Okeanomitos corallinicola gen. and sp. nov. (Nostocales, Cyanobacteria), a new toxic marine heterocyte-forming Cyanobacterium from a coral reef.

Cyanobacterial mats supplanting coral and spreading coral diseases in tropical reefs, intensified by environmental shifts caused by human-induced pressures, nutrient enrichment, and global climate change, pose grave risks to the survival of coral ecosystems. In this study, we characterized Okeanomitos corallinicola gen. and sp. nov., a newly discovered toxic marine heterocyte-forming cyanobacterium isolated from a coral reef ecosystem of the South China Sea. Phylogenetic analysis, based on the 16S rRNA gene and the secondary structure of the 16S-23S rRNA intergenic region, placed this species in a clade distinct from closely related genera, that is, Sphaerospermopsis stricto sensu, Raphidiopsis, and Amphiheterocytum. The O. corallinicola is a marine benthic species lacking gas vesicles, distinguishing it from other members of the Aphanizomenonaceae family. The genome of O. corallinicola is large and exhibits diverse functional capabilities, potentially contributing to the resilience and adaptability of coral reef ecosystems. In vitro assays revealed that O. corallinicola demonstrates notable cytotoxic activity against various cancer cell lines, suggesting its potential as a source of novel anticancer compounds. Furthermore, the identification of residual saxitoxin biosynthesis function in the genome of O. corallinicola, a marine cyanobacteria, supports the theory that saxitoxin genes in cyanobacteria and dinoflagellates may have been horizontally transferred between them or may have originated from a shared ancestor. Overall, the identification and characterization of O. corallinicola provides valuable contributions to cyanobacterial taxonomy, offering novel perspectives on complex interactions within coral reef ecosystems.

Recent Advances in Anti-Inflammatory Compounds from Marine Microorganisms.

Marine microbial secondary metabolites with diversified structures have been found as promising sources of anti-inflammatory lead compounds. This review summarizes the sources, chemical structures, and pharmacological properties of anti-inflammatory natural products reported from marine microorganisms in the past three years (2021-2023). Approximately 252 anti-inflammatory compounds, including 129 new ones, were predominantly obtained from marine fungi and they are structurally divided into polyketides (51.2%), terpenoids (21.0%), alkaloids (18.7%), amides or peptides (4.8%), and steroids (4.3%). This review will shed light on the development of marine microbial secondary metabolites as potential anti-inflammatory lead compounds with promising clinical applications in human health.

Carneusones A-F, Benzophenone Derivatives from Sponge-Derived Fungus Aspergillus carneus GXIMD00543.

Six benzophenone derivatives, carneusones A-F (1-6), along with seven known compounds (7-13) were isolated from a strain of sponge-derived marine fungus Aspergillus carneus GXIMD00543. Their chemical structures were elucidated by detailed spectroscopic data and quantum chemical calculations. Compounds 5, 6, and 8 exhibited moderate anti-inflammatory activity on NO secretion using lipopolysaccharide (LPS)-induced RAW 264.7 cells with EC50 values of 34.6 ± 0.9, 20.2 ± 1.8, and 26.8 ± 1.7 µM, while 11 showed potent effect with an EC50 value of 2.9 ± 0.1 µM.

Secofumitremorgins C and D, a pair of atropisomers from saltern-derived fungus Aspergillus fumigatus GXIMD00544.

A pair of atropisomers secofumitremorgins C (1a) and D (1b), together with fifteen known alkaloids (2-16), were isolated from a saltern-derived fungus Aspergillus fumigatus GXIMD00544. The structures of atropisomers 1a and 1b were elucidated by the detailed spectroscopic data, chemical reaction and quantum chemical calculations. Compounds 1 and 8 displayed antifungal spore germination effects against plant pathogenic fungus associated with sugarcane Fusarium sp. with inhibitory rates of 53% and 77% at the concentration of 100 µM, repectively. Atropisomers 1 also exhibited antifouling potential against Balanus amphitrite larval settlement with an inhibitory rate of 96% at the concentration of 100 µM.

Structured light 3-D sensing for scenes with discontinuous reflectivity: error removal based on scene reconstruction and normalization.

