Antitumor activity and transcriptome sequencing (RNA-seq) analyses of hepatocellular carcinoma cells in response to exposure triterpene-nucleoside conjugates.

Fifteen betulonic/betulinic acid conjugated with nucleoside derivatives were synthesized to enhance antitumor potency and water solubility. Among these, the methylated betulonic acid-azidothymidine compound (8c) exhibited a broad-spectrum of antitumor activity against three tested tumor cell lines, including SMMC-7721 (IC50 = 5.02 µM), KYSE-150 (IC50 = 5.68 µM), and SW620 (IC50 = 4.61 µM) and along with lower toxicity (TC50 > 100 µM) estimated by zebrafish embryos assay. Compared to betulinic acid (<0.05 µg/mL), compound 8c showed approximately 40-fold higher water solubility (1.98 µg/mL). In SMMC-7721 cells, compound 8c induced autophagy and apoptosis as its concentration increased. Transcriptomic sequencing analysis was used to understand the potential impacts of the underlying mechanism of 8c on SMMC-7721 cells. Transcriptomic studies indicated that compound 8c could activate autophagy by inhibiting the PI3K/AKT pathway in SMMC-7721 cells. Furthermore, in the xenograft mice study, compound 8c significantly slowed down the tumor growth, as potent as paclitaxel treated group. In conclusion, methylated betulonic acid-azidothymidine compound (8c) not only increases water solubility, but also enhances the potency against hepatocellular carcinoma cells by inducing autophagy and apoptosis, and suppressing the PI3K/Akt/mTOR signaling pathway.

Synthesis, Characterization, and Reactivity of a Synthetic End-On Cobalt(II) Alkyl Persulfide Complex as a Model Platform for Thiolate Persulfidation.

Persulfides (RSS-) are ubiquitous source of sulfides (S2-) in biology, and interactions between RSS- and bioinorganic metal centers play critical roles in biological hydrogen sulfide (H2S) biogenesis, signaling, and catabolism. Here, we report the use of contact-ion stabilized [Na(15-crown-5)][tBuSS] (1) as a simple synthon to access rare metal alkyl persulfide complexes and to investigate the reactivity of RSS- with transition metal centers to provide insights into metal thiolate persulfidation, including the fundamental difference between alkyl persulfides and alkyl thiolates. Reaction of 1 with [CoII(TPA)(OTf)]+ afforded the η1-alkyl persulfide complex [CoII(TPA)(SStBu)]+ (2), which was characterized by X-ray crystallography, UV-vis spectroscopy, and Raman spectroscopy. RSS- coordination to the Lewis acidic Co2+ center provided additional stability to the S-S bond, as evidenced by a significant increase in the Raman stretching frequency for 2 (vS-S = 522 cm-1, ΔvS-S = 66 cm-1). The effect of persulfidation on metal center redox potentials was further elucidated using cyclic voltammetry, in which the Co2+ → Co3+ oxidation potential of 2 (Ep,a = +89 mV vs SCE) is lowered by nearly 700 mV when compared to the corresponding thiolate complex [CoII(TPA)(StBu)]+ (3) (Ep,a = +818 mV vs SCE), despite persulfidation being generally seen as an oxidative post-translational modification. The reactivity of 2 toward reducing agents including PPh3, BH4-, and biologically relevant thiol reductant DTT led to different S2- output pathways, including formation of a dinuclear 2Co-2SH complex [CoII2(TPA)2(µ2-SH)2]2+(4).

Biochemical Characterization of a Marine Pseudoalteromonas citrea-Derived Fatty Acyl-AMP Ligase That Exhibits N-Acyl Amino Acid Synthetic Activity.

