Efficacy and safety of ongericimab given by prefilled syringe or autoinjector in primary hypercholesterolemia and mixed hyperlipidemia.

BACKGROUND AND AIMS: Limited evidence exist regarding the association between ongericimab, a novel recombinant humanized anti-PCSK9 monoclonal antibody, and primary hypercholesterolemia and mixed dyslipidemia. This study aimed to evaluate the efficacy and safety of ongericimab administered by prefilled syringe (PFS) or autoinjector (AI) in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia on stable optimized lipid-lowering therapy. METHODS AND RESULTS: A total of 255 patients on stable optimized lipid-lowering therapy were randomized in a 2:1:2:1 ratio to receive PFS for the subcutaneous injection of ongericimab 150 mg every 2 weeks (Q2W) or a matching placebo, or AI for the subcutaneous injection of ongericimab 150 mg Q2W or a matching placebo. The primary efficacy endpoint was the percent change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Safety was also evaluated. At week 12, the least squares mean percent changes were -72.7% (3.9%) for PFS and -71.1% (3.8%) for AI (all P < 0.001) compared to respective matching placebo groups. Beneficial effects were also seen for all secondary lipid parameters, notably with robust reduction in Lp (a). Treatment-emergent adverse events (TEAEs) and serious AEs with ongericimab were reported in 46.2% and 2.4% of patients, compared to 44.2% and 3.5% with placebo. CONCLUSION: In Chinese patients with primary hypercholesterolemia and mixed dyslipidemia, a 12-week treatment regimen with ongericimab administered by PFS or AI significantly reduced LDL-C and other lipid parameters, proving to be safe and well tolerated. Patients experienced consistent effects from PFS or AI devices. CLINICAL TRIAL REGISTRATION: CTR20220027; January 11, 2022; http://www.chinadrugtrials.org.cn/index.html.

Efficacy and Safety of Ongericimab in Chinese Patients With Primary Hypercholesterolemia and Mixed Dyslipidemia.

BACKGROUND: A phase 3 trial was conducted to evaluate the efficacy and safety of ongericimab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, as an add-on treatment to optimized lipid-lowering therapy in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia. METHODS AND RESULTS: A total of 806 patients who were receiving stable and optimized lipid-lowering therapy but did not achieve their low-density lipoprotein cholesterol (LDL-C) targets were enrolled and randomly assigned in a 2:1:2:1 ratio to receive either ongericimab 150 mg or matching placebo every 2 weeks, or ongericimab 300 mg or matching placebo every 4 weeks for 52 weeks. Efficacy and safety were evaluated in 802 patients who received at least 1 dose of ongericimab or placebo. The primary end point was the percentage change in LDL-C from baseline to week 24. Our findings demonstrated that the least-squares mean difference of percentage change in LDL-C from baseline to week 24 was -67.7% (95% CI, -72.5% to -63.0%; P<0.0001) in the ongericimab 150 mg every 2 weeks group compared with the placebo every 2 weeks group, and -61.2% (95% CI, -67.1% to -55.2%; P<0.0001) in the ongericimab 300 mg every 4 weeks group compared with the placebo every 4 weeks group. These reductions were sustained up to week 52. Furthermore, treatment with ongericimab favorably altered other lipid parameters. A similar incidence of adverse events was observed in the ongericimab and placebo groups. CONCLUSIONS: Ongericimab, as an add-on treatment to optimized lipid-lowering therapy, significantly reduced LDL-C and was well-tolerated in Chinese patients with primary hyperlipidemia and mixed dyslipidemia who did not achieve their LDL-C targets. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04781114.

In vitro generation of genetic diversity for directed evolution by error-prone artificial DNA synthesis.

