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Objective: The aim of this study was to assess right atrial (RA) function, including RA phase strain, via speckle-tracking echocardiography (STE) in a cohort of systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH) and in particular to explore the relationship between RA phase strain and the occurrence of cardiovascular events., Methods: STE analyses of RA function were evaluated in patients with SLE-PAH and in 33 healthy control subjects. Clinical associations, serum biomarkers, echocardiographic data, survival times, and adverse cardiovascular events were evaluated., Results: A total of 66 patients with SLE-PAH were enrolled; they were divided into two groups based on the occurrence of adverse clinical events. RA phase strain was significantly reduced in patients with events than in patients without events. The endpoint was defined as the combined outcome of all-cause mortality, right heart failure, and rehospitalization due to disease progression. During a mean follow-up of 17.2 ± 9.9 months, 23 patients (35%) reached the endpoint. Compared with patients with RA reservoir strain (RASr) ≥33.45%, patients with RASr < 33.45% had more adverse long-term outcomes (log rank p < .0001). RASr was independently associated with adverse clinical outcomes according to multivariate analysis (p = .010)., Conclusion: Our data suggest that RA function has prognostic value for SLE-PAH patients, and strain analysis revealed that the worse the RA function is, the worse the prognosis., (© 2024 Wiley Periodicals LLC.)

Bismuth produces different types of ordered superstructures on the InAs(100) surface, depending on the growth procedure and coverage. The (2 × 1) phase forms at completion of one Bi monolayer and consists of a uniformly oriented array of parallel lines of Bi dimers. Scanning tunneling and core level spectroscopies demonstrate its metallic character, in contrast with the semiconducting properties expected on the basis of the electron counting principle. The weak electronic coupling among neighboring lines gives rise to quasi one-dimensional Bi-derived bands with open contours at the Fermi level. Spin- and angle-resolved photoelectron spectroscopy reveals a giant Rashba splitting of these bands, in good agreement with ab initio electronic structure calculations. The very high density of the dimer lines, the metallic and quasi one-dimensional band dispersion and the Rashba-like spin texture make the Bi/InAs(100)-(2 × 1) phase an intriguing system, where novel transport regimes can be studied.

Context: Leucine-rich α-2-glycoprotein 1 (LRG1) has been implicated in the pathogenesis of diabetic complications, but its association with cognitive function remains unclear., Objective: Our primary objective is to investigate the longitudinal association between LRG1 and cognitive function in patients with type 2 diabetes mellitus (T2DM). Secondarily, we determine the causal relationship using Mendelian randomization (MR) and the role of arterial stiffness as a potential mediator., Methods: T2DM patients (n = 1039; age = 64.1 ± 6.4 years) were followed-up for 5.3 ± 1.2 years. Plasma LRG1 was measured at baseline using enzyme-linked immunosorbent assay. Baseline and follow-up cognitive function was assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). One-sample MR was performed with rs4806985 as plasma LRG1-associated single-nucleotide polymorphism. Mediation analysis was performed to examine if pulse wave velocity (PWV), an arterial stiffness index, mediated the association between plasma LRG1 and follow-up cognitive function., Results: Elevated baseline natural log (Ln)-transformed LRG1 was inversely associated with baseline and follow-up RBANS total score with adjusted coefficients -1.38 (95% CI -2.55 to -.21; P = .021) and -1.38 (95% CI -2.70 to -.07; P = .039), respectively. Genetically predicted higher levels of plasma LRG1 was associated with lower follow-up RBANS total score with coefficient -7.44 (95% CI -14.14 to -.74; P = .030) per unit increase in LnLRG1. Higher PWV accounted for 27.7% of the association between LnLRG1 and follow-up RBANS total score., Conclusion: Baseline plasma LRG1 was associated with lower cognitive function at follow-up in patients with T2DM, mediated by PWV. MR analysis provided evidence of an association between genetically influenced plasma LRG1 and lower cognitive function at follow-up., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The epitranscriptomic mark N 6 -methyladenosine (m 6 A) is the most common type of messenger RNA (mRNA) post-transcriptional modification in eukaryotes. With the discovery of the demethylase FTO (FAT MASS AND OBESITY-ASSOCIATED PROTEIN) in Homo Sapiens , this modification has been proven to be dynamically reversible. With technological advances, research on m 6 A modification in plants also rapidly developed. m 6 A modification is widely distributed in plants, which is usually enriched near the stop codons and 3'-UTRs, and has conserved modification sequences. The related proteins of m 6 A modification mainly consist of three components: methyltransferases (writers), demethylases (erasers), and reading proteins (readers). m 6 A modification mainly regulates the growth and development of plants by modulating the RNA metabolic processes and playing an important role in their responses to environmental signals. In this review, we briefly outline the development of m 6 A modification detection techniques; comparatively analyze the distribution characteristics of m 6 A in plants; summarize the methyltransferases, demethylases, and binding proteins related to m 6 A; elaborate on how m 6 A modification functions in plant growth, development, and response to environmental signals; and provide a summary and outlook on the research of m 6 A in plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiang, Zhang, Li, Xue, Zhang, Meng, Wang, Tan and Li.)

Zinc finger protein 180 (ZNF180) is a multifunctional protein that interacts with nucleic acids and regulates various cellular processes; however, the function of ZNF180 in colorectal cancer (CRC) remains unclear. The present study investigated the role and function of ZNF180 in CRC, and aimed to reveal the underlying molecular mechanism. The results revealed that ZNF180 was downregulated in CRC tissues and was associated with a good prognosis in patients with CRC. Additionally, the expression of ZNF180 was downregulated by methylation in CRC. In vivo and in vitro experiments revealed that ZNF180 overexpression was functionally associated with the inhibition of cell proliferation and the induction of apoptosis. Mechanistically, chromatin immunoprecipitation‑PCR and luciferase assays demonstrated that ZNF180 markedly regulated the transcriptional activity of methyltransferase 14, N6‑adenosine‑methyltransferase non‑catalytic subunit (METTL14) by directly binding to and activating its promoter region. Simultaneous overexpression of ZNF180 and knockdown of METTL14 indicated that the reduction of METTL14 could suppress the effects of ZNF180 on the induction of apoptosis. Clinically, the present study observed a significant positive correlation between ZNF180 and METTL14 expression levels, and low expression of ZNF180 and METTL14 predicted a poor prognosis in CRC. Overall, these findings revealed a novel mechanism by which the ZNF180/METTL14 axis may modulate apoptosis and cell proliferation in CRC. This evidence suggests that this axis may serve as a prognostic biomarker and therapeutic target in patients with CRC.