Activation of fatty acids as acyl-adenylates by fatty acid-AMP ligase (FAAL) is a well-established process contributing to the formation of various functional natural products. Enzymatic characterization of FAALs is pivotal for unraveling both the catalytic mechanism and its role in specific biosynthetic pathways. In this study, we recombinantly expressed and characterized a novel FAAL derived from marine Pseudoalteromonas citrea (PcFAAL). PcFAAL was a cold-adapted neutral enzyme, demonstrating optimal activity at 30 °C and pH 7.5. Notably, its specific activity relied on the presence of Mg2+; however, higher concentrations exceeding 10 mM resulted in inhibition of enzyme activity. Various organic solvents, especially water-immiscible organic solvents, demonstrated an activating effect on the activity of PcFAAL on various fatty acids. The specific activity exhibited a remarkable 50-fold increase under 4% (v/v) n-hexane compared to the aqueous system. PcFAAL displayed a broad spectrum of fatty acid substrate selectivity, with the highest specific activity for octanoic acid (C8:0), and the catalytic efficiency (kcat/Km) for octanoic acid was determined to be 1.8 nM-1·min-1. Furthermore, the enzyme demonstrated biocatalytic promiscuity in producing a class of N-acyl amino acid natural products, as verified by LC-ESI MS. Results indicated that the PcFAAL exhibits promiscuity towards 10 different kinds of amino acids and further demonstrated their potential value in the biosynthesis of corresponding functional N-acyl amino acids.

In Situ Etching-Hydrolysis Strategy To Construct an In-Plane ZnIn2S4/In(OH)3 Heterojunction with Enhanced CO2 Photoreduction Performance.

The in-plane heterojunctions with atomic-level thickness and chemical-bond-connected tight interfaces possess high carrier separation efficiency and fully exposed surface active sites, thus exhibiting exceptional photocatalytic performance. However, the construction of in-plane heterojunctions remains a significant challenge. Herein, we prepared an in-plane ZnIn2S4/In(OH)3 heterojunction (ZISOH) by partial conversion of ZnIn2S4 to In(OH)3 through the addition of H2O2. This in situ oxidation etching-hydrolysis approach enables the ZISOH heterojunction to not only preserve the original nanosheet morphology of ZnIn2S4 but also form an intimate interface. Moreover, generated In(OH)3 serves as an electron-accepting platform and also promotes the adsorption of CO2. As a result, the heterojunction exhibits a remarkably enhanced performance for photocatalytic CO2 reduction. The production rate and selectivity of CO reach 1760 µmol g-1 h-1 and 78%, respectively, significantly higher than those of ZnIn2S4 (842 µmol g-1 h-1 and 65%). This work puts forward a feasible and facile approach to construct in-plane heterojunctions to enhance the photocatalytic performance of two-dimensional metal sulfides.

Corrigendum to "Assessing pripherally inserted central catheter tip location in multiple postures: A case report" [Asia-Pacific J Oncol Nurs 10 (2023) 100238].

[This corrects the article DOI: 10.1016/j.apjon.2023.100238.].

Identification of novel TMEM231 gene splice variants and pathological findings in a fetus with Meckel Syndrome.

Background: Meckel Syndrome (MKS, OMIM #249000) is a rare and fatal autosomal recessive ciliopathy with high clinical and genetic heterogeneity. MKS shows complex allelism with other related ciliopathies such as Joubert Syndrome (JBTS, OMIM #213300). In MKS, the formation and function of the primary cilium is defective, resulting in a multisystem disorder including occipital encephalocele, polycystic kidneys, postaxial polydactyly, liver fibrosis, central nervous system malformations and genital anomalies. This study aimed to analyze the genotype of MKS patients and investigate the correlation between genotype and phenotype. Methods: A nonconsanguineous couple who conceived four times with a fetus affected by multiorgan dysfunction and intrauterine fetal death was studied. Whole exome sequencing (WES) was performed in the proband to identify the potentially pathogenic variant. Sanger sequencing was performed in family members. In silico tools were used to analyse the pathogenicity of the identified variants. cDNA TA-cloning sequencing was performed to validate the effects of intronic variants on mRNA splicing. Quantitative real-time PCR was performed to investigate the effect of the variants on gene expression. Immunofluorescence was performed to observe pathological changes of the primary cilium in kidney tissue from the proband. Results: Two splice site variants of TMEM231 (NM_001077418.2, c.583-1G>C and c.583-2_588delinsTCCTCCC) were identified in the proband, and the two variants have not been previously reported. The parents were confirmed as carriers. The two variants were predicted to be pathogenic by in silico tools and were classified as pathogenic/likely pathogenic variants according to the American College of Medical Genetics and Genomics guideline. cDNA TA cloning analysis showed that both splice site variants caused a deletion of exon 5. RT-PCR revealed that the expression of TMEM231 was significantly decreased and immunofluorescence showed that the primary cilium was almost absent in the proband's kidney tissue. Conclusion: We reported the clinical, genetic, molecular and histochemical characterisation of a family affected by MKS. Our findings not only extended the mutation spectrum of the TMEM231 gene, but also revealed for the first time the pathological aetiology of primary cilia in humans and provide a basis for genetic counselling of the parents to their offspring.

