Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis.

Allogeneic chimeric antigen receptor (CAR)-T cells hold great promise for expanding the accessibility of CAR-T therapy, whereas the risks of allograft rejection have hampered its application. Here, we genetically engineered healthy-donor-derived, CD19-targeting CAR-T cells using CRISPR-Cas9 to address the issue of immune rejection and treated one patient with refractory immune-mediated necrotizing myopathy and two patients with diffuse cutaneous systemic sclerosis with these cells. This study was registered at ClinicalTrials.gov (NCT05859997). The infused cells persisted for over 3 months, achieving complete B cell depletion within 2 weeks of treatment. During the 6-month follow-up, we observed deep remission without cytokine release syndrome or other serious adverse events in all three patients, primarily shown by the significant improvement in the clinical response index scores for the two diseases, respectively, and supported by the observations of reversal of inflammation and fibrosis. Our results demonstrate the high safety and promising immune modulatory effect of the off-the-shelf CAR-T cells in treating severe refractory autoimmune diseases.

Synergistic regulation at physiological, transcriptional and metabolic levels in tomato plants subjected to a combination of salt and heat stress.

With global warming and climate change, abiotic stresses often simultaneously occur. Combined salt and heat stress was a common phenomenon that was severe, particularly in arid/semi-arid lands. We aimed to reveal the systematic responsive mechanisms of tomato genotypes with different salt/heat susceptibilities to combined salt and heat stress. Morphological and physiological responses of salt-tolerant/sensitive and heat-tolerant/sensitive tomatoes at control, heat, salt and combined stress were investigated. Based on leaf Fv /Fm and H2 O2 content, samples from tolerant genotype at the four treatments for 36 h were taken for transcriptomics and metabolomics. We found that plant height, dry weight and net photosynthetic rate decreased while leaf Na+ concentration increased in all four genotypes under salt and combined stress than control. Changes in physiological indicators such as photosynthetic parameters and defence enzyme activities in tomato under combined stress were regulated by the expression of relevant genes and the accumulation of key metabolites. We screened five key pathways in tomato responding to a combination of salt and heat stress, such as oxidative phosphorylation (map00190). Synergistic regulation at morphological, physiological, transcriptional and metabolic levels in tomato plants was induced by combined stress. Heat stress was considered as a dominant stressor for tomato plants under the current combined stress. The oxidative phosphorylation pathway played a key role in tomato in response to combined stress, where tapped key genes (e.g. alternative oxidase, Aox1a) need further functional analysis. Our study will provide a valuable resource important for studying stress combination and improving tomato tolerance.

Population genomics analysis reveals footprints of selective breeding in a rapid-growth variety of Paulownia fortunei with apical dominance.

Paulownia fortunei is an ecologically and economically valuable tree cultivated for its rapid growth and high-quality timber. To enhance Paulownia germplasm, we have developed the elite variety QingT with patented advantages in growth rate and apical dominance. To illuminate the genetic basis of QingT's superior traits, here we harness comparative population genomics to analyze genomic variation patterns between QingT and common Paulownia. We performed whole-genome re-sequencing of 30 QingT and 30 common samples, detecting 15.6 million SNPs and 2.6 million indels. Phylogeny and population structure analyses robustly partitioned common and QingT into distinct groups which indicate robust genome stabilization. QingT exhibited reduced heterozygosity and linkage disequilibrium decay compared to common Paulownia, reflecting high recombination, indicating hybridizing effects with common white-flowered string is the source of its patented advantages. Genome selection scans uncovered 25 regions of 169 genes with elevated nucleotide diversity, indicating selection sweeps among groups. Functional analysis of sweep genes revealed upregulation of ribosomal, biosynthesis, and growth pathways in QingT, implicating enhanced protein production and developmental processes in its rapid growth phenotype. This study's insights comprehensively chart genomic variation during Paulownia breeding, localizing candidate loci governing agronomic traits, and underpinnings of future molecular breeding efforts to boost productivity.