Generating genetic diversity lies at the heart of directed evolution which has been widely used to engineer genetic parts and gene circuits in synthetic biology. With the ever-expanding application of directed evolution, different approaches of generating genetic diversity are required to enrich the traditional toolbox. Here we show in vitro generation of genetic diversity for directed evolution by error-prone artificial DNA synthesis (epADS). This approach comprises a three-step process which incorporates base errors randomly generated during chemical synthesis of oligonucleotides under specific conditions into the target DNA. Through this method, 200 ~ 4000 folds of diversification in fluorescent strength have been achieved in genes encoding fluorescent proteins. EpADS has also been successfully used to diversify regulatory genetic parts, synthetic gene circuits and even increase microbial tolerance to carbenicillin in a short time period. EpADS would be an alternative tool for directed evolution which may have useful applications in synthetic biology.

Dihydroartemisinin (DHA) inhibits myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagy.

Idiopathic pulmonary fibrosis (IPF) is caused by persistent micro-injuries and aberrant repair processes. Myofibroblast differentiation in lung is a key event for abnormal repair. Dihydroartemisinin(DHA), a well-known anti-malarial drug, have been shown to alleviate pulmonary fibrosis, but its mechanism is not clear. Ferroptosis is involved in the pathgenesis of many diseases, including IPF. Ferritinophagy is a form of cellular autophagy which regulates intracellular iron homeostasis. The function of DHA on myofibroblasts differentiation of pulmonary and whether related with ferroptosis and ferritinophagy are unknown now. Using human fetal lung fibroblast 1(HFL1) cell line and the qRT-PCR, immunofluorescent and Western blotting techniques, we found that after TGF-ß1 treatment, the levels of ɑ-SMA expression and ROS increased; the mRNA and protein levels of FTH1 and NCOA4, the content of Fe2+ and 4-HNE increased significantly at 6h, then gradually reduced with time. After DHA treatment, FHL1 cells appeared ferroptosis; the levels of α-SMA mRNA and protein reduced and the levels of ROS and 4-HNE increased; the Fe2+ levels decreased sharply at 6h, then increased with time, and were higher than normal since 24h; the mRNA and protein levels of FTH1 and NCOA4 decreased, exhibited a downward trend. These results show that Fe2+, ROS and lipid peroxidation are involved in and ferritinophagy is inhibited during fibroblast-to-myofibroblast differentiation; The depletion of Fe2+ at early stage induced by DHA treatment triggers the ferritinophagy in HFL1 cells, leading to degradation of FTH1 and NCOA4 and following increase of Fe2+ levels. DHA may inhibit the fibroblast-to-myofibroblast differentiation through inducing ferroptosis mediated by ferritinophagy.

Non-ribosomal peptide synthetase (NRPS)-encoding products and their biosynthetic logics in Fusarium.

Fungal non-ribosomal peptide synthetase (NRPS)-encoding products play a paramount role in new drug discovery. Fusarium, one of the most common filamentous fungi, is well-known for its biosynthetic potential of NRPS-type compounds with diverse structural motifs and various biological properties. With the continuous improvement and extensive application of bioinformatic tools (e.g., anti-SMASH, NCBI, UniProt), more and more biosynthetic gene clusters (BGCs) of secondary metabolites (SMs) have been identified in Fusarium strains. However, the biosynthetic logics of these SMs have not yet been well investigated till now. With the aim to increase our knowledge of the biosynthetic logics of NPRS-encoding products in Fusarium, this review firstly provides an overview of research advances in elucidating their biosynthetic pathways.

Exopolysaccharides of Paenibacillus polymyxa: A review.

Paenibacillus polymyxa (P. polymyxa) is a member of the genus Paenibacillus, which is a rod-shaped, spore-forming gram-positive bacterium. P. polymyxa is a source of many metabolically active substances, including polypeptides, volatile organic compounds, phytohormone, hydrolytic enzymes, exopolysaccharide (EPS), etc. Due to the wide range of compounds that it produces, P. polymyxa has been extensively studied as a plant growth promoting bacterium which provides a direct benefit to plants through the improvement of N fixation from the atmosphere and enhancement of the solubilization of phosphorus and the uptake of iron in the soil, and phytohormones production. Among the metabolites from P. polymyxa, EPS exhibits many activities, for example, antioxidant, immunomodulating, anti-tumor and many others. EPS has various applications in food, agriculture, environmental protection. Particularly, in the field of sustainable agriculture, P. polymyxa EPS can be served as a biofilm to colonize microbes, and also can act as a nutrient sink on the roots of plants in the rhizosphere. Therefore, this paper would provide a comprehensive review of the advancements of diverse aspects of EPS from P. polymyxa, including the production, extraction, structure, biosynthesis, bioactivity and applications, etc. It would provide a direction for future research on P. polymyxa EPS.

