SMS2, a Novel Allele of OsINV3, Regulates Grain Size in Rice.

Grain size has an important effect on rice yield. Although several key genes that regulate seed size have been reported in rice, their molecular mechanisms remain unclear. In this study, a rice small grain size 2 (sms2) mutant was identified, and MutMap resequencing analysis results showed that a 2 bp insertion in the second exon of the LOC_Os02g01590 gene resulted in a grain length and width lower than those of the wild-type Teqing (TQ). We found that SMS2 encoded vacuolar acid invertase, a novel allele of OsINV3, which regulates grain size. GO and KEGG enrichment analyses showed that SMS2 was involved in endoplasmic reticulum protein synthesis, cysteine and methionine metabolism, and propionic acid metabolism, thereby regulating grain size. An analysis of sugar content in young panicles showed that SMS2 reduced sucrose, fructose, and starch contents, thus regulating grain size. A haplotype analysis showed that Hap2 of SMS2 had a longer grain and was widely present in indica rice varieties. Our results provide a new theoretical basis for the molecular and physiological mechanisms by which SMS2 regulates grain size.

Breakdown of Temporal Coherence in Photon Condensates.

The temporal coherence of an ideal Bose gas increases as the system approaches the Bose-Einstein condensation threshold from below, with coherence time diverging at the critical point. However, counterexamples have been observed for condensates of photons formed in an externally pumped, dye-filled microcavity, wherein the coherence time decreases rapidly for increasing particle number above threshold. This Letter establishes intermode correlations as the central explanation for the experimentally observed dramatic decrease in the coherence time beyond critical pump power.

Clinical values of different specimen preparation methods for the diagnosis of lung cancer by EBUS-TBNA.

BACKGROUND AND OBJECTIVE: EBUS-TBNA has emerged as an important minimally invasive procedure for the diagnosis and staging of lung cancer. Our objective was to evaluate the effect of different specimen preparation from aspirates on the diagnosis of lung cancer. METHODS: 181 consecutive patients with known or suspected lung cancer accompanied by hilar / mediastinal lymphadenopathy underwent EBUS-TBNA from January 2019 to December 2022. Specimens obtained by EBUS-TBNA were processed by three methods: Traditional smear cytology of aspirates (TSC), liquid-based cytology of aspirates (LBC) and histopathology of core biopsies. RESULTS: EBUS-TBNA was performed in 181 patients on 213 lymph nodes, the total positive rate of the combination of three specimen preparation methods was 80.7%. The diagnostic positive rate of histopathology was 72.3%, TSC was 68.1%, and LBC was 65.3%, no significant differences was observed (p = 0.29); however, statistically significant difference was noted between the combination of three preparation methods and any single specimen preparation methods (p = 0.002). The diagnostic sensitivity of histopathology combined with TSC and histopathology combined with LBC were 96.5 and 94.8%, the specificity was 95.0% and 97.5%, the PPV was 98.8% and 99.4%, the NPV was 86.4% and 81.2%, the diagnostic accuracy was 96.2% and 95.3%, respectively; The sensitivity and accuracy of above methods were higher than that of single specimen preparation, but lower than that of combination of three preparation methods. CONCLUSION: When EBUS-TBNA is used for the diagnosis and staging of lung cancer, histopathology combined with TSC can achieve enough diagnostic efficiency and better cost-effectiveness.

NSUN2 relies on ALYREF to regulate Nrf2-mediated oxidative stress and alleviate Dox-induced liver injury.

