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Background The poor immunogenicity of solid tumors limits the efficacy ofanti-programmed cell death protein 1 (anti-PD1)-based immune checkpoint blockade (ICB); thus, less than 30% of patients with cancer exhibit a response. Currently, there is still a lack of effective strategies for improving tumor immunogenicity.Methods The antitumor effect of ultrasound-stimulated nanobubbles (USNBs) alone and in combination with an anti-PD1 antibody was evaluated in RM1 (prostate cancer), MC38 (colon cancer) and B16 (melanoma) xenograft mouse models. The phenotypes of antigen-presenting cells and CD8+ T cells were evaluated by flow cytometry. Damage-associated molecular pattern (DAMP) release, antigen release and tumor cell necrosis were assessed via western blot, flow cytometry, transmission electron microscopy and confocal microscopy.Results USNB promoted the infiltration and antitumor activity of CD8+ T cells. The combination of USNB and anti-PD1 blockade improved systemic antitumor immunity and resulted in an abscopal effect and long-term immune memory protection after complete tumor remission. Mechanistically, tumor-targeting USNB induced tumor cell necrosis through an ultrasound-mediated cavitation effect, which significantly increased DAMP release and tumor antigen presentation, consequently sensitizing tumors to ICB treatment.Conclusion The administration of USNB increased tumor immunogenicity by remodeling the tumor-immune microenvironment, providing a promising strategy for sensitizing poorly immunogenic solid tumors to immunotherapy in the clinic.

Small-cell lung cancer (SCLC) is a highly malignant, rapidly developing group of diseases with poor biological behavior. Most patients have extensive-stage SCLC (ES-SCLC) when they are first diagnosed. Standard chemotherapy is prone to relapse in a short period of time, and the patients’ median overall survival (OS) can reach only 13 months when chemotherapy is given in combination with PD-L1 inhibitors. To date, no studies have verified the efficacy and safety of the composite treatment of ES-SCLC with penpulimab and anlotinib despite some recognized data and advantages related to this regimen. Penpulimab, a novel PD-1 inhibitor with an IgG1 subtype, has a structural modification of the Fc segment which can prevent the immune cells from being phagocytosed or killed and can steadily avoid tumor immune escape. This case report describes a 71-year-old man who had ES-SCLC for 7 years which progressed after receiving standard systemic chemotherapy combined with radiotherapy. The third-line treatment of four cycles of anlotinib and carilizumab was discontinued because of grade 2 immune-related pneumonia despite the efficacy being evaluated as stable disease. After maintaining 22 months of progression-free survival, the patient relapsed and switched to a safer regimen of penpulimab combined with anlotinib to continue the treatment for four cycles. Partial response evaluation was confirmed twice, and the patient remained in good general condition. The combination of penpulimab and anlotinib can positively regulate the therapeutic effect by simultaneously acting on the tumor microenvironment and promoting blood vessel normalization. In general, this case provides support for the successful possibility of a rechallenge with immune checkpoint inhibitors, the better clinical efficacy of cross-line therapy with anlotinib, and the drug safety of penpulimab, suggesting a beneficial therapy for the clinical treatment of ES-SCLC.

Teachers' emotional states such as optimism and commitment have long been approved influential in second/foreign language education. Although many correlational investigations have been conducted on teacher optimism and commitment, their interaction and kinship with teachers' work engagement have been largely ignored in the literature. Considering this situation, the present mini-review aims to present the theoretical underpinnings, definitions, dimensions, and conceptualizations of these three important variables taken from positive psychology. Moreover, the present review can offer a number of practical implications for EFL teachers, teacher educators, program designers, school principals, and L2 researchers, and raise their awareness of the impact of inner emotions on teachers' academic performance. Finally, research gaps and future directions are provided for eager researchers to run similar and complementary studies in EFL contexts.

Logo design is related to the image of a company, unit, product, etc. A good logo can leave a deep impression on people and intuitively understand the content of the product. With the increasing emphasis on intellectual property protection, the design of logos should also pay more attention to the protection of property rights. It can be said that the logo of some big brands is enough to represent the enterprise itself; for example, seeing the red cross as a hospital. This paper aims to propose a logo design process and method under the background of intellectual property big data, so as to make the logo design more procedural and efficient, and to better focus on the protection of property rights. By introducing the relevant knowledge of logo design and trademark registration, it is indicated that trademark search can be used as an auxiliary tool for logo design. Combined with digital media and big data technology, a logo image recognition and classification method is designed so that the trademark registration and screening stage can avoid the infringement design to the greatest extent, so as to put forward the design process and method to improve the innovation ability of logo design. According to the research, the classification accuracy rate of the algorithm proposed in this paper is 91.5%, and the recognition rate of various defects is also above 95%. In addition, in design practice, the stability of design proposals should be monitored through multiple search methods using trademark search tools. If a high similarity is found in the search results, the design direction should be adjusted in time until the final design scheme is determined.

AimTo evaluate the efficacy of anti-seizure medications (ASMs), quinidine, and ketogenic diet therapy (KDT) for KCNT1-related epilepsy and to explore genotype-efficacy correlations.MethodsWe collected the data for KCNT1-related epilepsy cases from our hospital's medical records and the literature. In total, 50 patients received quinidine, 23 received classical KDT, and 15 received ASMs; all ASM data were from our hospital owing to the lack of detailed ASM data in the literature. The efficacy rates (ERs) of the treatments were compared; an ER that reduced the number of seizures by ≥50% was considered positive. Efficacy according to genotype was also assessed.ResultsThe ERs for the 30 patients at our hospital were 40, 26.7, 30, and 44.4% for all treatments, ASMs, quinidine, and KDT, respectively. For all patients (ours and those in previous reports), the overall ERs for quinidine and KDT were 26.0 and 43.5%, respectively (P = 0.135). The ERs for quinidine and KDT in functional domain variant-related epilepsy differed significantly (20.6 vs. 53.8%; P = 0.037).InterpretationKDT may be better at treating KCNT1-related epilepsy than quinidine; ASMs were the least effective. KDT is a viable treatment option for functional domain variant-related epilepsy.

