and practices scores were 3.54 ± 3.72 (possible range:0-10), 20.96 ± 3.19 (possible range:5-25) and 24.01 ± 4.95 (possible range:7-35), respectively. The structural equation model demonstrated that knowledge had direct effects on attitudes and practices, as indicated by a path coefficient of 0.714 (p < 0.001) and 1.510 (p < 0.001), respectively. Moreover, attitudes had direct effects on practices, with a path coefficient of 0.226 (p = 0.001). Conclusion: The findings revealed that reproductive-age women have insufficient knowledge, negative attitudes, and poor practices toward the uterine adenomyosis. Comprehensive training programs are needed to improve reproductive-age women practices in this area.

Ultra-compact and high-performance suspended aluminum scandium nitride Lamb wave humidity sensor with a graphene oxide layer.

The utilization of Microelectromechanical Systems (MEMS) technology holds great significance for developing compact and high-performance humidity sensors in human healthcare, and the Internet of Things. However, several drawbacks of the current MEMS humidity sensors limit their applications, including their long response time, low sensitivity, relatively large sensing area, and incompatibility with a complementary metal-oxide-semiconductor (CMOS) process. To address these problems, a suspended aluminum scandium nitride (AlScN) Lamb wave humidity sensor utilizing a graphene oxide (GO) layer is firstly designed and fabricated. The theoretical and experimental results both show that the AlScN Lamb wave humidity sensor exhibits high sensing performance. The mass loading sensitivity of the sensor is one order higher than that of the normal surface acoustic wave (SAW) humidity sensor based on an aluminum nitride (AlN) film; thus the AlScN Lamb wave humidity sensor achieves high sensitivity (∼41.2 ppm per % RH) with only an 80 nm-thick GO film. In particular, the as-prepared suspended AlScN Lamb wave sensors are able to respond to the wide relative humidity (0-80% RH) change in 2 s, and the device size is ultra-compact (260 µm × 72 µm). Moreover, the sensor has an excellent linear response in the 0-80% RH range, great repeatability and long-term stability. Therefore, this work brings opportunities for the development of ultra-compact and high-performance humidity sensors.

Surgical treatment improves overall survival of hepatocellular carcinoma with extrahepatic metastases after conversion therapy: a multicenter retrospective study.

Systemic therapy is typically the primary treatment choice for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. Some patients may achieve partial response (PR) or complete response (CR) with systemic treatment, leading to the possibility of their primary tumor becoming resectable. This study aimed to investigate whether these patients could achieve longer survival through surgical resection of their primary tumor. We retrospectively collected data from 150 HCC patients with extrahepatic metastases treated at 15 different centers from January 1st, 2015, to November 30th, 2022. We evaluated their overall survival (OS) and progress-free survival (PFS) and analyzed risk factors impacting both OS and PFS were analyzed. Patients who received surgical treatment had longer OS compared to those who did not (median OS 16.5 months vs. 11.3 months). However, there was no significant difference in progression-free survival between the two groups. Portal vein invasion (P = 0.025) was identified as a risk factor for poor prognosis in patients, while effective first-line treatment (P = 0.039) and surgical treatment (P = 0.005) were protective factors. No factors showed statistical significance in the analysis of PFS. Effective first-line treatment (P = 0.027) and surgical treatment (P = 0.006) were both independent protective factors for prolonging patient prognosis, while portal vein invasion was an independent risk factor (P = 0.044). HCC patients with extrahepatic metastases who achieve PR/CR with conversion therapy may experience longer OS through surgical treatment. This study is the first to analyze the clinical outcomes of patients receiving surgical treatment for HCC with extrahepatic metastases.

Bioinformatics analysis reveals multiple functional changes in astrocytes in temporal lobe epilepsy.