Direct hydrogen selenide (H2Se) release from activatable selenocarbamates.

Hydrogen selenide (H2Se) is a possible bioregulator, potential gasotransmitter, and important precursor in biological organoselenium compound synthesis. Early tools for H2Se research have benefitted from available mechanistic understanding of analogous small molecules developed for detecting or delivering H2S. A now common approach for H2S delivery is the use of small molecule thiocarbamates that can be engineered to release COS, which is quickly converted to H2S by carbonic anhydrase. To expand our understanding of the chemical underpinnings that enable H2Se delivery, we investigated whether selenocarbamates undergo similar chemistry to release carbonyl selenide (COSe). Using both light- and hydrolysis-activated systems, we demonstrate that unlike their lighter thiocarbamate congeners, selenocarbamates release H2Se directly with concomitant isocyanate formation rather than by the intermediate release of COSe. This reaction mechanism for direct H2Se release is further supported by computational investigations that identify a ΔΔG‡ ∼ 25 kcal mol-1 between the H2Se and COSe release pathways in the absence of protic solvent. This work highlights fundamentally new approaches for H2Se release from small molecules and advances the understanding of reactivity differences between reactive sulfur and selenium species.

Assessing pripherally inserted central catheter tip location in multiple postures: A case report.

This report presents a case involving a 21-year-old male patient with acute promyelocytic leukemia, where the peripherally inserted central catheter (PICC) tip location was diagnosed differently using ultrasound and computed tomography. The PICC was inserted into the left upper arm via the basilic vein. Echocardiography performed in the left lateral recumbent position suggested the PICC tip to be in the right atrium, deepest at the level of the tricuspid annulus. However, trans-catheter contrast-enhanced echocardiography, performed with a different posture involving left shoulder abduction and slight external rotation, revealed the tip to be at the cavo-atrial junction. Additionally, chest computed tomography, conducted in the supine position with raised arms, indicated the tip to be located at the upper one-third of the superior vena cava. These contradictory diagnoses can be attributed to the use of different body postures during the assessments. Considering the clinical efficacy and safety, it is crucial to fully consider the influence of multiple postures on PICC tip location during placement and determination. We recommend incorporating at least two opposite extreme daily postures to assess the nearest and farthest positions of the tip, ensuring effective and safe PICC placement and reducing the risk of complications.

Taming the Dichalcogenides: Isolation, Characterization, and Reactivity of Elusive Perselenide, Persulfide, Thioselenide, and Selenosulfide Anions.

Reactive sulfur species (RSS) and reactive selenium species (RSeS) play integral roles in hydrogen sulfide (H2S) and hydrogen selenide (H2Se) biological signaling pathways, and dichalcogenide anions are proposed transient intermediates that facilitate a variety of biochemical transformations. Herein we report the selective synthesis, isolation, spectroscopic and structural characterization, and fundamental reactivity of persulfide (RSS-), perselenide (RSeSe-), thioselenide (RSSe-), and selenosulfide (RSeS-) anions. The isolated chalcogenides do not rely on steric protection for stability and have steric profiles analogous to cysteine (Cys). Simple reduction of S8 or Se by potassium benzyl thiolate (KSBn) or selenolate (KSeBn) in the presence of 18-crown-6 afforded [K(18-crown-6)][BnSS] (1), [K(18-crown-6)][BnSeSe] (2), [K(18-crown-6][BnSSe] (3), and [K(18-crown-6][BnSeS] (4). The chemical structure of each dichalcogenide was confirmed by X-ray crystallography and solution-state 1H, 13C, and 77Se NMR spectroscopy. To advance our understanding of the reactivity of these species, we demonstrated that reduction of 1-4 by PPh3 readily generates E═PPh3 (E: S, Se), and reduction of 1, 3, and 4 by DTT readily produces HE-/H2E. Furthermore, 1-4 react with CN- to produce ECN-, which is consistent with the detoxifying effects of dichalcogenide intermediates in the Rhodanese enzyme. Taken together, this work provides new insights into the inherent structural and reactivity characteristics of dichalcogenides relevant to biology and advances our understanding of the fundamental properties of these reactive anions.

