Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction.

BACKGROUND: Leukemia stem cells (LSCs) are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia (AML), as they are protected by the bone marrow microenvironment (BMM) against conventional therapies. Gossypol acetic acid (GAA), which is extracted from the seeds of cotton plants, exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2. AIM: To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism. METHODS: In this study, LSCs were magnetically sorted from AML cell lines and the CD34+CD38- population was obtained. The expression of leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) and forkhead box M1 (FOXM1) was evaluated in LSCs, and the effects of GAA on malignancies and mitochondrial function were measured. RESULTS: LRPPRC was found to be upregulated, and GAA inhibited cell proliferation by degrading LRPPRC. GAA induced LRPPRC degradation and inhibited the activation of interleukin 6 (IL-6)/janus kinase (JAK) 1/signal transducer and activator of transcription (STAT) 3 signaling, enhancing chemosensitivity in LSCs against conventional chemotherapies, including L-Asparaginase, Dexamethasone, and cytarabine. GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC. Furthermore, GAA induced reactive oxygen species accumulation, disturbed mitochondrial homeostasis, and caused mitochondrial dysfunction. By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC, GAA resulted in the elimination of LSCs. Meanwhile, GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage. CONCLUSION: Taken together, the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

Low­dose venetoclax combined with azacitidine in older and frail patients with newly diagnosed acute myeloid leukaemia.

In the present study, the aim was to evaluate the clinical efficacy and safety of low-dose venetoclax combined with azacitidine for the treatment of older and frail patients with newly diagnosed acute myeloid leukaemia (AML). Data of 26 older patients with newly diagnosed AML admitted to Yuyao People's Hospital (Yuyao, China) between January 2021 and May 2023 were retrospectively analysed. The treatment regimens were as follows: Subcutaneous injection of 100 mg azacitidine on days 1-5 and 100 mg oral venetoclax on days 3-16 or 200 mg oral venetoclax on days 3-30. The median age of the 26 patients was 73 years. After the first course of treatment, the complete remission (CR) and CR with incomplete haematological recovery rate was 84.6%, and the objective response rate was 96.2%. The most common adverse events noted during treatment were haematological adverse events including grade 3/4 granulocytosis (57.7%), febrile neutropenia (30.8%), pulmonary infection (32.0%), thrombocytopenia (42.3%) and anaemia (42.3%). A total of 13 (50.0%) patients did not require platelet (PLT) infusion during treatment. The main non-haematological adverse reactions included gastrointestinal reactions such as nausea, vomiting and diarrhoea. Patients were followed up until December 2023, with a median follow-up time of 9.5 months (range, 1.9-26.0 months). Of the 26 patients, nine (34.6%) patients experienced relapse, with a mean recurrence time of 5.9 months. In conclusion, preliminary results indicated that low-dose venetoclax combined with azacitidine is effective and safe for the treatment of older and frail patients with newly diagnosed AML, providing a new treatment option for these patients.

The impact of SOX4-activated CTHRC1 transcriptional activity regulating DNA damage repair on cisplatin resistance in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the predominant subtype within the spectrum of lung malignancies. CTHRC1 has a pro-oncogenic role in various cancers. Here, we observed the upregulation of CTHRC1 in LUAD, but its role in cisplatin resistance in LUAD remains unclear. Bioinformatics analysis was employed to detect CTHRC1 and SRY-related HMG-box 4 (SOX4) expression in LUAD. Gene Set Enrichment Analysis predicted the enriched pathways related to CTHRC1. JASPAR and MotifMap databases predicted upstream transcription factors of CTHRC1. Pearson analysis was conducted to analyze the correlation between genes of interest. The interaction and binding relationship between CTHRC1 and SOX4 were validated through dual-luciferase and chromatin immunoprecipitation assays. Quantitative real-time polymerase chain reaction determined the expression of CTHRC1 and SOX4 genes. CCK-8 was performed to assess cell viability and calculate IC50 value. Flow cytometry examined the cell cycle. Comet assay and western blot assessed DNA damage. CTHRC1 and SOX4 were upregulated in LUAD. CTHRC1 exhibited higher expression in cisplatin-resistant A549 cells compared to cisplatin-sensitive A549 cells. Knockdown of CTHRC1 enhanced DNA damage during cisplatin treatment and increased the sensitivity of LUAD cells to cisplatin. Additionally, SOX4 modulated DNA damage repair (DDR) by activating CTHRC1 transcriptional activity, promoting cisplatin resistance in LUAD cells. SOX4 regulated DDR by activating CTHRC1, thereby enhancing cisplatin resistance in LUAD cells. The finding provides a novel approach to address clinical cisplatin resistance in LUAD, with CTHRC1 possibly serving as a candidate for targeted therapies in addressing cisplatin resistance within LUAD.