BACKGROUND: Doxorubicin (Dox) is associated with various liver injuries, limiting its clinical utility. This study investigates whether NSUN2 participates in Dox-induced liver injury and the associated molecular mechanism. METHODS: In vivo and in vitro liver cell injury models were constructed based on Dox therapy. The protein levels of NSUN2 and oxidative stress indicators Nrf2, HO-1, and NQO1 were evaluated by Western blot. The RNA binding potential was detected by RNA methylation immunoprecipitation (RIP). Additionally, the effect of NSUN2 on Nrf2 mRNA synthesis and localization was evaluated using an RNA fluorescence probe. RESULTS: NSUN2 was downregulated, and liver tissue suffered significant pathological damage in the Dox group. The levels of ALT and AST significantly increased. NSUN2 interference exacerbated Dox-induced liver cell damage, which was reversed by NSUN2 overexpression. RIP demonstrated that NSUN2 recognized and bound to Nrf2 mRNA. Western blot analysis showed the protein level of Nrf2 in the NSUN2-WT group was significantly higher than that of the control group, whereas there was no significant change in Nrf2 level in the mutant NSUN2 group. Luciferase analysis demonstrated that NSUN2 could recognize and activate the Nrf2 5'UTR region of LO2 cells. In addition, RIP analysis revealed that ALYREF could recognize and bind to Nrf2 mRNA and that ALYREF controls the regulatory effect of NSUN2 on Nrf2. CONCLUSION: NSUN2 regulates Dox-induced liver cell damage by increasing Nrf2 mRNA m5C methylation to inhibit inhibiting antioxidant stress. The regulatory effect of NSUN2 on Nrf2 depends on ALYREF.

Pharmacokinetics, Bioavailability, and Tissue Distribution of the Kirsten Rat Sarcoma Inhibitor Adagrasib in Rats Using UPLC-MS/MS.

Purpose: Adagrasib is a selective and reversible inhibitor of KRAS G12C, which significantly delays the progression of solid tumors. However, the absorption, distribution, metabolism, and excretion of adagrasib in vivo are unclear. This study explores the absorption and distribution of adagrasib in vivo. Methods: An ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method was established for the determination of adagrasib in the rat plasma and tissue. Sprague-Dawley rats were intravenous administrated (5 mg/kg) and oral administrated (30 mg/kg) with adagrasib, and the plasma concentration of adagrasib was determined. After single oral administration of adagrasib (30 mg/kg), the heart, liver, spleen, lung, kidney, intestine, and pancreas were excised. The organs were homogenized with saline solution, and the concentration of adagrasib in tissues was determined. Results: The intra- and inter-day accuracy were from 84.90% to 113.47%, and the precision was within ±15%. The matrix effect and recovery were within ±15%. The maximum plasma concentration (Cmax) of adagrasib was 677.45 ± 58.72 ng/mL. The elimination half-life time (t1/2) was 3.50 ± 0.21 h after oral administration and 2.08 ± 0.54 h after intravenous administration. The oral bioavailability was 50.72%. The highest concentrations of adagrasib in liver was 5047.80 ± 676.48 ng/g at 2 h after administration, and it was still detectable at 24 hours after administration. Conclusion: Adagrasib was slowly absorbed and cleared rapidly, and it was also widely distributed in vivo. This study provides a potential reference for adagrasib in clinical studies.

Fecal microbial gene transfer contributes to the high-grain diet-induced augmentation of aminoglycoside resistance in dairy cattle.