Chemical Synthesis and Antigenicity Evaluation of an Aminoglycoside Trisaccharide Repeating Unit of Pseudomonas aeruginosa Serotype O5 O-Antigen Containing a Rare Dimeric-ManpN3NA.

Pseudomonas aeruginosa bacteria are becoming increasingly resistant against multiple antibiotics. Therefore, the development of vaccines to prevent infections with these bacteria is an urgent medical need. While the immunological activity of lipopolysaccharide O-antigens in P. aeruginosa is well-known, the specific protective epitopes remain unidentified. Herein, we present the first chemical synthesis of highly functionalized aminoglycoside trisaccharide 1 and its acetamido derivative 2 found in the P. aeruginosa serotype O5 O-antigen. The synthesis of the trisaccharide targets is based on balancing the reactivity of disaccharide acceptors and monosaccharide donors. Glycosylations were analyzed by quantifying the reactivity of the hydroxyl group of the disaccharide acceptor using the orbital-weighted Fukui function and dual descriptor. The stereoselective formation of 1,2-cis-α-fucosylamine linkages was achieved through a combination of remote acyl participation and reagent modulation. The simultaneous SN2 substitution of azide groups at C2' and C2″ enabled the efficient synthesis of 1,2-cis-ß-linkages for both 2,3-diamino-D-mannuronic acids. Through a strategic orthogonal modification, the five amino groups on target trisaccharide 1 were equipped with a rare acetamidino (Am) and four acetyl (Ac) groups. Glycan microarray analyses of sera from patients infected with P. aeruginosa indicated that trisaccharides 1 and 2 are key antigenic epitopes of the serotype O5 O-antigen. The acetamidino group is not an essential determinant of antibody binding. The ß-D-ManpNAc3NAcA residue is a key motif for the antigenicity of serotype O5 O-antigen. These findings serve as a foundation for the development of glycoconjugate vaccines targeting P. aeruginosa serotype O5.

Improved drug-target interaction prediction with intermolecular graph transformer.

The identification of active binding drugs for target proteins (referred to as drug-target interaction prediction) is the key challenge in virtual screening, which plays an essential role in drug discovery. Although recent deep learning-based approaches achieve better performance than molecular docking, existing models often neglect topological or spatial of intermolecular information, hindering prediction performance. We recognize this problem and propose a novel approach called the Intermolecular Graph Transformer (IGT) that employs a dedicated attention mechanism to model intermolecular information with a three-way Transformer-based architecture. IGT outperforms state-of-the-art (SoTA) approaches by 9.1% and 20.5% over the second best option for binding activity and binding pose prediction, respectively, and exhibits superior generalization ability to unseen receptor proteins than SoTA approaches. Furthermore, IGT exhibits promising drug screening ability against severe acute respiratory syndrome coronavirus 2 by identifying 83.1% active drugs that have been validated by wet-lab experiments with near-native predicted binding poses. Source code and datasets are available at https://github.com/microsoft/IGT-Intermolecular-Graph-Transformer.

Evaluation of an E6/E7 PCR-capillary electrophoresis fragment analysis in the genotyping of human papillomavirus in archival FFPE samples of oropharyngeal cancer.

