Predictive Validity of Intrinsic Capacity Composite Scores for Risk of Frailty at 2 Years: A Comparison of 4 Scales.

OBJECTIVE: Intrinsic capacity (IC) and frailty are complementary constructs that encapsulate functional capacities of older adults. Although earlier studies suggest the utility of composite IC scores in predicting risk of frailty, key gaps remain with the lack of direct comparative studies between different IC scales and lack of a composite score based on the World Health Organization Integrated Care for Older People (ICOPE) tool. We aimed to compare different IC scales, including an ICOPE-based scale, in their predictive ability for risk of frailty at 2 years in healthy community-dwelling older adults. DESIGN: Cohort study. SETTING AND PARTICIPANTS: A total of 230 participants (age: 67.2 ± 7.4 years) from the GeriLABS-2 cohort study. METHODS: We derived composite scores by summing 4 IC domains (locomotion, cognition, vitality, and psychological). We compared composite scores of 4 scales: IC1-Chew 2021, range: 0-8; IC2-Liu 2021, range: 0-4; IC3-ICOPE, range: 0-4; IC4-modified ICOPE, range: 0-8. The primary outcome was risk of frailty using the modified Fried Frailty Phenotype. We performed logistic regression to examine the association of baseline composite IC with risk of frailty. We also examined the impact of individual domains and number of impaired domains on risk of frailty. RESULTS: Among 193 (83.9%) older adults who completed 2-year follow-up, 20 (10.4%) met criteria for risk of frailty. When adjusted for covariates, 2-point per domain scales (IC1/IC4) predicted increased risk of frailty (OR, 4.31; 95% CI, 1.55-11.96; OR, 5.00; 95% CI, 1.75-14.26). When further adjusted for baseline frailty, only IC4 remained significant (OR, 4.28; 95% CI, 1.45-12.60). Among the domains, impaired locomotion and vitality were associated with risk of frailty. Greater number of impaired domains predicted increased risk of frailty (IC1/IC2: ß = 0.18-0.19, P < .05). CONCLUSIONS AND IMPLICATIONS: Baseline composite IC score using 2-point per domain scales better predicted risk of frailty at 2 years, predicated on impaired locomotion/vitality and greater number of impaired domains. For early identification of healthy older adults at risk of frailty, an ICOPE-based scale should be considered, as it is effective and accessible.

CREB3 suppresses hepatocellular carcinoma progression by depressing AKT signaling through competitively binding with insulin receptor and transcriptionally activating RNA-binding motif protein 38.

cAMP responsive element binding protein 3 (CREB3), belonging to bZIP family, was reported to play multiple roles in various cancers, but its role in hepatocellular carcinoma (HCC) is still unclear. cAMP responsive element binding protein 3 like 3 (CREB3L3), another member of bZIP family, was thought to be transcription factor (TF) to regulate hepatic metabolism. Nevertheless, except for being TFs, other function of bZIP family were poorly understood. In this study, we found CREB3 inhibited growth and metastasis of HCC in vitro and in vivo. RNA sequencing indicated CREB3 regulated AKT signaling to influence HCC progression. Mass spectrometry analysis revealed CREB3 interacted with insulin receptor (INSR). Mechanistically, CREB3 suppressed AKT phosphorylation by inhibiting the interaction of INSR with insulin receptor substrate 1 (IRS1). In our study, CREB3 was firstly proved to affect activation of substrates by interacting with tyrosine kinase receptor. Besides, CREB3 could act as a TF to transactivate RNA-binding motif protein 38 (RBM38) expression, leading to suppressed AKT phosphorylation. Rescue experiments further confirmed the independence between the two functional manners. In conclusion, CREB3 acted as a tumor suppressor in HCC, which inhibited AKT phosphorylation through independently interfering interaction of INSR with IRS1, and transcriptionally activating RBM38.

The effect of instant tea on the aroma of duck meat.