Structured light-based 3-D sensing technique reconstructs the 3-D shape from the disparity given by pixel correspondence of two sensors. However, for scene surface containing discontinuous reflectivity (DR), the captured intensity deviates from its actual value caused by the non-ideal camera point spread function (PSF), thus generating 3-D measurement error. First, we construct the error model of fringe projection profilometry (FPP). From which, we conclude that the DR error of FPP is related to both the camera PSF and the scene reflectivity. The DR error of FPP is hard to be alleviated because of unknown scene reflectivity. Second, we introduce single-pixel imaging (SI) to reconstruct the scene reflectivity and normalize the scene with scene reflectivity "captured" by the projector. From the normalized scene reflectivity, pixel correspondence with error opposite to the original reflectivity is calculated for the DR error removal. Third, we propose an accurate 3-D reconstruction method under discontinuous reflectivity. In this method, pixel correspondence is first established by using FPP, and then refined by using SI with reflectivity normalization. Both the analysis and the measurement accuracy are verified under scenes with different reflectivity distributions in the experiments. As a result, the DR error is effectively alleviated while taking an acceptable measurement time.

Efficacy and Clinical Significance of the Zuogui Pill on Premature Ovarian Failure via the GDF-9/Smad2 Pathway.

Our study aims to investigate the efficacy and clinical significance of the Zuogui pill (ZGP) on premature ovarian failure (POF) via the GDF-9/Smad2 pathway. Changes in clinical symptoms in the control group (treated with Femoston alone) and the treatment group (treated with ZGP combined with Femoston) were assessed before and after treatment. Sex hormone levels, serum inflammatory cytokine levels, and ultrasound parameters were measured before and after treatment. POF rat models were established using cyclophosphamide and the POF rats were treated with Femoston, or ZGP combined with Femoston. GDF-9 and Smad2 expression levels were determined by RT-qPCR. The follicle-stimulating hormone (FSH), luteinizing hormone (LH), interleukin (IL)-6, and IL-21 levels, and the pulsatility index (PI) and resistance index (RI) values were decreased, while the estradiol (E2) and anti-Mullerian hormone (AMH) levels, antral follicle count (AFC), ovarian volume (OV), mean ovarian diameter (MOD), and peak systolic velocity (PSV) values were increased in the treatment group compared to the control group. After treatment with ZGP combined with Femoston, GDF-9 and Smad2 expression in the ovarian tissues of POF rats increased. ZGP has a therapeutic effect on POF via modulation of the GDF-9/Smad2 pathway.

Identification and bioactivity evaluation of miliusanes from Miliusa sinensis.

Miliusanes are a class of anticancer lead molecules belonging to meroterpenoids with an 18-carbon skeleton isolated from Miliusa plants. A phytochemical study of the plant M. sinensis was carried out to discover new miliusanes with diverse structural features in order to better understand their structure-activity relationship. As a result, 20 compounds including 12 new ones (7-14 and 17-20) belonging to two sub-classes of miliusanes were isolated and identified from the twigs and leaves of this plant. Their structures, including absolute configurations, were determined by spectroscopic analyses and electronic circular dichroism. The absolute stereochemistry of miliusane structures has also been confirmed for the first time through the single crystal X-ray diffraction analysis of miliusol (1). Bioactivity evaluation showed that some of the miliusane isolates potently inhibit cell growth of several human derived cancer cell lines with IC50 values ranging from 0.52 to 23.5 µM. Compound 11 demonstrated more potent cytotoxic activity than the known miliusol (1) in stomach cancer cells though its structure contains an unconjugated 1, 4-diketone system, which added a new structure-activity feature to miliusanes. The preliminary mechanism of action studies revealed that they could be a class of dual cell migration inhibitor and senescence inducer.

Stir-bar sorptive extraction based on hydroxyl-functionalized zirconium-metal-organic framework for the detection of three quinolones in actual samples.

A novel analytical method based on stir-bar sorptive extraction was proposed for the determination of three trace quinolones in fish and shrimp samples. UiO-66-(OH)2 , a hydroxyl-functionalized zirconium metal-organic framework, has been coated on frosted glass rods by an in situ growth method. The product, UiO-66-(OH)2 modified frosted glass rods, has been characterized and key parameters have been optimized in combination with ultra-high-performance liquid chromatography. The detection limits of enoxacin, norfloxacin, and ciprofloxacin were 0.48-0.8 ng ml-1 , and the detection concentrations were in the range of 10-300 ng ml-1 , showing a good linear relationship. This method was used for the determination of three quinolones in aquatic organisms, and the recoveries in spiked fish and shrimp muscle tissue samples were 74.8%-105.4% and 82.5%-115.8%, respectively. The relative standard deviations were less than 6.9%. The established method combined stir-bar sorptive extraction based on UiO-66-(OH)2 modified frosted glass rods with ultra-high-performance liquid chromatography, has good application prospects for the detection of quinolone residues in fish and shrimp muscle samples.