Exploring the complex spatiotemporal changes and colonization mechanism of microbial communities will enable microbial communities to be better used to serve agricultural and ecological operations. In addition, evaluating the impact of transgenic plants on endogenous microbial communities is necessary for their commercial application. In this study, microbial communities of Populus × euramericana ‘Neva’ carrying Cry1Ac-Cry3A-BADH genes (ECAA1 line), Populus × euramericana ‘Neva’ carrying Cry1Ac-Cry3A-NTHK1 genes (ECAB1 line), and non-transgenic Populus × euramericana ‘Neva’ from rhizosphere soil, roots, and phloem collected in different seasons were compared and analyzed. Our analyses indicate that the richness and diversity of bacterial communities were higher in the three Populus × euramericana ‘Neva’ habitats than in those of fungi. Bacterial and fungal genetic-distance-clustering results were similar; rhizosphere soil clustered in one category, with roots and phloem in another. The diversity and evenness values of the microbial community were: rhizosphere soil > phloem > root system. The bacterial communities in the three habitats were dominated by the Proteobacteria, and fungal communities were dominated by the Ascomycota. The community composition and abundance of each part were quite different; those of Populus × euramericana ‘Neva’ were similar among seasons, but community abundance fluctuated. Seasonal fluctuation in the bacterial community was greatest in rhizosphere soil, while that of the fungal community was greatest in phloem. The transgenic lines ECAA1 and ECAB1 had a bacterial and fungal community composition similar to that of the control samples, with no significant differences in community structure or diversity among the lines. The abundances of operational taxonomic units (OTUs) were low, and differed significantly among the lines. These differences did not affect the functioning of the whole specific community. Sampling time and location were the main driving factors of changes in the Populus × euramericana ‘Neva’ microbial community. Transgenic events did not affect the Populus × euramericana ‘Neva’ rhizosphere or endophytic microbial communities. This study provides a reference for the safety evaluation of transgenic plants and the internal colonization mechanism of microorganisms in plants.

Rock brittleness is a critical factor affecting the stimulation of shale oil reservoirs. For efficient development of the shale oil in Lucaogou Formation, Jimusar Sag, the brittleness of the sweet spots needs to be evaluated. In this paper, the triaxial compression, acoustic wave measurements, and three-point bending tests were carried out on the reservoir cores. Based on the prepeak energy characteristics of the stress-strain curve, the brittleness of different horizons was calculated, with the largest difference of 24.89%. An improved model based on dynamic elastic properties was proposed to evaluate the brittleness along the vertical pay zones, by which the continuous brittleness in the upper sweet spot was found more changeful than that in the lower sweet spot. The linear correlation coefficient between the brittleness from the improved model and that from the laboratory tests is 0.85, improving the accuracy by 21% and 27% respectively, compared with the conventional elastic property methods. From the characteristics of compression fractures and the length of the fracture process zone, it was found that the compression fractures were more complex and the fracture process zone length was shorter in a more brittle rock, verifying the reliability of the improvement model. The improved method based on dynamic elastic properties proposed in this paper is expected to guide the brittleness evaluation in other regions.

Building energy consumption is increasingly becoming a matter of global concern. A key aspect of this is the nature of building cold source systems and their effectiveness. However, choosing the cold source for a building is a complex decision-making process. The traditional evaluation method is relatively simple, and it is difficult to comprehensively consider multiple factors and their mutual influences, and it is even more difficult to increase the consideration of the whole life-cycle cost on this basis. Especially in China, the cost of extra-large public projects invested and constructed by the government plays a significant role in the decision-making process, and it should not be affected by other factors to change the decision-making. Therefore, this paper proposes a new decision-making system, which is based on value engineering (VE) and combined with analytic network process (ANP) to conduct a comprehensive study of project decision-making. Based on existing approaches to construction project evaluation and the selection of cold source systems, we establish an evaluation index for building cold source system functional models and network structures. This approach can take into account the impact of cost on decisions. We then present the results of a simulation-based case study of potential central air-conditioning cold source system solutions for the new Xiang’an New Airport in Xiamen, China. The corresponding value coefficients for conventional electric refrigeration, ice storage, and water storage were found to be 0.8262, 1.0049, and 1.2442, respectively. This suggests that water storage-based cooling offers the best technical and economic benefits for this project. It also confirms that the proposed decision support system can identify the modes with the highest value coefficients, which is one of the most effective methods for selecting a building cold source system scheme. Therefore, the system has the potential to support the effective selection of other building cold source schemes.

Various medicinal ingredients with different tastes are combined according to the theory of compatibility in Chinese materia medica to achieve a better efficacy, while the mechanism was not very clear. Here, the authors studied the interaction between ingredients and human transporters such as the kidney transporters OAT1 and OAT3, the liver transporters OATP1B1 and OATP1B3, and the intestine transporter OATP2B1 to discern the compatibility mechanism of ingredients with different tastes in the Yuanhuzhitong preparation (YHP) comprising Corydalis yanhusuo (CYH) and Angelica dahurica (AD), which could relieve pain by restraining the central system. The results show that tetrahydropalmatine (TDE), the major component of CYH, could be transported by OAT3 into kidney, OATP1B1 and OATP1B3 into liver, while imperatorin (IPT) and isoimperatorin (ISP), the two key components of AD, and AD extract showed strong inhibition to OAT1 and OAT3. What's more, AD extract also exerted strongly inhibition to human transporters OATP1B1 and OATP1B3. It was also detected that IPT, ISP, and AD extract significantly downregulated the expression of Oatp1a1, Oatp1a4, and Oatp1b2 of liver in mice. The in vivo results show that the concentration of TDE in liver and kidney significantly decreased, while the TDE concentration in blood and brain were both significantly enhanced in the presence of IPT, ISP, and AD extract. These results suggest that the ingredients in AD with pungent taste could enhance the exposure of TDE in blood and brain by inhibiting the uptake of TDE in liver and kidney. That is to say, TDE with bitter taste could “flood up” into the central nervous system to play its therapeutic effect by the cut-off of that into liver and kidney in the presence of ingredients within AD. This paper not only proves the meridian distribution of CYH in liver and kidney with the role of OAT3, OATP1B1, and OATP1B3, but also illustrates how to improve the efficacy of CYH by reasonable compatibility with AD. This study may offer a valuable clue to illustrate the mechanism of compatibility theory.

Abstract Background China has great student participation in STEM education. Chinese society has a progressive and positive attitude towards STEM as it is considered to provide more opportunities in life. Teachers play a vital role in the success of any STEM program in K-12 schools. However, teachers are facing instructional challenges because of the interdisciplinary nature of the STEM curriculum and the current typical school structure. The success of the STEM programs depends on teachers’ beliefs and their knowledge in adapting to instructional implementation of STEM concepts. Results The data (n = 216) was collected from STEM primary and secondary teachers from 25 provinces in mainland China. Exploratory factor analysis (EFA) was applied, and Pearson’s correlation analysis was used to examine the correlation between Chinese STEM teachers’ beliefs, knowledge, implementation, and the intrinsic challenges of STEM education; t tests and analysis of variance (ANOVA) were performed to ascertain whether there were differences. The structural equation model (SEM) was applied to identify interrelationships. The results indicated that Chinese STEM teachers encounter higher-level intrinsic challenges to instructional implementations based on their beliefs and knowledge. Teachers who utilize their experience of teaching science as their main discipline and then attempt to integrate STEM using mathematics and engineering are likely to encounter higher-level intrinsic challenges in implementation. Conclusion The intrinsic challenges perceived by Chinese teachers in the practice of STEM education can be predicted by their beliefs and knowledge base. Teachers who understand the nature and pedagogy of STEM education are more likely to encounter lower-level intrinsic challenges of STEM teaching, while teachers who utilize their main discipline when conducting integrated STEM learning activities through modeling based on science, technology, engineering, and mathematical problem situations are more likely to encounter higher-level intrinsic challenges. This study also reveals that there are some significant differences in the level of STEM teachers’ beliefs, knowledge base, instructional practice, and their intrinsic challenges based on their teaching grade, seniority, and experience of STEM training and teaching.

