Sleep-disordered breathing and nocturnal hypoxemia in chronic thromboembolic pulmonary disease.

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

[Effect and mechanism of Linggui Zhugan Decoction in regulating Sig1R on Angâ ¡-induced cardiomyocyte hypertrophy].

This study aims to explore the mechanism of Linggui Zhugan Decoction(LGZGD) in inhibiting Angiotensin Ⅱ(AngⅡ)-induced cardiomyocyte hypertrophy by regulating sigma-1 receptor(Sig1R). The model of H9c2 cardiomyocyte hypertrophy induced by AngⅡ in vitro was established by preparing LGZGD-containing serum and blank serum. H9c2 cells were divided into normal group, AngⅡ model group, 20% normal rat serum group(20% NSC), and 20% LGZGD-containing serum group. After the cells were incubated with AngⅡ(1 µmol·L~(-1)) or AngⅡ with serum for 72 h, the surface area of cardiomyocytes was detected by phalloidine staining, and the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase were detected by micromethod. The mitochondrial Ca~(2+) levels were detected by flow cytometry, and the expression levels of atrial natriuretic peptide(ANP), brain natriuretic peptide(BNP), Sig1R, and inositol 1,4,5-triphosphate receptor type 2(IP_3R_2) were detected by Western blot. The expression of Sig1R was down-regulated by transfecting specific siRNA for investigating the efficacy of LGZGD-containing serum on cardiomyocyte surface area, Na~+-K~+-ATPase activity, Ca~(2+)-Mg~(2+)-ATPase activity, mitochondrial Ca~(2+), as well as ANP, BNP, and IP_3R_2 protein expressions. The results showed that compared with the normal group, AngⅡ could significantly increase the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.01), and it could decrease the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+), and the expression of Sig1R(P<0.01). In addition, IP_3R_2 protein expression was significantly increased(P<0.01). LGZGD-containing serum could significantly decrease the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.05, P<0.01), and it could increase the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+ )(P<0.01), and the expression of Sig1R(P<0.05). In addition, IP_3R_2 protein expression was significantly decreased(P<0.05). However, after Sig1R was down-regulated, the effects of LGZGD-containing serum were reversed(P<0.01). These results indicated that the LGZGD-containing serum could inhibit cardiomyocyte hypertrophy induced by AngⅡ, and its pharmacological effect was related to regulating Sig1R, promoting mitochondrial Ca~(2+ )inflow, restoring ATP synthesis, and protecting mitochondrial function.

Insecure attachment and eating disorder symptoms: Intolerance of uncertainty and emotion regulation as mediators.

OBJECTIVE: Literature on eating disorder (ED) symptoms of Black, Indigenous, and People of Color (BIPOC) group is extremely scarce. This study aimed to understand the mechanisms underlying the associations between insecure attachment and ED symptoms and examine whether these mechanisms differed between White and BIPOC groups. METHOD: The study investigated direct and indirect relationship between attachment anxiety/avoidance and ED symptoms via intolerance of uncertainty (IU) and emotion regulation strategies of suppression and reappraisal. Further, we examined whether the proposed mechanisms equally represented White versus BIPOC using Multigroup Structural Equation Model (MG-SEM). A total of 1227 college students (48.50% BIPOC and 51.50% White) completed research questionnaires. RESULTS: Results showed that IU and suppression mediated the relations between insecure attachment and ED symptoms for both White and BIPOC groups. Uniquely, reappraisal mediated the relations between insecure attachment and ED symptoms for the White group, but not for the BIPOC group. DISCUSSION: The implications of the findings for culturally informed practice are discussed, including targeting increasing tolerability of uncertainties and improving emotion regulation to mitigate ED symptoms for those with insecure attachment.

Forest management positively reshapes the phyllosphere bacterial community and improves community stability.

Research has shown that forest management can improve the post-drought growth and resilience of Qinghai spruce in the eastern Qilian Mountains, located on the northeastern Tibetan Plateau. However, the impact of such management on the tree-associated phyllosphere microbiome is not yet fully understood. This study provides new evidence of positive forest management effects on the phyllosphere microbiome after extreme drought, from the perspectives of community diversity, structure, network inference, keystone species, and assembly processes. In managed Qinghai spruce forest, the α-diversity of the phyllosphere bacterial communities increased, whereas the ß-diversity decreased. In addition, the phyllosphere bacterial community became more stable and resistant, yet less complex, following forest management. Keystone species inferred from a bacterial network also changed under forest management. Furthermore, forest management mediated changes in community assembly processes, intensifying the influence of determinacy, while diminishing that of stochasticity. These findings support the hypothesis that management can re-assemble the phyllosphere bacterial community, enhance community stability, and ultimately improve tree growth. Overall, the study highlights the importance of forest management on the phyllosphere microbiome and furnishes new insights into forest conservation from the perspective of managing microbial processes and effects.

