The alpha-1A adrenergic receptor regulates mitochondrial oxidative metabolism in the mouse heart.

AIMS: The sympathetic nervous system regulates numerous critical aspects of mitochondrial function in the heart through activation of adrenergic receptors (ARs) on cardiomyocytes. Mounting evidence suggests that α1-ARs, particularly the α1A subtype, are cardioprotective and may mitigate the deleterious effects of chronic ß-AR activation by shared ligands. The mechanisms underlying these adaptive effects remain unclear. Here, we tested the hypothesis that α1A-ARs adaptively regulate cardiomyocyte oxidative metabolism in both the uninjured and infarcted heart. METHODS: We used high resolution respirometry, fatty acid oxidation (FAO) enzyme assays, substrate-specific electron transport chain (ETC) enzyme assays, transmission electron microscopy (TEM) and proteomics to characterize mitochondrial function comprehensively in the uninjured hearts of wild type and α1A-AR knockout mice and defined the effects of chronic ß-AR activation and myocardial infarction on selected mitochondrial functions. RESULTS: We found that isolated cardiac mitochondria from α1A-KO mice had deficits in fatty acid-dependent respiration, FAO, and ETC enzyme activity. TEM revealed abnormalities of mitochondrial morphology characteristic of these functional deficits. The selective α1A-AR agonist A61603 enhanced fatty-acid dependent respiration, fatty acid oxidation, and ETC enzyme activity in isolated cardiac mitochondria. The ß-AR agonist isoproterenol enhanced oxidative stress in vitro and this adverse effect was mitigated by A61603. A61603 enhanced ETC Complex I activity and protected contractile function following myocardial infarction. CONCLUSIONS: Collectively, these novel findings position α1A-ARs as critical regulators of cardiomyocyte metabolism in the basal state and suggest that metabolic mechanisms may underlie the protective effects of α1A-AR activation in the failing heart.

LINC00665 promotes glycolysis in lung adenocarcinoma cells via the let-7c-5p/HMMR axis.

Lung adenocarcinoma (LUAD) is one of the most lethal and common malignancies. The energy metabolism of LUAD is a critical factor affecting its malignant progression, and research on this topic can aid in the development of novel cancer treatment targets. Bioinformatics analysis of the expression of long non-coding RNA (lncRNA) LINC00665 in LUAD was performed. Downstream regulatory molecules of LINC00665 were predicted using the StarBase database. We used quantitative reverse transcription polymerase chain reaction and western blot to measure the expression at mRNA and protein levels, respectively. The effects of the LINC00665/let-7c-5p/HMMR axis on cell viability in vitro were tested by CCK-8 assay. The regulatory effects on glycolysis were analyzed by extracellular acidification rate, oxygen consumption rate, glucose uptake, adenosine triphosphate production, and lactate production. The predicted competitive endogenous RNA mechanism between LINC00665 and let-7c-5p/HMMR was verified by a dual-luciferase reporter gene assay. LINC00665 was upregulated in LUAD. Silencing LINC00665 inhibited tumor proliferation and reduced the glycolytic activity of tumor cells. Additionally, the expression of LINC00665 had a negative correlation with that of let-7c-5p, while the expression of HMMR was remarkably inhibited by let-7c-5p. HMMR could affect the development of LUAD by influencing glycolytic capacity. Mechanistically, LINC00665 acted as a molecular sponge to absorb let-7c-5p and targeted HMMR. Transfection of let-7c-5p inhibitor or overexpression of HMMR plasmid could reverse the inhibition in proliferation and glycolysis of LUAD cells induced by silencing of LINC00665. In summary, this study demonstrated that the LINC00665/let-7c-5p/HMMR regulatory axis promoted the tumorigenesis of LUAD by enhancing aerobic glycolysis, suggesting that this regulatory axis was an effective target for inhibiting LUAD progression and providing theoretical support for the development of new drugs for LUAD.