Acute cellular rejection (ACR) is a prevalent postoperative complication following liver transplantation (LT), exhibiting an increasing incidence of morbidity and mortality. However, the molecular mechanisms of ACR following LT remain unclear. To explore the genetic pathogenesis and identify biomarkers of ACR following LT, three relevant Gene Expression Omnibus (GEO) datasets consisting of data on ACR or non-ACR patients after LT were comprehensively investigated by computational analysis. A total of 349 upregulated and 260 downregulated differentially expressed genes (DEGs) and eight hub genes ( ISG15, HELZ2, HNRNPK, TIAL1, SKIV2L2, PABPC1, SIRT1, and PPARA ) were identified. Notably, HNRNPK , TIAL1 , and PABPC1 exhibited the highest predictive potential for ACR with AUCs of 0.706, 0.798, and 0.801, respectively. KEGG analysis of hub genes revealed that ACR following LT was predominately associated with ferroptosis, protein processing in the endoplasmic reticulum, complement and coagulation pathways, and RIG-I/NOD/Toll-like receptor signaling pathway. According to the immune cell infiltration analysis, γδT cells, NK cells, Tregs, and M1/M2-like macrophages had the highest levels of infiltration. Compared to SIRT1, ISG15 was positively correlated with γδT cells and M1-like macrophages but negatively correlated with NK cells, CD4 + memory T cells, and Tregs. In conclusion, this study identified eight hub genes and their potential pathways, as well as the immune cells involved in ACR following LT with the greatest levels of infiltration. These findings provide a new direction for future research on the underlying mechanism of ACR following LT., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Chun-Qiang Dong reports financial support was provided by The First Affiliated Hospital of 10.13039/501100011827Guangxi Medical University. Song-Qing He reports financial support was provided by The First Affiliated Hospital of 10.13039/501100011827Guangxi Medical University. Chun-Qiang Dong reports a relationship with The First Affiliated Hospital of 10.13039/501100011827Guangxi Medical University that includes: funding grants. Song-Qing He reports a relationship with The First Affiliated Hospital of 10.13039/501100011827Guangxi Medical University that includes: funding grants. No other conflicts of interest. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Land-use changes are an important factor affecting the change in carbon storage in terrestrial ecosystems. Exploring the relationship between land-use changes and carbon storage provides reliable data support for optimizing regional land-use structure and maintaining regional carbon balance. Taking Jiangxi Province as an example, we first analyzed the land-use changes; then simulated the land-use pattern under three scenarios (i.e., natural development, ecological priority, and economic development scenarios) in 2030 based on the PLUS model; and finally estimated the carbon storage change in the past (i.e., 1990-2020) and future periods (i.e., three scenarios in 2030) using the InVEST model, analyzed the spatial-temporal characteristics, and proposed the corresponding suggestions. The results showed:① The carbon storage in Jiangxi Province showed a downward trend from 1990 to 2020, with a total reduction of 4.58×10 7 t. The increase in the water bodies and construction land and the decrease in cultivated land, woodland, grassland, and unused land was the major cause. ② The carbon storage under natural development, ecological priority, and economic development scenarios in Jiangxi Province in 2030 were 2.20×10 9 , 2.24×10 9 and 2.19×10 9 t, respectively. ③ The carbon storage under the three scenarios showed similar spatial characteristics, wherein the high carbon storage was distributed in northern, northwest, and western regions, and the low carbon storage was distributed near the central region. These results can provide data support for future land spatial planning and improving the carbon storage of terrestrial ecosystems in Jiangxi Province.

Background:  This study aims to analyze breast cancer burden attributable to high body mass index (BMI) and high fasting plasma glucose (FPG) in China from 1990 to 2019., Methods: Data were obtained from the Global Burden of Disease (GBD) study 2019. Deaths and disability-adjusted life years (DALYs) were used for attributable burden, and age-period-cohort (APC) model was used to evaluate the independent effects of age, period and birth cohort., Results: In 2019, the age-standardized mortality and DALY rates of breast cancer attributable to high BMI were 1.107 (95% UI: 0.311, 2.327) and 29.990 (8.384, 60.713) per 100 000, and mortality and DALY rates attributable to high FPG were 0.519 (0.095, 1.226) and 13.662 (2.482, 32.425) per 100 000. From 1990 to 2019, the age-standardized mortality and DALY rates of breast cancer attributable to high BMI increased by 1.192% and 1.180%, and the trends of high FPG were not statistically significant. The APC results showed that the age effects of high BMI and high FPG-mortality and DALY rates increased, with the highest rates in the age group over 80 years. The birth cohort effects of high BMI showed "inverted V" shapes, while high FPG showed downward trends., Conclusions: Age was the main reason for the increase of attributable burden, and postmenopausal women were the high-risk groups. Therefore, targeted prevention measures should be developed to improve postmenopausal women's awareness and effectively reduce the prevalence of obesity and diabetes, thereby reducing the breast cancer burden caused by metabolic factors in China., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: The efficacy and safety of deep transcranial magnetic stimulation (dTMS) as an intervention for schizophrenia remain unclear. This systematic review examined the efficacy and safety of dTMS for schizophrenia., Methods: A systematic search of Chinese (WanFang and Chinese Journal Net) and English databases (PubMed, EMBASE, PsycINFO, and Cochrane Library) were conducted., Results: Three randomized clinical trials (RCTs) comprising 80 patients were included in the analyses. Active dTMS was comparable to the sham treatment in improving total psychopathology, positive symptoms, negative symptoms, and auditory hallucinations measured by the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Auditory Hallucinations Rating Scale (AHRS), respectively. Only one RCT reported the effects on neurocognitive function measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB), suggesting that dTMS may only improve one Stockings of Cambridge measure (i.e., subsequent times for five move problems). All three studies reported overall discontinuation rates, which ranged from 16.7% to 44.4%. Adverse events were reported in only one RCT, the most common being tingling/twitching (30.0%, 3/10), head/facial discomfort (30.0%, 3/10), and back pain (20.0%, 2/10)., Conclusion: This systematic review suggests that dTMS does not reduce psychotic symptoms in schizophrenia, but it shows potential for improving executive functions. Future RCTs with larger sample sizes focusing on the effects of dTMS on psychotic symptoms and neurocognitive function in schizophrenia are warranted to further explore these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mo, Shi, Yang, Lan, Deng, Huang, Tan, Pridmore, Ungvari, Xiang and Zheng.)

