B-seco Limonoids with anti-inflammatory activity from Tetradium fraxinifolium (Hook.) T.G.Hartley.

Fraxinifolines A-F (1-6), six new B-seco limonoids, together with four known A,D-di-seco ones, were isolated from the twigs with leaves of Tetradium fraxinifolium. Their structures with absolute configurations were elucidated on the basis of analysis of MS, NMR, single-crystal X-ray diffraction and biogenetic pathway. An anti-inflammatory bioassay in vitro showed limonoids 1-3 had significant immunosuppressive effect against the production of pro-inflammatory cytokines (IL-1ß and/or TNF-α) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

Response of Ecosystem Services to Land Use Change in Madagascar Island, Africa: A Multi-Scale Perspective.

"Land Use and Land Cover Change (LULCC)" is increasingly being affected by ecosystem services value. LULCC patterns have been subjected to significant changes over time, primarily due to an ever-increasing population. It is rare to attempt to analyze the influence of such changes on a large variety of ecosystem benefits in Madagascar island. The economic value of ecosystem services in Madagascar island is evaluated throughout the period from 2000 to 2019. The expansion of the human population affects the changing value of ecosystem services directly. The PROBA-V SR time series 300 m spatial resolution cover of land datasets from the "Climate Change Initiative of the European Space Agency (ESA)" were used to measure the values of ecosystem activities and the changes in those values caused by land use. A value transfer method was used to evaluate the value of ecosystem services to land use changes on Madagascar island. The findings show that from 2000 to 2019, at the annual rate of 2.17 percent, Madagascar island's ecosystem service value (ESV) grew to 6.99 billion US dollars. The components that greatly contributed to the total change of ESV were waste treatment, genetic resources, food production, and habitat/refugia. These components in 2000 contributed 21.27%, 20.20%, 17.38%, and 13.80% of the total ESV, and 22.55%, 19.76%, 17.29%, and 13.78% of the total ESV in 2019, respectively. Furthermore, it was found that there was a great change in LULCC. From 2000 to 2019, bare land, built-up land, cultivated land, savannah, and wetland increased while other LULCC types decreased. The sensitivity coefficient ranged from 0.649 to 1.000, <1, with forestland registering the highest values. Wetland is in the second position for the most important land cover category in Madagascar, considering the total value of the ecosystem. The value of ecosystem benefits per unit of the land area was higher on cultivated land, despite the relatively low fraction of cultivated land area across these eras. The sensitivity indices of seven land types from 2000 to 2019 were mapped to understand better the geographical distribution patterns of ESV's "equivalent value coefficient" (VC) across various land uses. It is suggested that the ESV should be included in Madagascar's government land-use plan to manage it effectively and efficiently with fewer negative effects on the ecosystem.

The dynamic relationships between landscape structure and ecosystem services: An empirical analysis from the Wuhan metropolitan area, China.

Environmental managers have been striving to optimize landscape structure to achieve a sustained supply of ecosystem services (ESs). However, we still lack a full understanding of the relationships between landscape structure and ESs due to the absence of thorough investigations on the variability of these relationships in space and time. To fill this critical gap, we assessed landscape structure alongside four important ESs (agricultural production (AP), carbon sequestration (CS), soil conservation (SC), and water retention (WR)) in the Wuhan metropolitan area (WMA), and then analyzed the spatiotemporal impacts of landscape structure on ESs from 2000 to 2020 using Geographically and Temporally Weighted Regression. The results show only AP maintained a stable growth trend over the past two decades, while the other ESs fluctuated considerably with a noticeable decline in SC and WR. The importance of landscape structure in influencing ESs varies by time and place, depending on the local landscape composition and configuration. In general, landscape composition has a stronger and less temporally stable impact on ESs compared to configuration. Furthermore, increases in landscape diversity, as measured through Shannon's diversity index, and the percentage of woodlands were found to contribute to the simultaneous benefits of multiple ESs, but in most cases the effects of landscape structure on different ESs were different or even opposite, suggesting that trade-offs are critical in landscape management. The findings highlight the complex response of ESs to dramatically changing landscapes in the WMA and can guide decision-makers in precise spatial arrangement and temporal adjustments to improve current landscape management.

Dynamic Variation of Ecosystem Services Value under Land Use/Cover Change in the Black Soil Region of Northeastern China.

