IL20Rb aggravates pulmonary fibrosis through enhancing bone marrow derived profibrotic macrophage activation.

Idiopathic pulmonary fibrosis (IPF) is one of the most fatal chronic interstitial lung diseases with unknown pathogenesis, current treatments cannot truly reverse the progression of the disease. Pulmonary macrophages, especially bone marrow derived pro-fibrotic macrophages, secrete multiple kinds of profibrotic mediators (SPP1, CD206, CD163, IL-10, CCL18…), thus further promote myofibroblast activation and fibrosis procession. IL20Rb is a cell-surface receptor that belongs to IL-20 family. The role of IL20Rb in macrophage activation and pulmonary fibrosis remains unclear. In this study, we established a bleomycin-induced pulmonary fibrosis model, used IL4/13-inducing THP1 cells to induce profibrotic macrophage (M2-like phenotype) polarization models. We found that IL20Rb is upregulated in the progression of pulmonary fibrosis, and its absence can alleviate the progression of pulmonary fibrosis. In addition, we demonstrated that IL20Rb promote the activation of bone marrow derived profibrotic macrophages by regulating the Jak2/Stat3 and Pi3k/Akt signaling pathways. In terms of therapeutic strategy, we used IL20Rb neutralizing antibodies for animal administration, which was found to alleviate the progression of IPF. Our results suggest that IL20Rb plays a profibrotic role by promoting profibrotic macrophage polarization, and IL20Rb may become a potential therapeutic target for IPF. Neutralizing antibodies against IL20Rb may become a potential drug for the clinical treatment of IPF.

Enhancing the efficient degradation of BPS using the BPNS-CdS composite catalyst under visible light.

Black phosphorus nanosheets (BPNS), a novel two-dimensional nanomaterial, find extensive applications in the field of photocatalysis. With the prohibition of bisphenol A (BPA), the utilization of bisphenol S (BPS), which is more resistant to degradation than BPA, has been steadily increasing. In this study, few-layer BPNS was prepared using an improved liquid-phase exfoliation method, showcasing its commendable specific surface area and notable adsorption capacity. Subsequently, a new type of nanocomposite material, BPNS-Cadmium sulfide (CdS), was hydrothermal synthesized involving BPNS and CdS. We conducted comparative assessments of BPNS, CdS, and their composite materials to identify the most efficient catalysts. Ultimately, we found that the composite material BPNS-CdS exhibited the highest capability for degrading BPS in an alkaline environment, achieving an impressive degradation rate of 86.9%. Notably, the degradation rate remained higher in an acidic environment compared to a neutral one. Through Electron Spin Resoance (ESR) experiments, it is revealed that BPNS-CdS, when exposed to visible light, generates •O2-, •OH, and h+ as confirmed. Additionally, we tested and validated the carrier separation and migration abilities of BPNS-CdS while also calculating the band gap for each material. Building upon these results, a possible photocatalysis mechanism experiment was proposed. Finally, the degradation products were analyzed using High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) and put forth a plausible pathway for the BPS degradation, and it was found that 4-Phenolsulfonic acid, Ethyl protocatechuate and Isophthalic acid are the main intermediates of BPS. This study contributes to a deeper understanding of the synergy between non-metallic catalysts like BPNS and metal catalysts like CdS. It also offers new insights into the degradation mechanisms and pathways for BPS.

Research Progress of Methods for Degradation of Bisphenol A.

Bisphenol A (BPA), an endocrine disruptor widely used in industrial production, is found in various environmental sources. Despite numerous reports on BPA degradation and removal, the details remain unclear. This paper aims to address this gap by providing a comprehensive review of BPA degradation methods, focusing on biological, physical, and chemical treatments and the factors that affect the degradation of BPA. Firstly, the paper uses VOSviewer software (version 1.6.15) to map out the literature on BPA degradation published in the past 20 years, which reveals the trends and research focus in this field. Next, the advantages and limitations of different BPA degradation methods are discussed. Overall, this review highlights the importance of BPA degradation to protect the environment and human health. The paper provides significant insights for researchers and policymakers to develop better approaches for BPA degradation and removal.

Genome-wide analysis of genomic imprinting in the endosperm and allelic variation in flax.