Interim analyses of a first-in-human phase 1/2 mRNA trial for propionic acidaemia.

Propionic acidaemia is a rare disorder caused by defects in the propionyl-coenzyme A carboxylase α or ß (PCCA or PCCB) subunits that leads to an accumulation of toxic metabolites and to recurrent, life-threatening metabolic decompensation events. Here we report interim analyses of a first-in-human, phase 1/2, open-label, dose-optimization study and an extension study evaluating the safety and efficacy of mRNA-3927, a dual mRNA therapy encoding PCCA and PCCB. As of 31 May 2023, 16 participants were enrolled across 5 dose cohorts. Twelve of the 16 participants completed the dose-optimization study and enrolled in the extension study. A total of 346 intravenous doses of mRNA-3927 were administered over a total of 15.69 person-years of treatment. No dose-limiting toxicities occurred. Treatment-emergent adverse events were reported in 15 out of the 16 (93.8%) participants. Preliminary analysis suggests an increase in the exposure to mRNA-3927 with dose escalation, and a 70% reduction in the risk of metabolic decompensation events among 8 participants who reported them in the 12-month pretreatment period.

Phosphorus stoichiometric homeostasis of submerged macrophytes and associations with interspecific interactions and community stability in Erhai Lake, China.

According to stoichiometric homeostasis theory, eutrophication is expected to increase the dominance of submerged macrophytes with low homeostatic regulation coefficients (H) relative to those with high H values, ultimately reducing macrophyte community stability. However, empirical evidence supporting this hypothesis is limited. In this study, we conducted a three-year tracking survey (seven sampling events) at 81 locations across three regions of Erhai Lake. We assessed the H values of submerged macrophyte species, revealing significant H values for phosphorus (P) and strong associations of HP values (range: 1.58-2.94) with species and community stability. Moreover, in plots simultaneously containing the dominant high-HP species, Potamogeton maackianus, and its low-HP counterpart, Ceratophyllum demersum, we explored the relationships among eutrophication, interspecific interaction shifts, and community dynamics. As the environmental P concentration increased, the dominance of P. maackianus decreased, while that of C. demersum increased. This shift coincided with reductions in community HP and stability. Our study underpins the effectiveness of H values for forecasting interspecific interactions among submerged macrophytes, thereby clarifying how eutrophication contributes to the decline in stability of the submerged macrophyte community.

The effect on income of providing near vision correction to workers in Bangladesh: The THRIVE (Tradespeople and Hand-workers Rural Initiative for a Vision-enhanced Economy) randomized controlled trial.

INTRODUCTION: Presbyopia, the leading cause of vision impairment globally, is common during working years. However, no trials have assessed presbyopia's impact on income. METHODS: In April 2017, we conducted a census among 59 Bangladesh villages to identify persons aged 35 to 65 years with presbyopia (presenting distance vision > = 6/12 bilaterally and correctable inability to see 6/13 at 40 cm with both eyes), who never had owned glasses. Participants were randomized (1:1) to receive immediate free reading glasses (intervention) or glasses delivered 8 months later (control). Visual demand of different jobs was stratified into three levels. Outcomes were between-group differences in the 8 month change in: self-reported monthly income (primary) and Near Vision Related Quality of Life (NVRQOL, secondary). RESULTS: Among 10,884 census participants, 3,655 (33.6%) met vision criteria and 863 (23.6%) comprised a sample enriched for near vision-intensive jobs, but 39 (4.52%) could not be reached. All participants allocated to intervention (n = 423, 51.3%) and control (n = 401, 48.7%) received the appropriate intervention, and follow-up was available for 93.4% and 96.8% respectively. Groups were similar at baseline in all characteristics: mean age was 47 years, 50% were male, 35% literate, and about half engaged in "most near vision-intensive" occupations. Glasses wear at 8-month follow-up was 88.3% and 7.81% in intervention and control respectively. At baseline, both the intervention and control groups had a self-reported median monthly income of US$35.3. At endline, the median income for the intervention group was US$47.1 compared with US$35.3 for control, a difference of 33.4%. Predictors of greater income increase in multivariate models included intervention group allocation (OR 1.45, 95% CI 1.12, 1.88, P = 0.005), male sex (OR 2.41, 95% CI 1.84, 3.16, P <0.001), and not engaging in income-producing work at baseline (OR 2.35, 95% CI 1.69, 3.26, P<0.001). CONCLUSION: Provision of reading glasses increases income in near vision-intensive occupations, and may facilitate return to work for those currently unemployed.