A better understanding of the dynamic variation in the ecosystem service value (ESV) under land use/cover change (LUCC) is conductive to improving ecosystem services and environmental protection. The present study took Landsat TM/ETM remote sensing images and socio-economic statistic data as data sources and extracted land-use data using RS and GIS technology at 5-year intervals from 1990 to 2020. Then, we interpreted the spatio-temporal characteristics of LUCC and analyzed ESV changes using the value equivalence method in the black soil region of northeastern China (BSRNC). The main results showed that land use changed significantly during the study period. Cultivated land continued to expand, especially paddy areas, which increased by 1.72 × 106 ha, with a relative change of 60.9% over 30 years. However, grassland decreased by 2.47 × 106 ha, with a relative change of -60.6% over 30 years. The ESV showed a declining trend, which decreased by CNY 607.96 million during 1990-2020. The decline in forest and grassland caused a significant decline in the ESV. Furthermore, the ESV sensitivity coefficients were less than one for all of the different categories of ecosystem services. LUCC has a considerable impact on ESV in the BSRNC, resulting in ecosystem function degradation. As a result, future policies must emphasize the relationship between food security and environmental protection in situations of significant land-use change.

Monoterpene indole alkaloids from Melodinus cochinchinensis (Lour.) Merr.

Melodicochinines A - D (1-4), four new monoterpene indole alkaloids (MIAs), along with 21 known ones, were isolated from the stems and twigs of Melodinus cochinchinensis. Their structures were elucidated on the basis of extensive spectroscopic analysis. A ubiquitin-rhodamine 110 assay showed that 11-methyloxytabersonine had potential inhibitory effect against ubiquitin-specific protease 7 (USP7).

Health inequities in COVID-19 vaccination among the elderly: Case of Connecticut.

BACKGROUND: In the United States, distribution plans for the COVID-19 vaccination were established at the state level. However, some states, such as Connecticut, followed an age-based strategy without considering occupations or co-morbid conditions due to its simplicity in implementation. This strategy raised concerns about exacerbating health inequities because it did not prioritize vulnerable communities, specifically, minorities and low-income groups. The study aims to examine the vaccination inequities among different population groups for people aged 65+. METHODS: A cross-sectional analysis of quantile-based independent sample t-test was employed to examine the relationship between eight social vulnerability indices (SVIs, i.e., below poverty, unemployed, without high school diploma, disability, minority, speaks English less than well, no vehicle, and mobile homes) and vaccination rates at the town level in Connecticut during the second phase of the vaccine distribution plan when individuals aged 65 and over were eligible. Negative binomial regressions were employed to further justify the relationships between SVIs and vaccination rates. RESULTS: The report shows that the differences in vaccination rates were statistically significant between the most vulnerable and the least vulnerable towns with respect to six SVIs (i.e., below poverty, without high school diploma, disability, minority, speaks English less than well, and no vehicle). The vaccination gap was greater for people aged 75+ than people aged 65-74. Among the selected SVIs, below poverty was negatively correlated with the vaccination rate for 75+, and without high school diploma was negatively correlated with both rates. CONCLUSIONS: This report reveals the significant health inequities in COVID-19 vaccination among the elderly population at the early vaccination phase. It can shed insights into health policy initiatives to improve vaccination coverage in the elderly communities, such as promoting onsite scheduling and increasing at-home vaccination services.

Polycyclic polyprenylated acylphloroglucinols from Hypericum choisianum.

Twenty-one polycyclic polyprenylated acylphloroglucinols, including three new compounds named as hyperichoisins A (3), B (14) and C (21), were isolated from the aerial parts of Hypericum choisianum. The structures of those new compounds were elucidated by analysis of mass, NMR data, and chiroptical properties. A bioassay showed that otogirinin B had significant inhibitory effect on cell proliferation of A549.

Polyprenylated acylphloroglucinols as deubiquitinating protease USP7 inhibitors from Hypericum hookerianum.

Hookerianones A - E (1-5), five new polyprenylated acylphloroglucinols (PPAPs), along with six known ones, were isolated from the aerial parts of Hypericum hookerianum. Their structures were elucidated by analyses of MS, NMR, chiroptical properties, biogenetic pathway, and/or single crystal X-ray diffraction. A ubiquitin-rhodamine 110 assay showed that furohyperforin and hypercalin C, two representative PPAPs in this plant, inhibited more than 90% USP7 at the concentration of 10 µM.

