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Background: Tuberculous peritonitis (TBP) is a chronic, diffuse inflammation of the peritoneum caused by Mycobacterium tuberculosis . The route of infection can be by direct spread of intraperitoneal tuberculosis (TB) or by hematogenous dissemination. The former is more common, such as intestinal TB, mesenteric lymphatic TB, fallopian tube TB, etc. , and can be the direct primary lesion of the disease., Case Summary: We present an older male patient with TBP complicated by an abdominal mass. The patient's preoperative symptoms, signs and imaging data suggested a possible abdominal tumor. After surgical treatment, the patient's primary diagnosis of TBP complicating an intraperitoneal tuberculous abscess was established by combining past medical history, postoperative pathology, and positive results of TB-related laboratory tests. The patient's symptoms were significantly reduced after surgical treatment, and he was discharged from the hospital with instructions to continue treatment at a TB specialist hospital and to undergo anti-TB treatment if necessary., Conclusion: This case report analyses the management of TBP complicated by intraperitoneal tuberculous abscess and highlights the importance of early definitive diagnosis in the hope of improving the clinical management of this type of disease., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The heightened risk of cardiovascular and cerebrovascular events is associated with the increased instability of atherosclerotic plaques. However, the lack of effective diagnostic biomarkers has impeded the assessment of plaque instability currently. This study was aimed to investigate and identify hub genes associated with unstable plaques through the integration of various bioinformatics tools, providing novel insights into the detection and treatment of this condition., Methods: Weighted Gene Co-expression Network Analysis (WGCNA) combined with two machine learning methods were used to identify hub genes strongly associated with plaque instability. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method was utilized to assess immune cell infiltration patterns in atherosclerosis patients. Additionally, Gene Set Variation Analysis (GSVA) was conducted to investigate the potential biological functions, pathways, and mechanisms of hub genes associated with unstable plaques. To further validate the diagnostic efficiency and expression of the hub genes, immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were performed on collected human carotid plaque and blood samples. Immunofluorescence co-staining was also utilized to confirm the association between hub genes and immune cells, as well as their colocalization with mitochondria., Results: The CIBERSORT analysis demonstrated a significant decrease in the infiltration of CD8 T cells and an obvious increase in the infiltration of M0 macrophages in patients with atherosclerosis. Subsequently, two highly relevant modules (blue and green) strongly associated with atherosclerotic plaque instability were identified. Through intersection with mitochondria-related genes, 50 crucial genes were identified. Further analysis employing least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms revealed six hub genes significantly associated with plaque instability. Among them, NT5DC3, ACADL, SLC25A4, ALDH1B1, and MAOB exhibited positive correlations with CD8 T cells and negative correlations with M0 macrophages, while kynurenine 3-monooxygenas (KMO) demonstrated a positive correlation with M0 macrophages and a negative correlation with CD8 T cells. IHC and RT-qPCR analyses of human carotid plaque samples, as well as ELISA analyses of blood samples, revealed significant upregulation of KMO and MAOB expression, along with decreased ALDH1B1 expression, in both stable and unstable samples compared to the control samples. However, among the three key genes mentioned above, only KMO showed a significant increase in expression in unstable plaque samples compared to stable plaque samples. Furthermore, the expression patterns of KMO in human carotid unstable plaque tissues and cultured mouse macrophage cell lines were assessed using immunofluorescence co-staining techniques. Finally, lentivirus-mediated KMO silencing was successfully transduced into the aortas of high-fat-fed ApoE-/- mice, with results indicating that KMO silencing attenuated plaque formation and promoted plaque stability in ApoE-/- mice., Conclusions: The results suggest that KMO, a mitochondria-targeted gene associated with macrophage cells, holds promise as a valuable diagnostic biomarker for assessing the instability of atherosclerotic plaques., (© 2024. The Author(s).)

The 5th edition of the World Health Organization (WHO) classification of haematolymphoid tumours used the hierarchical system to classify T-cell and NK-cell lymphoid proliferations and lymphomas (T/NK-LPD/LYM) based on research advances and clinicopathological characteristics of the diseases. In this edition of classification, tumour-like lesions were included, some tumors were added/deleted, the names or terms of certain diseases were refined, and the diagnostic criteria or subtypes of some diseases were revised. This group of diseases was reintegrated from non-clonal hyperplasia to highly aggressive lymphoma, which would further reflect the nature of T/NK-LPD/LYM and benefit to clinical application.

Erdheim-Chester disease (ECD) is a rare histiocytosis characterized by the foamy CD68+CD1a- histiocytes infiltrating multiple organs and tissues. ECD might be asymptomatic or present with variable manifestations. The diagnosis of ECD requires characteristic radiological findings and pathological features. Herein, we described a 52-year-old female patient who was admitted to our hospital for recurrent pericardial effusion for two months. She has a medical history of papillary thyroid carcinoma (PTC) and underwent a total thyroidectomy two years before admission. The radiological findings suggested a potential diagnosis of ECD. Cytological analysis of the effusion cytology specimen revealed CD68+CD1a - histiocytes, confirming the ECD diagnosis. The BRAF V600E mutation was identified in the histiocytes, prompting the administration of vemurafenib, a BRAF inhibitor. After two months of standard-dose vemurafenib treatment, the disease was well controlled with pericardial effusion regression., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Constitutive activation of Hedgehog (Hh) signaling has been implicated in many cancers including hepatocellular carcinoma (HCC). Among them, the terminal glioma-associated oncogene homolog 1 (Gli1) regulates the expression of critical genes in the Hh pathway. The current study aims to evaluate the anti-HCC effect of the Gli1 inhibitor, GANT61. In vitro analysis including cell counting kit-8 (CCK-8) assay, flow cytometry, and migration and invasion assay were adopted to evaluate the effect of GANT61 on HCC cell lines. In vivo, xenograft studies were also performed to verify the effect of GANT61 on HCC. By CCK-8 assay, we found that GANT61 could significantly reduce the growth of HCC cell lines Huh7 and hemophagocytic lymphohistiocytosis (HLE), and their IC 50 concentrations were 4.481 and 6.734 μM, respectively. Flow cytometry shows that GANT61 induced cell cycle arrest in the G2/M phase and accelerated apoptosis of both HLE and Huh7 cells. While migration and invasion assay shows that GANT61 weakens cells' migration and invasion ability. Besides that, GANT61 inhibits the expression of Gli1, FoxM1, CyclinD1, and Bcl-2, upregulates the level of Bax protein, and also reverses the epithelial-mesenchymal transition program by downregulating the expression of Vimentin and N-Cadherin and upregulating the expression of epithelial E-Cadherin expression. Furthermore, GANT61 inhibits the growth of subcutaneous xenografts of Huh7 cells in nude mice. Overall, this study suggests that Gli1 is a potential target for therapy and GANT61 shows promising therapeutic potential for future treatment in HCC., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Low-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type has a favorable outcome with radiation therapy alone, and the addition of chemotherapy shows no survival benefit. Nonetheless, a proportion of patients will relapse or progress, with a dismal outcome, highlighting the need for a novel therapeutic strategy. Promising preliminary findings indicate the efficacy of PD-1/PD-L1 inhibitors in extranodal natural killer/T-cell lymphoma, nasal type, with good toxicity profiles. Here we describe the design of a phase II study (CLCG-NKT-2101), which is evaluating the safety and efficacy of adding anti-PD-1 antibody to the current radiation therapy regimen in low-risk early-stage extranodal natural killer/T-cell lymphoma, nasal type patients. Tislelizumab will be added in an inductive and concurrent way to radiation therapy. The primary end point will be the complete response rate after induction immunotherapy. Clinical trial registration: ClinicalTrials.gov (NCT05149170).

