Circadian disturbance induces erectile dysfunction by impairing endothelial function.

ABSTRACT: In order to explore the impact of circadian disturbance on erectile function, we randomly divided 24 adult male rats into groups of control (light on at 8:00 a.m. and off at 8:00 p.m.), dark/dark (DD; constant dark), light/light (LL; constant light), and shift dark/light (DL; light off at 8:00 a.m. and on at 8:00 p.m.). Four weeks later, erectile function was measured and corpora cavernosa were harvested for analysis. The maximum intracavernous pressure (mICP) and mICP/mean arterial pressure (MAP) ratio in the DD, LL, and DL groups were significantly lower than that in the control group. The LL and DL groups showed significantly attenuated endothelial nitric oxide synthase (eNOS), while DD, LL, and DL showed reduced neuronal nitric oxide synthase (nNOS) at both mRNA and protein levels. The production of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) was inhibited by altered light/dark cycles to varying degrees. Circadian disturbance impaired endothelial function and contributed to erectile dysfunction. For the core circadian elements, mRNA expression of circadian locomotor output cycles kaput (Clock) and brain/muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) was elevated in the DL group, but their protein expression was not significantly changed. DD, LL, and DL increased period 1 (Per1) and Per3 levels, while LL and DL increased PER1 levels. No significant difference was found for Per2 levels, and PER2 and PER3 concentrations were not significantly changed. Moreover, LL and DL significantly increased cryptochrome-1 (CRY1) and CRY2 at both mRNA and protein levels. The altered light/dark rat model showed that circadian disturbance contributed to erectile dysfunction probably by impairing endothelial function. Meanwhile, the core circadian elements were detected in the corpora cavernosa, but these were disrupted. However, which circadian element regulates erectile function and how it works need further analysis.

Digital health care service reform and health inequity for older people: a quasi-natural experiment in China.

Objective: Addressing health inequity (HI) for older people is a pivotal global public health concern, as it impedes the process of healthy ageing. The digital health care service reform (DHSR) emerges as a progressive public health approach to enhance the health and well-being of older adults by providing comprehensive and equitable medical services. This study elucidates the association between DHSR and HI for older individuals to augment comprehension of DHSR implementation. Methods: The initiation of the action plan for smart health and eldercare (SHE) in 2017 serves as a quasi-natural experiment. Utilizing data from the China Health and Retirement Longitudinal Study (CHARLS) in 2015 and 2018, a propensity score matching (PSM) method was used to select samples, and a difference-in-differences (DID) regression was used to ascertain the net effect of DHSR on HI for older individuals in China. This methodology mitigates selection bias and segregates the DHSR effect from temporal shifts or other occurrences. Results: The PSM-DID analysis reveals that DHSR reduced the HI index for older individuals by 0.301 (p < 0.01). Heterogeneity analyses indicate that the effect of DHSR was more pronounced in older males (-0.333, p < 0.01) than females (-0.251, p < 0.05). The impact of DHSR was notably higher for older population in the western (-0.557, p < 0.01) and central regions (-0.318, p < 0.05) compared to the eastern region, where the relationship was statistically non-significant. Conclusion: The results demonstrate that DHSR plays a vital role in diminishing HI, fostering inclusive growth in public health. The study underscores the imperative of sustained DHSR endeavours and allocating resources to key older demographics to substantially mitigate HI.

Do Remittances Enhance Elderly Adults' Healthy Social and Physical Functioning? A Cross-Sectional Study in Nigeria.

Existing research demonstrates that the effect of remittances on different health outcomes of elderly adults in low-income countries with inadequate social security is inconclusive. The present study set out to fill this gap by examining the effects of receiving remittances on the healthy social and physical functioning of Nigeria's elderly adults. We also investigate the nonlinear association between remittances and social and physical functioning to identify the minimum amount required to engender healthy social and physical functioning in Nigerian elderly adults. This study utilized data from the 2018/2019 Nigerian Living Standard Survey (NLSS), which included 55,350 young people aged 12-44 (control group) and 18,937 elderly adults aged 45 and above (treatment group). We addressed our objectives using logistic regression-adjusted predicted probabilities and predictive margins. The results reveal that remittance recipients have higher healthy social functioning probabilities than non-recipients. We also found that the influence that remittances have on social functioning depends on the amount of the remittances received. Quantitatively, receiving more than NGN 1,200,000 in remittances ensures increased social functioning probabilities. Given the disparity between the average remittance amount of NGN 54,306.92 received by elderly adults and the NGN 1,200,000 threshold associated with healthy social functioning, bridging this gap is paramount for promoting social functioning among Nigerian elderly adults. We also discussed policy implications for fostering the healthy aging of the population in the interim.