Chiral crystals and molecules were recently predicted to form an intriguing platform for unconventional orbital physics. Here, we report the observation of chirality-driven orbital textures in the bulk electronic structure of CoSi, a prototype member of the cubic B20 family of chiral crystals. Using circular dichroism in soft x-ray angle-resolved photoemission, we demonstrate the formation of a bulk orbital-angular-momentum texture and monopolelike orbital-momentum locking that depends on crystal handedness. We introduce the intrinsic chiral circular dichroism, icCD, as a differential photoemission observable and a natural probe of chiral electron states. Our findings render chiral crystals promising for spin-orbitronics applications.

Pulmonary arterial hypertension (PAH) is a common complication of systemic lupus erythematosus (SLE), and PAH can cause right ventricle (RV) remodel and dyssynchrony. The aim of this study was to explore the value of RV dyssynchrony in predicting adverse clinical events in patients with systemic lupus erythematosus-aaociated pulmonary arterial hypertension (SLE-PAH) using two-dimensional speckle tracking echocardiography (2D-STE). A total of 53 patients with SLE-PAH were enrolled in this study. The dyssynchrony of the RV (RV-SD6) was evaluated by 2D-STE. The clinical data of all participants were collected, and routine cardiac function parameters were measured by two-dimensional echocardiography, and analyzed for their correlation with RV-SD6. The predictive value of RV-SD6 in clinical adverse event was evaluated. RV-SD6 was negatively correlated with RV-FLS, RV-FAC, and TAPSE (r = - 0.788, r = - 0.363 and r = - 0.325, respectively, all P < 0.01), while the correlation with RV-FLS was the strongest. linear regression analysis showed that RV-FLS was an independent risk factor for RV-SD6 (β = - 1.40, 95% CI - 1.65 ~ - 1.14, P < 0.001). Cox regression analysis showed that RV-SD6 was a predictor with clinical adverse events (HR = 1.03, 95% CI 1 ~ 1.06, P < 0.05). RV-SD6 was highly discriminative in predicting clinical adverse events (AUC = 0.764), at a cutoff of 51.10 ms with a sensitivity of 83.3% and specificity of 68.3%. RV-FLS was negatively correlated with RV-SD6 and was an independent risk factor for it. RV-SD6 can serve as an indicator for predicting the occurrence of adverse clinical events in SLE-PAH patients, with high sensitivity and specificity., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Ex vivo tissue culture of the human corpus cavernosum (CC) can be used to explore the tissue structural changes and complex signaling networks. At present, artificial CC-like tissues based on acellular or three-dimensional (3D)-printed scaffolds are used to solve the scarcity of primary penis tissue samples. However, inconvenience and high costs limit the wide application of such methods. Here, we describe a simple, fast, and economical method of constructing artificial CC-like tissue. Human CC fibroblasts (FBs), endothelial cells (ECs), and smooth muscle cells (SMCs) were expanded in vitro and mixed with Matrigel in specific proportions. A large number of bubbles were formed in the mixture by vortexing combined with pipette blowing, creating a porous, spongy, and spatial structure. The CC FBs produced a variety of signaling factors, showed multidirectional differentiation potential, and grew in a 3D grid in Matrigel, which is necessary for CC-like tissue to maintain a porous structure as a cell scaffold. Within the CC-like tissue, ECs covered the surface of the lumen, and SMCs were located inside the trabeculae, similar to the structure of the primary CC. Various cell components remained stable for 3 days in vitro , but the EC content decreased on the 7 th day. Wingless/integrated (WNT) signaling activation led to lumen atrophy and increased tissue fibrosis in CC-like tissue, inducing the same changes in characteristics as in the primary CC. This study describes a preparation method for human artificial CC-like tissue that may provide an improved experimental platform for exploring the function and structure of the CC and conducting drug screening for erectile dysfunction therapy., (Copyright © 2024 Copyright: © The Author(s)(2024).)

The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8 + T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8 + T cells contained a fraction of CD39 hi cells that constituted about 6.6% of total CD8 + T cells in tumors. These CD39 hi cells enriched for GC-infiltrating CD8 + T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39 hi CD8 + T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39 int and CD39 - CD8 + counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39 hi CD8 + T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39 hi CD8 + T cells correlated with tumor progression and independently predicted patients' poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8 + T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39 hi CD8 + T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: An important strategy to combat yield loss challenge is the development of varieties with increased tolerance to drought to maintain production. Improvement of crop yield under drought stress is critical to global food security., Methods: In this study, we performed multiomics analysis in a collection of 119 diverse rapeseed ( Brassica napus L.) varieties to dissect the genetic control of agronomic traits in two watering regimes [well-watered (WW) and drought stress (DS)] for 3 years. In the DS treatment, irrigation continued till the 50% pod development stage, whereas in the WW condition, it was performed throughout the whole growing season., Results: The results of the genome-wide association study (GWAS) using 52,157 single-nucleotide polymorphisms (SNPs) revealed 1,281 SNPs associated with traits. Six stable SNPs showed sequence variation for flowering time between the two irrigation conditions across years. Three novel SNPs on chromosome C04 for plant weight were located within drought tolerance-related gene ABCG16 , and their pleiotropically effects on seed weight per plant and seed yield were characterized. We identified the C02 peak as a novel signal for flowering time, harboring 52.77% of the associated SNPs. The 288-kbps LD decay distance analysis revealed 2,232 candidate genes (CGs) associated with traits. The CGs BIG1 - D , CAND1 , DRG3 , PUP10 , and PUP21 were involved in phytohormone signaling and pollen development with significant effects on seed number, seed weight, and grain yield in drought conditions. By integrating GWAS and RNA-seq, 215 promising CGs were associated with developmental process, reproductive processes, cell wall organization, and response to stress. GWAS and differentially expressed genes (DEGs) of leaf and seed in the yield contrasting accessions identified BIG1-D , CAND1 , and DRG3 genes for yield variation., Discussion: The results of our study provide insights into the genetic control of drought tolerance and the improvement of marker-assisted selection (MAS) for breeding high-yield and drought-tolerant varieties., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Salami, Heidari, Alizadeh, Batley, Wang, Tan, Dadkhodaie and Richards.)