Impact of exercise interventions on quality of life and depression in lung cancer patients: A systematic review and meta-analysis.

INTRODUCTION: Lung cancer is a leading cause of cancer-related mortality worldwide. Depression is also a common concern for lung cancer patients and is of concern because it negatively impacts overall well-being. This study summarizes the existing literature on the impact of exercise interventions on quality of life and depression in patients diagnosed with lung cancer. METHODS: A systematic search of electronic databases was performed to identify relevant randomized controlled trials (RCTs) investigating the effects of exercise interventions on depression and quality of life in patients with lung cancer. Two evaluators collected information from the chosen studies utilizing a standardized data extraction form. The quality of the studies was evaluated using the Cochrane risk of bias tool. RESULTS: Nine RCTs were included in the meta-analysis, with 798 participants. The pooled standardized mean difference (SMD) for the effect of exercise interventions on depression was -0.60, representing a statistically significant reduction in depression levels following exercise interventions (p < 0.001). The pooled SMD for the effect of exercise interventions on quality of life was 0.61, indicating a statistically significant association between quality of life and exercise interventions (p < 0.001). CONCLUSION: There is evidence that exercise may benefit the mental health of individuals with lung cancer, including improvements in depression symptoms and quality of life, based on the intervention studies reviewed here. Given the heterogeneity in findings, however, additional randomized controlled trials are needed to augment the existing findings. Nevertheless, there appears to be sufficient evidence for now to encourage primary care physicians to recommend exercise for patients with lung cancer, while offering guidelines on how to gradually and safely increase physical activity depending on the patient's health status.

RPL24 as a potential prognostic biomarker for cervical cancer treated by Cisplatin and concurrent chemoradiotherapy.

Cervical carcinoma (CC) is the one of most common gynecologic cancers worldwide. The ribosomal proteins (RPs) are essential for ribosome assembly and function, and it has been verified that the abnormal expression of RPs was closely associated with tumorigenesis. In this study, we found that the RP large subunit 24 (RPL24) expression level was upregulated after the CC cell lines SiHa and HeLa were treated with Cisplatin (CDDP) in vitro. Simultaneously, a nude mouse xenograft model was used to examine the effect of RPL24 on tumor growth in vivo, which showed that overexpression of RPL24 can suppress tumor growth. Furthermore, we proved that RPL24 expression increased after CC patients were treated with concurrent chemoradiotherapy (CCRT), and the higher expression of RPL24 predicted a better prognosis using clinical data from 40 CC patients, verified via the Kaplan-Meier Plotter and LOGpc. These results revealed that RPL24 can be considered a potential biomarker to predict the prognosis of CC patients and assess CCRT efficacy.

The Identification and Comparative Analysis of Non-Coding RNAs in Spores and Mycelia of Penicillium expansum.

