Combined therapy of dabrafenib and an anti-HER2 antibody-drug conjugate for advanced BRAF-mutant melanoma.

BACKGROUND: Melanoma is the most lethal skin cancer characterized by its high metastatic potential. In the past decade, targeted and immunotherapy have brought revolutionary survival benefits to patients with advanced and metastatic melanoma, but these treatment responses are also heterogeneous and/or do not achieve durable responses. Therefore, novel therapeutic strategies for improving outcomes remain an unmet clinical need. The aim of this study was to evaluate the therapeutic potential and underlying molecular mechanisms of RC48, a novel HER2-target antibody drug conjugate, either alone or in combination with dabrafenib, a V600-mutant BRAF inhibitor, for the treatment of advanced BRAF-mutant cutaneous melanoma. METHODS: We evaluated the therapeutic efficacy of RC48, alone or in combination with dabrafenib, in BRAF-mutant cutaneous melanoma cell lines and cell-derived xenograft (CDX) models. We also conducted signaling pathways analysis and global mRNA sequencing to explore mechanisms underlying the synergistic effect of the combination therapy. RESULTS: Our results revealed the expression of membrane-localized HER2 in melanoma cells. RC48 effectively targeted and inhibited the growth of HER2-positive human melanoma cell lines and corresponding CDX models. When used RC48 and dabrafenib synergically induced tumor regression together in human BRAF-mutant melanoma cell lines and CDX models. Mechanically, our results demonstrated that the combination therapy induced apoptosis and cell cycle arrest while suppressing cell motility in vitro. Furthermore, global RNA sequencing analysis demonstrated that the combination treatment led to the downregulation of several key signaling pathways, including the PI3K-AKT pathway, MAPK pathway, AMPK pathway, and FOXO pathway. CONCLUSION: These findings establish a preclinical foundation for the combined use of an anti-HER2 drug conjugate and a BRAF inhibitor in the treatment of BRAF-mutant cutaneous melanoma.

PIVKA-II combined with alpha-fetoprotein for the diagnostic value of hepatic tumors in children: a multicenter, prospective observational study.

BACKGROUND: To investigate whether protein induced by vitamin K antagonist-II (PIVKA-II) combined with alpha-fetoprotein (AFP) can improve the diagnostic and differential diagnostic accuracy of childhood hepatic tumors. METHODS: A multi-center prospective observational study was performed at nine regional institutions around China. Children with hepatic mass (Group T) were divided into hepatoblastoma group (Group THB) and hemangioendothelioma group (Group THE), children with extrahepatic abdominal mass (Group C). Peripheral blood was collected from each patient prior to surgery or chemotherapy. The area under the curve (AUROC) was used to evaluate the diagnostic efficiency of PIVKA-II and the combined tumor markers with AFP. RESULTS: The mean levels of PIVKA-II and AFP were both significantly higher in Group T than Group C (p = 0.001, p < 0.001), in Group THB than Group THE (p = 0.018, p = 0.013) and in advanced HB than non-advanced HB (p = 0.001, p = 0.021). For the diagnosis of childhood hepatic tumors, AUROC of PIVKA-II (cut-off value 32.6 mAU/mL) and AFP (cut-off value 120 ng/mL) was 0.867 and 0.857. The differential diagnostic value of PIVKA-II and AFP in hepatoblastoma from hemangioendothelioma was further assessed, AUROC of PIVKA-II (cut-off value 47.1mAU/mL) and AFP (cut-off value 560 ng/mL) was 0.876 and 0.743. The combined markers showed higher AUROC (0.891, 0.895 respectively) than PIVKA-II or AFP alone. CONCLUSIONS: The serum level of PIVKA-II was significantly higher in children with hepatic tumors, especially those with malignant tumors. The combination of PIVKA-II with AFP further increased the diagnostic performance. TRIAL REGISTRATION: Clinical Trials, NCT03645655. Registered 20 August 2018, https://www. CLINICALTRIALS: gov/ct2/show/NCT03645655 .

Application of recombinase polymerase amplification with CRISPR/Cas12a and multienzyme isothermal rapid amplification with lateral flow dipstick assay for Bactrocera correcta.