Methionine redox regulation of actin-interacting proteins primarily governs antioxidative signaling and response to the salvianolic acid B treatment in EA.hy926 cells.

Actin-interacting proteins are important molecules for filament assembly and cytoskeletal signaling within vascular endothelium. Disruption in their interactions causes endothelial pathogenesis through redox imbalance. Actin filament redox regulation remains largely unexplored, in the context of pharmacological treatment. This work focused on the peptidyl methionine (M) redox regulation of actin-interacting proteins, aiming at elucidating its role on governing antioxidative signaling and response. Endothelial EA.hy926 cells were subjected to treatment with salvianolic acid B (Sal B) and tert-butyl-hydroperoxide (tBHP) stimulation. Mass spectrometry was employed to characterize redox status of proteins, including actin, myosin-9, kelch-like erythroid-derived cap-n-collar homology-associated protein 1 (Keap1), plastin-3, prelamin-A/C and vimentin. The protein redox landscape revealed distinct stoichiometric ratios or reaction site transitions mediated by M sulfoxide reductase and reactive oxygen species. In comparison with effects of tBHP stimulation, Sal B treatment prevented oxidation at actin M325, myosin-9 M1489/1565, Keap1 M120, plastin-3 M592, prelamin-A/C M187/371/540 and vimentin M344. For Keap1, reaction site was transitioned within its scaffolding region to the actin ring. These protein M oxidation regulations contributed to the Sal B cytoprotective effects on actin filament. Additionally, regarding the Keap1 homo-dimerization region, Sal B preventive roles against M120 oxidation acted as a primary signal driver to activate nuclear factor erythroid 2-related factor 2 (Nrf2). Transcriptional splicing of non-POU domain-containing octamer-binding protein was validated during the Sal B-mediated overexpression of NAD(P)H dehydrogenase [quinone] 1. This molecular redox regulation of actin-interacting proteins provided valuable insights into the phenolic structures of Sal B analogs, showing potential antioxidative effects on vascular endothelium.

Primary pulmonary adenoid cystic carcinoma: A clinicopathological study of 64 patients.

BACKGROUND: This study aimed to investigate the clinicopathological features and prognostic indicators of primary pulmonary adenoid cystic carcinoma (PACC). METHODS: Clinical data were collected from 64 primary PACC patients and analyzed retrospectively at the Tianjin Medical University General Hospital, the West China Hospital of Sichuan University, the First Affiliated Hospital of Guangxi Medical University, and the Bishan Hospital of Chongqing Medical University from January 2003 to August 2023. The 64 patients (28 males and 36 females) were aged from 20 to 73 years, with a median age of 49 years and an average age of 49.3 years. RESULTS: Immunohistochemical staining showed that the tumors expressed CK7, S-100 protein, CK5/6, CD117, and p63. Seven patients underwent fluorescence in situ hybridization (FISH) testing and three were found to have myeloblastosis (MYB) gene translocation. In total, 53 patients underwent surgery, among whom 31 received only surgery and 22 received both surgery and postoperative chemoradiotherapy. In addition, 10 patients received chemoradiotherapy only, while one patient underwent treatment with traditional Chinese medicine. The overall survival rates in the first, third, and fifth years were 98.4%, 95.3%, and 87.5%, respectively. CONCLUSION: Prognostic analysis revealed that age, tumor size, lymph node metastasis status, margin status, and choice of treatment modality significantly influenced the patients' prognosis.

