HIPK2 phosphorylates HDAC3 for NF-κB acetylation to ameliorate colitis-associated colorectal carcinoma and sepsis.

Although inflammation is critical for the clearance of pathogens, uncontrolled inflammation also contributes to the development of multiple diseases such as cancer and sepsis. Since NF-κB-mediated transactivation in the nucleus is pivotal downstream of various stimuli to induce inflammation, searching the nuclear-localized targets specifically regulating NF-κB activation will provide important therapeutic application. Here, we have identified that homeodomain-interacting protein kinase 2 (HIPK2), a nuclear serine/threonine kinase, increases its expression in inflammatory macrophages. Importantly, HIPK2 deficiency or overexpression could enhance or inhibit inflammatory responses in LPS-stimulated macrophages, respectively. HIPK2-deficient mice were more susceptible to LPS-induced endotoxemia and CLP-induced sepsis. Adoptive transfer of Hipk2+/- bone marrow cells (BMs) also aggravated AOM/DSS-induced colorectal cancer. Mechanistically, HIPK2 bound and phosphorylated histone deacetylase 3 (HDAC3) at serine 374 to inhibit its enzymatic activity, thus reducing the deacetylation of p65 at lysine 218 to suppress NF-κB activation. Notably, the HDAC3 inhibitors protected wild-type or Hipk2-/- BMs-reconstituted mice from LPS-induced endotoxemia. Our findings suggest that the HIPK2-HDAC3-p65 module in macrophages restrains excessive inflammation, which may represent a new layer of therapeutic mechanism for colitis-associated colorectal cancer and sepsis.

Awareness, Attitude, and Knowledge Among the Healthcare Workers in China at the Onset of the Oversea Monkeypox Outbreak.

BACKGROUND: The outbreak of monkeypox in several nonendemic countries has been reported since May 2022. In the context of the COVID-19 pandemic, it is important to examine how healthcare workers (HCWs) respond to the monkeypox epidemic. Having been involved in the fight against COVID-19 resurgence for nearly 3 years, how HCWs in China respond to the oversea monkeypox outbreak remains unclear. OBJECTIVE: To investigate the awareness, perceived risk, attitude and knowledge about monkeypox among HCWs in China. DESIGN: A cross-sectional survey. PARTICIPANTS: Physicians and nurses from 13 hospitals in Suizhou, China, were contacted through membership of the Physicians' and Nurses' Association. MAIN MEASURES: Responses regarding their awareness, risk perception, attitude, behavior, and knowledge about the outbreak of monkeypox were collected anonymously during the second month of the outbreak between 15 and 21 June 2022. KEY RESULTS: Of the 395 physician and 1793 nurse respondents, most had heard of the oversea monkeypox outbreak (physicians 93%, nurses 88%). More than 30% thought there existed an infection risk for themselves or family members (physicians 42%, nurses 32%). Most agreed that HCWs should pay attention to the outbreak (physicians 98%, nurses 98%). More than half had actively sought expertise (physicians 62%, nurses 52%). Approximately half believed that monkeypox may be transmitted through sexual activity or respiratory droplets, or from mother to fetus in utero (physicians 50%, 62%, 55%; nurses 40%, 60%, and 48%, respectively). Some believed that mask-wearing, hand-washing, and glove-wearing can prevent monkeypox transmission (physicians 78%, 89%, 83%; nurses 77%, 86%, 76%, respectively). CONCLUSIONS: This study identified high awareness, high perceived risk, and pro-prevention attitudes among HCWs in China at the onset of the oversea multi-country monkeypox outbreak, but low levels of monkeypox-related knowledge. Immediate efforts are needed to fill in their knowledge gap, particularly regarding the transmission routes and prevention measures.

Stereodivergent Construction of [5,5]-Oxaspirolactones of Phainanoids.