BACKGROUND: Bactrocera correcta is a quarantine pest that negatively impacts the fruit and vegetable industry. Differentiating B. correcta from similar species, especially in non-adult stages, remains challenging. Rapid molecular identification techniques, such as recombinase polymerase amplification (RPA) combined with CRISPR/Cas12a and multienzyme isothermal rapid amplification with lateral flow dipstick (MIRA-LFD), play a crucial role in early monitoring and safeguarding agricultural production. Our study introduces two methods for the rapid visual identification of B. correcta. RESULTS: Bactrocera correcta specific RPA primers, CRISPR RNA (crRNA), and the LFD probe were designed based on the cox1 genes. The RPA reaction conditions were optimized (at 37 °C for 8 min) for effective template DNA amplification. Two nucleic acid detection methods were established to visualize RPA. In the RPA-CRISPR/Cas12a system, the optimal LbCas12a/crRNA concentration ratio was 200:400 nmol L-1 . Successful amplification was determined by the presence or absence of green fluorescence following 15 min incubation at 37 °C. The MIRA-LFD system achieved precise identification of the target species within 4 min at 37 °C. Both methods exhibited high specificity and sensitivity, allowing for detection from 1.0 × 10-1 ng µL-1 of DNA. Combined with rapid DNA extraction, rapid identification of individual B. correcta at different developmental stages was achieved, enhancing the practicality and convenience of the established methods. CONCLUSION: Our research findings demonstrate that both the RPA-CRISPR/Cas12a and MIRA-LFD methods for B. correcta detection was accurate and rapid (within 30 min and 10 min, respectively), at 37 °C. Our methods do not rely on expensive equipment, thus possess high practical value, providing improved identification solutions for port quarantine pests and field applications. © 2024 Society of Chemical Industry.

Combined inhibition of HER2 and VEGFR synergistically improves therapeutic efficacy via PI3K-AKT pathway in advanced ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is a prevalent malignancy in the female reproductive system, and developing effective targeted therapies for this disease remains challenging. The aim of this study was to use clinically-relevant OC models to evaluate the therapeutic effectiveness of RC48, an antibody-drug conjugate (ADC) targeting HER2, either alone or in combination with the VEGFR inhibitor Cediranib Maleate (CM), for the treatment of advanced OC. METHODS: OC tumor specimens and cell lines were analyzed to determine HER2 and VEGFR expression by Western blot, immunocytochemistry and immunofluorescence. Moreover, the OC cell lines, cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models were treated with RC48 and/or CM and then subjected to cell proliferation, viability, apoptosis, and tumor growth analyses to evaluate the feasibility of combination therapy for OC both in vitro and in vivo. Additionally, RNA-Seq was performed to investigate the critical mechanism underlying the combination therapy of RC48 and CM. RESULTS: Our results demonstrated that RC48 alone effectively targeted and inhibited the growth of HER2-positive OC tumors in both cell lines and PDX models. Furthermore, the combination of RC48 and CM synergistically induced tumor regression in human OC cell lines, as well as CDX and PDX models. Mechanistically, we observed that the combination treatment inhibited the growth of OC cells involved inducing apoptosis and suppressing cell motility. RNA-seq analysis provided further mechanistic insights and revealed that co-administration of RC48 and CM downregulated multiple cancer-related pathways, including the AKT/mTOR pathway, cell cycle, and cell proliferation. Notably, our data further confirmed that the PI3K-AKT pathway played a key role in the inhibition of proliferation triggered by combinational treatment of RC48 and CM in OC cells. CONCLUSIONS: These findings provide a preclinical framework supporting the potential of dual targeting HER2 and VEGFR as a promising therapeutic strategy to improve outcomes in patients with OC.

Loop-mediated isothermal amplification of economically important Ceratitis species (Diptera: Tephritidae).