A high-grain (HG) diet can rapidly lower the rumen pH and thus modify the gastrointestinal microbiome in dairy cattle. Although the prevalence of antibiotic resistance is strongly linked with the gut microbiome, the influences of HG diet on animals' gut resistome remain largely unexplored. Here, we examined the impact and mechanism of an HG diet on the fecal resistome in dairy cattle by metagenomically characterizing the gut microbiome. Eight lactating Holstein cattle were randomly allocated into two groups and fed either a conventional (CON) or HG diet for 3 weeks. The fecal microbiome and resistome were significantly altered in dairy cattle from HG, demonstrating an adaptive response that peaks at day 14 after the dietary transition. Importantly, we determined that feeding an HG diet specifically elevated the prevalence of resistance to aminoglycosides (0.11 vs 0.24 RPKG, P < 0.05). This diet-induced resistance increase is interrelated with the disproportional propagation of microbes in Lachnospiraceae, indicating a potential reservoir of aminoglycosides resistance. We further showed that the prevalence of acquired resistance genes was also modified by introducing a different diet, likely due to the augmented frequency of lateral gene transfer (LGT) in microbes (CON vs HG: 254 vs 287 taxa) such as Lachnospiraceae. Consequently, we present that diet transition is associated with fecal resistome modification in dairy cattle and an HG diet specifically enriched aminoglycosides resistance that is likely by stimulating microbial LGT.IMPORTANCEThe increasing prevalence of antimicrobial resistance is one of the most severe threats to public health, and developing novel mitigation strategies deserves our top priority. High-grain (HG) diet is commonly applied in dairy cattle to enhance animals' performance to produce more high-quality milk. We present that despite such benefits, the application of an HG diet is correlated with an elevated prevalence of resistance to aminoglycosides, and this is a combined effect of the expansion of antibiotic-resistant bacteria and increased frequency of lateral gene transfer in the fecal microbiome of dairy cattle. Our results provided new knowledge in a typically ignored area by showing an unexpected enrichment of antibiotic resistance under an HG diet. Importantly, our findings laid the foundation for designing potential dietary intervention strategies to lower the prevalence of antibiotic resistance in dairy production.

Pulmonary cryptococcosis coexisting with lung adenocarcinoma: A case report and review of the literature.

Pulmonary cryptococcosis (PC) is an invasive pulmonary fungal disease caused by Cryptococcus neoformans or Cryptococcus gattii. It often presents as a single nodule or mass on radiology, which is easily misdiagnosed as lung cancer or metastases. However, cases of PC coexisting with lung cancer are rare and when this scenario is encountered in clinical practice, it is easy to be misdiagnosed as metastatic lung cancer. The present study reported the case of a 65-year-old immunocompetent patient with PC coexisting with lung adenocarcinoma. Percutaneous lung biopsy was performed on the nodule in the anterior segment of the left upper lobe and the nodule in the posterior basal segment of the left lower lobe, which were diagnosed as primary adenocarcinoma and cryptococcus, respectively. Lung cancer was treated by surgery and PC was treated successfully by antifungal treatment. During the 5-year follow-up, contrast-enhanced CT showed no recurrence of either disease. This case reminds us of the possibility of dualism in the diagnosis of multiple pulmonary nodules based on CT examination, such as the coexistence of lung carcinoma and PC. In addition, early diagnosis and treatment contribute to good prognosis.

Advances of hafnium based nanomaterials for cancer theranostics.

Hafnium-based nanomaterials (Hf-NMs) have attracted the interest of numerous biomedical researchers by their unique properties. Recent years have witnessed significant advancements in the field of Hafnium-based nanomaterials, particularly in the context of cancer diagnosis and treatment. However, research in this area, especially concerning the clinical application of Hafnium-based nanomaterials, has not been thoroughly reviewed. This review will cover: 1) Classification and synthesis of Hafnium-based nanomaterials including Hafnium oxide nanomaterials, Hafnium Metal-Organic Frameworks/nanoscale coordination polymers (MOFs/NCPs); 2) Hafnium-based nanomaterials act as contrast enhancement agent for cancer imaging, and hafnium-based nanomaterials used for diagnosis in cancer liquid biopsy; 3) hafnium-based nanomaterials for cancer therapy, including hafnium-based nanomaterials for radiotherapy, hafnium-based nanomaterials for photodynamic therapy, hafnium-based nanomaterials for various combined therapy; and 4) Translation, toxicity, and safety for Hf-NMs in human and preclinical animal models. More attention will be given to the clinical translation of Hf-NMs in cancer.

Protein intrinsically disordered region prediction by combining neural architecture search and multi-objective genetic algorithm.