Background: Epigenetic alteration plays an essential role in the occurrence and development of extranodal natural killer/T cell lymphoma (ENKTL). Histone methyltransferase (HMT) KMT2D is an epigenetic regulator that plays different roles in different tumors, but its role and mechanism in ENKTL are still unclear., Methods: We performed immunohistochemical staining of 112 ENKTL formalin-fixed paraffin-embedded (FFPE) samples. Then, we constructed KMT2D knockdown cell lines and conducted research on cell biological behavior. Finally, to further investigate KMT2D-mediated downstream genes, ChIP-seq and ChIP -qPCR was performed., Results: The low expression of KMT2D was related to a decreased abundance in histone H3 lysine 4 mono- and trimethylation (H3K4me1/3). In KMT2D knockdown YT and NK-YS cells, cell proliferation was faster (P < 0.05), apoptosis was decreased (P < 0.05), the abundance of S phase cells was increased (P < 0.05), and the level of H3K4me1 was decreased. Notably, ChIP-seq revealed two crucial genes and pathways downregulated by KMT2D., Conclusions: KMT2D is a tumor suppressor gene that mediates H3K4me1 and influences ENKTL proliferation and apoptosis by regulating the cell cycle. Moreover, in ENKTL, serum- and glucocorticoid-inducible kinase-1 (SGK1) and suppressor of cytokine signaling-1 (SOCS1) are downstream genes of KMT2D., (© 2023. The Author(s) under exclusive licence to The Genetics Society of Korea.)

The present study aimed to investigate the clinical features, prognosis, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma (ENKTCL). This real-world study retrospectively reviewed 56 newly diagnosed advanced-stage non-nasal type ENKTCL patients from two large-scale Chinese cancer centers in the last 10-15 years and screened 139 newly diagnosed advanced-stage nasal type ENKTCLs admitted during the same period for comparison. The non-nasal type ENKTCLs exhibited significantly higher Ki-67 expression levels compared to nasal type disease (P = 0.011). With a median follow-up duration of 75.03 months, the non-nasal group showed slightly inferior survival outcomes without statistically significant differences compared to the nasal group (median overall survival (OS): 14.57 vs. 21.53 months, 5-year OS: 28.0% vs. 38.5%, P = 0.120). Eastern Cooperative Oncology Group (ECOG) score ≥ 2 (hazard ratio (HR) = 2.18, P = 0.039) and lactic dehydrogenase (LDH) elevation (HR = 2.44, P = 0.012) were significantly correlated with worse OS in the non-nasal group. First-line gemcitabine-based chemotherapy regimens showed a trend toward slightly improved efficacy and survival outcomes compared to non-gemcitabine-based ones in the present cohort of non-nasal ENKTCLs (objective response rate: 91.7% vs. 63.6%, P = 0.144; complete response rate: 50.0% vs. 33.3%, P = 0.502; median progression-free survival: 10.43 vs. 3.40 months, P = 0.106; median OS: 25.13 vs. 9.30 months, P = 0.125), which requires further validation in larger sample size studies. Advanced-stage non-nasal type patients could achieve comparable prognosis with nasal cases after rational therapy. The modified nomogram-revised index (including age, ECOG score, and LDH) and modified international prognostic index (including age, ECOG score, LDH, and number of extranodal involvement) functioned effectively for prognostic stratification in non-nasal type ENKTCLs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Astaxanthin is widely used in food, aquaculture, cosmetics, and pharmaceuticals due to its strong antioxidant activity and coloring ability, but its production from Phaffia rhodozyma remains the main challenge due to the high fermentation cost and low content of carotenoid. In this study, the production of carotenoids from food waste (FW) by a P. rhodozyma mutant was investigated. P. rhodozyma mutant screened by UV mutagenesis and flow cytometry could stably produce high carotenoids at 25°C, with carotenoid production (32.9 mg/L) and content (6.7 mg/g), respectively, increasing by 31.6% and 32.3% compared with 25 mg/L and 5.1 mg/g of wild strain. Interestingly, the carotenoid production reached 192.6 mg/L by feeding wet FW, which was 21% higher than batch culture. The 373 g vacuum freeze-dried products were obtained from the fermentation of 1 kg FW by P. rhodozyma, which contained 784 mg carotenoids and 111 mg astaxanthin. The protein, total amino acids, and essential amino acids content of the fermentation products were 36.6%, 40.5%, and 18.2% (w/w), respectively, and lysine-added fermentation products had the potential of high-quality protein feed source. This study provides insights for the high-throughput screening of mutants, astaxanthin production, and the development of the feed potential of FW., (© 2023 International Union of Biochemistry and Molecular Biology, Inc.)

The study investigated the treatment and prognosis of advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL). With a median follow-up of 75.03 months, the median overall survival (mOS) for the 195 newly diagnosed stage III/IV ENKTL patients was 19.43 months, and estimated 1-, 2-, 3- and 5-year OS were 59.5%, 46.3%, 41.8% and 35.1%, respectively. Chemotherapy (CT) + radiotherapy (RT) compared to CT alone (P = .007), and hematopoietic stem cell transplantation (HSCT) compared to non-HSCT (P < .001), both improved OS. For patients ≤60 years and ineligible for HSCT, other therapies with complete remission led to comparable OS (P = .141). Nine patients ever treated with chidamide achieved a median progression-free survival (mPFS) and mOS of 53.63 (range, 3.47-92.33) and 54.80 (range, 5.50-95.70) months, and four with chidamide maintenance therapy (MT) achieved a mPFS and mOS of 55.83 (range, 53.27-92.33) and 60.65 (range, 53.70-95.70) months, possibly providing an alternative option for non-HSCT patients. Non-anthracycline (ANT)- compared to ANT-, asparaginase (Aspa)- compared to non-Aspa- and gemcitabine (Gem)- compared to non-Gem-based regimens, prolonged PFS (P = .031; P = .005; P = .009) and OS (P = .010; P = .086; P = .003), respectively. Multivariate analysis demonstrated that Gem-based regimens improved PFS (HR = 0.691, P = .061) and OS (HR = 0.624, P = .037). Gem + Aspa combinations slightly improved PFS and OS compared to regimens containing Gem or Aspa alone (P > 0.05). First-line "intensive therapy," including CT (particularly Gem + Aspa regimens), RT, HSCT and alternative chidamide MT, was proposed and could improve long-term survival for advanced-stage ENKTLs. Ongoing prospective clinical studies may shed further light on the value of chidamide MT., (© 2023 UICC.)