Tea products, such as instant tea, have been shown to improve the aroma of meat products. However, the mechanisms by which tea products enhance meat aroma have not been adequately explained. In this study, we analyzed the impact of instant tea on the aroma of duck meat. Our results showed that treatment with instant tea led to increases in floral, baked, and grassy notes while reducing fishy and fatty notes. Several alcohols, aldehydes, ketones, indole and dihydroactinidiolide exhibited significantly increased OAVs. Conversely, certain saturated aldehydes, unsaturated aldehydes and alcohols displayed significantly decreased OAVs. The enhanced floral, baked and grassy notes were attributed to volatile compounds present in instant tea. The reduction in fishy and fatty notes was linked to polyphenols in instant tea interacting with nonanal, undecanal, (E)-2-octenal, (E)-2-nonenal, (E)-2-decenal, and 2,4-decadienal through hydrophobic interactions and electronic effects. This study enhances our understanding of how tea products improve meat aromas.

Multimodal imaging observation of primary vitreous cysts.

BACKGROUND: Primary vitreous cyst is a clinical variant delineated by the existence of a vesicle within the vitreous cavity from birth. This particular disease tends to be uncommon, and the underlying mechanisms contributing to its pathogenesis remain obscure. CASE PRESENTATION: A 37-year-old male patient manifested blurry vision and floaters in his right eye, a symptomology first noticed three months prior. Upon slit-lamp examination, a pigmented, round, 1 papilla diameter-sized mass was discerned floating in the vitreous. A meticulous examination of the floaters was conducted using an array of multimodal imaging techniques. Other potential conditions, including cysticercosis, toxoplasmosis, and tumors, were conclusively excluded through comprehensive diagnostic tests such as blood examinations, liver ultrasound, and cranial magnetic resonance imaging (MRI), resulting in the diagnosis of a primary vitreous cyst. The patient did not report any other discomforts and did not receive any subsequent interventions or treatments. CONCLUSION: We furnish an exhaustive case report of a patient diagnosed with a primary vitreous cyst. The incorporation of multimodal images in the characterization of the disease anticipates facilitating an enriched comprehension by medical practitioners.

Prognosis and therapeutic significance of IGF-1R-related signaling pathway gene signature in glioma.

Background: Glioma is the most common cancer of the central nervous system with poor therapeutic response and clinical prognosis. Insulin-like growth factor 1 receptor (IGF-1R) signaling is implicated in tumor development and progression and induces apoptosis of cancer cells following functional inhibition. However, the relationship between the IGF-1R-related signaling pathway genes and glioma prognosis or immunotherapy/chemotherapy is poorly understood. Methods: LASSO-Cox regression was employed to develop a 16-gene risk signature in the TCGA-GBMLGG cohort, and all patients with glioma were divided into low-risk and high-risk subgroups. The relationships between the risk signature and the tumor immune microenvironment (TIME), immunotherapy response, and chemotherapy response were then analyzed. Immunohistochemistry was used to evaluate the HSP90B1 level in clinical glioma tissue. Results: The gene risk signature yielded superior predictive efficacy in prognosis (5-year area under the curve: 0.875) and can therefore serve as an independent prognostic indicator in patients with glioma. The high-risk subgroup exhibited abundant immune infltration and elevated immune checkpoint gene expression within the TIME. Subsequent analysis revealed that patients in the high-risk subgroup benefited more from chemotherapy. Immunohistochemical analysis confirmed that HSP90B1 was overexpressed in glioma, with significantly higher levels observed in glioblastoma than in astrocytoma or oligodendrocytoma. Conclusion: The newly identified 16-gene risk signature demonstrates a robust predictive capacity for glioma prognosis and plays a pivotal role in the TIME, thereby offering valuable insights for the exploration of novel biomarkers and targeted therapeutics.

Porous tremella-like NiMoP/CoP network electrodes as an efficient electrocatalyst.

The design of efficient, stable and cost-effective electrocatalysts for the hydrogen evolution reaction holds substantial significance in water electrolysis, but it remains challenging. Tremella-like nickel-molybdenum bimetal phosphide encapsulated cobalt phosphide (NiMoP/CoP) with hierarchical architectures has been effectively synthesized on nickel foam (NF) via a straightforward hydrothermal followed by low-temperature phosphating method. Based on the unique structural benefits, it significantly increases the number of redox active centers, enhances the electrical conductivity of materials, and diminishes the ion diffusion path lengths, thereby promoting efficient electrolyte penetration and reducing the inherent resistance. The as-obtained NiMoP/CoP/NF electrocatalyst exhibited remarkable catalytic activity with an ultralow overpotential of 38 mV (10 mA cm-2) and low Tafel slope of 83 mV dec-1. The straightforward synthesis process and exceptional electrocatalytic properties of NiMoP/CoP/NF demonstrate great potential for the HER to replace the precious metal catalyst.