Abstract Exogenous melatonin (MT) was found to be an interesting tool for enhancing the resistance of rice to Xanthomonasoryzaepv. oryzae (Xoo)-caused bacterial blight (BB). However, the accurate comparison of the expression levels across samples was a challenging task. In this work, the stability of 10 common used housekeeping genes under Xoo-infection and MT supplementation in rice was analyzed using quantitative real-time PCR (qRT-PCR), and algorithms geNorm, NormFinder and BestKeeper. Our results indicated that most reference genes remained stable in Xoo-infected rice plants, while a number of reference genes were affected by MT supplementation. Among all studied genes, the transcript levels of 18S(18S ribosomal RNA) and UBC (Ubiquitin-conjugating enzyme E2) remained unaltered by Xoo infection, while UBC and UBQ5(Ubiquitin 5) were the most stable genes when examining simultaneous Xoo-infection and MT supplementation, demonstrating that UBC is a suitable reference gene for qRT-PCR data normalization in rice under Xoo-infection and MT supplementation.

Background Aspirin is a classic anti‐inflammatory drug and its anticancer effect has been previously explored in many types of cancer including colorectal cancer therapy. Programmed cell death‐ligand 1 (PD‐L1) is widely expressed in tumor cells and displays an inhibitory role in antitumor immunity. This study aimed to clarify the role of PD‐L1 in aspirin‐suppressed lung cancer. Methods The inhibitory effect of aspirin on lung cancer cell proliferation was assessed using an MTT cell viability assay. The role of aspirin in the modulation of PD‐L1 expression was analyzed by western blot or RT‐PCR assays. In lung cancer cells, the influence of aspirin on PD‐L1 promoter activity was detected using a luciferase reporter assay. The interaction of TAZ with PD‐L1 promoter in the cells, with or without aspirin administration, was tested via chromatin immunoprecipitation (ChIP) analysis. The function of PD‐L1 in aspirin‐mediated growth inhibition of lung cancer was examined using a cell viability assay. Results Following treatment with aspirin, lung cancer cell growth was markedly suppressed. Aspirin was able to markedly decrease the expression of PD‐L1 at the mRNA and protein levels in lung cancer cells. For the mechanism study, we found that the promoter of PD‐L1 was inactivated by aspirin via TAZ transcriptional coactivator in the cells. With regard to the functional investigation, aspirin was capable of resisting cell proliferation and PD‐L1 overexpression abolished aspirin‐depressed cell proliferation in lung cancer. Conclusions Aspirin suppressed the growth of lung cancer cells via targeting the TAZ/PD‐L1 axis.

Abstract Background Lycium barbarum and L. ruthenicum have been used as traditional medicinal plants in China and other Asian counties for centuries. However, the molecular mechanisms underlying fruit development and ripening, as well as the associated production of medicinal and nutritional components, have been little explored in these two species. Results A competitive transcriptome analysis was performed to identify the regulators and pathways involved in the fruit ripening of red wolfberry (L. barbarum) and black wolfberry (L. ruthenicum) using an Illumina sequencing platform. In total, 155,606 genes and 194,385 genes were detected in red wolfberry (RF) and black wolfberry (BF), respectively. Of them, 20,335, 24,469, and 21,056 genes were differentially expressed at three different developmental stages in BF and RF. Functional categorization of the differentially expressed genes revealed that phenylpropanoid biosynthesis, flavonoid biosynthesis, anthocyanin biosynthesis, and sugar metabolism were the most differentially regulated processes during fruit development and ripening in the RF and BF. Furthermore, we also identified 38 MYB transcription factor-encoding genes that were differentially expressed during black wolfberry fruit development. Overexpression of LrMYB1 resulted in the activation of structural genes for flavonoid biosynthesis and led to an increase in flavonoid content, suggesting that the candidate genes identified in this RNA-seq analysis are credible and might offer important utility. Conclusion This study provides novel insights into the molecular mechanism of Lycium fruit development and ripening and will be of value to novel gene discovery and functional genomic studies.

This study was conducted to determine the standardized ileal digestible amino acids (SID AA) and nitrogen-corrected apparent metabolizable energy (AMEn) contents of 6 wheats from different origins in China and incidentally to investigate the effects of exogenous xylanase addition on SID AA and AMEn determination in broiler chicks. A total of 480 chicks were divided into 48 cages of 10 birds each balanced for body weight and fed 8 types of diets in a completely randomized design (6 replicated cages per diet) from 21 to 26 d of age. The individual wheat constituted the only source of crude protein in a semi-purified experimental diet. A nitrogen-free diet was designed to estimate basal endogenous AA loss and determine the SID AA. Titanium oxide (0.3%) was used as an indigestibility marker, and nutrient digestibility and retention were determined by the substitution method. From day 24 to 26, excreta samples were collected for AMEn determination. On day 26, the birds were euthanized, and ileum contents were obtained for AA digestibility determination. Wheat from Gansu had greater (P

In order to cooperate the wind farm operators with grasping the operation status of wind power converter, a novel reliability assessment strategy is proposed based on supervisory control and data acquisition (SCADA) multistate parameters prediction of permanent magnet synchronous generator (PMSG) wind turbine. The strategy considers “off-line training, on-line matching and assessment”. The operation reliability of wind power converter is obtained via the analysis and weight computing of confidence level, prediction value and actual value of SCADA multistate parameters. In the “off-line training” part, first, the FP-Growth association algorithm is employed to analyze the confidence levels of SCADA variables to the faults of wind power converter. The variables with high confidence level are defined as SCADA multistate parameters. Afterwards, wavelet packet transform (WPT) and K-means algorithm are employed to decompose, reconstruct, normalize and cluster the time series (off-line data) of multistate parameters under normal operation of wind turbine, to improve the generalization capability of long short term memory (LSTM) prediction model. In the part of “on-line matching and assessment”, the actual value time series (on-line data) of multistate parameters are decomposed and reconstructed by WPT. Each normalized sample is matched to the closest cluster centroid, which is generated in the part of “off-line training”. Then the corresponding LSTM model is conducted to predict based on the each sample. The final prediction value is sum of prediction results of entire samples in clusters. Finally, the reliability of wind power converter is assessed by the proposed strategy. The effectiveness of proposed assessment strategy is verified by the experimental results on a PMSG wind power converter.