Epilepsy is a prevalent chronic neurological disorder characterized by recurrent seizures and brain dysfunction. Existing antiepileptic drugs (AEDs) mainly act on neurons and provide symptomatic control of seizures, but they do not modify the progression of epilepsy and may cause serious adverse effects. Increasing evidence suggests that reactive astrogliosis is critical in the pathophysiology of epilepsy. However, the function of reactive astrocytes in epilepsy has not been thoroughly explored. To provide a new perspective on the role of reactive astrocytes in epileptogenesis, we identified human astrocyte-specific genes and found 131 of these genes significantly differentially expressed in human temporal lobe epilepsy (TLE) datasets. Multiple astrocytic functions, such as cell adhesion, cell morphogenesis, actin filament-based process, apoptotic cell clearance and response to oxidative stress, were found to be promoted. Moreover, multiple altered astrocyte-specific genes were enriched in phagocytosis, perisynaptic astrocyte processes (PAPs), plasticity, and synaptic functions. Nine hub genes (ERBB2, GFAP, NOTCH2, ITGAV, ABCA1, AQP4, LRP1, GJA1, and YAP1) were identified by protein-protein interaction (PPI) network analysis. The correlation between the expression of these hub genes and seizure frequency, as well as epilepsy-related factors, including inflammatory mediators, complement factors, glutamate excitotoxicity and astrocyte reactivity, were analyzed. Additionally, upstream transcription factors of the hub genes were predicted. Finally, astrogliosis and the expression of the hub genes were validated in an epileptic rat model. Our findings reveal the various changes in astrocyte function associated with epilepsy and provide candidate astrocyte-specific genes that could be potential antiepileptogenic targets.

Kisspeptin prevents pregnancy loss by modulating the immune microenvironment at the maternal-fetal interface in recurrent spontaneous abortion.

PROBLEM: Immune factors are crucial in the development of recurrent spontaneous abortion (RSA). This study aimed to investigate whether kisspeptin regulates immune cells at the maternal-fetal interface and whether G protein-coupled receptor 54 (GPR54) is involved in this process, through which it contributes to the pathogenesis of RSA. METHOD OF STUDY: Normal pregnancy (NP) (CBA/J × BALB/c) and RSA (CBA/J × DBA/2) mouse models were established. NP mice received tail vein injections of PBS and KP234 (blocker of kisspeptin receptor), whereas RSA mice received PBS and KP10 (active fragment of kisspeptin). The changes in immune cells in mouse spleen and uterus were assessed using flow cytometry and immunofluorescence. The expression of critical cytokines was examined by flow cytometry, ELISA, Western blotting, and qPCR. Immunofluorescence was employed to detect the coexpression of FOXP3 and GPR54. RESULTS: The findings revealed that the proportion of Treg cells, MDSCs, and M2 macrophages in RSA mice was lower than that in NP mice, but it increased following the tail vein injection of KP10. Conversely, the proportion of these cells was reduced in NP mice after the injection of KP234. However, the trend of γδT cell proportion change is contrary to these cells. Furthermore, FOXP3 and GPR54 were coexpressed in mouse spleen and uterus Treg cells as well as in the human decidua samples. CONCLUSION: Our results suggest that kisspeptin potentially participates in the pathogenesis of RSA by influencing immune cell subsets at the maternal-fetal interface, including Treg cells, MDSC cells, γδT cells, and M2 macrophages.

Metabolomic landscape of macrophage discloses an anabolic signature of dengue virus infection and antibody-dependent enhancement of viral infection.

Dengue virus (DENV) infection causes dengue fever, the most prevalent arthropod-transmitted viral disease worldwide. Viruses are acellular parasites and obligately rely on host cell machinery for reproduction. Previous studies have indicated metabolomic changes in endothelial cell models and sera of animal models and patients with dengue fever. To probe the immunometabolic mechanism of DENV infection, here, we report the metabolomic landscape of a human macrophage cell model of DENV infection and its antibody-dependent enhancement. DENV infection of THP-1-derived macrophages caused 202 metabolic variants, of which amino acids occupied 23.7%, fatty acids 21.78%, carbohydrates 10.4%, organic acids 13.37%, and carnitines 10.4%. These metabolomic changes indicated an overall anabolic signature, which was characterized by the global exhaustion of amino acids, increases of cellular fatty acids, carbohydrates and pentoses, but decreases of acylcarnitine. Significant activation of metabolic pathways of glycolysis, pentose phosphate, amino acid metabolism, and tricarboxylic acid cycle collectively support the overall anabolism to meet metabolic demands of DENV replication and immune activation by viral infection. Totally 88 of 202 metabolic variants were significantly changed by DENV infection, 36 of which met the statistical standard (P<0.05, VIP>1.5) of differentially expressed metabolites, which were the predominantly decreased variants of acylcarnitine and the increased variants of fatty acids and carbohydrates. Remarkably, 11 differentially expressed metabolites were significantly distinct between DENV only infection and antibody-dependent enhancement of viral infection. Our data suggested that the anabolic activation by DENV infection integrates the viral replication and anti-viral immune activation.

