The role of serum lipid in predicting coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease: a cohort study.

OBJECTIVE: To assess the predictive value of the serum lipid profile for initial intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). METHODS: This retrospective cohort study enrolled patients with KD and divided them into IVIG-responsive and IVIG-resistant groups. They were also stratified based on the presence of CALs (CALs and non-CALs groups). Clinical, echocardiographic and biochemical values were evaluated. A subgroup analysis was performed on complete and incomplete KD. Predictors of initial IVIG resistance and CALs were determined by multivariate logistic regression analysis. RESULTS: A total of 649 KD patients were enrolled: 151 had CALs and 76 had initial IVIG resistance. Low-density lipoprotein cholesterol (LDL-C) was significantly lower in the IVIG-resistant group than in the IVIG-responsive group. LDL-C and apolipoprotein (Apo) B were significantly lower in the CALs group compared with the non-CALs group. Multivariate logistic regression failed to identify the serum lipid profile (LDL-C, Apo A or Apo B) as an independent risk factor for initial IVIG resistance or CALs in KD patients. CONCLUSION: KD patients might have dyslipidaemia in the acute phase, but the serum lipid profile might not be suitable as a single predictor for initial IVIG resistance or CALs.

ALKBH5-mediated m6A demethylation of pri-miR-199a-5p exacerbates myocardial ischemia/reperfusion injury by regulating TRAF3-mediated pyroptosis.

Myocardial ischemia‒reperfusion injury (MI/RI) is closely related to pyroptosis. alkB homolog 5 (ALKBH5) is abnormally expressed in the MI/RI models. However, the detailed molecular mechanism of ALKBH5 in MI/RI has not been elucidated. In this study, rats and H9C2 cells served as experimental subjects and received MI/R induction and H/R induction, respectively. The abundance of the targeted molecules was evaluated using RT-qPCR, Western blotting, immunohistochemistry, immunofluorescence, and enzyme-linked immunosorbent assay. The heart functions of the rats were evaluated using echocardiography, and heart injury was evaluated. Cell viability and pyroptosis were determined using cell counting Kit-8 and flow cytometry, respectively. Total m6A modification was measured using a commercial kit, and pri-miR-199a-5p m6A modification was detected by Me-RNA immunoprecipitation (RIP) assay. The interactions among the molecules were validated using RIP and luciferase experiments. ALKBH5 was abnormally highly expressed in H/R-induced H9C2 cells and MI/RI rats. ALKBH5 silencing improved injury and inhibited pyroptosis. ALKBH5 reduced pri-miR-199a-5p m6A methylation to block miR-199a-5p maturation and inhibit its expression. TNF receptor-associated Factor 3 (TRAF3) is a downstream gene of miR-199a-5p. Furthermore, in H/R-induced H9C2 cells, the miR-199a-5p inhibitor-mediated promotion of pyroptosis was reversed by ALKBH5 silencing, and the TRAF3 overexpression-mediated promotion of pyroptosis was offset by miR-199a-5p upregulation. ALKBH5 silencing inhibited pri-miR-199a-5p expression and enhanced pri-miR-199a-5p m6A modification to promote miR-199a-5p maturation and enhance its expression, thereby suppressing pyroptosis to alleviate MI/RI through decreasing TRAF3 expression.

Coexistence of pulmonary arterial hypertension and straight back syndrome in a patient with a novel BMPR2 variant affecting cytoplasmic tail domain.

BACKGROUND: Pathologic variants in the bone morphogenetic protein receptor-2 (BMPR2) gene cause a pulmonary arterial hypertension phenotype in an autosomal-dominant pattern with incomplete penetrance. Straight back syndrome is one of the causes of pseudo-heart diseases. To date, no cases of idiopathic or heritable pulmonary arterial hypertension with straight back syndrome have been reported. CASE PRESENTATION: A 30-year-old female was diagnosed with pulmonary arterial hypertension by right heart catheterization. Computed tomography revealed a decreased anteroposterior thoracic space with heart compression, indicating a straight back syndrome. Genetic analysis by whole exome sequencing identified a novel c.2423_2424delGT (p.G808Gfs*4) germline frameshift variant within BMPR2 affecting the cytoplasmic tail domain. CONCLUSIONS: This is the first report of different straight back characteristics in heritable pulmonary arterial hypertension with a novel germline BMPR2 variant. This finding may provide a new perspective on the variable penetrance of the pulmonary arterial hypertension phenotype.

Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Transcriptome-Wide N6-Methyladenosine Alternations in Pulmonary Arteries of Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats and Novel Therapeutic Targets.

N6-methyladenosine (m6A) is a post-transcriptional epigenetic change with transcriptional stability and functionality regulated by specific m6A-modifying enzymes. However, the significance of genes modified by m6A and enzymes specific to m6A regulation in the context of pulmonary arterial hypertension (PAH) remains largely unexplored. MeRIP-seq and RNA-seq were applied to explore variances in m6A and RNA expression within the pulmonary artery tissues of control and monocrotaline-induced PAH rats. Functional enrichments were analyzed using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. To screen candidate m6A-related genes, the STRING and Metascape databases were used to construct a protein-protein interaction network followed by a real-time PCR validation of their expression. The expression level of an m6A regulator was further investigated using immunohistochemical staining, immunofluorescence, and Western blot techniques. Additionally, proliferation assays were conducted on primary rat pulmonary artery smooth muscle cells (PASMCs). We identified forty-two differentially expressed genes that exhibited either hypermethylated or hypomethylated m6A. These genes are predominantly related to the extracellular matrix structure, MAPK, and PI3K/AKT pathways. A candidate gene, centromere protein F (CENPF), was detected with increased expression in the PAH group. Additionally, we first identified an m6A reader, leucine rich pentatricopeptide repeat containing (LRPPRC), which was downregulated in the PAH rat model. The in vitro downregulation of Lrpprc mediated by siRNA resulted in the enhanced proliferation and elevated expression of Cenpf mRNA in primary rat PASMCs. Our study revealed a modified transcriptome-wide m6A landscape and associated regulatory mechanisms in the pulmonary arteries of PAH rats, potentially offering a novel target for therapeutic strategies in the future.

The diagnostic value of GICA used for intraoperative lymph node FNA-Tg measurement to evaluate thyroid cancer metastases.

Objective: It is crucial to diagnose lymph node (LN) metastases (LNM) before or during thyroid carcinoma surgery. Measurement of thyroglobulin (Tg) in the fine needle aspirate washout (FNA-Tg) is useful to assist in the diagnosis of LNM for papillary thyroid carcinoma (PTC). This study aimed to assess the diagnostic performance of a new technique based on a colloidal gold-based immunochromatographic assay (GICA) for intraoperative FNA-Tg in diagnosing LNM. Clinical trial information: This study is registered with chictr.org.cn, ID: ChiCTR2200063561 (registered 11 September, 2022). Methods: This prospective study enrolled 51 PTC patients who underwent cervical LN dissection. A total of 150 LNs dissected from the central and lateral compartments were evaluated by FNA-Tg-GICA at three different time points and compared with frozen sections and the conventional Tg measurement method electrochemiluminescence immunoassay (ECLIA). Receiver operating characteristic curve (ROC) and area under the curve (AUC), cutoff value to discriminate benign and malignant LNs, sensitivity, specificity, and accuracy were provided. Results: The cutoff value of FNA-Tg to predict LNM was 110.83 ng/mL for ECLIA and 13.19 ng/mL, 38.69 ng/mL, and 77.17 ng/mL for GICA at 3, 10, and 15 min, respectively. There was no significant difference between the AUCs of GICA at different time points compared to using ECLIA and frozen sections. Besides, the diagnostic performance of GICA and ECLIA showed no significant difference in evaluating LNM from central and lateral compartments or between the TgAb-positive subgroup and TgAb-negative subgroup. Conclusion: GICA is a promising method for intraoperative FNA-Tg measurement and has high value in predicting LNM. It may be a novel alternative or supplementary method to frozen section or ECLIA.

Intrahepatic cholestasis of pregnancy: insights into pathogenesis and advances in omics studies.

Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-specific liver disease. It is characterized by pruritus, abnormal liver function and elevated total bile acid (TBA) levels, increasing the risk of maternal and fetal adverse outcomes. Its etiology remains poorly elucidated. Over the years, various omics techniques, including metabolomics, microbiome, genomics, etc., have emerged with the advancement of bioinformatics, providing a new direction for exploring the pathogenesis, diagnosis and treatment of ICP. In this review, we first summarize the role of bile acids and related components in the pathogenesis of ICP and then further illustrate the results of omics studies.