Fabric defect detection plays an important role in automated inspection and quality control in textile manufacturing. As the fabric images have complex and diverse textures and defects, traditional detection methods show a poor adaptability and low detection accuracy. Robust principal component analysis (RPCA) model that can be used to separate the image into object and background have proven applicable in fabric defect detection. However, how to represent texture feature of the fabric image more effectively is still problematic in this kind of method. In addition, the use of the traditional RPCA may result in low accuracy and more noises in sparse part. In this article, a novel fabric defect detection method based on multilevel deep features fusion and non-convex total variation regularized RPCA (NTV-RPCA) is proposed. Firstly, the image representation ability is well enhanced through multilevel deep features extracted by a convolutional neural network. Then, the non-convex total variation regularized RPCA is proposed in which total variation constraint significantly reduces the noises in sparse part and non-convex solution is more approximate to the authentic one. Next, multilevel saliency maps generated by the sparse matrixes are fused via RPCA to produce a more reliable detection result. Finally, the defect region is located by segmenting the fused saliency map via a threshold segmentation algorithm. Qualitative and quantitative experiments conducted on two public fabric image databases demonstrate that the proposed method improves the adaptability and detection accuracy comparing to the state-of-the-arts.

Angiotensin I-Converting Enzyme (ACE, CD143) Gene plays a crucial role in the pathology of carcinomas in many cancers including colorectal cancer (CRC). However, the methylation of ACE was rarely reported. In this study, our purpose was to investigate the methylation status of ACE and explored its prognostic value in CRC. The expression of ACE was detected by quantitative real-time polymerase chain reaction (qRT-PCR) analysis while the methylation status of ACE was measured via methylation-specific polymerase chain reaction (MSP). The result demonstrated that ACE expression was up-regulated in tumour tissues and HT-29 cells compared with the controls. ACE was also confirmed to be hypomethylated in CRC. Next, we evaluated the influence of ACE hypomethylation on cell growth. It was proved to be a favourable factor for the cell proliferation, cell colony forming, but an inhibitor for the cell apoptosis of CRC cells according to MST assay, colony forming assay and flow cytometry assay. ACE hypomethylation was also considered to be related to the prognosis of CRC through Cox regression analysis. Taken together, the over-expression of ACE was regulated by its hypomethylation and the ACE hypomethylation might be an independent prognostic indicator in CRC.

The emergence of the CRISPR-Cas9 system has triggered a technical revolution in mammalian genome editing. Compared to traditional gene-targeting strategies, CRISPR-Cas9 technology offers a more efficient and cost-effective approach for generating genetically modified animal models. However, off-target cleavage in CRISPR-mediated genome editing is a major concern in the analysis of phenotypes as well as the selection of therapeutic targets. Here, we analyzed whole-genome sequencing (WGS) data from two knock-out (KO) mouse strains generated by using the CRISPR-Cas9 system targeting the Mmd and Paqr8 loci. A total of nine individuals were sequenced including two parents, four F1 offspring and three uninjected control mice. Using GATK and bcftools software, we identified two off-target events in the founder mice. The two CRISPR-Cas9-induced off-target events were predictable using Cas-OFFinder and were not passed on to the offspring that we investigated. In addition, our results indicated that the number of CRISPR-Cas9-induced mutations was not statistically distinguishable from the background de novo mutations (DNMs).

Abstract In this paper, we study the degenerate parabolic system uti+Xα∗(aijαβ(z)Xβuj)=gi(z,u,Xu)+Xα∗fiα(z,u,Xu), $$ u_{t}^{i} + X_{\alpha }^{*} \bigl(a_{ij}^{\alpha \beta }(z){X_{\beta }} {u^{j}}\bigr) = {g_{i}}(z,u,Xu) + X_{\alpha }^{*} f_{i}^{\alpha }(z,u,Xu), $$ where X={X1,…,Xm} $X=\{X_{1},\ldots,X_{m} \}$ is a system of smooth real vector fields satisfying Hörmander’s condition and the coefficients aijαβ $a_{ij}^{\alpha \beta }$ are measurable functions and their skew-symmetric part can be unbounded. After proving the L2 $L^{2}$ estimates for the weak solutions, the higher integrability is proved by establishing a reverse Hölder inequality for weak solutions.

Three new species and one subspecies of the genus Amynthas are described from Guangxi Zhuang Autonomous Region, China: The new species are: Amynthas maximus Qiu & Dong, sp. nov. and Amynthas tortuosus Qiu & Dong, sp. nov., and Amynthas shengtangmontis Dong & Jiang, sp. nov., the subspecies is Amynthas shengtangmontis minusculus subsp. nov. All have four pairs of spermathecal pores in 5/6–8/9, which indicates that they should belong to the corticis-group. Their morphological characteristics are compared to other similar species in the corticis-group from China and other Asian countries, such as Amynthas pulvinus Sun & Jiang, 2013, Amynthas homosetus (Chen, 1938), Amynthas corticis (Kinberg, 1867), Amynthas dorsualis Sun & Qiu, 2013, and Amynthas carnosus (Goto & Hatai, 1899). In addition, the results presented are confirmed by the pairwise comparison of COI barcode sequences. The pairwise distances between each new species and the other eighteen corticis-group species are greater than 14.7% on average. Furthermore, the pairwise distance between A. shengtangmontis shengtangmontis and A. shengtangmontis minusculus is 10.7–11.4%.

Background There have been extensive debates on the interrelationships among the four major classes of Myriapoda—Chilopoda, Symphyla, Diplopoda, and Pauropoda. The core controversy is the position of Pauropoda; that is, whether it should be grouped with Symphyla or Diplopoda as a sister group. Two recent phylogenomic studies separately investigated transcriptomic data from 14 and 29 Myriapoda species covering all four groups along with outgroups, and proposed two different topologies of phylogenetic relationships. Methods Building on these studies, we extended the taxon sampling by investigating 39 myriapods and integrating the previously available data with three new transcriptomic datasets generated in this study. Our analyses present the phylogenetic relationships among the four major classes of Myriapoda with a more abundant taxon sampling and provide a new perspective to investigate the above-mentioned question, where visual genes’ identification were conducted. We compared the appearance pattern of genes, grouping them according to their classes and the visual pathways involved. Positive selection was detected for all identified visual genes between every pair of 39 myriapods, and 14 genes showed positive selection among 27 pairs. Results From the results of phylogenomic analyses, we propose that Symphyla is a sister group of Pauropoda. This stance has also received strong support from tree inference and topology tests.