Understanding Aging Policies in China: A Bibliometric Analysis of Policy Documents, 1978-2019.

Aging poses a big challenge in all aspects of social governance in China. A coherent and focused aging policy response that spans multiple sectors of government has been undertaken to achieve the goal of "Healthy Aging". From an historical perspective, this paper uses a bibliometric analysis method to probe into the evolution of Chinese aging policies from 1978 to 2019, and the roles of core government agencies in policy-making. We obtained 226 Chinese aging policies from the PKULaw Database and the websites of the government departments. Co-word analyses and network analyses were applied in mapping the topics of aging policies and collaboration among the agencies. Gephi software was used to visualize the most frequently used keywords and their network graphs. Findings are as follows. Firstly, the development of the aging policy system in China has undergone two phases, from focusing on basic security to emphasizing the rights and health of the elderly. Secondly, the network structure of aging policy-making departments presents a distinct edge-core layer. More and more government agencies have become involved in the formulation of aging policies. But collaboration among the agencies is insufficient. Thirdly, pilot promotion is the main tool for implementing aging policies.

Hepatoprotective lignans and triterpenoids from the roots of Kadsura longipedunculata.

Two new tetrahydrobenzocyclooctabenzofuranone lignans (1-2), a new dibenzocyclooctadiene lignan (3) and three new schiartane-type triterpenoids (4-6), together with six known compounds (7-12), were isolated from the roots of Kadsura longipedunculata. Their structures were elucidated by extensive NMR and HRESIMS spectroscopic data analysis. The absolute configurations of these compounds were determined by comparison of the experimental and calculated ECD spectra. Compound 12 exhibited moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells with cell survival rates of 53.04%.

Hepatoprotective Tetrahydrobenzocyclooctabenzofuranone Lignans from Kadsura longipedunculata.

Three new tetrahydrobenzocyclooctabenzofuranone lignan glucosides, longipedunculatins A-C (1-3), a new dibenzocyclooctadiene lignan glucoside, longipedunculatin D (4), a new dibenzocyclooctadiene lignan (5), five new tetrahydrobenzocyclooctabenzofuranone lignans (6-10), and two new simple lignans (11, 12) were isolated from the roots of Kadsura longipedunculata. Their structures and absolute configurations were established using a combination of MS, NMR, and experimental and calculated electronic circular dichroism data. Compound 7 showed moderate hepatoprotective activity against N-acetyl-p-aminophenol-induced toxicity in HepG2 cells with a cell survival rate at 10 µM of 50.8%. Compounds 2, 7, and 12 showed significant in vitro inhibitory effects with an inhibition rate of 55.1%, 74.9%, and 89.8% on nitric oxide production assays at 10 µM.

Repair Techniques for Failed Double-Eyelids Involving Restoration of Eyelid Anatomical Structure and Function.

BACKGROUND: This study aimed to evaluate techniques for repairing previously failed double-eyelid surgeries based on different anatomical structure injuries. METHODS: A total of 120 patients with failed double-eyelids in our hospital were enrolled and classified into four types according to their anatomical structure damage: type I, unsmooth radians of the double-eyelid line; type II, upper socket depression; type III, iatrogenic ptosis; and type IV, comprehensive damage. Accordingly, methods of restoration included orbital septum fat supplement, repair of levator palpebrae superioris, and treatment of scar. Postoperative follow-up time points were 1 week, 1 month, and 6 months. Outcome observations were binocular symmetry, fluency of double-eyelid, scar recovery, height and contour profile of the upper eyelid margin, and plumpness of the upper eyelid. The eyelid morphological score was evaluated using photographs of preoperative and 6-month postoperative data, and the effect of eyelid repair was evaluated objectively by statistical analysis. RESULTS: At 1 month after surgery, the height of the upper palpebral margin was maintained in most patients and located at 1-2 mm below the superior limbus. At 6 months after surgery, most patients had better restorative effects. Comparison of mean eyelid morphological scores showed a statistically significant improvement following surgery (P < 0.001). CONCLUSIONS: The technique of restoring eyelid anatomical structure in failed double-eyelids not only recovered the normal function of injured eyelids but also produced satisfactory aesthetic effects. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Structural characterization and immunological activity of polysaccharides from the tuber of Bletilla striata.