A stereodivergent synthesis of [5,5]-oxaspirolactones of phainanoids is presented herein. Through precisely tuning the inherent substitution differences on cyclopropanol, a palladium-catalyzed cascade carbonylative lactonization enables the stereodivergent synthesis of [5,5]-oxaspirolactones of phainanoids.

Prognosis and antibody profiles in survivors of critical illness from COVID-19: a prospective multicentre cohort study.

BACKGROUND: There is a need to assess the long-term outcomes of survivors of critical illness from COVID-19. METHODS: Ninety-two survivors of critical illness from COVID-19 from four hospitals in Hubei Province, China participated in this prospective cohort study. Multiple characteristics, including lung function (lung volumes, diffusing capacity for carbon monoxide, chest computed tomography scores, and walking capacity); immune status (SARS-CoV-2-neutralising antibody and all subtypes of immunoglobulin (Ig) G against SARS-CoV-2, immune cells in response to ex vivo antigen peptide stimuli, and lymphocyte count and its subtypes); liver, coagulation, and kidney functions; quality of life; cognitive function; and mental status, were assessed after 3, 6, and 12 months of follow-up. RESULTS: Amongst the 92 enrolled survivors, 72 (78%) patients required mechanical ventilation. At 12 months, the predicted percentage diffusing capacity of lung for carbon monoxide was 82% (inter-quartile range [IQR]: 76-97%) with a residual volume of 77 (64-88)%. Other lung function parameters and the 6-min walk test improved gradually over time and were almost back to normal by 12 months. The titres of IgG and neutralising antibody to COVID-19 remained high at 12 months compared with those of controls who were not infected with COVID-19, although IgG titres decreased significantly from 34.0 (IQR: 23.8-74.3) to 15.0 (5.8-24.3) AU ml-1 (P<0.001), whereas neutralising antibodies decreased from 29.99 (IQR: 19.43-53.93) AU ml-1 at 6 months to 19.75 (13.1-29.8) AU ml-1 (P<0.001) at 12 months. In general, liver, kidney, physical, and mental functions also improved over time. CONCLUSIONS: Survivors of critical illness from COVID-19 show some persistent long-term impairments in lung function. However, a majority of these tests were normal by 12 months. These patients still had detectable levels of neutralising antibodies against SARS-CoV-2 and all types of IgG at 12 months, but the levels had declined over this time period. CLINICAL TRIAL REGISTRATION: None.

When health care workers became patients with COVID-19: A qualitative study.

AIMS: This study aimed to describe the experiences of nurses and other health care workers who were infected with coronavirus disease 2019. METHODS: An empirical phenomenological approach was used. Sixteen participants were recruited in Wuhan using purposive and snowball sampling. Semistructured, in-depth interviews were conducted by telephone in February 2020. Interviews were transcribed verbatim and analysed following Colaizzi's method. RESULTS: Two themes emerged: (1) Intense emotional distress since becoming infected. Participants were fearful of spreading the virus to family and overwhelmed by a lack of information, experienced uncertainty and worried about treatment, felt lonely during isolation and reported moral distress about inadequate health care staffing. (2) Coping strategies were needed. They tried their best to address negative psychological reactions using their professional knowledge and gaining support from others and community resources. CONCLUSIONS: Preparedness for catastrophic events and providing timely and accurate information are major considerations in government policy development, related to pandemics and adequacy of health care personnel. Mental health resources and support, both short- and long-term should be anticipated for health care providers to alleviate their fear and anxiety.

Urticaria and increased risk of rheumatoid arthritis: a two-sample Mendelian randomisation study in European population.

