Herpes simplex virus type 1 strain 129 (H129) has represented a promising anterograde neuronal circuit tracing tool, which complements the existing retrograde tracers. However, the current H129 ...derived tracers are multisynaptic, neither bright enough to label the details of neurons nor capable of determining direct projection targets as monosynaptic tracer.
Based on the bacterial artificial chromosome of H129, we have generated a serial of recombinant viruses for neuronal circuit tracing. Among them, H129-G4 was obtained by inserting binary tandemly connected GFP cassettes into the H129 genome, and H129-ΔTK-tdT was obtained by deleting the thymidine kinase (TK) gene and adding tdTomato coding gene to the H129 genome. Then the obtained viral tracers were tested in vitro and in vivo for the tracing capacity.
H129-G4 is capable of transmitting through multiple synapses, labeling the neurons by green florescent protein, and visualizing the morphological details of the labeled neurons. H129-ΔTK-tdT neither replicates nor spreads in neurons alone, but transmits to and labels the postsynaptic neurons with tdTomato in the presence of complementary expressed TK from a helper virus. H129-ΔTK-tdT is also capable to map the direct projectome of the specific neuron type in the given brain regions in Cre transgenic mice. In the tested brain regions where circuits are well known, the H129-ΔTK-tdT tracing patterns are consistent with the previous results.
With the assistance of the helper virus complimentarily expressing TK, H129-ΔTK-tdT replicates in the initially infected neuron, transmits anterogradely through one synapse, and labeled the postsynaptic neurons with tdTomato. The H129-ΔTK-tdT anterograde monosynaptic tracing system offers a useful tool for mapping the direct output in neuronal circuitry. H129-G4 is an anterograde multisynaptic tracer with a labeling signal strong enough to display the details of neuron morphology.
The digestive system cancers are leading cause of cancer‐related death worldwide, and have high risks of morbidity and mortality. More and more long non‐coding RNAs (lncRNAs) have been studied to be ...abnormally expressed in cancers and play a key role in the process of digestive system tumour progression. Plasmacytoma variant translocation 1 (PVT1) seems fairly novel. Since 1984, PVT1 was identified to be an activator of MYC in mice. Its role in human tumour initiation and progression has long been a subject of interest. The expression of PVT1 is elevated in digestive system cancers and correlates with poor prognosis. In this review, we illustrate the various functions of PVT1 during the different stages in the complex process of digestive system tumours (including oesophageal cancer, gastric cancer, colorectal cancer, hepatocellular carcinoma and pancreatic cancer). The growing evidence shows the involvement of PVT1 in both proliferation and differentiation process in addition to its involvement in epithelial to mesenchymal transition (EMT). These findings lead us to conclude that PVT1 promotes proliferation, survival, invasion, metastasis and drug resistance in digestive system cancer cells. We will also discuss PVT1's potential in diagnosis and treatment target of digestive system cancer. There was a great probability PVT1 could be a novel biomarker in screening tumours, prognosis biomarkers and future targeted therapy to improve the survival rate in cancer patients.
Background
The malignancy of cholangiocarcinoma is highly pronounced, and it exhibits a propensity for recurrence and metastasis even in the presence of standard chemotherapy. The efficacy of ...adjuvant chemotherapy combined with immunotherapy in patients with resected cholangiocarcinoma needs to be substantiated.
Methods
Data from 101 patients with cholangiocarcinoma treated at the Sun Yat‐sen University Cancer Center between 2015 and 2020 were studied.
Results
After propensity score matching, there were no significant differences in baseline characteristics between patients in the combined adjuvant chemotherapy and immunotherapy group (AC + IM group) and the adjuvant chemotherapy alone group (AC group) (all p > 0.05). The AC + IM group demonstrated a statistically significant improvement in relapse‐free survival (RFS) compared to the AC group (p = 0.032). Likewise, the AC + IM group exhibited a significantly superior overall survival (OS) outcome when compared to the AC group (p = 0.044). Multivariate Cox analysis unveiled perineural invasion (p = 0.041), lymph node metastasis (p = 0.006), and postoperative immunotherapy (p = 0.008) as independent prognostic factors exerting a significant impact on the OS of patients. In the cohort of patients with perineural invasion, the AC + IM group exhibited significantly improved OS compared to the AC group (p = 0.0077). Similarly, within the subset of patients with lymph node metastasis, the AC + IM group exhibited a significantly superior OS outcome when compared to the AC group (p = 0.023).
