The protective effect of social support on all-cause and cardio-cerebrovascular mortality among middle-aged and older adults in the US.

The relationship between social support and mortality, especially cardio-cerebrovascular mortality, still has some limitations in the assessment of social support, sample selection bias, and short follow-up time. We used the data from 2005 to 2008 National Health and Nutrition Examination Survey to examine this relationship. The study analyzed a total of 6776 participants, divided into Group 1, Group 2, and Group 3 according to the social support score (0-1; 2-3; 4-5). Multivariable adjusted COX regression analyses of our study showed that Group 3 and Group 2 had a reduced risk of all-cause and cardio-cerebrovascular mortality (Group 3 vs 1, HR: 0.55, P < 0.001; HR: 0.4, P < 0.001; Group 2 vs 1, HR: 0.77, P = 0.017; HR: 0.58, P = 0.014) compared with Group 1. The same results were observed after excluding those who died in a relatively short time. Additionally, having more close friends, being married or living as married, and enough attending religious services were significantly related to a lower risk of mortality after adjustment. In brief, adequate social support is beneficial in reducing the risk of all-cause mortality and cardio-cerebrovascular mortality in middle-aged and older adults, especially in terms of attending religious services frequency, the number of close friends, and marital status.

Establishing thresholds of handgrip strength based on mortality using machine learning in a prospective cohort of Chinese population.

Background: The relative prognostic importance of handgrip strength (HGS) in comparison with other risk factors for mortality remains to be further clarified, and thresholds used for best identify high-risk individuals in health screening are not yet established. Using machine learning and nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), the study aimed to investigate the prognostic importance of HGS and establish sex-specific thresholds for health screening. Methods: A total of 6,762 participants from CHARLS were enrolled. A random forest model was built using 30 variables with all-cause mortality as outcome. SHapley Additive exPlanation values were applied to explain the model. Cox proportional hazard models and Harrell's C index change were used to validate the clinical importance of the thresholds. Results: Among the participants, 3,102 (45.9%) were men, and 622 (9.1%) case of death were documented follow-up period of 6.78 years. The random forest model identified HGS as the fifth important prognostic variable, with thresholds for identifying high-risk individuals were < 32 kg in men and < 19 kg in women. Low HGS were associated with all-cause mortality [HR (95% CI): 1.77 (1.49-2.11), p < 0.001]. The addition of HGS thresholds improved the predictive ability of an established office-based risk score (C-index change: 0.022, p < 0.001). Conclusion: On the basis of our thresholds, low HGS predicted all-cause mortality better than other risk factors and improved prediction of a traditional office-based risk score. These results reinforced the clinical utility of measurement of HGS in health screening.

Protocol for the PORT study: short-term perioperative rehabilitation to improve outcomes in cardiac valvular surgery - a randomised control trial.

INTRODUCTION: Perioperative rehabilitation (PORT) has shown a positive effect on patients undergoing cardiac surgery. However, there are minimal data on the impact of short-term PORT in cardiac surgery, which is associated with higher postoperative morbidity and mortality. The trial will assess the efficacy of short-term PORT in reducing in-hospital mortality, postoperative pulmonary complications and length of stay, compared with the usual care in cardiac surgical patients. METHODS AND ANALYSIS: This is a single-centre prospective, randomised, open, controlled trial with a 1:1 ratio. Consecutive 800 adult patients undergoing elective valve surgery will be randomised to either usual care or in-hospital short-term PORT that consists of education, inspiratory muscle training, active cycle of breathing techniques and early mobilisation. The primary outcome of this study will be a composite of in-hospital all-cause mortality, incidence of postoperative pulmonary complications and the ratio of postoperative hospitalisation >7 days. ETHICS AND DISSEMINATION: The PORT study was granted by the Medical Research Ethics Committee of Guangdong Provincial People's Hospital in August 2018. Findings will be disseminated to patients, clinicians and commissioning groups through peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT03709511.

Discovery and Biomimetic Semisynthesis of Spirophyllines A-D from Uncaria rhynchophylla.

Spirophyllines A-D (1-4), four new spirooxindole alkaloids all characterized by the spiro[pyrrolidin-3,3'-oxindole] core and a rare isoxazolidine ring, were isolated from Uncaria rhynchophylla. Their structures were determined by spectroscopic methods and confirmed by X-ray crystallography. Based on the biomimetic semisynthesis strategy, compounds 1-8 were synthesized in three steps via the key reactions of 1,3-dipolar cycloaddition and Krapcho decarboxylation from corynoxeine. Interestingly, compound 3 showed moderate inhibitory activity against the Kv1.5 potassium channel (IC50 = 9.1 µM).