Kajian Rintis Penilaian Literasi Digital: Kesediaan Guru Prasekolah Menggunakan Platform Pembelajaran dalam Talian untuk Pendidikan Pemakanan (A Pilot Study Assessing Digital Literacy: Preschool Teachers’ Readiness to Use Online Learning Platforms in Nutrition Education) / Jurnal Sains Kesihatan Malaysia

@#eToyBox is a learning management system for preschool teachers to improve their health literacy, which ultimately aims to improve children’s obesity-related behaviour. As part of the development process of eToyBox, assessment on digital literacy, acceptance of digitization of education materials, and perceived barriers in adopting online learning is needed. Fifty-four preschool teachers under the Community Development Department (KEMAS) in Kuala Lumpur, Selangor, and Sarawak, who participated in ToyBox Study Malaysia intervention in 2018, took part in this cross-sectional study. An online self-administered questionnaire was used to assess sociodemographic background, use of communication tools and media, and teacher’s views on adapting the ToyBox modules to digital education materials. Respondents were contacted, and questionnaire link was shared through WhatsApp messages. Most participants (74.0%) were Malay females aged 31 to 40 years old. Most participants had internet access (94.4%) and owned at least a smart phone, laptop or tablet (94.4%). Participants perceived their computer skills to be average (75.0%). Majority of respondents (65.0%) reported advanced and higher abilities in word processing and email, but only 22.0% in spreadsheet skills. The main barrier to accessing online material was unstable internet connection (74.1%). Most respondents (90.0%) agree that adapting effective modules to online learning will be beneficial for professional development and teaching practices. In conclusion, most participants supported digitizing Toybox Study Malaysia educational content and were comfortable 72 with its implementation via an online learning platform. The findings from this study can advise future development of online learning materials for preschool teachers in Malaysia.

Optimized allotopic expression of mitochondrial ND6 transgene restored complex I and apoptosis deficiencies caused by LHON-linked ND6 14484T > C mutation.

BACKGROUND: Leber's hereditary optic neuropathy (LHON) is a maternally inherited eye disease due to mutations in mitochondrial DNA. However, there is no effective treatment for this disease. LHON-linked ND6 14484T > C (p.M64V) mutation caused complex I deficiency, diminished ATP production, increased production of reactive oxygen species (ROS), elevated apoptosis, and impaired mitophagy. Here, we investigated if the allotopic expression of human mitochondrial ND6 transgene corrected the mitochondrial dysfunctions due to LHON-associated m.14484T > C mutation. METHODS: Nucleus-versions of ND6 was generated by changing 6 non-universal codons with universal codons and added to mitochondrial targeting sequence of COX8. Stable transfectants were generated by transferring human ND6 cDNA expressed in a pCDH-puro vector into mutant cybrids carrying the m.14484T > C mutation and control cybrids. The effect of allotopic expression of ND6 on oxidative phosphorylation (OXPHOS) was evaluated using Blue Native gel electrophoresis and extracellular flux analyzer. Assessment of ROS production in cell lines was performed by flow cytometry with MitoSOX Red reagent. Analyses for apoptosis and mitophagy were undertaken via flow cytometry, TUNEL and immunofluorescence assays. RESULTS: The transfer of human ND6 into the cybrids carrying the m.14484T > C mutation raised the levels of ND6, ND1 and ND4L but did not change the levels of other mitochondrial proteins. The overexpression of ND6 led to 20~23% increases in the assembly and activity of complex I, and ~ 53% and ~ 33% increases in the levels of mitochondrial ATP and ΔΨm in the mutant cybrids bearing m.14484T > C mutation. Furthermore, mutant cybrids with overexpression of ND6 exhibited marked reductions in the levels of mitochondrial ROS. Strikingly, ND6 overexpression markedly inhibited the apoptosis process and restored impaired mitophagy in the cells carrying m.14484T > C mutation. However, overexpression of ND6 did not affect the ND6 level and mitochondrial functions in the wild-type cybrids, indicating that this ND6 level appeared to be the maximum threshold level to maintain the normal cell function. CONCLUSION: We demonstrated that allotopic expression of nucleus-versions of ND6 restored complex I, apoptosis and mitophagy deficiencies caused by the m.14484T > C mutation. The restoration of m.14484T > C mutation-induced mitochondrial dysfunctions by overexpression of ND6 is a step toward therapeutic interventions for LHON and mitochondrial diseases.