Marine Natural Products from the Beibu Gulf: Sources, Chemistry, and Bioactivities.

Marine natural products (MNPs) play an important role in the discovery and development of new drugs. The Beibu Gulf of South China Sea harbors four representative marine ecosystems, including coral reefs, mangroves, seaweed beds, and coastal wetlands, which are rich in underexplored marine biological resources that produce a plethora of diversified MNPs. In our ongoing efforts to discover novel and biologically active MNPs from the Beibu Gulf, we provide a systematic overview of the sources, chemical structures, and bioactive properties of a total of 477 new MNPs derived from the Beibu Gulf, citing 133 references and covering the literature from the first report in November 2003 up to September 2022. These reviewed MNPs were structurally classified into polyketides (43%), terpenoids (40%), nitrogen-containing compounds (12%), and glucosides (5%), which mainly originated from microorganisms (52%) and macroorganisms (48%). Notably, they were predominantly found with cytotoxic, antibacterial, and anti-inflammatory activities. This review will shed light on these untapped Beibu Gulf-derived MNPs as promising lead compounds for the development of new drugs.

Plant-derived lignans as potential antiviral agents: a systematic review.

Medicinal plants are one of the most important sources of antiviral agents and lead compounds. Lignans are a large class of natural compounds comprising two phenyl propane units. Many of them have demonstrated biological activities, and some of them have even been developed as therapeutic drugs. In this review, 630 lignans, including those obtained from medicinal plants and their chemical derivatives, were systematically reviewed for their antiviral activity and mechanism of action. The compounds discussed herein were published in articles between 1998 and 2020. The articles were identified using both database searches (e.g., Web of Science, Pub Med and Scifinder) using key words such as: antiviral activity, antiviral effects, lignans, HBV, HCV, HIV, HPV, HSV, JEV, SARS-CoV, RSV and influenza A virus, and directed searches of scholarly publisher's websites including ACS, Elsevier, Springer, Thieme, and Wiley. The compounds were classified on their structural characteristics as 1) arylnaphthalene lignans, 2) aryltetralin lignans, 3) dibenzylbutyrolactone lignans, 4) dibenzylbutane lignans, 5) tetrahydrofuranoid and tetrahydrofurofuranoid lignans, 6) benzofuran lignans, 7) neolignans, 8) dibenzocyclooctadiene lignans and homolignans, and 9) norlignans and other lignoids. Details on isolation and antiviral activities of the most active compounds within each class of lignan are discussed in detail, as are studies of synthetic lignans that provide structure-activity relationship information.

Ex situ Ge-doping of CZTS nanocrystals and CZTSSe solar absorber films.

Cu2ZnSn(S,Se)4 (CZTSSe) is a promising material for thin-film photovoltaics, however, the open-circuit voltage (VOC) deficit of CZTSSe prevents the device performance from exceeding 13% conversion efficiency. CZTSSe is a heavily compensated material that is rich in point defects and prone to the formation of secondary phases. The landscape of these defects is complex and some mitigation is possible by employing non-stoichiometric conditions. Another route used to reduce the effects of undesirable defects is the doping and alloying of the material to suppress certain defects and improve crystallization, such as with germanium. The majority of works deposit Ge adjacent to a stacked metallic precursor deposited by physical vapour deposition before annealing in a selenium rich atmosphere. Here, we use an established hot-injection process to synthesise Cu2ZnSnS4 nanocrystals of a pre-determined composition, which are subsequently doped with Ge during selenisation to aid recrystallisation and reduce the effects of Sn species. Through Ge incorporation, we demonstrate structural changes with a negligible change in the energy bandgap but substantial increases in the crystallinity and grain morphology, which are associated with a Ge-Se growth mechanism, and gains in both the VOC and conversion efficiency. We use surface energy-filtered photoelectron emission microscopy (EF-PEEM) to map the surface work function terrains and show an improved electronic landscape, which we attribute to a reduction in the segregation of low local effective work function (LEWF) Sn(II) chalcogenide phases.

New 3-Acyl Tetramic Acid Derivatives from the Deep-Sea-Derived Fungus Lecanicillium fusisporum.

Seven rare C3-C6 reduced 3-acyl tetramic acid derivatives, lecanicilliumins A-G (1-7), along with the known analogue cladosporiumin D (8), were obtained from the extract of the deep-sea-derived fungus Lecanicillium fusisporum GXIMD00542 within the family Clavipitacae. Their structures were elucidated by extensive spectroscopic data analysis, quantum chemistry calculations and chemical reaction. Compounds 1, 2, 5-7 exhibited moderate anti-inflammatory activity against NF-κB production using lipopolysaccharide (LPS) induced RAW264.7 cells with EC50 values range of 18.49-30.19 µM.