Ceratitis is an economically important genus of fruit flies that originated in Africa, has a wide host range, and causes serious economic losses due to its invasive damage. As a result, it is critical to identify them accurately and quickly in the world. Loop-mediated isothermal amplification (LAMP), as one of the representatives of isothermal amplification technology, has been widely used in the rapid nucleic acid detection of human pathogens and has shown its advantages in the identification of insect agricultural pests. In this study, using the mitochondrial cox1 and cob genes as target genes, the rapid molecular identification of the Ceratitis FARQ complex, C. cosyra, and C. capitata was realized based on LAMP. The experimental conditions optimization results showed that F3/B3:FIP/BIP = 1:8 was the optimal primer concentration ratio and 63 °C was the optimal reaction temperature. The sensitivity of the primers obtained in this study can reach up to 0.01 ng/µl DNA. A loop-mediated isothermal amplification identification technology system was established based on rapid, rough DNA extraction and visual detection of Ceratitis economically important fruit flies. The positive reaction system changed from pink to khaki by visual detection. The identification flow can be completed within 1 hour, including sample processing, DNA extraction, and LAMP visual detection.

Prognosis signature for predicting the survival and immunotherapy response in esophageal carcinoma based on cellular senescence-related genes.

Background: Cellular senescence occurs throughout life and can play beneficial roles in a variety of physiological processes, including embryonic development, tissue repair, and tumor suppression. However, the relationship between cellular senescence-related genes (CSRGs) and immunotherapy in esophageal carcinoma (ECa) remains poorly defined. Methods: The data set used in the analysis was retrieved from TCGA (Research Resource Identifier (RRID): SCR_003193), GEO (RRID: SCR_005012), and CellAge databases. Data processing, statistical analysis, and diagram formation were conducted in R software (RRID: SCR_001905) and GraphPad Prism (RRID: SCR_002798). Based on CSRGs, we used the TCGA database to construct a prognostic signature for ECa and then validated it in the GEO database. The predictive efficiency of the signature was evaluated using receiver operating characteristic (ROC) curves, Cox regression analysis, nomogram, and calibration curves. According to the median risk score derived from CSRGs, patients with ECa were divided into high- and low-risk groups. Immune infiltration and immunotherapy were also analyzed between the two risk groups. Finally, the hub genes of the differences between the two risk groups were identified by the STRING (RRID: SCR_005223) database and Cytoscape (RRID: SCR_003032) software. Results: A six-gene risk signature (DEK, RUNX1, SMARCA4, SREBF1, TERT, and TOP1) was constructed in the TCGA database. Patients in the high-risk group had a worse overall survival (OS) was disclosed by survival analysis. As expected, the signature presented equally prognostic significance in the GSE53624 cohort. Next, the Area Under ROC Curve (AUC=0.854) and multivariate Cox regression analysis (HR=3.381, 2.073-5.514, P<0.001) also proved that the risk signature has a high predictive ability. Furthermore, we can more accurately predict the prognosis of patients with ECa by nomogram constructed by risk score. The result of the TIDE algorithm showed that ECa patients in the high-risk group had a greater possibility of immune escape. At last, a total of ten hub genes (APOA1, MUC5AC, GC, APOA4, AMBP, FABP1, APOA2, SOX2, MUC8, MUC17) between two risk groups with the highest interaction degrees were identified. By further analysis, four hub genes (APOA4, AMBP, FABP1, and APOA2) were related to the survival differences of ECa. Conclusions: Our study reveals comprehensive clues that a novel signature based on CSRGs may provide reliable prognosis prediction and insight into new therapy for patients with ECa.

Expert consensus on the clinical application of totally implantable venous access devices in the upper arm (2022 Edition).

With the widespread adoption of ultrasound guidance, Seldinger puncture techniques, and intracardiac electrical positioning technology for the placement of peripherally inserted central catheters in recent years, an increasing number of medical staff and patients now accept peripheral placement of totally implantable venous access devices (TIVADs) in the upper arm. This approach has the advantage of completely avoiding the risks of hemothorax, pneumothorax, and neck and chest scarring. Medical specialties presently engaged in this study in China include internal medicine, surgery, anesthesiology, and interventional departments. However, command over implantation techniques, treatment of complications, and proper use and maintenance of TIVAD remain uneven among different medical units. Moreover, currently, there are no established quality control standards for implantation techniques or specifications for handling complications. Thus, this expert consensus is proposed to improve the success rate of TIVAD implantation via the upper-arm approach, reduce complication rates, and ensure patient safety. This consensus elaborates on the technical indications and contraindications, procedures and technical points, treatment of complications, and the use and maintenance of upper-arm TIVAD, thus providing a practical reference for medical staff.