From ToyBox Study to eToyBox: Advancing Childhood Obesity Reduction in Malaysian Kindergartens.

Prevention and treatment of childhood obesity is a global concern, and in Malaysia, it is considered a national public health priority. Determinants of childhood obesity are multifactorial and include factors that directly and indirectly influence energy balance-related behaviours, including energy intake and energy expenditure. Interventions to address childhood obesity that have multiple components at different levels have been shown to be the most influential. The ToyBox-study is a childhood obesity intervention aimed at preschool-aged children and their families that had been shown to be effective in several European countries and so was chosen for adaption for the Malaysian setting. Materials were translated and adjusted for the Malaysian context and audience and implemented in kindergartens in Peninsular Malaysia and Sarawak. However, during the COVID-19 pandemic and lockdown, teaching transitioned to being online. This brought an opportunity to reach a wider audience and consider the long-term sustainability of the intervention, and thus eToybox was born. eToybox aims to bring support for healthy energy balance behaviours directly to the teachers, into kindergartens and homes, to encourage families to be active and eat healthily, and prevent or reduce obesity. Through online innovation, the Toybox Study Malaysia programme has been expanded to enhance its potential to impact the promotion of healthy lifestyles among preschoolers and their families, highlighting the importance of a holistic approach to preventing and treating childhood obesity in Malaysia.

Prognostic characteristics of T-cell mediated cell killing-related genes in lung adenocarcinoma.

Constituted by various heterogeneous cells, the tumor microenvironment (TME) is capable of promoting tumor proliferation, invasion, and metastasis through extensive crosstalk. The pivotal factor influencing the survival time of patients and their response to immunotherapy lies in the intratumoral immune environment. We obtained 112 differential genes related to T cell-mediated tumor killing in LUAD by employing bioinformatics analysis on the basis of the TCGA and TISIDB databases. Then the 6-gene prognostic risk score model (CA9, OIP5, TIMP1, SEC11C, FURIN, and TLR10) was constructed by conducting univariate LASSO as well as multivariate Cox regression analyses. The median risk score was taken as the threshold to classify the samples into two groups. Survival analysis revealed that the low-risk group exhibited a more favorable prognosis. Subsequently, the Cox regression analysis combined with clinical information (age, gender, and pathological stage) and the risk score of LUAD patients demonstrated the potential of this model as an independent prognostic factor. The nomogram established based on clinical information and a risk score in combination with the calibration curve indicated that this model had good predictive ability. Notable enrichment of the differential genes from the high- and low-risk groups was discovered in immune-associated processes or pathways, as shown by the GO and KEGG enrichment analyses. The combined use of single-sample gene enrichment analysis (ssGSEA) and immunophenoscore (IPS) demonstrated heightened immune infiltration and IPS scores in the low-risk group, indicating that immunotherapy was likely to show good efficacy in patients from this group. To sum up, the prognostic model of LUAD constructed based on T-cell-mediated cell killing-related genes was not only capable of screening the prognosis of LUAD patients but was also used for screening those LUAD patients with high sensitivity to immunotherapy. Our study offered novel insights into the clinical treatment and prognostic prediction of LUAD patients.

Bidirectional crosstalk of the cAMP/ROS-dependent signaling pathways in inflammatory macrophage: An activation of formononetin.