Genomic imprinting is an epigenetic phenomenon that causes biased expression of maternally and paternally inherited alleles. In flowering plants, genomic imprinting predominantly occurs in the triploid endosperm and plays a vital role in seed development. In this study, we identified 248 candidate imprinted genes including 114 maternally expressed imprinted genes (MEGs) and 134 paternally expressed imprinted genes (PEGs) in flax (Linum usitatissimum L.) endosperm using deep RNA sequencing. These imprinted genes were neither clustered in specific chromosomal regions nor well conserved among flax and other plant species. MEGs tended to be expressed specifically in the endosperm, whereas the expression of PEGs was not tissue-specific. Imprinted single nucleotide polymorphisms differentiated 200 flax cultivars into the oil flax, oil-fiber dual purpose flax and fiber flax subgroups, suggesting that genomic imprinting contributed to intraspecific variation in flax. The nucleotide diversity of imprinted genes in the oil flax subgroup was significantly higher than that in the fiber flax subgroup, indicating that some imprinted genes underwent positive selection during flax domestication from oil flax to fiber flax. Moreover, imprinted genes that underwent positive selection were related to flax functions. Thirteen imprinted genes related to flax seed size and weight were identified using a candidate gene-based association study. Therefore, our study provides information for further exploration of the function and genomic variation of imprinted genes in the flax population.

Molecular epidemiology and clinical characterization of human rhinoviruses circulating in Shanghai, 2012-2020.

Human rhinoviruses (HRVs) cause acute upper and lower respiratory tract infections and aggravation of asthma and chronic obstructive pulmonary disease. The 5' untranslated region (5' UTR) and the VP4/VP2 region are widely used for genotyping of HRVs. Members of the species Rhinovirus A and Rhinovirus C have been reported to be more frequently associated with severe disease than members of the species Rhinovirus B. We report the clinical and molecular epidemiological characteristics of HRVs circulating from 2012 to 2020 in Shanghai. A total of 5832 nasopharyngeal swabs from patients with acute respiratory infections were collected. A real-time reverse transcription polymerase chain reaction assay was used for virus detection. The 5' untranslated region and VP4/VP2 region were amplified and sequenced for genotyping and phylogenetic analysis. The overall rate of rhinovirus detection was 2.74% (160/5832), with members of species A, B, and C accounting for 68.13% (109/160), 20.00% (32/160), and 11.88% (19/160) of the total, respectively. A peak of HRV infection was observed in autumn (5.34%, 58/1087). Patients in the 3- to 14-year-old age group were the most susceptible to HRV infection (χ2 = 23.88, P = 0.017). Influenza virus and Streptococcus pneumoniae were detected more frequently than other pathogens in cases of coinfection. Recombination events were identified in 10 strains, which were successfully genotyped by phylogenetic analysis based on the 5' UTR-VP4/VP2 region but not the 5' UTR region alone. We observed a high degree of variability in the relative distribution of HRV genotypes and the prevalence of HRV infection in Shanghai and found evidence of recombination events in the portion of the genome containing the 5' UTR and the VP4/VP2 region between HRV-C strains and HRV-A-like strains. This study is important for surveillance of the spread of HRVs and the emergence of new variants.

Development of SERS-based immunoassay for the detection of cryptococcosis biomarker.

The surface-enhanced Raman scattering (SERS) technique has displayed a broad application prospect in disease diagnosis owing to its high sensitivity, fast responsiveness, and high specificity. In this study, we developed a SERS-based immunoassay for the detection of cryptococcal capsular polysaccharide (glucuronoxylomannan, GXM), which is an important biomarker of cryptococcosis. The coupled localized surface plasmon resonance effect between magnetic SERS substrates and SERS tags gave rise to an enhanced Raman signal upon the formation of sandwich complexes, which contributes to the sensitive and specific detection of GXM. As a result, the developed method provided a lower limit of detection (1.25 ng/mL) than conventional methods, such as latex agglutination, lateral flow assay, and enzyme-linked immunosorbent assay. Additionally, a recovery experiment was performed to detect GXM in human serum, which also validated the potential advantages of a SERS-based immunoassay in the clinical diagnosis of cryptococcosis.

Comparison between laparoscopic and abdominal radical hysterectomy for low-risk cervical cancer: a multicentre retrospective study.