BACKGROUND: Intrinsically disordered regions (IDRs) are widely distributed in proteins and related to many important biological functions. Accurately identifying IDRs is of great significance for protein structure and function analysis. Because the long disordered regions (LDRs) and short disordered regions (SDRs) share different characteristics, the existing predictors fail to achieve better and more stable performance on datasets with different ratios between LDRs and SDRs. There are two main reasons. First, the existing predictors construct network structures based on their own experiences such as convolutional neural network (CNN) which is used to extract the feature of neighboring residues in protein, and long short-term memory (LSTM) is used to extract the long-distance dependencies feature of protein residues. But these networks cannot capture the hidden feature associated with the length-dependent between residues. Second, many algorithms based on deep learning have been proposed but the complementarity of the existing predictors is not fully explored and used. RESULTS: In this study, the neural architecture search (NAS) algorithm was employed to automatically construct the network structures so as to capture the hidden features in protein sequences. In order to stably predict both the LDRs and SDRs, the model constructed by NAS was combined with length-dependent models for capturing the unique features of SDRs or LDRs and general models for capturing the common features between LDRs and SDRs. A new predictor called IDP-Fusion was proposed. CONCLUSIONS: Experimental results showed that IDP-Fusion can achieve more stable performance than the other existing predictors on independent test sets with different ratios between SDRs and LDRs.

Clinical characteristics and genetic expansion of 46,XY disorders of sex development children in a Chinese prospective study.

Diagnosis and management strategy of disorders of sex development (DSD) are difficult and various due to heterogeneous phenotype and genotype. Under widespread use of genomic sequencing technologies, multiple genes and mechanisms have been identified and proposed as genetic causes of 46,XY DSD. In this study, 178 46,XY DSD patients were enrolled and underwent gene sequencing (either whole-exome sequencing or targeted panel gene sequencing). Detailed clinical phenotype and genotype information were summarized which showed that the most common clinical manifestations were micropenis (56.74%, 101/178), cryptorchidism (34.27%, 61/178), and hypospadias (17.42%, 31/178). Androgen synthesis/action disorders and idiopathic hypogonadotropic hypogonadism were the most frequent clinical diagnoses, accounting, respectively, for 40.90 and 21.59%. From all next-generation sequencing results, 103 candidate variants distributed across 32 genes were identified in 88 patients. The overall molecular detection rate was 49.44% (88/178), including 35.96% (64/178) pathogenic/likely pathogenic variants and 13.48% (24/178) variants of uncertain significance. Of all, 19.42% (20/103) variants were first reported in 46,XY DSD patients. Mutation c.680G>A (p.R227Q) on SRD5A2 (steroid 5-alpha-reductase 2) (36.67%, 11/30) was a hotspot mutation in the Chinese population. Novel candidate genes related to DSD (GHR (growth hormone receptor) and PHIP (pleckstrin homology domain-interacting protein)) were identified. Overall, this was a large cohort of 46,XY DSD patients with a common clinical classification and phenotype spectrum of Chinese patients. Targeted gene panel sequencing covered most of the genes contributing to DSD, whereas whole-exome sequencing detected more candidate genes.

Conjugative transfer of streptococcal prophages harboring antibiotic resistance and virulence genes.

Prophages play important roles in the transduction of various functional traits, including virulence factors, but remain debatable in harboring and transmitting antimicrobial resistance genes (ARGs). Herein we characterize a prevalent family of prophages in Streptococcus, designated SMphages, which harbor twenty-five ARGs that collectively confer resistance to ten antimicrobial classes, including vanG-type vancomycin resistance locus and oxazolidinone resistance gene optrA. SMphages integrate into four chromosome attachment sites by utilizing three types of integration modules and undergo excision in response to phage induction. Moreover, we characterize four subtypes of Alp-related surface proteins within SMphages, the lethal effects of which are extensively validated in cell and animal models. SMphages transfer via high-frequency conjugation that is facilitated by integrative and conjugative elements from either donors or recipients. Our findings explain the widespread of SMphages and the rapid dissemination of ARGs observed in members of the Streptococcus genus.