Bacterial lipopolysaccharide (LPS) is a toxic stimulant to macrophage inflammation. Inflammation intersects cell metabolism and often directs host immunopathogenesis stress. We aim here at pharmacological discovering of formononetin (FMN) action, to which anti-inflammatory signaling spans across immune membrane receptors and second messenger metabolites. In ANA-1 macrophage stimulated by LPS, and simultaneous treatment with FMN, results show the Toll-like receptor 4 (TLR4) and estrogen receptor (ER) signals, in concert with reactive oxygen species (ROS) and cyclic adenosine monophosphate (cAMP), respectively. LPS stimulates inactivation of the ROS-dependent nuclear factor erythroid 2-related factor 2 (Nrf2) by upregulating TLR4, but it does not affect cAMP. However, FMN treatment not only activates Nrf2 signaling by TLR4 inhibition, but also it activates cAMP-dependent protein kinase activities by upregulating ER. The cAMP activity gives rise to phosphorylation (p-) of protein kinase A, liver kinase B1 and 5'-AMP activated protein kinase (AMPK). Moreover, bidirectional signal crosstalk is amplified between p-AMPK and ROS, as FMN combinational validation with AMPK activator/inhibitor/target small-interfering RNA or ROS scavenger. The signal crosstalk is well positioned serving as the 'plug-in' knot for rather long signaling axis, and the immune-to-metabolic circuit via ER/TLR4 signal transduction. Collectively, convergence of the FMN-activated signals drives significant reduction of cyclooxygenase-2, interleukin-6 and NLR family pyrin domain-containing protein 3, in LPS-stimulated cell. Although anti-inflammatory signaling is specifically related to the immune-type macrophage, the p-AMPK antagonizing effect arises from FMN combination with ROS scavenger H-bond donors. Information of our work assists in predictive traits against macrophage inflammatory challenges, using phytoestrogen discoveries.

Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos.

The low intrinsic growth capacity of neurons and an injury-induced inhibitory milieu are major contributors to the failure of sensory and motor functional recovery following spinal cord injury. Heat shock transcription factor 1 (HSF1), a master regulator of the heat shock response, plays neurogenetic and neuroprotective roles in the damaged or diseased central nervous system. However, the underlying mechanism has not been fully elucidated. In the present study, we used a gecko model of spontaneous nerve regeneration to investigate the potential roles of gecko HSF1 (gHSF1) in the regulation of neurite outgrowth and inflammatory inhibition of macrophages following spinal cord injury. gHSF1 expression in neurons and microglia at the lesion site increased dramatically immediately after tail amputation. gHSF1 overexpression in gecko primary neurons significantly promoted axonal growth by suppressing the expression of suppressor of cytokine signaling-3, and facilitated neuronal survival via activation of the mitogen-activated extracellular signal-regulated kinase/extracellular regulated protein kinases and phosphatidylinositol 3-kinase/protein kinase B pathways. Furthermore, gHSF1 efficiently inhibited the macrophage-mediated inflammatory response by inactivating IkappaB-alpha/NF-kappaB signaling. Our findings show that HSF1 plays dual roles in promoting axonal regrowth and inhibiting leukocyte inflammation, and provide new avenues of investigation for promoting spinal cord injury repair in mammals.

Solitary extramedullary plasmacytoma of the left main bronchus: A case report and literature review.

Tracheal tumors are rare, accounting for 0.1% of all malignancies. Squamous cell carcinoma and adenoid cystic carcinoma are the two most prevalent tracheal cancers. Less than 20 cases of extramedullary plasmacytoma in the trachea and main bronchus have ever been documented in the literature, making it extremely uncommon. Although the origin of these lesions is unclear, viral pathogenesis and persistent inflammation are thought to be the main causes. Clinically, these individuals exhibit vague symptoms such as stridor, a persistent cough, dyspnea, or wheezing, making a correct diagnosis difficult.

PGC-1α/NRF1-dependent cardiac mitochondrial biogenesis: A druggable pathway of calycosin against triptolide cardiotoxicity.