Retinal ischemia followed by reperfusion (IR) is a common cause of many ocular disorders, such as age-related macular degeneration (AMD), which leads to blindness in the elderly population, and proper therapies remain unavailable. Retinal pigment epithelial (RPE) cell death is a hallmark of AMD. Hyperbaric oxygen (HBO) therapy can improve IR tissue survival by inducing ischemic preconditioning responses. We conducted an in vitro study to examine the effects of HBO preconditioning on oxygen-glucose deprivation (OGD)-induced IR-injured RPE cells. RPE cells were treated with HBO (100% O 2 at 3 atmospheres absolute for 90 min) once a day for three consecutive days before retinal IR onset. Compared with normal cells, the IR-injured RPE cells had lower cell viability, lower peroxisome proliferator activator receptor-alpha (PPAR-α) expression, more severe oxidation status, higher blood-retinal barrier disruption and more elevated apoptosis and autophagy rates. HBO preconditioning increased PPAR-α expression, improved cell viability, decreased oxidative stress, blood-retinal barrier disruption and cellular apoptosis and autophagy. A specific PPAR-α antagonist, GW6471, antagonized all the protective effects of HBO preconditioning in IR-injured RPE cells. Combining these observations, HBO therapy can reverse OGD-induced RPE cell injury by activating PPAR-α signalling., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

In recent intelligent-robot-assisted surgery studies, an urgent issue is how to detect the motion of instruments and soft tissue accurately from intra-operative images. Although optical flow technology from computer vision is a powerful solution to the motion-tracking problem, it has difficulty obtaining the pixel-wise optical flow ground truth of real surgery videos for supervised learning. Thus, unsupervised learning methods are critical. However, current unsupervised methods face the challenge of heavy occlusion in the surgical scene. This paper proposes a novel unsupervised learning framework to estimate the motion from surgical images under occlusion. The framework consists of a Motion Decoupling Network to estimate the tissue and the instrument motion with different constraints. Notably, the network integrates a segmentation subnet that estimates the segmentation map of instruments in an unsupervised manner to obtain the occlusion region and improve the dual motion estimation. Additionally, a hybrid self-supervised strategy with occlusion completion is introduced to recover realistic vision clues. Extensive experiments on two surgical datasets show that the proposed method achieves accurate motion estimation for intra-operative scenes and outperforms other unsupervised methods, with a margin of 15% in accuracy. The average estimation error for tissue is less than 2.2 pixels on average for both surgical datasets.

Extranodal natural killer/T-cell lymphoma (ENKTL) with hepatosplenic involvement is rare, accounting for approximately 0.2% of ENKTL cases. The clinicopathologic features of ENKTL with hepatosplenic involvement are still poorly understood. Seven cases of ENKTL with hepatosplenic involvement were investigated retrospectively by clinical features, pathology, immunophenotype, genotype, Epstein-Barr virus (EBV) status, and survival analysis. The median age was 36 years; three patients (3/7) had a history of primary nasal ENKTL. Six cases (6/7) presented liver or spleen structures that were replaced by neoplasms, and the neoplastic cells displayed diffuse infiltration; one case (1/7) displayed neoplastic cells scattered in hepatic sinuses and portal areas. The cellular morphology and immunohistochemical features were similar to those of ENKTL involving other sites. Follow-up data were available in five of the seven patients. All five patients received first-line chemotherapy based on L-asparaginase. Three patients died, and two were still alive by the last follow-up. The median overall survival (OS) was 21 months. ENKTL with hepatosplenic involvement is rare, regardless of whether it is initial or secondary. There are two histopathologic patterns of ENKTL with hepatosplenic involvement, and L-asparaginase-based chemotherapy combined with AHSCT might yield good efficacy. Morphological features of ENKTL in the spleen and liver A The architecture of the spleen was affected, and dense infiltration of the neoplastic cells was observed in the left part; B Focal infiltration of the neoplastic cells was located in the red pulp; C Dense infiltration of the neoplastic cells in the liver, accompanied by fatty change of hepatocytes and congestion; D More neoplastic cells accumulated in sinusoidal region., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Limited research exists on factors influencing the place of death (POD) or hospital deaths among lymphoma patients in China, despite the country's significant burden of lymphoid neoplasms. This study aimed to describe the distribution of POD among lymphoma patients and identify the factors associated with hospital lymphoma deaths to provide evidence for developing targeted healthcare policies. Data in this study were obtained from the National Mortality Surveillance System (NMSS). The distribution of POD among individuals who died from lymphoma was analyzed, and factors influencing the choice of dying in the hospital were examined. Chi-square test was employed to analyze the differences in characteristic distributions. Multilevel logistic regression analysis was identify the relationship between hospital deaths due to lymphoma and individual factors, as well as socioeconomic contextual variables. During 2013-2021, there were 66772 lymphoma deaths reported by the NMSS, including 44327 patients (66.39%) who died at home and 21211 (31.77%) died in the hospital. Female patients, those had a higher level of educational attainment, retired individuals, those died of non-Hodgkin lymphoma, residents of urban areas, patients between the ages of 0 and 14, and unmarried individuals had a higher probability of dying in hospitals. Improving health care providers' understanding of palliative care for cancer patients and prioritizing accessible services are essential to enhance the quality of end-of-life care. These approaches ensure the equitable allocation of healthcare resources and provide diverse options for minorities with specific preferences regarding end-of-life care., Competing Interests: None., (AJCR Copyright © 2023.)