BACKGROUND: In recent years, a growing body of observational studies suggest that urticaria is associated with a higher risk of rheumatoid arthritis (RA). However, the causal association between urticaria and RA remains unknown. OBJECTIVE: To investigate the causal relationship of urticaria and RA in European populations by Mendelian randomisation (MR) approach. METHODS: We conducted two-sample MR analyses. Eleven single-nucleotide polymorphisms associated with urticaria were used as instrumental variables. The summary data on urticaria were derived from FinnGen Data Freeze 2. The summary data on RA were obtained from a published meta-analysis using European samples. Four MR methods were applied to the MR estimates. Three heterogeneity tests, including Cochran's Q test, single variant analysis, and leave-one-out variant analysis, were used. The pleiotropy and horizontal pleiotropy among instrumental variables were assessed with MR-Egger regression intercept, MR pleiotropy residual sum and outlier global test, and PhenoScanner. RESULTS: The MR analysis suggested that urticaria was causally associated with RA (odds ratio = 1.114, 95% confidence interval = 1.024-1.211, p = .011). No genetic pleiotropy or horizontal pleiotropy was revealed by MR-Egger regression intercept and MR pleiotropy residual sum and outlier global test. The sensitivity analysis results were relatively robust. CONCLUSIONS: The MR analysis suggested there was sufficient evidence to indicate urticaria is the cause of RA.

The association between type 1 and 2 diabetes mellitus and the risk of leukemia: a systematic review and meta-analysis of 18 cohort studies.

Diabetes mellitus (DM) is widely considered to be associated with the risk of diverse cancers; however, the association between DM and the risk of leukemia is still controversial. Thus, a detailed meta-analysis of cohort studies was conducted to elucidate this association. Eligible studies were screened through the electronic searches in PubMed, Web of Science, and Embase from their inception to August 11, 2020. Summary relative risks (RRs) and 95% confidence intervals (CIs) were computed through the random-effects model. Eighteen articles involving 10,516 leukemia cases among a total of 4,094,235 diabetic patients were included in this meta-analysis. Overall, twenty-five RRs were synthesized for type 2 diabetes mellitus (T2DM) and yielded a summary RR of 1.33 (95%CI, 1.21-1.47; p < 0.001). For type 1 diabetes mellitus (T1DM), 7 RRs were combined, however, the pooled RR was insignificant (RR, 1.08; 95%CI, 0.87-1.34; p = 0.48). Interestingly, the summary RR for East Asia (RR, 1.83, 95%CI, 1.63-2.06) was significantly higher than that for Europe (RR, 1.11, 95%CI, 1.06-1.15), Western Asia (RR, 1.40, 95%CI, 1.25-1.54), North America (RR, 1.14, 95%CI, 1.08-1.20), and Australia (RR, 1.47, 95%CI, 1.25-1.71). Moreover, we found that patients with a shorter T2DM duration (1-5 years) had a higher risk of leukemia compared to those with a longer duration (5.1-10 years). Overall, this meta-analysis suggests there is a moderately increased risk of leukemia among T2DM patients, but not in T1DM patients. Further investigation is warranted.

Relationship between eHealth literacy and psychological status during COVID-19 pandemic: A survey of Chinese residents.

AIMS: To investigate the eHealth literacy and the psychological status of Chinese residents during the COVID-19 pandemic and explore their interrelationship. BACKGROUND: The COVID-19 outbreak has placed intense psychological pressure on community residents. Their psychological status may be affected by eHealth literacy due to home isolation during this rampant pandemic. METHODS: This is a Web-based cross-sectional survey conducted on the JD Health platform, which resulted in 15,000 respondents having participated in this survey. The eHealth Literacy Questionnaire (EHLQ), Patient Health Questionnaire-9 (PHQ-9), Insomnia Severity Index (ISI) and Impact of Event Scale-Revised (IES-R) were used. The Pearson correlation was used to analyse the relationship between eHealth literacy and depression, insomnia and post-traumatic stress disorder. RESULTS: The score of eHealth literacy was 48.88 ± 8.46, and 11.4%, 6.8% and 20.1% of respondents experienced moderate to severe depression, insomnia and post-traumatic stress disorder. eHealth literacy negatively correlated with depression (r = -0.331), insomnia (r = -0.366) and post-traumatic stress disorder (r = -0.320). CONCLUSION: eHealth literacy is closely related to psychological status. Improving eHealth literacy may contribute to maintaining good psychological well-being. IMPLICATIONS FOR NURSING MANAGEMENT: It is necessary to strengthen the education of primary health care providers to enhance their ability to help community residents effectively use eHealth information.