Mitochondrion-related cardiotoxicity due to cardiotoxin stimuli is closely linked to abnormal activities of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), followed by co-inactivation of nuclear respiratory factor-1(NRF1). Pharmacological interventions targeting mitochondria may be effective for developing agents against cardiotoxicity. Herein, in triptolide-treated H9C2 cardiomyocytes, we observed defective mitochondrial biogenesis and respiration, characterized by depletion of mitochondrial mass and mitochondrial DNA copy number, downregulation of mitochondrial respiratory chain complexes subunits, and disorders of mitochondrial membrane potential and mitochondrial oxidative phosphorylation. Dysregulation of mitochondria led to cardiac pathological features, such as myocardial fiber fracture, intercellular space enlargement, and elevation of serum aspartate aminotransferase, creatine kinase isoenzyme, lactate dehydrogenase, and cardiac troponin I. However, following calycosin treatment, an active compound from Astragali Radix, the mitochondrion-related disorders at both cell and tissue levels were significantly ameliorated, which was facilitated by the activation of PGC-1α via deacetylation, followed by NRF1 co-activation. Calycosin-enhanced PGC-1α deacetylation is impelled by increasing sirtuin-1 expression and NAD+/NADH ratio. PGC-1α/NRF1 signaling in calycosin-mediated mitochondrial biogenesis protection was further confirmed by NRF1 knockdown and PGC-1α inhibition with SR18292. We conclude that calycosin ameliorated triptolide-induced cardiotoxicity by protecting PGC-1α/NRF1-dependent cardiac mitochondrial biogenesis and respiration, which is the druggable pathway for cardiotoxicity mitigation.

Human health risks associated with metals in paddy plant (Oryza sativa) based on target hazard quotient and target cancer risk.

Paddy plants (Oryza sativa) contaminated with metals could be detrimental to human health if the concentrations of metals exceed the permissible limit. Thus, this study aims to assess the risk of the concentrations of As, Se, Cu, Cr, Co, and Ni and their distributions in various parts (roots, stems, leaves, and grains) of paddy plants collected from Sekinchan, Malaysia. Both soil and plant samples were digested according to the United States Environmental Protection Agency (USEPA) Method 3050B and the metal concentrations were determined by the Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). The highest mean translocation factor (TF) was from soil to roots (TF roots/soil ranged from 0.12 to 6.15) and the lowest was from leaves to grain (TF grain/leaves ranged from 0.06 to 0.87). Meanwhile, the bioaccumulation factor (BAF) for all metals was less than 1.0 indicating that paddy plants only absorb metals from the soil but do not accumulate in the grains. The average daily intake for As (1.15 ± 0.25 µg/kg/day) has exceeded the limit proposed by ATSDR and IRIS USEPA (0.30 µg/kg/day). Target cancer risk (TR) of 1.10 × 10-3 for As through rice consumption indicates that the potential cancer risk exists in one out of 1000 exposed individuals. The results from this study could serve as a reference for researchers and policymakers to monitor and formulate strategies in managing As and other metals in paddy plants, especially in Southeast Asian countries.

The First High-quality Reference Genome of Sika Deer Provides Insights into High-tannin Adaptation.

Sika deer are known to prefer oak leaves, which are rich in tannins and toxic to most mammals; however, the genetic mechanisms underlying their unique ability to adapt to living in the jungle are still unclear. In identifying the mechanism responsible for the tolerance of a highly toxic diet, we have made a major advancement by explaining the genome of sika deer. We generated the first high-quality, chromosome-level genome assembly of sika deer and measured the correlation between tannin intake and RNA expression in 15 tissues through 180 experiments. Comparative genome analyses showed that the UGT and CYP gene families are functionally involved in the adaptation of sika deer to high-tannin food, especially the expansion of the UGT family 2 subfamily B of UGT genes. The first chromosome-level assembly and genetic characterization of the tolerance to a highly toxic diet suggest that the sika deer genome may serve as an essential resource for understanding evolutionary events and tannin adaptation. Our study provides a paradigm of comparative expressive genomics that can be applied to the study of unique biological features in non-model animals.

A super pan-genomic landscape of rice.