Penicillium expansum is the most popular post-harvest pathogen and causes blue mold disease in pome fruit and leads to significant economic losses worldwide every year. However, the fundamental regulation mechanisms of growth in P. expansum are unclear. Recently, non-coding RNAs (ncRNAs) have attracted more attention due to critical roles in normalizing gene expression and maintaining cellular genotypes in organisms. However, the research related to ncRNAs in P. expansum have not been reported. Therefore, to provide an overview of ncRNAs on composition, distribution, expression changes, and potential targets in the growth process, a comparative transcriptomic analysis was performed on spores and mycelia of P. expansum in the present study. A total of 2595 novel mRNAs, 3362 long non-coding RNAs (lncRNAs), 10 novel microRNAs (miRNAs), 86 novel small interfering RNAs (siRNAs), and 11,238 circular RNAs (circRNAs) were predicted and quantified. Of these, 1482 novel mRNAs, 5987 known mRNAs, 2047 lncRNAs, 40 miRNAs, 38 novel siRNAs, and 9235 circRNAs were differentially expressed (DE) in response to the different development stages. Afterward, the involved functions and pathways of DE RNAs were revealed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database enrichment analysis. The interaction networks between mRNAs, lncRNAs, and miRNAs were also predicted based on their correlation coefficient of expression profiles. Among them, it was found that miR168 family members may play important roles in fungal growth due to their central location in the network. These findings will contribute to a better understanding on regulation machinery at the RNA level on fungal growth and provide a theoretical basis to develop novel control strategies against P. expansum.

GTS-21 alleviates murine collagen-induced arthritis through inhibition of peripheral monocyte trafficking into the synovium.

Emerging preclinical and clinical evidence reveals a critical role for the cholinergic anti-inflammatory pathway (CAP) in mediating rheumatoid arthritis (RA). Activation of CAP via vagus nerve stimulation or alpha 7 nicotinic acetylcholine receptor (α7nAChR) agonists has previously been shown to significantly reduce inflammation and improve outcomes in animal models of experimental arthritis. In this study, we sought to determine the protective mechanism of CAP on inflammatory arthritis, specifically RA, by using a selective α7nAChR agonist, GTS-21, to examine the role of CAP in the recruitment of monocytes/macrophages into the synovium in a collagen-induced arthritis (CIA) mouse model. We found that GTS-21 ameliorated systemic and local synovial inflammation, thereby reducing synovial macrophage infiltration in CIA mice. Using in vivo imaging, we further demonstrated that GTS-21 suppressed the trafficking of monocytes into inflamed joints, while our in vitro Transwell assay data confirmed that GTS-21 reduced the migratory ability of monocytes. In addition, we found that GTS-21 reduced the number of peripheral inflammatory monocytes and down-regulated expression of the chemokines CCR2 and CCR5 on monocytes and CCL2 in the paw tissue. GTS-21 also mediated the expression levels of the adhesion molecules LFA-1 and VLA-4 on monocytes and VCAM-1 in the paw tissue, thereby blocking monocyte adhesion to the extracellular matrix. Together, our data demonstrate that GTS-21 alleviates arthritis by inhibiting peripheral monocyte trafficking into the synovium. Our findings describe a novel mechanism through which the cholinergic signaling pathway can reduce synovial inflammation in RA patients.

Impacts of climate change and anthropogenic stressors on runoff variations in major river basins in China since 1950.

Runoff is one of the main components of hydrological cycle and an important index for water resources evaluation, understanding the runoff change and their causes is vital to water resource management. In the study, we analyzed the runoff change and the impacts of climate change and land use alteration on runoff variation based on natural runoff and previous studies in China. The results showed that there was a significant increasing trend in the annual runoff during 1961-2018 (p < 0.05), with change rate of 0.4 mm/a and abrupt point at 1999 across China, climate change dominated the runoff variation with a contribution of 54 %. In previous studies, the runoff of the major basins in China had a downward trend on the whole (-0.99 mm/a) except Continental River Basin (CRB) showed an increasing trend (0.25 mm/a), the abrupt points were mainly concentrated in 1991-2000, and human activity was the leading factor of runoff change with the contribution of 54 % across China. Human activity was the dominant factor of runoff change in Songhua and Liao River Basin (SLRB), Yellow River Basin (YRB), Hai River Basin (HRB) and Pearl River Basin (PRB), the contribution was >56 %, while climate change was the dominant factor of runoff change in Huai River Basin (HuRB), CRB, and Yangtze River Basin (YZRB). Overall, there was a significant correlation between runoff and precipitation, unused land, urban and grassland in China. We concluded that runoff change and the contribution of climate change and human activities varies greatly among different basins. The findings in this work can shed light on the quantitative understanding of runoff changes in national scale and offer a scientific basis for sustainable water management.