Multi-cohort comprehensive analysis unveiling the clinical value and therapeutic effect of GNAL in glioma.

Clinical data indicates that glioma patients have poor treatment outcomes and clinical prognosis. The role of olfactory signaling pathway-related genes (OSPRGs) in glioma has not been fully elucidated. In this study, we aimed to investigate the role and relationship between OSPRGs and glioma. Univariate and multivariate Cox regression analyses were performed to assess the relationship between OSPRGs and the overall survival of glioma based on public cohorts, and the target gene (G Protein Subunit Alpha L, GNAL) was screened. The association of GNAL expression with clinicopathological characteristics, gene mutation landscape, tumor immune microenvironment (TIME), deoxyribonucleic acid (DNA) methylation, and naris-occlusion controlled genes (NOCGs) was performed. Immunohistochemistry was used to evaluate GNAL level in glioma. Further analysis was conducted to evaluate the drug sensitivity, immunotherapy response, and functional enrichment of GNAL. GNAL was an independent prognostic factor, and patients with low GNAL expression have a poor prognosis. Expression of GNAL was closely associated with clinicopathological characteristics, DNA methylation, and several immune-related pathways. Immune infiltration analysis indicated that GNAL levels were negatively correlated with immune scores. GNAL low-expression group showed efficacy with anti-PD-1 therapy. Ten compounds with significantly different half-maximal inhibitory concentration (IC50) values between the GNAL high and low-expression groups were identified. Furthermore, its expression was associated with several immune cells, immune-related genes, and NOCGs. The expression of GNAL is closely associated with clinicopathological characteristics, TIME, and the response to therapeutic interventions, highlighting its potential as a prognostic biomarker for glioma.

Genetic and pharmacologic p32-inhibition rescue CHCHD2-linked Parkinson's disease phenotypes in vivo and in cell models.

BACKGROUND: Mutations in CHCHD2 have been linked to Parkinson's disease, however, their exact pathophysiologic roles are unclear. The p32 protein has been suggested to interact with CHCHD2, however, the physiological functions of such interaction in the context of PD have not been clarified. METHODS: Interaction between CHCHD2 and p32 was confirmed by co-immunoprecipitation experiments. We studied the effect of p32-knockdown in the transgenic Drosophila and Hela cells expressing the wild type and the pathogenic variants of hCHCHD2. We further investigated the rescue ability of a custom generated p32-inhibitor in these models as well as in the human fibroblast derived neural precursor cells and the dopaminergic neurons harboring hCHCHD2-Arg145Gln. RESULTS: Our results showed that wildtype and mutant hCHCHD2 could bind to p32 in vitro, supported by in vivo interaction between human CHCHD2 and Drosophila p32. Knockdown of p32 reduced mutant hCHCHD2 levels in Drosophila and in vitro. In Drosophila hCHCHD2 models, inhibition of p32 through genetic knockdown and pharmacological treatment using a customized p32-inhibitor restored dopaminergic neuron numbers and improved mitochondrial morphology. These were correlated with improved locomotor function, reduced oxidative stress and decreased mortality. Consistently, Hela cells expressing mutant hCHCHD2 showed improved mitochondrial morphology and function after treatment with the p32-inhibitor. As compared to the isogenic control cells, large percentage of the mutant neural precursor cells and dopaminergic neurons harboring hCHCHD2-Arg145Gln contained fragmented mitochondria which was accompanied by lower ATP production and cell viability. The NPCs harboring hCHCHD2-Arg145Gln also had a marked increase in α-synuclein expression. The p32-inhibitor was able to ameliorate the mitochondrial fragmentation, restored ATP levels, increased cell viability and reduced α-synuclein level in these cells. CONCLUSIONS: Our study identified p32 as a modulator of CHCHD2, possibly exerting its effects by reducing the toxic mutant hCHCHD2 expression and/or mitigating the downstream effects. Inhibition of the p32 pathway can be a potential therapeutic intervention for CHCHD2-linked PD and diseases involving mitochondrial dysfunction.