Background: Genome-wide association studies (GWAS) have reported single-nucleotide polymorphisms (SNPs) in the VRK serine/threonine kinase 2 gene (VRK2) showing genome-wide significant associations with major depression, but the regulation effect of the risk SNPs on VRK2 as well as their roles in the illness are yet to be elucidated., Methods: Based on the summary statistics of major depression GWAS, we conducted population genetic analyses, epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to identify the functional SNPs regulating VRK2; we also carried out behavioral assessments, dendritic spine morphological analyses, and phosphorylated 4D-label-free quantitative proteomics analyses in mice with Vrk2 repression., Results: We identified a SNP rs2678907 located in the 5' upstream of VRK2 gene exhibiting large spatial overlap with enhancer regulatory marks in human neural cells and brain tissues. Using luciferase reporter gene assays and eQTL analyses, the depression risk allele of rs2678907 decreased enhancer activities and predicted lower VRK2 mRNA expression, which is consistent with the observations of reduced VRK2 level in the patients with major depression compared with controls. Notably, Vrk2 -/- mice exhibited depressive-like behaviors compared to Vrk2 +/+ mice and specifically repressing Vrk2 in the ventral hippocampus using adeno-associated virus (AAV) lead to consistent and even stronger depressive-like behaviors in mice. Compared with Vrk2 +/+ mice, the density of mushroom and thin spines in the ventral hippocampus was significantly altered in Vrk2 -/- mice, which is in line with the phosphoproteomic analyses showing dysregulated synapse-associated proteins and pathways in Vrk2 -/- mice., Conclusions: Vrk2 deficiency mice showed behavioral abnormalities that mimic human depressive phenotypes, which may serve as a useful murine model for studying the pathophysiology of depression., (© 2023. The Author(s).)

Objective: To analyze the clinicopathological features, molecular changes and prognostic factors in angioimmunoblastic T-cell lymphoma (AITL)., Methods: Sixty-one cases AITL diagnosed by Department of Pathology of Peking University Cancer Hospital were collected with their clinical data. Morphologically, they were classified as typeⅠ[lymphoid tissue reactive hyperplasia (LRH) like]; typeⅡ[marginal zone lymphoma(MZL)like] and type Ⅲ [peripheral T-cell lymphoma, not specified (PTCL-NOS) like]. Immunohistochemical staining was used to evaluate the presence of follicular helper T-cell (TFH) phenotype, proliferation of extra germinal center (GC) follicular dendritic cells (FDCs), presence of Hodgkin and Reed-Sternberg (HRS)-like cells and large B transformation. The density of Epstein-Barr virus (EBV) + cells was counted with slides stained by Epstein-Barr virus encoded RNA (EBER) in situ hybridization on high power field (HPF). T-cell receptor / immunoglobulin gene (TCR/IG) clonality and targeted exome sequencing (TES) test were performed when necessary. SPSS 22.0 software was used for statistical analysis., Results: Morphological subtype (%): 11.4% (7/61) cases were classified as type Ⅰ; 50.8% (31/61) as type Ⅱ; 37.8% (23/61) as type Ⅲ. 83.6% (51/61) cases showed classical TFH immunophenotype. With variable extra-GC FDC meshwork proliferation (median 20.0%); 23.0% (14/61) had HRS-like cells; 11.5% (7/61) with large B transformation. 42.6% (26/61) of cases with high counts of EBV. 57.9% (11/19) TCR + /IG - , 26.3% (5/19) TCR + /IG + , 10.5% (2/19) were TCR － /IG － , and 5.3% (1/19) TCR － /IG + . Mutation frequencies by TES were 66.7% (20/30) for RHOA , 23.3% (7/30) for IDH2 mutation, 80.0% (24/30) for TET2 mutation, and 33.3% (10/30) DNMT3A mutation. Integrated analysis divided into four groups: (1) IDH2 and RHOA co-mutation group (7 cases): 6 cases were type Ⅱ, 1 case was type Ⅲ; all with typical TFH phenotype; HRS-like cells and large B transformation were not found; (2) RHOA single mutation group (13 cases): 1 case was type Ⅰ, 6 cases were type Ⅱ, 6 cases were type Ⅲ; 5 cases without typical TFH phenotype; 6 cases had HRS-like cells, and 2 cases with large B transformation. Atypically, 1 case showed TCR － /IG － , 1 case with TCR － /IG + , and 1 case with TCR + /IG + ; (3) TET2 and/or DNMT3A mutation alone group (7 cases): 3 cases were type Ⅱ, 4 cases were type Ⅲ, all cases were found with typical TFH phenotype; 2 cases had HRS-like cells, 2 cases with large B transformation, and atypically; (4) non-mutation group (3 cases), all were type Ⅱ, with typical TFH phenotype, with significant extra-GC FDC proliferation, without HRS-like cells and large B transformation. Atypically, 1 case was TCR － /IG － . Univariate analysis confirmed that higher density of EBV positive cell was independent adverse prognostic factors for both overall survival (OS) and progression free survival(PFS), ( P =0.017 and P =0.046)., Conclusion: Pathological diagnoses of ALTL cases with HRS-like cells, large B transformation or type Ⅰ are difficult. Although TCR/IG gene rearrangement test is helpful but still with limitation. TES involving RHOA , IDH2 , TET2 , DNMT 3 A can robustly assist in the differential diagnosis of those difficult cases. Higher density of EBV positive cells counts in tumor tissue might be an indicator for poor survival.

Background: The gastrointestinal (GI) tract is the second most frequent extranasal involvement site for ENKTL. This study aimed to explore the clinicopathological features, treatment models, survival outcomes, and prognosis of gastrointestinal ENKTL (GI-ENKTL)., Methods: The clinical data of GI-ENKTL patients were extracted from the China Lymphoma Collaborative Group (CLCG) database and were analyzed retrospectively., Results: A total of 30 patients were enrolled, with a male/female ratio of 4:1 and a median age of 42 years. Twenty-nine patients received chemotherapy, of whom 15 patients received asparaginase-based (ASP-based) regimens. Moreover, seven received surgery and three received radiotherapy. The overall response an d complete remission rates were 50.0% and 30.0% for the whole cohort, 50.0% and 37.5% for patients treated with ASP-based regimens, and 50.0% and 25.0% for those treated with non-ASP-based regimens, respectively. The median follow-up was 12.9 months and the 1-year overall survival rate was 40.0% for the whole cohort. For those patients in an early stage, ASP-based regimens resulted in a superior 1-year progression-free survival rate compared to non-ASP-based regimens (100.0% vs. 36.0%, p = .07). However, ASP-based regimens did not improve survival in patients at an advanced stage., Conclusion: GI-ENKTL still has a poor prognosis, even in the era of modern asparaginase-based treatment strategies., (© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Background: Anaplastic lymphoma kinase (ALK)-positive histiocytosis, a novel rare histiocytic proliferation, was first described in 2008; it occurs in early infancy with liver and hematopoietic involvement. The spectrum was subsequently broadened to include localized diseases in older children and young adults. However, its full clinicopathological features and molecular lineage have not been fully elucidated., Results: Here, we report four cases of multisystem ALK-positive histiocytosis without hematopoietic involvement. Clinically, three patients were adults aged between 32 and 51 years. Two patients', whose main manifestations were intracranial mass and numerous micronodules in the thoracoabdominal cavity organs and skin papules respectively, had a partial response to ALK inhibitors after surgery. One patient presented with mediastinal neoplasm without surgical treatment, and progressive disease occurred after two years of ALK inhibitor therapy. The fourth patient was a 17-month-old male with a large intracranial mass and presented with a poor response to ALK inhibitor and chemoradiotherapy; he died eight months after surgery. Pathologically, the histiocytes were large, with abundant eosinophilic cytoplasm, and mixed with variable numbers of foamy cells and Touton giant cells. Interstitial fibrosis was also observed. Histiocytes were positive for macrophage markers (CD68 and CD163) and ALK. KIF5B-ALK fusions were detected in two cases, EML4-ALK in one, and both DCTN1-ALK and VRK2-ALK fusions were detected in one case., Conclusions: We observed that ALK inhibitors present robust and durable responses in adult patients but a poor response in young children with central nervous system involvement. There is no consensus on the optimal treatment regimen and long-term prognosis requires further observation. Moreover, every unusual histiocytic proliferative lesion, especially unresectable and multisystem involvement, should be routinely tested for ALK immunohistochemical staining to identify this rare disease., (© 2023. The Author(s).)

