Oncogenic functions and therapeutic potentials of targeted inhibition of SMARCAL1 in small cell lung cancer.

Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by high frequency loss-of-function mutations in tumor suppressors with a lack of targeted therapy due to absence of high frequency gain-of-function abnormalities in oncogenes. SMARCAL1 is a member of the ATP-dependent chromatin remodeling protein SNF2 family that plays critical roles in DNA damage repair and genome stability maintenance. Here, we showed that SMARCAL1 was overexpressed in SCLC patient samples and was inversely associated with overall survival of the patients. SMARCAL1 was required for SCLC cell proliferation and genome integrity. Mass spectrometry revealed that PAR6B was a downstream SMARCAL1 signal molecule which rescued inhibitory effects caused by silencing of SMARCAL1. By screening of 36 FDA-approved clinically available agents related to DNA damage repair, we found that an aza-anthracenedione, pixantrone, was a potent SMARCAL1 inhibitor which suppressed the expression of SMARCAL1 and PAR6B at protein level. Pixantrone caused DNA damage and exhibited inhibitory effects on SCLC cells in vitro and in a patient-derived xenograft mouse model. These results indicated that SMARCAL1 functions as an oncogene in SCLC, and pixantrone as a SMARCAL1 inhibitor bears therapeutic potentials in this deadly disease.

Comprehensive analysis of exosome gene LYPD3 and prognosis/immune cell infiltration in lung cancer.

Background: Lung cancer (LC) is a leading cause of cancer-associated mortality worldwide, with high incidence and mortality rates. Ly6/PLAUR domain containing 3 (LYPD3) is a tumorigenic and highly glycosylated cell surface protein that has been rarely reported in LC. This study aimed to explore the prognostic role and immune cell infiltration of LYPD3 in LC. Methods: We used ExoCarta, a database of exosomal proteins and RNA, to select exosomes in LC. The Tumor Immune Estimation Resource (TIMER) and Human Protein Atlas (HPA) databases were utilized to compare the expression of LYPD3 in LC. We applied Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Kaplan-Meier (KM) plotter to evaluate the prognostic prediction performance of LYPD3. Biological processes (BPs), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and gene set enrichment analysis (GSEA) analyses were performed to illustrate the possible role of LYPD3 in LC. The correlations between LYPD3 and immune cell infiltration were explored using Tumor and Immune System Interaction Database (TISIDB), GEPIA2, and TIMER. R software was used for statistical analysis and mapping. Results: A total of 904 exosome molecules were screened in LC. Further analysis showed that the up-regulation of LYPD3 in these 904 exosome molecules was associated with poor prognosis in LC. Pan-cancer analyses revealed that the expression of LYPD3 varied in many cancers, particularly in LC. Clinical correlation analysis indicated that LYPD3 was associated with stage and T classification in LC. We observed that LYPD3 co-expression genes were associated with cell cycle, DNA replication, proteasome, and regulation of the actin cytoskeleton by GSEA. Moreover, LYPD3 was associated with immune modulators. Immunophenoscores (IPS) and IPS-CTLA4 were significantly different between the high LYPD3 group and low LYPD3 group. Additionally, the median half maximal inhibitory concentration (IC50) of bexarotene, cyclopamine, etoposide, and paclitaxel in LYPD3 high group was significantly lower than that in LYPD3 low group. Conclusions: LYPD3 is involved in many BPs of LC, such as regulating immune cell infiltration and affecting prognosis. Therefore, LYPD3 may have potential value as a biomarker for prognosis and immunotherapy in LC.

Combined effects of binary mixtures of 17ß-estradiol and testosterone in western mosquitofish (Gambusia affinis) after full life-cycle exposure.