Conclusion
Combining postoperative adjuvant chemotherapy with immunotherapy extends the RFS and OS of patients with cholangiocarcinoma following radical resection.
Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving ...standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options.
This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18–65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III–IVA, excluding T3–4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12–16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m2 body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111.
Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33–42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% 95% CI 80·4–90·6) than in the standard therapy group (75·7% 69·9–81·9), with a stratified hazard ratio of 0·50 (95% CI 0·32–0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 9% patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group.
The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma.
The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation.
For the Chinese translation of the abstract see Supplementary Materials section.
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•Working principle of supercapacitors (SCs) is introduced.•Recent advances on electrode materials for flexible SCs are reviewed.•Various ways to enhance the performance of flexible ...SCs are discussed.•Current challenges and future prospect of flexible SCs are suggested.
In recent years, with the rapid economic development, real-time monitoring of human health has received extensive attention. Wearable health monitoring equipment with good malleability and resistance to distortion makes great progress. The flexible supercapacitors integrated into the textile are characterized by a simple production process, low cost, fast charge,-discharge speed, and long cycle life. Therefore it has superior performance and broad research prospects. This review mainly introduces the recent advances and challenges of flexible supercapacitors, focusing on various flexible substrates' synthesis and performance. It summarizes the most representative flexible electrode materials at this stage. The future development trend and direction of flexible supercapacitors are discussed as well. Finally, the challenges in practical applications are considered.
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•PI-coated BaTiO3 nanoparticles with ‘core-shell’-like structure were prepared.•PI@BT nanoparticles exhibited good dispersion in the PVDF composites.•The composites showed high ...dielectric constant and low dielectric loss.•PI interlayer exhibited dual effects in the composites.
Polymeric dielectric materials recently attract much attention due to their good comprehensive performances. However, it is still challenging to prepare polymeric dielectric materials with high dielectric constant, low dielectric loss and high breakdown strength. In this work, insulated polyimide (PI) interlayer with nanoscale thickness was coated on the surface of barium titanate (BaTiO3, BT) through the in-situ polymerization and subsequent thermal imidization treatment. The hybrid nanoparticles exhibited the typical ‘core-shell’-like structure with strong interfacial interaction between BT and PI. Different from the serious aggregation of BT nanoparticles, the PI@BT nanoparticles exhibited good dispersion in the poly(vinylidene fluoride) (PVDF) composite. There was strong interfacial interaction between PI and PVDF, which resulted in the decrease of crystallinity of the PVDF matrix at relatively high filler content. The flexible PVDF/PI@BT composites exhibited largely enhanced dielectric constant, suppressed dielectric loss and enhanced breakdown strength compared with the common PVDF/BT composites. It was suggested that the intense interfacial polarization at the interface between PI and BT contributed to the largely enhanced dielectric constant while the reduced interfacial polarization at the interface between PI and PVDF contributed to the suppressed dielectric loss. This work demonstrates that the nanoengineering of the interface between BT and PVDF using PI is an alternative way to fabricate the dielectric materials with excellent comprehensive performances.
A new sample of 204 low-mass black holes (LMBHs) in active galactic nuclei (AGNs) is presented with black hole masses in the range of (1-20) × 105 M . The AGNs are selected through a systematic ...search among galaxies in the Seventh Data Release (DR7) of the Sloan Digital Sky Survey (SDSS), and careful analyses of their optical spectra and precise measurement of spectral parameters. Combining them with our previous sample selected from SDSS DR4 makes it the largest LMBH sample so far, totaling over 500 objects. Some of the statistical properties of the combined LMBH AGN sample are briefly discussed in the context of exploring the low-mass end of the AGN population. Their X-ray luminosities follow the extension of the previously known correlation with the O iii luminosity. The effective optical-to-X-ray spectral indices OX, albeit with a large scatter, are broadly consistent with the extension of the relation with the near-UV luminosity L2500 . Interestingly, a correlation of OX with black hole mass is also found, with OX being statistically flatter (stronger X-ray relative to optical) for lower black hole masses. Only 26 objects, mostly radio loud, were detected in radio at 20 cm in the FIRST survey, giving a radio-loud fraction of 4%. The host galaxies of LMBHs have stellar masses in the range of 108.8-1012.4 M and optical colors typical of Sbc spirals. They are dominated by young stellar populations that seem to have undergone continuous star formation history.