Fusarium-Derived Secondary Metabolites with Antimicrobial Effects.

Fungal microbes are important in the creation of new drugs, given their unique genetic and metabolic diversity. As one of the most commonly found fungi in nature, Fusarium spp. has been well regarded as a prolific source of secondary metabolites (SMs) with diverse chemical structures and a broad spectrum of biological properties. However, little information is available concerning their derived SMs with antimicrobial effects. By extensive literature search and data analysis, as many as 185 antimicrobial natural products as SMs had been discovered from Fusarium strains by the end of 2022. This review first provides a comprehensive analysis of these substances in terms of various antimicrobial effects, including antibacterial, antifungal, antiviral, and antiparasitic. Future prospects for the efficient discovery of new bioactive SMs from Fusarium strains are also proposed.

Calcium Enrichment in Edible Mushrooms: A Review.

Calcium is one of the essential minerals that enhances various biological activities, including the regulation of blood pressure, the prevention of osteoporosis and colorectal adenomas. Calcium-enriched edible mushrooms can be considered as one of the important daily sources of calcium in foods. Calcium accumulation in edible mushrooms is an effective way to enhance its activities because the organic state of calcium metabolites in edible mushrooms can be formed from the original inorganic calcium. The main calcium sources for calcium-enriched edible mushrooms' cultivation are CaCO3, CaCl2 or Ca(NO3)2. The growth and metabolic process of edible mushrooms are significantly influenced by calcium enrichment. Generally, Ca at low levels is good for the production of edible mushrooms, whereas the reverse phenomenon for the growth of edible mushrooms at high Ca contents is observed. In addition, metabolites, for example, phenolics, flavonoids, polysaccharides, enzymes, minerals, etc., are improved when edible mushrooms are enriched at a moderate level of calcium. This review summarized the literature regarding the influence of calcium enrichment on edible mushrooms' growth and major metabolites. Furthermore, the mechanisms of calcium enrichment in edible mushrooms were highlighted. Understanding calcium-enriched mechanisms in edible mushrooms would not only be beneficial to manipulate the cultivation of edible mushrooms having excellent biological activities and high levels of active Ca, but it would also contribute to the applications of calcium enrichment products in food industries.

Marine Organisms as a Prolific Source of Bioactive Depsipeptides.

Depsipeptides, an important group of polypeptides containing residues of hydroxy acids and amino acids linked together by amide and ester bonds, have potential applications in agriculture and medicine. A growing body of evidence demonstrates that marine organisms are prolific sources of depsipeptides, such as marine cyanobacteria, sponges, mollusks, microorganisms and algae. However, these substances have not yet been comprehensively summarized. In order to enrich our knowledge about marine depsipeptides, their biological sources and structural features, as well as bioactivities, are highlighted in this review after an extensive literature search and data analysis.

Clonorchis sinensis legumain promotes migration and invasion of cholangiocarcinoma cells via regulating tumor-related molecules.

BACKGROUND: Clonorchis sinensis infection causes serious pathological changes in the bile duct and is highly correlated with cholangiocarcinoma. The excretory-secretory products (ESP) of C. sinensis play a critical role in the oncogenesis and progression of cholangiocarcinoma, while the components and precise mechanism remain unclear. Here, we evaluated the function of C. sinensis legumain (Cslegumain) in promoting the invasion and migration of cholangiocarcinoma cells and the mechanism involved. METHODS: The structural and molecular characteristics of Cslegumain were predicted and analyzed using the online program Phyre2. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining were performed to test the transcriptional level of Cslegumain and its localization in the adult. Native Cslegumain was detected by western blotting assay. The effects of Cslegumain on the proliferation, invasion and migration of cholangiocarcinoma cells were checked using CCK-8 assay, Matrigel transwell assay and scratch wound healing assay. Expression levels of tumor-related molecules regulated by Cslegumain were evaluated by qRT-PCR and western blotting assay. RESULTS: Cslegumain showed high similarity with human legumain in the secondary and tertiary structures and displayed higher transcriptional levels in the adult worm than in the metacercariae. Native Cslegumain was detected in a catalytic form and was localized mainly in the intestine of the C. sinensis adult and epithelial cells of the intrahepatic bile duct. After transfection into RBE cells, Cslegumain showed high ability in promoting the invasion and migration but not the proliferation of cholangiocarcinoma RBE cells. Furthermore, the expression levels of some molecules including E-cadherin and N-cadherin were downregulated, while the levels of α-actinin 4, ß-catenin and inducible nitric oxide synthase (iNOS) were upregulated. CONCLUSIONS: Our findings indicated that Cslegumain showed very similar structures as those of human legumain and could promote the invasion and migration of cholangiocarcinoma cells by regulating some tumor-related molecules.