Accumulating evidence has demonstrated that high-risk human papillomaviruses (HR-HPVs) are involved in the etiology of a subset of oropharyngeal squamous cell carcinoma (OPSCC). In this regard, the International Agency for Research on Cancer (IARC) has recommended direct molecular HPV testing. So far, there is no agreement on the most appropriate method for HPV detection on OPSCC formalin-fixed paraffin-embedded (FFPE) materials. In this study, we aimed to evaluate the performance of the high-sensitive SureX HPV assay in OPSCC FFPE tissues compared with LiPA-25 and p16ink4a immunostaining. A retrospective series of FFPE primary OPSCC cases were diagnosed between 2008 and 2019 and provided by the Henan Cancer Hospital, China. The level of agreement of two assays was determined using Cohen's Kappa (κ) statistics. A total of 230 FFPE OPSCC samples from tumor resections (n = 160) and diagnostic biopsies (n = 70) were detected. Sixty-six (28.7%) and 70 (30.4%) samples were identified as HPV-DNA-positive by LiPA-25 and SureX, respectively, of which HPV16 was largely the most common type (95.5% vs 94.3%). We found a perfect concordance between LiPA-25 and SureX for HPV-DNA status (κ = 0.906, 95% CI: 0.875-0.937) and for HPV16 (κ = 0.925, 95% CI: 0.897-0.953). In addition, SureX and p16ink4a immunostaining had a perfect concordance (κ = 0.917, 95% CI: 0.888-0.946). Moreover, the HPV-driven fraction, based on double positivity for HPV-DNA and p16ink4a, was similar between SureX (63 of 230, 27.4%) and LiPA-25 (60 of 230, 26.1%). Similar results were found in samples from resections and biopsies. SureX and LiPA-25 are comparable. SureX could be used for routine HPV-DNA detection and genotyping on archival OPSCC FFPE tissues.

Aberrant accumulation of ceramides in mitochondria triggers cell death by inducing autophagy in Arabidopsis.

Sphingolipids are membrane lipids and play critical roles in signal transduction. Ceramides are central components of sphingolipid metabolism that are involved in cell death. However, the mechanism of ceramides regulating cell death in plants remains unclear. Here, we found that ceramides accumulated in mitochondria of accelerated cell death 5 mutant (acd5), and expression of mitochondrion-localized ceramide kinase (ACD5) suppressed mitochondrial ceramide accumulation and the acd5 cell death phenotype. Using immuno-electron microscopy, we observed hyperaccumulation of ceramides in acer acd5 double mutants, which are characterized by mutations in both ACER (alkaline ceramidase) and ACD5 genes. The results confirmed that plants with specific ceramide accumulation exhibited localization of ceramides to mitochondria, resulting in an increase in mitochondrial reactive oxygen species production. Interestingly, when compared with the wild type, autophagy-deficient mutants showed stronger resistance to ceramide-induced cell death. Lipid profiling analysis demonstrated that plants with ceramide accumulation exhibited a significant increase in phosphatidylethanolamine levels. Furthermore, exogenous ceramide treatment or endogenous ceramide accumulation induces autophagy. When exposed to exogenous ceramides, an increase in the level of the autophagy-specific ubiquitin-like protein, ATG8e, associated with mitochondria, where it directly bound to ceramides. Taken together, we propose that the accumulation of ceramides in mitochondria can induce cell death by regulating autophagy.

Characteristics of human papillomavirus prevalence and infection patterns among women aged 25-64 according to age groups and cytology results in Ordos City, China.

BACKGROUND: The assessment of human papillomavirus (HPV) genotype distribution in terms of age and cervical lesions could contribute to the adoption of more targeted preventive approaches to specific populations against cervical cancer. The current study was conducted in Ordos City, China, with the aim of analyzing the HPV genotypes prevalence and infection patterns within a hospital-based population. METHODS: The analysis included a total of 26,692 women aged 25-64 who underwent cervical cancer screening between January 1st, 2019, and June 30th, 2022, in Ordos City. These women had valid results for both the polymerase chain reaction (PCR)-reverse dot blot (RDB) HPV test and the liquid-based cytology (thinprep cytologic test/TCT). Data were extracted from the database of KingMed Diagnostics laboratories. The prevalence of HPV genotypes within different age groups and cytology diagnoses were calculated. RESULTS: Among 26,692 women, 7136 (26.73%) women were HPV positive, 5696 (21.34%) women were high-risk HPV (HR-HPV) positive, and 2102 (7.88%) women had multiple HPV infections. The most frequently detected HPV genotypes were HPV16 (4.72%) and HPV52 (4.15%), ranking as the first and second most prevalent genotypes, respectively. The prevalence of HR-HPV increased with age groups and severity of cervical lesions. Notably, the positive rate of HR-HPV among women aged 35-64 years showed a decreasing trend over the respective years, ranging from 26.00 to 19.70% (Ptrend < 0.001). CONCLUSION: In conclusion, the epidemiology of HPV genotypes partly reflects the effectiveness of regional cervical cancer prevention and control efforts in the past. These findings can inform future initiatives concerning HPV vaccination and screening in the region.