The ^{18}O(α,γ)^{22}Ne reaction is critical for AGB star nucleosynthesis due to its connection to the abundances of several key isotopes, such as ^{21}Ne and ^{22}Ne. However, the ambiguous resonance energy and spin-parity of the dominant 470 keV resonance leads to substantial uncertainty in the ^{18}O(α,γ)^{22}Ne reaction rate for the temperature of interest. We have measured the resonance energies and strengths of the low-energy resonances in ^{18}O(α,γ)^{22}Ne at the Jinping Underground Nuclear Astrophysics experimental facility (JUNA) with improved precision. The key 470 keV resonance energy has been measured to be E&#95;{α}=474.0±1.1  keV, with such high precision achieved for the first time. The spin-parity of this resonance state is determined to be 1^{-}, removing discrepancies in the resonance strengths in earlier studies. The results significantly improve the precision of the ^{18}O(α,γ)^{22}Ne reaction rates by up to about 10 times compared with the previous data at typical AGB temperatures of 0.1-0.3 GK. We demonstrate that such improvement leads to precise ^{21}Ne abundance predictions, with an impact on probing the origin of meteoritic stardust SiC grains from AGB stars.

Surgical scene segmentation provides critical information for guidance in micro-neurosurgery. Segmentation of instruments and critical tissues contributes further to robot assisted surgery and surgical evaluation. However, due to the lack of relevant scene segmentation dataset, scale variation and local similarity, micro-neurosurgical segmentation faces many challenges. To address these issues, a high correlative non-local network (HCNNet), is proposed to aggregate multi-scale feature by optimized non-local mechanism. HCNNet adopts two-branch design to generate features of different scale efficiently, while the two branches share common weights in shallow layers. Several short-term dense concatenate (STDC) modules are combined as the backbone to capture both semantic and spatial information. Besides, a high correlative non-local module (HCNM) is designed to guide the upsampling process of the high-level feature by modeling global context generated from the low-level feature. It filters out confused pixels of different classes in the non-local correlation map. Meanwhile, a large segmentation dataset named NeuroSeg is constructed, which contains 15 types of instruments and 3 types of tissues that appear in meningioma resection surgery. The proposed HCNNet achieves the state-of-the-art performance on NeuroSeg, it reaches an inference speed of 54.85 FPS with the highest accuracy of 59.62% mIoU, 74.7% Dice, 70.55% mAcc and 87.12% aAcc., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gui-bin Bian reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

sn-1,2-diacylglycerol (sn-1,2-DAG)-mediated activation of protein kinase Cε (PKCε) is a key pathway that is responsible for obesity-related lipid metabolism disorders, which induces hepatic insulin resistance and type 2 diabetes. No small molecules have been previously reported to ameliorate these diseases through this pathway. Here, we screened and identified the phytochemical atractylenolide II (AT II) that reduces the hepatic sn-1,2-DAG levels, deactivates PKCε activity, and improves obesity-induced hyperlipidemia, hepatosteatosis, and insulin resistance. Furthermore, using the ABPP strategy, the diacylglycerol kinase family member DGKQ was identified as a direct target of AT II. AT II may act on a novel drug-binding pocket in the CRD and PH domains of DGKQ to thereby allosterically regulate its kinase activity. Moreover, AT II also increases weight loss by activating DGKQ-AMPK-PGC1α-UCP-1 signaling in adipose tissue. These findings suggest that AT II is a promising lead compound to improve obesity-induced insulin resistance., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To explore the effect of nootkatone (NKT) on chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and the mechanism underlying NKT improving the depressive-like behaviors., Methods: The CUMS-induced depression model was established in mice. Fifty mice were randomized into 5 groups (n=10) in accordance with a random number table: control group, CUMS group, CUMS + NKT (6 mg/kg) group, CUMS + NKT (12 mg/kg) group, and CUMS + ketamine group. From the 22th day, NKT (6 or 12 mg/kg) or ketamine (0.5 mg/kg) was given with intragastric administration every day for 21 days. Behavioral tests including forced swimming test (FST), tail suspension test (TST), sucrose preference test (SPT) and open-field test (OFT) were carried out. The mRNA and protein expressions of interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor (TNF)-α in hippocampus were assessed using quantitative realtime polymerase chain reaction (PCR), Western blot analysis, and enzyme linked immunosorbent assay. The nuclear factor-κB (NF-κB)/NOD-like receptor 3 (NLRP3) inflammasome pathway was analyzed using Western blot and immunofluorescence analysis., Results: NKT treatment improved CUMS-induced depressive-like behaviors in mice (P<0.05 or P<0.01). NKT significantly decreased the mRNA and protein levels of IL-1β, IL-18, IL-6, and TNF-α in hippocampus of CUMS mice (P<0.05 or P<0.01). Furthermore, NKT repressed CUMS-induced activation of NF-κB signaling and NLRP3 inflammasome (P<0.01). More important, Nigericin, a NLRP3 activator, destroyed the effect of NKT on repressing neuroinflammation and improving depressive-like behaviors (P<0.05 or P<0.01)., Conclusion: NKT ameliorates the depressive-like symptoms, in part by repressing NF-κB/NLRP3-mediated neuroinflammation., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Biological invasions have significant ecological and economic impacts. Much attention is therefore focussed on predicting establishment and invasion success. Trait-based approaches are showing much promise, but are mostly restricted to investigations of plants. Although the application of these approaches to animals is growing rapidly, it is rare for arthropods and restricted mostly to investigations of thermal tolerance. Here we study the extent to which desiccation tolerance and its phenotypic plasticity differ between introduced (nine species) and indigenous (seven species) Collembola, specifically testing predictions of the 'ideal weed' and 'phenotypic plasticity' hypotheses of invasion biology. We do so on the F2 generation of adults in a full factorial design across two temperatures, to elicit desiccation responses, for the phenotypic plasticity trials. We also determine whether basal desiccation resistance responds to thermal laboratory natural selection. We first show experimentally that acclimation to different temperatures elicits changes to cuticular structure and function that are typically associated with water balance, justifying our experimental approach. Our main findings reveal that basal desiccation resistance differs, on average, between the indigenous and introduced species, but that this difference is weaker at higher temperatures, and is driven by particular taxa, as revealed by phylogenetic generalised least squares approaches. By contrast, the extent or form of phenotypic plasticity does not differ between the two groups, with a 'hotter is better' response being most common. Beneficial acclimation is characteristic of only a single species. Laboratory natural selection had little influence on desiccation resistance over 8-12 generations, suggesting that environmental filtering rather than adaptation to new environments may be an important factor influencing Collembola invasions., Competing Interests: 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., (© 2022 The Author(s).)