SARC-F and modified versions using arm and calf circumference: Diagnostic performance for sarcopenia screening and the impact of obesity.

AIM: SARC-F is limited by low sensitivity for sarcopenia identification. As surrogates of muscle mass, mid-arm circumference (MAC) and/or calf circumference have been proposed as additions to SARC-F to enhance sarcopenia identification. The aim of this study was to evaluate the diagnostic performance of SARC-F, SARC-CalF, SARC-F + MAC, and SARC-CalF + MAC in sarcopenia detection, and to assess the impact of obesity on their diagnostic performance. METHODS: We studied 230 healthy non-frail community-dwelling older adults age >50 years. We performed receiver operating characteristic curve analysis for SARC-F, SARC-CalF, SARC-F + MAC and SARC-CalF + MAC against sarcopenia diagnosed by the Asian Working Group for Sarcopenia (AWGS) 2019 as the reference standard. Obesity was defined by high waist circumference (men ≥90 cm, women ≥80 cm). We performed subgroup analysis to compare between obese and non-obese groups. RESULTS: The prevalence of sarcopenia was 27.0% by AWGS 2019. SARC-CalF + MAC had the best diagnostic performance (area under the curve [AUC] 0.74, 95% confidence interval [CI] 0.67-0.81; sensitivity 66.1%; specificity 69.1%), followed by SARC-CalF (AUC 0.70, 95% CI 0.62-0.78; sensitivity 21.0%; specificity 95.8%). SARC-F (AUC 0.57, 95% CI 0.49-0.66; sensitivity 0%; specificity 100%) performed significantly worsethan its modified versions (P < 0.05). There was higher accuracy of sarcopenia identification in obese compared with non-obese groups for SARC-F + MAC (AUC 0.75, 95% CI 0.65-0.85 vs. 0.58, 95% CI 0.46-0.70) and SARC-CalF + MAC (AUC 0.75, 95% CI 0.66-0.85 vs. 0.70, 95% CI 0.59-0.81). CONCLUSIONS: The addition of arm circumference to SARC-CalF confers better diagnostic accuracy for sarcopenia identification, especially in the obese group. Thus, MAC may complement SARC-CalF for community screening of sarcopenia amongst healthy community-dwelling older adults by increasing sensitivity for the detection of sarcopenic obesity. Geriatr Gerontol Int 2024; 24: 182-188.

Targeting MMP9 in CTNNB1 mutant hepatocellular carcinoma restores CD8+ T cell-mediated antitumour immunity and improves anti-PD-1 efficacy.

OBJECTIVE: The gain of function (GOF) CTNNB1 mutations (CTNNB1 GOF ) in hepatocellular carcinoma (HCC) cause significant immune escape and resistance to anti-PD-1. Here, we aimed to investigate the mechanism of CTNNB1 GOF HCC-mediated immune escape and raise a new therapeutic strategy to enhance anti-PD-1 efficacy in HCC. DESIGN: RNA sequencing was performed to identify the key downstream genes of CTNNB1 GOF associated with immune escape. An in vitro coculture system, murine subcutaneous or orthotopic models, spontaneously tumourigenic models in conditional gene-knock-out mice and flow cytometry were used to explore the biological function of matrix metallopeptidase 9 (MMP9) in tumour progression and immune escape. Single-cell RNA sequencing and proteomics were used to gain insight into the underlying mechanisms of MMP9. RESULTS: MMP9 was significantly upregulated in CTNNB1 GOF HCC. MMP9 suppressed infiltration and cytotoxicity of CD8+ T cells, which was critical for CTNNB1 GOF to drive the suppressive tumour immune microenvironment (TIME) and anti-PD-1 resistance. Mechanistically, CTNNB1 GOF downregulated sirtuin 2 (SIRT2), resulting in promotion of ß-catenin/lysine demethylase 4D (KDM4D) complex formation that fostered the transcriptional activation of MMP9. The secretion of MMP9 from HCC mediated slingshot protein phosphatase 1 (SSH1) shedding from CD8+ T cells, leading to the inhibition of C-X-C motif chemokine receptor 3 (CXCR3)-mediated intracellular of G protein-coupled receptors signalling. Additionally, MMP9 blockade remodelled the TIME and potentiated the sensitivity of anti-PD-1 therapy in HCC. CONCLUSIONS: CTNNB1 GOF induces a suppressive TIME by activating secretion of MMP9. Targeting MMP9 reshapes TIME and potentiates anti-PD-1 efficacy in CTNNB1 GOF HCC.