Objectives: CD4 + T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor-infiltrating CD4 + T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown., Methods: A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD-1 on CD4 + T cells in the different samples was analysed by flow cytometry. GC-infiltrating CD4 + T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC-infiltrating T cells was investigated by inhibiting CD39 enzymatic activity., Results: In comparison with CD4 + T cells from the non-tumor tissues, significantly more GC-infiltrating CD4 + T cells expressed CD39. Most GC-infiltrating CD39 + CD4 + T cells exhibited CD45RA - CCR7 - effector-memory phenotype expressing more exhaustion-associated inhibitory molecules and transcription factors and produced less TNF-α, IFN-γ and cytolytic molecules than their CD39 - CD4 + counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF-α and IFN-γ production. Finally, increased percentages of GC-infiltrating CD39 + CD4 + T cells were positively associated with disease progression and patients' poorer overall survival., Conclusion: Our study demonstrates that CD39 expression defines GC-infiltrating CD4 + T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Myelodysplastic syndrome (MDS) may present with specific skin lesions, such as leukaemia cutis, which is a well known poor prognostic marker of leukaemia with a high risk of acute leukaemic transformation. However, less is known regarding non-specific cutaneous manifestations of MDS including the prevalence, types and their prognostic and therapeutic significance, which we aimed to determine through this systematic review. We searched electronic databases (PubMed, Medline and EMBASE) from inception up to 26 January 2023 for studies reporting cutaneous manifestations of MDS. Eighty eight articles (case reports n  = 67, case series n  = 21), consisting of 134 patients were identified. We identified 6 common cutaneous manifestations: neutrophilic dermatoses ( n  = 64), vasculitis ( n  = 21), granulomatous ( n  = 8), connective tissue disease (CTD) ( n  = 7; composed of dermatomyositis ( n  = 5), cutaneous lupus erythematosus ( n  = 1), and systemic sclerosis ( n  = 1)), panniculitis ( n  = 4), immunobullous ( n  = 1), and other ( n  = 29). Cutaneous features either occurred at time of MDS diagnosis in 25.3%, preceding the diagnosis in 34.7% (range 0.5-216 months), or after diagnosis in 40.0% (range 1-132 months). Prognosis was poor (40.2% death) with 34.1% progressing to acute myeloid leukaemia (AML). 50% of those with MDS who progressed to AML had neutrophilic dermatoses ( p  = 0.21). Myelodysplastic syndrome was fatal in 39.2% of neutrophilic dermatoses (median time from onset of cutaneous manifestation: 12 months), 50% of vasculitis (7.5 months), 62.5% of granulomatous (15.5 months) and 14.3% of CTD (7 months). Recognition of patterns of cutaneous features in MDS will improve early diagnosis and risk stratification according to subtype and associated prognosis., Competing Interests: None to declare., (© 2023 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

NR0B1 is frequently activated in hepatocellular carcinoma (HCC). However, the role of NR0B1 is controversial in HCC. In this study, we observed that NR0B1 was an independent poor prognostic factor, negatively correlated with the overall survival of HCC and the relapse-free survival of patients treated with sorafenib. Meanwhile, NR0B1 promoted the proliferation, migration, and invasion of HCC cells, inhibited sorafenib-induced apoptosis, and elevated the IC50 of sorafenib in HCC cells. NR0B1 was further displayed to increase sorafenib-induced autophagic vesicles and activate Beclin1/LC3-II-dependent autophagy pathway. Finally, NR0B1 was revealed to transcriptionally suppress GSK3β that restrains AMPK/mTOR-driven autophagy and increases BAX-mediated apoptosis. Collectively, our study uncovered that the ectopic expression of NR0B1 augmented sorafenib-resistance in HCC cells by activating autophagy and inhibiting apoptosis. Our findings supported that NR0B1 was a detrimental factor for HCC prognosis., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Low temperature is a critical environmental stress factor that restricts crop growth and geographical distribution, significantly impacting crop quality and yield. When plants are exposed to low temperatures, a series of changes occur in their external morphology and internal physiological and biochemical metabolism. This article comprehensively reviews the alterations and regulatory mechanisms of physiological and biochemical indices, such as membrane system stability, redox system, fatty acid content, photosynthesis, and osmoregulatory substances, in response to low-temperature stress in plants. Furthermore, we summarize recent research on signal transduction and regulatory pathways, phytohormones, epigenetic modifications, and other molecular mechanisms mediating the response to low temperatures in higher plants. In addition, we outline cultivation practices to improve plant cold resistance and highlight the cold-related genes used in molecular breeding. Last, we discuss future research directions, potential application prospects of plant cold resistance breeding, and recent significant breakthroughs in the research and application of cold resistance mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wang, Sarwar, Zhang, Geng, Zhu and Tan.)

Introduction: Biochemical and metabolic processes help plants tolerate the adverse effects of drought. In plants accumulating bioactive compounds, understanding the genetic control of the biosynthesis of biochemical pathways helps the discovery of candidate gene (CG)-metabolite relationships., Methods: The metabolic profile of flowers in 119 rapeseed ( Brassica napus ) accessions was assessed over two irrigation treatments, one a well-watered (WW) condition and the other a drought stress (DS) regime. We integrated information gained from 52,157 single-nucleotide polymorphism (SNP) markers, metabolites, and transcriptomes to identify linked SNPs and CGs responsible for the genetic control of flower phenolic compounds and regulatory elements., Results: In a genome-wide association study (GWAS), of the SNPs tested, 29,310 SNPs were qualified to assess the population structure and linkage disequilibrium (LD), of which several SNPs for radical scavenging activity (RSA) and total flavanol content (TFLC) were common between the two irrigation conditions and pleiotropic SNPs were found for chlorogenic and coumaric acids content. The principal component analysis (PCA) and stepwise regression showed that chlorogenic acid and epicatechin in WW and myricetin in DS conditions were the most important components for RSA. The hierarchical cluster analysis (HCA) showed that vanillic acid, myricetin, gallic acid, and catechin were closely associated in both irrigation conditions. Analysis of GWAS showed that 60 CGs were identified, of which 18 were involved in stress-induced pathways, phenylpropanoid pathway, and flavonoid modifications. Of the CGs, PAL1 , CHI , UGT89B1 , FLS3 , CCR1 , and CYP75B137 contributed to flavonoid biosynthetic pathways. The results of RNA sequencing (RNA-seq) revealed that the transcript levels of PAL , CHI , and CYP75B137 known as early flavonoid biosynthesis-related genes and FLS3 , CCR1 , and UGT89B1 related to the later stages were increased during drought conditions. The transcription factors (TFs) NAC035 and ERF119 related to flavonoids and phenolic acids were upregulated under drought conditions., Discussion: These findings expand our knowledge on the response mechanisms to DS, particularly regarding the regulation of key phenolic biosynthetic genes in rapeseed. Our data also provided specific linked SNPs for marker-assisted selection (MAS) programs and CGs as resources toward realizing metabolomics-associated breeding of rapeseed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The Handling Editor HR declared a past co-authorship with the author JB., (Copyright © 2024 Salami, Heidari, Batley, Wang, Tan, Richards and Tan.)