Estrogens and androgens are typical steroid hormones and often occur together in contaminated aquatic environments, but their mixed effects in aquatic organisms have been less well reported. In this study, the endocrine disrupting effects of binary mixtures of 17ß-estradiol (E2) and testosterone (T) in western mosquitofish (Gambusia affinis) were assessed by analyzing the sex ratio, secondary sex characteristics, gonadal histology, and transcriptional expression of target genes related to the hypothalamic-pituitary-gonadal (HPG) axis in G. affinis (from embryos) continuously exposed to E2 (50 ng/L), T (T1: 50 ng/L; T2: 200 ng/L), and mixtures of both (E2 + T1: 50 + 50 ng/L; E2 + T2: 50 + 200 ng/L) for 119 d. The results showed that exposure to E2 + T1 and E2 + T2 reduced the length ratio of ray 4/6 ratio in male G. affinis, suggesting feminized phenomenon in male G. affinis. Furthermore, 16.7-38.5 % of female G. affinis showed masculinized anal fins and hemal spines when exposed to T alone and in combination with E2. Importantly, the transcriptional levels of certain target genes related to the HPG axis were significantly altered in G. affinis following exposure to E2 and T alone and in combinations. Moreover, exposure to E2 and T in combinations can lead to combined effects (such as synergistic and antagonistic effects) on the transcriptional levels of some genes. These results collectively suggest that exposure to environmentally relevant concentrations of E2 and T alone and in mixtures can impact the endocrine system of G. affinis, and may pose potential risks in aquatic systems.

Age- and Gender-Specific Reference Intervals for the Fasting Serum Lipid Levels in a Pediatric Population Aged 0-＜15 Years in Nanjing, China.

AIMS: The lipid reference intervals (RIs) that are currently used for children in China are not based on studies of the local population and normally do not consider age or gender differences. This study aimed to establish age- and sex-specific RIs for the fasting serum lipid levels in the pediatric population aged 0 - 15 years in Nanjing, China. METHODS: 5,866 children aged 3 days to ＜15 years were recruited to establish serum lipid RIs, and the triglyceride (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) levels were analyzed using the Roche cobas702 automatic biochemical analyzer. Low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (nHDL-C) levels were calculated (LDL-C=TC-HDL-C-TG/5, and nHDL-C=TC-HDL-C). Smoothed percentile curves for the boys and girls were generated using the LMS method. Age- and sex-specific RIs were the determined according to the methods recommended by the Clinical and Laboratory Standards Institute EP28-A3c guidelines. RESULTS: This study showed that the serum lipid levels varied considerably throughout childhood and adolescence, with sex differences, especially in infants aged less than 2 years and puberty. Based on the Harris-Boyd method, sex partitions were required for ages ＜6 months in the TC indicator and for ages ≤ 28 days in LDL-C and nHDL-C. Age partitions were also required for all serum lipid parameters. CONCLUSIONS: We established age- and sex-specific RIs for TG, TC, HDL-C, LDL-C, and nHDL-C parameters in children aged 0 days to ＜15 years in Nanjing, China. These data are thus considered to be useful for the screening of dyslipidemia in children and adolescents.

Interaction of 17α-ethinylestradiol and methyltestosterone in western mosquitofish (Gambusia affinis) across two generations.

The interactions between estrogen and androgen in aquatic animals remain largely unknown. In this study, two generations (F0 and F1) of western mosquitofish (Gambusia affinis) were continuously exposed to 17α-ethinylestradiol (EE2, 10 ng/L), methyltestosterone (MT, 10 ng/L (MTL); 50 ng/L (MTH)), and mixtures (EE2+MTL and EE2+MTH). Various endpoints, including sex ratio (phenotypic and genetic), secondary sex characteristics, gonadal histology, and transcriptional profile of genes, were examined. The results showed that G. affinis exposed to MTH and EE2+MTH had a > 89.7 % of phenotypic males in F1 generation, with 34.5 and 50.0 % of these males originated from genetic females, respectively. Moreover, females from F0 and F1 generations exposed to MTH and EE2+MTH exhibited masculinized anal fins and skeletons. The combined effect of MT and EE2 on most endpoints was dependent on MT. Furthermore, significant transcriptional alterations in certain target genes were observed in both the F0 and F1 generations by EE2 and MT alone and by mixtures, showing some degree of interactions. These findings that the effects of EE2+MTH were primarily on the phenotypic sex of G. affinis in offspring generation suggest that G. affinis under chronic exposure to the binary mixture contaminated water could have sex-biased populations.