The Association Between the Composite Dietary Antioxidant Index and Frailty Symptoms: Mediating Effects of Oxidative Stress.

Background: There is growing evidence that an antioxidant diet is a protective factor against frailty. However, few studies have examined the effect of comprehensive dietary antioxidants on frailty symptoms. The aim of this study was to examine the relationships between the composite dietary antioxidant index (CDAI) and frailty and the underlying mechanisms involved. Methods: Based on the National Health and Nutrition Survey (NHANES) 2003-2018, this study included 11,277 older persons aged ≥60 years. In this study, frailty was defined as having a total score >0.21 on the 49-item frailty index. Six dietary antioxidants were selected for use in calculating the CDAI. A weighted multiple logistic regression model with subgroup analysis and restricted cubic splines (RCSs) were used to examine the association between the CDAI and frailty. To examine the role of oxidative stress, mediation analyses were also conducted. Results: The association between the CDAI score and frailty risk was significant according to the multivariate model. Compared with participants in tertile 1, participants in both tertile 2 and tertile 3 had lower odds of developing frailty symptoms (OR=0.86; 95% CI=0.75-0.97; P=0.02; and OR=0.81; 95% CI=0.70-0.93; P=0.003). According to the subgroup analyses, the differences in interactions were not statistically significant. There was also a potential nonlinear relationship between the CDAI score and frailty risk. The serum albumin concentration and uric acid concentration had significant mediating effects on the association between the CDAI score and frailty index, with 19.25% (P=0.002) and 21.26% (P < 0.001) of the total, respectively. Conclusion: Frailty is negatively associated with the CDAI score, which may be partially mediated by oxidative stress.

Clinical analysis of Gabriele-de Vries caused by YY1 mutations and literature review.

BACKGROUND: Gabriele-de Vries syndrome is a rare autosomal dominant genetic disease characterized by global development delay/intellectual disability, delayed language development, feeding difficulties, and distinctive facial dysmorphism. It is caused by pathogenic variants in YY1. METHODS: The current report describes a female patient with motor delay and a facial dysmorphism phenotype. We identified pathogenic mutations in the patient by whole-exome sequencing and confirmed them by Sanger sequencing. RESULTS: A novel heterozygous frameshift mutation NM_003403.5:c.458_476del (p. V153fs*97) in the YY1 gene was detected in the proband. Finally, we provide a case-based review of the clinical features associated with Gabriele-de Vries syndrome. A total of 28 patients with genetic abnormalities and clinical phenotypes have been reported in the literature thus far. CONCLUSIONS: The mutation site is reported for the first time, and its discovery would expand the mutation spectrum of the YY1 gene. The main clinical manifestations of Gabriele-de Vries syndrome are developmental delay/intellectual disability, craniofacial dysplasia, intrauterine growth delay, low birth weight, feeding difficulties, and rare congenital malformations. Genetic tests are crucial techniques for its diagnosis because of its nonspecific clinical manifestations.

The prognostic value of age-adjusted Charlson comorbidity index in laparoscopic resection for hilar cholangiocarcinoma.

The prognostic role of the Age-Adjusted Charlson Comorbidity Index (ACCI) in hilar cholangiocarcinoma patients undergoing laparoscopic resection is unclear. To evaluate ACCI's effect on overall survival (OS) and recurrence-free survival (RFS), we gathered data from 136 patients who underwent laparoscopic resection for hilar cholangiocarcinoma at Zhengzhou University People's Hospital between 1 June 2018 and 1 June 2022. ACCI scores were categorized into high ACCI (ACCI > 4.0) and low ACCI (ACCI ≤ 4.0) groups. We examined ACCI's association with OS and RFS using Cox regression analyses and developed an ACCI-based nomogram for survival prediction. Our analysis revealed that higher ACCI scores (ACCI > 4.0) (HR = 2.14, 95%CI: 1.37-3.34) were identified as an independent risk factor significantly affecting both OS and RFS in postoperative patients with hilar cholangiocarcinoma (p < 0.05). TNM stage III-IV (HR = 7.42, 95%CI: 3.11-17.68), not undergoing R0 resection (HR = 1.58, 95%CI: 1.01-2.46), hemorrhage quantity > 350 mL (HR = 1.92, 95%CI: 1.24-2.97), and not receiving chemotherapy (HR = 1.89, 95%CI: 1.21-2.95) were also independent risk factors for OS. The ACCI-based nomogram accurately predicted the 1-, 2-, and 3-year OS rates, with Area Under the Curve (AUC) values of 0.818, 0.844, and 0.924, respectively. Calibration curves confirmed the nomogram's accuracy, and decision curve analysis highlighted its superior predictive performance. These findings suggest that a higher ACCI is associated with a worse prognosis in patients undergoing laparoscopic resection for hilar cholangiocarcinoma. The ACCI-based nomogram could aid clinicians in making accurate predictions about patient survival and facilitate individualized treatment planning.