Yttrium chloride induces ferroptosis in cardiomyocytes via iron accumulation and triggers cardiac lipid peroxidation and inflammation that cause heart adverse events in mice.

The growing presence of yttrium (Y) in the environment raises concern regarding its safety and toxicity. However, limited toxicological data are available to determine cardiotoxicity of Y and its underlying mechanisms. In the present study, yttrium chloride (YCl3) intervention with different doses was performed in male Kunming mice for the toxicological evaluation of Y in the heart. After 28 days of intragastric administration, 500 mg/kg·bw YCl3 induces iron accumulation in cardiomyocytes, and triggers ferroptosis through the glutathione peroxidase 4 (GPX4)/glutathione (GSH)/system Xc- axis via the inhibition of Nrf2 signaling pathway. This process led to cardiac lipid peroxidation and inflammatory response. Further RNA sequencing transcriptome analysis found that many genes involved in ferroptosis and lipid metabolism-related pathways were enriched. The ferroptosis induced by YCl3 in cardiomyocytes ultimately caused cardiac injury and dysfunction in mice. Our findings assist in the elucidation of the potential subacute cardiotoxicity of Y3+ and its underlying mechanisms.

Precise diagnosis and targeted therapy of nodal T-follicular helper cell lymphoma (T-FHCL).

Nodal T-follicular helper cell lymphoma (T-FHCL) derived from T-follicular helper (Tfh) cell falls into a heterogeneous category of peripheral T-cell lymphoma (PTCL). Due to the limited number of therapeutic regimens and limited first-line efficacy, T-FHCL has a poor prognosis, and there is an urgent need for effective targeted therapies. With advancements in sequencing technologies, especially single-cell sequencing and next-generation sequencing, more specific genetic aberrations characteristic of T-FHCL can be discovered, allowing for precise molecular diagnosis and specific research on novel agents. Many biomarker-targeting agents, used either alone or in combination, have been tested, and they have generally enhanced the therapeutic outcomes of T-FHCL. Histone deacetylase inhibitors achieve significant clinical benefits in the treatment of T-FHCL, especially in combination therapy. Chimeric antigen receptor T-cell (CAR-T-cell) immunotherapies, hematopoietic stem cell transplantation, and other potential agents merit further study.

Therapeutic efficacy of a MMAE-based anti-DR5 drug conjugate Oba01 in preclinical models of pancreatic cancer.

Pancreatic cancer (PC) is among the most aggressive malignancies associated with a 5-year survival rate of <9%, and the treatment options remain limited. Antibody-drug conjugates (ADCs) are a new class of anticancer agents with superior efficacy and safety profiles. We studied the antitumor activity of Oba01 ADC and the mechanism underlying the targeting of death receptor 5 (DR5) in preclinical PC models. Our data revealed that DR5 was highly expressed on the plasma membrane of PC cells and Oba01 showed potent in vitro antitumor activity in a panel of human DR5-positive PC cell lines. DR5 was readily cleaved by lysosomal proteases after receptor-mediated internalization. Monomethyl auristatin E (MMAE) was then released into the cytosol to induce G2/M-phase growth arrest, cell death via apoptosis induction, and the bystander effect. Furthermore, Oba01 mediated cell death via antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. For improved potency, we investigated the synergetic effect of Oba01 in combination with approved drugs. Oba01 combined with gemcitabine showed better antiproliferative activity than either standalone treatment. In cell- and patient-derived xenografts, Oba01 showed excellent tumoricidal activity in mono- or combinational therapy. Thus, Oba01 may provide a novel biotherapeutic approach and a scientific basis for clinical trials in DR5-expressing patients with PC.

Conversion mechanism of thermal plasma-enhanced CH4-CO2 reforming system to syngas under the non-catalytic conditions.