Simultaneous production of high-valued carbon nanotubes and hydrogen from catalytic pyrolysis of waste plastics: The role of cellulose impurity.

Upcycling waste plastics into valuable carbon nanotubes (CNTs) and hydrogen via catalytic pyrolysis is a sustainable strategy to mitigate white pollution. However, real-world plastics are complex and generally contain organic impurities, such as cellulose, which have a non-negligible impact on the catalytic pyrolysis process and product distribution. In this study, cellulose was chosen as a model compound to distinguish the effects of oxygen-containing components on the CNTs and hydrogen production during the catalytic pyrolysis of waste polypropylene. Different amounts of cellulose were mixed with polypropylene to regulate the O/C mass ratio of the feedstock, and the relationship between the O/C mass ratio and the yield of products has been built quantificationally. The results revealed that the relative content of CNTs increased to over 95%, and the stability and purity of carbon deposition increased accordingly when the O/C mass ratio is 0.05. This could be ascribed to the etching effects caused by small amounts of H2O and CO2 on amorphous carbon. However, further increasing the amount of cellulose caused the deactivation of the Fe-Ni catalyst. This not only decreased the carbon yield but had an adverse impact on its morphology and graphitization, leading to the increase of amorphous carbon. This study can provide fundamental guidance for the efficient utilization of waste plastics that take advantage of organic impurities in waste plastic to promote the formation of high-purity CNTs.

Characterization of the off-flavor from Pichia pastoris GS115 during the overexpression of an α-l-rhamnosidase.

The off-flavor of Pichia pastoris strains is a negative characteristic of proteins overexpressed with this yeast. In the present study, P. pastoris GS115 overexpressing an α-l-rhamnosidase was taken as the example to characterize the off-flavor via sensory evaluation, gas chromatography-mass spectrometer, gas chromatography-olfaction, and omission test. The result showed that the off-flavor was due to the strong sweaty note, and moderate metallic and plastic notes. Four volatile compounds, that is, tetramethylpyrazine, 2,4-di-tert-butylphenol, isovaleric acid, and 2-methylbutyric acid, were identified to be major contributors to the sweaty note. Dodecanol and 2-acetylbutyrolactone were identified to be contributors to the metallic and plastic notes, respectively. It is the first study on the off-flavor of P. pastoris strains, helping understand metabolites with off-flavor of this yeast. Interestingly, it is the first study illustrating 2-acetylbutyrolactone and dodecanol with plastic and metallic notes, providing new information about the aromatic contributors of biological products. IMPORTANCE: The methylotrophic yeast Pichia pastoris is an important host for the industrial expression of functional proteins. In our previous studies, P. pastoris strains have been sniffed with a strong off-flavor during the overexpression of various functional proteins, limiting the application of these proteins. Although many yeast strains have been reported with off-flavor, no attention has been paid to characterize the off-flavor in P. pastoris so far. Considering that P. pastoris has advantages over other established expression systems of functional proteins, it is of interest to identify the compounds with off-flavor synthesized in the overexpression of functional proteins with P. pastoris strains. In this study, the off-flavor synthesized from P. pastoris GS115 was characterized during the overexpression of an α-l-rhamnosidase, which helps understand the aromatic metabolites with off-flavor of P. pastoris strains. In addition, 2-acetylbutyrolactone and dodecanol were newly revealed with plastic and metallic notes, enriching the aromatic contributors of biological products. Thus, this study is important for understanding the metabolites with off-flavor of P. pastoris strains and other organisms, providing important knowledge to improve the flavor of products yielding with P. pastoris strains and other organisms. ONE-SENTENCE SUMMARY: Characterize the sensory and chemical profile of the off-flavor produced by one strain of P. pastoris in vitro.

One-pot self-assembled bimetallic sulfide particle cluster-supported three-dimensional graphene aerogel as an efficient electrocatalyst for the oxygen evolution reaction.