Exploring the potential mechanism of Heng-Gu-Gu-Shang-Yu-He-Ji therapy for osteoporosis based on network pharmacology and transcriptomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Heng-Gu-Gu-Shang-Yu-He-Ji (Osteoking, OK) is a well-known formula for fracture therapy. In clinic, OK is effective in treating fractures while alleviating osteoporosis (OP) symptoms. However, active components of OK and the associated molecular mechanisms remain not fully elucidated. AIM OF THE STUDY: This study aims to systematically evaluate the anti-osteoporosis efficacy of OK and for the first time combine network pharmacology with high-throughput whole gene transcriptome sequencing to study its underlying mechanism. MATERIALS AND METHODS: In this study, the osteoporosis model was established by the castration of both ovaries. The level of serum bone turnover factor was detected by enzyme-linked immunosorbent assay. Micro-CT and HE staining were used to observe the changes of bone histopathology, and nano-indentation technique was used to detect the biomechanical properties of rat bone. The main active Chemical components of OK were identified using UPLC-DAD. Efficacy verification and mechanism exploration were conducted by network pharmacology, molecular docking, whole gene transcriptomics and in vivo experiments. RESULTS: In our study, OK significantly improved bone microarchitecture and bone biomechanical parameters in OVX rats, reduced osteoclast indexes such as C-telopeptide of type I collage (CTX-I) and increased Osteoprotegerin (OPG)/Receptor activator of NF-κB ligand (RANKL) levels. Mechanistically, PI3K/AKT pathway was a common pathway for genome enrichment analysis (KEGG) of both network pharmacology and RNA-seq studies. G protein-ß-like protein (GßL), Ribosomal-protein S6 kinase homolog 2 (S6K2), and Phosphoinositide 3-kinase (PI3K) appeared differentially expression in the PI3K-AKT signaling pathway. These results were also confirmed by qRT-PCR and immunohistochemistry. CONCLUSIONS: OK may be used to treat osteoporosis, at least partly by activating PI3K/AKT/mTORC1 signaling pathway.

Hypoxia-inducible factor-1: Regulatory mechanisms and drug therapy in myocardial infarction.

Myocardial infarction (MI), an acute cardiovascular disease characterized by coronary artery blockage, inadequate blood supply, and subsequent ischemic necrosis of the myocardium, is one of the leading causes of death. The cellular, physiological, and pathological responses following MI are complex, involving multiple intertwined pathological mechanisms. Hypoxia-inducible factor-1 (HIF-1), a crucial regulator of hypoxia, plays a significant role in of the development of MI by modulating the behavior of various cells such as cardiomyocytes, endothelial cells, macrophages, and fibroblasts under hypoxic conditions. HIF-1 regulates various post-MI adaptive reactions to acute ischemia and hypoxia through various mechanisms. These mechanisms include angiogenesis, energy metabolism, oxidative stress, inflammatory response, and ventricular remodeling. With its crucial role in MI, HIF-1 is expected to significantly influence the treatment of MI. However, the drugs available for the treatment of MI targeting HIF-1 are currently limited, and most contain natural compounds. The development of precision-targeted drugs modulating HIF-1 has therapeutic potential for advancing MI treatment research and development. This study aimed to summarize the regulatory role of HIF-1 in the pathological responses of various cells following MI, the diverse mechanisms of action of HIF-1 in MI, and the potential drugs targeting HIF-1 for treating MI, thus providing the theoretical foundations for potential clinical therapeutic targets.

Single pararectus approach combined with three-dimensional guidance for the treatment of acetabular fracture.