Pan-genomes from large natural populations can capture genetic diversity and reveal genomic complexity. Using de novo long-read assembly, we generated a graph-based super pan-genome of rice consisting of a 251-accession panel comprising both cultivated and wild species of Asian and African rice. Our pan-genome reveals extensive structural variations (SVs) and gene presence/absence variations. Additionally, our pan-genome enables the accurate identification of nucleotide-binding leucine-rich repeat genes and characterization of their inter- and intraspecific diversity. Moreover, we uncovered grain weight-associated SVs which specify traits by affecting the expression of their nearby genes. We characterized genetic variants associated with submergence tolerance, seed shattering and plant architecture and found independent selection for a common set of genes that drove adaptation and domestication in Asian and African rice. This super pan-genome facilitates pinpointing of lineage-specific haplotypes for trait-associated genes and provides insights into the evolutionary events that have shaped the genomic architecture of various rice species.

Integrated Metabolomic-Transcriptomic Analysis Reveals Diverse Resource of Functional Ingredients From Persimmon Leaves of Different Varieties.

Persimmon leaves are used for making persimmon leaf tea or as functional ingredients due to their enrichment in flavonoids, the beneficial mineral contents, and favorable flavors contributed by volatile aroma compounds. The varieties/cultivars had a significant influence on the quality and flavor of persimmon leaf tea. In this study, the integrated metabolomic-transcriptomic analysis was conducted to investigate the potential in flavonoid biosynthesis, mineral absorption, and degradation of aromatic compounds from tender leaves of "Diospyros kaki. Heishi" (HS), "Diospyros kaki Thunb. Nishimurawase" (NM), and "Diospyros kaki Thunb. Taifu" (TF), using rootstock "Diospyros Lotus Linn" (DL) as the control. The metabolomic analysis showed that 382, 391, and 368 metabolites were differentially accumulated in the comparison of DL vs. HS, DL vs. NM, and DL vs. TF, respectively, and 229 common metabolites were obtained by comparative analysis. By RNA sequencing, 182,008 unigenes with 652 bp of mean length were annotated and 2,598, 3,503, and 3,333 differentially expressed genes (DEGs) were detected from the comparison of DL vs. HS, DL vs. NM, and DL vs. TF, respectively. After the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, 6, 6, and 3 DEGs [with | log2(fold change)| ≥ 1 simultaneously in the three comparisons] involved in flavonoid biosynthesis, mineral absorption, and degradation of aromatic compounds, respectively, were selected for quantitative reverse transcription-polymerase chain reaction (qRT-PCR) validation and the consistent trends of the relative expression level of each DEG with RNA sequencing (RNA-seq) data were observed. Based on the transcriptomic analysis and qRT-PCR validation, it was observed that the leaves of HS, NM, and TF had the greatest level of mineral absorption, flavonoid biosynthesis, and degradation of aromatic compounds, respectively. In addition, a positive correlation between the 15 DEGs and their metabolites was observed by the conjoint analysis. Thus, the tender leaves of HS, NM, and TF could be recommended for the production of persimmon leaf tea rich in mineral elements, flavonoid, and aroma compounds, respectively.

Pulmonary mucoepidermoid carcinoma: A clinicopathological study of 45 patients.

Pulmonary mucoepidermoid carcinoma (PMEC) is uncommon. The purpose of this study was to evaluate the clinicopathological features, diagnostic criteria, treatment options, and prognostic factors relating to primary PMEC. Clinical data on 45 patients with primary PMEC were collected and analyzed retrospectively at Tianjin Medical University General Hospital and the First People' Hospital of Longquanyi District Chengdu from January 2008 to December 2020. The 45 patients (25 males and 20 females) ranged in age from 22 to 72 years, with a median age of 49 and an average age of 47.7. All the patients underwent surgery, with 32 receiving only surgery and 13 receiving both surgery and postoperative chemotherapy. A total of 34 instances of low-grade tumors and 11 cases of high-grade tumors were discovered during postoperative pathological diagnosis. Forty-five patients were followed for 13 to 78 months, and four died during this period. In all four instances, a lung infection unrelated to the tumor was determined to be the cause of death. The MAML2 gene translocation was detected in 40 of 45 patients, with 34 of them testing positive. Radical surgery with lymph node dissection is an efficient treatment for PMEC. The prognosis is poor for patients with advanced disease, a negative MAML2 gene translocation, lymph node metastases, and high-grade tumors.