Usefulness of the Duke Activity Status Index to Assess Exercise Capacity and Predict Risk Stratification in Patients with Pulmonary Arterial Hypertension.

Exercise capacity is an important component of risk assessment for pulmonary arterial hypertension (PAH). We investigated the association of the Duke Activity Status Index (DASI) with peak oxygen consumption (peakVO2) and explored whether the DASI can discriminate the high-risk individuals in patients with PAH, according to peakVO2 < 11 mL/min/kg. A total of 89 patients were evaluated using cardiopulmonary exercise testing (CPET) and DASI. The correlation between the DASI and peakVO2 was measured by univariate analysis, and a receiver operating characteristic (ROC) curve analysis was conducted. The DASI was correlated with peakVO2 in the univariate analysis. The ROC curve analysis revealed that the DASI had a discriminative value for identifying the individuals with a high risk in PAH patients (p < 0.001), with an area under ROC curve (AUC) of 0.79 (95% CI: 0.67-0.92). Similar results were observed in patients with PAH associated with congenital heart disease (CHD-PAH), (p = 0.001), with an AUC of 0.80 (95% CI: 0.658-0.947). Therefore, DASI reflects exercise capacity in patients with PAH and has good ability to discriminate patients with a low risk and a high risk, and it may be included in the risk assessment of PAH.

Temporal Trends and Differences in Sexuality among Depressed and Non-Depressed Adults in the United States.

This study aimed to examine temporal trends and differences in sexuality between depressed and non-depressed adults aged 18-59 in the United States from 2005 to 2016. A total of 21,437 people (5432 with depression) were enrolled in this cross-sectional study. From 2005-2008 to 2013-2016, the average age at first sexual intercourse decreased, while the proportion of normal frequency of sexual activity and heterosexual sexual orientation increased among all the participants. Some differences in sexuality were found between the depressed and non-depressed groups. The average age at first sexual intercourse (p < 0.001), the proportion of normal frequency of sexual activity (p < 0.001), and heterosexual sexual orientation (p < 0.001) were lower in depressed participants, and the differences did not change over time (pfor trend = 0.926 of average age at first sexual intercourse, pfor trend = 0.823 of normal frequency of sexual activity, pfor trend = 0.926 of heterosexual sexual orientation). Moreover, these differences were associated with marital status (pfor interaction < 0.001 by average age at first sexual intercourse), employment status (pfor interaction < 0.001 by average age at first sexual intercourse), education status (pfor interaction = 0.023 by heterosexual sexual orientation) and family income status (pfor interaction = 0.013 by average age at first sexual intercourse and pfor interaction = 0.017 by normal frequency of sexual activity). In conclusion, the study found that the age at first sexual intercourse decreased and the frequency of sexual intercourse increased in all the participants, and differences in sexuality between depressed and non-depressed participants were present; however, these differences had no further increase or decrease during the 12-year period. These differences were associated with marital status, employment status, education status, and family income status. These findings show differences in sexuality between depressed and non-depressed patients but are somewhat different from previous studies; the results may provide directions for future research and social work.

Development and structure-activity relationships of tanshinones as selective 11ß-hydroxysteroid dehydrogenase 1 inhibitors.

11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1) represents a promising drug target for metabolic syndrome, including obesity and type 2 diabetes. Our initial screen of a collection of natural products from Danshen led to the identification of tanshinones as the potent and selective 11ß-HSD1 inhibitors. To improve the druggability and explore the structure-activity relationships (SARs), more than 40 derivatives have been designed and synthesized using tanshinone IIA and cryptotanshinone as the starting materials. More than 10 derivatives exhibited potent in vitro 11ß-HSD1 inhibitory activity and good selectivity over 11ß-HSD2 across human and mouse species. Based on the biological results, SARs were further discussed, which was also partially rationalized by a molecular docking model of 1 bound to the 11ß-HSD1. Remarkably, compounds 1, 17 and 30 significantly inhibited 11ß-HSD1 in 3T3-L1 adipocyte and in livers of ob/ob mice, which merits further investigations as anti-diabetic agents. This study not only provides a series of novel selective 11ß-HSD1 inhibitors with promising therapeutic potentials in metabolic syndromes, but also expands the boundaries of the chemical and biological spaces of tanshinones.