Clinical efficacy of acupoint catgut embedding in the treatment of allergic rhinitis: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of acupoint catgut embedding in the treatment of allergic rhinitis by Meta-analysis. METHODS: Pubmed, Web of Science, Embase, Elsevier, CNKI, and VIP databases were searched for clinical randomized controlled trials (RCTS) on acupoint catgut embedding for allergic rhinitis from the establishment of the database to December 30, 2022. RevMan5.4 and Stata12 software were used for Meta-analysis. RESULTS: A total of 17 articles were included, involving 1231 patients. Meta-analysis showed that the total effective rate of acupoint catgut embedding for allergic rhinitis was higher than that of the control group [Pooled Odds Ratio = 5.19, 95%CI (3.14, 8.58), P < 0.00001]. Sensitivity analysis indicated that the total effective rate of acupoint catgut embedding in the treatment of allergic rhinitis was stable. The efficacy of the acupoint embedding group was better than that of the western medicine group [OR = 5.78, 95%CI (3.25, 10.27), P < 0.00001]. Acupoint embedding decreased serum IL-33 levels [MD = -70.79, 95%CI (-102.60, -38.98), P < 0.0001] and improved TNNSS score [MD = -0.25, 95%CI (-0.40, -0.11), P = 0.0005] was statistically different from the control group. CONCLUSION: Acupoint catgut embedding in the treatment of allergic rhinitis has a certain effect, but the accuracy of this conclusion still needs to be verified by higher-quality RCT in the later stage.

An Ultrathin Composite Polymer Electrolyte Dual-Reinforced by a Polymer of Intrinsic Microporosity (PIM-1) and Poly(tetrafluoroethylene) (PTFE) Porous Membrane.

The performances of solid-state polymer electrolytes are urgently required to be further improved for high energy density lithium metal batteries. Herein, a highly reinforced ultrathin composite polymer electrolyte (PLPP) is successfully fabricated in a large scale by densely filling the well-dispersed mixture of polyethylene oxide (PEO), Li-salt (LiTFSI) and a polymer of intrinsic microporosity (PIM-1) into porous poly(tetrafluoroethylene) (PTFE) matrix. Based on the macro-plus-micro synergistic enhancement of the PTFE with excellent mechanical properties and the soluble PIM-1 with suitable functional groups, the PLPP electrolyte exhibits excellent properties including mechanical stress, thermal stability, lithium-ion transference number, voltage window and ionic conductivity, which are all superior to the typical PEO/LiTFSI electrolytes. As a result, the Li/PLPP/Li symmetric cell can stably cycle for > 2000 h, and the LiFePO4 /PLPP/Li full cell exhibits excellent rate performance (>10 C) and high cycling stability with an initial capacity of 158.8 mAh g-1 and a capacity retention of 78.8% after 300 cycles. In addition, the excellent mechanical properties as well as the wide voltage window reasonably result in the stable operation of full cells with either high-loading cathode up to 28.1 mg cm-2 or high voltage cathode with high energy density.

Shared Genetic Architecture between Parkinson's Disease and Brain Structural Phenotypes.

BACKGROUND: Patients with Parkinson's disease (PD) have consistently demonstrated brain structure abnormalities, indicating the presence of shared etiological and pathological processes between PD and brain structures; however, the genetic relationship remains poorly understood. OBJECTIVE: The aim of this study was to investigate the extent of shared genetic architecture between PD and brain structural phenotypes (BSPs) and to identify shared genomic loci. METHODS: We used the summary statistics from genome-wide association studies to conduct MiXeR and conditional/conjunctional false discovery rate analyses to investigate the shared genetic signatures between PD and BSPs. Subsequent expression quantitative trait loci mapping in the human brain and enrichment analyses were also performed. RESULTS: MiXeR analysis identified genetic overlap between PD and various BSPs, including total cortical surface area, average cortical thickness, and specific brain volumetric structures. Further analysis using conditional false discovery rate (FDR) identified 21 novel PD risk loci on associations with BSPs at conditional FDR < 0.01, and the conjunctional FDR analysis demonstrated that PD shared several genomic loci with certain BSPs at conjunctional FDR < 0.05. Among the shared loci, 16 credible mapped genes showed high expression in the brain tissues and were primarily associated with immune function-related biological processes. CONCLUSIONS: We confirmed the polygenic overlap with mixed directions of allelic effects between PD and BSPs and identified multiple shared genomic loci and risk genes, which are likely related to immune-related biological processes. These findings provide insight into the complex genetic architecture associated with PD. © 2023 International Parkinson and Movement Disorder Society.