Competency of malaria laboratory diagnosis at national and provincial levels at the beginning of malaria post-elimination phase, China.

BACKGROUND: Qualified malaria diagnosis competency has contributed to the great achievement of malaria elimination in China. After eliminating malaria, it is still critical to the prevention of re-establishment of malaria transmission in China. This study was aimed to assess the malaria detection competency at national and provincial levels in China at the beginning of malaria post-elimination phase. METHODS: In the present study, different competency assessment activities on the laboratory malaria diagnosis were carried out for national and provincial malaria diagnostic laboratories based on the WHO scoring schedules, including malaria microscopy or nucleic acid amplification tests (NAAT), at the beginning of malaria post-elimination phase (2021-2022) in China. RESULTS: A total of 60 slides for malaria microscopy and 10 specimen for NAAT were included into the WHO External Quality Assessments of malaria parasite qualitative detection and species identification, and the scoring rate was 96.6% (microscopy: 171/177) and 85.0% (NAAT: 17/20), respectively. Moreover, 124 samples were included into the national NAAT quality assessment, and an accuracy of 87.9% (109/124) was found without significance among reference laboratories and non-reference laboratories. CONCLUSIONS: The findings suggest that there is still a need for sustained strengthening of malaria detection competency, particularly in the areas of parasite counting and detection of low-density parasitemia, to ensure prompt detection of the sources of infection and accurate identification of Plasmodium species, and contribute to case management and focus disposal, thereby effectively preventing the malaria re-establishment.

A multicenter, randomized, open-label, phase 2 clinical study of telitacicept in adult patients with generalized myasthenia gravis.

BACKGROUND AND PURPOSE: This study aimed to investigate the clinical efficacy and safety of telitacicept in patients with generalized myasthenia gravis (gMG) who tested positive for acetylcholine receptor antibodies or muscle-specific kinase antibodies and were receiving standard-of-care therapy. METHODS: Patients meeting the eligibility criteria were randomly assigned to receive telitacicept subcutaneously once a week for 24 weeks in addition to standard-of-care treatment. The primary efficacy endpoint was the mean change in the quantitative myasthenia gravis (QMG) score from baseline to week 24. Secondary efficacy endpoints included mean change in QMG score from baseline to week 12 and gMG clinical absolute score from baseline to week 24. Additionally, safety, tolerability and pharmacodynamics were assessed. RESULTS: Twenty-nine of the 41 patients screened were randomly selected and enrolled. The mean (± standard deviation [SD]) reduction in QMG score from baseline to week 24 was 7.7 (± 5.34) and 9.6 (± 4.29) in the 160 mg and 240 mg groups, respectively. At week 12, mean reductions in QMG scores for these two groups were 5.8 (± 5.85) and 9.5 (± 5.03), respectively, indicating rapid clinical improvement. Safety analysis revealed no adverse events leading to discontinuation or mortalities. All patients showed consistent reductions in serum immunoglobulin (Ig) A, IgG and IgM levels throughout the study. CONCLUSION: Telitacicept demonstrated safety, good tolerability and reduced clinical severity throughout the study period. Further validation of the clinical efficacy of telitacicept in gMG will be conducted in an upcoming phase 3 clinical trial.

Appraisal of evidence reliability and applicability of Paxlovid as treatment for SARS-COV-2 infection: A systematic review.