Associations Among Depression, Hemoglobin A1c Level, and Prognosis in Patients With Coronary Artery Disease: A Prospective Study.

Background: Depression is ubiquitous in patients with coronary artery disease (CAD). The relationship between depression and hemoglobin A1c (HbA1c) is controversial. The combined effect of high HbA1c and depression on prognosis is unclear, especially in non-diabetic CAD patients. We sought to explore these associations. Methods: 558 CAD patients were included in this prospective study. Patients were grouped by HbA1c levels and the status of clinical depression. The average follow-up period was about 2.2 years, and Cox proportional hazards models were used to compare the differences of prognosis in all the groups. Results: Clinical depression had no associations with HbA1c in all CAD patients (P for Pearson correlation = 0.74). In the all four groups, compared to group 1 (patients without clinical depression and low HbA1c), group 3 (without clinical depression and high HbA1c) had a higher risk of MACE (adjusted hazard ratio [aHR], 1.97; 95% confidence interval [CI], 1.2-3.25) and composite events (aHR, 1.67; 95% CI, 1.09-2.053). Group 4 (patients with clinical depression and high HbA1c) had higher HRs for MACE (aHR, 2.9; 95%CI, 1.32-6.38) and composite events (aHR, 2.12; 95% CI, 1.06-4.25). In CAD patients without diabetes, patients with clinical depression and high HbA1c had a higher risk of MACE (HR, 2.71; 95% CI, 1.02-7.19), non-cardiac readmission (HR,3.48; 95% CI, 1.26-9.57) and composite events (HR,2.44; 95% CI, 1.08-5.53) than those with no clinical depression and low HbA1c. In patients with comorbidities of depression and diabetes, patients with depression and high HbA1c more likely to experienced non-cardiac readmissions (HR, 4.49; 95% CI, 1.31-15.38) than patients with no depression and low HbA1c only. In all the above analysis, p-values for interaction between clinical depression and HbA1c were not statistically significant. Conclusions: The presence of both depression and high HbA1c lead to a worse prognosis in CAD patients than one risk factor alone, no matter with or without the comorbidity of diabetes in these CAD patients. For patients with CAD and depression, lower HbA1c may be required.

Eleven undescribed alkaloids from the rhizomes of Sinomenium acutum and their IDO1 and TDO inhibitory activities.

Eleven previously undescribed alkaloids, named sinometumines A-K, along with three known alkaloids, were isolated from the rhizomes of Sinomenium acutum. The chemical structures of these unreported compounds were established using extensive spectroscopic methods (IR, UV, HRESIMS, and NMR), and their absolute configurations were determined by single crystal X-ray diffraction analyses and calculated electronic circular dichroism spectroscopy (ECD). Sinometumine D was the first aporphine-type derived alkaloid inner salt with a rearranged dibenzofuran ring backbone. Sinometumine E was a rare protoberberine-type alkaloid with a complex 6/6/6/6/6/6 hexacyclic skeleton. This was the first report of alkaloids with these two skeletons isolated from S. acutum. All isolates were evaluated for their inhibitory activities against indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO). Lysicamine possessed noteworthy inhibitory activities as an IDO1/TDO dual inhibitor with IC50 values of 6.22 ± 0.26 µM and 23.76 ± 2.93 µM, respectively, and liriodenine revealed moderate dual inhibition with IC50 values of 31.65 ± 4.44 µM and 15.64 ± 0.26 µM. The intermolecular interactions and binding modes between lysicamine and IDO1/TDO were elaborated by molecular docking studies.

Spiroligustolides A and B: Two pairs of enantiomeric spiro-orthoester-containing phthalide dimers as Cav3.1 calcium channel inhibitors from Ligusticum Chuanxiong Hort.

Two pairs of unprecedented enantiomeric phthalide dimers, spiroligustolides A (1a/1b) and B (2a/2b), featuring a unique spiroorthoster linkage between two monomeric units to form a 5/6/5/6/6-fused ring system, were isolated from the roots of Ligusticum chuanxiong. The structures and relative configurations of 1 and 2 were determined by HR-ESI-MS, IR, and NMR spectroscopic data, coupled with single-crystal X-ray diffraction analysis, and the absolute configurations of 1a, 1b, 2a, and 2b were established by comparing the experimental and calculated electronic circular dichroism (ECD) data. Plausible biosynthetic pathway for 1 and 2 was proposed. Moreover, compounds 1, 1b, and 2b showed remarkable inhibitory activities on Cav3.1 calcium channel with IC50 values of 8.34, 7.08, and 8.60 µM, respectively.

seco-Prezizanne Sesquiterpenes and Prenylated C6-C3 Compounds from the Fruits of Illicium lanceolatum A. C. Smith.