Release and impact of China's "Second List of Rare Diseases".

On September 18, 2023, the National Health Commission of China officially announced the "Second List of Rare Diseases". This list of 86 rare diseases, drafted in accordance with the "Working Procedures for Drafting the List of Rare Diseases", marks the second release of a rare disease list since the initial list was issued in May 2018. Following the release of the first batch, the Chinese Government introduced various policies to enhance the diagnosis and treatment of rare diseases, to promote the research on, development of, production of, and availability of rare disease medications in China, and to improve medication access for patients with rare diseases. Consequently, this has elevated the level of rare disease diagnosis and treatment, ensuring greater accessibility to treatment for affected individuals. The expansion of the rare disease list through the release of the "Second List of Rare Diseases" will further enhance rare disease management, increase awareness, improve diagnosis and treatment, facilitate the development and availability of more rare disease medications, establish a comprehensive support system for patients with rare diseases, and ultimately benefit a larger number of individuals affected by rare diseases. The definition of rare diseases in China should be refined by explicitly establishing corresponding criteria based on incidence, prevalence, or the number of affected individuals. Additionally, the mechanism for removal of diseases from rare disease lists should be enhanced, and prompt adjustments should be made regarding diseases that do not align with the selection principles of the list, taking into consideration environmental changes.

The role of MOTS-c-mediated antioxidant defense in aerobic exercise alleviating diabetic myocardial injury.

Myocardial remodeling and dysfunction are commonly observed in type 2 diabetes mellitus (T2DM). Aerobic exercise can partly alleviate diabetes-induced myocardial dysfunction through its antioxidant actions. MOTS-c is a potential exercise mimic. This study aimed to investigate the effects of MOTS-c on improving diabetic heart function and its mechanism and to identify whether MOTS-c improved antioxidant defenses due to aerobic exercise. Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection. Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks. Myocardial ultrastructure was assessed using transmission electron microscopy (TEM), myocardial lipid peroxidation levels (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) levels were assessed using colorimetric methods, and molecular analyses including MOTS-c, Kelch-like ECH-associated protein 1 (Keap1), Nuclear factor E2-related factor 2 (Nrf2), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)and phospho-AMPK (p-AMPK) were examined using Western blot. The results showed that MOTS-c, with or without exercise, reduced myocardial ultrastructural damage and improved glucolipid metabolism and cardiac function in T2DM. Furthermore, MOTS-c increased antioxidant markers such as SOD, CAT, and the protein expression of myocardial MOTS-c, Keap1, Nrf2, and p-AMPK. MOTS-c with exercise treatment reduced myocardial MDA and increased p-AMPK significantly comparing to only exercise or MOTS-c alone. Our findings suggest that MOTS-c may be a helpful supplement for overcoming exercise insufficiency and improving myocardial structure and function in diabetes.

Structural Isomers: Small Change with Big Difference in Anion Storage.

Organic electrode materials are promising for batteries. However, the reported organic electrodes are often facing the challenges of low specific capacity, low voltage, poor rate capability and vague charge storage mechanisms, etc. Isomers are good platform to investigate the charge storage mechanisms and enhance the performance of batteries, which, however, have not been focused in batteries. Herein, two isomers are reported for batteries. As a result, the isomer tetrathiafulvalene (TTF) could store two monovalent anions reversibly, deriving an average discharge voltage of 1.05 V and a specific capacity of 220 mAh g-1 at a current density of 2 C. On the other hand, the other isomer tetrathianaphthalene could only reversibly store one monovalent anion and upon further oxidation, it would undergo an irreversible solid-state molecular rearrangement to TTF. The molecular rearrangement was confirmed by electrochemical performances, X-ray diffraction patterns, nuclear magnetic resonance spectra, and 1H detected heteronuclear multiple bond correlation spectra. These results suggested the small structural change could lead to a big difference in anion storage, and we hope this work will stimulate more attention to the structural design for boosting the performance of organic batteries.