P53 prognostic cut-off values differ between studies of mantle cell lymphoma (MCL), and its immunohistochemistry (IHC) interpretation is still based on semiquantitative estimation, which might be inaccurate. This study aimed to investigate the optimal cut-off value for p53 in predicting prognosis of patients with MCL and the possible use of computer image analysis to identify the positive rate of p53. We calculated p53 positive rate using QuPath software and compared it with the data obtained by manual counting and semiquantitative estimation. Survival curves were generated by using the Youden index and the Kaplan-Meier method. The chi-squared (χ2) test was used to compare MIPI, Ann Arbor stage, and cell morphology with p53. Spearman rank correlation test and Bland-Altman analysis were used to compare manual counting, computer image analysis and semiquantitative estimation, as well as the consistency between different observers. The optimal cut-off value of p53 for predicting prognosis was 20% in MCL patients. Patients with p53 ≥ 20% had a significantly worse overall survival (OS) than those with p53 < 20% (P < 0.0001). MCL patients with MIPI intermediate to high risk, Ann Arbor stage III-IV, and blastoid/pleomorphic variant cell morphology had more p53 ≥ 20%. There was a strong correlation between computer image analysis and manual counting of p53 from the same areas in MCL tissues (Spearman's rho = 0.966, P < 0.0001). The results of computer analysis are completely consistent between observers, and computer image analysis of Ki-67 can predict the prognosis of MCL patients. MCL patients with p53 ≥ 20% had a shorter OS and a tendency for MIPI intermediate to high risk, Ann Arbor stage III-IV, and blastoid/pleomorphic variant. Computer image analysis could determine the actual positive rate of p53 and Ki-67 and is a more attractive alternative than semiquantitative estimation in MCL., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The ^{13}C(α,n)^{16}O reaction is the main neutron source for the slow-neutron-capture process in asymptotic giant branch stars and for the intermediate process. Direct measurements at astrophysical energies in above-ground laboratories are hindered by the extremely small cross sections and vast cosmic-ray-induced background. We performed the first consistent direct measurement in the range of E&#95;{c.m.}=0.24 to 1.9 MeV using the accelerators at the China Jinping Underground Laboratory and Sichuan University. Our measurement covers almost the entire intermediate process Gamow window in which the large uncertainty of the previous experiments has been reduced from 60% down to 15%, eliminates the large systematic uncertainty in the extrapolation arising from the inconsistency of existing datasets, and provides a more reliable reaction rate for the studies of the slow-neutron-capture and intermediate processes along with the first direct determination of the alpha strength for the near-threshold state.

The purpose of this study was to uncover potential diagnostic indicators of pulmonary arterial hypertension (PAH), evaluate the function of immune cells in the pathogenesis of the disease, and find innovative treatment targets and medicines with the potential to enhance prognosis. Gene Expression Omnibus was utilized to acquire the PAH datasets. We recognized differentially expressed genes (DEGs) and investigated their functions utilizing R software. Weighted gene coexpression network analysis, least absolute shrinkage and selection operators, and support vector machines were used to identify biomarkers. The extent of immune cell infiltration in the normal and PAH tissues was determined using CIBERSORT. Additionally, the association between diagnostic markers and immune cells was analyzed. In this study, 258DEGs were used to analyze the disease ontology. Most DEGs were linked with atherosclerosis, arteriosclerotic cardiovascular disease, and lung disease, including obstructive lung disease. Gene set enrichment analysis revealed that compared to normal samples, results from PAH patients were mostly associated with ECM-receptor interaction, arrhythmogenic right ventricular cardiomyopathy, the Wnt signaling pathway, and focal adhesion. FAM171B was identified as a biomarker for PAH (area under the curve = 0.873). The mechanism underlying PAH may be mediated by nave CD4 T cells, resting memory CD4 T cells, resting NK cells, monocytes, activated dendritic cells, resting mast cells, and neutrophils, according to an investigation of immune cell infiltration. FAM171B expression was also associated with resting mast cells, monocytes, and CD8 T cells. The results suggest that PAH may be closely related to FAM171B with high diagnostic performance and associated with immune cell infiltration, suggesting that FAM171B may promote the progression of PAH by stimulating immune infiltration and immune response. This study provides valuable insights into the pathogenesis and treatment of PAH., Competing Interests: The authors state that the publication of this work does not involve any conflicts of interest., (Copyright © 2022 Lai-Hao Qu et al.)

Aim: Coronary artery disease (CAD) is a heterogeneous disorder with high morbidity, mortality, and healthcare costs, representing a major burden on public health. Here, we aimed to improve our understanding of the genetic drivers of ferroptosis and necroptosis and the clustering of gene expression in CAD in order to develop novel personalized therapies to slow disease progression. Methods: CAD datasets were obtained from the Gene Expression Omnibus. The identification of ferroptosis- and necroptosis-related differentially expressed genes (DEGs) and the consensus clustering method including the classification algorithm used km and distance used spearman were performed to differentiate individuals with CAD into two clusters (cluster A and cluster B) based expression matrix of DEGs. Next, we identified four subgroup-specific genes of significant difference between cluster A and B and again divided individuals with CAD into gene cluster A and gene cluster B with same methods. Additionally, we compared differences in clinical information between the subtypes separately. Finally, principal component analysis algorithms were constructed to calculate the cluster-specific gene score for each sample for quantification of the two clusters. Results: In total, 25 ferroptosis- and necroptosis-related DEGs were screened. The genes in cluster A were mostly related to the neutrophil pathway, whereas those in cluster B were mostly related to the B-cell receptor signaling pathway. Moreover, the subgroup-specific gene scores and CAD indices were higher in cluster A and gene cluster A than in cluster B and gene cluster B. We also identified and validated two genes showing upregulation between clusters A and B in a validation dataset. Conclusion: High expression of CBS and TLR4 was related to more severe disease in patients with CAD, whereas LONP1 and HSPB1 expression was associated with delayed CAD progression. The identification of genetic subgroups of patients with CAD may improve clinician knowledge of disease pathogenesis and facilitate the development of methods for disease diagnosis, classification, and prognosis., 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 © 2022 Liu, Li, Zhan, Qu, Xiong, Hou, Wang, Wei and Liu.)