Stable Axially Chiral Isomers of Arylnaphthalene Lignan Glycosides with Antiviral Potential Discovered from Justicia procumbens.

Arylnaphthalene lignans (ANLs) were known to have axial chirality due to the biphenyl skeleton with hindered rotation at the single bond. However, the stable ANL atropisomers have not been isolated from nature until the present study. Phytochemical separation of the methanol extract of the stems and barks of Justicia procumbens led to the isolation of 11 ANL glycosides including four pairs of new atropisomers with stable confirmations at room temperature. Their structures were deduced from elucidation of the extensive spectral data, and their absolute configurations were determined by the circular dichroism, electronic circular dichroism, and X-ray methods as well as the total synthesis of one pair of the atropisomers. The ANL compounds were evaluated for their antiviral potential, and it was found that they displayed great antiviral activity discrepancy between a pair of atropisomers due to the geometric orientation. The 1'P-oriented atropisomers showed much more significant antiviral potency than their corresponding 1'M-oriented counterparts. The biological activity discrepancy caused by the axial chirality will not only inspire synthetic design of novel ANL atropisomers to enrich the structural diversity, but also provide important hints to direct the synthetic approaches toward the antiviral drug development of ANL compounds.

1,3-Benzodioxole-based fibrate derivatives as potential hypolipidemic and hepatoprotective agents.

A series of target compounds 1,3-benzodioxole-based fibrate derivatives were designed and synthesized. All the target compounds were preliminarily evaluated by hyperlipidemia mice induced by Triton WR-1339, in which compound 12 displayed a greater anti-hyperlipidemia activity than other compounds as well as positive drug fenofibrate (FF). 12 showed a significant reduction of plasma lipids, such as triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterin (LDL-C), in high fat diet (HFD) induced hyperlipidemic mice. In addition, hepatic transaminases (AST and ALT) were ameliorated after administration of 12, in particular the AST, and the histopathological examination showed that 12 improved the hepatic lipid accumulation. The expression of PPAR-α involved in lipids metabolism was up-regulated in the liver tissues of 12-treated group. Other significant activity such as antioxidant, and anti-inflammation was confirmed and reinforced the effects of 12 as a potential hypolipidemia and hepatoprotective agent.

The combination of sesamol and clofibric acid moieties leads to a novel potent hypolipidemic agent with antioxidant, anti-inflammatory and hepatoprotective activity.

Oxidative stress and inflammation have been considered the main factors in the liver injury of clofibrate (CF). To obtain a novel antihyperlipidemic agent with antioxidant, anti-inflammation and hepatoprotection, the combination of sesamol and clofibric acid moieties was performed and achieved sesamol-clofibrate (CF-Sesamol). CF-Sesamol showed significant hypolipidemia effects in hyperlipidemia mice induced by Triton WR 1339, reducing TG by 38.8% (P < 0.01) and TC by 35.1% (P < 0.01). CF-Sesamol also displayed an alleviating effect on hepatotoxicity. The hepatic weight and hepatic coefficient were decreased. The amelioration of liver function was observed, such as aspartate and lactate transaminases (AST and ALT), alkaline phosphatase (ALP) and total proteins (TP) levels. Liver histopathological examination showed that hepatocyte necrosis, cytoplasmic loosening, nuclear degeneration and inflammatory cell infiltration reduced obviously by treatment with CF-Sesamol. Related molecular mechanisms on hepatoprotection showed that CF-Sesamol up-regulated Nrf2 and HO-1 expression and down-regulated p-NF-κB p65 expression in hepatic tissues. CF-Sesamol has significant antioxidant and anti-inflammatory effects. Plasma antioxidant enzymes such as SOD and CAT increased, anti-lipid peroxidation product MDA decreased. The expression of TNF-α and IL-6 inflammatory cytokines in liver was significantly lower than that in the CF group. The results indicated that CF-Sesamol exerted more potent antihyperlipidemic effects and definite hepatoprotective activity partly through the Nrf2/NF-κB-mediated signaling pathway.

Structural simplification and bioisostere principle lead to Bis-benzodioxole-fibrate derivatives as potential hypolipidemic and hepatoprotective agents.