Alopecines A-E, five chloro-containing matrine-type alkaloids with immunosuppressive activities from the seeds of Sophora alopecuroides.

Alopecines A-E (1-5), five unusual matrine-type alkaloids featuring with an additional dichlorocyclopropane (1-3) or a di/tri-chloromethyl (4/5) attached on the D ring, were isolated from the seeds of Sophora alopecuroides. Their structures and absolute configurations were elucidated by extensive spectroscopic techniques, and X-ray diffraction analyses or time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations. Alkaloid 4 exhibited potent inhibitory effects on the proliferation of ConA-induced T lymphocytes or LPS-induced B cells with IC50 value of 3.98 or 3.74 µM, respectively.

Diverse lignans with anti-inflammatory activity from Urceola rosea.

Seventeen structurally diverse lignans, comprising six new compounds, ecdysanols A (1), B (11), C - E (13-15), and F (17), were isolated from the caulis of Urceola rosea. The structures and absolute configurations of these new compounds were elucidated by means of extensive analysis of mass and NMR data, as well as chiroptical properties. A bioassay in vitro showed that all lignans possessed anti-inflammatory effects by inhibiting the production of TNF-α, NO and/or IL-6 in LPS-stimulated RAW264.7 cells. Ecdysanol F (17) showed the most strongly effect against NO and IL-6 levels.

Flueggenoids A - E, new dinorditerpenoids from Flueggea virosa.

A phytochemical investigation on the twigs and leaves of Flueggea virosa (Euphorbiaceae) led to the isolation of flueggenoids A - E (1-5), five new 13-methyl-ent-podocarpanes, together with eleven known compounds (6-16). Their structures and absolute configurations were elucidated on the basis of extensive MS and NMR data analysis, and/or single-crystal X-ray diffraction, time-dependent density functional theory (TDDFT)-based electronic circular dichroism (ECD) calculations, and chemical transformation. All isolates were evaluated for anti-HCV activity, the results showed that terpenoids of F. virosa had nonnegligible contribution for the anti-HCV activity.

Triterpenoids, megastigmanes and hydroxycinnamic acid derivatives from Anisomeles indica.

Six triterpenoids (1-6), four megastigmanes (7-10) and five hydroxycinnamic acid derivatives (11-15) were isolated from the aerial part of Anisomeles indica (Lamiaceae). Of these components, compound 1 was identified to be a new triterpenoid with the structure of 2α,3α,19α-trihydroxyurs-12,20(30)-dien-28-oic acid based on extensive analysis of MS, 1D and 2D NMR spectroscopic data, while compounds 2-13 were obtained for the first time from Anisomeles species.

Limonoids from the fruits of Swietenia macrophylla with inhibitory activity against H2O2-induced apoptosis in HUVECs.

The fruits of Swietenia macrophylla (skyfruits) are commercially used as healthcare products to improve blood circulation. An investigation of active ingredients of skyfruits led to the isolation of four new limonoids, swietemacrolides A-D (1-4), together with ten known limonoids (5-14) and one proto-limonoid (15). Their structures were elucidated on the basis of MS and NMR data analysis. Swietemacrolide C (3) at the concentration of 10 µM showed significant protective effect on H2O2-induced apoptosis in human umbilical vascular endothelial cells (HUVECs), while swieteliacate D (5) displayed moderate anti-apoptotic activity.

Pyramidatine (Z88) Sensitizes Vincristine-Resistant Human Oral Cancer (KB/VCR) Cells to Chemotherapeutic Agents by Inhibition of P-glycoprotein.