Two new seco-prezizaane-type sesquiterpenes, 2ß-hydroxy-6-deoxyneoanisatin (1) and 3,4-anhydro-2-oxo-1α-hydroxy-6-deoxyneoanisatin (2), and two new prenylated C6 -C3 compounds, illilanceofunones A (3) and B (4), were obtained from the fruits of Illicium lanceolatum, along with four known prenylated C6 -C3 compounds (5-8). Their structures were proposed through HR-ESI-MS, 1 H, 13 C, and 2D NMR data interpretation. Moreover, the absolute configuration of 1 and 2 were further assigned by single-crystal X-ray diffraction analysis and electronic circular dichroism (ECD) calculations, respectively. Illihenryipyranol A (6) exhibited neuroprotective activity against MPP+ -induced PC12 cell damage in a dose-dependent manner.

Rhynchines A-E: Cav3.1 Calcium Channel Blockers from Uncaria rhynchophylla.

Rhynchines A-E (1-5), five new indole alkaloids with an unprecedented skeleton, were isolated from Uncaria rhynchophylla. The new skeleton was characterized by an indole moiety and a 2-oxa-8-azatricyclo[6,5,01,5,01,8]tridecane core, forming a unique 6/5/7/5/5 ring system. Their structures were determined by nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, infrared spectroscopy, and calculated electronic circular dichroism (ECD) and were confirmed by X-ray crystallography. Interestingly, 1 and 2 showed strong inhibitory activities against the Cav3.1 calcium channel with IC50 values of 6.86 and 10.41 µM.

Network Analyses of the Differential Expression of Heat Shock Proteins in Glioma.

Heat shock protein (HSP) is a family of highly conserved protein, which exists widely in various organisms and has a variety of important physiological functions. Currently, there is no systematic analysis of HSPs in human glioma. The aim of this study was to investigate the characteristics of HSPs through constructing protein-protein interaction network (PPIN) considering the expression level of HSPs in glioma. After the identification of the differentially expressed HSPs in glioma tissues, a specific PPIN was constructed and found that there were many interactions between the differentially expressed HSPs in glioma. Subcellular localization analysis shows that HSPs and their interacting proteins distribute from the cell membrane to the nucleus in a multilayer structure. By functional enrichment analysis, gene ontology analysis, and Kyoto Encyclopedia of Genes and Genomes pathway analysis, the potential function of HSPs and two meaningful enrichment pathways was revealed. In addition, nine HSPs (DNAJA4, DNAJC6, DNAJC12, HSPA6, HSP90B1, DNAJB1, DNAJB6, DNAJC10, and SERPINH1) are prognostic markers for human brain glioma. These analyses provide a full view of HSPs about their expression, biological process, as well as clinical significance in glioma.

Associations between air pollution and outpatient visits for allergic rhinitis in Xinxiang, China.

Several epidemiological studies have investigated the adverse health effects of air pollution, but studies reporting its effects on allergic rhinitis (AR) are limited, especially in developing countries having the most severe pollution. Limited studies have been conducted in China, but their results were inconsistent. So, we conducted a time-series study to evaluate the acute effect of six air pollutants (fine particulate matter [PM2.5], particulate matter with diameter less than 10 µm [PM10], sulfur dioxide [SO2], nitrogen dioxide [NO2], ozone [O3], and carbon monoxide [CO]) on hospital outpatient visits for AR in Xinxiang, China from January 1, 2015, to December 31, 2018. An over-dispersed Poisson generalized additive model adjusting for weather conditions, long-term trends, and day of the week was used. In total, 14,965 AR outpatient records were collected during the study period. Results found that each 10 µg/m3 increase in PM2.5, PM10, SO2, NO2, O3, and CO corresponded to 0.70% (95% confidence interval 0.00-1.41%), 0.79% (0.35-1.23%), 3.43% (1.47-5.39%), 4.54% (3.01-6.08%), 0.97% (- 0.11-2.05%), and 0.07% (0.02-0.12%) increments in AR outpatients on the current day, respectively. In the stratification analyses, statistically stronger associations were observed with PM2.5, PM10, SO2, NO2, and CO for AR outpatients < 15 years of age than in those 15-65 and ≥ 65 years of age, whereas the opposite result was found with O3. Associations between PM10, SO2, NO2, O3, and AR outpatients were higher in the warm season than those in the cool season. This study suggests that exposure to PM2.5, PM10, SO2, NO2, and CO was associated with increased AR risk and children younger than 15 years might be more vulnerable.

