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Abstract Background Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery. Methods In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern. Results From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences. Conclusions We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.

In microgravity, atoms can be prepared to a lower temperature and manipulated with a longer time. The Cold Atom Physics Research Rack (CAPR) in Chinese Space Station, which aims to prepare quantum degenerate gas for deep cooling and quantum simulation in microgravity, has been designed, realized, and validated. We built an integrated CAPR, consisting of a physical system, an all-fiber 780 nm laser system and a low phase noise 1064 nm fiber laser system, and an electrical driving and controlling system. With the CAPR, a 87Rb quantum degenerate gas with 1.2 × 105 atoms and a temperature below 30 nK was achieved on ground. In this article, we also show the robustness of the rack, based on the experimental results before and after the simulation of the vibration and impact during the launch.

Abstract Background To study lymphatic recurrence distribution after radical surgery in the real world and guide clinical tumor volume delineation for regional lymph nodes during postoperative radiotherapy for lower thoracic squamous cell esophageal carcinomas. Methods We enrolled patients who underwent radical esophagectomy, without radiation before or after surgery, at 3 cancer hospitals. Patients were classified into groups according to tumor locations. We included patients with tumors in the lower thoracic segment and analyzed the postoperative lymph node recurrence mode. A cutoff value of 10% was used to differentiate high-risk lymph node drainage areas from others. Results We enrolled 1905 patients in the whole study series, including 652 thoracic esophageal carcinomas that met our inclusion criteria; there were 241 cases of lower thoracic esophageal carcinomas. 1st, 2nd, 4th, 7th, 8th groups of lymph nodes, according to the 8th edition of the AJCC classification, displayed as high-risk recurrence areas, representing 17.8%, 23.9%, 11.7%, 10.9% and 12.2% of lymph node recurrence. Stage III-IV tumors located in the lower segment of the thoracic esophagus showed a tendency to recur in the left gastric nodes (7.9%) and celiac nodes (10.6%). Conclusions According to our results, we recommended including the 4th, 7th and 8th groups of lymph nodes in the radiation field, and for patients with stage III-IV disease, the 17th and 20th groups of nodes should be irradiated during postoperative treatment. Whether including 1st/2nd groups in preventive irradiation needed more proofs.

The Cold Atom Physics Rack (CAPR) of Chinese space station will be launched at the end of 2022. The important goal of CAPR is to achieve BEC at 100 pk. In order to obtain ultracold atoms in microgravity of space station, we propose a two-stage cooling scheme using all-optical trap with different waist beams. The cold atom cloud obtained by this scheme is composed of condensate and thermal atoms around condensate. The design of our two-stage cooling scheme will effectively reduce the temperature of the thermal atom cloud and the effective temperature generated by the interaction energy of the condensate. The atomic temperature of 5 nk is obtained from the ground test experiment, and the corresponding temperature under the microgravity condition of the space station is theoretically predicted to be less than 100 pk. Taking the advantages of ultracold temperature and long-time detection, many scientific experiments will be arranged. In this paper, the ground test experiments based on ground principle prototype and pre-prototype for CAPR are also introduced.

The advent of the intelligence age has injected new elements into the development of literature. The synergic modification of Anglo-American (AAL) traumatic narrative (TN) literature by artificial intelligence (AI) technology and interactive design (ID) psychology will produce new possibilities in literary creation. First, by studying natural language processing (NLP) technology, this study proposes a modification language model (LM) based on the double-layered recurrent neural network (RNN) algorithm and constructs an intelligent language modification system based on the improved LM model. The results show that the performance of the proposed model is excellent; only about 30% of the respondents like AAL literature; the lack of common cultural background, appreciation difficulties, and language barriers have become the main reasons for the decline of reading willingness of AAL literature. Finally, AI technology and ID psychology are used to modify a famous TN work respectively and synergically, and the modified work is appreciated by respondents to collect their comments. The results corroborate that 62% of the respondents like original articles, but their likability scores have decreased for individually modified work by AI or ID psychology. In comparison, under the synergic modification efforts of AI and ID psychology, the popularity of the modified work has increased slightly, with 65% of the respondents showing a likability to read. Therefore, it is concluded that literary modification by single ID psychology or AI technology will reduce the reading threshold by trading off the literary value of the original work. The core of literary creation depends on human intelligence, and AI might still not be able to generate high-standard literary works independently because human minds and thoughts cannot be controlled and predicted by machines. The research results provide new ideas and improvement directions for the field of AI-assisted writing.