Genotypic and phenotypic features of dyslipidemia in a sample of pediatric patients in China.

BACKGROUND: Dyslipidemia, especially hypercholesterolemia is of significant clinical interest. Precise diagnosis is not paid enough attention to about the management of pediatric patients with hypercholesterolemia, which is especially apparent in China. Given this, we designed this study to confirm the specific molecular defects associated with hypercholesterolemia using whole-exome sequencing (WES) to be helpful for precise diagnosis and treatment. METHODS: Pediatric patients were enrolled using specific criteria and their clinical information were recorded for later evaluation in conjunction with the WES completed for each of these patients. RESULTS: Our criteria allowed for the initial enrollment of 35 patients, 30 of whom (aged 1.02-12.99 years) underwent successful genetic sequencing and clinical investment. Positive results were obtained in 63.33% (19/30) of these patients. We identified 25 variants in 30 pediatric patients with persistent hypercholesterolemia, seven of them were novel and variants in LDLR and ABCG5/ABCG8 ranks first and second, respectively. Further analysis revealed that the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB) and lipoprotein (a) were higher in patients with positive genetic results. CONCLUSION: Our study enriched the genetic and phenotypic spectra for hypercholesterolemia in young patients. Genetic testing is important for the prognostics and treatment of pediatric patients. Heterozygous ABCG5/8 variants may be underestimated in pediatric patients with hypercholesterolemia.

Applications of CRISPR screening to lung cancer treatment.

Lung cancer is an extremely aggressive and highly prevalent disease worldwide, and it is one of the leading causes of cancer death. Deciphering intrinsic genetic mechanism, finding new targets, and overcoming drug resistance are the key to lung cancer treatment. High-throughput CRISPR screening has been extensively used to obtain the genes related to cancers including lung cancer. This review describes CRISPR/Cas9 or CRISPR/dCas9-based technologies for high-throughput screening. We summarize the applications of CRISPR screening technology in exploring the mechanism of lung cancer development in vivo or in vitro, overcoming drug resistance, improving the effect of immunotherapy, and discovering new therapeutic targets. This review highlights the potential of CRISPR screening in combination with tumor barcoding and high-throughput sequencing (Tuba-seq) to precisely quantify the impact of alterations in many tumor suppressor genes on lung cancer.

Novel clinical biomarkers in blood and pleural effusion for diagnosing patients with tuberculosis distinguishing from malignant tumor.

Pleural effusion (PE) is a common manifestation of tuberculosis (TB) and malignant tumors but tuberculous PE (TPE) is difficult to distinguish from malignant PE (MPE), especially by noninvasive detection indicators. This study aimed to find effective detection indices in blood and PE for differentiating TB from a malignant tumor. A total of 815 patients who were diagnosed with TB or cancer in Hubei Shiyan Taihe Hospital from 2014 to 2017 were collected. Amongst them, 717 were found to have PE by thoracoscopy. Clinical characteristics, patients' blood parameters and PE indicator information were summarized for analysis. Patients with MPE had higher percentages to be bloody and negative of Rivalta test in PE than those with TPE. For clinical indicators, comparison of the specific parameters in blood showed that 18 indicators were higher in the TPE group than in the MPE group. By contrast, 12 indicators were higher in the MPE group than in the TPE group (P < .01). In addition, in PE tests, 3 parameters were higher in the TPE group, whereas other 4 parameters were higher in the MPE group (P < .01). Then, for clinical diagnosing practice, ROC analysis and principal component analysis were applied. The top 6 relevant indicators with area under curve over 0.70 were screened out as follows: hydrothorax adenosine dehydrogenase (pADA, 0.90), hydrothorax high-sensitivity C reactive protein (0.79), percentage of blood monocyte (sMONp, 0.75), blood high-sensitivity C reactive protein (sHsCRP, 0.73), erythrocyte sedimentation rate (0.71) and blood D-dimer (0.70). Moreover, logistic regression model revealed that a specific combination of 3 biomarkers, namely, pADA, sMONp and sHsCRP, could enhance the distinguishment of TB from malignant tumor with PE (area under curve = 0.944, 95% confidence interval = 0.925-0.964). The diagnostic function of the top single marker pADA in patients from different groups was analyzed and it was found to maintain high specificity and sensitivity. The 6 indicators, namely, pADA, hydrothorax high-sensitivity C reactive protein, sMONp, sHsCRP, sESR and blood D-dimer, showed significant diagnostic value for clinicians. Further, the combination of pADA, sMONp and sHsCRP has high accuracy for differential diagnosis for the first time. Most interestingly, the single marker pADA maintained high specificity and sensitivity in patients with different statuses and thus has great value for rapid and accurate diagnosis of suspected cases.