CIP2A induces PKM2 tetramer formation and oxidative phosphorylation in non-small cell lung cancer.

Tumor cells are usually considered defective in mitochondrial respiration, but human non-small cell lung cancer (NSCLC) tumor tissues are shown to have enhanced glucose oxidation relative to adjacent benign lung. Here, we reported that oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) inhibited glycolysis and promoted oxidative metabolism in NSCLC cells. CIP2A bound to pyruvate kinase M2 (PKM2) and induced the formation of PKM2 tetramer, with serine 287 as a novel phosphorylation site essential for PKM2 dimer-tetramer switching. CIP2A redirected PKM2 to mitochondrion, leading to upregulation of Bcl2 via phosphorylating Bcl2 at threonine 69. Clinically, CIP2A level in tumor tissues was positively correlated with the level of phosphorylated PKM2 S287. CIP2A-targeting compounds synergized with glycolysis inhibitor in suppressing cell proliferation in vitro and in vivo. These results indicated that CIP2A facilitates oxidative phosphorylation by promoting tetrameric PKM2 formation, and targeting CIP2A and glycolysis exhibits therapeutic potentials in NSCLC.

Causes of recurrence of paediatric inguinal hernia after single-port laparoscopic closure.

PURPOSE: This paper explores the causes of paediatric inguinal hernia (PIH) recurrence after single-port laparoscopic percutaneous extraperitoneal closure (SPLPEC). METHOD: From January 2015 to December 2020, the clinical data of 3480 children with PIHs who underwent SPLPEC were retrospectively reviewed, including 644 children who underwent SPLPEC with a homemade single-hook hernia needle from January 2015 to December 2016 and 2836 children who underwent the SPLPEC with a double-hook hernia needle and hydrodissection from January 2017 to December 2020. There were 39 recurrences (including communicating hydrocele) during the 2-5 years of follow-up. The findings of redo-laparoscopy were recorded and correlated with the revised video of the first operation to analyse the causes of recurrence. RESULT: Thirty-three males and 6 females experienced recurrence, and 8 patients had a unilateral communicating hydrocele. The median time to recurrence was 7.1 months (0-38). There were 20 cases (3.11%) in the single-hook group and 19 cases (0.67%) in the double-hook group. Based on laparoscopic findings, recurrence most probably resulted from multiple factors, including uneven tension of the ligation (10 cases), missing part of the peritoneum (14 cases), loose ligation (8 cases), broken knot (5 cases), and knot reaction (2 cases). All children who underwent repeat SPLPEC were cured by double ligations or reinforcement with medial umbilical ligament. CONCLUSION: The main cause of recurrence is improper ligation. Tension-free and complete PIH ligation are critical to the success of surgery, which requires avoiding the peritoneum skip area and the subcutaneous and muscular tissues. Redo-laparoscopic surgery was suitable for the treatment of recurrent inguinal hernia (RIH). For giant hernias, direct ligation of the internal ring incorporating the medial umbilical ligament (DIRIM) may be needed.

Selenium Concentration Is Positively Associated with Triglyceride-Glucose Index and Triglyceride Glucose-Body Mass Index in Adults: Data from NHANES 2011-2018.