Thermal plasma activation of CH4-CO2 reforming (CRM) to syngas under non-catalytic conditions is an efficient and clean technology for the large-scale utilization of hydrocarbon resources and the conversion of greenhouse gases. This study investigates the equilibrium state and transformation mechanism of a CRM reaction system activated by thermal plasma through experimental, thermodynamic, and kinetic analyses. The experimental results illustrated that the CO2 conversion rate and H2 selectivity showed a downward trend with an increase in the CO2/CH4 molar ratio, whereas the CH4 conversion rate and CO selectivity showed the opposite trend. When CO2/CH4 molar ratio was 6/4, the selectivity for CO and H2 increased to 87.0 % and 80.8 %, respectively. Excess CO2 promotes the partial oxidation of CH4 to eliminate carbon deposition, resulting in an H2/CO molar ratio value closer to 1. Thermodynamic results show that the thermal-plasma-initiated CRM reaction can reach thermodynamic equilibrium more easily than the conventional catalyzed reactions, achieving much higher feedstock gas conversion without carbon deposition. The kinetic results obtained from the PSR model revealed that CH4 and CO2 were cleaved to form free radicals at the instant of contact with the plasma flame. O, H, and other particles generated in the form of free radicals rapidly collided with each other and transformed into CO and H2, accelerating the reaction process. The results presented in this study will help reveal the transformation mechanism of the CRM reaction activated by thermal plasma under non-catalytic conditions and provide a new perspective for studying CRM reactions.

Impact of Urbanization on Ecosystem Services Balance in the Han River Ecological Economic Belt, China: A Multi-Scale Perspective.

Urbanization intensification seriously interferes with the supply capacity and demand level of ecosystem services (ESs); therefore, it affects the balance state of ESs. Coordination of urbanization development and ecosystem protection in the ecological economic belt is vital for ecological protection and high-quality development of the ecological economic belt. However, previous studies lacked multi-scale analysis of the impact of urbanization elements on the ESs balance index (ESBI) in the ecological economic belt. In this study, a geographically weighted regression model was employed to measure the spatial non-stationary patterns associated with the impact of urbanization elements on the ESBI at 5 km and 10 km in the Han River Ecological Economic Belt (HREEB) in China based on land use data. The main findings were shown as follows. The supply capacity and demand level of ESs in the HREEB increased from 2000 to 2020 simultaneously, while the ESBI showed a decreasing trend. In mountainous areas, the ESBIs were evidently higher than those in the plain areas. During the study period, the urbanization level in the HREEB improved evidently, and the urbanization levels of the middle and lower reaches of the Hanjiang River were relatively high. Significant spatial dependence between urbanization elements and the ESBI was identified. Urbanization had significant positive and negative impacts on ESBI, and there were significant differences among different scales. The findings of this study can act as a decision-making reference for ecological protection and high-quality development of the HREEB and can also provide a perspective for exploring the impact of urbanization on the ESBI of the ecological economic belt in other similar regions.

Spatial Transcriptomics Analysis Reveals that CCL17 and CCL22 are Robust Indicators of a Suppressive Immune Environment in Angioimmunoblastic T Cell Lymphoma (AITL).

BACKGROUND: T cell lymphoma is a complex and highly aggressive clinicopathological entity with a poor outcome. The angioimmunoblastic T-cell lymphoma (AITL) tumor immune microenvironment is poorly investigated. METHODS: Here, to the best of our knowledge, spatial transcriptomics was applied for the first time to study AITL. RESULTS: Using this method, we observed that AITL was surrounded by cells bearing immune-suppressive markers. CCL17 and CCL22, the dominant ligands for CCR4, were up-regulated, while the expression of natural killer (NK) cell and CD8+ cytotoxic T lymphocyte (CTL) markers decreased. Colocalization of Treg cells with the CD4+ TFH-GC region was also deduced from the bioinformatic analysis. The results obtained with spatial transcriptomics confirm that AITL has a suppressive immune environment. Chemotherapy based on the CHOP regimen (cyclophosphamide, doxorubicin, vincristine plus prednisone) induced complete remission (CR) in this AITL patient. However, the duration of remission (DoR) remains a concern. CONCLUSIONS: This study demonstrates that AITL has an immune suppressive environment and suggests that anti-CCR4 therapy could be a promising treatment for this lethal disease.

A computational method for large-scale identification of esophageal cancer-related genes.