ABSTRACT Lyme disease (LD) is a heavy public health burden. The most common manifestations of LD include erythema migrans (EM), Lyme neuroborreliosis (LNB), and Lyme arthritis (LA). The efficacy and safety of antibiotics for treating LD is still controversial. Thus, we performed a network meta-analysis (NMA) to obtain more data and tried to solve this problem. We searched studies in the databases of Embase and PubMed from the date of their establishments until 22 April 2021. Odds ratios (ORs) were used to assess dichotomous outcomes. A total of 31 randomized controlled trials (RCTs) involving 2,748 patients and 11 antibiotics were included. Oral amoxicillin (1.5 g/day), oral azithromycin (0.5 g/day), injectable ceftriaxone, and injectable cefotaxime were effective for treating LD (range of ORs, 1.02 to 1,610.43). Cefuroxime and penicillin were safe for treating LD (range of ORs, 0.027 to 0.98). Amoxicillin was effective for treating EM (range of ORs, 1.18 to 25.66). Based on the results, we thought oral amoxicillin (1.5 g/day), oral azithromycin (0.5 g/day), injectable ceftriaxone, and injectable cefotaxime were effective for treating LD. Cefuroxime and penicillin were safe for treating LD. Amoxicillin was effective for treating EM. We did not observe evidence proving the advantage of doxycycline in efficacy and safety for treating LD, LA, LNB, and EM of children or adults. We did not have sufficient data to prove the significant difference of efficacy for treating LA and LNB in adults and LD in children, the significant difference of safety of oral drugs for treating LD, and the significant difference of safety of drugs for treating EM. IMPORTANCE Some previous studies investigated the efficacy and safety of antibiotics for treating Lyme disease (LD). However, due to technical limitations, several questions regarding the routes of drug administration and the dosages of drug are still unclear, which might be causing problems for clinicians. Hence, we performed network meta-analysis (NMA) to quantitatively analyze the clinical data published during the last 40 years. Here, we demonstrate the evidence regarding the efficacy and safety of antibiotics commonly used for treating LD in adults and children. We found that amoxicillin, azithromycin, ceftriaxone, and cefotaxime were effective for treating LD, but we did not observe significant efficacy and safety of doxycycline for treating LD.

Background: The nucleus accumbens associated 1 (NACC1) gene is a transcription factor member of the BTB/POZ family. A de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 may define a syndrome characterized by intellectual disability, infantile epilepsy, congenital cataract, and feeding difficulties.Case Presentation: We report a new case with a neurodevelopmental disorder characterized by severe intellectual disability, infantile epilepsy, congenital cataract, and feeding difficulties. Brain MRI reveals brain dysplasia. We observe a de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 gene in this case. Now, the child regularly goes to the hospital for rehabilitation training (once a month). Sodium Valproate (10 mg/kg/day) and Clobazam (10 mg/kg/day) are used in the treatment of epilepsy. A total of three articles were screened, and two papers were excluded. The search revealed one article related to a syndrome caused by a de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1; they screened the main clinical features of eight cases of a syndrome, which were summarized and analyzed.Conclusions: The NACC1 gene is a member of the BTB/POZ family of transcription factors. A de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 may define a syndrome characterized by intellectual disability, infantile epilepsy, congenital cataract, and feeding difficulties. At present, there is no effective cure. In the future, we need more cases to determine the phenotype–genotype correlation of NACC1 variants. Many questions remain to be answered, and many challenges remain to be faced. Future transcriptional studies may further clarify this rare, recurrent variant, and could potentially lead to targeted therapies.

Defect engineering is a promising strategy for supported catalysts to improve the catalytic activity and durability. Here, we selected the carbon (C) matrix enriched with topological defects to serve as the substrate material, in which the topological defects can act as anchoring centers to trap Pt nanoparticles for driving the O2 reduction reactions (ORRs). Both experimental characterizations and theoretical simulations revealed the strong Pt-defect interaction with enhanced charge transfer on the interface. Despite a low Pt loading, the supported catalyst can still achieve a remarkable 55 mV positive shift of half-wave potential toward ORR in O2-saturated 0.1 M HClO4 electrolyte compared with the commercial Pt catalyst on graphitized C. Moreover, the degeneration after 5,000 voltage cycles was negligible. This finding indicates that the presence of strong interaction between Pt and topological C defects can not only stabilize Pt nanoparticles but also optimize the electronic structures of Pt/C catalysts toward ORR.

Summary: The DREAM (dimerization partner [DP], retinoblastoma [Rb]-like, E2F, and MuvB) complex controls cellular quiescence by repressing cell-cycle and other genes, but its mechanism of action is unclear. Here, we demonstrate that two C. elegans THAP domain proteins, LIN-15B and LIN-36, co-localize with DREAM and function by different mechanisms for repression of distinct sets of targets. LIN-36 represses classical cell-cycle targets by promoting DREAM binding and gene body enrichment of H2A.Z, and we find that DREAM subunit EFL-1/E2F is specific for LIN-36 targets. In contrast, LIN-15B represses germline-specific targets in the soma by facilitating H3K9me2 promoter marking. We further find that LIN-36 and LIN-15B differently regulate DREAM binding. In humans, THAP proteins have been implicated in cell-cycle regulation by poorly understood mechanisms. We propose that THAP domain proteins are key mediators of Rb/DREAM function.

Acute lung injury (ALI) is a syndrome caused by an excessive inflammatory response characterized by intractable hypoxemia both inside and outside the lung, for which effective therapeutic drugs are lacking. Atractylodis rhizoma, a traditional Chinese medicine, has excellent anti-inflammatory and antiviral properties in addition to protecting the integrity of the cellular barrier. However, few studies of Atractylodis rhizoma for the treatment of ALI have been published, and its mechanism of action remains unclear. In the present study, the chemical composition of the ethanolic extract of Atractylodis rhizoma (EEAR) was initially clarified by high performance liquid chromatography (HPLC), after which it was studied in vivo using a lipopolysaccharide (LPS)-induced ALI rat model. Treatment with EEAR significantly reduced the lung wet/dry (W/D) ratio, neutrophil infiltration, and malondialdehyde (MDA) and myeloperoxidase (MPO) formation, and enhanced superoxide dismutase (SOD) and glutathione (GSH) depletion in rats with ALI, thereby improving lung barrier function and effectively reducing lung injury. In addition, EEAR significantly reduced histopathological changes, decreased the expression of inflammatory factors (such as tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), inducible nitric oxide synthase (INOS), and cyclooxygenase-2 (COX-2)), and inhibited the activation of the NF-κB signaling pathway, thus reducing inflammation. In addition, EEAR was found to also reduce oxidative stress in ALI by upregulating the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream proteins heme oxygenase-1 (HO-1) and NADPH quinone acceptor oxidoreductase 1 (NQO-1). EEAR also reduced LPS-induced inflammatory factor expression in THP-1 cells in vitro by inhibition of the NF-κB signaling pathway, and reduced damage from lipopolysaccharide (LPS)-induced oxidative stress in THP-1 cells by promoting the expression of Nrf2 and its downstream targets HO-1 and NQO-1, the molecular mechanism of which was consistent with in vivo observations. Therefore, we conclude that EEAR attenuates oxidative stress and inflammatory responses via TLR4/NF-κB and Keap1/Nrf2 signaling pathways to alleviate LPS-induced ALI, suggesting that Atractylodis rhizoma is a potential drug candidate for the treatment of ALI.