Compiling evidence supports that selenium plays a vital role in glucose metabolism. Triglyceride-glucose index (TyG) and triglyceride-glucose-body mass index (TyG-BMI) are commonly used in epidemiologic studies to evaluate insulin resistance and cardiovascular disease (CVD) risks. This study is aimed to investigate the association between whole blood selenium concentration and TyG and TyG-BMI. A total of 6290 participants (age ≥ 20 years) from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 were included. Multiple linear regression models were used to examine the association between blood selenium quartiles and TyG and TyG-BMI. Subgroup analysis stratified by diabetes status was also performed. The adjusted model showed a positive association between TyG and blood selenium concentration (ß [95%CI] = 0.099 [0.063, 0.134], p < 0.001) and TyG-BMI (ß [95%CI] = 3.185 [2.102, 4.268], p < 0.001). The association persisted after stratification by diabetes status (p < 0.001). Participants were stratified into four quartiles based on selenium concentration (Q1: 1.08-2.24 µmol/L, Q2: 2.25-2.42 µmol/L, Q3: 2.43-2.62 µmol/L, Q4: 2.63-8.08). Compared with the Q1 group, TyG in the Q3 and Q4 groups was significantly higher (ß = 0.075 [95%CI 0.039 to 0.112] and ß = 0.140 [95%CI 0.103 to 0.176], respectively). Additionally, TyG-BMI in the Q2, Q3, and Q4 groups was higher than that in the Q1 group (ß = 1.189 [95%CI 0.065 to 2.314], ß = 2.325 [95%CI 1.204 to 3.446], and ß = 4.322 [95%CI 3.210 to 5.435], respectively). Blood level of selenium was positively associated with TyG and TyG-BMI, indicating that excessive blood selenium may be associated with impaired insulin sensitivity and increased risk of cardiovascular disease.

[The objectification of ashi point diagnosis and treatment].

Ashi points play a significant role in the clinical localization and qualitative diagnosis of acupuncture, as well as in selecting acupoints along the meridians and applying tonifying or reducing techniques. This paper introduces the theoretical basis and existing technical methods of objectification of ashi point diagnosis and treatment. It proposes that using sensory quantitative testing to determine the temperature and tenderness thresholds of ashi points could help to identify the pathological characteristics of "cold" "heat" "deficiency" or "excess" of ashi points. In addition, the possibility of objectification of ashi point diagnosis-treatment plan is explored from three perspectives, precision of selection of ashi point therapy, objectification of effect evaluation of ashi point analgesia, and differentiation of the studies on ashi point analgesic mechanism, aiming to provide new research ideas for the modernization of traditional Chinese acupuncture.

T Cell Invigoration is Associated with the Clinical Response to Anti-PD-1-Based Immunotherapy in Non-Small Cell Lung Cancer.

Purpose: Immune checkpoint inhibitors (ICIs) have been developed for clinical application and proven effective for non-small cell lung cancer (NSCLC). Blockade of the programmed cell death 1 (PD-1) protein can partially reinvigorate circulating exhausted-phenotype CD8+ T cells (Tex cells) in preclinical models, however the clinical implication in anti-PD-1-based immunotherapy in NSCLC is unknown. Methods: Serum specimens were obtained before and during treatment from 145 patients with NSCLC patients who received anti-PD-1 treatment and their prognoses were followed-up. Indicators such as cell subpopulations, T cell invigoration were detected by clinical laboratory testing. Survival curves were estimated by the Kaplan-Meier method, Cox regression analysis was used to identify factors associated with prognoses of NSCLC patients. Results: The expressions of Ki-67 in PD-1+/CD8+ T cells in most NSCLC patients (97 of 145 cases) increased after treatment. The responding Ki-67+/CD8+ T cell population was mainly CD45RAlo CD27hi, containing cells with high expression of CTLA-4, PD-1, and 2B4 and low expression of NKG2-D (P < 0.0001). The maximum fold change of Ki-67+/PD-1+/CD8+T cells in treatment cycles and the tumor burden determined by imaging may be associated with survival. Patients with higher Ki-67 expression on PD-1+CD8+ T-cells (pretreatment) had statistically significant increased progression-free survival (PFS). A Ki-67 expression to tumor burden ratio greater than 0.6 at the 1st cycle of anti-PD-1 immunotherapy was associated with improvement of PFS and overall survival (P < 0.05). Conclusion: Activation of circulating Tex cells before or during therapy related to tumor burden may be associated with clinical efficacy of anti-PD-1 immune therapy in NSCLC.