A Case of Peripheral Precocious Puberty May Be Caused by a Diet Containing Phytosterols in a 20-Month-Old Boy.

INTRODUCTION: Precocious puberty in boys generally remains an etiology. In addition to the causes of endogenous hormone changes, endocrine-disrupting chemicals of exogenous substances may interfere with children's pubertal development. CASE PRESENTATION: A 20-month-old boy presented with peripheral precocious puberty may be due to a phytosterol-containing diet. The patient came to see a doctor because of acne, hairiness, increased penis size, and coarse voice. Genital examination revealed a Tanner stage of 2 for pubic hair and a stretched penile length of 5 cm, which disagreed with the prepubertal testicular volume (2 mL bilaterally). At the same time, he was found to have pigmentation on both nipples and areola. The concentrations of estradiol and testosterone increased significantly. Since the age of 6 months, the patient had taken food added with a large amount of chicken essence seasoning (a flavoring in Chinese cooking), with an average of 15 g of this seasoning a day. A kind of phytosterol (C29H48O) was detected in chicken essence seasoning by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). After avoidance of the chicken essence seasoning, the patient's sex hormone levels decreased, all clinical symptoms returned to normal, and no further development of secondary sexual characteristics was detected. CONCLUSION: This phytosterol-containing diet may be responsible for the sexual development of this patient. However, the mechanism of how phytosterols affect the process of development in children needs to be further explored.

Identification and functional analysis of novel SOX11 variants in Chinese patients with Coffin-Siris syndrome 9.

SOX11 is a transcription factor belonging to the sex determining region Y-related high-mobility group box family that plays a vital role in early embryogenesis and neurogenesis. De novo variants in SOX11 have been initially reported to cause a rare neurodevelopmental disorder, mainly referred to Coffin-siris syndrome 9 (CSS9, OMIM# 615866) which is characterized with growth deficiency, intellectual disability (ID), microcephaly, coarse facies, and hypoplastic nails of the fifth fingers and/or toes. A recent large-scale cohort study suggests that SOX11 variation would result in a clinically and molecularly distinct disease from CSS. Here, we describe three unrelated Chinese cases with variable phenotype, mainly involving developmental delay, ID, short statute, microcephaly, facial deformities (i.e., prominent forehead, arched eye brow, flat nasal bridge, broad nose and short philtrum), and cryptorchidism. Whole-exome sequencing (WES) revealed three novel heterozygous variants in the SOX11 gene, including two missense variants of c.337T>C (p.Y113H) and c.425C>G (p.A142G), and one nonsense variant of c.820A>T (p. K142*). Luciferase reporting assay shows that the two missense variants impair the transcriptional activity of the SOX11 target gene GDF5. Additionally, WES uncovered a 4,300 kb deletion involving the region of 1q24.2-q25.1 (hg19,chr1:169,433,149-173,827,682) in patient 1, which also contributes to the condition of the patient. In summary, this is the first report of Chinese cases with de novo variants of SOX11. Our study partially supports the previous observation that the phenotype caused by SOX11 variants somewhat differs from classical CSS.