Cystic fibrosis (CF) is a lethal autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Nuclease-mediated precise gene editing (PGE) represents a promising therapy for CF, for which an efficient strategy that is free of viral vector, drug selection, and reporter enrichment (VDR free) is desirable. Here we compared different transfection methods (lipofectamine versus electroporation) and formats (plasmid DNA versus ribonucleoprotein) in delivering the CRISPR/Cas9 elements along with single-stranded oligodeoxynucleotides (ssODNs) to clinically relevant cells targeting major CFTR mutation loci. We demonstrate that, among different combinations, electroporation of CRISPR/Cas9 and guide RNA (gRNA) ribonucleoprotein (Cas9 RNP) is the most effective one. By using this VDR-free method, 4.8% to 27.2% efficiencies were achieved in creating dF508, G542X, and G551D mutations in a wild-type induced pluripotent stem cell (iPSC) line. When it is applied to a patient-derived iPSC line carrying the dF508 mutation, a greater than 20% precise correction rate was achieved. As expected, genetic correction leads to the restoration of CFTR function in iPSC-derived proximal lung organoids, as well as in a patient-derived adenocarcinoma cell line CFPAC-1. The present work demonstrates the feasibility of gene editing-based therapeutics toward monogenic diseases such as CF.

Existing animal models of cystic fibrosis (CF) have provided key insights into CF pathogenesis but have been limited by short lifespans, absence of key phenotypes, and/or high maintenance costs. Here, we report the CRISPR/Cas9-mediated generation of CF rabbits, a model with a relatively long lifespan and affordable maintenance and care costs. CF rabbits supplemented solely with oral osmotic laxative had a median survival of approximately 40 days and died of gastrointestinal disease, but therapeutic regimens directed toward restoring gastrointestinal transit extended median survival to approximately 80 days. Surrogate markers of exocrine pancreas disorders were found in CF rabbits with declining health. CFTR expression patterns in WT rabbit airways mimicked humans, with widespread distribution in nasal respiratory and olfactory epithelia, as well as proximal and distal lower airways. CF rabbits exhibited human CF–like abnormalities in the bioelectric properties of the nasal and tracheal epithelia. No spontaneous respiratory disease was detected in young CF rabbits. However, abnormal phenotypes were observed in surviving 1-year-old CF rabbits as compared with WT littermates, and these were especially evident in the nasal respiratory and olfactory epithelium. The CF rabbit model may serve as a useful tool for understanding gut and lung CF pathogenesis and for the practical development of CF therapeutics.

It is of great interest to explore effective approaches to overcome the stress of heavy metals and achieve simultaneous enhanced acetate production and heavy metal removal in the biocathodes of microbial electrosynthesis (MES) systems. Herein, the magnetic field and the loaded Fe3O4 were employed to synergetically improve both acetate production and Cr(VI) removal in the Serratia marcescens Q1 catalyzed cathode of MES. This was accomplished via increase in the circuital current and the S. marcescens release of different amounts and components of extracellular polymeric substances dominantly harboring of outer membrane c-type cytochromes, reaching 2.6 ± 0.1 mg/L/h (acetate production) and 2.3 ± 0.1 mg/L/h (Cr(VI) removal) at a circuital current of 1.4 ± 0.0 A/m2. These values were 4.2-fold (acetate production), 1.3-time (Cr(VI) removal) and 2.2-fold (circuital current) of those in the absence of magnetic field and Fe3O4. Increasing initial Cr(VI) from 60 mg/L to 120 mg/L similarly achieved more acetate production (3.3–4.2 folds) and higher circuital current (2.1–2.2 folds) than those at a Cr(VI) of 60 mg/L in the absence of magnetic field and Fe3O4, confirming the positive influential magnetic field and loaded Fe3O4 for efficient system performance at these high levels of Cr(VI). This study provides an alternative and environmentally benign approach for achieving simultaneous efficient acetate production and Cr(VI) removal, opening up the feasibility of sustainable treatment of heavy metals-contaminated organics-barren waters and wastewaters.