Genome-Wide Analysis of WUSCHEL-Related Homeobox Gene Family in Sacred Lotus (Nelumbo nucifera).

WUSCHEL-related homeobox (WOX) is a plant-specific transcription factor (TF), which plays an essential role in the regulation of plant growth, development, and abiotic stress responses. However, little information is available on the specific roles of WOX TFs in sacred lotus (Nelumbo nucifera), which is a perennial aquatic plant with important edible, ornamental, and medicinal values. We identified 15 WOX TFs distributing on six chromosomes in the genome of N. nucifera. A total of 72 WOX genes from five species were divided into three clades and nine subclades based on the phylogenetic tree. NnWOXs in the same subclades had similar gene structures and conserved motifs. Cis-acting element analysis of the promoter regions of NnWOXs found many elements enriched in hormone induction, stress responses, and light responses, indicating their roles in growth and development. The Ka/Ks analysis showed that the WOX gene family had been intensely purified and selected in N. nucifera. The expression pattern analysis suggested that NnWOXs were involved in organ development and differentiation of N. nucifera. Furthermore, the protein-protein interaction analysis showed that NnWOXs might participate in the growth, development, and metabolic regulation of N. nucifera. Taken together, these findings laid a foundation for further analysis of NnWOX functions.

Nine-year follow-up of lenalidomide plus rituximab as initial treatment for mantle cell lymphoma.

Although chemoimmunotherapy is the current standard of care for initial treatment of mantle cell lymphoma (MCL), newer data suggest that there may be a role for a chemotherapy-free approach. We report the 9-year follow-up results of a multicenter, phase 2 study of lenalidomide plus rituximab (LR) as the initial treatment of MCL. The LR doublet is used as induction and maintenance until progression, with optional discontinuation after 3 years. We previously reported an overall response rate of 92% in evaluable patients, with 64% achieving a complete response. At a median follow-up of 103 months, 17 of 36 evaluable patients (47%) remain in remission. The 9-year progression-free survival and overall survival were 51% and 66%, respectively. During maintenance, hematologic adverse events included asymptomatic grade 3 or 4 cytopenia (42% neutropenia, 5% thrombocytopenia, and 3% anemia) and mostly grade 1 to 2 infections managed in the outpatient setting (50% upper respiratory infections, 21% urinary tract infections, 16% sinusitis, 16% cellulitis, and 13% pneumonia, with 5% requiring hospitalization). More patients developed grade 1 and 2 neuropathy during maintenance therapy (29%) than during induction therapy (8%). Twenty-one percent of patients developed secondary malignancies, including 5% with invasive malignancies, whereas the remainder were noninvasive skin cancers treated with local skin-directed therapy. Two patients permanently discontinued therapy because of concerns of immunosuppression during the COVID-19 pandemic. With long-term follow-up, LR continues to demonstrate prolonged, durable responses with manageable safety as initial induction therapy. This trial was registered at www.clinicaltrials.gov as #NCT01472562.

Global prevalence of poor sleep quality in military personnel and veterans: A systematic review and meta-analysis of epidemiological studies.

Poor sleep quality is prevalent among members of the military but rates of poor sleep quality vary between studies. This study examined the global prevalence of poor sleep quality in military personnel and veterans as well as possible moderators of prevalence differences between studies. PubMed, EMBASE, Web of Science, and PsycINFO were systematically searched from their inception dates to September 1, 2022. Studies were included if they were conducted on military personnel and/or veterans and prevalence estimates of poor sleep quality could be generated from assessments with standardized tools. A random-effects model was used to calculate the pooled prevalence and its 95% confidence intervals (CIs). Fifty-nine studies (N = 28,100) were included for analysis with sample sizes ranging from 14 to 8481. Two studies were rated as "high quality" (3.39%), while 57 were rated as "moderate quality" (96.61%). The overall pooled prevalence of poor sleep quality in military personnel and veterans was 69.00% (95% CI: 62.33-75.30%); pooled rates were 57.79% (95% CI: 49.88-65.50%) and 82.88% (95% CI: 74.08-90.21%) for active duty personnel and veterans, respectively. Subgroup analyses indicated study region, study design, sampling method, Pittsburg Sleep Quality Index cut-off values, and service type moderated prevalence of poor sleep quality. Meta-regression analyses indicated sample size, mean age, depression and posttraumatic stress disorder (PTSD) were associated with prevalence differences between studies. Poor sleep quality was more common in both active duty military personnel and veterans who were older and those who reported PTSD or depression. Regular monitoring of sleep quality and sleep hygiene should be promoted in this population. More relevant studies in middle- and low-income countries should also be conducted.