PURPOSE: To compare oncological outcomes of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for low-risk cervical cancer. METHOD: We retrospectively compared the 3-year overall survival (OS) and 3-year disease-free survival (DFS) of 1269 low-risk cervical cancer patients with FIGO 2009 stage IA2, IB1 and IIA1 with a tumour size < 2 cm, no lymphovascular space invasion (LVSI), superficial stromal invasion and no lymph node involvement on imaging, and who received LRH (n = 672) and ARH (n = 597) between 2009 and 2018 at 47 hospitals. RESULTS: In the total study population, LRH and ARH showed similar 3-year OS (98.6% vs. 98.9%, P = 0.850) and DFS rates (95.7% vs. 96.4%, P = 0.285). LRH was not associated with worse 3-year OS (HR 0.897, 95% CI 0.287-2.808, P = 0.852) or DFS (HR 0.692, 95% CI 0.379-1.263, P = 0.230) as determined by multivariable analysis. After propensity score matching in 1269 patients, LRH (n = 551) and ARH (n = 551) still showed similar 3-year OS (98.4% vs. 98.8%, P = 0.704) and DFS rates (95.5% vs. 96.3%, P = 0.249). LRH was still not associated with worse 3-year OS (HR 0.816, 95% CI 0.262-2.541, P = 0.725) or DFS (HR 0.694, 95% CI 0.371-1.296, P = 0.251). CONCLUSION: Among patients with low-risk cervical cancers < 2 cm, no LVSI, superficial stromal invasion, and no lymph node involvement on imaging, no significant differences were observed in 3-year OS or DFS rates between LRH and ARH.

Evolutionary dynamics of group A and B respiratory syncytial virus in China, 2009-2018.

Respiratory syncytial virus (RSV) is a major cause of acute respiratory tract infections in children and is a public health threat globally. To investigate the spatiotemporal dynamics of RSV evolution, we performed systematic phylogenetic analysis using all available sequences from the GenBank database, together with sequences from Shanghai, China. Both RSV-A and RSV-B appear to have originated in North America, with an inferred origin time of 1954.0 (1938.7-1967.6) and 1969.7 (1962.6-1975.5), respectively. BA-like strains of RSV-B, with a 60-nt insertion, and the ON1 strain of RSV-A, with a 72-nt insertion, emerged in 1997.6 (1996.2-1998.6) and 2010.1 (2009.1-2010.3), respectively. Since their origin, both genotypes have gradually replaced the former circulating genotypes to become the dominant strain. The population dynamic of RSV-A showed a seasonal epidemic pattern with obvious expansion in the periods of 2006-2007, 2010-2011, 2011-2012, and 2013-2014. Thirty fixed amino acid substitutions were identified during the divergence of NA4 from GA1 genotypes of RSV-A, and 13 were found during the divergence of SAB4 from GB1 of RSV-B. Importantly, ongoing evolution has occurred since the emergence of ON1, including four amino acid substitutions (I208L, E232G, T253K, and P314L). RSV-A genotypes GA5, NA4, NA1, and ON1 and RSV-B genotypes CB1, SAB4, BA-C, BA10, BA7, and BA9 were co-circulating in China from 2005 to 2015. In particular, RSV-A genotype ON1 was first detected in China in 2011, and it completely replaced GA2 to become the predominant strain after 2016. These data provide important insights into the evolution and epidemiology of RSV.

Comparison of survival outcomes between laparoscopic surgery and abdominal surgery for radical hysterectomy as primary treatment in patients with stage IB2/IIA2 cervical cancer.

OBJECTIVE: To investigate the long-term oncological outcomes of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for the treatment of stage IB2/IIA2 cervical cancer without preoperative adjuvant therapy. METHODS: We conducted a multicenter, retrospective, case-matching study. The differences in overall survival (OS) and disease-free survival (DFS) between the LRH and ARH were compared under the conditions of real-world study and case-control matching (1:1 matching). RESULTS: There was no significant difference in the outcomes of LRH (n = 580) and ARH (n = 1653) in 5-year OS and DFS (OS: 80.6% vs. 86.1%, p = 0.421; DFS: 78.6% vs. 80.7%, p = 0.376). After 1:1 matching, there was no difference in 5-year OS and DFS between LRH (n = 554) and ARH (n = 554) (OS: 80.4% vs. 84.5%, p = 0.993; DFS: 79.0% vs. 78.8%, p = 0.695). Before and after matching, the surgical approach was not an independent risk factor for 5-year OS and DFS, and postoperative adjuvant therapy affected patient prognosis. Further subgroup analysis suggested that there was no difference in LRH (n = 313) and ARH (n = 1092) in 5-year OS or DFS in patients who underwent standard postoperative adjuvant therapy (OS: 83.0% vs. 87.7%, p = 0.992; DFS: 79.0% vs. 82.5%, p = 0.323). After 1:1 pairing, the 5-year OS and DFS in LRH (n = 295) and ARH (n = 295) showed no difference. Before and after matching, the surgical approach was not an independent risk factor affecting the 5-year OS and DFS. CONCLUSIONS: There was no difference in the oncological outcomes between laparoscopic and abdominal surgery in patients with stage IB2/IIA2 cervical cancer without preoperative adjuvant therapy. CLINICAL TRIALS: The ethical approval number is NFEC-2017-135, and the clinical research registration number is CHiCTR1800017778 (International Clinical Trials Registry Platform Search Port, http://apps.who.int/trialsearch/).