Scope: The study aims to investigate the role of the sulfur microbial diet in the survival of ovarian cancer (OC)., Methods and Results: A prospective cohort study is conducted with 703 patients diagnosed with OC between 2015 and 2020. Diet information is collected using a validated food frequency questionnaire. Deaths are ascertained up to March 31, 2021, via the death registry linkage. During the follow-up period (median: 37.2 months, interquartile range: 24.7-50.2 months), 130 deaths are observed. A higher sulfur microbial diet score is significantly associated with an increased risk of all-cause mortality among OC patients (tertile 3 vs tertile 1: HR = 1.93, 95% CI = 1.11-3.35). Each 1-standard deviation increment in the sulfur microbial diet score increases the all-cause mortality risk by 33% (95% CI = 1.04-1.71). Stratified analysis shows that significant associations are found in OC patients diagnosed over 50 years of age, with body mass index ≥24  kg m -2 , who changed their diet after diagnosis, or without residual lesions., Conclusions: Adherence to the sulfur microbial diet, characterized by high intakes of red meats and processed meats, and low intakes of fruits, vegetables, and whole grains, is associated with poor survival in OC patients., (© 2023 Wiley-VCH GmbH.)

Background: Certified training must be provided for lay vision screeners prior to their conduct of a vision screening programme. However, the effectiveness of trained lay screeners does deteriorate over time. This study aims to evaluate the effectiveness of a recertification vision screening training module using the KieVision ™ Preschool Vision Screening Kit for preschool teachers in Malaysia., Methods: This was a randomised control trial. Fifty-nine preschool teachers previously enrolled in a Knowledge Transfer Programme were divided into a Study Group ( n = 31) to receive recertification training and a Control Group ( n = 28) to attend briefing sessions. Subjects was then asked to perform vision screening on 15 preschool children aged 4 years old-6 years old at their respective premises, then verified by optometrists after 2 weeks from the initial screening on the same children., Results: A total of 894 children were screened, with the Study Group and Control Group screened 49.7% and 50.3%, respectively. There was higher validity in vision screening findings from the Study Group (sensitivity = 66.7%, positive predictive value (PPV) = 61.5%) compared to the Control Group (sensitivity = 36.0 %, PPV = 40.9%)., Conclusion: Teachers who received recertification training were more competent in detecting children's vision impairment using KieVision ™ Preschool Vision Screening Kit. Thus, timely recertification training should be emphasised to ensure sustainable consistency and reliability of vision screening programmes conducted by lay vision screeners., Competing Interests: Conflict of Interest: None., (© Penerbit Universiti Sains Malaysia, 2023.)

Sclerotinia sclerotiorum (Lib.) de Bary is a highly destructive fungal pathogen that seriously damages the yield and quality of Brassica napus worldwide. The complex interaction between the B. napus and S. sclerotiorum system has presented significant challenges in researching rapeseed defense strategies. Here, we focus on the infection process of S. sclerotiorum , the defense mechanisms of rapeseed, and recent research progress in this system. The response of rapeseed to S. sclerotiorum is multifaceted; this review aims to provide a theoretical basis for rapeseed defense strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Wang, Sarwar and Tan.)

Ferroptosis has demonstrated significant potential in treating radiochemotherapy-resistant cancers, but its efficacy can be affected by recently discovered ferroptosis suppressors. In this study, we discovered that NR0B1 protects against erastin- or RSL3-induced ferroptosis in lung cancer cells. Transcriptomic analysis revealed that NR0B1 significantly interfered with the expression of 12 ferroptosis-related genes, and the expression level of NR0B1 positively correlated with that of c-JUN, NRF2, and CBS. We further revealed that NR0B1 suppression of ferroptosis depended on the activities of c-JUN, NRF2, and CBS. NR0B1 directly promoted the expression of NRF2 and c-JUN and indirectly upregulated CBS expression through enhancing NRF2 and/or c-JUN transcription. Moreover, we showed that NR0B1 depletion restrained xenograft tumor growth and facilitated RSL3-induced ferroptosis in the tumors. In conclusion, our findings uncover that NR0B1 suppresses ferroptosis by activating the c-JUN/NRF2-CBS signaling pathway in lung cancer cells, providing new evidence for the involvement of NR0B1 in drug resistance during cancer therapy., Competing Interests: None., (AJCR Copyright © 2023.)

Fermi surfaces of transition metals, which describe all thermodynamical and transport quantities of solids, often fail to be modeled by one-electron mean-field theory due to strong correlations among the valence electrons. In addition, relativistic spin-orbit coupling pronounced in heavier elements lifts the degeneracy of the energy bands and further modifies the Fermi surface. Palladium and rhodium, two 4d metals attributed to show significant spin-orbit coupling and electron correlations, are ideal for a systematic and fundamental study of the two fundamental physical phenomena and their interplay in the electronic structure. In this study, we explored the Fermi surface of the 4d noble metals palladium and rhodium obtained via high-resolution constant initial state momentum microscopy. The complete 3D-Fermi surfaces of palladium and rhodium were tomographically mapped using soft X-ray photon energies from 34 eV up to 660 eV. To fully capture the orbital angular momentum of states across the Fermi surface, the Fermi surface tomography was performed using p- and s- polarized light. Applicability and limitations of the nearly-free electron final state model in photoemission are discussed using a complex band structure model supported by experimental evidence. The significance of spin-orbit coupling and electron correlations across the Fermi surfaces will be discussed within the context of the photoemission results. State-of-the-art fully relativistic Korringa-Kohn-Rostoker (KKR) calculations within the one-step model of photoemission are used to support the experimental results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to investigate the splenic tissue damage of environmental biological drug avermectin to freshwater cultured carp and to evaluate the effect of silybin on the splenic tissue damage of carp induced by avermectin. A total of 60 carp were divided into 4 groups with 15 carp in each group, including the control group fed with basic diet, experimental group fed with basal diet and exposed to avermectin (avermectin group), experimental group fed with basal diet supplement silybin (silybin group), and experimental group fed with basal diet supplement silybin and exposed to avermectin (silybin + avermectin group). The whole test period lasted for 30 days, and spleen tissue was collected for analysis. In this study, H&E staining, mitochondrial purification and membrane potential detection, ATP detection, DHE staining, biochemical tests, qPCR, immunohistochemistry, and apoptosis staining were used to evaluate the biological processes of spleen tissue injury, mitochondrial function, oxidative stress, apoptosis, and endoplasmic reticulum stress. The results show that silybin protected carp splenic tissue damage caused by chronic avermectin exposure, decreased mitochondrial membrane potential, decreased ATP content, ROS accumulation, oxidative stress, apoptosis, and endoplasmic reticulum stress. Silybin may ameliorate the splenic tissue damage of cultured freshwater carp caused by environmental biopesticide avermectin by alleviating mitochondrial dysfunction and inhibiting PERK-ATF4-CHOP-driven mitochondrial apoptosis. Adding silybin into the diet becomes a feasible strategy to resist the pollution of avermectin and provides a theoretical basis for creating a good living environment for freshwater carp., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The focus of the study is to examine the function of TYMSOS in immune escape of breast cancer, which is the most frequently diagnosed malignancy among women globally. Our study demonstrated that upregulated TYMSOS was associated with unfavorable prognosis and immune escape in breast cancer. TYMSOS promoted the malignant phenotypes of breast cancer cells, and reduced the cytotoxicity of NK92 cells on these cells. CBX3 was a downstream effector in TYMSOS-induced malignant phenotypes in breast cancer cells. Mechanistic studies showed that TYMSOS facilitated CBX3-mediated transcriptional repression of ULBP3, and it also promoted SYVN1-mediated ubiquitin-proteasomal degradation of ULBP3. TYMSOS promoted cell growth, metastasis, and immune escape via CBX3/ULBP3 or SYVN1/ULBP3 axis. The in vivo studies further showed that silencing of TYMSOS repressed tumor growth and boosted NK cell cytotoxicity. In sum, TYMSOS boosted breast cancer metastasis and immune escape via CBX3/ULBP3 or SYVN1/ULBP3 axis., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