Role of lens in early refractive development: evidence from a large cohort of Chinese children.

AIMS: To document longitudinal changes in spherical equivalent refraction (SER) and related biometric factors during early refractive development. METHODS: This was a prospective cohort study of Chinese children, starting in 2018 with annual follow-ups. At each visit, children received cycloplegic autorefraction and ocular biometry measurements. Lens power (LP) was calculated using Bennett's formula. Children were divided into eight groups based on baseline age: the 3-year-old (n=426, 49.77% girls), 4-year-old (n=834, 47.36% girls), 6-year-old (n=292, 46.58% girls), 7-year-old (n=964, 43.46% girls), 9-year-old (n=981, 46.18% girls), 10-year-old (n=1181, 46.32% girls), 12-year-old (n=504, 49.01%) and 13-year-old (n=644, 42.70%) age groups. RESULTS: This study included right-eye data from 5826 children. The 3-year-old and 4-year-old age groups demonstrated an inflection point in longitudinal SER changes at a mild hyperopic baseline SER (+1 to +2 D), with children with more myopic SER showing hyperopic refractive shifts while those with more hyperopic SER showing myopic shifts. The hyperopic shift in SER was mainly attributed to rapid LP loss and was rarely seen in the older age groups. Axial elongation accelerated in the premyopia stage, accompanied by a partially counter-balancing acceleration of LP loss. For children aged 3-7 years, those with annual SER changes <0.25 D were all mildly hyperopic at baseline (mean: 1.23 D, 95% CI 1.20 to 1.27 D). CONCLUSION: Our findings suggest that during early refractive development, refractions cluster around or above +1.00 D. There is a pushback process in which increases in the rate of LP occur in parallel with increases in axial elongation.

HBV PreC interacts with SUV39H1 to induce viral replication by blocking the proteasomal degradation of viral polymerase.

Hepatitis B e antigen (HBeAg) seropositivity during the natural history of chronic hepatitis B (CHB) is known to coincide with significant increases in serum and intrahepatic HBV DNA levels. However, the precise underlying mechanism remains unclear. In this study, we found that PreC (HBeAg precursor) genetic ablation leads to reduced viral replication both in vitro and in vivo. Furthermore, PreC impedes the proteasomal degradation of HBV polymerase, promoting viral replication. We discovered that PreC interacts with SUV39H1, a histone methyltransferase, resulting in a reduction in the expression of Cdt2, an adaptor protein of CRL4 E3 ligase targeting HBV polymerase. SUV39H1 induces H3K9 trimethylation of the Cdt2 promoter in a PreC-induced manner. CRISPR-mediated knockout of endogenous SUV39H1 or pharmaceutical inhibition of SUV39H1 decreases HBV loads in the mouse liver. Additionally, genetic depletion of Cdt2 in the mouse liver abrogates PreC-related HBV replication. Interestingly, a negative correlation of intrahepatic Cdt2 with serum HBeAg and HBV DNA load was observed in CHB patient samples. Our study thus sheds light on the mechanistic role of PreC in inducing HBV replication and identifies potential therapeutic targets for HBV treatment.

SnO2QDs sensitized ZnFe2O4spheres with enhanced acetone sensing performance.

Herein, SnO2QDs (<10 nm) with small size instead of conventional nanoparticles was employed to modify ZnFe2O4to synthesize porous and heterogeneous SnO2/ZnFe2O4(ZFSQ) composites for gas sensing. By an immersion process combined with calcination treatment, the resultant porous ZFSQ composites with different contents of SnO2QDs were obtained, and their sensing properties were investigated. Compared with bare ZnFe2O4and SnO2QDs, porous ZFSQ composites based-sensors showed much improved sensor response to acetone. For contrast, the sensor performance of ZFSQ composites was also compared with that of ZnFe2O4sphere modified by SnO2nanoparticles with different size. The porous ZFSQ composite with 5 wt% SnO2QDs (ZFSQ-5) showed a better acetone sensing response than that of other ZFSQ composites, and it exhibited a high response value of 110-100 ppm of acetone and a low detection limit of 0.3 ppm at 240 °C. In addition to the rich heterojunctions and porous structure, the size effect of SnO2QDs was other indispensable reasons for the improved sensor performance. Finally, the ZFSQ-5 composite sensor was attempted to be applied for acetone sensing in exhaled breath, suggesting its great potential in monitoring acetone.