Treatment-related pneumonitis after thoracic radiotherapy/chemoradiotherapy combined with anti-PD-1 monoclonal antibodies in advanced esophageal squamous cell carcinoma.

PURPOSE: This study aims to evaluate the risk factors of treatment-related pneumonitis (TRP) following thoracic radiotherapy/chemoradiotherapy combined with anti-PD­1 monoclonal antibodies (mAbs) in patients with advanced esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively reviewed 97 patients with advanced ESCC who were treated with thoracic radiotherapy/chemoradiotherapy combined with anti-PD­1 mAbs. Among them, 56 patients received concurrent radiotherapy with anti-PD­1 mAbs and 41 patients received sequential radiotherapy with anti-PD­1 mAbs. The median prescribed planning target volume (PTV) dose was 59.4 Gy (range from 50.4 to 66 Gy, 1.8-2.2 Gy/fraction). Clinical characteristics, the percentage of lung volume receiving more than 5-50 Gy in increments of 5 Gy (V5-V50, respectively) and the mean lung dose (MLD) were analyzed as potential risk factors for TRP. RESULTS: 46.4% (45/97), 20.6% (20/97), 20.6% (20/97), 4.1% (4/97), and 1.0% (1/97) of the patients developed any grade of TRP, grade 1 TRP, grade 2 TRP, grade 3 TRP, and fatal (grade 5) TRP, respectively. Anti-PD­1 mAbs administered concurrently with radiotherapy, V5, V10, V15, V25, V30, V35, V40 and MLD were associated with the occurrence of grade 2 or higher TRP. Concurrent therapy (P = 0.010, OR = 3.990) and V5 (P = 0.001, OR = 1.126) were independent risk factors for grade 2 or higher TRP. According to the receiver operating characteristic (ROC) curve analysis, the optimal V5 threshold for predicting grade 2 or higher TRP was 55.7%. CONCLUSION: The combination of thoracic radiotherapy/chemoradiotherapy with anti-PD­1 mAbs displayed a tolerable pulmonary safety profile. Although the incidence of TRP was high, grade 1-2 TRP accounted for the majority. Anti-PD­1 mAbs administered concurrently with radiotherapy and the lung V5 were significantly associated with the occurrence of grade 2 or higher TRP. Therefore, it seems safer to control V5 below 55% in clinical, especially for the high-risk populations receiving concurrent therapy.

Identification and functional marker development of SbPLSH1 conferring purple leaf sheath in sorghum.

KEY MESSAGE: We identified a SbPLSH1gene conferring purple leaf sheath in sorghum (sorghumbicolor(L.) Moench)and developed a functional markerfor it. The purple leaf sheath of sorghum, a trait mostly related to anthocyanin deposition, is a visually distinguishable morphological marker widely used to evaluate the purity of crop hybrids. We aimed to dissect the genetic mechanism for leaf sheath color to mine the genes regulating this trait. In this study, two F2 populations were constructed by crossing a purple leaf sheath inbred line (Gaoliangzhe) with two green leaf sheath inbred lines (BTx623 and Silimei). Based on the results of bulked-segregant analysis sequencing, bulk-segregant RNA sequencing, and map-based cloning, SbPLSH1 (Sobic.006G175700), which encodes a bHLH transcription factor on chromosome 6, was identified as the candidate gene for purple leaf sheath in sorghum. Genetic analysis demonstrated that overexpression of SbPLSH1 in Arabidopsis resulted in anthocyanin deposition and purple petiole, while two single-nucleotide polymorphism (SNP) variants on the exon 6 resulted in loss of function. Further haplotype analysis revealed that there were two missense mutations and one cis-acting element mutation in SbPLSH1, which are closely associated with leaf sheath color in sorghum. Based on the variations, a functional marker (LSC4-2) for marker-assisted selection was developed, which has a broad-spectrum capability of distinguishing leaf sheath color in natural variants. In summary, this study lays a foundation for analyzing the genetic mechanism for sorghum leaf sheath color.