Estrogen alleviates acute and chronic itch in mice.

Itching is associated with various skin diseases, including atopic dermatitis and allergic dermatitis, and leads to repeated scratching behavior and unpleasant sensation. Although clinical and laboratory research data have shown that estrogen is involved in regulating itch, the molecular and cellular basis of estrogen in itch sensation remains elusive. In the present study, it was found that estrogen-treated mice exhibited reduced scratching bouts when challenged with histamine, chloroquine, the proteinase-activated receptor-2 activating peptide SLIGRL-NH2 (SLIGRL), compound 48/80, and 5-hydroxytryptamine when compared with mice in the placebo group. Moreover, estrogen also suppressed scratching bouts in the mouse model of chronic itch induced by acetone-ether-water treatment. Notably, consistent with the behavioral tests, the present RNA-seq analysis showed that estrogen treatment caused significantly reduced expression levels of itch-related molecules such as Mas-related G-protein coupled receptor member A3, neuromedin B and natriuretic polypeptide b. In addition, estradiol attenuated histamine-induced and chloroquine-induced calcium influx in dorsal root ganglion neurons. Collectively, the data of the present study suggested that estrogen modulates the expression of itch-related molecules and suppresses both acute and chronic itch in mice.

Linc-UROD stabilizes ENO1 and PKM to strengthen glycolysis, proliferation and migration of pancreatic cancer cells.

Pancreatic cancer (PC) is a fatal malignancy, threatening human health in worldwide. Long non-coding RNAs (lncRNAs) have been acknowledged to be essential regulators in various biological processes of human cancers. However, the role of some novel lncRNAs in PC remain to be explored. In this study, we focused on the function and molecular mechanism of a novel lncRNA linc-UROD (also named TCONS_00002016 or XLOC_000166) in PC. The expression of linc-UROD was found to be upregulated in PC cells. The results of loss-of-function assays demonstrated that linc-UROD knockdown suppressed cell proliferation and migration, induced cell cycle G0/G1 arrest, and accelerated apoptosis of PC cells. Through mechanistic experiments, we found that IGF2BP3 stabilized linc-UROD through METTL3-mediated m6A modification. In addition, linc-UROD enhances the stability of ENO1 and PKM through interacting with them to inhibit ubiquitination. Detection on glucose consumption, pyruvate kinase activity and lactate production indicated that linc-UROD accelerated glycolysis of PC cells through PKM/ENO1-mediated pathway. To summarize, linc-UROD stabilized by IGF2BP3/METTL3 contributes to glycolysis and malignant phenotype of PC cells by stabilizing ENO1 and PKM. The findings suggest that linc-UROD may be a novel therapeutic target for PC patients.

Revealing Academic Evolution and Frontier Pattern in the Field of Uveitis Using Bibliometric Analysis, Natural Language Processing, and Machine Learning.

