Extending the Record of Terpenes from Soft Coral Sarcophyton mililatensis.

In the present study, a new polyoxygenated cembranoid named sarcomililatol H (1) as well as six known terpenes 2-7 with different skeletons were isolated from South China Sea soft coral Sarcophyton mililatensis. Based on the comprehensive analyses of 1D and 2D NMR spectroscopic data, the structure of the new compound 1 was established. This new cembranoid was characterized by the presence of the rarely encountered tetrahydropyran ring with the ether linkage across C-2 and C-12. By applying the time-dependent density functional theory electronic circular dichroism (TDDFT ECD) approach, the absolute configuration of sarcomililatol H (1) was determined. All of the isolates were subjected to the anti-inflammatory and anti-tumor bioassays. However, none of them was active in these evaluations. Additionally, the preliminary virtual screening of inhibitory against SARS-CoV-2 by molecular docking showed that diterpene 1 could be regarded as a SARS-CoV-2 main protease (Mpro ) inhibitor (binding energy: -7.63 kcal/mol). The discovery of these terpenes has expanded the chemical diversity and complexity of terpenes from the species S. mililatensis.

Cembrane Diterpenes Possessing Nonaromatic Oxacycles from the Hainan Soft Coral Sarcophyton mililatensis.

Documents on the chemical composition of the soft coral Sarcophyton mililatensis are sparse. The present investigation of the Hainan soft coral S. mililatensis resulted in the discovery of six new cembrane diterpenes, sarcoxacyclols A-F (1-6) and four known analogs (7-10). Their structures were elucidated by extensive spectroscopic analysis along with a comparison with the data in current literature. The nonaromatic oxacycles in their structures were the rarely found tetrahydrofuran ether across C-1 and C-12 and tetrahydropyran ether across C-1 and C-11, respectively. Moreover, the absolute configuration of compound 4 was established unambiguously by X-ray diffraction analysis using Ga Kα radiation (λ = 1.34139 Å). Based on the biogenetical consideration, the absolute configurations of other five new compounds were tentatively assumed. Assessment of the bioactivity for these secondary metabolites revealed that compound 1 exhibited significant tumor necrosis factor (TNF)-α inhibitory activity (IC50 = 9.5 µmol/L), similar to the positive control dexamethasone (IC50 = 8.7 µmol/L), but no obvious cytotoxicity towards RAW264.7 cells (CC50 > 50 µmol/L). The preliminary molecular docking suggested the crucial roles of the hydroxyl and acetoxyl groups in the computational prediction of the binding mode between the diterpene and the protein.

Guided Isolation of An Uncommon Cembranoid Orthoester, Sarcotortin A, and Three Skeletal Diverse Terpenoids from the Hainan Soft Coral Sarcophyton tortuosum Based on Molecular Networking Strategy.

Applying the emerging molecular networking strategy, an uncommon cembranoid orthoester, sarcotortin A (1), featuring a 3/14/8/5-fused scaffold, an unusual eunicellane-type diterpenoid, sarcotorolide A (2), and two new biscembranoids, ximaolides M and N (7 and 8), along with nine known terpenoids 3-6 and 9-13 were isolated from the Hainan soft coral Sarcophyton tortuosum. The structure and absolute configuration of all new compounds were established by a combination of spectroscopic data, X-ray diffraction analysis, and/or quantum chemical computational approaches. The plausible biogenetic relationship among these skeletally different terpenoids was proposed and discussed. In in vitro bioassay, new compound 7 exhibited a remarkable inhibitory activity against protein tyrosine phosphatases 1B (PTP1B) with the IC50 value of 8.06 µM. In addition, compounds 4 and 10 displayed significant inhibitory effects on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophages cells with the IC50 values of 19.13 and 16.45 µM, respectively. Compound 9 showed interesting cytotoxicity against H1975, MDA-MB231, A549, and H1299 cancer cell lines with IC50 values of 31.59, 34.96, 43.87, and 27.93 µM, respectively.

Recent advances on marine mollusk-derived natural products: chemistry, chemical ecology and therapeutical potential.

Covering: 2011-2021Marine mollusks, which are well known as rich sources of diverse and biologically active natural products, have attracted significant attention from researchers due to their chemical and pharmacological properties. The occurrence of some of these marine mollusk-derived natural products in their preys, predators, and associated microorganisms has also gained interest in chemical ecology research. Based on previous reviews, herein, we present a comprehensive summary of the recent advances of interesting secondary metabolites from marine mollusks, focusing on their structural features, possible chemo-ecological significance, and promising biological activities, covering the literature from 2011 to 2021.