The role of noncoding RNA and its diagnostic potential in intrahepatic cholestasis of pregnancy: a research update.

Intrahepatic cholestasis of pregnancy (ICP) is a common liver disorder that generally occurs during the second or third trimester of pregnancy. It rarely causes any harm to the mother; however, it can result in short- and long-term complications in the offspring. Therefore, it is crucial to diagnose and treat this condition to avoid poor pregnancy outcomes. The identification of novel markers with potential diagnostic, prognostic, and therapeutic utility in ICP has gained attention. Noncoding RNAs (ncRNAs), including microRNA, long noncoding RNA, and circular RNA, are a type of transcripts that are not translated into proteins. They possess vital biological functions, including transcriptional and translational regulation and DNA, RNA, and protein interactions. The pathogenesis of ICP is related to the aberrant expression of several circulating or placenta-related ncRNAs. In this review, we summarized all recent findings on ncRNAs and ICP and outlined the concepts that form the basis for the early diagnosis and targeted treatment of ICP.

Prognostic significance of preoperative lymphocyte to monocyte ratio in patients with signet ring gastric cancer.

BACKGROUND: The ratio of lymphocytes to monocytes (LMR) has been shown to be an effective predictor of gastric cancer prognosis. However, its predictive accuracy for signet ring gastric cancer is currently not well understood. AIM: To evaluate the prognosis predictive accuracy of preoperative LMR in signet ring gastric cancer. METHODS: A total of 212 signet ring gastric cancer patients admitted at the Xiangya Hospital of Central South University, Department of Gastrointestinal Surgery, from January 2012 to December 2016 were enrolled in the study. The prognosis predictive accuracy of preoperative LMR was explored based on the area under the receiver operating characteristic. Factors that significantly affect the survival of patients were identified using single factor analysis, and those that were independently associated with signet ring gastric cancer were identified through multivariate analysis. RESULTS: The results of the single factor analysis revealed a strong correlation between the survival of signet ring gastric cancer patients and several factors, including tumor invasion (χ2 = 49.726; P < 0.001), lymph node metastasis (χ2 = 30.269; P < 0.001), pTNM stage (χ2 = 49.322; P < 0.001), surgical approach (χ2 = 8.489; P = 0.004), age (t = -2.213; P < 0.028), carcinoembryonic antigen (CEA) (Z = -3.265; P = 0.001), platelet-to-lymphocyte ratio (Z = -2.196; P = 0.028), LMR (Z = -2.226; P = 0.026), ALB (t = 3.284; P = 0.001), prognostic nutritional index (t = -3.789; P < 0.001) and FIB (Z = -3.065; P = 0.002). Furthermore, the multivariate analysis further demonstrated that age (HR: 0.563, 95%CI: 0.363-0.873), tumor invasion depth (HR: 0.226, 95%CI: 0.098-0.520), pTNM stage (HR: 0.444, 95%CI: 0.255-0.771), preoperative CEA level (HR: 0.597, 95%CI: 0.386-8.790), and preoperative LMR level (HR: 1.776, 95%CI: 1.150-2.741) were independent factors influencing the prognosis of signet ring gastric cancer. CONCLUSION: In signet ring gastric cancer patients, a low preoperative LMR level predicts poor prognosis. The death risk ratio of the low LMR group compared to the high LMR group is 1.776.

A porous polyacrylonitrile (PAN)/covalent organic framework (COF) fibrous membrane photocatalyst for highly efficient and ultra-stable hydrogen evolution.

Photocatalytic water splitting has been regarded as one of the most promising technologies to generate hydrogen as an ideal energy carrier in the future. However, most of the experience for such process are derived from the researches based on the suspension powder photocatalysts under a stirring condition and a practical scaling application is urgently calling for the high-efficient panel reactors based on the membrane photocatalysts. Herein, we develop a new series of flexible and ultrastable membrane photocatalysts through a controllable growth of covalent organic framework (COF) photocatalysts on the polyacrylonitrile (PAN) electrospun fiber membrane. Multiple characterization techniques verify the successful anchoring of the COF-photocatalysts on the PAN fibers, forming a three-dimensional porous PAN/COF membrane photocatalyst with excellent light absorption ability, high specific surface area, and good hydrophily. As a result, the optimized PAN/COF membrane photocatalyst exhibits excellent hydrogen evolution rate up to 1.25 mmol g-1h-1 under visible-light irradiation without stirring, which is even higher than that of the corresponding suspension COF-powder photocatalyst with stirring. In particular, the PAN/COF membrane photocatalyst demonstrates a much more superior hydrogen evolution stability and also a much better recyclability. This study gives some experience for the practical scaling application of solar-driven water splitting.