PURPOSE: Numerous uveitis articles were published in this century, underneath which hides valuable intelligence. We aimed to characterize the evolution and patterns in this field. METHODS: We divided the 15,994 uveitis papers into four consecutive time periods for bibliometric analysis, and applied latent Dirichlet allocation topic modeling and machine learning techniques to the latest period. . RESULTS: The yearly publication pattern fitted the curve: 1.21335x2 - 4,848.95282x + 4,844,935.58876 (R2 = 0.98311). The USA, the most productive country/region, focused on topics like ankylosing spondylitis and biologic therapy, whereas China (mainland) focused on topics like OCT and Behcet disease. The logistic regression showed the highest accuracy (71.6%) in the test set. CONCLUSION: In this century, a growing number of countries/regions/authors/journals are involved in the uveitis study, promoting the scientific output and thematic evolution. Our pioneering study uncovers the evolving academic trends and frontier patterns in this field using bibliometric analysis and AI algorithms.

Synthesis and reactivity of a tris(carbene) zinc chloride complex.

The [PhB(tBuIm)3]1- ligand has gained increased attention since it was first reported in 2006 due to its ability to stabilize highly reactive first row transition metal complexes. In this work, we investigate the coordination chemistry of this ligand with redox-inert zinc to understand how a zinc metal center behaves in such a strong coordinating environment. The PhB(tBuIm)3ZnCl (1) complex can be formed via deprotonation of [PhB(tBuIm)3][OTf]2 followed by the addition of ZnCl2. Salt metathesis reaction with nucleophilic n-BuLi yields the highly carbon-rich zinc coordination complex PhB(tBuIm)3ZnBu (2) with three carbene atom donors and one carbanion donor. In contrast, reaction of complex 1 with a less nucleophilic polysulfide reagent, [K.18-C-6]2[S4], leads to the formation of a tetrahedral zinc tetrasulfido complex via protonation of one carbene donor to form PhB(tBuIm)2(tBuImH)Zn(κ2-S4) (3).

Resveratrol's neural protective effects for the injured embryoid body and cerebral organoid.

OBJECTIVE: Resveratrol (RSV) is a polyphenol compound found in grapes, veratrum and other plants. It has been reported that RSV has anti-inflammatory, anti-oxidant, anti-cancer and other pharmacological effects. However, the impacts of RSV on development of nervous system are not understood well. The study aims to investigate RSV's neuroprotective effect during development and to provide a health care for pregnant women and their fetuses with RSV supplementation. METHODS: In this study, we induced human induced pluripotent stem cells (hiPSCs) to form the embryoid bodies (EBs) and cerebral organoids (COs) with 3 dimensional (3D) culture. In the meantime, D-galactose (D-gal, 5 mg/ml) was used to make nervous injury model, and on the other hand, RSV with various doses, such as 2 µm/L, 10 µm/L, 50 µm/L, were applied to understand its neuroprotection. Therefore, the cultures were divided into control group, D-gal nervous injury group and RSV intervention groups. After that, the diameters of EBs and COs were measured regularly under a reverted microscope. In the meantime, the neural proliferation, cell apoptosis and the differentiation of germ layers were detected via immunofluorescence. RESULTS: (1) D-gal could delay the development of EBs and COs; (2) RSV could rescue the atrophy of EBs and COs caused by D-gal; (3) RSV showed its neuroprotection, through promoting the neural cell proliferation, inhibiting apoptosis and accelerating the differentiation of germ layers. CONCLUSION: RSV has a neuroprotective effect on the development of the nervous system, suggesting RSV supplementation may be necessary during the health care of pregnancy and childhood.

Synthesis and Biological Evaluation of Novel Allobetulon/Allobetulin-Nucleoside Conjugates as AntitumorAgents.

Allobetulin is structurally similar tobetulinic acid, inducing the apoptosis of cancer cells with low toxicity. However, both of them exhibited weak antiproliferation against several tumor cell lines. Therefore, the new series of allobetulon/allobetulin-nucleoside conjugates 9a-10i were designed and synthesized for potency improvement. Compounds 9b, 9e, 10a, and 10d showed promising antiproliferative activity toward six tested cell lines, compared to zidovudine, cisplatin, and oxaliplatin based on their antitumor activity results. Among them, compound 10d exhibited much more potent antiproliferative activity against SMMC-7721, HepG2, MNK-45, SW620, and A549 human cancer cell lines than cisplatin and oxaliplatin. In the preliminary study for the mechanism of action, compound 10d induced cell apoptosis and autophagy in SMMC cells, resulting in antiproliferation and G0/G1 cell cycle arrest by regulating protein expression levels of Bax, Bcl-2, and LC3. Consequently, the nucleoside-conjugated allobetulin (10d) evidenced that nucleoside substitution was a viable strategy to improve allobetulin/allobetulon's antitumor activity based on our present study.