The heavy metal zinc (Zn) is known to be transmitted in the food chain; however, the effect of Zn stress on beans and herbivorous insects is largely unclear. This study aimed to investigate the resistance of broad bean plants to Zn stress and the consequent changes in their physiological and biochemical metabolism by simulating heavy metal pollution in soil. Simultaneously, the effects of aphid progeny treated with different Zn concentrations on the expression of carbohydrate and related genes were analyzed. The results showed that Zn had no effect on the germination rate of broad beans, but other effects mainly manifested as follows. (1) Chlorophyll content decreased. (2) The total soluble sugar and Zn content in stems and leaves increased with increasing Zn content. (3) The proline content first increased and then decreased with increasing Zn content. (4) The height of the seedlings indicates that low concentrations promote growth and high concentrations inhibit growth. In addition, only the first-generation fecundity decreased significantly when aphids fed on heavy metal broad beans. Continuous high Zn levels increase the trehalose content of aphid F1 and F2, while F3 decreases. These results can not only provide a theoretical basis for exploring the impact of soil heavy metal pollution on ecosystems but also preliminarily evaluate the possibility of broad beans as a means of pollution remediation.

Background: Hyperlinear palms are described as a feature of loss-of-function (LoF) variants in filaggrin (FLG)., Objectives: To explore the phenotype of participants (age < 31 years) with atopic eczema of Bangladeshi ancestry from East London and investigate which factors best associate with LoF FLG variants., Methods: A cross-sectional study with participants recruited between May 2018 and December 2020. Patterns of palmar linearity were categorized and modelled with the Eczema Area and Severity Index (EASI), transepidermal water loss (TEWL), skin hydration (SH) and LoF FLG variants., Results: There were 506 complete cases available. Five palm patterns were noted. The 'prominent diamond' pattern associated best with EASI [marginal effects (ME) 2.53, 95% confidence interval (CI) 1.74-3.67], SH (ME 0.85, 95% CI 0.78-0.96) and TEWL (ME 1.32, 95% CI 1.11-1.62). Using five palm patterns had some ability to discriminate LoF FLG variants [area under the receiver operator characteristic (AUROC) 76.32%, 95% CI 71.91-80.73], improving to 77.99% (73.70-82.28) with the addition of SH. In subgroup analysis with only fine perpendicular/prominent diamond patterns the AUROC was 89.11% (95% CI 84.02-94.19)., Conclusions: This was a single-centre study design with humans classifying clinical patterns. The stability of temperature and humidity was not guaranteed across TEWL and SH measurements despite using a climate-controlled room. Palm patterns associate with EASI and TEWL. The fine perpendicular/prominent diamond patterns are markers to detect the absence/presence of LoF FLG variants, respectively., Competing Interests: Conflicts of interest E.A.O’T. has received research funding paid to the university from Kamari Pharma and Unilever, consulting fees paid to the university from Azitra Inc., Kamari Pharma, Palvella Therapeutics and Timber Pharma unrelated to this work. All other authors have no conflicts of interest to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Plantar Heel Pain (PHP) is a common disorder with many treatment pathways and is not self-limiting, hence prognostic information concerning recovery or recalcitrance is needed to guide practice. In this systematic review, we investigate which prognostic factors are associated with favourable or unfavourable PHP outcomes., Methods: MEDLINE, Web of Science, EMBASE, Scopus and PubMed electronic bibliographic databases were searched for studies evaluating baseline patient characteristics associated with outcomes in prospective longitudinal cohorts or after specific interventions. Cohort, clinical prediction rule derivation and single arms of randomised controlled trials were included. Risk of bias was evaluated with method-specific tools and evidence certainty with GRADE., Results: The review included five studies which evaluated 98 variables in 811 participants. Prognostic factors could be categorised as demographics, pain, physical and activity-related. Three factors including sex and bilateral symptoms (HR: 0.49[0.30-0.80], 0.33[0.15-0.72], respectively) were associated with a poor outcome in a single cohort study. The remaining four studies reported twenty factors associated with a favourable outcome following shockwave therapy, anti-pronation taping and orthoses. Heel spur (AUC = 0.88[0.82-0.93]), ankle plantar-flexor strength (Likelihood ratio (LR): 2.17[1.20-3.95]) and response to taping (LR = 2.17[1.19-3.90]) were the strongest factors predicting medium-term improvement. Overall, the study quality was low. A gap map analysis revealed an absence of research that included psychosocial factors., Conclusions: A limited number of biomedical factors predict favourable or unfavourable PHP outcomes. High quality, adequately powered, prospective studies are required to better understand PHP recovery and should evaluate the prognostic value of a wide range of variables, including psychosocial factors., (© 2023. Crown.)