To flip or not: Case series of coronary angioplasty in patients with right-sided heart.

Coronary angioplasty in patients with a right-sided heart may be difficult due to challenges in engaging the coronary arteries, interpreting angiogram, and further delivering intracoronary therapies. We present our experience of percutaneous coronary intervention in two cases and propose a practical algorithm to approach cardiac catheterization in these patients.

Precise Synthesis of Diastereomers of Spiro-oxindole Derivatives through Dynamic Covalent Transformation.

In this study, [1+2+2] cyclization of tryptamine-derived isocyanides with 3-ylideneoxindoles was systematically investigated. A series of structurally complex spiro-oxindole derivatives were obtained. Characteristic dynamic covalent chemistry was observed and confirmed by experiments and density functional theory calculation. Through the regulation of the solvent, temperature, and time, the precise and stereodivergent synthesis of spiro-oxindoles was achieved.

Fusobacterium nucleatum bacteremia complicated with intracranial Porphyromonas gingivalis and HSV-1 infection: a case report and literature review.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) belongs to the genus Fusobacterium, which is a gram-negative obligate anaerobic bacterium. Bacteremia associated with F. nucleatum is a serious complication, which is not common in clinic, especially when it is combined with other intracranial pathogenic microorganism infection. We reported for the first time a case of F. nucleatum bacteremia combined with intracranial Porphyromonas gingivalis (P. gingivalis) and herpes simplex virus type 1(HSV-1) infection. CASE PRESENTATION: A 60-year-old woman was admitted to our hospital with a headache for a week that worsened for 2 days. Combined with history, physical signs and examination, it was characterized as ischemic cerebrovascular disease (ICVD). F. nucleatum was detected in blood by matrix-assisted laser desorption/ionization time-offight mass spectrometry (MALDI-TOF-MS). Meanwhile, P. gingivalis and HSV-1 in cerebrospinal fluid (CSF) were identified by metagenome next generation sequencing (mNGS). After a quick diagnosis and a combination of antibiotics and antiviral treatment, the patient recovered and was discharged. CONCLUSION: To our knowledge, this is the first report of intracranial P. gingivalis and HSV-1 infection combined with F. nucleatum bacteremia.

Folate-modified liposomes mediate the co-delivery of cisplatin with miR-219a-5p for the targeted treatment of cisplatin-resistant lung cancer.

Cisplatin (DDP) resistance, often leading to first-line chemotherapy failure in non-small cell lung cancer (NSCLC), poses a significant challenge. MiR-219a-5p has been reported to enhance the sensitivity of human NSCLC to DDP. However, free miR-219a-5p is prone to degradation by nucleases in the bloodstream, rendering it unstable. In light of this, our study developed an efficient nanodrug delivery system that achieved targeted delivery of DDP and miR-219a-5p by modifying liposomes with folate (FA). Based on the results of material characterization, we successfully constructed a well-dispersed and uniformly sized (approximately 135.8 nm) Lipo@DDP@miR-219a-5p@FA nanodrug. Agarose gel electrophoresis experiments demonstrated that Lipo@DDP@miR-219a-5p@FA exhibited good stability in serum, effectively protecting miR-219a-5p from degradation. Immunofluorescence and flow cytometry experiments revealed that, due to FA modification, Lipo@DDP@miR-219a-5p@FA could specifically bind to FA receptors on the surface of tumor cells (A549), thus enhancing drug internalization efficiency. Safety evaluations conducted in vitro demonstrated that Lipo@DDP@miR-219a-5p@FA exhibited no significant toxicity to non-cancer cells (BEAS-2B) and displayed excellent blood compatibility. Cellular functional experiments, apoptosis assays, and western blot demonstrated that Lipo@DDP@miR-219a-5p@FA effectively reversed DDP resistance in A549 cells, inhibited cell proliferation and migration, and further promoted apoptosis. In summary, the Lipo@DDP@miR-219a-5p@FA nanodrug, through specific targeting of cancer cells and reducing their resistance to DDP, significantly enhanced the anti-NSCLC effects of DDP in vitro, providing a promising therapeutic option for the clinical treatment of NSCLC.