During the service life of offshore pipelines, many start-up and shut-down cycles take place, possibly leading to significant cyclic loads. Fatigue failure may occur, resulting in serious environmental pollution and loss of property. The study aims to assess the fatigue strength of single-sided girth welds in offshore pipelines under these specific fatigue loads. The longitudinal stress range caused by the variation of the pipeline’s internal pressure and temperature is calculated. The effective notch strain approach is used to assess the fatigue strength of welds. The plastic behaviour of the weld root is investigated for a study case to justify the use of low-cycle fatigue assessment approaches. The effect of weld root geometry on the notch stress factor is studied to identify the dominant geometrical parameters. The fatigue strength of the study case is assessed, and some limitations of the assessment are discussed. The results show that the plastic behaviour of the weld root is only significant for severe local stress concentrations, which is mainly governed by the axial misalignment, weld root angle and the weld root bead width. If the fatigue damage at failure is 0.1, a limited number of start-up and shut-down cycles are allowed during the service life of the pipeline for the study case, indicating the necessity of fatigue strength assessment.

Different cloud-top heights (CTHs) have different degrees of atmospheric heating, which is an important factor for weather forecasting and aviation safety. AHIs (Advanced Himawari Imagers) on the Himawari-8 satellite are a new generation of visible and infrared imaging spectrometers characterized by a wide observation range and a high temporal resolution. In this paper, a cloud-top height retrieval algorithm based on XGBoost is proposed. The algorithm comprehensively utilizes AHI L1 multi-channel radiance data and calculates the input parameters of the generated model according to the characteristics of the cloud phase, texture, and the local brightness temperature change of the cloud. In addition, the latitude, longitude, solar zenith angle and satellite zenith angle are input into the model to further constrain the influence of the geographical and spatial factors such as the sea and land location, on CTH. Compared with the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) cloud-top height data (CTHCAL), the results show that: the algorithm retrieved the cloud-top height (CTHXGB) with a mean error (ME) of 0.3 km, a standard deviation (Std) of 1.72 km, and a root mean square error (RMSE) of 1.74 km. Additionally, it improves the problem of the large systematic deviation in the cloud-top height products released by the Japan Meteorological Agency (CTHJMA), especially for ice clouds and multi-layer clouds with ice clouds on the top layer. For water clouds below 2 km and multi-layer clouds with water clouds at the top, the algorithm solves the systematically serious CTHJMA problem. XGBoost can effectively distinguish between different cloud scenarios within the model, which is robust and suitable for CTH retrieval.

Cereal and legume intercropping could improve cereal yield, but the role of intercropping in grain quality still lacks a full understanding. A two-year bi-factorial trial was conducted to investigate the role of two planting patterns (mono-cropped wheat (MW) and intercropped wheat+faba bean (IW)) and four nitrogen (N) fertilization levels (N0, no N fertilizer applied to both wheat and faba bean; N1, 90 and 45 kg N ha–1 applied to wheat and faba bean; N2, 180 and 90 kg N ha–1 applied to wheat and faba bean; N3, 270 and 135 kg N ha–1 applied to wheat and faba bean), as well as their interaction on the productivity of wheat grain yield (GY) and quality. The results showed that intercropping increased both the yields of wheat grain protein and amino acids (AAs) relative to MW in both years. No difference in Aas content between IW and MW was found but the 9% grain protein content (GPC) of IW was higher than that of MW in 2020. By contrast, wheat gliadin content was increased by 8–14% when wheat was intercropped with faba bean in both years, and some AAs fractions including essential and non-essential AAs were increased under N0 and N1 levels but declined at the N3 level. This means that intercropping increased the grain quality either for protein and AAs content or for fractions. There was no negative relationship between GPC and GY in the present study, and intercropping tended to increase GPC with increasing GY. In conclusion, wheat and faba bean mainly affected GPC and fractions rather than AAs, and intercropping presented a potential to improve both wheat quality and yield concurrently. Modulated N rates benefitted the stimulation of intercropping advantages in terms of grain yield and quality in the southwest of China and similar regions.

Traveling-wave ultrasonic motors (TWUSMs) have strong nonlinearity and uncertainty, which are sensitive to the environment, disturbances, and load changes. Thus, precision control of TWUSMs is hard to achieve with traditional methods for complex driving mechanisms. A nominal-model-based sliding-mode control strategy with strong robustness is proposed to achieve accurate speed control of TWUSMs. Firstly, a second-order nominal model of the speed difference and output torque was deduced to construct a nonlinear sliding-mode surface; then, a nonlinear sliding-mode controller was designed with the collaborative regulation of frequency and the amplitude of two-phase control voltages. The global asymptotic stability of the controller was proved under bounded disturbances and parameter uncertainty. Finally, the effectiveness and accurate control were testified to and verified by the simulations and experiments, which showed good robustness and a disturbance rejection of the strategy for TWUSMs, with strong nonlinearity and uncertainty.

Due to the limitations of taxon sampling and differences in results from the available data, the phylogenetic relationships of the Myriapoda remain contentious. Therefore, we try to reconstruct and analyze the phylogenetic relationships within the Myriapoda by examining mitochondrial genomes (the mitogenome). In this study, typical circular mitogenomes of Mecistocephalus marmoratus and Scolopendra subspinipes were sequenced by Sanger sequencing; they were 15,279 bp and 14,637 bp in length, respectively, and a control region and 37 typical mitochondrial genes were annotated in the sequences. The results showed that all 13 PCGs started with ATN codons and ended with TAR codons or a single T; what is interesting is that the gene orders of M. marmoratus have been extensively rearranged compared with most Myriapoda. Thus, we propose a simple duplication/loss model to explain the extensively rearranged genes of M. marmoratus, hoping to provide insights into mitogenome rearrangement events in Myriapoda. In addition, our mitogenomic phylogenetic analyses showed that the main myriapod groups are monophyletic and supported the combination of the Pauropoda and Diplopoda to form the Dignatha. Within the Chilopoda, we suggest that Scutigeromorpha is a sister group to the Lithobiomorpha, Geophilomorpha, and Scolopendromorpha. We also identified a close relationship between the Lithobiomorpha and Geophilomorpha. The results also indicate that the mitogenome can be used as an effective mechanism to understand the phylogenetic relationships within Myriapoda.

Background: Sudden cardiac death (SCD) is a common cause of death in hypertrophic cardiomyopathy (HCM), but identification of patients at a high risk of SCD is challenging. The study aimed to validate the three SCD risk stratifications recommended by the 2011 ACCF/AHA guideline, the 2014 ESC guideline, and the 2020 AHA/ACC guideline in Chinese HCM patients.Methods: The study population consisted of a consecutive cohort of 511 patients with HCM without a history of SCD event. The endpoint was a composite of SCD or an equivalent event (appropriate implantable cardioverter defibrillator therapy or successful resuscitation after cardiac arrest).Results: During a follow-up of 4.7 ± 1.7 years, 15 patients (2.9%) reached the SCD endpoint and 12 (2.3%) were protected by implantable cardioverter defibrillator for primary prevention. A total of 13 (2.8%) patients experiencing SCD events were misclassified as low-risk patients by the 2011 ACCF/AHA guideline, 12 (2.3%) by the 2014 ESC model, and 7 (1.6%) by the 2020 AHA/ACC guideline. The SCD risk stratification in the 2020 AHA/ACC guideline showed greater area under the curve (0.71; 95% CI 0.56–0.87, p < 0.001) than the one in the 2011 ACCF/AHA guideline (0.52; 95% CI 0.37–0.67, p = 0.76) and 2014 ESC guideline (0.68; 95% CI 0.54–0.81, p = 0.02).Conclusion: The SCD risk stratification recommended by the 2020 AHA/ACC guideline showed a better discrimination than previous stratifications in Chinese patients with HCM. A larger multicenter, independent, and prospective study with long-term follow-up would be warranted to validate our result.