Gender Differences in Mental Health of Bereaved Parents in an Only-Child Society: Evidence From China.

This study examined gender differences in mental health of bereaved parents related to the gender of deceased only child in China, an only-child society with traditional culture of son preference, using data drawn from the China Family Planning Survey on Vulnerable Households in 2017. The findings indicated that parents with deceased only child suffered from more negative mental health symptoms than nonbereaved parents. For only-child-death families, there were no statistically significant gender differences in mental health of parents, and the gender of the deceased only child was basically unrelated to maternal/paternal mental health. Due to the implementation of one-child policy in China, both sons and daughters are highly prized and equally relied on by aging parents owing to the irreplaceability of the only child, which might moderate the effects of traditional culture of son preference on bereaved parental mental health.

Monoacylglycerol Lipase Inactivation by Using URB602 Mitigates Myocardial Damage in a Rat Model of Cardiac Arrest.

OBJECTIVES: Monoacylglycerol lipase participates in organ protection by regulating the hydrolysis of the endocannabinoid 2-arachidonoylglycerol. This study investigated whether blocking monoacylglycerol lipase protects against postresuscitation myocardial injury and improves survival in a rat model of cardiac arrest and cardiopulmonary resuscitation. DESIGN: Prospective randomized laboratory study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rat (n = 96). INTERVENTIONS: Rats underwent 8-minute asphyxia-based cardiac arrest and resuscitation. Surviving rats were randomly divided into cardiopulmonary resuscitation + URB602 group, cardiopulmonary resuscitation group, and sham group. One minute after successful resuscitation, rats in the cardiopulmonary resuscitation + URB602 group received a single dose of URB602 (5 mg/kg), a small-molecule monoacylglycerol lipase inhibitor, whereas rats in the cardiopulmonary resuscitation group received an equivalent volume of vehicle solution. The sham rats underwent all of the procedures performed on rats in the cardiopulmonary resuscitation and cardiopulmonary resuscitation + URB602 groups minus cardiac arrest and asphyxia. MEASUREMENTS AND MAIN RESULTS: Survival was recorded 168 hours after the return of spontaneous circulation (n = 22 in each group). Compared with vehicle treatment (31.8%), URB602 treatment markedly improved survival (63.6%) 168 hours after cardiopulmonary resuscitation. Next, we used additional surviving rats to evaluate myocardial and mitochondrial injury 6 hours after return of spontaneous circulation, and we found that URB602 significantly reduced myocardial injury and prevented myocardial mitochondrial damage. In addition, URB602 attenuated the dysregulation of endocannabinoid and eicosanoid metabolism 6 hours after return of spontaneous circulation and prevented the acceleration of mitochondrial permeability transition 15 minutes after return of spontaneous circulation. CONCLUSIONS: Monoacylglycerol lipase blockade may reduce myocardial and mitochondrial injury and significantly improve the resuscitation effect after cardiac arrest and cardiopulmonary resuscitation.

Inhibition of Fatty Acid Amide Hydrolase Improves Depressive-Like Behaviors Independent of Its Peripheral Antinociceptive Effects in a Rat Model of Neuropathic Pain.