Ultra-Fast Selenol-Yne Click (SYC) Reaction Enables Poly(selenoacetal) Covalent Adaptable Network Formation.

The emergence of covalent adaptable networks (CANs) based on dynamic covalent bonds (DCBs) presents a promising avenue for achieving resource recovery and utilization. In this study, we discovered a novel dynamic covalent bond called selenacetal, which is obtained through a double click reaction between selenol and activated alkynes. Density functional theory (DFT) calculations demonstrated that the ΔG for the formation of selenoacetals ranges from 12 to 18 kJ mol-1, suggesting its potential for dynamic reversibility. Dynamic exchange experiments involving small molecules and polymers provide substantial evidence supporting the dynamic exchange properties of selenoacetals. By utilizing this highly efficient click reaction, we successfully synthesized dynamic materials based on selenoacetal with remarkable reprocessing capabilities without any catalysts. These materials exhibit chemical recycling under alkaline conditions, wherein selenoacetal (SA) can decompose into active enone selenide (ES) and diselenides. Reintroducing selenol initiates a renewed reaction with the enone selenide, facilitating material recycling and yielding a newly developed dynamic material exhibiting both photo- and thermal responsiveness. The results underscore the potential of selenoacetal polymers in terms of recyclability and selective degradation, making them a valuable addition to conventional covalent adaptable networks.

Hsa_circRNA_102051 regulates colorectal cancer proliferation and metastasis by mediating Notch pathway.

BACKGROUND: The purpose of this study was to investigate the role of hsa_circRNA_102051 in colorectal cancer (CRC) and its effect on the stemness of tumor cells. METHODS: CircRNA microarray was under analysis to screen differentially expressed novel circRNAs in the pathology of CRC. Quantitative real-time PCR was used to detect the relative RNA expression in CRC cells and samples. The effects of hsa_circRNA_102051 on biological functions in CRC cells were accessed both in vitro and in vivo. FISH, RIP and luciferase reporter assay were conducted to confirm the regulatory correlations between hsa_circRNA_102051 and miR-203a, as well as miR-203a and BPTF. Xenograft models were applied to further verify the impacts and fluctuations of hsa_circRNA_102051/miR-203a/BPTF. Moreover, the mechanism how hsa_circRNA_102051 affected the Notch signals was also elucidated. RESULTS: Hsa_circRNA_102051 was up-regulated in CRC tissues and cell lines, capable to promote the growth and invasion of CRC. In addition, hsa_circRNA_102051 could enhance stemness of CRC cells. BPTF was identified as downstream factors of hsa_circRNA_102051, and miR-203a was determined directly targeting both hsa_circRNA_102051 and BPTF as an intermediate regulator. Hsa_circRNA_102051 in CRC could block miR-203a expression, and subsequently activated BPTF. Hsa_circRNA_102051/miR-203a/BPTF axis modulated stemness of CRC cells by affecting Notch pathway. CONCLUSIONS: Our findings provided new clues that hsa_circRNA_102051 might be a potential predictive or prognostic factor in CRC, which induced the fluctuation of downstream miR-203a/BPTF, and subsequently influenced tumor growth, activities and stemness. Thereinto, the Notch signals were also involved. Hence, the hsa_circRNA_102051/miR-203a/BPTF axis could be further explored as a therapeutic target for anti-metastatic therapy in CRC patients.

Chemoradiotherapy combined with immunotherapy in stage III non-small cell lung cancer: a systematic review and meta-analysis of efficacy and safety outcomes.