Mitochondria-associated endoplasmic reticulum membrane (MAM): a dark horse for diabetic cardiomyopathy treatment.

Diabetic cardiomyopathy (DCM), an important complication of diabetes mellitus (DM), is one of the most serious chronic heart diseases and has become a major cause of heart failure worldwide. At present, the pathogenesis of DCM is unclear, and there is still a lack of effective therapeutics. Previous studies have shown that the homeostasis of mitochondria and the endoplasmic reticulum (ER) play a core role in maintaining cardiovascular function, and structural and functional abnormalities in these organelles seriously impact the occurrence and development of various cardiovascular diseases, including DCM. The interplay between mitochondria and the ER is mediated by the mitochondria-associated ER membrane (MAM), which participates in regulating energy metabolism, calcium homeostasis, mitochondrial dynamics, autophagy, ER stress, inflammation, and other cellular processes. Recent studies have proven that MAM is closely related to the initiation and progression of DCM. In this study, we aim to summarize the recent research progress on MAM, elaborate on the key role of MAM in DCM, and discuss the potential of MAM as an important therapeutic target for DCM, thereby providing a theoretical reference for basic and clinical studies of DCM treatment.

Microsurgical Vitrectomy with Pars Plana Incision for the Removal of Posterior Segment Intraocular Foreign Bodies.

This study describes a pars plana incision surgical technique combined with 23 or 25-gauge vitrectomy in the management of intraocular foreign bodies (IOFBs) and to assess its anatomical and functional results. Sixteen patients with ocular trauma complicated with IOFB were enrolled in our study. The mean preoperative visual acuity was 2.01 ± 0.55 LogMAR, and the mean postoperative visual acuity at the final visit was improved to 0.91 ± 0.58 LogMAR (p < 0.001). Until the last follow-up, all IOFBs were successfully removed and anatomic success was obtained. Complications, such as endophthalmitis, silicone oil-dependent, and ocular hypotonia, were not observed. Microsurgical vitrectomy with modified pars plana incision is a safe and effective procedure in the treatment of retained IOFB, especially associated with transparent lens and posterior segment injury.

Significance of Aneuploidy in Predicting Prognosis and Treatment Response of Uveal Melanoma.

AIMS: This study aimed to improve personalized treatment strategies and predict survival outcomes for patients with uveal melanoma (UM). BACKGROUND: Copy number aberrations (CNAs) have been considered as a main feature of metastatic UM. OBJECTIVE: This study was designed to explore the feasibility of using copy number variation (CNV) in UM classification, prognosis stratification and treatment response. METHODS: The CNV data in the TCGA-UVM cohort were used to classify the samples. The differentially expressed genes (DEGs) between subtypes were screened by the "Limma" package. The module and hub genes related to aneuploidy score were identified by performing weighted gene co-expression network analysis (WGCNA) on the DEGs. Univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis were employed to train the hub genes for developing a prognosis model for UM. Finally, the expression levels of the screened prognostic key genes were verified in UM cells, and the cell migration and invasion abilities were detected using real-time quantitative PCR (qRT-PCR) and transwell assay. RESULTS: The UM samples were divided into 3 CNV subtypes, which differed significantly in overall survival (OS) and disease-specific survival (DSS). C1 had the shortest OS and DSS and the highest level of immune infiltration. A total of 2036 DEGs were obtained from the three subtypes. Eighty hub genes with the closest correlation with aneuploidy scores were selected by WGCNA. Univariate Cox and LASSO regression-based analyses finally determined eight genes as the key prognostic genes, including HES6, RNASEH2C, NQO1, NUDT14, TTYH3, GJC1, FKBP10, and MRPL24. A prognostic model was developed using the eight genes, demonstrating a strong prediction power. Differences in the response to immunotherapy among patients in different risk groups were significant. We found that high-risk patients were more sensitive to two drugs (Palbociclib_ 1054 and Ribociclib_1632), while low-risk patients were more sensitive to AZD1208_1449, ERK_2440_1713, Mirin_1048, and Selumetinib_1736. CONCLUSION: UM in this study was divided into three CNV subtypes, and a model based on eight aneuploidy score-related genes was established to evaluate the prognosis and drug treatment efficacy of UM patients. The current results may have the potential to help the clinical decision-making process for UM management.