This study aimed to clarify the beneficial effect and the clinical application value of Paxlovid in the treatment of coronavirus disease-19 (COVID-19) through a systematic review. Databases including PubMed, Cochrane Library, Chinese Clinical Trial Registry, and ClinicalTrials.gov were systematically searched for interventional or observational studies on the efficacy and safety of Paxlovid in the treatment of SARS-COV-2. The relative and absolute effect sizes for the outcomes were calculated based on the data reported in the original intervention literature. The external applicability of the evidence was analysed in terms of clinical application scenarios, patient willingness, and cost utility. One interventional and three observational studies were conducted. Four studies published in 2022, had participation sample sizes ranging 1780-109,254. Based on the randomised controlled trial data, the risk of all-cause mortality, all-cause death, and hospitalisation was significantly reduced in the Paxlovid group. Serious adverse events were reduced during the study. Based on observational studies, Paxlovid can significantly reduce the risk of death and hospitalisation in older patients with COVID-19 (moderate certainty) and improve in-hospital disease progression, composite disease progression, and viral load (low certainty). Paxlovid did not improve the outcomes of death and hospitalisation (low certainty) in patients aged <65 years. As per the economic utility analysis, the economic cost of reducing one death dramatically decreased with increasing age. Early use of Paxlovid in the older adult population with COVID-19 is beneficial. However, in the setting of limited resources, Paxlovid should be prioritised for older patients.

Comparative evaluation of two clinical sampling techniques for HPV detection in male genital sites: a randomized controlled study.

AIMS: The optimal sampling methods for detecting human papillomavirus (HPV) in male genital sites remain unclear. This study aimed to assess the performance, acceptability, and comfort of two sampling techniques for male genital HPV detection. METHODS AND RESULTS: A total of 490 men aged 18-45 were randomly assigned in a 1:1 ratio to undergo either the rub-brush (nail file followed by swab) or brush-only method (swab only) for sampling at external genitalia sites (PGS) and perineum/perianal (PA) sites. HPV distribution, specimen validity (ß-globin as a quality reference), and participant acceptability and comfort were evaluated between the two sampling methods. The brush-only method demonstrated non-inferiority in detecting 14 high-risk HPV types (16/18/31/33/35/39/45/51/52/56/58/59/66/68) compared to the rub-brush method in both PGS (18.9% vs. 16.9%) and PA (10.5% vs. 11.9%). Although no significant differences were observed in positive rates for other HPV types, the brush-only method had a significantly higher invalid rate in PA (8.5% vs. 1.5%). Approximately 85.0% of participants reported good acceptability and comfort with both sampling methods, regardless of anatomical sites. CONCLUSIONS: This study suggests comparable performance, acceptability and comfort between the two sampling techniques for HPV detection. However, the rub-brush method may offer an advantage in higher sample validity.

Amonafide-based H2O2-responsive theranostic prodrugs: Exploring the correlation between H2O2 level and anticancer efficacy.

Leveraging the elevated hydrogen peroxide (H2O2) levels in cancer cells, H2O2-activated prodrugs have emerged as promising candidates for anticancer therapy. Notably, the efficacy of these prodrugs is influenced by the varying H2O2 levels across different cancer cell types. In this context, we have developed a novel H2O2-activated prodrug, PBE-AMF, which incorporates a phenylboronic ester (PBE) motif. Upon H2O2 exposure, PBE-AMF liberates the fluorescent and cytotoxic molecule amonafide (AMF), functioning as a theranostic agent. Our studies with PBE-AMF have demonstrated a positive correlation between intracellular H2O2 concentration and anticancer activity. The breast cancer cell line MDA-MB-231, characterized by high H2O2 content, showed the greatest susceptibility to this prodrug. Subsequently, we replaced the PBE structure with phenylboronic acid (PBA) to obtain the prodrug PBA-AMF, which exhibited enhanced stability, aqueous solubility, and tumor cell selectivity. This selectivity is attributed to its affinity for sialic acid, which is overexpressed on the surfaces of cancer cells. In vitro assays confirmed that PBA-AMF potently and selectively inhibited the proliferation of MDA-MB-231 cells, while sparing non-cancerous MCF-10A cells. Mechanistic investigations indicated that PBA-AMF impedes tumor proliferation by inhibiting DNA synthesis, reducing ATP levels, inducing apoptosis, and arresting the cell cycle. Our work broadens the range of small molecule H2O2-activated anticancer theranostic prodrugs, which are currently limited in number. We anticipate that the applications of PBA-AMF will extend to a wider spectrum of tumors and other diseases associated with increased H2O2 levels, thereby offering new horizons in cancer diagnostics and treatment.