Background Since the success of the PACIFIC trial, durvalumab has become the clear standard of care for many patients with stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CRT). However, the duration of immune consolidation and the efficacy and safety of different immune agents remain unclear. We conducted a systematic review of relevant studies. Methods We searched all the relevant studies in PubMed, Embase and Cochrane Library databases. We also reviewed abstracts of relevant conferences, to prevent omissions. The meta-analysis was performed using Stata version 16.0. Results Chemoradiotherapy combined with immunotherapy can improve PFS (HR: 0.60, 95%CI :0.55-0.60) and OS (HR: 0.59, 95%CI :0.53-0.66) compared with no immunotherapy. The pooled 24-month PFS and 24-month OS rates were 48.1% (95% CI, 43.5%-52.7%) and 71.3% (95% CI, 67.3%-75.2%), respectively. Subgroup analysis showed that 24-month OS rates were 60.7% (95%CI, 51.0%-70.3%) and 77.4% (95%CI, 73.2%-81.7%) at 1 year and 2 years of immune consolidation, respectively. The pooled 1-year completion rate for immune consolidation was 35.6% (95%CI, 31.3%-39.8%). The pooled rate of pneumonitis for all grades was 41.7% (95%CI, 31.9%-51.9%). The pooled rate of pneumonitis ≥ grade 3 was 6.7% (95%CI, 5.0%-8.5%). The incidence of pneumonitis ≥ grade 3 after 1 year of immunotherapy is 4.8% (95%CI, 3.1%-6.5%). The incidence of pneumonitis ≥ grade 3 after 2 years of immunotherapy is 5.1% (95%CI, 2.9%-7.3%). Conclusions Prolonging the duration of immunotherapy consolidation increases survival benefits in patients with stage III NSCLC without causing higher side effects. Older patients, due to high incidence of pneumonia and low immunotherapy completion rate, have less survival benefit.

Influencing factors and predictive model of postoperative infection in patients with primary hepatic carcinoma.

BACKGROUND: The purpose of this study was to explore the risk factors for postoperative infection in patients with primary hepatic carcinoma (PHC), build a nomogram prediction model, and verify the model to provide a better reference for disease prevention, diagnosis and treatment. METHODS: This single-center study included 555 patients who underwent hepatobiliary surgery in the Department of Hepatobiliary Surgery of Tianjin Third Central Hospital from January 2014 to December 2021, and 32 clinical indicators were selected for statistical analysis. In this study, Lasso logistic regression was used to determine the risk factors for infection after liver cancer resection, establish a predictive model, and construct a visual nomogram. The consistency index (C-index), calibration curve, and receiver operating characteristic (ROC) curve were used for internal validation, and decision curve analysis (DCA) was used to analyze the clinical applicability of the predictive model. The bootstrap method was used for intramodel validation, and the C-index was calculated to assess the model discrimination. RESULTS: Among the 555 patients, 279 patients met the inclusion criteria, of whom 48 had a postoperative infection, with an incidence rate of 17.2%. Body mass index (BMI) (P = 0.022), alpha-fetoprotein (P = 0.023), total bilirubin (P = 0.016), intraoperative blood loss (P < 0.001), and bile leakage (P < 0.001) were independent risk factors for infection after liver cancer surgery. The nomogram was constructed and verified to have good discriminative and predictive ability. DCA showed that the model had good clinical applicability. The C-index value verified internally by the bootstrap method results was 0.818. CONCLUSION: Postoperative infection in patients undergoing hepatectomy may be related to risk factors such as BMI, preoperative AFP level, TBIL level, intraoperative blood loss and bile leakage. The prediction model of the postoperative infection nomogram established in this study can better predict and estimate the risk of postoperative infection in patients undergoing hepatectomy.

Clonal Hematopoiesis and the Heart: a Toxic Relationship.