Comprehensive Relationship Analysis of the Long Noncoding RNAs (lncRNAs) and the Target mRNAs in Response to the Infection of Edwardsiella anguillarum in European eel (Anguilla anguilla) Inoculated with Freund's Adjuvant.

Freund's complete adjuvant (FCA) and incomplete adjuvant (FIA), generally applied in subunit fishery vaccine, have not been explored on the molecular mechanism of the non-specific immune enhancement. As long noncoding RNAs (lncRNAs) play vital regulating roles in various biological activities, in this study, we examined the genome-wide expression of transcripts in the liver of European eel (Anguilla anguilla, Aa) inoculated with FCA and FIA (FCIA) to elucidate the regulators of lncRNAs in the process of Edwardsiella anguillarum (Ea) infection and Aa anti-Ea infection using strand-specific RNA-seq. After eels were challenged by Ea at 28 days post the first inoculation (dpi), compared to the control uninfected eels (Li group), the control infected eels (Con_Li group) showed severe bleeding, hepatocyte atrophy, and thrombi formed in the hepatic vessels of the liver, although eels inoculated with FCIA (FCIA_Li group) also formed slight thrombi in the hepatic vessels. Compared to the FCIA_Li group, there was about 10 times colony-forming unit (cfu) in the Con_Li group per 100 µg liver tissue, and the relative percent survival (RPS) of eels was 50% in FCIA_Li vs Con_Li. Using high-throughput transcriptomics, differential expressed genes (DEGs) and transcripts were identified and the results were verified using fluorescence real-time polymerase chain reaction (qRT-PCR). Interactions between the differential expressed lncRNAs (DE-lncRNAs) and the target DEGs were explored using Cytoscape according to their co-expression and co-location relationship. We found 13,499 lncRNAs (10,176 annotated and 3423 novel lncRNAs) between 3 comparisons of Con_Li vs Li, FCIA_Li vs Li, and FCIA_Li vs Con_Li, of which 111, 110, and 129 DE-lncRNAs were ascertained. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs targeted by DE-lncRNAs revealed these DEGs mainly involved in single-organism cellular process in BP, membrane in CC and binding in MF, and KEGG pathways showed that the target DEGs in co-expression and co-location enriched in cell adhesion molecules. Finally, 118 DE-lncRNAs target 1161 DEGs were involved in an interaction network of 8474 co-expression and 333 co-location-related links, of which 16 DE-lncRNAs play vital roles in anti-Ea infection. Taken together, the interaction networks revealed that DE-lncRNAs underlies the process of Ea infection and Aa anti-Ea infection.

Chemotherapy with a TP Regimen in Combination with Stereotactic Radiotherapy Could Significantly Optimize the Clinical Efficacy of NSCLC Treatment.

The changes in lifestyle and bad living habits have a significant impact on the health of people, resulting in an increasing prevalence of lung cancer. The most prevalent kind of lung cancer is nonsmall cell lung cancer (NSCLC), which accounts for around 80% of all cases. Chemotherapy is a common treatment method in clinical practice with certain negative effects. The primary goal of this study is to investigate the clinical efficacy of stereotactic radiotherapy in combination with a docetaxel plus cisplatin (TP) chemotherapy regimen in patients with nonsmall cell lung cancer (NSCLC) and their impact on the levels of cytokeratin fragment 21-1 (CYFRA21-1) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in NSCLC patients. Eighty patients who were admitted to the hospital between November 2016 and November 2019 were recruited and assigned to receive either chemotherapy with a TP regimen (the control group) or chemotherapy with a TP regimen plus stereotactic radiotherapy (the observation group). The WHO response evaluation criteria (REC) for solid tumors were adopted to analyze short-term efficacy, and the Karnofsky performance status (KPS) score was used to assess the quality of life by recording adverse reactions in the blood system, kidney, gastrointestinal tract, bladder, nervous system, and heart. The levels of CYFRA21-1 and MALAT1 in serum before and after the treatment were determined and compared. As a result, the observation group showed higher total efficacy and MALAT1 level, better quality of life, and lower CYFRA21-1 level than the control group (P < 0.05). Stereotactic radiotherapy plus TP regimen chemotherapy resulted in significantly better progression-free survival, overall survival, survival rate, and long-term prognosis versus chemotherapy alone. Moreover, combined therapy was associated with a lower incidence of hemoglobin reduction, gastrointestinal reaction, and renal impairment versus TP regimen chemotherapy (P < 0.05). Therefore, we concluded that stereotactic radiotherapy plus chemotherapy with a TP regimen significantly optimizes the clinical efficacy of the NSCLC treatment.