Sinuhirtone A, An Uncommon 17,19-Dinorxeniaphyllanoid, and Nine Related New Terpenoids from the Hainan Soft Coral Sinularia hirta.

Chemical investigation of the Hainan soft coral Sinularia hirta resulted in the isolation and identification of a library of sixteen structurally diverse terpenoids, including a dinorditerpenoid with an uncommon 17,19-dinorxeniaphyllane skeleton, namely sinuhirtone A (7), six new xeniaphyllane-type diterpenoids (1-6), one new norxeniaphyllanoid (8), two new norcaryophyllene-type sesquiterpenoids (9 and 10), together with six known related compounds (11-16). Compounds 1-3 are three new furanone-containing xeniaphyllane-type diterpenoids. The structures of the new compounds, including their absolute configurations, were determined by extensive spectroscopic analysis and a series of quantum chemical calculations, including quantum mechanical-nuclear magnetic resonance (QM-NMR), time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD), and optical rotatory dispersion (ORD) methods. A plausible biosynthetic connection between new compounds 1-9 was also proposed. New compounds 2-4, 7, and 8 were evaluated for in vitro cytotoxicity against four cancer cell lines.

Preliminary study of hemodynamics of iliac venous compression syndrome using magnetic resonance imaging.

OBJECTIVE: In clinical practice, the degree of iliac vein stenosis has often been inconsistent with the symptoms of chronic venous disease (CVD). To the best of our knowledge, no clinical studies have evaluated the hemodynamic changes associated with iliac vein stenosis. Magnetic resonance imaging (MRI) can noninvasively provide hemodynamic information. In the present study, we assessed the degree of stenosis associated with iliac venous compression syndrome and the relationships between iliac venous compression syndrome-induced, MRI-determined hemodynamic changes and lower limb symptoms. METHODS: Stenosis severity, the presence of collateral vessels, and flow rate (FR) differences between the common and external iliac veins secondary to iliac vein stenosis were measured using MRI in 69 patients with CVD. Villalta scores were used as a measure of symptom severity for all patients, and the percentage of change in the Villalta score was used as a measure of symptom improvement for the patients who had received iliac vein stents. Symptom severity for all patients, a subgroup of patients with iliac vein compression (affected limbs), and a group of patients with unilateral iliac vein compression treated with stents was correlated with stenosis, differences in the external and common iliac vein FRs (<0-mL/s group, indicating stenosis-induced decreased common iliac vein flow, and ≥0-mL/s group), and stenosis-induced collateral vessel formation. RESULTS: Iliac vein stenosis severity and FR differences in all affected limbs were correlated with the Villalta scores of the affected limbs (stenosis: r = 0.38, P < .001, n = 95; FR difference: r = -0.44, P < .001). In the unilateral compression subgroup, stenosis severity, FR differences, and the presence of collateral vessels were not associated with significant changes in contralateral symptoms. In the endovascular treatment subgroup, both lower limbs exhibited significant improvement after stent implantation (affected limb symptom remission, 64.6% ± 18.2%, n = 15; contralateral limb symptom remission, 49.1% ± 29.1%, n = 11). The rate of symptom remission was greater for patients with decreased iliac vein flow in the affected limbs (<0-mL/s group: 74.6% ± 16.4%, n = 7; ≥0-mL/s group: 52.2% ± 16.6%, n = 6; P = .032). CONCLUSIONS: Iliac vein stenosis, the presence of collateral vessels, and decreased FRs due to stenosis correlated significantly with lower limb symptom severity. Endovascular treatment yielded good outcomes in patients with stenosis >50%. A decreased iliac venous FR could indicate a better response to stent implantation and could be used in the diagnosis and guiding decisions to treat iliac venous compression.

Chemical constituents from the South China sea soft coral Sinularia humilis.

A new diterpenoid with an unusual capnosane skeleton, sinuhumilol A (1), alone with twelve known diverse compounds (2-13), were isolated from the South China Sea soft coral Sinularia humilis. Their structures and stereochemistry were elucidated by extensive spectroscopic analysis, quantum chemical calculations, and/or by the comparison of the spectroscopic data with those reported in the literature. In bioassay, compound 11 exhibited interesting specific cytotoxicity against the human colon adenocarcinoma cell line HT-29 with IC50 value of 12.5 µM.