The preparation of an electrocatalyst for the oxygen evolution reaction (OER) with high catalytic activity, good long-term durability and rapid reaction kinetics through interface engineering is of great significance. Herein, we have developed a bimetallic sulfide particle cluster-supported three-dimensional graphene aerogel (FeNiS@GA), which serves as an efficient electrocatalyst for OER, by a one-step hydrothermal method. Profiting from the synergy of the FeNiS particle cluster with high capacitance and GA with its three-dimensional porous nanostructure, FeNiS@GA shows a high specific surface area, large pore volume, low contact resistance, and decreases the electron and ion transport routes. FeNiS@GA exhibits outstanding OER activity (when the current density is 50 mA cm-2, the overpotential is 341 mV), low Tafel slope (63.87 mV dec-1) and remarkable stability in alkaline solutions, outperforming FeNiS, NiS@GA, FeS@GA and RuO2. Due to its simple synthesis process and excellent electrocatalytic performance, FeNiS@GA shows great potential to replace noble metal-based catalysts in practical applications.

Polysulfide induced synthesis of a MoS2 self-supporting electrode with wide-layer-spacing for efficient electrocatalytic water splitting.

Efficient non-noble metal bifunctional electrocatalysts can increase the conversion rate of electric energy in the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). Herein, a ball & sheet MoS2/Ni3S2 composite with wide-layer-spacing and high 1T-rich MoS2 is assembled on nickel foam (NF) via a two-step solvothermal method with polymeric sulfur (S-r-DIB) as the sulfur source. The obtained material serves as both the cathode and the anode toward overall water splitting in an alkaline electrolyte. The results proved that the interpenetration of MoS2/Ni3S2-p with a ball and sheet structure increased the material active surface area and exposed more catalytic active sites, which contributed to the penetration of solution and the transfer of charge/hydrion. Meanwhile, two different semiconductors of MoS2 and Ni3S2 along with the presence of ample active sulfur edge sites and few-layer, wide-layer-spacing structures of MoS2 lead to an outstanding electrocatalytic activity. In particular, the electrodes of MoS2/Ni3S2-p only need a battery voltage of 1.55 V at 10 mA cm-2. The bifunctional electrocatalyst MoS2/Ni3S2-p also shows excellent stability at large current densities during the electrochemical test.

Zirconium metal-organic cage decorated with squaramides imparts dual activation for chemical fixation of CO2 under mild conditions.

A "two-in-one" dual activation strategy has been developed to give high-density hydrogen-bonding (HB) active units and Lewis acid (LA) active centres by immobilizing squaramides into metal-organic cages (MOCs). The obtained MOC served as an efficient catalyst for the chemical fixation of CO2 under mild conditions up to 99% yields with good recyclability, and the mechanism of high catalytic activity has been further explored.

TRIM55 Promotes Proliferation of Hepatocellular Carcinoma Through Stabilizing TRIP6 to Activate Wnt/ß-Catenin Signaling.

Purpose: Tripartite motif containing 55 (TRIM55) is a member of the TRIM family and functions as an E3 ubiquitin ligase. It acts as a cancer promoter or suppressor in the malignant processes of multiple cancers. However, its proliferative function in hepatocellular carcinoma (HCC) has been poorly studied, and its underlying molecular mechanism remains unclear. In the present study, we investigated the role of TRIM55 in HCC and its mechanism of promoting HCC proliferation. Materials and Methods: Protein expression levels of TRIM55 were measured in paired HCC and normal tissue samples using immunohistochemical (IHC) staining. The correlation between TRIM55 and clinical features was evaluated by statistical analysis. At the same time, overexpression and knockdown experiments, cycloheximide (CHX) interference experiments, ubiquitination, co-immunoprecipitation and immunofluorescence staining experiments, as well as animal experiments were used to evaluate the potential mechanism that TRIM55 promotes proliferation of hepatocellular carcinoma in vitro and in vivo. Results: TRIM55 expression in HCC specimens was higher compared with the corresponding non-tumor tissues. The overall survival and disease-free survival time of patients with high TRIM55 expression were shorter than those with low expression of TRIM55. Functionally, TRIM55 promoted the proliferation of HCC cells and accelerated the growth of HCC xenografts. Mechanistically, TRIM55 interacted with thyroid receptor interacting protein 6 (TRIP6) and regulate its stability by influencing the ubiquitination process, thereby affecting the Wnt signaling pathway. Conclusion: Our results indicate that TRIM55 promotes HCC proliferation by activating Wnt signaling pathways by stabilizing TRIP6. Therefore, targeting TRIM55 may be an effective therapeutic strategy to inhibit HCC growth.