Analgesic diterpenoids with diverse carbon skeletons from the leaves of Rhododendron auriculatum.

Sixteen diterpenoids including nine undescribed ones, named rhodoauriculatols A-I, were isolated from the leaves of Rhododendron auriculatum Hemsl. Sixteen diterpenoids belong to seven diverse carbon skeletons, which were classified into 1,10-seco-grayanane, 1,10:2,3-diseco-grayanane, A-homo-B-nor-ent-kaurane, ent-kaurane, 4,5-seco-ent-kaurane, leucothane, and grayanane, respectively. Their structures were determined by the detailed HRESIMS, 1D and 2D NMR, UV, and IR data analysis, and their absolute configurations were established by single crystal X-ray diffraction analysis, electronic circular dichroism (ECD) data analysis, ECD calculation, as well as chemical methods. Rhodoauriculatols A-C possess a rare 1,10-seco-grayanane diterpene skeleton. Rhodoauriculatol D is the second example of the 1,10:2,3-diseco-grayanane diterpenoids, and rhodoauriculatol E is the fourth example of the A-homo-B-nor-ent-kaurane diterpenoids. Rhodomicranone E was reported as a natural product for the first time. All the isolated sixteen diterpenoids showed analgesic activities in the acetic acid-induced writhing test. Rhodoauriculatols B, E-G, rhodomicranone E, pierisformoside F, and micranthanoside A showed significant analgesic activities with the inhibition rates over 40%, and their preliminary structures-activity relationships were studied.

Rhodojaponin II attenuates kidney injury by regulating TGF-ß1/Smad pathway in mice with adriamycin nephropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhododendron molle G. Don (Ericaceae) (RM) is a natural medicinal plant. Its root extracts have been applied in clinic and proved to be effective in chronic glomerulonephritis and rheumatoid arthritis in China. Surprising, little is understood about the key compound of RM and the exact mechanisms underlying its treatment on kidney diseases. In this study, we will explore whether rhodojaponin II (R-II), as the important compound of RM, also exerts the major effect. MATERIALS AND METHODS: Mouse model of focal segmental glomerulosclerosis was induced by single dose of adriamycin injection. Induced adriamycin nephropathy (ADRN) mice were treated individually with RM root extract (5 mg/kg, n = 5), RM root extract (60 mg/kg, n = 5), R-II (0.04 mg/kg, n = 6) or captopril (30 mg/kg, n = 5) for five weeks. Podocyte marker (nephrin and podocin) expressions were examined by immunohistochemical staining and Western Blot analysis. Fibronectin level was evaluated by immunohistochemical staining and Western Blot analysis. Interstitial infiltrated inflammatory cells (CD4+ T cells, CD8+ T cells, and CD68+ macrophages) were examined with immunohistochemical staining. The expressions of NF-ĸB p-p65 and TGF-ß1/Smad pathway associated key proteins, such as TGF-ß1, Smad3, phosphorylated-Smad3 (p-Smad3), and Smad7, were analyzed respectively by Western Blot analysis. RESULTS: RM root extract (5 mg/kg) and its important compound R-II (0.04 mg/kg) significantly ameliorated proteinuria, podocyte injury, and glomerulosclerosis, meanwhile, they hampered interstitial fibrosis in mice with ADRN. R-II significantly reduced NF-ĸB p65 phosphorylation, interstitial infiltrated CD4+ T cells, CD8+ T cells, and CD68+ macrophages, at the same time, down-regulated TGF-ß1 and p-Smad3 protein expressions in mice with ADRN. CONCLUSION: RM root extract, R-II, could effectively ameliorate proteinuria and kidney injury in ADRN, related to its anti-inflammatory effects, as well as suppression of TGF-ß1/Smad signaling pathway.

Cassiabudanols A and B, Immunostimulative Diterpenoids with a Cassiabudane Carbon Skeleton Featuring a 3-Oxatetracyclo[6.6.1.02,6.010,14]pentadecane Scaffold from Cassia Buds.