Background: Surgery for acetabular fractures involving both columns is difficult and traumatic, making it necessary to explore a minimally invasive and accurate surgical method. Methods: This retrospective case-control study analyzed the clinical data of 34 patients and divided them into two groups: a control group (9 males and 8 females) and a research group (11 males and 6 females) with acetabular fractures involving the anterior and posterior columns. All patients were placed in the supine position via the pararectus approach. A three-dimensional (3D) guide was placed at the position where the posterior column screw was inserted in the second window, and a posterior column screw was placed percutaneously on the medial side of the iliac spine in the research group. The operation time, intraoperative blood loss, and fracture union time of the two groups were recorded. Pelvic radiographs and computed tomography (CT) scans were routinely performed before and after surgery to evaluate reduction and fixation. Residual gap and step displacement were measured using a standardized CT-based method after the surgery. Hip mobility was assessed according to the modified Merle, d'Aubigné, and Postel criteria. Results: All patients were followed up for 6-30 (16.941±6.571) months. The operation times of the two groups were 126 [interquartile range (IQR), 95-133] min (control group) and 110 (IQR, 85-124) min (research group), the intraoperative blood losses were 430 (IQR, 290-550) mL (control group) and 380 (IQR, 260-500) mL (research group). All patients achieved bone healing, with a union time of 15 (IQR, 12-17) weeks (control group) and 13 (IQR, 11.5-15) weeks (research group). According to the standardized CT-based method, the reduction after surgery was acceptable in 13 (control group) and 14 (research group) of these patients (defined as a gap <5 mm or a step-off <1 mm), and the anatomical reduction rates were 76.47% and 82.35%, respectively. Conclusions: The use of a single pararectus approach combined with 3D guide-assisted percutaneous anterograde posterior column screws can shorten the operation time and place effective posterior column screws precisely with minimal invasiveness. At the same time, the acetabular reduction and functional recovery are satisfactory, and there are fewer postoperative complications, which makes this procedure an ideal surgical option.

Relationship between sleep and serum inflammatory factors in patients with major depressive disorder.

BACKGROUND: At present, the relationship between sleep and inflammatory factors is not clear. The aim of this study was to investigate the relationship between specific inflammatory factors and sleep in MDD patients. METHODS: We measured and compared clinical features and 10 peripheral blood inflammatory factors in 40 MDD patients with sleep disorders, 80 MDD patients without sleep disorders, and 80 healthy controls. Correlation analysis and multiple linear regression analysis were used to explore the relationship between sleep and inflammatory factors. RESULT: The levels of IL-1ß, IL-2, IL-6, IL-8, IL-10, CRP, TNF-α, CXCL-1, CXCL-2, and IFN-γ were different among the three groups(all p<0.05).Poor sleep quality was significantly negatively correlated with IL-2 and IL-8 (all p<0.01), and significantly positively correlated with IL-6, IL-10, CRP, TNF-α, CXCL-1, CXCL-2 and IFN-γ (all p<0.01). IL-8 could significantly negatively predict the deterioration of sleep quality (p<0.001), and TNF-a and IFN-γ could significantly positively predict the deterioration of sleep quality (all p<0.05). LIMITATIONS: The self-rating scale was used in this study. CONCLUSIONS: Inflammatory factors are disrupted in patients with sleep disorders. The lower the level of IL-8 in peripheral blood of MDD patients, the higher the TNF-a and IFN-γ, and the worse the quality of sleep.

Blockade of C5aR1 alleviates liver inflammation and fibrosis in a mouse model of NASH by regulating TLR4 signaling and macrophage polarization.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an advanced form of chronic fatty liver disease, which is a driver of hepatocellular carcinoma. However, the roles of the C5aR1 in the NASH remain poorly understood. Here, we aimed to investigate the functions and mechanisms of the C5aR1 on hepatic inflammation and fibrosis in murine NASH model. METHODS: Mice were fed a normal chow diet with corn oil (ND + Oil), a Western diet with corn oil (WD + Oil) or a Western diet with carbon tetrachloride (WD + CCl4) for 12 weeks. The effects of the C5a-C5aR1 axis on the progression of NASH were analyzed and the underlying mechanisms were explored. RESULTS: Complement factor C5a was elevated in NASH mice. C5 deficiency reduced hepatic lipid droplet accumulation in the NASH mice. The hepatic expression levels of TNFα, IL-1ß and F4/80 were decreased in C5-deficient mice. C5 loss alleviated hepatic fibrosis and downregulated the expression levels of α-SMA and TGFß1. C5aR1 deletion reduced inflammation and fibrosis in NASH mice. Transcriptional profiling of liver tissues and KEGG pathway analysis revealed that several pathways such as Toll-like receptor signaling, NFκB signaling, TNF signaling, and NOD-like receptor signaling pathway were enriched between C5aR1 deficiency and wild-type mice. Mechanistically, C5aR1 deletion decreased the expression of TLR4 and NLRP3, subsequently regulating macrophage polarization. Moreover, C5aR1 antagonist PMX-53 treatment mitigated the progression of NASH in mice. CONCLUSIONS: Blockade of the C5a-C5aR1 axis reduces hepatic steatosis, inflammation, and fibrosis in NASH mice. Our data suggest that C5aR1 may be a potential target for drug development and therapeutic intervention of NASH.