The incidence of esophageal cancer has obvious genetic susceptibility. Identifying esophageal cancer-related genes plays a huge role in the prevention and treatment of esophageal cancer. Through various sequencing methods, researchers have found only a small number of genes associated with esophageal cancer. In order to improve the efficiency of esophageal cancer genetic susceptibility research, this paper proposes a method for large-scale identification of esophageal cancer-related genes by computational methods. In order to improve the efficiency of esophageal cancer genetic susceptibility research, this paper proposes a method for large-scale identification of esophageal cancer-related genes by computational methods. This method fuses graph convolutional network and logical matrix factorization to effectively identify esophageal cancer-related genes through the association between genes. We call this method GCNLMF which achieved AUC as 0.927 and AUPR as 0.86. Compared with other five methods, GCNLMF performed best. We conducted a case study of the top three predicted genes. Although the association of these three genes with esophageal cancer has not been reported in the database, studies by other reseachers have shown that these three genes are significantly associated with esophageal cancer, which illustrates the accuracy of the prediction results of GCNLMF.

Slurryability and Influencing Mechanism of Hydrophobic Structures in Additive-Coal-Water Ternary System.

This study investigates the effects of additive adsorption onto coal particles on surface properties, hydrophobic groups on the slurryability, and the moisture occurrence form on the performance of coal water slurry (CWS). Mechanisms related to the different hydrophobic structures of the additives are proposed. The adsorption method of sulfonated acetone formaldehyde enhances the adsorption capacity of coal surfaces but is not conducive to slurrying. Sodium lignin sulfonate has hydrophobic ends with nonpolar aromatic groups, three-dimensional macromolecular structures, and complex branched chains, which provide CWS with good stability and slurryability. Naphthalenesulfonate formaldehyde has a double benzene ring structure and provides the thick but nonuniform adsorption layers on coal surfaces. The many amorphous structures and low molecular weights of sodium humic sulfonate lead to nonuniform hydration films and poor slurryability. The results of this paper provide guidance for improving synergism in coal-water-additive systems and enhancing slurry performance.

Acute abdomen caused by torsion of the omentum: A pediatric case report.

RATIONALE: Torsion of the omentum and infarction are rare and unusual disorders that often present as acute abdominal pain in the population. The diagnosis of omental torsion is based on clinical and imaging examinations. PATIENT CONCERNS: A 7-year-old girl presented with acute right lower quadrant abdominal pain, with symptoms resembling acute appendicitis. DIAGNOSIS: The patient was diagnosed with omental torsion based on imaging and laparoscopy. INTERVENTIONS: Laparoscopic exploration was performed. OUTCOMES: The patient was discharged seven days after satisfactory postoperative recovery. LESSONS: Omental torsion should be included in the differential diagnosis of acute abdominal pain, particularly in patients with free hemorrhagic fluid in the abdominal cavity and pelvis.

Spatially Non-Stationary Response of Carbon Emissions to Urbanization in Han River Ecological Economic Belt, China.

Within the context of the "30·60 dual carbon" goal, China's low-carbon sustainable development is affected by a series of environmental problems caused by rapid urbanization. Revealing the impacts of urbanization on carbon emissions (CEs) is conducive to low-carbon city construction and green transformation, attracting the attention of scholars worldwide. The research is rich concerning the impacts of urbanization on CEs but lacking in studies on their spatial dependence and heterogeneity at multiple different scales, especially in areas with important ecological statuses, such as the Han River Ecological Economic Belt (HREEB) in China. To address these gaps, this study first constructed an urbanization level (UL) measurement method. Then, using a bivariate spatial autocorrelation analysis and geographically weighted regression model, the spatial relationships between UL and CEs from 2000 to 2020 were investigated from a multiscale perspective. The results were shown as follows. The total CEs in the HREEB witnessed an upsurge in the past two decades, which was mainly dispersed in the central urban areas of the HREEB. The ULs in different regions of the HREEB varied evidently, with high levels in the east and low levels in the central and western regions, while the overall UL in 2020 was higher than that in 2000, regardless of the research scale. During the study period, there was a significant, positive spatial autocorrelation between UL and CEs, and similar spatial distribution characteristics of the bivariate spatial autocorrelation between CEs and UL at different times, and different scales were observed. UL impacted CEs positively, but the impacts varied at different grid scales during the study period. The regression coefficients in 2020 were higher than those in 2000, but the spatial distribution was more scattered, and more detailed information was provided at the 5 km grid scale than at the 10 km grid scale. The findings of this research can advance policy enlightenment for low-carbon city construction and green transformation in HREEB and provide a reference for CE reduction in other similar regions of the world.