LncRNA-encoded peptides: unveiling their significance in cardiovascular physiology and pathology-current research insights.

Long non-coding RNAs (lncRNAs), which are RNA transcripts exceeding 200 nucleotides were believed to lack any protein-coding capacity. But advancements in -omics technology have revealed that some lncRNAs have small open reading frames (sORFs) that can be translated by ribosomes to encode peptides, some of which have important biological functions. These encoded peptides subserve important biological functions by interacting with their targets to modulate transcriptional or signalling axes, thereby enhancing or suppressing cardiovascular disease (CVD) occurrence and progression. In this review, we summarize what is known about the research strategy of lncRNA-encoded peptides, mainly comprising predictive websites/tools and experimental methods that have been widely used for prediction, identification, and validation. More importantly, we have compiled a list of lncRNA- encoded peptides, with a focus on those that play significant roles in cardiovascular physiology and pathology, including ENSRNOT (RNO)-sORF6/RNO-sORF7/RNO-sORF8, dwarf open reading frame (DOWRF), myoregulin (NLN), etc. Additionally, we have outlined the functions and mechanisms of these peptides in cardiovascular physiology and pathology, such as cardiomyocyte hypertrophy, myocardial contraction, myocardial infarction, and vascular remodelling. Finally, an overview of the existing challenges and potential future developments in the realm of lncRNA-encoded peptides was provided, with consideration given to prospective avenues for further research. Given that many lncRNA-encoded peptides have not been functionally annotated yet, their application in CVD diagnosis and treatment still requires further research.

Multidimensional engineering of Escherichia coli for efficient synthesis of L-tryptophan.

Development of microbial cell factory for L-tryptophan (L-trp) production has received widespread attention but still requires extensive efforts due to weak metabolic flux distribution and low yield. Here, the riboswitch-based high-throughput screening (HTS) platform was established to construct a powerful L-trp-producing chassis cell. To facilitate L-trp biosynthesis, gene expression was regulated by promoter and N-terminal coding sequences (NCS) engineering. Modules of degradation, transport and by-product synthesis related to L-trp production were also fine-tuned. Next, a novel transcription factor YihL was excavated to negatively regulate L-trp biosynthesis. Self-regulated promoter-mediated dynamic regulation of branch pathways was performed and cofactor supply was improved for further L-trp biosynthesis. Finally, without extra addition, the yield of strain Trp30 reached 42.5 g/L and 0.178 g/g glucose after 48 h of cultivation in 5-L bioreactor. Overall, strategies described here worked up a promising method combining HTS and multidimensional regulation for developing cell factories for products in interest.

Genome-scale targeted mutagenesis in Brassica napus using a pooled CRISPR library.

The recently constructed mutant libraries of diploid crops by the CRISPR-Cas9 system have provided abundant resources for functional genomics and crop breeding. However, because of the genome complexity, it is a big challenge to accomplish large-scale targeted mutagenesis in polyploid plants. Here, we demonstrate the feasibility of using a pooled CRISPR library to achieve genome-scale targeted editing in an allotetraploid crop of Brassica napus A total of 18,414 sgRNAs were designed to target 10,480 genes of interest, and afterward, 1104 regenerated transgenic plants harboring 1088 sgRNAs were obtained. Editing interrogation results revealed that 93 of the 178 genes were identified as mutated, thus representing an editing efficiency of 52.2%. Furthermore, we have discovered that Cas9-mediated DNA cleavages tend to occur at all the target sites guided by the same individual sgRNA, a novel finding in polyploid plants. Finally, we show the strong capability of reverse genetic screening for various traits with the postgenotyped plants. Several genes, which might dominate the fatty acid profile and seed oil content and have yet to be reported, were unveiled from the forward genetic studies. Our research provides valuable resources for functional genomics, elite crop breeding, and a good reference for high-throughput targeted mutagenesis in other polyploid plants.