Screening of four key genes in esophageal carcinoma based on TCGA and GEO data and verification of anti-proliferative effect of LAPTM4B knockdown in esophageal carcinoma cells invitro.

Esophageal carcinoma (ESCA) is one of the most prevalent and aggressive malignancies of the gastrointestinal tract and constitutes sixth primary cause of cancer-related death worldwide. It is urgently needed to identify effective therapeutic targets. Differentially expressed genes (DEGs) involved in ESCA were identified via bioinformatics analysis. Four DEGs were selected for further analysis using Gene Expression Profiling Interactive Analysis, Human Protein Atlas, UALCAN web portal, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. 5-ethynyl-2'-deoxyuridine incorporation and cell counting kit-8 assays were used to evaluate cell proliferation. Western blot analysis was used to detect the protein levels of lysosomal-associated transmembrane protein 4B (LAPTM4B), Notch1, hairy and enhancer of split 1 (Hes1), and hairy and enhancer of split-related with YRPW motif 1 (Hey1). Results showed that LAPTM4B, Bcl-2 homology domain 3 (BH3)-interacting domain death agonist (BID), epithelial cell transforming sequence 2 (ECT2), and aurora kinase A (AURKA) were upregulated in several types of tumors including ESCA and correlated with tumor stage and tumor histology based on bioinformatics analysis. KEGG pathway analysis suggested that LAPTM4B-associated genes were significantly enriched in Notch pathway. Meanwhile, BID-, ECT2-, and AURKA-correlated genes were particularly enriched in p53 signaling pathway. Additionally, we found that LAPTM4B silencing inhibited cell proliferation and Notch pathway in ESCA cells. Notch1 overexpression abrogated LAPTM4B knockdown-induced proliferation reduction in ESCA cells. In conclusion, LAPTM4B silencing inhibited proliferation in ESCA cells by inactivating the Notch pathway.

The Influence of Heavy Metals on Gastric Tumorigenesis.

Objectives: This study aimed to observe the relationship among heavy metals concentration, microsatellite instability (MSI), and human epidermal growth factor receptor type 2 (HER2) gene amplification in gastric cancer (GC) patients. Methods: The concentrations of 18 heavy metals in the plasma of GC patients and healthy controls were measured by inductive coupled plasma emission spectrometry (ICP-MS). MSI detection was conducted by detecting 5 microsatellite repeat markers by PCR analysis. HER2 gene amplification was detected by fluorescence in situ hybridization (FISH). The relationship among heavy metal elements, tumor biomarkers, HER2 amplification, and MSI status was analyzed by Pearson correlation analysis. Results: A total of 105 GC patients and 62 healthy controls were recruited in this study. The concentration of arsenic (As), chromium (Cr), cuprum (Cu), mercury (Hg), manganese (Mn), lead (Pb), stibium (Sb), selenium (Se), stannum (Sn), strontium (Sr), thallium (Tl), vanadium (V), and zinc (Zn) were significantly different between GC patients and controls. Among 105 GC patients, including 87 microsatellite-stable (MSS) samples and 18 MSI samples, the concentration of Ga is significantly higher in the MSI group than that in the MSS group. Meanwhile, in 97 GC patients having detected HER2 gene amplification, 69 of 97 had negative HER2 gene amplification and the rest 28 GC patients had positive HER2 gene amplification. The concentration of Hg, Sn, and Tl is noticeably higher in the HER2 positive group than in the HER2 negative group. Only Sb was positively correlated with MSI, but none of these heavy metals was correlated with HER2 gene amplification. Conclusions: The results indicated that Sb has significant positive correlation with the MSI status, which suggests that Sb may cause MSI in GC. However, further research studies are required to elucidate the mechanisms in the near feature.