Two water-soluble polysaccharides, BSP-1 and BSP-2, were extracted and purified from the tuber of Bletilla striata. The molecular weights of BSP-1 and BSP-2 were 83.54 kDa and 12.60 kDa, respectively. The composition and proportion of BSP-1 and BSP-2 were mannose and glucose in molar ratios of 4.0:1.0 and 3.0:1.0 respectively. The two polysaccharides had a linear backbone, consisting mainly of repeating ß­1,4­linked d­mannosyl residues and ß­1,4­linked d­glucosyl residues. BSP-1 exhibited immunomodulatory effects by increasing the thymus and spleen indices of immunocompromised model mice.

Computationally Assisted Assignment of the Kadsuraols, a Class of Chemopreventive Agents for the Control of Liver Cancer.

Kadsuraols A-C (1-3), which are tetrahydrocyclobutaphenanthrofuranone-type lignans with a new carbon skeleton comprising a four-membered ring across C-1'-C-8, have been isolated from the roots of Kadsura longipedunculata. Their structures and absolute configurations were unambiguously determined using nuclear magnetic resonance, X-ray diffraction crystallography, DP4+ calculations, and computed and experimental electronic circular dichroism spectra. Kadsuraol C (3) exhibited hepatoprotective activity against N-acetyl- p-aminophenol (APAP)-induced toxicity. The compounds showed no cytotoxicity at 10 µM in a zone assay.

Hepatoprotective Dibenzocyclooctadiene and Tetrahydrobenzocyclooctabenzofuranone Lignans from Kadsura longipedunculata.

Five new dibenzocyclooctadiene lignans, longipedlignans A-E (1-5), five new tetrahydrobenzocyclooctabenzofuranones (6-10), and 18 known analogues (11-28) were isolated from the roots of Kadsura longipedunculata. Compounds 6-10 are new spirobenzofuranoid-dibenzocyclooctadiene-type lignans. Their structures and absolute configurations were established using a combination of MS, NMR, and electronic circular dichroism data. Spirobenzofuranoids 6 and 15 showed moderate hepatoprotective activity against N-acetyl- p-aminophenol-induced toxicity in HepG2 cells with cell survival rates at 10 µM of 52.2% and 50.2%, respectively.

Assignment of the absolute configuration of hepatoprotective highly oxygenated triterpenoids using X-ray, ECD, NMR J-based configurational analysis and HSQC overlay experiments.

BACKGROUND: The plants of the genus Kadsura are widely distributed in China, South Korea, and Japan. Their roots and stems are traditionally used to treat blood diseases and pain. The main bioactive constituents of Kadsura longipedunculata comprise highly oxygenated triterpenoids. Schiartane-type nortriterpenoids showed anti-HIV, anti-HBV, and cytotoxic bioactivities. For such compounds, the absolute configuration influences the bioactivities, and hence its unambiguous determination is essential. In this work, the absolute configurations of three highly oxygenated schiartane-type nortriterpenoids were unequivocally assigned using X-ray, ECD, and J-based configuration analysis and HSQC overlay data. METHODS: The ethanol extract of Kadsura longipedunculata Finet et Gagnep was purified by column chromatography using silica, Sephadex LH-20, and ODS as substrates. To help assign the absolute configuration of schiartane-type nortriterpenoids, X-ray diffraction analysis, ECD experiment compared to ab initio computed data, DP4+ analysis, HSQC overlay, NOESY, and J-based configuration analysis were carried out. Hetero- and homo-nuclear coupling constants were extracted from HETLOC experiments. RESULTS: Three new highly oxygenated triterpenoids, micrandilactone I (1), micrandilactone J (2), and 22,23-di-epi-micrandilactone J (3) were isolated. Their 2D structures were solved using NMR and HRESIMS data and their absolute configurations were elucidated using X-ray diffraction analysis, ECD experimental results compared to ab initio computed spectra, HSQC overlay, DP4+, NOESY, and J-based configuration analysis. Micrandilactone I (1) and 22,23-di-epi-micrandilactone J (3) showed moderate hepatoprotective activity against APAP-induced toxicity in HepG2 cells with cell survival rates of 53.0 and 50.2%, respectively, at 10µM (bicyclol, 49.0%), while micrandilactone J (2) was inactive. GENERAL SIGNIFICANCE: This is the first comprehensive stereochemical assignment of a non-crystalline schiartane-type nortriterpenoid like 3. This general protocol may contribute towards solving the problems hampering the assignment of the absolute configurations of other members of this class of nortriterpenoids.