Cold atom clocks are among the most precise measuring devices and play key roles in everyday life and scientific explorations. Here the authors demonstrate the first in-orbit atomic clock using cold Rb atoms operating in microgravity and opening possibilities of space surveys and tests of fundamental physics.

The spaceborne double-pulse integrated-path differential absorption (IPDA) light detection and ranging (LIDAR) system was found to be helpful in observing atmospheric CO2 and understanding the carbon cycle. The airborne experiments of a scale prototype of China’s planned spaceborne IPDA LIDAR was implemented in 2019. A problem with data inversion caused by the detector module nonlinearity was found. Through many experiments, the amplifier circuit board (ACB) of the detector module was proved to be the main factor causing the nonlinearity. Through amplifier circuit optimization, the original bandwidth of the ACB was changed to 1 MHz by using a fifth-order active filter. Compared with the original version, the linearity of optimized ACB is improved from 42.6% to 0.0747%. The optimized ACB was produced and its linearity was verified by experiments. In addition, the output waveform of the optimized ACB changes significantly, which will affect the random error (RE) of the optimized IPDA LIDAR system. Through the performance simulation, the RE of more than 90% of the global area is less than 0.728 ppm. Finally, the transfer model of the detector module was given, which will be helpful for the further optimization of the CO2 column-averaged dry-air mixing ratio (XCO2) inversion algorithm.

Hepatocellular carcinoma (HCC) is the second leading cause of mortality among cancers. It has been found that long noncoding RNAs (lncRNAs) are involved in many human cancers, including liver cancer. It has been identified that carcinogenic and tumor-suppressing lncRNAs are associated with complex processes in liver cancer. These lncRNAs may participate in a variety of pathological and biological activities, such as cell proliferation, apoptosis, invasion, and metastasis. Here, we review the regulation and function of lncRNA in liver cancer and evaluate the potential of lncRNA as a new goal for liver cancer.

Individuals with cystic fibrosis (CF) often experience gastrointestinal (GI) abnormalities. In recent years, the intestinal microbiome has been postulated as a contributor to the development of CF-associated GI complications, hence representing a potential therapeutic target for treatment. We recently developed a rabbit model of CF, which is shown to manifest many human patient-like pathological changes, including intestinal obstruction. Here, we investigated the feces microbiome in young CF rabbits in the absence of antibiotics treatment. Stool samples were collected from seven- to nine-week-old CF rabbits (n = 7) and age-matched wild-type (WT) rabbits (n = 6). Microbiomes were investigated by iTag sequencing of 16S rRNA genes, and functional profiles were predicted using PICRUSt. Consistent with reports of those in pediatric CF patients, the fecal microbiomes of CF rabbits are of lower richness and diversity than that of WT rabbits, with a marked taxonomic and inferred functional dysbiosis. Our work identified a new CF animal model with the manifestation of intestinal dysbiosis phenotype. This model system may facilitate the research and development of novel treatments for CF-associated gastrointestinal diseases.