Postoperative Onset and Detection of SARS-CoV-2 in Surgically Resected Specimens From Gastrointestinal Cancer Patients With Pre/Asymptomatic COVID-19.

OBJECTIVE: To describe the epidemiologic features and clinical courses of gastrointestinal cancer patients with pre/asymptomatic COVID-19 and to explore evidence of SARS-CoV-2 in the surgically resected specimens. SUMMARY BACKGROUND DATA: The advisory of postponing or canceling elective surgeries escalated a worldwide debate regarding the safety and feasibility of performing elective surgical procedures during this pandemic. Limited data are available on gastrointestinal cancer patients with pre/asymptomatic COVID-19 undergoing surgery. METHODS: Clinical data were retrospectively collected and analyzed. Surgically resected specimens of the cases with confirmed COVID-19 were obtained to detect the expression of ACE2 and the presence of SARS-CoV-2. RESULTS: A total of 52 patients (male, 34) with a median age 62.5 years were enrolled. All the patients presented no respiratory symptoms or abnormalities on chest computed tomography before surgery. Six patients (11.5%) experienced symptom onset and were confirmed to be COVID-19. All were identified to be preoperatively pre/asymptomatic, as 5 were with SARS-CoV-2 presenting in cytoplasm of enterocytes or macrophages from the colorectal tissues and 1 had symptom onset immediately after surgery. The case fatality rate in patients with COVID-19 was 16.7%, much higher than those without COVID-19 (2.2%). CONCLUSIONS: Gastrointestinal cancer patients with pre/asymptomatic COVID-19 were at high risk of postoperative onset and death. At current pandemic, elective surgery should be postponed or canceled. It highlights the need for investigating the full clinical spectrum and natural history of this infection. The early colorectal tropism of SARS-CoV-2 may have major implications on prevention, diagnosis, and treatment of COVID-19.

Metformin and pancreatic cancer survival: Real effect or immortal time bias?

High heterogeneity has been reported among cohort studies investigating the association between metformin and pancreatic cancer survival. Immortal time bias may be one importance source of heterogeneity, as it is widely present in previous cohort studies and may severely impair the validity. Our study aimed to examine whether metformin therapy improves pancreatic cancer survival, and to assess the impact of immortal time bias on the effect estimation of metformin in cohort studies. PubMed, EMbase and SciVerse Scopus were searched. Pooled relative risks (RRs) were derived using a random-effects model. Pooled RR from the six studies without immortal time bias showed no association between metformin and mortality in pancreatic cancer patients (RR 0.93, 95% CI 0.82, 1.05; p = 0.22 and I2 = 75%). In contrast, pooled RR from the nine studies with immortal time bias showed a reduction of 24% in mortality associated with metformin (RR 0.76, 95% CI 0.69, 0.84; p < 0.001 and I2 = 1%). From a meta-regression model, existence of immortal time bias was associated with a reduction of 18% in the effect estimate of metformin on pancreatic cancer survival (ratio of RR 0.82, 95% CI 0.70, 0.96; p = 0.02). In conclusions, cumulative evidence from cohort studies does not support a beneficial effect of metformin on pancreatic cancer survival. The association between metformin and pancreatic cancer survival has been greatly exaggerated in previous cohort studies due to the wide existence of immortal time bias. More rigorous designs and statistical methods are needed to account for immortal time bias.

Metformin and Reduced Risk of Cancer in the Hong Kong Diabetes Registry: Real Effect or Immortal Time Bias?