Pod shattering is a seed dispersal strategy and an important agronomical trait in domesticated crops. The relationship between pod shattering and pod morphology in the genus Medicago is well known; however, the detailed mechanism underlying pod dehiscence in Medicago ruthenica, a perennial legume used for forage production, is unknown. Here, the pod ventral sutures of shatter-resistant and shatter-susceptible M. ruthenica genotypes were examined at 8, 12, 16, and 20 d after flowering. The mechanism of pod shattering was analyzed through microscopic observations, polygalacturonase (PG) and cellulase (CE) activity analyses, and RNA-sequencing (RNA-Seq), and the results were verified via reverse transcriptase-quantitative polymerase chain reaction. Pod shattering at the ventral suture in M. ruthenica occurs via a combination of two mechanisms: degradation of the middle lamella at the abscission layers (ALs) and detachment of lignified cells on either side of the ALs triggered by physical forces. Increased PG and CE activities in the pod ventral suture are essential for AL cell-autolysis in the shatter-susceptible genotype. RNA-Seq revealed that 11 genes encoding PG and CE were highly expressed in the ventral sutures of the shatter-susceptible genotype. The expression levels of auxin biosynthesis-related genes decreased in the AL cells and they were negatively associated with pod dehiscence. These results enhance our understanding of the pod shattering mechanism not only in M. ruthenica but also in other leguminous plants., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

We herein present an overview of the upcoming 5 th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4 th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5 th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms., (© 2022. The Author(s).)

Background and Aims: The clinical outcome of relapsed and refractory (RR) extranodal natural killer/T-cell lymphoma (ENKTL) is poor. It is necessary to identify RR patients in ENKTL and find novel therapeutic targets to improve the prognosis of patients with RR ENKTL., Methods: A total of 189 ENKTL patients with effective clinical characteristics were enrolled. Paraffin specimens were collected for PD-L1 expression identification. Kaplan-Meier curve analysis was performed for survival analysis. Whole exome sequencing (WES) was performed for identifying the mutational characterization of RR and effective treatment (ET) patients., Results: Univariate and multivariate Cox proportional hazards regression analysis showed that negative PD-L1 expression (HR = 1.132, 95% CI = 0.739-1.734, P = 0.036) was an independent predictor of poor prognosis in patients with ENKTL. The overall survival (OS) of PD-L1 positive patients was significantly higher than that of PD-L1 negative patients ( P = 0.009). Then, we added PD-L1 expression as a risk factor to the model of Prognostic Index of Natural Killer Lymphoma (PINK), and named as PINK+PD-L1. The PINK+PD-L1 model can significantly distinguish RR patients, ET patients, and the whole cohort. Moreover, our data showed that PD-L1 expression was lower than 25% in most RR patients, suggesting that RR subtypes may be associated with low expression of PD-L1 ( P = 0.019). According to the whole exome sequencing (WES), we found that the mutation frequencies of JAK-STAT ( P = 0.001), PI3K-AKT ( P = 0.02) and NF-kappa B ( P < 0.001) pathways in RR patients were significantly higher than those in ET patients., Conclusion: Patients tend to show RR when PD-L1 expression is lower than 25%. The model of PINK+PD-L1 can stratify the risk of different groups and predict OS in ENKTL patients. The mutational profile of ENKTL patients with RR is different from that of patients with ET., Competing Interests: Author XS, JW, and YL were employed by OrigiMed Inc. The remaining 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 © 2022 Gao, Zhang, Shi, Liu, Wang, Zhang and Liu.)