[Primary cilium acts as an oxygen sensor in PC12 cells].

Objective: To investigate the function of primary cilium as an oxygen sensor in PC12 cells. Methods: The PC12 cells were transfected with IFT88 siRNA. The nuclear translocation of hypoxia inducible factor-1α (HIF-1α), nuclear factor erythroid-2 related factor 2 (Nrf2), and ciliogenesis were observed by immunofluorescence staining; and the mRNA expressions of HIF-1α, Nrf2, vascular endothelial growth factor (VEGF) and superoxide dismutase (SOD) were detected by real-time RT-PCR. Results: The ciliogenesis was inhibited in PC12 cells transfected with IFT88 siRNA. In hypoxia group and scramble control group, nuclear translocations of HIF-1α and Nrf2 were observed and mRNA expressions of HIF-1α, Nrf2, VEGF were increased, and those of SOD were decreased. While in PC12 cells transfected with IFT88 siRNA, nuclear translocations of HIF-1α and Nrf2 were not observed, and mRNA expressions of HIF-1α, Nrf2, VEGF were inhibited, and mRNA expression of SOD was increased. Conclusion: Primary cilia may act as an oxygen sensor to transfer the information related to hypoxia and oxidative stress into cells, activating intracellular defense mechanism against the hypoxic injuries.

Clinical features of 10 cases of eyelid sporotrichosis in Jilin Province (Northeast China).

OBJECTIVE: Sporotrichosis is a common subcutaneous mycosis caused by an infection with dimorphic fungus Sporothrix schenckii. We present a series of patients with eyelid sporotrichosis and study the clinical and histopathological presentation, microbiology, treatment options, and outcome. METHODS: A retrospective case-series study of patients with a clinical diagnosis of eyelid sporotrichosis. Records were examined to obtain information regarding patient demographics, presenting symptoms and signs, histopathological examination, microbiology, management, and outcomes. RESULTS: Ten patients (4 men, 6 women; mean age 46.5 years, range 3-81 years) were included. Based on their clinical manifestations, eyelid sporotrichosis was classified into 3 major forms: (i) fixed cutaneous (6/10 cases), (ii) lymphocutaneous (3/10 cases), and (iii) eyelid abscess (1/10 cases). All the cases were treated with a terbinafine 12-week regimen. Nodules, papules, and abscesses regressed after treatment. No recurrence was discovered after a 12-week follow-up. CONCLUSIONS: Eyelid sporotrichosis has typical features of clinical manifestations. Histopathological examination and tissue culture are helpful for diagnosis. Confirmed cases normally require long-term systematic treatment with antifungal agents, but surgical removal is normally unnecessary.

TRIM45, a novel human RBCC/TRIM protein, inhibits transcriptional activities of ElK-1 and AP-1.

The tripartite motif (TRIM) proteins play important roles in a variety of cellular functions including cell proliferation, differentiation, development, oncogenesis, and apoptosis. In this study, we report the identification and characterization of the human tripartite motif-containing protein 45 (TRIM45), a novel member of the TRIM family, from a human embryonic heart cDNA library. TRIM45 has a predicted 580 amino acid open reading frame, encoding a putative 64-kDa protein. The N-terminal region harbors a RING finger, two B-boxes, and a predicted alpha-helical coiled-coil domain, which together form the RBCC/TRIM motif found in a large family of proteins, whereas the C-terminal region contains a filamin-type immunoglobulin (IG-FLMN) domain. Northern blot analysis indicates that TRIM45 is expressed in a variety of human adult and embryonic tissues. In the cell, TRIM45 protein is expressed both in cytoplasm and in cell nucleus. Overexpression of TRIM45 in COS-7 cells inhibits the transcriptional activities of ElK-1 and AP-1. These results suggest that TRIM45 may act as a new transcriptional repressor in mitogen-activated protein kinase signaling pathway.