BACKGROUND: Whether metformin reduces cancer risk has been hotly debated. One common opinion is that the observed beneficial effects of metformin are the consequence of immortal time bias. OBJECTIVE: To examine whether the observed beneficial effects of metformin on cancer risk are the consequence of immortal time bias. DESIGN: Retrospective cohort study. PARTICIPANTS: A cohort of 3485 patients who started metformin before or at enrollment, 1226 patients who initiated metformin after enrollment, and an unexposed group of 1392 patients who never used metformin. MAIN MEASURES: Metformin users were categorized into 11 groups in terms of length of time between metformin initiation and enrollment. The percent changes in immortal person-time were calculated for each group. RESULTS: As the groups of current metformin users (n = 3485) were added sequentially to the metformin group with potential immortal time bias (n = 1226), the proportion of immortal person-time decreased gradually by 74%. As the immortal time decreased, the association between metformin and cancer risk remained statistically significant (uncorrected hazard ratio 0.54, 95% confidence interval 0.42-0.69, P < 0.0001). CONCLUSION: The change in the association between metformin and cancer is small compared with the changes in the proportion of immortal time, suggesting that immortal time bias does not account for the observed beneficial effect of metformin on cancer risk. Further studies are warranted to confirm this finding in other cohort studies.

Rising Mortality Rate of Cervical Cancer in Younger Women in Urban China.

BACKGROUND: In recent decades, much effort has been made in China to reduce the burden of cervical cancer. OBJECTIVE: Our study's purpose was to examine trends of cervical cancer mortality in each 5-year age group for urban and rural Chinese women, respectively. DESIGNS: Retrospective analysis of cervical cancer mortality from 1987 to 2015 from the World Health Organization Cancer Mortality Database and China Health Statistical Yearbooks. PARTICIPANTS: Chinese women. MAIN MEASURES: Trends were examined using annual percent change (APC) and average annual percent change (AAPC) via Joinpoint regression models for each 5-year age group in urban and rural areas, respectively. RESULTS: In urban China, mortality rate of cervical cancer increased significantly among urban women aged 25-54 years (AAPC 2.12~5.49%), in contrast to a decline trend among urban women older than 60 years (AAPC - 3.61~- 5.35%). In rural China, cervical cancer rates declined in all age groups, but the magnitude was smaller in women aged 30-54 years (AAPC - 0.59~- 2.20%) compared to women older than 55 years (AAPC - 3.06~- 4.33%). CONCLUSION: Mortality rate of cervical cancer is rising at an alarming rate in younger women in urban China. Timely intervention is required for these vulnerable populations.

The effect of metformin on biomarkers and survivals for breast cancer- a systematic review and meta-analysis of randomized clinical trials.

Observational studies show a beneficial effect of adjuvant metformin therapy on breast cancer survivals, but data from randomized clinical trials are lacking. This study systematically evaluated the evidence from randomized clinical trials currently available. Ten studies were retrieved, comprising 1520 breast cancer patients. Metformin therapy reduced the levels of insulin and HOMA-IR, sex hormones and sex hormone-binding globulin, Ki67, caspase-3, p-Akt, obesity, hs-CRP, blood glucose and lipid profile. Two studies reported conflicting results on survival outcomes. The overall survival was nonsignificantly better in the metformin arm than the control arm (pooled rate ratio 0.89, 95% confidence interval 0.68-1.18, P = 0.43). The progression-free survival was not different between the arms (pooled rate ratio 0.96, 95% confidence interval 0.86-1.06, P = 0.39). These findings provide in vivo evidence in human, supporting an antitumor effect of metformin on breast cancer. Further clinical trials with larger sample size are warranted.

Three-Dimensional Measurement Method of Four-View Stereo Vision Based on Gaussian Process Regression.