Cytokine Storm in Acute Viral Respiratory Injury: Role of Qing-Fei-Pai-Du Decoction in Inhibiting the Infiltration of Neutrophils and Macrophages through TAK1/IKK/NF-[Formula: see text]B Pathway.

COVID-19 has posed unprecedented challenges to global public health since its outbreak. The Qing-Fei-Pai-Du decoction (QFPDD), a Chinese herbal formula, is widely used in China to treat COVID-19. It exerts an impressive therapeutic effect by inhibiting the progression from mild to critical disease in the clinic. However, the underlying mechanisms remain obscure. Both SARS-CoV-2 and influenza viruses elicit similar pathological processes. Their severe manifestations, such as acute respiratory distress syndrome (ARDS), multiple organ failure (MOF), and viral sepsis, are correlated with the cytokine storm. During flu infection, QFPDD reduced the lung indexes and downregulated the expressions of MCP-1, TNF-[Formula: see text], IL-6, and IL-1[Formula: see text] in broncho-alveolar lavage fluid (BALF), lungs, or serum samples. The infiltration of neutrophils and inflammatory monocytes in lungs was decreased dramatically, and lung injury was ameliorated in QFPDD-treated flu mice. In addition, QFPDD also inhibited the polarization of M1 macrophages and downregulated the expressions of IL-6, TNF-[Formula: see text], MIP-2, MCP-1, and IP-10, while also upregulating the IL-10 expression. The phosphorylated TAK1, IKK[Formula: see text]/[Formula: see text], and I[Formula: see text]B[Formula: see text] and the subsequent translocation of phosphorylated p65 into the nuclei were decreased by QFPDD. These findings indicated that QFPDD reduces the intensity of the cytokine storm by inhibiting the NF-[Formula: see text]B signaling pathway during severe viral infections, thereby providing theoretical and experimental support for its clinical application in respiratory viral infections.

Expanding the mutational spectrum of ZTTK syndrome: A de novo variant with global developmental delay and malnutrition in a Chinese patient.

BACKGROUND: Zhu-Tokita-Takenouchi-Kim (ZTTK, OMIM 617140) syndrome is a severe multisystem developmental disorder characterized by intellectual disability, developmental delay, cortical malformations, epilepsy, visual problems, musculoskeletal abnormalities, and congenital malformations. ZTTK syndrome is caused by a heterozygous pathogenic variant of the SON gene (NM_138927) at chromosome 21q22.1. The purpose of this study was to investigate the pathogenesis of a 6-month-old Chinese child who exhibited global developmental delay, muscle weakness, malnutrition, weight loss, and strabismus, brain abnormality, immunological system abnormalities. METHODS: The little girl was tested for medical exome sequencing (MES) and mtDNA sequencing in trio. And, the mutation was validated by Sanger sequencing. RESULTS: A novel de novo frameshift variant, c.1845_1870del26 (p.G616Sfs*61), in the SON gene was found in the proband. CONCLUSION: We described a 6-month-old Chinese child with global developmental delay caused by pathogenic de novo mutation c.1845_1870del26 (p.G616Sfs*61) in the SON. Apart from a founder mutation, we reviewed the phenotypic abnormalities and genotypes in 79 individuals. The data showed that global developmental delay is accompanied by other system disorders. Our findings expanded the mutational spectrum of ZTTK syndrome and provide genetic counseling of baby with global developmental delay.