Changes in the light environment have an important effect on crop growth and yield. To clarify the effects of intercropping and the application of nitrogen on the yield of wheat and light within the crop canopy, the relationship between light and yield and their response to nitrogen fertilizer were studied. In a 2-year field experiment, the characteristics of growth, light, biomass, and yield of wheat were measured using three cropping arrangements (monocropped wheat, monocropped faba beans, and intercropped wheat/faba beans) and four levels of applied nitrogen, in groups termed N0 (0 kg/ha), N1 (90 kg/ha), N2 (180 kg/ha), and N3 (270 kg/ha). The results demonstrated that the application of nitrogen fertilizer increased wheat plant height, spike leaf length and width, and the number of leaves while significantly decreasing wheat canopy light transmittance (LT) and canopy photosynthetic active radiation transmittance (PART), by 7.5–71.1 and 12.7–75.1%, respectively. There was a significantly increased canopy photosynthetic active radiation interception rate (IPAR) of 7.5–97.8% and an increase in biomass of 9.6–38.4%, of which IPAR, biomass, and yield were highest at the N2 level. Compared with monocropping, intercropping increased parameters of wheat growth to varying degrees. Intercropping decreased LT and PART by 10.8–46.4 and 15.7–58.7%, respectively, but increased IPAR by 0.1–66.0%, wheat biomass and yield by 7.5–17.4 and 27.7–47.2%, respectively. The mean yield of intercropped wheat increased by 35.8% over 2 years, while the mean land equivalent ratio (LER) was 1.36, for which a values greater than 1 indicates that wheat and faba bean intercropping is advantageous. Correlation analysis demonstrated that there was a very significant negative correlation between wheat LT and yield, while simultaneously demonstrating a very significant positive correlation between PART and IPAR with yield, indicating that the efficient interception and utilization of light energy in intercropping was the basis for the higher biomass and yield of wheat. In summary, wheat/faba bean intercropping and the application of nitrogen at 180 kg/ha were effective in increasing wheat yield.

To our knowledge, no studies have reported the use of anlotinib in the treatment of locally cancerous nasopharyngeal inverted papillomas that cannot be operated on or treated with radiotherapy. Here, we report a case of a 53-year-old woman diagnosed with recurrent local canceration of nasopharynx papilloma. Magnetic resonance imaging (MRI) showed that the right parapharyngeal space, nasopharynx, and ethmoid sinus were changed, and recurrence was considered. There was no indication for surgery or radiotherapy. Imaging showed that the tumor had obvious enhancement and abundant blood vessels. Immunohistochemistry showed that vascular endothelial growth factor receptor (VEGFR) 2 expression was positive in papilloma tissue and in local canceration tissue of the papilloma. After the patient’s consent was obtained, anlotinib treatment was started in May and ended in November 2019. Then, the patient was treated with intensity-modulated radiotherapy (IMRT) with planning gross tumor volume (PGTV) 66 Gy, planning clinical tumor volume 1 (PCTV1) 60 Gy, and planning clinical tumor volume 2 (PCTV2) 54 Gy in 33 fractions. No disease recurrence was reported at 4 months after radiotherapy.

The development of the low dislocation density of the Si-based GaAs buffer is considered the key technical route for realizing InAs/GaAs quantum dot lasers for photonic integrated circuits. To prepare the high-quality GaAs layer on the Si substrate, we employed an engineered Ge-buffer on Si, used thermal cycle annealing, and introduced filtering layers, e.g., strained-layer superlattices, to control/reduce the threading dislocation density in the active part of the laser. In this way, a low defect density of 2.9 × 107 cm−2 could be achieved in the GaAs layer with a surface roughness of 1.01 nm. Transmission electron microscopy has been applied to study the effect of cycling, annealing, and filtering layers for blocking or bending threading-dislocation into the InAs QDs active region of the laser. In addition, the dependence of optical properties of InAs QDs on the growth temperature was also investigated. The results show that a density of 3.4 × 1010 InAs quantum dots could be grown at 450 °C, and the photoluminescence exhibits emission wavelengths of 1274 nm with a fullwidth at half-maximum (FWHM) equal to 32 nm at room temperature. The laser structure demonstrates a peak at 1.27 μm with an FWHM equal to 2.6 nm under a continuous-wave operation with a threshold current density of ∼158 A/cm2 for a 4-μm narrow-ridge width InAs QD device. This work, therefore, paves the path for a monolithic solution for photonic integrated circuits when III−V light sources (which is required for Si photonics) are grown on a Ge-platform (engineered Ge-buffer on Si) for the integration of the CMOS part with other photonic devices on the same chip in near future.

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has severely affected socio-economic conditions and people’s life. The lung is the major target organ infected and (seriously) damaged by SARS-CoV-2, so a comprehensive understanding of the virus and the mechanism of infection are the first choices to overcome COVID-19. Recent studies have demonstrated the enormous value of human organoids as platforms for virological research, making them an ideal tool for researching host–pathogen interactions. In this study, the various existing lung organoids and their identification biomarkers and applications are summarized. At the same time, the seven coronaviruses currently capable of infecting humans are outlined. Finally, a detailed summary of existing studies on SARS-CoV-2 using lung organoids is provided and includes pathogenesis, drug development, and precision treatment. This review highlights the value of lung organoids in studying SARS-CoV-2 infection, bringing hope that research will alleviate COVID-19-associated lung infections.

The realization of high-performance Si-based III-V quantum-dot (QD) lasers has long attracted extensive interest in optoelectronic circuits. This manuscript presents InAs/GaAs QD lasers integrated on an advanced GaAs virtual substrate. The GaAs layer was originally grown on Ge as another virtual substrate on Si wafer. No patterned substrate or sophisticated superlattice defect-filtering layer was involved. Thanks to the improved quality of the comprehensively modified GaAs crystal with low defect density, the room temperature emission wavelength of this laser was allocated at 1320 nm, with a threshold current density of 24.4 A/cm−2 per layer and a maximum single-facet output power reaching 153 mW at 10 °C. The maximum operation temperature reaches 80 °C. This work provides a feasible and promising proposal for the integration of an efficient O-band laser with a standard Si platform in the near future.