The bis-benzodioxole-fibrate hybrids were designed by structural simplification and bioisostere principle. Lipids lowering activity was preliminarily screened by Triton WR 1339 induced hyperlipidemia mice model, in which T3 showed the best hypolipidemia, decreasing plasma triglyceride (TG) and total cholesterol (TC), which were better than sesamin and fenofibrate (FF). T3 was also found to significantly reduce TG, TC and low density lipoprotein cholesterin (LDL-C) both in plasma and liver tissue of high fat diet (HFD) induced hyperlipidemic mice. In addition, T3 showed hepatoprotective activity, which the noteworthy amelioration in liver aminotransferases (AST and ALT) was evaluated and the histopathological observation exhibited that T3 inhibited lipids accumulation in the hepatic and alleviated liver damage. The expression of PPAR-α receptor involved lipids metabolism in liver tissue significantly increased after T3 supplementation. Other potent activity, such as antioxidation and anti-inflammation, was also observed. The molecular docking study revealed that T3 has good affinity activity toward to the active site of PPAR-α receptor. Based on these findings, T3 may serve as an effective hypolipidemic agent with hepatoprotection.

Impact of treatment delays on vitiligo during the COVID-19 pandemic: A retrospective study.

Due to the COVID-19 pandemic, routine treatments are delayed to some extent and their negative impacts have been widely reported. However, virtually nothing is known about vitiligo in the context of COVID-19. Therefore, we analyzed treatment delays and its impact on vitiligo, aiming to provide suggestions on vitiligo management within this special period. We performed a retrospective cohort study on 322 patients who visited our clinics at least 2 times from January to December 2020, and their medical records and photographs were reviewed. Patients were divided into normal (n = 155) and late group (n = 167) based on whether experienced treatment delays. As for the active cases, the late group showed higher progression rate than normal group (35 of 86 [40.7%] vs. 10 of 81 [12.3%]; p = 0.002). Moreover, we observed higher recurrence rate in delay group than those of normal group (26 of 81[32.1%] vs. 9 of 74 [12.2%]; p = 0.018) among stable cases. Further univariate and multivariate analysis determined treatment delays as the most important independent risk factor for disease progression and recurrence, and maintenance therapy (>2 years) as a protective factor against recurrence. This study, for the first time, revealed the independent adverse impact of treatment delays on the progression and recurrence of vitiligo and indicated the significance of continuous treatment for halting progression and long-term maintenance therapy for preventing recurrence for vitiligo, which should be highly valued in the management of vitiligo during the COVID-19 pandemic.

3,4-Dihydroxyphenethyl nitrate with nitric oxide releasing, antioxidant, hypoglycemic and hypolipidemic effects.

Nitric oxide (NO) dysfunction, oxidative stress, and dyslipidemia are main risk factors associated with the pathophysiology of diabetic complications. In this study, 3,4-dihydroxyphenethyl nitrate (HT-ONO2) was designed, synthesized and evaluated, which incorporated hydroxytyrosol (HT) and nitrate. HT-ONO2 significantly exhibited hypoglycemic activity after oral administration to diabetic mice induced by streptozocin (STZ). HT-ONO2 also potently decreased plasma triglyceride (TG), total cholesterol (TC) in hyperlipidemia mice induced by Triton WR 1339. Meanwhile, HT-ONO2 displayed NO-releasing and antioxidant activity both in diabetic and hyperlipidemia mice and in vitro. Moreover, HT-ONO2 shown definite vasodilation and α-glucosidase inhibition activity in vitro. The results suggested that the hybrid hydroxytyrosol-based nitrate with NO supplement, antioxidant, hypoglycemia and hypolipidemia provided a potential multi-target agent to ameliorate the diabetes mellitus and its complications.

Antimalarial Activity of Plant Metabolites.

Malaria, as a major global health problem, continues to affect a large number of people each year, especially those in developing countries. Effective drug discovery is still one of the main efforts to control malaria. As natural products are still considered as a key source for discovery and development of therapeutic agents, we have evaluated more than 2000 plant extracts against Plasmodium falciparum. As a result, we discovered dozens of plant leads that displayed antimalarial activity. Our phytochemical study of some of these plant extracts led to the identification of several potent antimalarial compounds. The prior comprehensive review article entitled “Antimalarial activity of plant metabolites” by Schwikkard and Van Heerden (2002) reported structures of plant-derived compounds with antiplasmodial activity and covered literature up to the year 2000. As a continuation of this effort, the present review covers the antimalarial compounds isolated from plants, including marine plants, reported in the literature from 2001 to the end of 2017. During the span of the last 17 years, 175 antiplasmodial compounds were discovered from plants. These active compounds are organized in our review article according to their plant families. In addition, we also include ethnobotanical information of the antimalarial plants discussed.