Sex Difference in the Association Between Eating Away From Home and the Risk of High Serum Uric Acid in South China.

Background: The prevalence of high serum uric acid is increasingly rising in recent years, and diet behavior is perceived to be associated with it. This study aimed to explore the relationship between eating away from home (EAFH) and the risk of high serum uric acid in adults in South China. Methods: The data utilized in this study were from Guangdong Nutrition and Health Survey (NHS) 2015. Serum uric acid concentration was detected. EAFH in the past week was investigated. We defined EAFH as food consumption away from home. Dietary data were collected by 24-h recalls on 3 consecutive days. A generalized linear mixed-effects model was applied to compute the odds ratio (OR) and its corresponding 95% CI. Results: A total of 3,489 individuals were included in this study. A 1.27-fold OR (95% CI: 1.05-1.52, P = 0.012) of high serum uric acid was identified in adults with EAFH in comparison with those without EAFH. With respect to men, a 1.66-fold OR (95% CI: 1.3-2.1, P < 0.001) of high serum uric acid was observed. We also observed that men with EAFH had higher intakes of red meat, poultry, vegetable, carbohydrate, protein, fat, and total energy, while a lower grain intake than those without EAFH. However, there was a lack of significant association between EAFH and the odds ratio of high serum uric acid in women. Women with EAFH did not have higher consumptions of red meat, vegetable, fish, fat, and water than those without EAFH. Conclusions: This study found that EAFH was associated with an increased odds ratio of high serum uric acid in men, but not in women.

Sinusiaetone A, an Anti-inflammatory Norditerpenoid with a Bicyclo[11.3.0]hexadecane Nucleus from the Hainan Soft Coral Sinularia siaesensis.

A novel norditerpenoid, sinusiaetone A (1), featuring an uncommon bicyclo[11.3.0]hexadecane carbon skeleton, and four polyoxygenated cembranoids (2-5) were isolated from the Hainan soft coral Sinularia siaesensis. Their structures were established by spectroscopic analysis, X-ray diffraction, quantum chemical computational approaches, and/or a modified Mosher's method. A plausible biosynthetic pathway of 1 and its biogenetic relationship with 2-5 were proposed. New compounds 1-3 displayed an interesting inhibitory activity against lipopolysaccharide-induced inflammation in BV-2 microglial cells.

Further new cembranoids from the South China Sea soft coral Sarcophyton trocheliophorum.

Two new cembranoids, ximaosarcophytols A (1) and B (2), together with three related known ones (3-5), were isolated from the soft coral Sarcophyton trocheliophorum collected off the Ximao Island, Hainan Province, China. Their structures including the absolute configurations were elucidated by extensive spectroscopic analysis, TDDFT/ECD (time-dependent density functional theory/electronic circular dichroism) calculations and comparison with the reported data.

New lobane-type diterpenoids from the Xisha soft coral Sinularia polydactyla.

Lobane-type diterpenoids are not frequently discovered from marine soft corals. In this paper, three new lobane type diterpenes, 13-methoxyloba-8,10,15(16),17(18)-tetraene (1), 8,10,13(15)Z,16E-lobatetraene (2) and 19-hydroxy-lobatetraene (3), and a new natural compound, 17,18-epoxyloba-16-acetoxy-8,10,13(15)-trien (4), co-occurring with a known related diterpenoid, 18-methoxyloba-8,10,13(15),16(17)-tetraene (5), were isolated from the South China Sea soft coral Sinularia polydactyla. The structures of new compounds were determined by extensive spectroscopic analysis and by comparison with those reported in the literature. In bioassay, all the isolates were inactive on antibacterial, PTP1B inhibitory, and immunological activities. This study increased the chemical diversity of marine diterpenoids.

Next-generation sequencing identifies rare pathogenic and novel candidate variants in a cohort of Chinese patients with syndromic or nonsyndromic hearing loss.