Catalytic Activity of Various Carbons during the Microwave-Initiated Deep Dehydrogenation of Hexadecane.

Carbon materials have been widely used as microwave susceptors in many chemical processes because they are highly effective at transforming incoming electromagnetic energy for local (hot spot) heating. This property raises the intriguing possibility of using the all-pervasive carbonaceous deposits in operating heterogeneous catalytic processes to augment the catalytic performance of microwave-initiated reactions. Here, the catalytic activities of a range of carbon materials, together with carbon residues produced from a "test" reaction-the dehydrogenation of hexadecane under microwave-initiated heterogeneous catalytic processes, have been investigated. Despite the excellent microwave absorption properties observed among these various carbons, only activated carbons and graphene nanoplatelets were found to be highly effective for the microwave-initiated dehydrogenation of hexadecane. During the dehydrogenation of hexadecane on a Fe/SiC catalyst, active carbon species were formed at the early stage of the reactions but were subsequently transformed into filamentous but catalytically inert carbons that ultimately deactivated the operating catalyst.

Saliva specimen complements anal swab in assessing patients with COVID-19 for discharge from hospital.

Since December 2019, coronavirus disease 2019 (COVID-19) caused by SARS coronavirus 2 (SARS-CoV-2) has spread and threatens public health worldwide. The recurrence of SARS-CoV-2 RNA detection in patients after discharge from hospital signals a risk of transmission from such patients to the community and challenges the current discharge criteria of COVID-19 patients. A wide range of clinical specimens has been used to detect SARS-CoV-2. However, to date, a consensus has not been reached regarding the most appropriate specimens to use for viral RNA detection in assessing COVID-19 patients for discharge. An anal swab sample was proposed as the standard because of prolonged viral detection. In this retrospective longitudinal study of viral RNA detection in 60 confirmed COVID-19 patients, we used saliva, oropharyngeal/nasopharyngeal swab (O/N swab) and anal swab procedures from admission to discharge. The conversion times of saliva and anal swab were longer than that of O/N swab. The conversion time of hyper sensitive-CRP was the shortest and correlated with that of CT scanning and viral detection. Some patients were found to be RNA-positive in saliva while RNA-negative in anal swab while the reverse was true in some other patients, which indicated that false negatives were inevitable if only the anal swab is used for evaluating suitability for discharge. These results indicated that double-checking for viral RNA using multiple and diverse specimens was essential, and saliva could be a candidate to supplement anal swabs to reduce false-negative results and facilitate pandemic control.

Combining clinical examination with exome sequencing for the diagnosis and treatment of Marfan syndrome: a case series of 6 families from China.

BACKGROUND: Marfan syndrome (MFS) is a rare autosomal dominant connective tissue disorder. Diagnosing MFS can be challenging as the disease's severity and clinical manifestations differ between pathogenic variants, and because a lack of published information currently exists on phenotype-genotype correlations. This report aims to underline the clinical manifestations associated with fibrillin-1 (FBN1) gene mutations by assessing MFS in 6 families from China. METHODS: We diagnosed 6 patients and their relatives with MFS by combining a clinical examination (based on the 2010 revised Ghent nosology criteria) with a targeted next-generation sequencing analysis. The functional analysis of the causal mutations and clinical details of the affected patients were then assessed. RESULTS: We identified 6 pathogenic mutations in FBN1, including 1 novel frameshift, 1 nonsense, and 4 missense mutations. Most uniquely, mitral valve prolapses (MVP) and ectopia lentis (EL) were found in the cysteine-related mutations. Typically, facial symptoms of MFS are observed in frameshift or nonsense mutants, not in cysteine-related ones. Furthermore, the patients with premature terminal codons had a more serious skin condition than patients with missense mutations, partly indicating the important effect FBN1 has on skin. CONCLUSIONS: This study expands the mutation spectrum of MFS and highlights possible genotype-phenotype correlations, thereby improving the early diagnosis and symptomatic treatment of the disease.