Multisensor systems can overcome the limitation of measurement range of single-sensor systems, but often require complex calibration and data fusion. In this study, a three-dimensional (3D) measurement method of four-view stereo vision based on Gaussian process (GP) regression is proposed. Two sets of point cloud data of the measured object are obtained by gray-code phase-shifting technique. On the basis of the characteristics of the measured object, specific composite kernel functions are designed to obtain the initial GP model. In view of the difference of noise in each group of point cloud data, the weight idea is introduced to optimize the GP model, which is the data fusion based on Bayesian inference method for point cloud data. The proposed method does not require strict hardware constraints. Simulations for the curve and the high-order surface and experiments of complex 3D objects have been designed to compare the reconstructing accuracy of the proposed method and the traditional methods. The results show that the proposed method is superior to the traditional methods in measurement accuracy and reconstruction effect.

Portable System for Box Volume Measurement Based on Line-Structured Light Vision and Deep Learning.

Portable box volume measurement has always been a popular issue in the intelligent logistic industry. This work presents a portable system for box volume measurement that is based on line-structured light vision and deep learning. This system consists of a novel 2 × 2 laser line grid projector, a sensor, and software modules, with which only two laser-modulated images of boxes are required for volume measurement. For laser-modulated images, a novel end-to-end deep learning model is proposed by using an improved holistically nested edge detection network to extract edges. Furthermore, an automatic one-step calibration method for the line-structured light projector is designed for fast calibration. The experimental results show that the measuring range of our proposed system is 100-1800 mm, with errors less than ±5.0 mm. Theoretical analysis indicates that within the measuring range of the system, the measurement uncertainty of the measuring device is ±0.52 mm to ±4.0 mm, which is consistent with the experimental results. The device size is 140 mm × 35 mm × 35 mm and the weight is 110 g, thus the system is suitable for portable automatic box volume measurement.

A New Vegetation Index Based on Multitemporal Sentinel-2 Images for Discriminating Heavy Metal Stress Levels in Rice.

Heavy metal stress in crops is a worldwide problem that requires accurate and timely monitoring. This study aimed to improve the accuracy of monitoring heavy metal stress levels in rice by using multiple Sentinel-2 images. The selected study areas are in Zhuzhou City, Hunan Province, China. Six Sentinel-2 images were acquired in 2017, and heavy metal concentrations in soil were measured. A novel vegetation index called heavy metal stress sensitive index (HMSSI) was proposed. HMSSI is the ratio between two red-edge spectral indices, namely the red-edge chlorophyll index (CIred-edge) and the plant senescence reflectance index (PSRI). To demonstrate the capability of HMSSI, the performances of CIred-edge and PSRI in discriminating heavy metal stress levels were compared with that of HMSSI at different growth stages. Random forest (RF) was used to establish a multitemporal monitoring model to detect heavy metal stress levels in rice based on HMSSI at different growth stages. Results show that HMSSI is more sensitive to heavy metal stress than CIred-edge and PSRI at different growth stages. The performance of a multitemporal monitoring model combining the whole growth stage images was better than any other single growth stage in distinguishing heavy metal stress levels. Therefore, HMSSI can be regarded as an indicator for monitoring heavy metal stress levels with a multitemporal monitoring model.

[Mortality trend in nasopharynx cancer in Chinese resident from 1987 to 2015].

OBJECTIVE: To analyze epidemical features, distribution and time trend for nasopharynx cancer deaths in China from 1987 to 2015.
 Methods: Negative binomial regression model was used to explore population-level risk factors for nasopharynx cancer deaths and a joinpoint regression model was used to estimate annual changes in nasopharynx cancer mortality in various populations.
 Results: A falling trend in age-standardized nasopharynx cancer mortality rates was observed among Chinese residents with the average annual percent change (AAPC) at -2.97% among urban female residents and -2.60% among rural female residents (P<0.05), -2.01% among urban male residents, and -1.68% among rural male residents (P<0.05), respectively. It decreased yearly for urban male aged over 85 years with AAPC at -1.54% and the age-specific mortality rates decreased yearly for the urban female aged over 85 years with AAPC at -0.60%, the age-specific mortality rates decreased yearly for rural male residents aged more than 65 years with AAPC at -0.56% and for rural female residents aged more than 85 with AAPC at 1.17%, with no significant difference (P<0.05). The nasopharynx cancer deaths risks were higher in urban residents than those in rural residents (OR=1.11, P<0.01), and they were also higher in male residents than those in female residents (OR=2.34, P<0.01). A 5-year increment in age was associated with a 23% increase in nasopharynx cancer mortality (OR=1.23, P<0.01) and a one year increment in calendar year was related to a 2% decrease in mortality (OR=0.98, P<0.01). 
 Conclusion: There was a significant gender and age difference in a decreased trend of nasopharynx cancer mortality among Chinese residents in a long period; no increased trend was observed in the overall populations over 85 years old.