BACKGROUND: Neuropathic pain is often associated with depression. Enhancing endocannabinoids by fatty acid amide hydrolase (FAAH) inhibitors relieves neuropathic pain and stress-induced depressive-like behaviors in animal models. However, it is unclear whether FAAH inhibitor can relieve neuropathic pain-induced depression by or not by its antinociceptive effects. METHODS: Adult male Wistar rats with chronic constriction injury (CCI) to the sciatic nerve were treated with the systemic FAAH inhibitor URB597 (5.8 mg·kg·day, intraperitoneally) or peripherally acting FAAH inhibitor URB937 (1.6 mg·kg·d, intraperitoneally; n = 11-12). The treatment was applied from the 15th day after surgery and continued for 15 days. Mechanical withdrawal threshold was examined by Von Frey test before surgery and on the 28th day after CCI. Depressive-like behaviors were evaluated by forced swimming test (FST) and novelty-suppressed feeding (NSF) after 15-day treatment. The levels of anandamide and 2-arachidonoylglycerol in hippocampus were examined by liquid chromatography and mass spectrometry. Hippocampal neurogenesis including proliferation, differentiation, and survival of newborn cells was assessed by immunohistochemistry. RESULTS: After CCI injury, the rats developed significantly nociceptive and depressive-like behaviors, indicated by persistent mechanical hypersensitivity in Von Frey test, significantly prolonged immobility time in FST (sham: 84.2 ± 13.4 seconds versus CCI: 137.9 ± 18.8 seconds; P < .001), and protracted latency to feed in NSF (sham: 133.4 ± 19.4 seconds versus CCI: 234.9 ± 33.5 seconds; P < .001). For the CCI rats receiving treatment, compared to vehicle placebo group, pain threshold was increased by both URB597 (3.1 ± 1.0 vs 11.2 ± 1.2 g; P < .001) and URB937 (3.1 ± 1.0 vs 12.1 ± 1.3 g; P < .001). Immobility time of FST was reduced by URB597 (135.8 ± 16.6 vs 85.3 ± 17.2 seconds; P < .001) but not by URB937 (135.8 ± 16.6 vs 129.6 ± 17.8 seconds; P = .78). Latency to feed in NSF was also reduced by URB597 (235.9 ± 30.5 vs 131.8 ± 19.8 seconds; P < .001) but not by URB937 (235.9 ± 30.5 vs 232.2 ± 33.2 seconds; P = .72). Meanwhile, CCI decreased the number of proliferating cells and reduced survival of new mature neurons in hippocampus. URB597 but not URB937 treatment improved these cellular deficits. CONCLUSIONS: Inhibition of FAAH can improve depressive-like behaviors induced by neuropathic pain independent of its peripheral antinociceptive action. Enhanced neurogenesis in hippocampus might contribute to the antidepressive effects of URB597.

UNC13A variant rs12608932 is associated with increased risk of amyotrophic lateral sclerosis and reduced patient survival: a meta-analysis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with both genetic and environmental risk factors. Previous studies trying to find an association between ALS and unc-13 homolog A (UNC13A) gene variants have shown inconsistent results. This study aimed to conduct a meta-analysis of the association between the C allele of rs12608932, a single-nucleotide polymorphism located in an intron of UNC13A, and risk of ALS and patient survival. METHODS: PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases were systematically searched for genome-wide association studies or case-control studies published up to January 2019 on the association between this variant in UNC13A and risk and/or prognosis of ALS. Data from eligible studies were extracted and analyzed. RESULTS: The pooled data (28,072 patients with sporadic ALS and 56,545 controls) showed that rs12608932(C) was associated with an increased risk of ALS (OR = 1.13, 95%CI 1.07-1.20). Subgroup analysis revealed that rs12608932(C) increased the risk of sporadic ALS in non-Asian individuals, including those from the USA and Europe (OR 1.17, 95%CI 1.10-1.25, P < 0.000), but not in Japanese or Chinese subjects (OR 1.01, 95%CI 0.92-1.10, P = 0.85). The available data demonstrated that the CC genotype decreased the survival time of patients with ALS (OR 1.33, 95%CI 1.19-1.49, P < 0.001). CONCLUSION: The present meta-analysis suggests that rs12608932(C) is associated with increased ALS susceptibility, especially in Caucasian and European subjects, and that the CC genotype of rs12608932 is associated with reduced ALS patient survival.

Coenzyme Q biosynthesis in the biopesticide Shenqinmycin-producing Pseudomonas aeruginosa strain M18.