Study on the coordinated development of urban competitiveness and energy-carbon emission reduction in China.

The urban competitiveness (UC) evaluation system is multidimensional and complex. This paper takes the simulated annealing (SA) model as the projection pursuit (PP) optimization to achieve a comprehensive assessment of competitiveness of 277 Chinese cities from 2011 to 2019, accompanied by energy saving and carbon-emission reduction (ESCER) as environmental measurements, to explore whether the two can meet the Porter hypothesis through coupling coordination degree (CCD). Further using spatiotemporal autocorrelation and obstacle degree model to uncover spatiotemporal features and interfering factors of coordinated development. Key findings include: (1) UC and ESCER show a slightly fluctuating upward trend during the research period, with apparent spatial variations. The eastern coastal region has a robust UC, while the less competitive central and western regions benefit from natural conditions, excelling in ESCER. (2) 87% of cities have achieved coordinated development between competitiveness and ESCER. Some coastal areas, often with a high CCD, are improving resource use efficiency and environmental benefits through economic agglomeration. From the perspective of the CCD collaboration network, the positive correlation accounts for about 85%, which reveals that most adjacent regions can cooperate on the road of coordinated development. (3) While differences exist in the coordinated development of UC-ESCER across various regions, social factors predominantly influence the obstacles affecting coordinated development. Specifically, a substantial barrier to the concordant progression of most cities is the number of patent applications, underscoring the pivotal role of innovation in aligning UC with ESCER.

Sodium hyaluronate and pranoprofen improve visual function and reduce inflammation in patients with dry eye.

OBJECTIVE: The aim of this study was to investigate the clinical use of sodium hyaluronate (SH) combined with pranoprofen in treating patients with dry eye. METHODS: A total of 117 patients with dry eye who were treated in the Traditional Chinese Medicine Hospital of Kunshan from March 2020 and May 2022 were included. According to the therapy approaches, they were treated with SH (SH group), pranoprofen (pranoprofen group), and SH combined with pranoprofen (joint group) (n = 39). RESULTS: The effective rates of dry eye were 79.49%, 74.36% and 94.87% in the SH group, the pranoprofen group and the joint group, respectively (p < 0.05). After treatment, the tear BUT and SIT in the joint group were all prominently increased than those in the other two groups (p < 0.05). The corneal fluorescein staining and dry eye symptom scores in the joint group after treatment were dramatically lower than those in the other two groups (p < 0.001). After treatment, the visual contrast sensitivity (12 c/d, 18 c/d and 24 c/d) in the joint group was markedly higher than those in the other two groups (p < 0.001). The CPR, TNF-α, IFN-γ and IL-1ß levels in the joint group were notably decreased than those in other two groups (p < 0.001). After treatment, the VRQOL quality-of-life scores in the joint group were significantly higher than those in the other two groups (p < 0.05). CONCLUSION: SH combined with pranoprofen showed clear therapeutic benefit in treating dry eye, and the curative effect was more favorable than with either medication alone.

Blood pressure variability and prognostic significance in traumatic brain injury: analysis of the eICU-CRD database.