Numerous studies have shown that pesticide residues in tea exceeding the maximum residue limits (MRL) can cause harmful effects on the human body. There are many limitations in the existing analytical methods for pesticide residues in tea, so new analytical methods need to be developed. We developed a limit test method that combines thin-layer chromatography with Raman imaging microscopy (TLC-RIM). Seven residual pesticide components in tea (Avermectin, Methomyl, Carbendazim, Imidacloprid, Chlorothalonil, Azoxystrobin, and Acetamiprid) could be preliminarily separated by TLC and then irradiated by a 532 nm laser. Raman spectra of seven pesticides obtained by Raman imaging microscopy could be used to test whether the pesticide residues in tea exceed the MRL. The limits of detection of the seven pesticides were 0.04, 0.10, 0.24, 0.20, 0.12, 0.12, and 1.0 mg/mL, respectively. The simulated positive test showed that the matrix in tea did not interfere with the test of the seven pesticides. When the pesticides were tested within 8 h, the RSD of the peak heights of the seven pesticides were 1.2%~9.6%; the test results of three batches of tea showed that the imidacloprid in one batch of tea exceeded its MRL, and the results were consistent with that by UPLC-MS/MS. The TLC-RIM is fast, sensitive, stable, specific, and reliable.

This paper studies a class of variational inequalities with degenerate parabolic operators and symmetric structure, which is an extension of the parabolic equation in a bounded domain. By solving a series of penalty problems, the existence and uniqueness of the solutions in the weak sense are proved by the energy method and a limit process.

Background: Traumatic brain injury (TBI) often results in persistent cognitive impairment and psychiatric symptoms, while lesion location and severity are not consistent with its clinical complaints. Previous studies found cognitive deficits and psychiatric disorders following TBI are considered to be associated with prefrontal and medial temporal lobe lesions, however, the location and extent of contusions often cannot fully explain the patient′s impairments. Thus, we try to find the structural changes of gray matter (GM) and white matter (WM), clarify their correlation with psychiatric symptoms and memory following TBI, and determine the brain regions that primary correlate with clinical measurements. Methods: Overall, 32 TBI individuals and 23 healthy controls were recruited in the study. Cognitive impairment and psychiatric symptoms were examined by Mini-Mental State Examination (MMSE), Hospital Anxiety and Depression Scale (HADS), and Wechsler Memory Scale-Chinese Revision (WMS-CR). All MRI data were scanned using a Siemens Prisma 3.0 Tesla MRI system. T1 MRI data and diffusion tensor imaging (DTI) data were processed to analyze GM volume and WM microstructure separately. Results: In the present study, TBI patients underwent widespread decrease of GM volume in both cortical and subcortical regions. Among these regions, four brain areas including the left inferior temporal gyrus and medial temporal lobe, supplementary motor area, thalamus, and anterior cingulate cortex (ACC) were highly implicated in the post-traumatic cognitive impairment and psychiatric complaints. TBI patients also underwent changes of WM microstructure, involving decreased fractional anisotropy (FA) value in widespread WM tracts and increased mean diffusivity (MD) value in the forceps minor. The changes of WM microstructure were significantly correlated with the decrease of GM volume. Conclusions: TBI causes widespread cortical and subcortical alterations including a reduction in GM volume and change in WM microstructure related to clinical manifestation. Lesions in temporal lobe may lead to more serious cognitive and emotional dysfunction, which should attract our high clinical attention.

The present study investigates the response of natural gas consumption to temperature on the basis of observations during heating season (middle November–middle March) for the period 2002–2021 in Beijing, China, and then estimates temperature-related changes in the gas consumption under future scenarios by using climate model simulations from the Coupled Model Intercomparison Project Phase 6. Observational evidence suggests that the daily natural gas consumption normalized by gross domestic product is linearly correlated with the daily average temperature during heating season in the past two decades in Beijing. Hence, a linear regression model is built to estimate temperature-related changes in the natural gas consumption under future scenarios. Corresponding to a rising trend in the temperature, the natural gas consumption shows a decrease trend during 2015–2100 under both the SSP245 and the SSP585 scenarios. In particular, the temperature would increase rapidly from early 2040s to the end of 21st century under the SSP585 scenario, leading to an obvious reduction in the natural gas consumption for heating in Beijing. Relative to that in the present day (1995–2014), the natural gas consumption would show a reduction of approximately 9% (±4%) at the end of 21st century (2091–2100) under the SSP245 scenario and approximately 22% (±7%) under the SSP585 scenario.

BackgroundWith the improvement of clinical treatment outcomes in diffuse large B cell lymphoma (DLBCL), the high rate of relapse in DLBCL patients is still an established barrier, as the therapeutic strategy selection based on potential targets remains unsatisfactory. Therefore, there is an urgent need in further exploration of prognostic biomarkers so as to improve the prognosis of DLBCL.MethodsThe univariable and multivariable Cox regression models were employed to screen out gene signatures for DLBCL overall survival (OS) prediction. The differential expression analysis was used to identify representative genes in high-risk and low-risk groups, respectively, where student t test and fold change were implemented. The functional difference between the high-risk and low-risk groups was identified by the gene set enrichment analysis.ResultsWe conducted a systematic data analysis to screen the candidate genes significantly associated with OS of DLBCL in three NCBI Gene Expression Omnibus (GEO) datasets. To construct a prognostic model, five genes (CEBPA, CYP27A1, LST1, MREG, and TARP) were then screened and tested using the multivariable Cox model and the stepwise regression method. Kaplan–Meier curve confirmed the good predictive performance of this five-gene Cox model. Thereafter, the prognostic model and the expression levels of the five genes were validated by means of an independent dataset. High expression levels of these five genes were significantly associated with favorable prognosis in DLBCL, both in training and validation datasets. Additionally, further analysis revealed the independent value and superiority of this prognostic model in risk prediction. Functional enrichment analysis revealed some vital pathways responsible for unfavorable outcome and potential therapeutic targets in DLBCL.ConclusionWe developed a five-gene Cox model for the clinical outcome prediction of DLBCL patients. Meanwhile, potential drug selection using this model can help clinicians to improve the clinical practice for the benefit of patients.

BackgroundLyme neuroborreliosis (LNB) is one of the most dangerous manifestations of Lyme disease, but the pathogenesis and inflammatory mechanisms are not fully understood.MethodsCultured explants from the frontal cortex of rhesus monkey brain (n=3) were treated with live Borrelia burgdorferi (Bb) or phosphate-buffered saline (PBS) for 6, 12, and 24 h. Total protein was collected for sequencing and bioinformatics analysis. In addition, changes in protein expression in the explants over time following Bb treatment were screened.ResultsWe identified 1237 differentially expressed proteins (DEPs; fold change ≥1.5 or ≤0.67, P-value ≤0.05). One of these, growth-associated protein 43 (GAP-43), was highly expressed at all time points in the explants. The results of the protein-protein interaction network analysis of DEPs suggested that GAP-43 plays a role in the neuroinflammation associated with LNB. In HMC3 cells incubated with live Bb or PBS for 6, 12, and 24 h, real-time PCR and western blot analyses confirmed the increase of GAP-43 mRNA and protein, respectively.ConclusionsElevated GAP-43 expression is a potential marker for LNB that may be useful for diagnosis or treatment.