Sludge reduction and microbial community evolution of activated sludge induced by metabolic uncoupler o-chlorophenol in long-term anaerobic-oxic process.

Excess sludge management is a restrictive factor for the development of municipal wastewater treatment plants. The addition of metabolic uncouplers has been proven to be effective in sludge reduction. However, the long-term effect of metabolic uncoupler o-chlorophenol (oCP) on the biological wastewater treatment system operated in anaerobic-oxic mode is still unclear. To this end, two parallel reactors operated in anaerobic-oxic mode with and without 10 mg/L of oCP addition were investigated for 91 days. The results showed that 56.1 ± 2.3% of sludge reduction was achieved in the oCP-added system, and the nitrogen and phosphorus removal ability were negatively affected. Dosing oCP stimulated the formation of microbial products and increased the DNA concentration, but resulted in a decrease in the electronic transport activity of activated sludge. Microbial community analysis further demonstrated that a significant reduction of bacterial richness and diversity occurred after oCP dosing. However, after stopping oCP addition, the pollutant removal ability of activated sludge was gradually increased, but the sludge yield, as well as species richness and diversity, did not recover to the previous level. This study will provide insightful guidance on the long-term application of metabolic uncouplers in the activated sludge system.

An Adaptive Alternating Magnetic Interference Suppression (AAIS) Algorithm for Geomagnetic Vector Measurement.

To achieve high-precision vector measurement values in a geomagnetic field, it is necessary to develop methods for overcoming alternating magnetic interference (AMI), which is generated by electrical equipment. This paper proposes the adaptive alternating magnetic interference suppression (AAIS) algorithm. In this algorithm, first, only a triaxial fluxgate sensor measures the magnetic field data. The time-frequency diagram of the total magnetic field is obtained quickly through short-time Fourier transform and wavelet transform. Additionally, the time and frequency of AMI appearance are analyzed. Then, the triaxial adaptive notch filter suppresses the three-component related magnetic interference. Herein, simulation and actual experiments are performed to verify the effectiveness of AAIS. The results indicate that the algorithm can quickly detect the frequencies of AMI from the total magnetic field and adaptively fit their amplitude and phase on the vector magnetic field. Finally, AAIS can suppress the interference effectively. The AAIS algorithm realizes error compensation for the vector measurement values by the total magnetic field, which effectively improves the vector measurement accuracy of the geomagnetic field. We highlight that the AAIS algorithm is effective for AMIs of different frequencies, numbers, and intensities without reference sensors. Our work has practical implications in airborne, vehicle-mounted, and shipborne geomagnetic vector detection.

Genetic regulation and fermentation strategy for squalene production in Schizochytrium sp.

Squalene, as an important terpenoid, is extensively used in the medicine and health care fields owing to its functions of anti-oxidation, blood lipid regulation and cancer prevention. The marine microalgae, Schizochytrium sp., which acts as an excellent strain with potential of high squalene production was selected as the starting strain. The overexpressed strain with sqs gene got the reduced biomass and lipid, while the squalene titer was increased by 79.6% ± 4.7% to 12.8 ± 0.2 mg/L. In order to further increase squalene production, the recombinant strain (HS strain) with sqs and hmgr gene co-overexpression was further constructed. The biomass and squalene titer of the HS strain were increased by 13.6% ± 1.2% and 88.8% ± 5.3%, respectively, which indicated the carbon flux of the mevalonate pathway was enhanced for squalene accumulation. Regarding the squalene synthesis is completely coupled with cell growth, fermentation strategy to prolong the logarithmic growth phase was conducive to improve squalene production. Under the condition of optimal composition and concentrated medium, the squalene titer of HS strain was 27.0 ± 1.3 mg/L, which was 2.0 times that of the basal medium condition (13.5 ± 0.4 mg/L). This study which combined the metabolic engineering and fermentation strategy provides a new strategy for squalene production in Schizochytrium sp. KEY POINTS: •The overexpression of sqs and hmgr genes promoted carbon metabolism for squalene. •The optimal and concentrated media can increase squalene yield.