Coenzyme Q (ubiquinone) is a redox-active isoprenylated benzoquinone commonly found in living organisms. The biosynthetic pathway for this lipid has been extensively studied in Escherichia coli and Saccharomyces cerevisiae; however, little is known in Pseudomonas aeruginosa. In this study, we observed that CoQ9 is the predominant coenzyme Q synthesized by the Shenqinmycin-producing strain M18. BLASTP and domain organization analyses identified 15 putative genes for CoQ biosynthesis in M18. The roles of 5 of these genes were genetically and biochemically investigated. PAM18_4662 encodes a nonaprenyl diphosphate synthase (Nds) and determines the number of isoprenoid units of CoQ9 in M18. PAM18_0636 (coq7PA) and PAM18_5179 (ubiJPA) are essential for aerobic growth and CoQ9 biosynthesis. Deletion of ubiJPA, ubiBPA and ubiKPA led to reduced CoQ biosynthesis and an accumulation of the CoQ9 biosynthetic intermediate 3-nonaprenylphenol (NPP). Moreover, we also provide evidence that the truncated UbiJPA interacts with UbiBPA and UbiKPA to affect CoQ9 biosynthesis by forming a regulatory complex. The genetic diversity of coenzyme Q biosynthesis may provide targets for the future design of specific drugs to prevent P. aeruginosa-related infections.

Biotechnological potential of a rhizosphere Pseudomonas aeruginosa strain producing phenazine-1-carboxylic acid and phenazine-1-carboxamide.

Bacterial phenazine metabolites belong to a group of nitrogen-containing heterocyclic compounds with antimicrobial activities. In this study, a rhizosphere Pseudomonas aeruginosa strain PA1201 was isolated and identified through 16S rDNA sequence analysis and fatty acid profiling. PA1201 inhibited the growth of various pathogenic microorganisms, including Rhizotonia solani, Magnaporthe grisea, Fusarium graminearum, Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicola, and Staphylococcus aureus. High Performance Liquid Chromatography showed that PA1201 produced high levels of phenazine-1-carboxylic acid (PCA), a registered green fungicide 'Shenqinmycin' with the fermentation titers of 81.7 mg/L in pigment producing medium (PPM) and 926.9 mg/L in SCG medium containing soybean meal, corn steep liquor and glucose. In addition, PA1201 produced another antifungal metabolite, phenazine-1-carboxaminde (PCN), a derivative of PCA, with the fermentation titers of 18.1 and 489.5 mg/L in PPM and SCG medium respectively. To the best of our knowledge, PA1201 is a rhizosphere originating P. aeruginosa strain that congenitally produces the highest levels of PCA and PCN among currently reported P. aeruginosa isolates, which endows it great biotechnological potential to be transformed to a biopesticide-producing engineering strain.

Engineering the central biosynthetic and secondary metabolic pathways of Pseudomonas aeruginosa strain PA1201 to improve phenazine-1-carboxylic acid production.

The secondary metabolite phenazine-1-carboxylic acid (PCA) is an important component of the newly registered biopesticide Shenqinmycin. We used a combined method involving gene, promoter, and protein engineering to modify the central biosynthetic and secondary metabolic pathways in the PCA-producing Pseudomonas aeruginosa strain PA1201. The PCA yield of the resulting strain PA-IV was increased 54.6-fold via the following strategies: (1) blocking PCA conversion and enhancing PCA efflux pumping; (2) increasing metabolic flux towards the PCA biosynthetic pathway through the over-production of two DAHP synthases and blocking the synthesis of 21 secondary metabolites; (3) increasing the PCA precursor supply through the engineering of five chorismate-utilizing enzymes; (4) engineering the promoters of two PCA biosynthetic gene clusters. Strain PA-IV produced 9882 mg/L PCA in fed-batch fermentation, which is twice as much as that produced by the current industrial strain. Strain PA-IV was also genetically stable and comparable to Escherichia coli in cytotoxicity.

[Isolation, identification and characterization of rice rhizobacterium Pseudomonas aeruginosa PA1201 producing high level of biopesticide "Shenqinmycin" and phenazine-1-carboxamide].