BACKGROUND: Hearing loss (HL) is a common sensory disorder in humans characterized by extreme clinical and genetic heterogeneity. In recent years, next-generation sequencing (NGS) technologies have proven to be highly effective and powerful tools for population genetic studies of HL. Here, we analyzed clinical and molecular data from 21 Chinese deaf families who did not have hotspot mutations in the common deafness genes GJB2, SLC26A4, GJB3, and MT-RNR1. METHOD: Targeted next-generation sequencing (TGS) of 127 known deafness genes was performed in probands of 12 families, while whole-exome sequencing (WES) or trio-WES was used for the remaining nine families. RESULTS: Potential pathogenic mutations in a total of 12 deafness genes were identified in 13 probands; the mutations were observed in GJB2, CDH23, EDNRB, MYO15A, OTOA, OTOF, TBC1D24, SALL1, TMC1, TWNK, USH1C, and USH1G, with eight of the identified mutations being novel. Further, a copy number variant (CNV) was detected in one proband with heterozygous deletion of chromosome 4p16.3-4p15.32. Thus, the total diagnostic rate using NGS in our deafness patients reached 66.67% (14/21). CONCLUSIONS: These results expand the mutation spectrum of deafness-causing genes and provide support for the use of NGS detection technologies for routine molecular diagnosis in Chinese deaf populations.

Correction to: Association between dietary acid load and the risk of hypertension among adults from South China: result from nutrition and health survey (2015-2017).

It was highlighted that in the original article [1] the data on categorical variables was wrongly arranged in Table 1 and there was an incorrect statement in the fourth paragraph of the Discussion section.

Association between dietary acid load and the risk of hypertension among adults from South China: result from nutrition and health survey (2015-2017).

BACKGROUND: Higher dietary acid load (DAL) was considered to be associated with an elevated risk of hypertension, while related data from mainland China remains scarce and incomplete. We aim to evaluate the association between DAL and the risk of hypertension among adults from South China. METHODS: We conducted a nutrition and health survey in Guangdong Province located in southern China from 2015 to 2017. A four-stage probability sampling method was utilized to select representative samples of citizens aged ≥18 years old. DAL was assessed by potential renal acid load (PRAL) and net endogenous acid production (NEAP). Participants were divided to 4 groups (Q1-Q4) according to the quartile points of PRAL or NEAP distributions. Generalized linear mixed effects models were applied to evaluate the association between DAL and the risk of hypertension. RESULTS: A total of 3501 individuals were eligible for this study and 45.9% was male participants. Hypertension rate was 30.7%. A higher PRAL was associated with higher prevalence rate of hypertension among the male (P-trend = 0.03). OR for Q2 was 1.34 (95%CI, 0.94-1.91), Q3 was 1.53 (95%CI = 1.08, 2.16) and Q4 was 1.51 (95%CI, 1.08-2.16) among the male. However, as for total participants, the female, the participants with ≤55 years or participants with > 55 years, the associations were lack of significance. With respect to association between NEAP and hypertension, non-significant results were identified. CONCLUSIONS: The current study indicated male hypertension was associated with higher PRAL, while given to this study was cross-sectional design, further studies are warranted to verify the association.

Elevated hypertension risk associated with higher dietary acid load: A systematic review and meta-analysis.

BACKGROUND & AIMS: The association between dietary acid load and hypertension risk is inconclusive. We conducted a systematic review and meta-analysis to summarize effect of dietary acid load on blood pressure. METHODS: A comprehensively search was performed in electronic databases including EMBASE, PubMed, Web of Science and Chinese National Knowledge Infrastructure. Summary ORs and their corresponding 95% CIs were computed assuming a randomized model or fixed model. RESULTS: Ten publications comprising 4 cohort and 6 cross-sectional studies were eligible for meta-analysis. There were 8 studies about potential renal acid load (PRAL) and 4 about net endogenous acid production (NEAP). Essential hypertension was statistically associated with higher PRAL (OR = 1.14, 95% CI = 1.02-1.17). Our findings also demonstrated a positive impact of higher PRAL on elevating both diastolic pressure (WMD = 0.96, 95% CI = 0.67-1.26) and systolic pressure (WMD = 1.57, 95% CI = 1.12-2.03). A 35% increased risk of hypertension associated with higher NEAP was identified (OR = 1.35, 95% CI = 1.03-1.78). CONCLUSIONS: The current study suggests that dietary acid load might be potential risk factor of hypertension.

Benefit-risk assessment of commonly consumed fish species from South China Sea based on methyl mercury and DHA.