BACKGROUND: Preliminary evidence demonstrates that visit-to-visit systolic blood pressure (SBP) variability is a prognostic factor of TBI. However, literature regarding the impact of initial blood pressure management on the outcomes of TBI patients is limited. We aimed to further validate the clinical significance of BPV on the prognostic outcomes of patients with TBI. METHODS: We performed the analysis by using individual patient-level data acquired from the eICU-CRD, which collected 200,859 ICU admissions of 139,367 patients in 2014 and 2015 from 208 US hospitals. Adult patients with traumatic intraparenchymal hemorrhage or contusion were included. The primary outcome was in-hospital mortality and the secondary outcome was discharge-home rate. Blood pressure variability (BPV) was calculated according to standard criteria: at least six measurements were taken in the first 24 h (hyperacute group) and 36 over days 2-7 (acute group). We estimated the associations between BPV and outcomes with logistic and proportional odds regression models. The key parameter for BPV was standard deviation (SD) of SBP, categorized into quintiles. We also calculated the average real variability (ARV), as well as maximum, minimum, and mean SBP for comparison in our analysis. RESULTS: We studied 1486 patients in the hyperacute group and 857 in the acute group. SD of SBP had a significant association with the in-hospital mortality for both the hyperacute group (highest quintile adjusted OR 2.28 95% CI 1.18-4.42; ptrend<0.001) and the acute group (highest quintile adjusted OR 2.17, 95% CI 1.08-4.36; ptrend<0.001). The strongest predictors of primary outcome were SD of SBP in the hyperacute phase and minimum SBP in the acute phase. Associations were similar for the discharge-home rate (for the hyperacute group, highest quintile adjusted OR 0.58, 95% CI 0.37-0.89; ptrend<0.001; for the acute group OR 0.55, 95% CI 0.32-0.95; ptrend<0.001). CONCLUSION: Systolic BPV seems to predict a poor outcome in patients with TBI. The benefits of early treatment to maintain appropriate SBP level might be enhanced by smooth and sustained control.

An unusual cause of life-threatening upper gastrointestinal bleeding.

A previously healthy 56-year-old female was hospitalized with intermittent melena and transient syncope for 1-month duration. Physical examination on admission showed heart rate was 105 beats per minute and blood pressure was 89/55 mmHg. Her hemoglobin was 6.7 g/dl. She received fluid infusion, blood transfusion, acid suppression and hemostasis treatment. Abdominal enhanced computed tomography (CT) demonstrated a well-defined mass with uniform adipose density in the antrum measuring 4 × 5 cm. Gastroscopy revealed a giant submucosal tumor with superficial ulceration in anterior wall of the gastric antrum. Endoscopic ultrasound (EUS) showed a homogeneous, well-circumscribed, hyperechoic mass originated from the submucosa layer. Distal partial gastrectomy was performed. Postoperative histopathology examination of the resected specimen revealed the tumor was composed of closely arranged and uniformly shaped proliferative mature adipocytes, which located in the submucosa layer with superficial mucosal ulcer. The patient was diagnosed as giant gastric lipoma with superficial ulcer and no symptoms was observed in 3 months follow-up.

Application effectiveness of "Youxin-1" in genetic diversity and structure analysis of local chickens.

China's local chicken breeds are rich in resources, and have formed different germplasm characteristics in the process of long-term selection and evolution. Scientific assessment of population genetic diversity and identification of inter-breed genetic structure are of great value to the protection and innovative utilization of local chicken breed resource. In order to evaluate the application effectiveness of 23K SNP chip "Youxin-1" in the analysis of genetic diversity and genetic structure of local chickens, we used RADseq to identify genomic genetic variation of 21 local chicken breeds and developed 23K chip "Youxin-1". The genetic statistics of each variety were calculated based on two sets of SNP data, and correlation, fitting and phylogenetic analysis were carried out to evaluate the application effectiveness of the chip. The results showed that the observed heterozygosity (Ho), polymorphism information content (PIC), inbred coefficient (FROH) and genetic differentiation coefficient (Fst) calculated based on the two SNP data sets were basically consistent in the 21 local chicken breeds. The genetic diversity of Langya chicken (LA), Piao chicken (PJ) and Wenchang chicken (WC) was relatively rich. The genetic diversity of Bian chickens (BJ), Langshan chickens (LS), Gushi chickens (GS), Dongxiang blue-eggshell chickens (DX) and Beijing fatty chickens (BY) was relatively poor, and the correlation coefficients of Ho, PIC, FROH and average Fst in the two groups were 0.794, 0.901, 0.926 and 0.984, respectively, all reaching extremely significant levels (P<0.01) with a high degree of fit (P<0.001) and R2 were 0.644, 0.827, 0.916 and 0.927. For the two sets of SNP data, the evolutionary tree constructed by neighbor-joining (NJ) method and maximum likelihood (ML) method was reasonable, and the 21 local chicken breeds were generally divided into six categories, which was consistent with the formation history and geographical distribution of the varieties. The 23K chip also realized reasonable clustering of the five new varieties without individual deviation. There are some differences in the estimation of genetic statistics using SNP with different densities, and data standardization is needed. 23K chip has good efficacy in the analysis of genetic diversity and structure of local chickens.