Successful cardiopulmonary resuscitation of cardiac arrest induced by massive pulmonary embolism under general anesthesia: a case report.

Background: While pulmonary embolism (PE) is a common occurrence, a large life-threatening PE is not. Herein, we discuss the case of a patient with a life-threatening PE that occurred under general anesthesia. Case presentation: We present the case of a 59-year-old male patient who was at bed rest for several days due to trauma, which resulted in femoral and rib fractures and a lung contusion. The patient was scheduled for femoral fracture reduction and internal fixation under general anesthesia. After disinfection and surgical towel laying, there was a sudden occurrence of severe PE and cardiac arrest; the patient was successfully resuscitated. Computed tomography pulmonary angiography (CTPA) was performed to confirm the diagnosis, and the patient's condition improved after thrombolytic therapy. Unfortunately, the patient's family eventually discontinued treatment. Discussion: Massive PE frequently occurs suddenly, may endanger a patient's life at any point in time, and cannot be diagnosed quickly on the basis of clinical manifestations. Although the vital signs fluctuate greatly and there is insufficient time to conduct more tests, some factors such as special disease history, electrocardiography, end-tidal carbon dioxide, and blood gas analysis may help us determine the preliminary diagnosis; however, the final diagnosis is made using CTPA. Current treatment options include thrombectomy, thrombolysis, and early anticoagulation, of which thrombolysis and early anticoagulation are the most feasible. Conclusion: Massive PE is a life-threatening disease that requires early diagnosis and timely treatment to save patients' lives.

Significant Functional Differences Between Dopamine D4 Receptor Polymorphic Variants Upon Heteromerization with α1A Adrenoreceptors.

The functional role of the dopamine D4 receptor (D4R) and its main polymorphic variants has become more evident with the demonstration of heteromers of D4R that control the function of frontal cortico-striatal neurons. Those include heteromers with the α2A adrenoceptor (α2AR) and with the D2R, localized in their cortical somato-dendritic region and striatal nerve terminals, respectively. By using biophysical and cell-signaling methods and heteromer-disrupting peptides in mammalian transfected cells and rat brain slice preparations, here we provide evidence for a new functionally relevant D4R heteromer, the α1AR-D4R heteromer, which is also preferentially localized in cortico-striatal glutamatergic terminals. Significant differences in allosteric modulations between heteromers of α1AR with the D4.4R and D4.7R polymorphic variants could be evidenced with the analysis of G protein-dependent and independent signaling. Similar negative allosteric modulations between α1AR and D4R ligands could be demonstrated for both α1AR-D4.4R and α1AR-D4.7R heteromers on G protein-independent signaling, but only for α1AR-D4.4R on G protein-dependent signaling. From these functional differences, it is proposed that the D4.4R variant provides a gain of function of the α1AR-mediated noradrenergic stimulatory control of cortico-striatal glutamatergic neurotransmission, which could result in a decrease in the vulnerability for impulse control-related neuropsychiatric disorders and increase in the vulnerability for posttraumatic stress disorder.

Preparation of carbon nanotubes by catalytic pyrolysis of dechlorinated PVC.

Plastic waste is attracting growing interest for its utilization potential as a valuable resource. However, conventional thermochemical methods can hardly achieve high-value utilization of certain plastics, such as polyvinyl chloride (PVC) characterized with high chlorine content. Here, a low-temperature aerobic pretreatment method was introduced to realize high-efficiency dechlorination of PVC, and then the dechlorinated PVC was used to prepare carbon nanotubes (CNTs) by a catalytic pyrolysis. The results demonstrate that oxygen can significantly promote the HCl release in a pretty low-temperature range (260-340 °C). Chlorine was almost completely eliminated at 280 °C under 20 % oxygen concentration. Compared to untreated PVC, using the dechlorinated PVC as raw material, higher carbon deposition was obtained and over 60 % CNTs could be collected from the carbon deposition. This study provides a high-value utilization way for the production of CNTs from waste PVC.