A Gas Flow Measurement System Based on Lead Zirconate Titanate Piezoelectric Micromachined Ultrasonic Transducer.

Ultrasonic flowmeter is one of the most widely used devices in flow measurement. Traditional bulk piezoelectric ceramic transducers restrict their application to small pipe diameters. In this paper, we propose an ultrasonic gas flowmeter based on a PZT piezoelectric micromachined ultrasonic transducer (PMUT) array. Two PMUT arrays with a resonant frequency of 125 kHz are used as the sensitive elements of the ultrasonic gas flowmeter to realize alternate transmission and reception of ultrasonic signals. The sensor contains 5 × 5 circular elements with a size of 3.7 × 3.7 mm2. An FPGA with a resolution of ns is used to process the received signal, and a flow system with overlapping acoustic paths and flow paths is designed. Compared with traditional measurement methods, the sensitivity is greatly improved. The flow system achieves high-precision measurement of gas flow in a 20 mm pipe diameter. The flow measurement range is 0.5-7 m/s and the relative error of correction is within 4%.

Late-onset cblC deficiency around puberty: a retrospective study of the clinical characteristics, diagnosis, and treatment.

BACKGROUND: cblC deficiency is the most common type of methylmalonic aciduria in China. Late-onset patients present with various non-specific symptoms and are usually misdiagnosed. The purpose of this study is to investigate the clinical features of patients with late-onset cblC deficiency and explore diagnosis and management strategies around puberty. RESULTS: This study included 56 patients (35 males and 21 females) with late-onset cblC deficiency who were admitted to our clinic between 2002 and September 2021. The diagnosis was confirmed by metabolic and genetic tests. The clinical and biochemical features, disease triggers, outcome, and associated genetic variants were examined. The onset age ranged from 10 to 20 years (median age, 12 years). Fifteen patients (26.8%) presented with symptoms after infection or sports training. Further, 46 patients (82.1%) had neuropsychiatric diseases; 11 patients (19.6%), cardiovascular diseases; and 6 patients (10.7%), pulmonary hypertension. Renal damage was observed in 6 cases (10.7%). Genetic analysis revealed 21 variants of the MMACHC gene in the 56 patients. The top five common variants detected in 112 alleles were c.482G > A (36.6%), c.609G > A (16.1%), c.658_660delAAG (9.8%), c.80A > G (8.0%), and c.567dupT (6.3%). Thirty-nine patients carried the c.482G > A variant. Among 13 patients who exhibited spastic paraplegia as the main manifestation, 11 patients carried c.482G > A variants. Six patients who presented with psychotic disorders and spastic paraplegia had compound heterozygotic c.482G > A and other variants. All the patients showed improvement after metabolic treatment with cobalamin, L-carnitine, and betaine, and 30 school-aged patients returned to school. Two female patients got married and had healthy babies. CONCLUSIONS: Patients with late-onset cblC deficiency present with a wide variety of neuropsychiatric symptoms and other presentations, including multiple organ damage. As a result, cb1C deficiency can easily be misdiagnosed as other conditions. Metabolic and genetic studies are important for accurate diagnosis, and metabolic treatment with cobalamin, L-carnitine, and betaine appears to be beneficial.

Preoperative Oral Carbohydrate Levels in Patients with Type 2 Diabetes Mellitus: The Clinical Guiding Significance of Free Fatty Acids.