PURPOSE OF REVIEW: Clonal hematopoiesis (CH) refers to the expansion of hematopoietic stem cell clones and their cellular progeny due to somatic mutations, mosaic chromosomal alterations (mCAs), or copy number variants which naturally accumulate with age. CH has been linked to increased risk of blood cancers, but CH has also been linked to adverse cardiovascular outcomes. RECENT FINDINGS: A combination of clinical outcome studies and mouse models have offered strong evidence that CH mutations either correlate with or cause atherosclerosis, diabetes mellitus, chronic kidney disease, heart failure, pulmonary hypertension, aortic aneurysm, myocardial infarction, stroke, aortic stenosis, poor outcomes following transcatheter aortic valve replacement (TAVR) or orthotopic heart transplant, death or need of renal replacement therapy secondary to cardiogenic shock, death from cardiovascular causes at large, and enhance anthracycline cardiac toxicity. Mechanistically, some adverse outcomes are caused by macrophage secretion of IL-1ß and IL-6, neutrophil invasion of injured myocardium, and T-cell skewing towards inflammatory phenotypes. CH mutations lead to harmful inflammation and arterial wall invasion by bone marrow-derived cells resulting in poor cardiovascular health and outcomes. Blockade of IL-1ß or JAK2 signaling are potential avenues for preventing CH-caused cardiovascular morbidity and mortality.

Magnetic induction heating and drug release properties of magnetic carbon nanotubes.

AIM: The use of magnetic carbon nanotubes for multi-modal cancer treatment, incorporating both hyperthermia and drug delivery functions, has drawn substantial interest. Yet, the present method of regulating hyperthermia temperature involves manually adjusting the magnetic field intensity, adding to the complexity and difficulty of clinical applications. This study seeks to design novel magnetic carbon nanotubes capable of self-temperature regulation, and investigate their drug loading and release characteristics. METHODS: Using the co-precipitation method, we synthesized magnetic carbon nanotubes with a Curie temperature of 43 °C. A comprehensive investigation was conducted to analyze their morphology, crystal structure, and magnetic characteristics. To enhance their functionality, chitosan and sodium alginate modifications were introduced, enabling the loading of the antitumor drug doxorubicin hydrochloride (DOX) into these magnetic carbon nanotubes. Subsequently, the loading and release properties of DOX were investigated within the modified magnetic nanotubes. RESULTS: Under alternating magnetic field, magnetic carbon nanotubes exhibit self-regulating properties by undergoing a magnetic phase transition, maintaining temperatures around 43 °C as required for hyperthermia. On the other hand, during magnetic induction heating, the release percentage of DOX reached 23.5% within 2 h and 71.7% within 70 h at tumor pH conditions, indicating their potential for sustained drug release. CONCLUSIONS: The prepared magnetic carbon nanotubes can effectively regulate the temperature during hyperthermia treatment while ensuring controlled drug release, which presents a promising method for preparing nanomaterials that synergistically enhance magnetic hyperthermia and chemotherapy drugs.

High-normal serum uric acid predicts macrovascular events in patients with type 2 diabetes mellitus without hyperuricemia based on a 10-year cohort.