Ceramides regulate defense response by binding to RbohD in Arabidopsis.

Sphingolipids, a class of bioactive lipids, play a critical role in signal transduction. Ceramides, which are central components of sphingolipid metabolism, are involved in plant development and defense. However, the mechanistic link between ceramides and downstream signaling remains unclear. Here, the mutation of alkaline ceramidase in a ceramide kinase mutant acd5 resulted in spontaneous programmed cell death early in development and was accompanied by ceramide accumulation, while other types of sphingolipids, such as long chain base, glucosylceramide, and glycosyl inositol phosphorylceramide, remained at the same level as the wild-type plants. Analysis of the transcriptome indicated that genes related to the salicylic acid (SA) pathway and oxidative stress pathway were induced dramatically in acer acd5 plants. Comparison of the level of reactive oxygen species (ROS), SA, and ceramides in the wild-type and acer acd5 plants at different developmental stages indicated that the acer acd5 mutant exhibited constitutive activation of SA and ROS signaling, which occurred simultaneously with the alteration of ceramides. Overexpressing NahG in the acer acd5 mutant could completely suppress its cell death and ceramide accumulation, while benzo-(1,2,3)-thiadiazole-7-carbothioc acid S-methyl ester treatment restored its phenotype again. Moreover, we found that the plasma membrane of acer acd5 mutant was the main site of ROS production. Ceramides accumulated in the plasma membrane of acer acd5, directly binding and activating the NADPH oxidase RbohD and promoting hydrogen peroxide generation and SA- or defense-related gene activation. Our data illustrated that ceramides play an essential role in plant defense.

Overdamped Phonon Diffusion and Nontrivial Electronic Structure Leading to a High Thermoelectric Figure of Merit in KCu5Se3.

Thermoelectric copper selenides are highly attractive owing to not only their constituent nontoxic, abundant elements but also their ultralow liquid-like lattice thermal conductivity (κlat). For the first time, the promising thermoelectric properties of the new KCu5Se3 are reported herein, showing a high power factor (PF = 9.0 µWcm-1 K-2) and an intrinsically ultralow κlat = 0.48 Wm-1 K-1. The doped K1-xBaxCu5Se3 (x = 0.03) realizes a figure-of-merit ZT = 1.3 at 950 K. The crystallographic structure of KCu5Se3 allows complex lattice dynamics that obey a rare dual-phonon transport model well describing a high scattering rate and an extremely short phonon lifetime that are attributed to interband phonon tunneling, confinement of the transverse acoustic branches, and temperature-dependent anharmonic renormalization, all of which generate an unprecedently high contribution of the diffusive phonons (70% at 300 K). The overall weak chemical bonding feature of KCu5Se3 gives K+ cations a quiescence behavior that further blocks the heat flux transfer. In addition, the valence band edge energy dispersion of KCu5Se3 is quasilinear that allows a large Seebeck coefficient even at high hole concentrations. These in-depth understandings of the ultralow lattice thermal conductivity provide new insights into the property-oriented design and synthesis of advanced complex chalcogenide materials.