Even though a growing number of reports indicated favorable health effects with fish consumption, kinds of hazardous substances in fish were detected in fish and to be exceeded advisory limitation. Benefit-risk assessment of commonly consumed fish is urgently needed. We conducted fish consumption survey and fish sampling in the coast of South China Sea to assess benefit-risk effect of commonly consumed fish species. For local residents, weekly methyl mercury (MeHg) exposures from commonly consumed fish species ranged from 0.12 to 2.11 µg/kg bw. Apart from Muraenesox cinereus and Acanthopagrus latus, the rest of 92% (23/25) fish species were at low risk of MeHg exposure. Daily docosahexaenoic acid intakes via consuming specific fish were between 42.18 and 1687.04 mg/day. A total of 72% (18/25) fish species could provide 200 mg/day of DNA for local residents. Benefit-risk assessment assuming intelligence quotient (IQ) score model showed net IQ point gains between 1.53 and 5.65 points with consuming various fish species, indicative of large distinction of health benefit from various fish species. This study suggests commonly consumed fish species from China South Sea could bring much more positive effect than negative effect. Species-specific fish should be considered when providing recommendations of fish consumption. Muraenesox cinereus and Acanthopagrus latus should be minded with risk of MeHg exposure in taking large amounts.

Author Correction: Regional variation limits applications of healthy gut microbiome reference ranges and disease models.

In the version of this article originally published, in the sentence "Applying the same approach to obesity (Fig. 2b), MetS (Fig. 2c) and fatty liver (Fig. 2d) yielded similar results," two figure panels were cited incorrectly. The data for obesity are in Fig. 2c, and the data for MetS are in Fig. 2b. The sentence has been updated with the correct citations in the print, PDF and HTML versions of the article.

Linking gut microbiota, metabolic syndrome and economic status based on a population-level analysis.

BACKGROUND: The metabolic syndrome (MetS) epidemic is associated with economic development, lifestyle transition and dysbiosis of gut microbiota, but these associations are rarely studied at the population scale. Here, we utilised the Guangdong Gut Microbiome Project (GGMP), the largest Eastern population-based gut microbiome dataset covering individuals with different economic statuses, to investigate the relationships between the gut microbiome and host physiology, diet, geography, physical activity and socioeconomic status. RESULTS: At the population level, 529 OTUs were significantly associated with MetS. OTUs from Proteobacteria and Firmicutes (other than Ruminococcaceae) were mainly positively associated with MetS, whereas those from Bacteroidetes and Ruminococcaceae were negatively associated with MetS. Two hundred fourteen OTUs were significantly associated with host economic status (140 positive and 74 negative associations), and 157 of these OTUs were also MetS associated. A microbial MetS index was formulated to represent the overall gut dysbiosis of MetS. The values of this index were significantly higher in MetS subjects regardless of their economic status or geographical location. The index values did not increase with increasing personal economic status, although the prevalence of MetS was significantly higher in people of higher economic status. With increased economic status, the study population tended to consume more fruits and vegetables and fewer grains, whereas meat consumption was unchanged. Sedentary time was significantly and positively associated with higher economic status. The MetS index showed an additive effect with sedentary lifestyle, as the prevalence of MetS in individuals with high MetS index values and unhealthy lifestyles was significantly higher than that in the rest of the population. CONCLUSIONS: The gut microbiome is associated with MetS and economic status. A prolonged sedentary lifestyle, rather than Westernised dietary patterns, was the most notable lifestyle change in our Eastern population along with economic development. Moreover, gut dysbiosis and a Western lifestyle had an additive effect on increasing MetS prevalence.

Regional variation limits applications of healthy gut microbiome reference ranges and disease models.

Dysbiosis, departure of the gut microbiome from a healthy state, has been suggested to be a powerful biomarker of disease incidence and progression1-3. Diagnostic applications have been proposed for inflammatory bowel disease diagnosis and prognosis4, colorectal cancer prescreening5 and therapeutic choices in melanoma6. Noninvasive sampling could facilitate large-scale public health applications, including early diagnosis and risk assessment in metabolic7 and cardiovascular diseases8. To understand the generalizability of microbiota-based diagnostic models of metabolic disease, we characterized the gut microbiota of 7,009 individuals from 14 districts within 1 province in China. Among phenotypes, host location showed the strongest associations with microbiota variations. Microbiota-based metabolic disease models developed in one location failed when used elsewhere, suggesting that such models cannot be extrapolated. Interpolated models performed much better, especially in diseases with obvious microbiota-related characteristics. Interpolation efficiency decreased as geographic scale increased, indicating a need to build localized baseline and disease models to predict metabolic risks.