BACKGROUND: Multi-drug resistance (MDR) remains a major impediment in cancer therapy. A major goal for scientists is to discover more effective compounds that are able to circumvent MDR and simultaneously have minimal adverse side effects. OBJECTIVE: In the present study, we aim to determine the anti-MDR effects of pyramidatine (Z88), a cinnamic acid-derived bisamide compound isolated from the leaves of Aglaia perviridis, on KB/VCR (vincristineresistant human oral cancer cells) and MCF-7/ADR (adriamycin-resistant human breast adenocarcinoma) cells. METHODS: Cell viability and average resistant fold (RF) of Z88 were examined by Cell Counting Kit-8 (CCK-8) assay. Flow cytometry, western blot, RT-PCR, Rhodamine 123 accumulation assay and P-glycoprotein (P-gp) ATPase assay were used to demonstrate the anti-MDR activity and mechanism of Z88. RESULTS: The average RF of Z88 is 0.09 and 0.51 in KB/VCR and MCF-7/ADR cells. A CCK-8 assay showed that Z88 could enhance the cytotoxicity of VCR toward KB/VCR cells. A FACS analysis revealed that Z88 could enhance the VCR-induced apoptosis as well as G2/M arrest in a dose-dependent manner in KB/VCR cells. Western blot results showed that the expression levels of PARP, Bax, and cyclin B1 all increased after treatment with 0.2 µmol/L (µM) of VCR combined with 10 µM of Z88 for 24 h in KB/VCR cells. Z88 also could enhance the accumulation of rhodamine 123. Further studies showed that Z88 could inhibit the verapamil stimulated Pgp ATPase activity. Additionally, qPCR detection and western blot assays revealed that Z88 could decrease the expression of P-gp at both RNA and protein level. CONCLUSION: Z88 exerted potent anti-MDR activity in vitro and its mechanisms are associated with dualinhibition of the function and expression of P-gp. These findings encourage efforts to develop more effective reversal agents to circumvent MDR based on Z88.

Highly oxygenated and structurally diverse diterpenoids from Euphorbia helioscopia.

A phytochemical investigation on the aerial part of Euphorbia helioscopia (Euphorbiaceae) led to the isolation of 22 highly oxygenated diterpenoids with structural types of ent-abietane, ent-kaurane, lathyrane, ent-atisane and ingenane. 17 of them, named euphelionolides A - N, 16-epi-18-hydroxy-abbeokutone, as well as eupheliotriols A and B, were identified to be previously undescribed compounds by extensive analysis of spectroscopic data. The stereostructures of euphelionolides A - K were determined by single crystal X-ray diffraction combined with analysis of substituent effects and comparison of optical characteristics. Eupheliotriol B is the first example of natural occurring lathyrol with 12Z-ene, while ent-atisanes are the first reported from the title plant. Furthermore, euphelionolides F and L exhibited significant cytotoxicity against MCF-7 and PANC-1 cell lines.

The synthesis of dendroflorin.

The first synthesis of dendroflorin has been achieved in 10 steps with an overall yield of 5.5%. The key step in the synthesis features the biphenyl structure is built through Suzuki-Miyaura reaction. In addition, the ortho-localization effect induced by aromatic substituent during the bromination of intermediate 8 is also observed and discussed.

Triterpenoids from the barks of Terminalia chebula.

Two new triterpenoids, termichebuloside A (1), an unusual dimeric triterpenoid saponin, and termichebulolide (2), an oleanolic acid-type lactone, along with 11 known triterpenoids, were isolated from MeOH extract of the barks of Terminalia chebula. The structures of 1 and 2 were elucidated to be arjunglucoside I-(3-O-19',23-O-19')-18,19-seco-19-hydroxyarjunglucoside I (1) and 2α,3ß,23-trihydroxyolean-11,13(18)-dien-28,19ß-olide (2), respectively, on the basis of spectroscopic evidences and biogenetic consideration.

The resolution of aglinin A epimers and their NMR assignments.

Aglinin A (1) is a mixture of C(24)-epimeric 20S,24-epoxy-24,25-dihydroxy-3,4-secodammar-4(28)-en-3-oic acid and present in plants of the family Meliaceae. The two epimers of 1 were resolved through an acetonide reaction, and the absolute configurations of two derivatives were deduced by the analysis of their (13)C NMR differences induced by γ-gauche or steric effect. Based on it, the (13)C NMR assignment of 24R-1 and 24S-1 was also established.

Arylnaphthalene lignan glycosides and other constituents from Phyllanthus reticulatus.

Two new arylnaphthalene lignan glycosides, named reticulatusides A (1) and B (2), together with eight known compounds were isolated from the 95% EtOH extract of the whole plant of Phyllanthus reticulatus. The structures of the new compounds were elucidated by spectroscopic methods.

Lamiolactone, a new iridoid lactone from Lamiophlomis rotata.

Lamiolactone (1), a new iridoid lactone, together with five known iridoids, were isolated from the 95% EtOH extract of the roots of Lamiophlomis rotata. The structure of 1 was elucidated to be methyl antirrhinolide-4-carboxylate on the basis of spectroscopic analysis.