BACKGROUND AND AIMS: The upper limits of normal serum uric acid (SUA) or the lower limits of hyperuricemia were frequently set at 420 or 360 µmol/L (7.0 or 6.0 mg/dL). We aimed to explore the association between high-normal SUA (360 ≤ SUA≤420 µmol/L) and incidence of macrovascular and renal events based on a 10-year cohort with type 2 diabetes mellitus (T2DM) to explore which cut-off was more appropriate. METHODS AND RESULTS: A total of 2988 patients with T2DM without hyperuricemia (SUA≤420 µmol/L) were included and followed up. Cox proportional hazards models and restricted cubic spline regression were used to evaluate the relationship between baseline SUA (as continuous and categorical variable) and macrovascular and renal events. Patients were grouped as low-normal (SUA<360 µmol/L) and high-normal groups based on baseline SUA, and the latter group had higher incidence of macrovascular events. Multivariate Cox regression analysis indicated that baseline levels of SUA were significantly associated with cardiovascular (HR = 1.385, 95%CI:1.190-1.613, P < 0.001) and peripheral vascular events (HR = 1.266, 95%CI:1.018-1.574, P = 0.034), and the linear association existed. Moreover, fully adjusted multivariable Cox analyses indicated high-normal SUA increased the risks of cardiovascular (HR = 1.835, 95%CI:1.319-2.554, P < 0.001) and peripheral vascular events (HR = 1.661, 95%CI:1.000-2.760, P = 0.050) compared to low-normal SUA. CONCLUSIONS: Baseline SUA levels were positively associated with cardiovascular and peripheral vascular events, and high-normal SUA increased the risks of these events in patients with T2DM even without hyperuricemia. A threshold value for SUA of 360 µmol/L should be more appropriate in terms of predicting macrovascular events risks compared to the value of 420 µmol/L.

Information dissemination during public health emergencies: analysing the international flow of COVID-19-related news.

A large-scale exchange of information between media across national borders is frequently observed when a worldwide public health emergency occurs. This study investigated the global news citation network in the early stage of the COVID-19 pandemic by analysing the network structure at different levels to identify important nodes and the relationships among news organisations. The results show that COVID-19-related international news flow had a complex and unequal pattern, with a few countries and media outlets occupying a prominent place in the network and three media groups played key but different roles in disseminating the news. It was jointly influenced by national traits, the relatedness between countries, and the pandemic emergency with public health risks. From a global perspective, the media of the United States, mainland China, and the United Kingdom played the most important parts in collaboration within the world media system in the early stage of the COVID-19 pandemic.

Thermally Responsive Selenide-containing Materials Based on Transalkylation of Selenonium Salts.

Covalent adaptable networks (CANs) possess unique properties as a result of their internal dynamic bonds, such as self-healing and reprocessing abilities. In this study, we report a thermally responsive C-Se dynamic covalent chemistry (DCC) that relies on the transalkylation exchange between selenonium salts and selenides, which undergo a fast transalkylation reaction in the absence of any catalyst. Additionally, we demonstrate the presence of a dissociative mechanism in the absence of selenide groups. After incorporation of this DCC into selenide-containing polymer materials, it was observed that the cross-linked networks display varying dynamic exchange rates when using different alkylation reagents, suggesting that the reprocessing capacity of selenide-containing materials can be regulated. Also, by incorporating selenonium salts into polymer materials, we observed that the materials exhibited good healing ability at elevated temperatures as well as excellent solvent resistance at ambient temperature. This novel dynamic covalent chemistry thus provides a straightforward method for the healing and reprocessing of selenide-containing materials.

Sub-shot-noise-limited phase estimation via single-mode inputs.

In 1981, Caves pointed out that the phase sensitivity of a Mach-Zehnder interferometer with single-mode inputs is bounded by the shot-noise limit. The quantum Fisher information analysis shows that this statement holds true for the scenario where two antisymmetric phase shifts occur in two arms, but it is invalid for the scenario where an unknown phase is embedded in one of two arms. In this paper, we focus on the phase sensitivity directed against the latter scenario. The optimal single-mode input is discussed by analyzing common states, including displaced squeezed states, displaced number states, squeezed number states, Schrödinger cat states and completely mixed states. We find that the best choice is a squeezed vacuum state and show the specific measurement scheme which is capable of saturating the corresponding phase sensitivity limit. In addition, we study the effects of several realistic factors-anti-squeezing noise, photon loss and dark counts-on the phase sensitivity. Our results suggest that sub-shot-noise-limited phase sensitivity is attainable with low noise or loss, which paves the way for practical metrology.

A promising Prognostic risk model for advanced renal cell carcinoma (RCC) with immune-related genes.