The demand for greenhouse gas measurement has increased dramatically due to global warming. A 1.57-μm airborne double-pulse integrated-path differential absorption (IPDA) light detection and ranging (LIDAR) system for CO2 concentration measurement was developed. The airborne field experiments of this IPDA LIDAR system were conducted at a flight altitude of approximately 7 km, and the weak echo signal of the ocean area was successfully received. The matched filter algorithm was applied to the retrieval of the weak signals, and the pulse integration method was used to improve the signal-to-noise ratio. The inversion results of the CO2 column-averaged dry-air mixing ratio (XCO2) by the scheme of averaging after log (AVD) and the scheme of averaging signals before log were compared. The AVD method was found more effective for the experiment. The long-term correlation between the changing trends of XCO2 retrieved by the IPDA LIDAR system and CO2 dry-air volume mixing ratio measured by the in-situ instrument reached 92%. In the steady stage of the open area (30 km away from the coast), which is almost unaffected by the residential areas, the mean value of XCO2 retrieved by the IPDA LIDAR system was 414.69 ppm, with the standard deviation being 1.02 ppm. Compared with the CO2 concentration measured by the in-situ instrument in the same period, bias was 1.30 ppm. The flight path passed across the ocean, residential, and mountainous areas, with the mean value of XCO2 of the three areas being 419.35, 429.29, and 422.52 ppm, respectively. The gradient of the residential and ocean areas was 9.94 ppm, with that of the residential and mountainous areas being 6.77 ppm. Obvious gradients were found in different regions.

Fluid office documents, as semi-structured data often represented by Extensible Markup Language (XML) are important parts of Big Data. These office documents have different formats, and their matching Application Programming Interfaces (APIs) depend on developing platform and versions, which causes difficulty in custom development and information retrieval from them. To solve this problem, we have been developing an office document query (ODQ) language which provides a uniform method to retrieve content from documents with different formats and versions. ODQ builds common document model ontology to conceal the format details of documents and provides a uniform operation interface to handle office documents with different formats. The results show that ODQ has advantages in format independence, and can facilitate users in developing documents processing systems with good interoperability.

Aiming at the common problems of intelligent document platform-dependency, this paper proposes an MVC-based (Model View Controller-based) intelligent document model using UIML (User Interface Markup Language). The model is made on the basis of the previous work of our team, and the difference is that the new model separates user interface and interaction descriptions from the view component to make the intelligent document model much more independent of platform and programming language. To verify the intelligent document model, we implemented a prototype, which can support intelligent operations. The test result shows that our approach is correct. The model not only follows MVC framework, but also provides good flexibility and independence.

Abstract Background Several studies have demonstrated that SIV infection progresses more slowly to experimental AIDS in Chinese rhesus macaques (Ch Rhs) than in Indian rhesus macaques (Ind Rhs). Here we investigated the dynamic and functional changes in dendritic cell (DC) subsets in SIVmac239-infected Ch Rhs. Results The numbers of both mDC and pDC strongly fluctuated but were not significantly changed during the acute and chronic phases of infection. However, the concentration of both poly (I:C)-induced IL-12 and HSV-1-induced IFN-α significantly increased in the acute phase of infection but returned to normal levels at the chronic phase of infection. The peak of IFN-α emerged earlier than that of IL-12, and it had a significantly positive correlation with IL-12, which indicated that IFN-α may initiate the immune activation. We also found that only the concentration of IFN-α was positively correlated with CD4+ T-cell counts, but it was negatively correlated with viral load. Conclusion High levels of IFN-α in the early stage of infection may contribute to effective control of virus replication, and normal levels of IFN-α during chronic infection may help Ch Rhs resist the disease progression. The change in DC subsets dynamics and cytokine production may help further our understanding of why Ch Rhs are able to live longer without progressing to an AIDS-like illness.