Background: Survival after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) remains poor because of high incidences of recurrence. The risk factors, patterns, and long-term prognosis in patients with early recurrence and late recurrence (ER and LR) for PDAC after PD were studied., Methods: Data from patients who underwent PD for PDAC were analyzed. Recurrence was divided into ER (ER ≤1 years) and LR (LR >1 years) using the time to recurrence after surgery. Characteristics and patterns of initial recurrence, and postrecurrence survival (PRS) were compared between patients with ER and LR., Results: Among the 634 patients, 281 (44.3%) and 249 (39.3%) patients developed ER and LR, respectively. In the multivariate analysis, preoperative CA19-9 levels, resection margin status, and tumor differentiation were significantly associated with both ER and LR, while lymph node metastasis and perineal invasion were associated with LR. Patients with ER, when compared with patients with LR, showed a significantly higher proportion of liver-only recurrence ( P <0.05), and worse median PRS (5.2 vs. 9.3 months, P <0.001). Lung-only recurrence had a significantly longer PRS when compared with liver-only recurrence ( P <0.001). Multivariate analysis demonstrated that ER and irregular postoperative recurrence surveillance were independently associated with a worse prognosis ( P <0.001)., Conclusion: The risk factors for ER and LR after PD are different for PDAC patients. Patients who developed ER had worse PRS than those who developed LR. Patients with lung-only recurrence had a significantly better prognosis than those with other recurrent sites., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Robotic pancreaticoduodenectomy (RPD) has been reported to be safe and feasible for patients with pancreatic ductal adenocarcinoma (PDAC) of the pancreatic head. This study aimed to analyze the surgical outcomes and risk factors for poor long-term prognosis of these patients., Methods: Data from patients who underwent RPD for PDAC of pancreatic head were retrospectively analyzed. Multivariate Cox regression analysis was used to seek the independent prognostic factors for overall survival (OS), and an online nomogram calculator was developed based on the independent prognostic factors., Results: Of the 273 patients who met the inclusion criteria, the median operative time was 280.0 minutes, the estimated blood loss was 100.0 mL, the median OS was 23.6 months, and the median recurrence-free survival (RFS) was 14.4 months. Multivariate analysis showed that preoperative carbohydrate antigen 19-9 (CA19-9) [hazard ratio (HR) = 2.607, 95% confidence interval (CI): 1.560-4.354, P < 0.001], lymph node metastasis (HR = 1.429, 95% CI: 1.005-2.034, P = 0.047), tumor moderately (HR = 3.190, 95% CI: 1.813-5.614, P < 0.001) or poorly differentiated (HR = 5.114, 95% CI: 2.839-9.212, P < 0.001), and Clavien-Dindo grade ≥ III (HR = 1.657, 95% CI: 1.079-2.546, P = 0.021) were independent prognostic factors for OS. The concordance index (C-index) of the nomogram constructed based on the above four independent prognostic factors was 0.685 (95% CI: 0.640-0.729), which was significantly higher than that of the AJCC staging (8th edition): 0.541 (95% CI: 0.493-0.589) (P < 0.001)., Conclusions: This large-scale study indicated that RPD was feasible for PDAC of pancreatic head. Preoperative CA19-9, lymph node metastasis, tumor poorly differentiated, and Clavien-Dindo grade ≥ III were independent prognostic factors for OS. The online nomogram calculator could predict the OS of these patients in a simple and convenient manner., (Copyright © 2022. Published by Elsevier B.V.)

Machine learning (ML) models for skin cancer recognition may have variable performance across different skin phototypes and skin cancer types. Overall performance metrics alone are insufficient to detect poor subgroup performance. We aimed (1) to assess whether studies of ML models reported results separately for different skin phototypes and rarer skin cancers, and (2) to graphically represent the skin cancer training datasets used by current ML models. In this systematic review, we searched PubMed, Embase and CENTRAL. We included all studies in medical journals assessing an ML technique for skin cancer diagnosis that used clinical or dermoscopic images from 1 January 2012 to 22 September 2021. No language restrictions were applied. We considered rarer skin cancers to be skin cancers other than pigmented melanoma, basal cell carcinoma and squamous cell carcinoma. We identified 114 studies for inclusion. Rarer skin cancers were included by 8/114 studies (7.0%), and results for a rarer skin cancer were reported separately in 1/114 studies (0.9%). Performance was reported across all skin phototypes in 1/114 studies (0.9%), but performance was uncertain in skin phototypes I and VI from minimal representation of the skin phototypes in the test dataset (9/3756 and 1/3756, respectively). For training datasets, although public datasets were most frequently used, with the most widely used being the International Skin Imaging Collaboration (ISIC) archive (65/114 studies, 57.0%), the largest datasets were private. Our review identified that most ML models did not report performance separately for rarer skin cancers and different skin phototypes. A degree of variability in ML model performance across subgroups is expected, but the current lack of transparency is not justifiable and risks models being used inappropriately in populations in whom accuracy is low., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Management of gait-related problems in children and young people with Cerebral Palsy (CYPwCP) is complex and requires an interprofessional approach. Irrespective of underlying mechanisms, instrumented gait analysis (IGA) can provide quantification of gait to support clinical decision-making for CYPwCP when planning treatment interventions., Aim: This scoping review aimed to determine the impact of instrumented gait analysis (IGA) on treatment decision-making for CYPwCP, paying particular attention to interprofessional decision-making., Method: PubMed, EMBASE, Web of Science and Scopus databases were searched from inception to October 2019 for studies including CYPwCP age<25 years. The PRISMA ScR protocol was followed, and Quality was assessed with the Downs and Black (D&B) scale. Influences on decision-making were coded according to the International Classification of Functioning, Disability and Health for Children and Youth framework (ICF-CY)., Results: Seventeen studies (1144 patients, 2.8-23 years) of varying quality (mean D&B = 17.2, range = 11-26) were included. Studies considered IGA influence at three decision-making stages 'Clinical Planning', 'Treatment Performed' and 'Follow up'. Child and Family, and Clinician and Service-centred factors had a high impact on engagement with IGA recommendations., Interpretation: IGA guided recommendations can differ from initial clinical plans, and often lead to modification of the treatment ultimately performed. The effect on individual patients' outcomes when treatment recommendations based on instrumented gait analysis are followed is not yet clear and warrants further research. The differences in clinicians' engagement with IGA recommendations occur due to an array of Child and Family, and Clinician and Service-centred factors. Overall, IGA leads to less surgical recommendations, and has the potential to influence conservative gait-related management in CYPwCP., Competing Interests: Declaration of competing interest None of the authors have any personal or financial relationships with other people or organisations that could inappropriately influence this work., (© 2022 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Cysteine-rich receptor-like kinases (CRKs) are transmembrane proteins that bind to the calcium ion to regulate stress-signaling and plant development-related pathways, as indicated by several pieces of evidence. However, the CRK gene family hasn’t been inadequately examined in Brassica napus. In our study, 27 members of the CRK gene family were identified in Brassica napus, which are categorized into three phylogenetic groups and display synteny relationship to the Arabidopsis thaliana orthologs. All the CRK genes contain highly conserved N-terminal PKINASE domain; however, the distribution of motifs and gene structure were variable conserved. The functional divergence analysis between BnaCRK groups indicates a shift in evolutionary rate after duplication events, demonstrating that BnaCRKs might direct a specific function. RNA-Seq datasets and quantitative real-time PCR (qRT-PCR) exhibit the complex expression profile of the BnaCRKs in plant tissues under multiple stresses. Nevertheless, BnaA06CRK6-1 and BnaA08CRK8 from group B were perceived to play a predominant role in the Brassica napus stress signaling pathway in response to drought, salinity, and Sclerotinia sclerotiorum infection. Insights gained from this study improve our knowledge about the Brassica napus CRK gene family and provide a basis for enhancing the quality of rapeseed.