BACKGROUND: Renal cell carcinoma (RCC) is a third most common tumor of the urinary system. Nowadays, Immunotherapy is a hot topic in the treatment of solid tumors, especially for those tumors with pre-activated immune state. METHODS: In this study, we downloaded genomic and clinical data of RCC samples from The Cancer Genome Atlas (TCGA) database. Four immune-related genetic signatures were used to predict the prognosis of RCC by Cox regression analysis. Then we established a prognostic risk model consisting of the genes most related to prognosis from four signatures to value prognosis of the RCC samples via Kaplan-Meier (KM) survival analysis. An independent data from International Cancer Genome Consortium (ICGC) database were used to test the predictive stability of the model. Furthermore, we performed landscape analysis to assess the difference of gene mutant in the RCC samples from TCGA. Finally, we explored the correlation between the selected genes and the level of tumor immune infiltration via Tumor Immune Estimation Resource (TIMER) platform. RESULTS: We used four genetic signatures to construct prognostic risk models respectively and found that each of the models could divide the RCC samples into high- and low-risk groups with significantly different prognosis, especially in advanced RCC. A comprehensive prognostic risk model was constructed by 8 candidate genes from four signatures (HLA-B, HLA-A, HLA-DRA, IDO1, TAGAP, CIITA, PRF1 and CD8B) dividing the advanced RCC samples from TCGA database into high-risk and low-risk groups with a significant difference in cancer-specific survival (CSS). The stability of the model was verified by independent data from ICGC database. And the classification efficiency of the model was stable for the samples from different subgroups. Landscape analysis showed that mutation ratios of some genes were different between two risk groups. In addition, the expression levels of the selected genes were significantly correlated with the infiltration degree of immune cells in the advanced RCC. CONCLUSIONS: Sum up, eight immune-related genes were screened in our study to construct prognostic risk model with great predictive value for the prognosis of advanced RCC, and the genes were associated with infiltrating immune cells in tumors which have potential to conduct personalized treatment for advanced RCC.

Cloning and characterization of four enzymes responsible for cyclohexylamine degradation from Paenarthrobacter sp. TYUT067.

Paenarthrobacter sp. TYUT067 is a soil bacterium that can degrade and use cyclohexylamine as the sole source of carbon and energy. However, the responsible enzymes involved in cyclohexylamine degradation by TYUT067 have not been cloned and characterized in detail yet. In this study, four possible cyclohexylamine degradation genes, one cyclohexylamine oxidase (Pachao), two cyclohexanone monooxygenases (Pachms) and one lactone hydrolase (Pamlh) were successfully cloned and heterologous expressed in Escherichia coli T7 host cells. The four enzymes were purified and characterized. The optimal pH and temperature of the purified enzymes toward their own substrates were 7.0 (PaCHAO), 8.0 (PaCHM1), 9.0 (PaCHM2 and PaMLH) and 30 °C (PaCHAO and PaMLH), 40 °C (PaCHM2) and 45 °C (PaCHM1), respectively, with KM of 1.1 mM (PaCHAO), 0.1 mM (PaCHM1), 0.1 mM (PaCHM2) and 0.8 mM (PaMLH), and yielding a catalytic efficiency kcat/KM of 16.1 mM-1 s-1 (PaCHAO), 1.0 mM-1 s-1 (PaCHM1), 5.0 mM-1 s-1 (PaCHM2) and 124.4 mM-1 s-1 (PaMLH). In vitro mimicking the cyclohexylamine degradation pathway was conducted by using the combined three cyclohexylamine degradation enzymes (PaCHAO, PaCHM2 and PaMLH) with 10-50 mM cyclohexylamine, 100% conversion of cyclohexylamine could be finished within 12 h without any detected intermediates. The current study confirmed the enzymes responsible for cyclohexylamine degradation in TYUT067 for the first time, provide basic information for further investigation and application of these specific enzymes in pollution control.