[Joinpoint regression analysis for the mortality trend of breast cancer in Chinese female from 1987 to 2014].

OBJECTIVE: To analyze the current situation for the mortality of Chinese female breast cancer and the trend of change in the past thirty years, and to provide scientific basis for prevention and control of breast cancer in China. 
 Methods: The mortality data of breast cancer in Chinese female from 1987 to 2014 were collected, the trends of age-standardized rates and age-adjusted rates were described, and the variations via Joinpoint regression models were analyzed.
 Results: From 1987 to 2014, the mortality for the urban female breast cancer was greater than that for the rural females. There was a downward trend for urban women with an average decrease of 0.3% for each year (P=0.06). While the average annual change for rural females showed an upward trend (AAPC=1.26%, P<0.01). The gap between urban and rural females is narrowing gradually. The 40-59 age-adjusted rate for urban females decreased first and then it was increased with time moving forward. The mortality for rural females was continuously increased.
 Conclusion: From 1987 to 2014, the breast cancer mortality for urban females was overall higher than that for rural females. The mortality for rural females was continuously increased in the past years. The gap between urban and rural females is narrowing. We should pay specific attention to the prevention and treatment of breast cancer for the rural females.

Wogonin enhances intracellular adiponectin levels and suppresses adiponectin secretion in 3T3-L1 adipocytes.

As an insulin sensitizer and modulator of inflammatory responses, adiponectin has become a therapeutic target for insulin resistance, diabetes, and diabetes-related complications. Wogonin possesses anti-oxidative, anti-inflammatory, and anti-diabetic abilities. However, its effect on generation and secretion of adiponectin is ill-defined in adipocytes. Here, we demonstrated that wogonin administration augmented intracellular adiponectin levels and attenuated adiponectin release in a dose- and time-dependent manner in mature 3T3-L1 adipocytes, along with a suppression of PKCδ phosphorylation. Wogonin treatment also prevented PKCδ overexpression-induced reduction of intracellular adiponectin levels and enhancement of adiponectin release. In addition, wogonin supplementation dramatically increased AMPK phosphorylation and SirT1 expression. Inhibition of either AMPK or SirT1 mitigated wogonin action on adiponectin production and release. Furthermore, inhibition of AMPK by its specific inhibitor markedly reduced wogonin-enhanced mRNA and protein expressions of SirT1. These results suggested that wogonin regulated expression and secretion of adiponectin via PKCδ/AMPK/SirT1 signaling pathway in mature 3T3-L1 adipocytes.

Total synthesis and confirmation of the revised structures of jiangrines A, C and D.

Our previous total synthesis of the proposed structures of jiangrines C and D shows that the characteristic data of synthetic samples did not match those of the natural ones, prompting us to revise their structures. Accordingly, we now accomplished the total synthesis of jiangrines A, C and D, which confirms our deduction that their molecular skeletons should compose of 2,3-disubstituted pyrrole instead of 2,5-disubstituted pyrrole. Our current synthesis features a silver-catalyzed [3 + 2] cycloaddition between a terminal alkyne and isocyanide, and was completed concisely in only seven linear steps.