Plant-pathogen interactions induce a signal transmission series that stimulates the plant's host defense system against pathogens and this, in turn, leads to disease resistance responses. Plant innate immunity mainly includes two lines of the defense system, called pathogen-associated molecular pattern-triggered immunity (PTI) and effector-triggered immunity (ETI). There is extensive signal exchange and recognition in the process of triggering the plant immune signaling network. Plant messenger signaling molecules, such as calcium ions, reactive oxygen species, and nitric oxide, and plant hormone signaling molecules, such as salicylic acid, jasmonic acid, and ethylene, play key roles in inducing plant defense responses. In addition, heterotrimeric G proteins, the mitogen-activated protein kinase cascade, and non-coding RNAs (ncRNAs) play important roles in regulating disease resistance and the defense signal transduction network. This paper summarizes the status and progress in plant disease resistance and disease resistance signal transduction pathway research in recent years; discusses the complexities of, and interactions among, defense signal pathways; and forecasts future research prospects to provide new ideas for the prevention and control of plant diseases.

Melanoma can frequently metastasize to the brain with severe consequences. However, variation of melanoma brain metastases (MBM) development among populations is not well studied, and underlying mechanisms and risk factors for MBM development are not consistently documented. We conducted a systematic literature review (SLR) including a total of 39 articles to evaluate the proportion of melanoma patients who are diagnosed with, or develop, brain metastases, and summarize the risk factors of MBM. The average proportion of MBM was calculated and weighted by the sample size of each study. Meta-analyses were conducted for the selected risk factors using a random-effects model. The proportion of MBM at diagnosis was 33% (975 with MBM out of 2948 patients) among patients with cutaneous melanoma (excluding acral) and 23% (651/2875) among patients with cutaneous mixed with other types of melanoma. The proportion at diagnosis was lower among populations with mucosal (9/96, 9%) or uveal (4/184, 2%) melanoma and among populations outside the United States and Europe. Meta-analysis demonstrated that male vs. female gender and left-sided tumors vs. right-sided were significantly associated with increased risk of melanoma brain metastases. These data may help clinicians to assess an individual patient's risk of developing melanoma brain metastases.

Background: Distal cholangiocarcinoma (DCC) is a malignancy associated with a short survival time. In this study, we aimed to create an online nomogram calculator to predict early recurrence and long-term survival in patients with DCC after pancreaticoduodenectomy., Methods: A total of 486 patients with DCC were included. An online nomogram calculator was developed and validated in training, internal validation and external validation cohorts, respectively., Results: Of the 486 patients who met the inclusion criteria, we allocated 240, 120, and 126 patients to the training, internal validation, and external validation cohorts, respectively. Multivariable analysis showed that preoperative CA19-9, maximum tumor diameter, perineural invasion, and tumor differentiation were significant risk factors for early recurrence in patients with DCC. Incorporating these four factors, the nomogram achieved good AUC values of 0.788, 0.771, and 0.723 for predicting early recurrence in the training, internal validation, and external validation cohorts, respectively. Notably, this nomogram also had good power to predict overall survival. The discrimination ability of the nomogram was evaluated by dividing the predicted probabilities of early recurrence and survival into two risk groups in the training cohort (low risk ≤ 132; high risk > 132; P < .001). Time-dependent ROC and decision curve analysis further revealed that the nomogram provided higher diagnostic capacity and superior net benefit compared to other staging systems., Conclusion: This study developed and validated a web-based nomogram calculator that was capable of predicting early recurrence and long-term prognosis in patients with DCC after pancreaticoduodenectomy with high degrees of stability and accuracy., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Competing Interests: Conflicts of interest Professor O’Toole has received funding for the university from Palvella Therapeutics (consultancy), Timber Pharma (consultancy), and Kamari Pharma (research grant and consultancy). Dr Hansen has received support from Palvella as a principal investigator for a clinical study in pachyonychia. Drs Tan, Steele and Thomas and Ms Schwartz have no conflicts of interest to declare.

Background: Pancreatoduodenectomy is the only potentially curative treatment for distal cholangiocarcinoma (DCC). In this study, we sought to compare the perioperative and oncological outcomes of robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD) based on a multicenter propensity score-matched study., Methods: Consecutive patients with DCC who underwent RPD or OPD from five centers in China between January 2014 and June 2019 were included. A 1:1 propensity score matching (PSM) was performed. Univariable and multivariable Cox regression analyses were used to identify independent prognosis factors for overall survival (OS) and recurrence-free survival (RFS) of these patients., Results: A total of 217 patients and 228 patients underwent RPD and OPD, respectively. After PSM, 180 patients in each group were enrolled. There were no significant differences in operative time, lymph node harvest, intraoperative transfusion, vascular resection, R0 resection, postoperative major morbidity, reoperation, 90-day mortality, and long-term survival between the two groups before and after PSM. Whereas, compared with the OPD group, the RPD group had significantly lower estimated blood loss (150.0 ml vs. 250.0 ml; P < 0.001), and a shorter postoperative length of stay (LOS) (12.0 days vs. 15.0 days; P < 0.001). Multivariable analysis showed carbohydrate antigen 19-9 (CA19-9), R0 resection, N stage, perineural invasion, and tumor differentiation significantly associated with OS and RFS of these patients., Conclusions: RPD was comparable to OPD in feasibility and safety. For patients with DCC, RPD resulted in similar oncologic and survival outcomes as OPD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)