Background: It is still controversial whether preoperative oral carbohydrate (POC) should be applied to patients with type 2 diabetes mellitus (T2DM) in the enhanced recovery after surgery (ERAS) protocol. There is no relevant consensus or indicators to provide guidance as to whether T2DM patients should take POC. Methods: In total, 164 T2DM patients who underwent laparoscopic hepatectomy were analyzed. According to the level of blood free fatty acids (FFAs) and whether the patients received POC, the patients were divided into 6 groups: the low FFA carbohydrate group (LFFAC group), low FFA fasting water group (LFFAF group), medium FFA carbohydrate group (MFFAC group), medium FFA fasting water group (MFFAF group), high FFA carbohydrate group (HFFAC group) and high FFA fasting water group (HFFAF group). Results: Patients with low FFA levels showed better perioperative blood glucose control and a lower incidence of postoperative complications than those in the medium and high FFA groups, especially when patients received POC. Further analyses revealed that the postoperative plasma concentrations of IL-6 and TNF-α were significantly decreased in the POC group compared with the fasting water group, except for patients with high FFA levels. Receiver operating characteristic (ROC) curve analysis revealed that when the FFA concentration was higher than 0.745 mmol/L, the risk of poor blood glucose control during the perioperative period was increased. Conclusions: FFAs have clinical guiding significance for the application of POC in patients with T2DM under ERAS administration. T2DM patients with low FFAs are more suitable for receiving POC.

New SFT2-like Vesicle Transport Protein (SFT2L) Enhances Cadmium Tolerance and Reduces Cadmium Accumulation in Common Wheat Grains.

Cadmium (Cd) is one of the most toxic heavy metal elements to the environment, which seriously threatens the safe production of food crops. In this study, we identified a novel function of the cytomembrane TaSFT2L protein in wheat (Triticum aestivum). Expression of the TaSFT2L gene in yeast showed no transport activities for Cd, which could explain the role of TaSFT2L in metal tolerance. It was observed that increased autophagic activity in roots caused by silencing of TaSFT2L enhanced Cd tolerance. Transgenic wheat revealed that RNA interference (RNAi) lines enhanced the wheat growth concerning the increased shoot or root elongation, dry weight, and chlorophyll accumulation. Furthermore, RNAi lines decreased root-to-grain Cd translocation in wheat by nearly 68% and Cd accumulation in wheat grains by 53%. Meanwhile, the overexpression lines displayed a compromised growth response and increased Cd accumulation in wheat tissues, compared to wild type. These findings show that TaSFT2L is a key gene involved in regulation of Cd translocation in wheat, and its silencing to form transgenic wheat can inhibit Cd accumulation. This has the ability to alleviate the food chain-associated impact of environmental pollution on human health.

Overexpression of BACH1 mediated by IGF2 facilitates hepatocellular carcinoma growth and metastasis via IGF1R and PTK2.

Background: Accumulating studies manifest that BTB and CNC homology 1 (BACH1) facilitates multiple malignancies progression and metastasis, and targeting the BACH1 pathway enhances antitumor efficacy. Nevertheless, the exact mechanism of BACH1 promoting growth and metastasis and its therapeutic significance in hepatocellular carcinoma (HCC) remain unclear. Methods: The expression of BACH1 in human HCC specimens and HCC cell lines was analyzed by quantitative RT-PCR (RT-qPCR), western blot, and immunohistochemistry (IHC). The invasiveness and metastasis of HCC cells in vitro and in vivo were evaluated using transwell assays and orthotopic xenograft models. The luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays were performed to explore the transcriptional regulation of insulin-like growth factor 1 receptor (IGF1R) and protein tyrosine kinase 2 (PTK2) by BACH1. Results: BACH1 was prominently upregulated in human HCC samples and elevated BACH1 expression was associated with poor overall survival (OS) and high recurrence rates of HCC patients. BACH1 facilitated growth and metastasis of HCC by upregulating cell motility-related genes IGF1R and PTK2. Notably, insulin-like growth factor 2 (IGF2), the ligand of IGF1R, in turn upregulated BACH1 expression through the IGF1R-ERK1/2-ETS1 cascades, thus forming a positive feedback loop to provoke HCC growth and metastasis. Moreover, combining IGF1R inhibitor linsitinib with PTK2 inhibitor defactinib prominently suppressed BACH1-mediated HCC growth and metastasis. Conclusions: These results demonstrated the tumorigenic and pro-metastatic role of BACH1 in HCC, which could be a promising biomarker for predicting poor prognosis and selecting patients who could benefit from combination therapy of IGF1R-targeted and PTK2-directed.