Polyketides as Secondary Metabolites from the Genus Aspergillus.

Polyketides are an important class of structurally diverse natural products derived from a precursor molecule consisting of a chain of alternating ketone and methylene groups. These compounds have attracted the worldwide attention of pharmaceutical researchers since they are endowed with a wide array of biological properties. As one of the most common filamentous fungi in nature, Aspergillus spp. is well known as an excellent producer of polyketide compounds with therapeutic potential. By extensive literature search and data analysis, this review comprehensively summarizes Aspergillus-derived polyketides for the first time, regarding their occurrences, chemical structures and bioactivities as well as biosynthetic logics.

Whole-Genome Sequence Analysis of an Endophytic Fungus Alternaria sp. SPS-2 and Its Biosynthetic Potential of Bioactive Secondary Metabolites.

As one of the commonly isolated endophytic fungi, Alternaria has been known for the production of numerous secondary metabolites (SMs). However, its detailed genomic features and SM biosynthetic potential have not been extensively studied thus far. The present work focuses on the whole-genome sequencing and assembly of an endophytic strain Alternaria sp. SPS-2 derived from Echrysantha chrysantha Lindl. and gene annotation using various bioinformatic tools. The results of this study suggested that the genome of strain SPS-2 was 33.4 Mb in size with a GC content of 51% and an N50 scaffold of 2.6 Mb, and 9789 protein-coding genes, including 644 CAZyme-encoding genes, were discovered in strain SPS-2 through KEGG enrichment analysis. The antiSMASH results indicated that strain SPS-2 harbored 22 SM biosynthetic gene clusters (BGCs), 14 of which are cryptic and unknown. LS-MS/MS and GNPS-based analyses suggested that this endophytic fungus is a potential producer of bioactive SMs and merits further exploration and development.

A Novel Synthetic Antibody Library with Complementarity-Determining Region Diversities Designed for an Improved Amplification Profile.

Antibody discovery by phage display consists of two phases, i.e., the binding phase and the amplification phase. Ideally, the selection process is dominated by the former, and all the retrieved clones are amplified equally during the latter. In reality, the amplification efficiency of antibody fragments varies widely among different sequences and, after a few rounds of phage display panning, the output repertoire often includes rapidly amplified sequences with low or no binding activity, significantly diminishing the efficiency of antibody isolation. In this work, a novel synthetic single-chain variable fragment (scFv) library with complementarity-determining region (CDR) diversities aimed at improved amplification efficiency was designed and constructed. A previously reported synthetic scFv library with low, non-combinatorial CDR diversities was panned against protein A superantigen, and the library repertoires before and after the panning were analyzed by next generation sequencing. The enrichment or depletion patterns of CDR sequences after panning served as the basis for the design of the new library. Especially for CDR-H3 with a higher and more random diversity, a machine learning method was applied to predict potential fast-amplified sequences among a simulated sequence repertoire. In a direct comparison with the previous generation library, the new library performed better against a panel of antigens in terms of the number of binders isolated, the number of unique sequences, and/or the speed of binder enrichment. Our results suggest that the amplification-centric design of sequence diversity is a valid strategy for the construction of highly functional phage display antibody libraries.