[Construction of ecological network with protected areas as the main region in Guangzhou City, China]. / 以自然保护地为主体的广州市域生态网络构建.

In the context of the national ecological security development strategy, constructing regional ecological networks centered on protected areas and ecological corridors has become an urgent issue in protected areas system development of China. We focused on strengthening ecological connections between protected areas in Guangzhou, identified the ecological resource patches, ecological corridors, and ecological nodes by using Invest model, connectivity analysis, circuit theory models, and graph-theoretical network structure evaluation, and constructed an ecological network for the Guangzhou with nature reserves as the core. The results showed that 52 ecological resource patches were identified in the study area, covering a total area of 1450.01 km2. Nature reserves accounted for 76.4% of the total area, forming the main part of the ecological resource patches. 115 ecological corridors were identified, with a total length of 900.56 km and an average length of 7.83 km. Furthermore, 72 ecological key points were identified, covering a total area of 17.57 km2, and 81 ecological breakpoints, with a total area of 35.9 km2. The network structure indices (α=0.65, ß=2.21, and γ=0.77) indicated a reasonably structured and well-connected network. By exploring pathways for constructing regional ecological networks under the protected areas system and enriching the application of circuit theory models in ecological network construction, this study provides scientific basis for regional ecological security and biodiversity conservation.

Longitudinal Changes in Choroidal Thickness Varied With Refractive Progression in Myopic and Non-Myopic Children: A Two-Year Cohort Study.

Purpose: To evaluate the longitudinal changes in subfoveal choroidal thickness (SFCT) in children with different refractive status. Methods: A total of 2290 children 3 to 14 years old who attended the first year of kindergarten (G0), first year of primary school (G1), fourth year of primary school (G4), or first year of junior high school (G7) in Guangzhou, China, were recruited and followed up for 2 years. All participants received cycloplegic autorefraction, axial length measurement and SFCT measurement using a CIRRUS HD-OCT device. Children were divided into groups of persistent non-myopia (PNM), persistent myopia (PM), or newly developed myopia (NDM). Children in the PNM and PM groups were further divided into subgroups of stable refraction (absolute mean annual spherical equivalent refraction [SER] change < 0.5 D) and refractive progression (absolute mean annual SER change ≥ 0.5 D). Results: The mean ± SD ages for the G1 to G7 cohorts were 3.89 ± 0.30, 6.79 ± 0.47, 9.71 ± 0.34, and 12.54 ± 0.38, years, respectively. SFCT consistently decreased in the NDM group across the G1 to G7 cohorts (all P < 0.001) and exhibited variability across different age cohorts in the PNM and PM groups. Further subgroup analysis revealed significant thickening of SFCT in the PNM-stable group among the G0, G1, and G7 cohorts (all P < 0.05), whereas it remained stable among all cohorts in the PM-stable group (all P > 0.05). Conversely, SFCT exhibited thinning in the G4 and G7 cohorts in the PM-progressive group (both P < 0.01) and for the entire cohort of children in the PNM-progressive group (P = 0.012). Conclusions: SFCT increased in nonmyopic children with stable refraction, remained stable in myopic children maintained stable refraction, and decreased in those with refractive progression, whether they were myopic or not.

Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study.

OBJECTIVE: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. METHOD: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. RESULTS: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006). CONCLUSION: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

Asperustins A-J: Austocystins with Immunosuppressive and Cytotoxic Activities from Aspergillus ustus NRRL 5856.

Ten new (1-10) and nine known (11-19) austocystins, along with four known anthraquinones (20-23), were isolated from the culture of Aspergillus ustus NRRL 5856 by bioactivity-guided fractionation. The structures of the new compounds were elucidated by spectroscopic data analysis, X-ray crystallographic study, the modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD spectral analysis, and comparison of the experimental ECD spectra with those of the similar analogues. Compounds 1-8 represent the first examples of austocystins with a C-4' oxygenated substitution. The absolute configuration of 1″-hydroxy austocystin D (11) was determined by single-crystal X-ray diffraction and consideration of its biosynthetic origin. Compounds 5, 9, and 11 exhibited significant inhibitory effects against the proliferation of ConA-induced T cells with IC50 values of 1.1, 1.0, and 0.93 µM, respectively. Furthermore, these compounds suppressed the expression of IL-6 in a dose-dependent manner. Compounds 10-12 and 14 showed pronounced cytotoxicities against MCF-7 with IC50 values of 3.9, 1.3, 0.46, and 2.3 µM, respectively.