OBJECTIVE: To identify bacterial strains with the inhibitory activity to rice pathogens, and to evaluate their potentials for the development of new biopesticides. METHODS: Rice rhizosphere Pseudomonas strains were isolated using 1-aminocyclopropane-1-carboxylic acid as the sole carbon source. Strain PA1201 was further identified through morphological analysis, biochemical characterization, 16S rDNA sequence analysis and phospholipid fatty acid profiling. Qualitative and quantitative analysis of the production of the green pesticide Shenqinmycin as well as phenazine-1-carboxamide produced by PA1201 was done by HPLC. Cytotoxicity of PA1201 was evaluated using human alveolar epithelial cell line A549 and Drosophila melanogaster as hosts. RESULTS: Strain PA1201 inhibited Rhizotonia solani Kuhn and Xanthomonas oryzae pv. oryzae, the causal agents of rice sheath blight and bacterial blight, respectively. It was further identified as Pseudomonas aeruginosa PA1201, which produces shenqinmycin and phenazine-1-carboxamide. The fermentation titer of shenqinmycin and phenazine-1-carboxamide in the PPM medium was 81.7 mg/L and 18. 1 mg/L, respectively. In the medium supplemented with soybean meal and corn steep liquor, the level of shenqinmycin and phenazine-1-carboxamide reached 926. 9 mg/L and 489. 5 mg/L. PA1201 also produced high level of extracellular protease and was toxic to human cell line and fruit fly. CONCLUSION: Strain PA1201 could be engineered for higher yield of Shenqinmycin or for a new biopesticide.

Design, synthesis, and biological evaluation of novel trifluoromethyl indoles as potent HIV-1 NNRTIs with an improved drug resistance profile.

A novel series of trifluoromethyl indole derivatives have been designed, synthesized and evaluated for anti-HIV-1 activities in MT-2 cells. The hydrophobic constant, acute toxicity, carcinogenicity and mutagenicity were predicted. Trifluoromethyl indoles 10i and 10k showed extremely promising activities against WT HIV-1 with IC50 values at the low nanomolar level, similar to efavirenz, better than nevirapine, and also possessed higher potency towards the drug-resistant mutant strain Y181C than nevirapine. Preliminary SAR and docking studies of detailed binding mode provided some insights for discovery of more potent NNRTIs.

An R2R3-MYB Transcriptional Factor LuMYB314 Associated with the Loss of Petal Pigmentation in Flax (Linum usitatissimum L.).

The loss of anthocyanin pigments is one of the most common evolutionary transitions in petal color, yet the genetic basis for these changes in flax remains largely unknown. In this study, we used crossing studies, a bulk segregant analysis, genome-wide association studies, a phylogenetic analysis, and transgenic testing to identify genes responsible for the transition from blue to white petals in flax. This study found no correspondence between the petal color and seed color, refuting the conclusion that a locus controlling the seed coat color is associated with the petal color, as reported in previous studies. The locus controlling the petal color was mapped using a BSA-seq analysis based on the F2 population. However, no significantly associated genomic regions were detected. Our genome-wide association study identified a highly significant QTL (BP4.1) on chromosome 4 associated with flax petal color in the natural population. The combination of a local Manhattan plot and an LD heat map identified LuMYB314, an R2R3-MYB transcription factor, as a potential gene responsible for the natural variations in petal color in flax. The overexpression of LuMYB314 in both Arabidopsis thaliana and Nicotiana tabacum resulted in anthocyanin deposition, indicating that LuMYB314 is a credible candidate gene for controlling the petal color in flax. Additionally, our study highlights the limitations of the BSA-seq method in low-linkage genomic regions, while also demonstrating the powerful detection capabilities of GWAS based on high-density genomic variation mapping. This study enhances our genetic insight into petal color variations and has potential breeding value for engineering LuMYB314 to develop colored petals, bast fibers, and seeds for multifunctional use in flax.

Liquid biopsy in lung cancer.

Lung cancer is a highly prevalent malignancy worldwide and the primary cause of mortality. The absence of systematic and standardized diagnostic approaches for identifying potential pulmonary nodules, early-stage cancers, and indeterminate tumors has led clinicians to consider tissue biopsy and pathological sections as the preferred method for clinical diagnosis, often regarded as the gold standard. The conventional tissue biopsy is an invasive procedure that does not adequately capture the diverse characteristics and evolving nature of tumors. Recently, the concept of 'liquid biopsy' has gained considerable attention as a promising solution. Liquid biopsy is a non-invasive approach that facilitates repeated analysis, enabling real-time monitoring of tumor recurrence, metastasis, and response to treatment. Currently, liquid biopsy includes circulating tumor cells, circulating cell-free DNA, circulating tumor DNA, circulating cell-free RNA, extracellular vesicles, and other proteins and metabolites. With rapid progress in molecular technology, liquid biopsy has emerged as a highly promising and intriguing approach, yielding compelling results. This article critically examines the significant role and potential clinical implications of liquid biopsy in the diagnosis, treatment, and prognosis of lung cancer.