Genomic and AntiSMASH Analyses of Marine-Sponge-Derived Strain Aspergillus niger L14 Unveiling Its Vast Potential of Secondary Metabolites Biosynthesis.

Aspergillus niger is one of the most important sources of secondary metabolites (SMs), with a wide array of pharmacological effects, including anti-inflammatory, antitumor, immunomodulatory and antioxidant effects. However, the biosynthetic analysis of these bioactive components has been rarely reported owing to the lack of high-quality genome sequences and comprehensive analysis. In this study, the whole genome of one marine-sponge-derived strain A. niger L14 was sequenced and assembled as well as in-depth bioinformatic analysis. The results indicated that the sequence assembly of strain L14 generated one high-quality genome with a total size of 36.1 Mb, a G + C content of 45.3% and an N50 scaffold of 4.2 Mb. Gene annotation was extensively deployed using various BLAST databases, including non-redudant (Nr) protein sequence, nucleotide (Nt) sequence, Swiss-Prot, Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) as well as Pathogen Host Interactions (PHI) and Carbohydrate-active enzymes (CAZy) databases. AntiSMASH analysis revealed that this marine strain harbors a total of 69 SMs biosynthesis gene clusters (BGCs), including 17 PKSs, 18 NRPSs, 21 NRPS-likes, 9 terpenes, 2 indoles, 1 betalactone and 1 siderophore, suggesting its biosynthetic potential to produce a wide variety of SMs. These findings will assist in future investigations on the genetic basis of strain L14 and provide insights into its new bioactive SMs for new drug discovery.

Adverse obstetric and perinatal outcomes in 2333 singleton pregnancies conceived after different endometrial preparation protocols: a retrospective study in China.

BACKGROUP: Frozen-thawed embryo transfer is rising worldwide. One adverse effect of programmed frozen embryo transfer (FET) reported in some studies is an increased risk of adverse obstetric and perinatal outcomes. Meanwhile, body mass index (BMI) also has adverse effect on obstetric and perinatal outcomes. In this study, we investigated that the influence of different endometrial preparation protocols on obstetric and perinatal outcomes and the role of BMI in it. METHOD: This retrospective cohort study included 2333 singleton deliveries after frozen-thaw embryo transfer at our centre between 2014 and 2021, including 550 cycles with programmed FET, 1783 cycles with true natural cycle FET (tNC-FET). In further analysis according to BMI grouped by Asian criterion, group A (18.5 kg/m2 ≤ BMI < 24.00 kg/m2) included 1257 subjects, group B (24 kg/m2 ≤ BMI < 28.00 kg/m2) included 503 subjects and group C (BMI ≥ 28 kg/m2) included 573 subjects. Baseline characteristics of the two groups were compared and analyzed. Binary logistic regression analyses were performed to explore the association between obstetric and perinatal outcomes and endometrial preparation protocols. RESULTS: There were no significant differences in the placenta previa, gestational diabetes mellitus(GDM), preterm premature rupture of membranes (PPROM), cesarean section (CS) and macrosomia between the tNC-FET and programmed FET groups (P > 0.05). The programmed FET cycles were associated to a higher risk of pregnancy-induced hypertension (PIH) compared with the tNC-FET cycles (7.3% vs 4.4%, crude OR 1.71[1.16-2.54]; adjusted OR 1.845[1.03-3.30]). After dividing the patients into three groups according to the BMI, The programmed FET cycles were associated to a higher risk of PIH in group C (14.4% vs 6.2%, crude OR 2.55 [1.42-4.55]; adjusted OR 4.71 [1.77-12.55]) compared with the tNC-FET cycles. But there was no statistically significant difference in group A and group B. Programmed FET group compared with the tNC-FET group, the risk of PIH increase as the body mass index increase. CONCLUSION: This study showed a tendency toward increasing risk of PIH in programmed FET cycle compared with the tNC-FET cycle, and the risk of PIH increases as BMI increases. Increased risk of preterm birth and low birth weight is linked to increased risk of PIH.