In Asian populations with non-small-cell lung cancer (NSCLC), EGFR mutations are highly prevalent, occurring in roughly half of these patients. Studies have revealed that individuals with EGFR mutation typically fare worse with immunotherapy. In patients who received EGFR tyrosine kinase inhibitor (TKI) treatment followed by anti-PD-1 therapy, poor results were observed. The underlying mechanism remains unclear. We used high-resolution flow cytometry and ELISA to detect the circulating level of small extracellular vesicle (sEV) PD-L1 in NSCLC individuals with EGFR mutations before and after receiving TKIs. The secretion amount of sEV PD-L1 of lung cancer cell lines with EGFR mutations under TKI treatment or not were detected using high-resolution flow cytometry and Western blotting. The results revealed that patients harboring EGFR mutations exhibit increased levels of sEV PD-L1 in circulation, which inversely correlated with the presence of CD8+ T cells in tumor tissues. Furthermore, tumor cells carrying EGFR mutations secrete a higher quantity of PD-L1-positive sEVs. TKI treatment appeared to amplify the levels of PD-L1-positive sEVs in the bloodstream. Mutation-induced and TKI-induced sEVs substantially impaired the functionality of CD8+ T cells. Importantly, our findings indicated that EGFR mutations and TKI therapies promote secretion of PD-L1-positive sEVs via distinct molecular mechanisms, namely the HRS and ALIX pathways, respectively. In conclusion, the increased secretion of PD-L1-positive sEVs, prompted by genetic alterations and TKI administration, may contribute to the limited efficacy of immunotherapy observed in EGFR-mutant patients and patients who have received TKI treatment. [ABSTRACT FROM AUTHOR]

Objective: Small extracellular vesicle (sEV)‐mediated intercellular communication is increasingly the key for the understanding of venous malformations (VMs). This study aims to clarify the detailed changes of sEVs in VMs. Subjects and Methods: Fifteen VM patients without treatment history and twelve healthy donors were enrolled in the study. sEVs were isolated from both fresh lesions and cell supernatant, and were examined by western blotting, nanoparticle tracking analysis and transmission electron microscopy. Western blot analysis, immunohistochemistry and immunofluorescence were adopted to screening candidate regulator of sEV size. Specific inhibitors and siRNA were employed to validate the role of dysregulated p‐AKT/vacuolar protein sorting‐associated protein 4B (VPS4B) signaling on the size of sEVs in endothelial cells. Results: The size of sEVs derived from both VM lesion tissues and cell model was significantly increased. VPS4B, whose expression level was mostly significantly downregulated in VM endothelial cells, was responsible for the size change of sEVs. Targeting abnormal AKT activation corrected the size change of sEVs by recovering the expression level of VPS4B. Conclusion: Downregulated VPS4B in endothelial cells, resulted from abnormally activated AKT signaling, contributed to the increased size of sEVs in VMs. [ABSTRACT FROM AUTHOR]

The MIKCC-type MADS-box gene family is involved in the regulation of fower development. A total of 109 members of the MIKCC-type MADS-box gene family were identifed in blueberry. According to the phylogenetic tree, these 109 MIKCC-type MADS-box proteins were divided into 13 subfamilies, which were distributed across 40 Scafolds. The results of the conserved motif analysis showed that among 20 motifs, motifs 1, 3, and 9 formed the MADS-box structural domain, while motifs 2, 4, and 6 formed the K-box structural domain. The presence of 66 pairs of fragment duplication events in blueberry suggested that gene duplication events contributed to gene expansion and functional diferentiation. Additionally, the presence of cis-acting elements revealed that VcFLC2, VcAG3, and VcSVP9 might have signifcant roles in the endo-dormancy release of fower buds. Meanwhile, under chilling conditions, VcAP3.1 and VcAG7 might facilitate fower bud dormancy release. VcSEP11 might promote fowering following the release of endo-dormancy, while the elevated expression of VcAP1.7 (DAM) could impede the endo-dormancy release of fower buds. The efect of gibberellin (GA4+7) treatment on the expression pattern of MIKCC-type MADS-box genes revealed that VcAP1.4, VcAP1.6, VcAP3.1, VcAG3, and VcFLC2 might promote fower bud endo-dormancy release, while VcAP3.2, VcSEP11, and VcSVP9 might inhibit its endo-dormancy release. These results indicated that VcAP1.4, VcAP1.6, VcAP1.7 (DAM), VcAP3.1, VcAG3, VcAG7, VcFLC2, and VcSVP9 could be selected as key regulatory promoting genes for controlling the endo-dormancy of blueberry fower buds. [ABSTRACT FROM AUTHOR]