Two novel diterpenoids, cassiabudanols A (1) and B (2), were isolated from cassia buds. Their structures were determined by comprehensive spectroscopic analysis and single-crystal X-ray diffraction. Compounds 1 and 2 possess an unprecedented 11,14- cyclo-8,14:12,13-di- seco-isoryanodane (cassiabudane) carbon skeleton featuring a unique 3-oxatetracyclo[6.6.1.02,6.010,14]pentadecane bridged system, and their biosynthetic pathways are proposed. Compounds 1 and 2 exhibited significant immunostimulative activity, and the mode of action of 2 involves upregulating CD4+ and CD8+ T cells and downregulating Tregs.

Grayanane Diterpenoid Glucosides from the Leaves of Rhododendron micranthum and Their Bioactivities Evaluation.

Thirteen new grayanane diterpenoid glucosides, 3- epi-grayanoside B (1), micranthanosides A-E (2-6), 7α-hydroxygrayanoside C (7), micranthanoside F (8), 14ß-acetyoxymicranthanoside F (9), micranthanoside G (10), 14- O-acetylmicranthanoside G (11), 14ß-hydroxypieroside A (12), and micranthanoside H (13), and six known analogues (14-19) were isolated from the leaves of Rhododendron micranthum. The structures of 1-19 were elucidated based on spectroscopic analysis, comparison with literature, and chemical methods. The absolute configurations of 3- epi-grayanoside B (1) and micranthanosides A (2) and C (4) were defined by single-crystal X-ray diffraction analysis. This is the first report of the crystal structures of grayanane diterpenoid glucosides. 3- epi-Grayanoside B (1) represents the first example of a 3α-oxygrayanane diterpenoid glucoside, and micranthanosides A-D (2-5) are the first examples of 5α-hydroxy-1-ß H-grayanane diterpenoids. In addition, micranthanosides C-F (4-6 and 8) and 14ß-acetyoxymicranthanoside F (9) represent the first examples of grayanane glucosides with the glucosylation at C-16. All the grayanane diterpenoid glucosides 1-19 were assayed for their anti-inflammatory, antitumor, and PTP1B inhibitory activities, but did not show significant activities at 40 µM. Grayanane diterpenoid glucosides 1-18 were evaluated for their antinociceptive activity, and compounds 2, 3, 7-10, 12, 13, and 16 showed significant antinociceptive effects with percentage inhibitions in excess of 50%.

The protein-protein interaction network and clinical significance of heat-shock proteins in esophageal squamous cell carcinoma.

Heat-shock proteins (HSPs), one of the evolutionarily conserved protein families, are widely found in various organisms, and play important physiological functions. Nevertheless, HSPs have not been systematically analyzed in esophageal squamous cell carcinoma (ESCC). In this study, we applied the protein-protein interaction (PPI) network methodology to explore the characteristics of HSPs, and integrate their expression in ESCC. First, differentially expressed HSPs in ESCC were identified from our previous RNA-seq data. By constructing a specific PPI network, we found differentially expressed HSPs interacted with hundreds of neighboring proteins. Subcellular localization analyses demonstrated that HSPs and their interacting proteins distributed in multiple layers, from membrane to nucleus. Functional enrichment annotation analyses revealed known and potential functions for HSPs. KEGG pathway analyses identified four significant enrichment pathways. Moreover, three HSPs (DNAJC5B, HSPA1B, and HSPH1) could serve as promising targets for prognostic prediction in ESCC, suggesting these HSPs might play a significant role in the development of ESCC. These multiple bioinformatics analyses have provided a comprehensive view of the roles of heat-shock proteins in esophageal squamous cell carcinoma.

Mollebenzylanols A and B, Highly Modified and Functionalized Diterpenoids with a 9-Benzyl-8,10-dioxatricyclo[5.2.1.01,5]decane Core from Rhododendron molle.

Two highly modified and functionalized diterpenoids, mollebenzylanols A (1) and B (2), and a known grayanane diterpenoid rhodojaponin III (3) were isolated from Rhododendron molle. Their structures were determined by spectroscopic data analysis, an electronic circular dichroism (ECD) exciton chirality method, ECD calculations, and X-ray diffraction analysis of the p-bromobenzoate ester of 1 (1a). Compounds 1 and 2 possess an unprecedented diterpene carbon skeleton featuring a unique 9-benzyl-8,10-dioxatricyclo[5.2.1.01,5]decane core, and their plausible biosynthetic pathways are proposed. Their PTP1B inhibitory activity and modes of action were investigated.