OsUGE3-mediated cell wall polysaccharides accumulation improves biomass production, mechanical strength, and salt tolerance.

Cell walls constitute the majority of plant biomass and are essential for plant resistance to environmental stresses. It is promising to improve both plant biomass production and stress resistance simultaneously by genetic modification of cell walls. Here, we report the functions of a UDP-galactose/glucose epimerase 3 (OsUGE3) in rice growth and salt tolerance by characterizing its overexpressing plants (OsUGE3-OX) and loss-of-function mutants (uge3). The OsUGE3-OX plants showed improvements in biomass production and mechanical strength, whereas uge3 mutants displayed growth defects. The OsUGE3 exhibits UDP-galactose/glucose epimerase activity that provides substrates for polysaccharides polymerization, consistent with the increased biosynthesis of cellulose and hemicelluloses and strengthened walls in OsUGE3-OX plants. Notably, the OsUGE3 is ubiquitously expressed and induced by salt treatment. The uge3 mutants were hypersensitive to salt and osmotic stresses, whereas the OsUGE3-OX plants showed improved tolerance to salt and osmotic stresses. Moreover, OsUGE3 overexpression improves the homeostasis of Na+ and K+ and induces a higher accumulation of hemicelluloses and soluble sugars during salt stress. Our results suggest that OsUGE3 improves biomass production, mechanical strength, and salt stress tolerance by reinforcement of cell walls with polysaccharides and it could be targeted for genetic modification to improve rice growth under salt stress.

A novel CEP57 variant associated with mosaic variegated aneuploidy syndrome in a Chinese female presenting with short stature, microcephaly, brachydactyly, and small teeth.

BACKGROUND: Mosaic variegated aneuploidy (MVA) syndrome is a rare, autosomal recessive genetic disease. Here, we report an ultra-rare case of MVA syndrome associated with a CEP57 variant. METHODS: We retrospectively analyzed the clinical data of a 9-year-old female patient and surveyed her family members. Whole-exome sequencing and karyotype analysis were performed; suspected mutations were verified using Sanger sequencing. RESULTS: The patient presented with intrauterine growth restriction, short stature, microcephaly, facial dysmorphism, brachydactyly, and small teeth, and she showed unsatisfactory response to GH replacement therapy. Laboratory tests revealed high insulin-like growth factor-1 levels. Karyotype analysis of the peripheral blood showed mosaic variegated aneuploidies. Whole-exome and Sanger sequencing revealed a novel homozygous nonsense variant, NM_014679.4: c.312 T > G, in CEP57 that leads to translation termination (p.Tyr104*). The parents were heterozygous carriers of the identified variant. CONCLUSION: This study presents an ultra-rare case of CEP57-driven MVA syndrome, identifying a novel homozygous nonsense variant of CEP57 (p.Tyr104*). Our findings enrich the CEP57 mutational spectrum and emphasize the importance of genetic testing in patients with microcephaly and short stature. Furthermore, we conclude that growth hormone treatment is ineffective in such patients.