We aim to investigate the mechanisms underlying the beneficial effects of exercise rehabilitation (ER) and/or astragaloside (AST) in counteracting amyloid-beta (Aβ) pathology. Aβ oligomers were microinjected into the bilateral ventricles to induce Aβ neuropathology in rats. Neurobehavioral functions were evaluated. Cortical and hippocampal expressions of both BDNF/TrkB and cathepsin D were determined by the western blotting method. The rat primary cultured cortical neurons were incubated with BDNF and/or AST and ANA12 followed by exposure to aggregated Aβ for 24 h. In vivo results showed that ER and/or AST reversed neurobehavioral disorders, downregulation of cortical and hippocampal expression of both BDNF/TrkB and cathepsin D, neural pathology, Aβ accumulation, and altered microglial polarization caused by Aβ. In vitro studies also confirmed that topical application of BDNF and/or AST reversed the Aβ-induced cytotoxicity, apoptosis, mitochondrial distress, and synaptotoxicity and decreased expression of p-TrkB, p-Akt, p-GSK3β, and β-catenin in rat cortical neurons. The beneficial effects of combined ER (or BDNF) and AST therapy in vivo and in vitro were superior to ER (or BDNF) or AST alone. Furthermore, we observed that any gains from ER (or BDNF) and/or AST could be significantly eliminated by ANA-12, a potent BDNF/TrkB antagonist. These results indicate that whereas ER (or BDNF) and/or AST attenuate Aβ pathology by reversing BDNF/TrkB signaling deficits and mitochondrial dysfunction, combining these two potentiates each other's therapeutic effects. In particular, AST can be an alternative therapy to replace ER., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Anopheles anthropophagus (Xu and Feng 1975) is the major vector of malaria in Eastern and Southern China. The species An. anthropophagus is considered a synonym of An. lesteri (Baisas & Hu, 1936), although they differ in several key biological characteristics. Here, we report the complete mitochondrial genome of An. anthropophagus for the first time. The mitogenome of An. anthropophagus is a typical circular, double-stranded molecule with a total length of 15,413 base pairs, and contains 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and an AT-rich control region. A phylogenetic analysis of the complete mitogenomes of 16 species of Anopheles (Culicidae) revealed that An. anthropophagus is closely related to An. sinensis (Wiedemann 1828), in the family Culicidae. The An. anthropophagus mitogenome provides new data for further taxonomic and phylogenetic studies of the genus Anopheles ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: This study determined the predictive value of CRMP4 promoter methylation in prostate tissues collected by core needle biopsies for a postoperative upgrade of Gleason Score (GS) to ≥8 in patients with low-risk PCa., Method: A retrospective analysis of the clinical data was conducted from 631 patients diagnosed with low-risk PCa by core needle biopsy at multiple centers and then underwent Radical Prostatectomy (RP) from 2014-2019. Specimens were collected by core needle biopsy to detect CRMP4 promoter methylation. The pathologic factors correlated with the postoperative GS upgrade to ≥8 were analyzed by logistic regression. The cut-off value for CRMP4 promoter methylation in the prostate tissues collected by core needle biopsy was estimated from the ROC curve in patients with a postoperative GS upgrade to ≥8., Result: Multivariate logistic regression showed that prostate volume, number of positive cores, and CRMP4 promoter methylation were predictive factors for a GS upgrade to ≥8 (OR: 0.94, 95% CI: 0.91-0.98, P =0.003; OR: 3.16, 95% CI: 1.81-5.53, P <0.001; and OR: 1.43, 95% CI: 1.32-1.55, P <0.001, respectively). The positive predictive rate was 85.2%, the negative predictive rate was 99.3%, and the overall predictive rate was 97.9%. When the CRMP4 promoter methylation rate was >18.00%, the low-risk PCa patients were more likely to escalate to high-risk patients. The predictive sensitivity and specificity were 86.9% and 98.8%, respectively. The area under the ROC curve (AUC) was 0.929 (95% CI: 0.883-0.976; P <0.001). The biochemical recurrence (BCR)-free survival, progression-free survival (PFS), and cancer-specific survival (CSS) were worse in patients with CRMP4 methylation >18.0% and postoperative GS upgrade to ≥8 than in patients without an upgrade ( P ≤ 0.002)., Conclusion: A CRMP4 promoter methylation rate >18.00% in prostate cancer tissues indicated that patients were more likely to escalate from low-to-high risk after undergoing an RP. We recommend determining CRMP4 promoter methylation before RP for low-risk PCa patients., 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 © 2022 Qin, Lu, Yang, Wang, Chen, Liu, Chen, Zhou, Pan, Li, Ren, Liu, Liu, Qian, Yi, Lai, Qu, Gao, Xu, Chen and Zhuo.)

A new fluorescence probe method for the detection of Hg(II) in serum was established, which has the detection limit of 3.57 nM and quantification limit of 5 nM, based on the electrostatic induced agglomeration quenching and complexation between Hg(II) and silicon-nitrogen-doped carbon nanodots (Si/N-CDs). Furthermore, the fluorescence probe also showed the satisfactory results in the determination of Hg(II) in human serum. Subsequently, take advantage of the uric acid (UA) to recover the fluorescence of the Si/N-CDs-Hg(II) complex probe, another enzyme-free ways to determine UA was developed. The complex probe can selectively detect the UA content in the 0.5-30 μM range, and its detection limit can reach 0.14 μM, which has successfully detected the UA in total serum, and the results were no significant difference comparing with the controls., 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 © 2021 Elsevier B.V. All rights reserved.)

Objective: To explore the relationship between sleep duration and depressive symptoms in middle-aged and elderly people. Methods: A total of 11 931 middle-aged and elderly people aged ≥55 years who participated in the baseline survey of the "Community Cohort Study of Specialized Nervous System Diseases" in China from 2018 to 2019 were selected to obtain basic information about their lifestyle, food intake frequency, disease history, sleep duration. The body height and weight were measured, and body mass index (BMI) were calculated. The subjects with depressive symptoms were screened with the Geriatric Depression Scale (GDS-30). Restricted cubic spline model and multivariate logistic regression model were used to analyze the relationship between sleep duration and depressive symptoms. Results: Among the middle-aged and elderly people aged ≥55 years, 17.79% reported sleep duration less than 7 hours, 16.84% reported that their sleep duration ≥9 hours, and the detection rate of depression symptoms was 7.95%. After adjusting for factors such as region, age, gender, the restricted cubic spline results showed the U-shaped relationship between sleep duration and the risk for depressive symptoms, the results of multivariate logistic regression analysis showed that the risk for depressive symptom in middle-aged and elderly people aged ≥55 years with sleep duration ≤5 hours, 6 hours, and ≥9 hours were 1.749(95% CI :1.279-2.392), 1.284(95% CI :1.021-1.615) and 1.260(95% CI :1.033-1.538) times higher compared with the counterparts with sleep duration 7-8 hours, the risk for depressive symptom in women with sleep duration ≤5 hours, 6 hours and ≥9 hours were 2.115 (95% CI :1.473-3.038), 1.605(95% CI :1.213-2.123) and 1.313(95% CI :1.011-1.705) times higher, respectively, compared with counterparts with sleep duration 7-8 hours, the risk for depressive symptoms in 55-64-year-old middle-aged and elderly people with sleep duration ≤5 hours and ≥9 hours were 1.806 (95% CI :1.014-3.217) and 1.478 (95% CI :1.060-2.061) times higher compared with counterparts with sleep duration 7-8 hours, and the risk for depressive symptoms in elderly people aged 65-74 years with sleep duration ≤5 hours was 2.112 (95% CI :1.327-3.361)times higher compared with counterparts with sleep duration 7-8 hours, the differences were all significant ( P <0.05). There was no statistically significant association between sleep duration and depressive symptoms in men and in elderly people aged ≥75 years ( P >0.05). Conclusion: Insufficient or prolonged sleep was independently associated with depressive symptoms in middle-aged and elderly people, showing a U-shaped relationship, especially in women and in middle-aged and elderly people aged 55-64 years.

Fluorine is one of the most interesting elements in nuclear astrophysics, where the ^{19}F(p,α)^{16}O reaction is of crucial importance for Galactic ^{19}F abundances and CNO cycle loss in first generation Population III stars. As a day-one campaign at the Jinping Underground Nuclear Astrophysics experimental facility, we report direct measurements of the essential ^{19}F(p,αγ)^{16}O reaction channel. The γ-ray yields were measured over E&#95;{c.m.}=72.4-344  keV, covering the Gamow window; our energy of 72.4 keV is unprecedentedly low, reported here for the first time. The experiment was performed under the extremely low cosmic-ray-induced background environment of the China JinPing Underground Laboratory, one of the deepest underground laboratories in the world. The present low-energy S factors deviate significantly from previous theoretical predictions, and the uncertainties are significantly reduced. The thermonuclear ^{19}F(p,αγ)^{16}O reaction rate has been determined directly at the relevant astrophysical energies.