Arginase from Priestia megaterium and the Effects of CMCS Conjugation on Its Enzymological Properties.

Arginase has shown promising potential in treating cancers by arginine deprivation therapy; however, low enzymatic activity and stability of arginase are impeding its development. This study was aimed to improve the enzymological properties of a marine bacterial arginase by carboxymethyl chitosan (CMCS) conjugation. An arginase producing marine bacterium Priestia megaterium strain P6 was isolated and identified. The novel arginase PMA from the strain was heterologously expressed, purified, and then conjugated to CMCS by ionic gelation with calcium chloride as the crosslinking agent. Enzymological properties of both PMA and CMCS-PMA conjugate were determined. The optimum temperature for PMA and CMCS-PMA at pH 7 were 60 °C and 55 °C, respectively. The optimum pH for PMA and CMCS-PMA at 37 °C were pH 10 and 9, respectively. CMCS-PMA showed higher thermostability than PMA over 55-70 °C and higher pH stability over pH 4-11 with the highest pH stability at pH 7. At 37 °C and pH of 7, i.e., around the human blood temperature and pH, CMCS-PMA was higher than the free PMA in enzymatic activity and stability by 24% and 21%, respectively. CMCS conjugation not only changed the optimum temperature, optimum pH, and enzymatic activity of PMA, but also improved its pH stability and temperature stability, and thus made it more favorable for medical application.

Diploid and tetraploid genomes of Acorus and the evolution of monocots.

Monocots are a major taxon within flowering plants, have unique morphological traits, and show an extraordinary diversity in lifestyle. To improve our understanding of monocot origin and evolution, we generate chromosome-level reference genomes of the diploid Acorus gramineus and the tetraploid Ac. calamus, the only two accepted species from the family Acoraceae, which form a sister lineage to all other monocots. Comparing the genomes of Ac. gramineus and Ac. calamus, we suggest that Ac. gramineus is not a potential diploid progenitor of Ac. calamus, and Ac. calamus is an allotetraploid with two subgenomes A, and B, presenting asymmetric evolution and B subgenome dominance. Both the diploid genome of Ac. gramineus and the subgenomes A and B of Ac. calamus show clear evidence of whole-genome duplication (WGD), but Acoraceae does not seem to share an older WGD that is shared by most other monocots. We reconstruct an ancestral monocot karyotype and gene toolkit, and discuss scenarios that explain the complex history of the Acorus genome. Our analyses show that the ancestors of monocots exhibit mosaic genomic features, likely important for that appeared in early monocot evolution, providing fundamental insights into the origin, evolution, and diversification of monocots.

Combination of Transcriptomics and Proteomics Reveals Differentially Expressed Genes and Proteins in the Skin of EDAR Gene-Targeted and Wildtype Cashmere Goats.

Cashmere goats play a pivotal role in the animal hair industry and are economically valuable. Cashmere is produced through the periodic growth of secondary hair follicles. To improve their yield of cashmere, the regulatory mechanisms of cashmere follicle growth and development need to be analysed. Therefore, in this study, EDAR gene-targeted cashmere goats were used as an animal model to observe the phenotypic characteristics of abnormal hair growth and development at the top of the head. Transcriptomic and proteomic techniques were used to screen for differentially expressed genes and proteins. In total, 732 differentially expressed genes were identified, including 395 upregulated and 337 downregulated genes. In addition, 140 differentially expressed proteins were identified, including 69 upregulated and 71 downregulated proteins. These results provide a research target for elucidating the mechanism through which EDAR regulates hair follicle growth in cashmere goats. It also enriches the available data on the regulatory network involved in hair follicle growth.

Air pollution, EGFR mutation, and cancer initiation.

Swanton et al.1 find that PM2.5 exposure is associated with EGFR/KRAS-driven lung cancer incidence. PM2.5 increases EGFR pre-mutated alveolar type II cell progenitor function and tumorigenic activity through interstitial macrophage-secreted IL-1ß, providing potential prevention approaches to inhibit cancer initiation.