A highly enantioselective NH insertion reaction of α‐diazoketones was developed by using cooperative catalysis by dirhodium(II) carboxylates and chiral spiro phosphoric acids. The insertion reaction ...provides a new access route to diverse chiral α‐aminoketones, which are versatile building blocks in organic synthesis, with fast reaction rates, good yields and high enantioselectivity under mild and neutral conditions.
Spiro inspiration: A highly enantioselective NH insertion reaction of α‐diazoketones was developed by using cooperative catalysis by dirhodium(II) carboxylates and chiral spiro phosphoric acids. The insertion reaction provides a new access route to diverse chiral α‐aminoketones, which are versatile building blocks in the organic synthesis, with fast reaction rates, good yields and high enantioselectivity under mild and neutral conditions.
To identify the features of Chinese genetic prion diseases.
Suspected Creutzfeldt-Jakob disease (CJD) cases that were reported under CJD surveillance were diagnosed and subtyped using the diagnostic ...criteria issued by the WHO. The general information concerning the patient, their clinical, MRI and EEG data, and the results of CSF 14-3-3 and PRNP sequencing were carefully collected from the database of the national CJD surveillance program and analyzed using the SPSS 11.5 statistical software program.
Since 2006, 69 patients were diagnosed with genetic prion diseases and as having 15 different mutations. The median age of the 69 patients at disease onset was 53.5 years, varying from 19 to 80 years. The majority of patients displaying clinical symptoms were in the 50-59 years of age. FFI, T188K gCJD and E200K were the three most common subtypes. The disease appeared in the family histories of 43.48% of the patients. The clinical manifestations varied considerably among the various diseases. Patients who carried mutations in the N-terminus displayed a younger age of onset, were CSF 14-3-3 negative, had a family history of the condition, and experienced a longer duration of the condition. The clinical courses of T188K were significantly shorter than those of FFI and E200K gCJD, while the symptoms in the FFI group appeared at a younger age and for a longer duration. Moreover, the time intervals between the initial neurologist visit to the final diagnosis were similar among patients with FFI, T188K gCJD, E200K gCJD and other diseases.
The features of Chinese genetic prion diseases are different from those seen in Europe and other Asian countries.
Groundwater may contain radioactive substances which can be dangerous to human health. Concentrations of natural radionuclides polonium (Po), thorium (Th), uranium (U), and radium (Ra) isotopes were ...measured in groundwater samples collected from different locations in the vicinity of the Waste Isolation Pilot Plant (WIPP) site in Carlsbad, New Mexico. The average values of gross activity concentrations of 210Po, 228Th, 238U, 234U, 226Ra and 228 Ra isotopes were determined to be 1.62 Bq L-1 in shallow groundwater and 5.88 Bq L-1 in deep groundwater, respectively. The total radioactivity in deep groundwater was higher than that in shallow groundwater, and most of the radioactivity in the water is from 226Ra. Furthermore, the effective doses for ingestion of natural radionuclides were about 0.333 mSv y−1 for shallow groundwater and about 1.338 mSv y−1 for deep groundwater samples, which are higher than the World Health Organization (WHO, 2017) guideline level (0.1 mSv y−1) for drinking water. Ra dominated the total ingestion dose, contributing 93.06 % and 75.40 % of the total effective doses to the deep and shallow groundwater, respectively. The ingrowth and decay of natural radionuclides suggested that 228Ra/226Ra ratio can be a useful indicator of the source of radioactive contamination. The radioactivity data obtained from the investigated groundwater samples can be used to establish a baseline for radioactivity levels in groundwater around the WIPP site.
•Deep groundwater has higher radium radioactivity and salinity than shallow groundwater.•The radioactivity in groundwater is most likely from natural resources.•Monitoring of trends of groundwater radioactivity levels at the Waste Isolation Pilot Plant is needed.•Radium is the major contributor to the total effective doses for groundwater.•Total effective doses for groundwater exceed the WHO limit level for drinking water.
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